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Saito H, Tanabe H, Hirai H, Higa M, Tanaka K, Yamaguchi S, Maimaituxun G, Masuzaki H, Kazama JJ, Shimabukuro M. Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study. J Diabetes Investig 2024; 15:1444-1456. [PMID: 39058327 PMCID: PMC11442850 DOI: 10.1111/jdi.14272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 07/07/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
AIMS/INTRODUCTION The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. MATERIALS AND METHODS Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. RESULTS Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. CONCLUSIONS Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.
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Affiliation(s)
- Haruka Saito
- Department of Diabetes, Endocrinology, and MetabolismFukushima Medical University School of MedicineFukushimaJapan
| | - Hayato Tanabe
- Department of Diabetes, Endocrinology, and MetabolismFukushima Medical University School of MedicineFukushimaJapan
| | - Hiroyuki Hirai
- Department of Diabetes, Endocrinology, and MetabolismFukushima Medical University School of MedicineFukushimaJapan
- Shirakawa Kosei General HospitalFukushimaJapan
| | - Moritake Higa
- Department of Diabetes and Lifestyle‐Related Disease CenterTomishiro Central HospitalOkinawaJapan
| | - Kenichi Tanaka
- Department of Nephrology and HypertensionFukushima Medical University School of MedicineFukushimaJapan
| | - Satoshi Yamaguchi
- Department of Diabetes, Endocrinology, and MetabolismFukushima Medical University School of MedicineFukushimaJapan
- Department of CardiologyNakagami HospitalOkinawaJapan
| | - Gulinu Maimaituxun
- Department of Diabetes, Endocrinology, and MetabolismFukushima Medical University School of MedicineFukushimaJapan
| | - Hiroaki Masuzaki
- Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine)University of the RyukyusOkinawaJapan
| | - Junichiro J Kazama
- Department of Nephrology and HypertensionFukushima Medical University School of MedicineFukushimaJapan
| | - Michio Shimabukuro
- Department of Diabetes, Endocrinology, and MetabolismFukushima Medical University School of MedicineFukushimaJapan
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Pramanik S, Mondal S, Palui R, Ray S. Type 2 diabetes in children and adolescents: Exploring the disease heterogeneity and research gaps to optimum management. World J Clin Pediatr 2024; 13:91587. [PMID: 38947996 PMCID: PMC11212753 DOI: 10.5409/wjcp.v13.i2.91587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/07/2024] [Accepted: 04/18/2024] [Indexed: 06/07/2024] Open
Abstract
Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic minorities. Despite the rise in T2DM in children and adolescents, the pathophysiology and progression of disease in this population are not clearly understood. Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM. Furthermore, the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients, mostly due to the challenges of implementing clinical trials. A better understanding of the mechanisms underlying the de-velopment and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies. This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.
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Affiliation(s)
- Subhodip Pramanik
- Department of Endocrinology, Neotia Getwel Multi-specialty hospital, Siliguri 734010, West Bengal, India
| | - Sunetra Mondal
- Department of Endocrinology, NRS Medical College and Hospital, Kolkata 700014, West Bengal, India
| | - Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Sayantan Ray
- Department of Endocrinology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar 751019, Odisha, India
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Mottl AK, Tryggestad JB, Isom S, Gubitosi-Klug RA, Henkin L, White NH, D'Agostino R, Hughan KS, Dolan LM, Drews KL. Major adverse events in youth-onset type 1 and type 2 diabetes: The SEARCH and TODAY studies. Diabetes Res Clin Pract 2024; 210:111606. [PMID: 38493952 PMCID: PMC11103672 DOI: 10.1016/j.diabres.2024.111606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/20/2024] [Accepted: 03/04/2024] [Indexed: 03/19/2024]
Abstract
AIMS To determine contemporary incidence rates and risk factors for major adverse events in youth-onset T1D and T2D. METHODS Participant interviews were conducted once during in-person visits from 2018 to 2019 in SEARCH (T1D: N = 564; T2D: N = 149) and semi-annually from 2014 to 2020 in TODAY (T2D: N = 495). Outcomes were adjudicated using harmonized, predetermined, standardized criteria. RESULTS Incidence rates (events per 10,000 person-years) among T1D participants were: 10.9 ophthalmologic; 0 kidney; 11.1 nerve, 3.1 cardiac; 3.1 peripheral vascular; 1.6 cerebrovascular; and 15.6 gastrointestinal events. Among T2D participants, rates were: 40.0 ophthalmologic; 6.2 kidney; 21.2 nerve; 21.2 cardiac; 10.0 peripheral vascular; 5.0 cerebrovascular and 42.8 gastrointestinal events. Despite similar mean diabetes duration, complications were higher in youth with T2D than T1D: 2.5-fold higher for microvascular, 4.0-fold higher for macrovascular, and 2.7-fold higher for gastrointestinal disease. Univariate logistic regression analyses in T1D associated age at diagnosis, female sex, HbA1c and mean arterial pressure (MAP) with microvascular events. In youth-onset T2D, composite microvascular events associated positively with MAP and negatively with BMI, however composite macrovascular events associated solely with MAP. CONCLUSIONS In youth-onset diabetes, end-organ events were infrequent but did occur before 15 years diabetes duration. Rates were higher and had different risk factors in T2D versus T1D.
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Affiliation(s)
- Amy K Mottl
- University of North Carolina Kidney Center, UNC School of Medicine, Chapel Hill, NC, United States.
| | - Jeanie B Tryggestad
- University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Scott Isom
- Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States
| | - Rose A Gubitosi-Klug
- Rainbow Babies and Children's Hospital and Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Leora Henkin
- Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States
| | - Neil H White
- Washington University in St. Louis School of Medicine, St. Louis, MO, United States
| | - Ralph D'Agostino
- Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States
| | - Kara S Hughan
- UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States
| | - Lawrence M Dolan
- University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Kimberly L Drews
- The Biostatistics Center, George Washington University, Rockville, MD, United States
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Chen J, Wu K, Lin Y, Huang M, Xie S. Association of triglyceride glucose index with all-cause and cardiovascular mortality in the general population. Cardiovasc Diabetol 2023; 22:320. [PMID: 37993902 PMCID: PMC10666367 DOI: 10.1186/s12933-023-02054-5] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 11/06/2023] [Indexed: 11/24/2023] Open
Abstract
OBJECTIVE The Triglyceride-glucose (TyG) index, a novel indicator of insulin resistance, has been associated with mortality from coronary artery diseases, ischemic stroke, and heart failure. In recent years, much emphasis has been placed on the relationship between the TyG index and mortality in the general population. However, the impact of age on the association between TyG and all-cause and cardiovascular mortality remains controversial. This study investigated the link between the TyG index and all-cause and cardiovascular mortality, emphasizing differences between older and non-older populations. METHODS Data from the National Health and Nutrition Examination Survey (2009-2018), encompassing 20,194 participants, were analyzed. The baseline TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models with restricted cubic splines and trend tests were employed to explore the association between the TyG index and all-cause and cardiovascular mortality, with emphasis on age-specific analysis. Subgroup analysis was conducted to examine whether the TyG index's association with mortality varied across different subgroups. Additionally, receiver operating characteristic curves were used to compare the predictive ability of the TyG index with the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality. RESULTS Over a median follow-up period of 105 months, all-cause mortality accounted for 13.345% of cases, and cardiovascular mortality accounted for 3.387%. Kaplan-Meier curves showed a significant increase in all-cause and cardiovascular mortality with higher TyG index values (both P for log-rank test < 0.001). However, during Cox proportional hazards regression analysis, no linear trend was observed between the TyG index and all-cause or cardiovascular mortality after adjusting for confounding factors (all-cause mortality: P for trend = 0.424; cardiovascular mortality: P for trend = 0.481). Restricted cubic splines revealed a non-linear association between the baseline TyG index and all-cause and cardiovascular mortality in the overall population (all-cause mortality: Non-linear P = 0.003; cardiovascular mortality: Non-linear P = 0.034). The effect of the TyG index was consistent across most subgroups in terms of all-cause and cardiovascular mortality, with no significant interaction with randomized factors (all-cause mortality: P for interaction = 0.077-0.940, cardiovascular mortality: P for interaction = 0.173-0.987), except for the age subgroup (all-cause mortality: P for interaction < 0.001, cardiovascular mortality: P for interaction < 0.001). Further age-specific analysis revealed that the association between the TyG index and all-cause and cardiovascular mortality remained significant in patients aged < 65 but not in those aged ≥ 65. Interestingly, a non-linear association was observed between the TyG index and all-cause mortality in individuals aged < 65 (Non-linear P = 0.011), while a linear relationship was observed with cardiovascular mortality, showing an upward trend (Non-linear P = 0.742, P for trend = 0.010). Further stratification according to age yielded similar results only in patients aged 45-64 (all-cause mortality: Non-linear P = 0.001 and cardiovascular mortality: Non-linear P = 0.902, P for trend = 0.015). Compared to HOMA-IR, the TyG index demonstrated superior predictive performance for all-cause and cardiovascular mortality (all-cause mortality: 0.620 vs. 0.524, P < 0.001; cardiovascular mortality: 0.623 vs. 0.537, P < 0.001). CONCLUSIONS This study established a significant association between the TyG index and all-cause and cardiovascular mortality in the general population, particularly among individuals aged < 65. Notably, a non-linear association with all-cause mortality was observed in those aged < 65, while a linear relationship with cardiovascular mortality was found.
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Affiliation(s)
- Jiaqi Chen
- Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Yongzhong Street, Wenzhou, 325000, Zhejiang, China
| | - Kangxiang Wu
- Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Yongzhong Street, Wenzhou, 325000, Zhejiang, China
| | - Yiying Lin
- Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Yongzhong Street, Wenzhou, 325000, Zhejiang, China
| | - Mingyuan Huang
- Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Yongzhong Street, Wenzhou, 325000, Zhejiang, China.
| | - Shanghe Xie
- Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Yongzhong Street, Wenzhou, 325000, Zhejiang, China.
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Esposito P, Picciotto D, Cappadona F, Costigliolo F, Russo E, Macciò L, Viazzi F. Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes. World J Diabetes 2023; 14:1450-1462. [PMID: 37970131 PMCID: PMC10642421 DOI: 10.4239/wjd.v14.i10.1450] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/18/2023] [Accepted: 08/28/2023] [Indexed: 10/09/2023] Open
Abstract
Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.
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Affiliation(s)
- Pasquale Esposito
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Daniela Picciotto
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Francesca Cappadona
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Francesca Costigliolo
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Elisa Russo
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Lucia Macciò
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
| | - Francesca Viazzi
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
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Wang Y, Pang X, Gu C, Li C, Li B, Zhou C, Chen H, Zheng Z. Different associations of anthropometric indices with diabetic retinopathy and diabetic kidney disease in chinese patients with type 2 diabetes mellitus. Acta Diabetol 2023; 60:1187-1198. [PMID: 37179497 DOI: 10.1007/s00592-023-02111-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 04/27/2023] [Indexed: 05/15/2023]
Abstract
AIMS To investigate the associations of anthropometric indices, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist circumference (WC) and hip circumference (HC), with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS This cross-sectional study evaluated 5226 Chinese participants with T2DM at three hospitals between 2005 and 2016. Logistic regression models and restricted cubic spline analysis were used to assess the associations of anthropometric indices with DR and DKD. RESULTS A BMI of around 25 kg/m2 was related to a low risk of DR (OR based on the third fifth: 0.752, 95%CI: 0.615-0.920). Besides, HC had an inverse association with DR in men independently of BMI (OR based on the highest fifth: 0.495, 95%CI: 0.350-0.697). In the restricted cubic spline models, BMI, WHtR, WC, and HC showed J-shaped associations with DKD, while WHR showed an S-shaped association with DKD. Compared to the lowest fifth, the odds ratios (OR) based on the highest fifth of BMI, WHR, WHtR, WC and HC for DKD were 1.927 (1.572-2.366), 1.566 (1.277-1.923), 1.910 (1.554-2.351), 1.624 (1.312-2.012) and 1.585 (1.300-1.937) respectively in multivariable models. CONCLUSIONS A median BMI and a large hip might be related to a low risk of DR, while lower levels of all the anthropometric indices were associated with a lower risk of DKD. Our findings suggested maintain a median BMI, a low WHR, a low WHtR and a large hip for prevention of DR and DKD.
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Affiliation(s)
- Yujie Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Xin Pang
- Department of Ophthalmology, Haiyan County People's Hospital, No.901 Yanhu West Road, Wuyuan Street, Haiyan County, Jiaxing, Zhejiang Province, China
| | - Chufeng Gu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Chenxin Li
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Bo Li
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Chuandi Zhou
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Haibing Chen
- Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, Tongji University, No.301 Yanan Zhong Road, Shanghai, China.
| | - Zhi Zheng
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, China.
- National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.
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Lee J, Lee SH, Yoon KH, Cho JH, Han K, Yang Y. Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea. Sci Rep 2023; 13:10100. [PMID: 37344516 DOI: 10.1038/s41598-023-36711-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 06/08/2023] [Indexed: 06/23/2023] Open
Abstract
We investigated the risk of developing chronic kidney disease (CKD) in patients with young-onset Type 2 diabetes (YOD, diagnosed age < 40 years). We enrolled 84,384 patients aged 20-64 who started anti-diabetic medication between 2010 and 2011 from the Korea National Health Insurance Sharing Service; patients with Type 1 diabetes or a history of CKD were excluded. Multivariate logistic regression analyses were performed to adjust for YOD-distinct variables and compare the incidence of CKD between YOD and late-onset diabetes (LOD, diagnosed age ≥ 40 years). During the median observation period of 5.16 years (interquartile range: 4.58-5.77 years), 1480 out of 77,039 LOD patients and 34 out of 7345 YOD patients developed CKD. Patients with YOD had distinct baseline characteristics compared with the patients with LOD. The odds ratio of developing CKD in patients with YOD over LOD was 1.70 (95% CI 1.15-2.51) after adjusting clinically distinct variables. The increased CKD odds in YOD compared with LOD was greater in the non-smoking group (OR 2.03, 95% CI 1.26-3.26) than in the smoking group (OR 1.49, 95% CI 0.74-2.98, p = 0.0393 for interaction). Among YOD patients, hypertension (34.76% vs. 64.71%, p = 0.0003), dyslipidemia (46.87% vs. 73.53%, p = 0.0019), and sulfonylurea use (35.54% vs. 52.94%, p = 0.0345) were associated with CKD development. YOD patients have a greater risk of developing CKD than LOD patients after adjusting clinically distinct variables.
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Affiliation(s)
- Joonyub Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung-Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Republic of Korea
| | - Kun-Ho Yoon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Republic of Korea
| | - Jae Hyoung Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Republic of Korea
- Catholic Smart Health Care Center, The Catholic University of Korea, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul, 06978, Korea.
| | - Yeoree Yang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- Catholic Smart Health Care Center, The Catholic University of Korea, Seoul, Korea.
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Do DV, Han G, Abariga SA, Sleilati G, Vedula SS, Hawkins BS. Blood pressure control for diabetic retinopathy. Cochrane Database Syst Rev 2023; 3:CD006127. [PMID: 36975019 PMCID: PMC10049880 DOI: 10.1002/14651858.cd006127.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
BACKGROUND Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Concurrent blood pressure control has been advocated for this purpose, but individual studies have reported varying conclusions regarding the effects of this intervention. OBJECTIVES To summarize the existing evidence regarding the effect of interventions to control blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. SEARCH METHODS We searched several electronic databases, including CENTRAL, and trial registries. We last searched the electronic databases on 3 September 2021. We also reviewed the reference lists of review articles and trial reports selected for inclusion. SELECTION CRITERIA We included randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to more intense versus less intense blood pressure control; to blood pressure control versus usual care or no intervention on blood pressure (placebo); or to one class of antihypertensive medication versus another or placebo. DATA COLLECTION AND ANALYSIS Pairs of review authors independently reviewed the titles and abstracts of records identified by the electronic and manual searches and the full-text reports of any records identified as potentially relevant. The included trials were independently assessed for risk of bias with respect to outcomes reported in this review. MAIN RESULTS We included 29 RCTs conducted in North America, Europe, Australia, Asia, Africa, and the Middle East that had enrolled a total of 4620 type 1 and 22,565 type 2 diabetic participants (sample sizes from 16 to 4477 participants). In all 7 RCTs for normotensive type 1 diabetic participants, 8 of 12 RCTs with normotensive type 2 diabetic participants, and 5 of 10 RCTs with hypertensive type 2 diabetic participants, one group was assigned to one or more antihypertensive agents and the control group to placebo. In the remaining 4 RCTs for normotensive participants with type 2 diabetes and 5 RCTs for hypertensive type 2 diabetic participants, methods of intense blood pressure control were compared to usual care. Eight trials were sponsored entirely and 10 trials partially by pharmaceutical companies; nine studies received support from other sources; and two studies did not report funding source. Study designs, populations, interventions, lengths of follow-up (range less than one year to nine years), and blood pressure targets varied among the included trials. For primary review outcomes after five years of treatment and follow-up, one of the seven trials for type 1 diabetics reported incidence of retinopathy and one trial reported progression of retinopathy; one trial reported a combined outcome of incidence and progression (as defined by study authors). Among normotensive type 2 diabetics, four of 12 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; two trials reported combined incidence and progression. Among hypertensive type 2 diabetics, six of the 10 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; five of the 10 trials reported combined incidence and progression. The evidence supports an overall benefit of more intensive blood pressure intervention for five-year incidence of diabetic retinopathy (11 studies; 4940 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.73 to 0.92; I2 = 15%; moderate certainty evidence) and the combined outcome of incidence and progression (8 studies; 6212 participants; RR 0.78, 95% CI 0.68 to 0.89; I2 = 42%; low certainty evidence). The available evidence did not support a benefit regarding five-year progression of diabetic retinopathy (5 studies; 5144 participants; RR 0.94, 95% CI 0.78 to 1.12; I2 = 57%; moderate certainty evidence), incidence of proliferative diabetic retinopathy, clinically significant macular edema, or vitreous hemorrhage (9 studies; 8237 participants; RR 0.92, 95% CI 0.82 to 1.04; I2 = 31%; low certainty evidence), or loss of 3 or more lines on a visual acuity chart with a logMAR scale (2 studies; 2326 participants; RR 1.15, 95% CI 0.63 to 2.08; I2 = 90%; very low certainty evidence). Hypertensive type 2 diabetic participants realized more benefit from intense blood pressure control for three of the four outcomes concerning incidence and progression of diabetic retinopathy. The adverse event reported most often (13 of 29 trials) was death, yielding an estimated RR 0.87 (95% CI 0.76 to 1.00; 13 studies; 13,979 participants; I2 = 0%; moderate certainty evidence). Hypotension was reported in two trials, with an RR of 2.04 (95% CI 1.63 to 2.55; 2 studies; 3323 participants; I2 = 37%; low certainty evidence), indicating an excess of hypotensive events among participants assigned to more intervention on blood pressure. AUTHORS' CONCLUSIONS Hypertension is a well-known risk factor for several chronic conditions for which lowering blood pressure has proven to be beneficial. The available evidence supports a modest beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to five years, particularly for hypertensive type 2 diabetics. However, there was a paucity of evidence to support such intervention to slow progression of diabetic retinopathy or to affect other outcomes considered in this review among normotensive diabetics. This weakens any conclusion regarding an overall benefit of intervening on blood pressure in diabetic patients without hypertension for the sole purpose of preventing diabetic retinopathy or avoiding the need for treatment for advanced stages of diabetic retinopathy.
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Affiliation(s)
- Diana V Do
- Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA
| | - Genie Han
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Samuel A Abariga
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | | | - Barbara S Hawkins
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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9
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Bjornstad P, Chao LC, Cree-Green M, Dart AB, King M, Looker HC, Magliano DJ, Nadeau KJ, Pinhas-Hamiel O, Shah AS, van Raalte DH, Pavkov ME, Nelson RG. Youth-onset type 2 diabetes mellitus: an urgent challenge. Nat Rev Nephrol 2023; 19:168-184. [PMID: 36316388 PMCID: PMC10182876 DOI: 10.1038/s41581-022-00645-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2022] [Indexed: 11/05/2022]
Abstract
The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are more limited than for adult patients. Intermediate complications of youth-onset T2DM, such as increased albuminuria, often develop in late childhood or early adulthood, and end-stage complications, including kidney failure, develop in mid-life. The increasing frequency, earlier onset and greater severity of childhood obesity in the past 50 years together with increasingly sedentary lifestyles and an increasing frequency of intrauterine exposure to diabetes are important drivers of the epidemic of youth-onset T2DM. The particularly high risk of the disease in historically disadvantaged populations suggests an important contribution of social and environmental factors, including limited access to high-quality health care, healthy food choices and opportunities for physical activity as well as exposure to stressors including systemic racism and environmental pollutants. Understanding the mechanisms that underlie the development and aggressive clinical course of youth-onset T2DM is key to identifying successful prevention and management strategies.
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Affiliation(s)
| | - Lily C Chao
- Children's Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
| | | | - Allison B Dart
- Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
| | - Malcolm King
- University of Saskatchewan College of Medicine, Saskatoon, Saskatchewan, Canada
| | - Helen C Looker
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Monash University, School of Public Health and Preventive Medicine, Melbourne, Australia
| | | | - Orit Pinhas-Hamiel
- Paediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Amy S Shah
- Cincinnati Children's Hospital and The University of Cincinnati, Cincinnati, OH, USA
| | | | - Meda E Pavkov
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Robert G Nelson
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
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10
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Looker HC, Chang DC, Baier LJ, Hanson RL, Nelson RG. Diagnostic criteria and etiopathogenesis of type 2 diabetes and its complications: Lessons from the Pima Indians. Presse Med 2023; 52:104176. [PMID: 37783422 PMCID: PMC10805453 DOI: 10.1016/j.lpm.2023.104176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/28/2023] [Accepted: 07/19/2023] [Indexed: 10/04/2023] Open
Abstract
The Phoenix Epidemiology and Clinical Research Branch of the National Institute of Diabetes and Digestive and Kidney Diseases has conducted prospective studies of diabetes and its complications in the Pima Indians living in Arizona, USA for over 50 years. In this review we highlight areas in which these studies provided vital insights into the criteria used to diagnose type 2 diabetes, the pathophysiologic changes that accompany the development of type 2 diabetes, and the course and determinants of diabetes complications-focusing specifically on diabetic kidney disease. We include data from our longitudinal population-based study of diabetes and its complications, studies on the role of insulin resistance and insulin secretion in the pathophysiology of type 2 diabetes, and in-depth studies of diabetic kidney disease that include measures of glomerular function and research kidney biopsies. We also focus on the emerging health threat posed by youth-onset type 2 diabetes, which was first seen in the Pima Indians in the 1960s and is becoming an increasing issue worldwide.
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Affiliation(s)
- Helen C Looker
- Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Douglas C Chang
- Obesity and Diabetes Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Leslie J Baier
- Diabetes Molecular Genetics Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Robert L Hanson
- Diabetes Genetic Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Robert G Nelson
- Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
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11
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Cho Y, Park HS, Huh BW, Seo SH, Seo DH, Ahn SH, Hong S, Suh YJ, Kim SH. Prevalence and risk of diabetic complications in young-onset versus late-onset type 2 diabetes mellitus. DIABETES & METABOLISM 2022; 48:101389. [PMID: 36255061 DOI: 10.1016/j.diabet.2022.101389] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 09/08/2022] [Accepted: 09/14/2022] [Indexed: 06/16/2023]
Abstract
AIMS To compare the prevalence and risk of diabetic complications between people with young-onset and late-onset type 2 diabetes mellitus (T2DM). METHODS In this observational study, 10,447 people with T2DM had at least one study of diabetic complications: retinopathy, neuropathy, chronic kidney disease (CKD), carotid artery plaque. We use odds ratios to compare complications between young-onset T2DM (YOD) and late-onset T2DM (LOD). RESULTS We compare 1,791 people with YOD (diagnosed < 40 years) and 8,656 with LOD (diagnosed ≥ 40 years). The YOD had a higher prevalence of these complications than the LOD (p < 0.011) after adjustment for confounding factors. Further adjustment for diabetes duration greatly attenuated the odds ratios however, neuropathy remained significantly more frequent in people with YOD (adjusted odds ratio: 1.39, 95% confidence interval: 1.13-1.71, p = 002). In cluster analysis on the 2,126 study participants who were diagnosed with T2DM within the previous two years, 47% of the YOD group were in the severe insulin-deficient diabetes cluster in comparison to 23% LOD; 28% and 44% respectively were in the mild age-related diabetes. CONCLUSION People with YOD had a higher prevalence of complications than those with LOD, but this was mostly attributed to a longer duration of diabetes. However, the prevalence of neuropathy remained significantly higher even after adjusting for factors including the duration of diabetes.
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Affiliation(s)
- Yongin Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Hye-Sun Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Wook Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Seong Ha Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Da Hea Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seong Hee Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seongbin Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Young Ju Suh
- Department of Biomedical Sciences, Inha University College of Medicine, Incheon, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea.
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12
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Kelsey MM, Zeitler PS, Nadeau KJ, Shah AS. Type 2 diabetes in youth: Rationale for use of off-label antidiabetic agents. Pediatr Diabetes 2022; 23:615-619. [PMID: 35524343 PMCID: PMC9378434 DOI: 10.1111/pedi.13350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 04/06/2022] [Accepted: 05/02/2022] [Indexed: 12/30/2022] Open
Affiliation(s)
- Megan M Kelsey
- Department of Pediatrics, Section of Endocrinology and Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Philip S Zeitler
- Department of Pediatrics, Section of Endocrinology and Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Kristen J Nadeau
- Department of Pediatrics, Section of Endocrinology and Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Amy S Shah
- Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
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13
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Fan Y, Lau ESH, Wu H, Yang A, Chow E, So WY, Kong APS, Ma RCW, Chan JCN, Luk AOY. Incidence of long-term diabetes complications and mortality in youth-onset type 2 diabetes: A systematic review. Diabetes Res Clin Pract 2022; 191:110030. [PMID: 35934175 DOI: 10.1016/j.diabres.2022.110030] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 06/17/2022] [Accepted: 08/01/2022] [Indexed: 11/16/2022]
Abstract
AIMS This systematic review aims to assess the incidence of chronic kidney disease (CKD), cardiovascular disease (CVD) and mortality in people with type 2 diabetes diagnosed <20 years. METHODS We searched MEDLINE, Embase and Cochrane Library for longitudinal studies published between 1 January 2000 and 31 November 2021. RESULTS Seventeen studies (15 reporting CKD, 3 reporting CVD, 5 reporting mortality) from seven countries of sample size ranging between 96 and 4,141 were eligible. Most studies were conducted in North America and Europe (n = 14). Diabetes duration at enrolment varied from 0 to 8.3 years and follow-up duration from 1 to 12.6 years. The incidence rates (per 1,000 person-year) of albuminuria ranged between 12.4 and 114.8, macroalbuminuria or proteinuria between 10 and 35.0, end-stage kidney disease (ESKD) between 0.4 and 25.0, CVD between 3.7 and 19.5, and mortality between 1.0 and 18.6. The highest incidence rates of albuminuria, ESKD and mortality were recorded in Australian Aboriginal and Pima Indian populations. Youth-onset type 2 diabetes was associated with greater risk of developing CKD compared with type 1 diabetes in most studies. CONCLUSION Studies reporting CVD in youth-onset type 2 diabetes are scarce. Estimated incidence rates of CKD and mortality in youth-onset type 2 diabetes varied across different study populations, potentially higher in indigenous people. Youth with type 2 diabetes are at higher risk of adverse kidney outcomes than their type 1 counterparts. More studies are needed in regions outside of North America and Europe.
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Affiliation(s)
- Yingnan Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Wing-Yee So
- Hong Kong Hospital Authority, Kowloon, Hong Kong, China
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
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14
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Childhood and adolescent onset type 2 diabetes mellitus (CAT2DM): The yoke of the young diabetics. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2022. [DOI: 10.1016/j.cegh.2022.101101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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15
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Şen S, Özalp Kızılay D, Taneli F, Özen Ç, Ertan P, Özunan İ, Yıldız R, Ersoy B. Urinary NGAL is a Potential Biomarker for Early Renal Injury in Insulin Resistant Obese Non-diabetic Children. J Clin Res Pediatr Endocrinol 2021; 13:400-407. [PMID: 34013756 PMCID: PMC8638630 DOI: 10.4274/jcrpe.galenos.2021.2021.0020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE Neutrophil gelatinase-associated lipocalin (NGAL) is one of the new biomarkers for detecting acute renal injury. There are studies showing the relationship between NGAL and renal injury in obese children. The aim of this study was to investigate whether urinary levels of NGAL, kidney injury molecule-1, and serum cystatin C are increased in insulin resistance (IR) patients before the development of diabetes. METHODS Cross-sectional, case-controlled study that included non-diabetic obese children and adolescent patients with IR and a non-diabetic obese control group with no IR, who attended a tertiary center pediatric endocrinology outpatient clinic between 2016-2018. Those with diabetes mellitus and/or known renal disease were excluded. NGAL and creatinine (Cr) levels were evaluated in the morning spot urine from all participants. Serum renal function was evaluated. RESULTS Thirty-six control and 63 IR patients were included in the study, of whom 68 (68.7%) were girls. The mean age of all participants was 13.12±2.64 years and no statistically significant difference was found between the two groups in terms of age or gender distribution. Median (range) spot urinary NGAL (u-NGAL) values in the IR group were significantly higher at 26.35 (7.01-108.7) ng/mL than in the control group at 19.5 (3.45-88.14) ng/mL (p=0.018). NGAL/Cr ratio was also significantly higher in the IR group compared to the control group (p=0.018). CONCLUSION Obese pediatric patients with IR were shown to have elevated levels of u-NGAL, a marker of renal injury. u-NGAL examination may show early renal injury before development of diabetes.
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Affiliation(s)
- Semra Şen
- Celal Bayar University Faculty of Medicine, Department of Pediatrics, Manisa, Turkey,* Address for Correspondence: Celal Bayar University Faculty of Medicine, Department of Pediatrics, Manisa, Turkey Phone: +90 236 444 42 28 E-mail:
| | - Deniz Özalp Kızılay
- Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrionology, Manisa, Turkey
| | - Fatma Taneli
- Celal Bayar University Faculty of Medicine, Department of Medical Biochemistry, Manisa, Turkey
| | - Çınar Özen
- Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Nephrology, Manisa, Turkey
| | - Pelin Ertan
- Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Nephrology, Manisa, Turkey
| | - İpek Özunan
- Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Nephrology, Manisa, Turkey
| | - Raziye Yıldız
- Celal Bayar University Faculty of Medicine, Department of Medical Biochemistry, Manisa, Turkey
| | - Betül Ersoy
- Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrionology, Manisa, Turkey
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16
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Wu S, Zhao Z, Liu S, Li M, Wang T, Wang S, Xu M, Chen Y, Dai M, Zhang D, Yu X, Tang X, Hu R, Ye Z, Shi L, Su Q, Yan L, Qin G, Wan Q, Chen G, Gao Z, Wang G, Shen F, Luo Z, Qin Y, Chen L, Huo Y, Li Q, Zhang Y, Liu C, Wang Y, Wu S, Yang T, Deng H, Chen L, Zhao J, Mu Y, Xu Y, Bi Y, Lu J, Xu Y, Wang W, Ning G. The association between age at diagnosis of type 2 diabetes and albuminuria in Chinese adults: A nationwide population study. J Diabetes 2021; 13:987-997. [PMID: 34259386 DOI: 10.1111/1753-0407.13213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/08/2021] [Accepted: 07/07/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen-detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self-reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.
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Affiliation(s)
- Shujing Wu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shanshan Liu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shuangyuan Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Meng Dai
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Di Zhang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xuefeng Yu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xulei Tang
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Ruying Hu
- Zhejiang Provincial Center for Disease Control and Prevention, Zhejiang, China
| | - Zhen Ye
- Zhejiang Provincial Center for Disease Control and Prevention, Zhejiang, China
| | - Lixin Shi
- Affiliated Hospital of Guiyang Medical College, Guiyang, China
| | - Qing Su
- Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Li Yan
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guijun Qin
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qin Wan
- The Affiliated Hospital of Luzhou Medical College, Luzhou, China
| | - Gang Chen
- Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China
| | - Zhengnan Gao
- Dalian Municipal Central Hospital, Dalian Medical University, Dalian, China
| | - Guixia Wang
- The First Hospital of Jilin University, Changchun, China
| | - Feixia Shen
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zuojie Luo
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yingfen Qin
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Li Chen
- Qilu Hospital of Shandong University, Jinan, China
| | - Yanan Huo
- Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China
| | - Qiang Li
- The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yinfei Zhang
- Central Hospital of Shanghai Jiading District, Shanghai, China
| | - Chao Liu
- Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China
| | - Youmin Wang
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Shengli Wu
- Karamay Municipal People's Hospital, Xinjiang, China
| | - Tao Yang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Huacong Deng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lulu Chen
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiajun Zhao
- Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
| | - Yiming Mu
- Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yiping Xu
- Clinical Trials Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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17
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Affiliation(s)
- Wah Yang
- First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Cunchuan Wang
- First Affiliated Hospital of Jinan University, Guangzhou, China
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18
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The epidemiology, clinical, biochemical, immunological and radiological features of youth onset type 2 diabetes mellitus in the state of Qatar. Diabetol Int 2021; 13:381-386. [DOI: 10.1007/s13340-021-00548-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 10/01/2021] [Indexed: 01/16/2023]
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19
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Sundström J, Kristófi R, Östlund O, Bennet L, Eliasson B, Jansson S, Leksell J, Almby K, Lundqvist M, Eriksson JW. A registry-based randomised trial comparing an SGLT2 inhibitor and metformin as standard treatment of early stage type 2 diabetes (SMARTEST): Rationale, design and protocol. J Diabetes Complications 2021; 35:107996. [PMID: 34389234 DOI: 10.1016/j.jdiacomp.2021.107996] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/08/2021] [Accepted: 07/19/2021] [Indexed: 11/30/2022]
Abstract
AIM SGLT2 inhibitors have been shown to reduce cardiovascular and renal complications in type 2 diabetes (T2D) patients at high cardiovascular risk. Metformin is currently widely used as initial monotherapy in T2D but lacks convincing data to show that it reduces risk of complications. We aim to compare the SGLT2 inhibitor dapagliflozin and metformin as first-line T2D medication with regard to development of complications in a registry-based randomised controlled trial. METHODS The SGLT2 inhibitor or metformin as standard treatment of early stage type 2 diabetes (SMARTEST) trial will enrol 4300 subjects at 30-40 study sites in Sweden who will be randomised 1:1 to either metformin or dapagliflozin. Participants must have T2D duration <4 years, no prior cardiovascular disease, and be either drug-naïve or on monotherapy for T2D. RESULTS The primary endpoint is a composite of all-cause death, major adverse cardiovascular events and occurrence or progression of microvascular complications (retinopathy, nephropathy, diabetic foot lesions). Secondary endpoints include individual components of the primary endpoint, start of insulin therapy, risk factor biomarkers, patient-reported outcome measures, and cost-effectiveness analysis. Outcomes will primarily be assessed using nationwide healthcare registries. CONCLUSIONS The SMARTEST trial will investigate whether dapagliflozin is superior to metformin in preventing complications in early stage T2D. (Clinicaltrials.gov identifier NCT03982381, EudraCT 2019-001046-17).
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Affiliation(s)
- Johan Sundström
- Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, Australia
| | - Robin Kristófi
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | | | - Louise Bennet
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Björn Eliasson
- Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Stefan Jansson
- Institution of Medical Sciences, University Health Care Research Center, Örebro University, Örebro, Sweden; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
| | - Janeth Leksell
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Kristina Almby
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Martin Lundqvist
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Jan W Eriksson
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
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20
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Yang YS, Han K, Sohn TS, Kim NH. Young-onset type 2 diabetes in South Korea: a review of the current status and unmet need. Korean J Intern Med 2021; 36:1049-1058. [PMID: 34503316 PMCID: PMC8435510 DOI: 10.3904/kjim.2021.379] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 08/26/2021] [Indexed: 12/27/2022] Open
Abstract
The prevalence of young-onset (diagnosis at age < 40 years) type 2 diabetes mellitus (T2DM) is increasing globally. Young-onset T2DM has a common pathophysiology of glucose dysregulation as in late-onset T2DM. However, it presents a greater association with obesity and a more rapid decline in β-cell function than late-onset T2DM. Accumulating evidence indicates that disease progression in young-onset T2DM is rapid, resulting in early and frequent development of microvascular and macrovascular complications, as well as premature death. Improper management and low adherence to medical therapy are important issues in young-onset T2DM. This review discusses the epidemiology, disease entity, and clinical issues associated with young-onset T2DM. We also present the prevalence and clinical characteristics of patients with young-onset T2DM in South Korea.
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Affiliation(s)
- Ye Seul Yang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Tae Seo Sohn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Correspondence to Nam Hoon Kim, M.D. Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Korea Tel: +82-2-920-5421 Fax: +82-2-953-9355 E-mail:
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21
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Pyle L, Kelsey MM. Youth-onset type 2 diabetes: translating epidemiology into clinical trials. Diabetologia 2021; 64:1709-1716. [PMID: 34075436 DOI: 10.1007/s00125-021-05480-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 03/10/2021] [Indexed: 12/17/2022]
Abstract
Globally, the proportion of new diagnoses of youth-onset diabetes represented by type 2 diabetes is increasing, and youth with type 2 diabetes commonly have complications and comorbidities, as well as a higher rate of mortality. In this review, we summarise what is known about the natural progression of youth-onset type 2 diabetes from published clinical trials and large-scale prospective epidemiological studies. It is important to note that the robust pathophysiological and treatment data specifically related to individuals with a diabetes onset at ≤20 years of age largely hails from the USA. Youth-onset type 2 diabetes is characterised by pathophysiological heterogeneity and inadequate glycaemic control, highlighting the need for new treatment approaches and innovative study designs in populations of varied genetic and cultural backgrounds.
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Affiliation(s)
- Laura Pyle
- Section of Paediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA
| | - Megan M Kelsey
- Section of Paediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
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22
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Nelson RG, Knowler WC, Kretzler M, Lemley KV, Looker HC, Mauer M, Mitch WE, Najafian B, Bennett PH. Pima Indian Contributions to Our Understanding of Diabetic Kidney Disease. Diabetes 2021; 70:1603-1616. [PMID: 34285119 PMCID: PMC8385607 DOI: 10.2337/dbi20-0043] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 05/23/2021] [Indexed: 11/13/2022]
Abstract
Prospective studies in informative populations are crucial to increasing our knowledge of disease. In this perspective, we describe a half century of studies in an American Indian population that transformed our understanding of kidney disease in type 2 diabetes, now recognized as the leading cause of kidney failure worldwide. Serial examinations conducted for many years that included the collection of data and samples across multiple domains captured an unprecedented volume of clinical, physiologic, morphometric, genomic, and transcriptomic data. This work permitted us to extensively characterize the course and determinants of diabetic kidney disease, its pathophysiologic underpinnings, and important secular trends of urgent concern to populations worldwide, including the emergence of youth-onset type 2 diabetes and its effect on development of diabetic kidney disease in midlife. By combining these data using the tools of integrative biology, we are developing new mechanistic insights into the development and progression of diabetic kidney disease in type 2 diabetes. These insights have already contributed to the identification and successful therapeutic targeting of a novel pathway in DKD. We anticipate that this work will continue to expand our understanding of this complex disease and influence its management in the coming years.
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Affiliation(s)
- Robert G Nelson
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
| | - William C Knowler
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
| | - Matthias Kretzler
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Kevin V Lemley
- Department of Pediatrics, University of Southern California Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, CA
| | - Helen C Looker
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
| | - Michael Mauer
- Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN
| | - William E Mitch
- Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Behzad Najafian
- Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA
| | - Peter H Bennett
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
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23
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Fornari E, Barbetti F, Iafusco D, Lombardo F, Miraglia Del Giudice E, Rabbone I, Mozzillo E. Type 2 diabetes in pediatrics. Minerva Pediatr (Torino) 2021; 73:549-562. [PMID: 34286947 DOI: 10.23736/s2724-5276.21.06530-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Type 2 diabetes (T2D) in adolescents has become an increasing health concern throughout the world and its prevention and screening should be implemented in pediatric care. As clinical features at presentation, in some cases can be similar to type 1 diabetes and family history can be in favour of a monogenic form of diabetes, it is pivotal for physicians to be aware of youth-onset T2D specificities to ensure an accurate diagnosis. The global increase of overweight and obesity can complicate the diagnostic process and makes it essential to apply a systematic approach to each new diagnosis. Microvascular complications may be present at the time of diagnosis and chronic complications are frequent and need to be screened regularly. Regular screening of comorbidities should also be performed. Childhood T2D should be followed up by pediatric diabetes units to avoid diagnostic errors and delay in care. A multidisciplinary approach, by an experienced team, is pivotal to provide treatment options targeting the unique needs of pediatric patients. Treatment programs must include the whole family and address all the aspects of the care (lifestyle, pharmacological therapy, psychological aspects, complications and comorbidities). An organized process of transition to adult care is essential.
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Affiliation(s)
- Elena Fornari
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Fabrizio Barbetti
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Dario Iafusco
- Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Fortunato Lombardo
- Department of Human Pathology in Adult and Developmental Age, University of Messina, Messina, Italy
| | - Emanuele Miraglia Del Giudice
- Department of the Woman, of the Child, of General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Ivana Rabbone
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Enza Mozzillo
- Regional Center of Pediatric Diabetes, Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy -
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24
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Amutha A, Ranjit U, Anjana RM, Shanthi R CS, Rajalakshmi R, Venkatesan U, Muthukumar S, Philips R, Kayalvizhi S, Gupta PK, Sastry NG, Mohan V. Clinical profile and incidence of microvascular complications of childhood and adolescent onset type 1 and type 2 diabetes seen at a tertiary diabetes center in India. Pediatr Diabetes 2021; 22:67-74. [PMID: 32333449 DOI: 10.1111/pedi.13033] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 04/09/2020] [Accepted: 04/15/2020] [Indexed: 12/22/2022] Open
Abstract
AIM To study the clinical characteristics and incidence of microvascular complications among childhood and adolescent onset type 1 (T1DM) and type 2 diabetes (T2DM) seen at a tertiary care diabetes center in India. METHODS From our electronic medical records, we retrieved clinical and biochemical details of 4555 individuals with childhood and adolescent onset diabetes (diagnosed below the age of 20 years) seen between 1992 and 2017. T1DM was diagnosed if there was history of ketoacidosis or fasting C-peptide <0.3 PMol/mL and stimulated C-peptide <0.6 PMol/mL or if insulin treatment was required from the time of diagnosis. T2DM was diagnosed based on absence of ketosis, or fasting C-peptide ≥0.6 PMol/mL and stimulated >1.0 PMoL/mL, or response to oral hypoglycemic agents for more than 2 years. We calculated the incidence rates of retinopathy (presence of at least one definite microaneurysm by retinal photography), nephropathy (urinary albumin excretion ≥30 μg/mg of creatinine) and neuropathy (vibration perception threshold ≥20 V) per 1000 person-years of follow up. RESULTS Among the 4555 individuals with childhood and adolescent-onset diabetes, 71.4% had T1DM, 19.5% T2DM and 9.1% other forms of diabetes. Age at first visit and duration of diabetes were significantly higher in T2DM when compared to T1DM. The age adjusted incidence of retinopathy was 52.9/1000 person years (Confidence Intervals [CI]: 42.9-62.8) in T1DM and 49.8/1000 person years (CI 30.8-68.8) in T2DM; nephropathy, 6.2 (CI 3.3-9.0) and 13.8 (CI 5.6-22.0); and neuropathy, 8.8(CI 3.6-14.0) and 24.0 (CI 9.8-38.2) in T1DM and T2DM, respectively. CONCLUSION The incidence of microvascular complications is high among childhood and adolescent-onset T1DM and T2DM and these calls for more aggressive control of diabetes.
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Affiliation(s)
- Anandakumar Amutha
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Unnikrishnan Ranjit
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Ranjit Mohan Anjana
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | | | | | | | | | - Routray Philips
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Sengottuvel Kayalvizhi
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Prasanna Kumar Gupta
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | | | - Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
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25
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Can nasal septum deviation be one of the factors affecting diabetic retinopathy? JOURNAL OF SURGERY AND MEDICINE 2020. [DOI: 10.28982/josam.784139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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26
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Miravet-Jiménez S, Pérez-Unanua M, Alonso-Fernández M, Escobar-Lavado F, González-Mohino Loro B, Piera-Carbonell A. Manejo de la diabetes mellitus tipo 2 en adolescentes y adultos jóvenes en atención primaria. Semergen 2020; 46:415-424. [DOI: 10.1016/j.semerg.2019.11.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 11/04/2019] [Accepted: 11/05/2019] [Indexed: 12/20/2022]
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Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE. Young-onset type 2 diabetes mellitus - implications for morbidity and mortality. Nat Rev Endocrinol 2020; 16:321-331. [PMID: 32203408 DOI: 10.1038/s41574-020-0334-z] [Citation(s) in RCA: 254] [Impact Index Per Article: 50.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/13/2020] [Indexed: 12/20/2022]
Abstract
Accumulating data suggest that type 2 diabetes mellitus (T2DM) in younger people (aged <40 years), referred to as young-onset T2DM, has a more rapid deterioration of β-cell function than is seen in later-onset T2DM. Furthermore, individuals with young-onset T2DM seem to have a higher risk of complications than those with type 1 diabetes mellitus. As the number of younger adults with T2DM increases, young-onset T2DM is predicted to become a more frequent feature of the broader diabetes mellitus population in both developing and developed nations, particularly in certain ethnicities. However, the magnitude of excess risk of premature death and incident complications remains incompletely understood; likewise, the potential reasons for this excess risk are unclear. Here, we review the evidence pertaining to young-onset T2DM and its current and future burden of disease in terms of incidence and prevalence in both developed and developing nations. In addition, we highlight the associations of young-onset T2DM with premature mortality and morbidity.
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Affiliation(s)
- Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia.
| | - Julian W Sacre
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Jessica L Harding
- Division of Diabetes Translation, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA
| | - Edward W Gregg
- Faculty of Medicine, School of Public Health, Imperial College, London, UK
| | - Paul Z Zimmet
- Monash University, Department of Diabetes, Melbourne, Victoria, Australia
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia
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28
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Barrett T, Jalaludin MY, Turan S, Hafez M, Shehadeh N. Rapid progression of type 2 diabetes and related complications in children and young people-A literature review. Pediatr Diabetes 2020; 21:158-172. [PMID: 31804738 PMCID: PMC7028065 DOI: 10.1111/pedi.12953] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 10/25/2019] [Accepted: 12/02/2019] [Indexed: 01/05/2023] Open
Abstract
Type 2 diabetes (T2D) is suggested to progress faster in children and young people vs type 1 diabetes (T1D) in the same age group and T2D in adults. We reviewed the evidence base for this. A literature search was performed of PubMed-indexed publications between 2000 and 2018, for the terms "pediatric" and "T2D." Results were combined and filtered for those relating to "progression." Searches of abstract books from Latin American and Asian congresses were performed to include these populations. Pediatric populations were defined as <25 completed years of age. Of the articles and congress abstracts found, 30 were deemed relevant. Dividing the studies into categories based on how T2D progresses, we found the following: (a) yearly beta-cell function deterioration was shown to be 20% to 35% in children with T2D compared with 7% to 11% in adults with T2D, despite similar disease durations; (b) retinopathy progression was likely dependent on diabetes duration rather than diabetes type; however, nephropathy, neuropathy and probably hypertension progressed faster in youth-onset T2D vs T1D. Nephropathy progression was similar to adults with T2D, allowing for disease duration. Youth with T2D had a worse cardiovascular (CV) risk profile than youth with T1D, and a faster progression to CV death. (c) Progression to treatment failure was faster in youth-onset T2D vs adult-onset T2D. Substantial evidence exists for faster progression of T2D in pediatric patients vs T1D or adult-onset T2D. New treatments targeting the pathology are needed urgently to address this issue.
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Affiliation(s)
- Timothy Barrett
- Institute of Cancer and Genomic SciencesUniversity of BirminghamBirminghamUK
| | | | - Serap Turan
- Department of Pediatrics, Subdivision of Endocrinology and DiabetesMarmara University, School of MedicineIstanbulTurkey
| | - Mona Hafez
- Diabetes and Endocrinology Unit, Department of PediatricsCairo UniversityCairoEgypt
| | - Naim Shehadeh
- Endocrinology, Diabetes & Metabolism InstituteRambam Health Care CampusHaifaIsrael
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Investigation of the Mechanism Underlying Calcium Dobesilate-Mediated Improvement of Endothelial Dysfunction and Inflammation Caused by High Glucose. Mediators Inflamm 2019; 2019:9893682. [PMID: 31780874 PMCID: PMC6855025 DOI: 10.1155/2019/9893682] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 08/15/2019] [Accepted: 09/16/2019] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Calcium dobesilate (CaD) is widely used to treat diabetic retinopathy. Recent studies have demonstrated that CaD exerts protective effects against diabetic nephropathy. The aim of this study was to elucidate the molecular and cellular mechanisms underlying the protective effects of CaD. Methods Human umbilical vein endothelial cells (HUVECs) were cultured with different D-glucose concentrations to determine the effects of high glucose on HUVEC gene expression. HUVECs were also incubated with CaD (25 μM, 50 μM, and 100 μM) for 3 days to determine the effects of CaD on HUVEC viability. db/db mice were treated with CaD. 2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) blocked the nuclear factor-κB (NF-κB) pathway in HUVECs. A pentraxin 3 (PTX3) small interfering RNA (siRNA) intervention experiment was performed in the cells. An adenovirus-encapsulated PTX3 siRNA intervention experiment was performed in db/db mice. Western blot and real-time PCR analyses were used to detect PTX3, p-IKBa/IKBa (I-kappa-B-alpha), and p-eNOS/eNOS (endothelial nitric oxide synthase) expression in mice and HUVECs. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining were used to observe renal tissue damage in mice. PTX3 expression was observed by immunohistochemical staining. Results CaD downregulated the expression of PTX3 and p-IKBa/IKBa and upregulated the expression of p-eNOS/eNOS in vitro. When TPCA-1 was used, high glucose induced high PTX3 expression, and the expression of p-eNOS/eNOS increased. After PTX3 gene silencing, the expression of p-eNOS/eNOS also increased. In vivo, CaD reduced the expression of PTX3 and p-IKBa/IKBa in the kidneys of db/db mice and increased the expression of p-eNOS/eNOS. After PTX3 gene silencing, the urine protein and renal function of db/db mice were ameliorated, the glomerular extracellular matrix was decreased, and the expression of p-eNOS/eNOS was increased. Conclusions Our results suggested that CaD may inhibit the expression of PTX3 by altering the IKK/IKB/NF-κB pathway, thereby improving endothelial dysfunction in HUVECs. PTX3 may be a potential therapeutic target for DKD.
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30
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Reinhardt M, Cushman TR, Thearle MS, Krakoff J. Epicardial adipose tissue is a predictor of decreased kidney function and coronary artery calcification in youth- and early adult onset type 2 diabetes mellitus. J Endocrinol Invest 2019; 42:979-986. [PMID: 30674009 DOI: 10.1007/s40618-019-1011-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 01/16/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE To examine the association of epicardial and pericardial fat volume (EFV, PFV) with cardiovascular risk factors and kidney function in Native Americans of southwestern heritage with youth and early adult onset type 2 diabetes mellitus (T2DM) versus healthy controls. METHODS Using computed tomography, we quantified EFV and PFV in 149 Native Americans (92 women, 57 men), 95 of which had T2DM (38 diagnosed prior to age 20 years). Duration of T2DM, mean carotid arterial mass (AM), coronary artery calcification (CAC), IL-6, and estimated glomerular filtration rate eGFRcr(CKD-EPI) were measured. RESULTS EFV and PFV were associated with BMI (r = 0.37, p < 0.0001; r = 0.26, p = 0.001) and did not differ between onset age-groups and controls (p > 0.05). EFV was associated with AM only in controls (r = 0.51, p < 0.0001). After adjustment for BMI, T2DM duration, HbA1C, age, and sex, EFV was a predictor of CAC and IL-6 concentrations in early adult onset T2DM (β = 0.05 ± 0.02 cm3, p = 0.03; β = 0.05 ± 0.01 pg/ml/cm3, p = 0.002). EFV and PFV were independent predictors of reduced eGFRcr(CKD-EPI) in the youth onset T2DM group (β = -0.3 ± 0.08 ml/min/cm3, p = 0.001; β = -0.25 ± 0.05 ml/min/cm3, p < 0.0001). CONCLUSIONS Epicardial fat volume may be a risk factor for heart disease in individuals with early adult onset T2DM and a predictor of decreased kidney function in individuals with youth onset T2DM.
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Affiliation(s)
- M Reinhardt
- Obesity and Diabetes Clinical Research Section, Department of Health and Human Services, Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 N. 16th Street, Phoenix, AZ, 85016, USA.
- Department of Diagnostic and Interventional Radiology, University of Leipzig Medical Center, Liebigstraße 20, 04103, Leipzig, Germany.
| | - T R Cushman
- Obesity and Diabetes Clinical Research Section, Department of Health and Human Services, Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 N. 16th Street, Phoenix, AZ, 85016, USA
| | - M S Thearle
- Obesity and Diabetes Clinical Research Section, Department of Health and Human Services, Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 N. 16th Street, Phoenix, AZ, 85016, USA
| | - J Krakoff
- Obesity and Diabetes Clinical Research Section, Department of Health and Human Services, Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 N. 16th Street, Phoenix, AZ, 85016, USA
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Mora-Ortiz M, Nuñez Ramos P, Oregioni A, Claus SP. NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice. Metabolomics 2019; 15:89. [PMID: 31179513 PMCID: PMC6556514 DOI: 10.1007/s11306-019-1548-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 05/24/2019] [Indexed: 12/29/2022]
Abstract
INTRODUCTION The rapid expansion of Type 2 Diabetes (T2D), that currently affects 90% of people suffering from diabetes, urges us to develop a better understanding of the metabolic processes involved in the disease process in order to develop better therapies. The most commonly used model for T2D research is the db/db (BKS.Cg-Dock7 < m > +/+ Lepr < db >/J) mouse model. Yet, a systematic 1H NMR based metabolomics characterisation of most tissues in this animal model has not been published. Here, we provide a systematic organ-specific metabolomics analysis of this widely employed model using NMR spectroscopy. OBJECTIVES The aim of this study was to characterise the metabolic modulations associated with T2D in db/db mice in 18 relevant biological matrices. METHODS High-resolution 1H-NMR and 2D-NMR spectroscopy were applied to 18 biological matrices of 12 db/db mice (WT control n = 6, db/db = 6) aged 22 weeks, when diabetes is fully established. RESULTS 61 metabolites associated with T2D were identified. Kidney, spleen, eye and plasma were the biological matrices carrying the largest metabolomics modulations observed in established T2D, based on the total number of metabolites that showed a statistical difference between the diabetic and control group in each tissue (16 in each case) and the strength of the O-PLS DA model for each tissue. Glucose and glutamate were the most commonly associated metabolites found significantly increased in nine biological matrices. Investigated sections where no increase of glucose was associated with T2D include all intestinal segments (i.e. duodenum, jejunum, ileum and colon). Microbial co-metabolites such as acetate and butyrate, used as carbon sources by the host, were identified in excess in the colonic tissues of diabetic individuals. CONCLUSIONS The metabolic biomarkers identified using 1H NMR-based metabolomics will represent a useful resource to explore metabolic pathways involved in T2D in the db/db mouse model.
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Affiliation(s)
- Marina Mora-Ortiz
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights Campus, P.O. Box 226, Reading, RG6 6AP, UK.
- Department of Twin Research, Kings' College London, St Thomas' Hospital Campus, Westminster Bridge Road, London, SE1 7EW, UK.
| | - Patricia Nuñez Ramos
- Facultad de Medicina, Universidad de Extremadura, Campus de Badajoz, C.P. 06006, Badajoz, Spain
| | - Alain Oregioni
- MRC Biomedical NMR Centre, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
| | - Sandrine P Claus
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights Campus, P.O. Box 226, Reading, RG6 6AP, UK.
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Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by the American Diabetes Association. Diabetes Care 2018; 41:2648-2668. [PMID: 30425094 PMCID: PMC7732108 DOI: 10.2337/dci18-0052] [Citation(s) in RCA: 216] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Silva Arslanian
- Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, University of Pittsburgh, Pittsburgh, PA
- Center for Pediatric Research in Obesity and Metabolism, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - Fida Bacha
- Children's Nutrition Research Center, Texas Children's Hospital and Baylor College of Medicine, Houston, TX
| | - Margaret Grey
- Yale School of Nursing, New Haven, CT
- Yale School of Medicine, New Haven, CT
| | | | - Neil H White
- Washington University School of Medicine in St. Louis, St. Louis, MO
| | - Philip Zeitler
- Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO
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Geletu AH, Teferra AS, Sisay MM, Teshome DF. Incidence and predictors of chronic kidney diseases among type 2 diabetes mellitus patients at St. Paul's Hospital, Addis Ababa, Ethiopia. BMC Res Notes 2018; 11:532. [PMID: 30064516 PMCID: PMC6069572 DOI: 10.1186/s13104-018-3618-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 07/19/2018] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVE This study aimed to estimate the incidence of chronic kidney disease and its predictors among newly diagnosed type 2 diabetes patients attending St. Paul's Hospital, Addis Ababa, Ethiopia. RESULTS The overall incidence of chronic kidney disease was a major public health issue among type 2 diabetes mellitus patients with 2178 (95% CI 12,801, 21,286) cases per 10,000 patient-months. Moreover, 62(14.25%) patients in the sample experienced chronic kidney disease. Old age [adjusted hazard ratio (AHR) = 1.06, 95%CI 1.03, 1.09], no diabetic retinopathy [AHR = 0.13, 95%CI 0.07-0.24], high density lipoprotein cholesterol ≥ 40 mg/dl [AHR = 0.55, 95%CI 0.31, 0.97] and high body mass index [AHR = 1.17, 95%CI 1.1, 1.25] were common factors for chronic kidney diseases.
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Affiliation(s)
- Alemayehu Hussen Geletu
- Department of Reproductive Health, School of Public Health, College of Medicine and Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Alemayehu Shimeka Teferra
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, 196, Gondar, Ethiopia
| | - Malede Mequanent Sisay
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, 196, Gondar, Ethiopia
| | - Destaw Fetene Teshome
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, 196, Gondar, Ethiopia
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Paddock E, Looker HC, Piaggi P, Knowler WC, Krakoff J, Chang DC. One-Hour Plasma Glucose Compared With Two-Hour Plasma Glucose in Relation to Diabetic Retinopathy in American Indians. Diabetes Care 2018; 41:1212-1217. [PMID: 29622542 PMCID: PMC5961391 DOI: 10.2337/dc17-1900] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 03/15/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We compared the ability of 1- and 2-h plasma glucose concentrations (1h-PG and 2h-PG, respectively), derived from a 75-g oral glucose tolerance test (OGTT), to predict retinopathy. 1h-PG and 2h-PG concentrations, measured in a longitudinal study of an American Indian community in the southwestern U.S., a population at high risk for type 2 diabetes, were analyzed to assess the usefulness of the 1h-PG to identify risk of diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS Cross-sectional (n = 2,895) and longitudinal (n = 1,703) cohorts were assessed for the prevalence and incidence of DR, respectively, in relation to deciles of 1h-PG and 2h-PG concentrations. Areas under the receiver operating characteristic (ROC) curves for 1h-PG and 2h-PG were compared with regard to predicting DR, as assessed by direct ophthalmoscopy. RESULTS Prevalence and incidence of DR, based on direct ophthalmoscopy, changed in a similar manner across the distributions of 1h-PG and 2h-PG concentrations. ROC analysis showed that 1h-PG and 2h-PG were of similar value in identifying prevalent and incident DR using direct ophthalmoscopy. 1h-PG cut points of 230 and 173 mg/dL were comparable to 2h-PG cut points of 200 mg/dL (type 2 diabetes) and 140 mg/dL (impaired glucose tolerance), respectively. CONCLUSIONS 1h-PG is a useful predictor of retinopathy risk, has a predictive value similar to that of 2h-PG, and may be considered as an alternative glucose time point during an OGTT.
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Affiliation(s)
- Ethan Paddock
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
| | - Helen C Looker
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
| | - Paolo Piaggi
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
| | - William C Knowler
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
| | - Jonathan Krakoff
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
| | - Douglas C Chang
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
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Huo L, Magliano DJ, Rancière F, Harding JL, Nanayakkara N, Shaw JE, Carstensen B. Impact of age at diagnosis and duration of type 2 diabetes on mortality in Australia 1997-2011. Diabetologia 2018; 61:1055-1063. [PMID: 29473119 DOI: 10.1007/s00125-018-4544-z] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 11/27/2017] [Indexed: 12/21/2022]
Abstract
AIMS/HYPOTHESIS Current evidence suggests that type 2 diabetes may have a greater impact on those with earlier diagnosis (longer duration of disease), but data are limited. We examined the effect of age at diagnosis of type 2 diabetes on the risk of all-cause and cause-specific mortality over 15 years. METHODS The data of 743,709 Australians with type 2 diabetes who were registered on the National Diabetes Services Scheme (NDSS) between 1997 and 2011 were examined. Mortality data were derived by linking the NDSS to the National Death Index. All-cause mortality and mortality due to cardiovascular disease (CVD), cancer and all other causes were identified. Poisson regression was used to model mortality rates by sex, current age, age at diagnosis, diabetes duration and calendar time. RESULTS The median age at registration on the NDSS was 60.2 years (interquartile range [IQR] 50.9-69.5) and the median follow-up was 7.2 years (IQR 3.4-11.3). The median age at diagnosis was 58.6 years (IQR 49.4-67.9). A total of 115,363 deaths occurred during 7.20 million person-years of follow-up. During the first 1.8 years after diabetes diagnosis, rates of all-cause and cancer mortality declined and CVD mortality was constant. All mortality rates increased exponentially with age. An earlier diagnosis of type 2 diabetes (longer duration of disease) was associated with a higher risk of all-cause mortality, primarily driven by CVD mortality. A 10 year earlier diagnosis (equivalent to 10 years' longer duration of diabetes) was associated with a 1.2-1.3 times increased risk of all-cause mortality and about 1.6 times increased risk of CVD mortality. The effects were similar in men and women. For mortality due to cancer (all cancers and colorectal and lung cancers), we found that earlier diagnosis of type 2 diabetes was associated with lower mortality compared with diagnosis at an older age. CONCLUSIONS/INTERPRETATION Our findings suggest that younger-onset type 2 diabetes increases mortality risk, and that this is mainly through earlier CVD mortality. Efforts to delay the onset of type 2 diabetes might, therefore, reduce mortality.
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Affiliation(s)
- Lili Huo
- Department of Endocrinology, Beijing Jishuitan Hospital, Beijing, People's Republic of China
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Level 4, 99 Commercial Road, Melbourne, VIC, 3004, Australia
| | - Dianna J Magliano
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Level 4, 99 Commercial Road, Melbourne, VIC, 3004, Australia.
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
| | - Fanny Rancière
- Inserm, U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Research Centre, Villejuif, France
- Paris Descartes University, Sorbonne Paris Cité, UMR1153, Paris, France
| | - Jessica L Harding
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Level 4, 99 Commercial Road, Melbourne, VIC, 3004, Australia
| | - Natalie Nanayakkara
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Jonathan E Shaw
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Level 4, 99 Commercial Road, Melbourne, VIC, 3004, Australia
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Bendix Carstensen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
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Zhou Y, Yuan J, Qi C, Shao X, Mou S, Ni Z. Calcium dobesilate may alleviate diabetes‑induced endothelial dysfunction and inflammation. Mol Med Rep 2017; 16:8635-8642. [PMID: 29039485 PMCID: PMC5779917 DOI: 10.3892/mmr.2017.7740] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 06/16/2017] [Indexed: 12/12/2022] Open
Abstract
Diabetic kidney disease (DKD) is a leading cause of end‑stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D‑glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC proliferation via cell counting kit‑8 assays. In addition, HUVEC angiogenesis was investigated via migration assays and fluorescein isothiocyanate (FITC)‑labelled bovine serum albumin (BSA) permeability assays. The content or distribution of markers of endothelial dysfunction [vascular endothelial growth factor (VEGF), VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule (ICAM)‑1, monocyte chemotactic protein (MCP)‑1 and pentraxin‑related protein (PTX3)] was evaluated via reverse transcription‑quantitative polymerase chain reaction and western blotting. HG treatment induced increased in VEGF, VEGFR, endocan, ICAM‑1, MCP‑1 and PTX3 mRNA and protein expression in HUVECs. HG treatment for 24 to 48 h increased cell proliferation in a time‑dependent manner, but the cell proliferation rate was decreased at 72 h of HG treatment. Conversely, CaD inhibited abnormal cell proliferation. HG treatment also significantly enhanced HVUEC migration compared to the control treatment. In contrast, CaD treatment partially inhibited HUVEC migration compared to HG exposure. HG‑treated HUVECs exhibited increased FITC‑BSA permeability compared to control cells cultured in medium alone; however, CaD application prevented the HG‑induced increase in FITC‑BSA permeability and suppressed HG‑induced overexpression of endothelial markers (VEGF, VEGFR‑2, endocan) and inflammation markers (ICAM‑1, MCP‑1, PTX3) in HUVECs. CaD has angioprotective properties and protects endothelial cells partly by ameliorating HG‑induced inflammation. The current results demonstrated the potential applicability of CaD to the treatment of diabetic nephropathy, particularly during the early stages of this disease.
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Affiliation(s)
- Yijun Zhou
- Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
| | - Jiangzi Yuan
- Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
| | - Chaojun Qi
- Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
| | - Xinghua Shao
- Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
| | - Shan Mou
- Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
| | - Zhaohui Ni
- Department of Nephrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
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Koye DN, Shaw JE, Reid CM, Atkins RC, Reutens AT, Magliano DJ. Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies. Diabet Med 2017; 34:887-901. [PMID: 28164387 DOI: 10.1111/dme.13324] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/31/2017] [Indexed: 12/26/2022]
Abstract
AIMS The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. METHODS A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. RESULTS A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR < 60 ml/min/1.73 m2 using the Modification of Diet on Renal Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. CONCLUSIONS The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR < 60 ml/min/1.73 m2 is ~ 2-4% per year. Despite the wide variation in methods and study design, within a particular category of kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes.
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Affiliation(s)
- D N Koye
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - J E Shaw
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - C M Reid
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
- School of Public Health, Curtin University, Perth, Australia
| | - R C Atkins
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - A T Reutens
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - D J Magliano
- Department of Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
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Reddy S, Amutha A, Rajalakshmi R, Bhaskaran R, Monickaraj F, Rangasamy S, Anjana RM, Abhijit S, Gokulakrishnan K, Das A, Mohan V, Balasubramanyam M. Association of increased levels of MCP-1 and cathepsin-D in young onset type 2 diabetes patients (T2DM-Y) with severity of diabetic retinopathy. J Diabetes Complications 2017; 31:804-809. [PMID: 28336215 DOI: 10.1016/j.jdiacomp.2017.02.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Revised: 01/25/2017] [Accepted: 02/13/2017] [Indexed: 02/08/2023]
Abstract
AIM Young onset type 2 diabetes patients (T2DM-Y) have been shown to possess an increased risk of developing microvascular complications particularly diabetic retinopathy. However, the molecular mechanisms are not clearly understood. In this study, we investigated the serum levels of monocyte chemotactic protein 1 (MCP-1) and cathepsin-D in patients with T2DM-Y without and with diabetic retinopathy. METHODS In this case-control study, participants comprised individuals with normal glucose tolerance (NGT=40), patients with type 2 diabetes mellitus (T2DM=35), non-proliferative diabetic retinopathy (NPDR=35) and proliferative diabetic retinopathy (PDR=35). Clinical characterization of the study subjects was done by standard procedures and MCP-1 and cathepsin-D were measured by ELISA. RESULTS Compared to control individuals, patients with T2DM-Y, NPDR and PDR exhibited significantly (p<0.001) higher levels of MCP-1. Cathepsin-D levels were also significantly (p<0.001) higher in patients with T2DM-Y without and with diabetic retinopathy. Correlation analysis revealed a positive association (p<0.001) between MCP-1 and cathepsin-D levels. There was also a significant negative correlation of MCP1/cathepsin-D with C-peptide levels. The association of increased levels of MCP-1/cathepsin-D in patients with DR persisted even after adjusting for all the confounding factors. CONCLUSION As both MCP-1 and cathepsin-D are molecular signatures of cellular senescence, we suggest that these biomarkers might be useful to predict the development of retinopathy in T2DM-Y patients.
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Affiliation(s)
- Sruthi Reddy
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Anandakumar Amutha
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Ramachandran Rajalakshmi
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Regin Bhaskaran
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Finny Monickaraj
- Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Sampathkumar Rangasamy
- Neurogenomics Division, Translational Genomics Research Institute, (TGen), Phoenix, AZ, USA
| | - Ranjit Mohan Anjana
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Shiny Abhijit
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Kuppan Gokulakrishnan
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Arup Das
- Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Viswanathan Mohan
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India
| | - Muthuswamy Balasubramanyam
- Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India..
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Naylor LH, Davis EA, Kalic RJ, Paramalingam N, Abraham MB, Jones TW, Green DJ. Exercise training improves vascular function in adolescents with type 2 diabetes. Physiol Rep 2016; 4:4/4/e12713. [PMID: 26887327 PMCID: PMC4759041 DOI: 10.14814/phy2.12713] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro‐ and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13–21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym‐based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow‐mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual‐energy X‐ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic–hyperinsulinemic clamp protocol, cardiorespiratory fitness (V˙O2peak), and muscular strength (1RM). Exercise training increased FMD (P < 0.05), microvascular function (P < 0.05), total lean mass (P < 0.05), and muscle strength (P < 0.001). There were no changes in cardiorespiratory fitness, body weight, BMI, or M. In the control group, body weight (P < 0.01), BMI (P < 0.01), and total fat mass (P < 0.05) increased. At week 24, improvements in vascular function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes.
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Affiliation(s)
- Louise H Naylor
- School of Sport Science, Exercise & Health, The University of Western Australia, Crawley, Australia
| | - Elizabeth A Davis
- School of Paediatric and Child Health, The University of Western Australia, Crawley, Australia Telethon Kids Institute, The University of Western Australia, Subiaco, Australia Department of Endocrinology and Diabetes, Princess Margaret Hospital, Subiaco, Australia
| | - Rachelle J Kalic
- Telethon Kids Institute, The University of Western Australia, Subiaco, Australia Department of Endocrinology and Diabetes, Princess Margaret Hospital, Subiaco, Australia
| | - Niru Paramalingam
- Telethon Kids Institute, The University of Western Australia, Subiaco, Australia Department of Endocrinology and Diabetes, Princess Margaret Hospital, Subiaco, Australia
| | - Mary B Abraham
- School of Paediatric and Child Health, The University of Western Australia, Crawley, Australia Department of Endocrinology and Diabetes, Princess Margaret Hospital, Subiaco, Australia
| | - Timothy W Jones
- School of Paediatric and Child Health, The University of Western Australia, Crawley, Australia Telethon Kids Institute, The University of Western Australia, Subiaco, Australia Department of Endocrinology and Diabetes, Princess Margaret Hospital, Subiaco, Australia
| | - Daniel J Green
- School of Sport Science, Exercise & Health, The University of Western Australia, Crawley, Australia Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
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40
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Oester IMB, Kloppenborg JT, Olsen BS, Johannesen J. Type 2 diabetes mellitus in Danish children and adolescents in 2014. Pediatr Diabetes 2016; 17:368-73. [PMID: 26111830 DOI: 10.1111/pedi.12291] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 05/07/2015] [Accepted: 05/26/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/OBJECTIVE The global increase in childhood obesity has in some countries been followed by an increase in type 2 diabetes mellitus (T2DM); however, the prevalence of T2DM among Danish children and adolescents is currently unknown. The aims of this cross-sectional study were to determine the prevalence of T2DM in children and adolescents in Denmark together with status on treatment, metabolic control, and late diabetic complications. METHODS Individuals were identified in the Danish Registry for Diabetes in Children and Adolescents (DanDiabKids), and clinical information regarding these was obtained from the respective pediatric departments. RESULTS In total, seven young individuals (three boys) with T2DM were identified, according to the American Diabetes Association (ADA)/International Society of Pediatric and Adolecent Diabetes (ISPAD) guidelines, leading to a prevalence of T2DM at 0.6/100 000 inhabitants in Denmark. Only three of the patients had hyperglycemic symptoms at diagnosis. One boy was overweight and six were obese (two boys). Currently, no patients fulfill the treatment target of glycosylated hemoglobin (HbA1c) <7.0% (53 mmol/mol) according to the guidelines for treatment of diabetes. CONCLUSIONS In 2014, there is no increasing prevalence of T2DM in children and adolescents in Denmark. Nevertheless, the current treatment regimen is not satisfying, as none of the patients truly fulfill the treatment target.
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Affiliation(s)
| | | | | | - Jesper Johannesen
- Department of Pediatrics, Copenhagen University Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
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Amutha A, Mohan V. Diabetes complications in childhood and adolescent onset type 2 diabetes-a review. J Diabetes Complications 2016; 30:951-7. [PMID: 26970673 DOI: 10.1016/j.jdiacomp.2016.02.009] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 01/09/2016] [Accepted: 02/07/2016] [Indexed: 12/15/2022]
Abstract
Diabetes mellitus is one of the most common endocrine disorders in children. Earlier, diabetes in children was almost exclusively type 1 diabetes. Recently, the scenario has changed and increasing numbers of children and adolescent T2DM are being diagnosed. As the epidemic of T2DM shifts to children and adolescents, there is an increased risk of development of micro and macrovascular complications. This could potentially affect the economy of the nation apart from posing a large burden to the individual and his or her family. Prevention and treatment are especially important, given the fact that onset at an early age increases the risk of developing micro and macrovascular complications due to increased duration of exposure to hyperglycemia and other metabolic abnormalities. Diagnosing children and adolescents with T2DM early and instituting good control of all risk factors could yield good results in the prevention of long term complications of diabetes. This review focuses on the prevalence of complications of diabetes among children and adolescents with T2DM.
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Affiliation(s)
- Anandakumar Amutha
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, Gopalapuram, Chennai, India
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, Gopalapuram, Chennai, India.
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Fathy C, Patel S, Sternberg P, Kohanim S. Disparities in Adherence to Screening Guidelines for Diabetic Retinopathy in the United States: A Comprehensive Review and Guide for Future Directions. Semin Ophthalmol 2016; 31:364-77. [PMID: 27116205 DOI: 10.3109/08820538.2016.1154170] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Diabetic retinopathy (DR) is the leading cause of new-onset blindness in American adults aged 20-74 years old. The number of diabetics living with diagnosed DR increased by 89%, from 4.06 million to 7.69 million, between 2000 and 2010. Projected numbers from the Vision Health Initiative by the CDC predict that the rate of DR will triple by 2050, from 5.5 million people living with DR to 16 million. Screening guidelines aim to detect cases early because the treatments for DR can reduce severe vision loss by up to 94%. However, adherence to these guidelines is quite low. It is estimated that more than half of patients with diabetes may fail to receive necessary screening. Risk factors for non-screening discussed in this study include low health literacy, lack of access to care, pregnancy, physician adherence to guidelines, unique factors present in different minority populations, gender and age disparities, and living in rural regions. This paper also aims to address potential interventions that may improve adherence rates.
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Affiliation(s)
- Cherie Fathy
- a Department of Ophthalmology and Visual Sciences , Vanderbilt University Medical Center , Nashville , TN , USA
| | - Shriji Patel
- a Department of Ophthalmology and Visual Sciences , Vanderbilt University Medical Center , Nashville , TN , USA
| | - Paul Sternberg
- a Department of Ophthalmology and Visual Sciences , Vanderbilt University Medical Center , Nashville , TN , USA
| | - Sahar Kohanim
- a Department of Ophthalmology and Visual Sciences , Vanderbilt University Medical Center , Nashville , TN , USA
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Hannon TS, Arslanian SA. The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes. Ann N Y Acad Sci 2015; 1353:113-37. [PMID: 26448515 DOI: 10.1111/nyas.12939] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 08/17/2015] [Accepted: 08/19/2015] [Indexed: 12/18/2022]
Abstract
The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high-risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in β cell function and relative insulin deficiency in the absence of diabetes-related immune markers. In contrast to adult T2D, the decline in β cell function in youth T2D is three- to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes-related morbidity and mortality at younger ages.
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Affiliation(s)
- Tamara S Hannon
- Indiana University School of Medicine, Department of Pediatrics, Sections of Pediatric Endocrinology & Diabetology and Pediatric Comparative Effectiveness Research, Indianapolis, Indiana
| | - Silva A Arslanian
- Children's Hospital of University of Pittsburgh Medical Center, Department of Pediatrics, Divisions of Weight Management and Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Pittsburgh, Pennsylvania
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Svensson MK, Tyrberg M, Nyström L, Arnqvist HJ, Bolinder J, Östman J, Gudbjörnsdottir S, Landin-Olsson M, Eriksson JW. The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors. Diabetes Metab Res Rev 2015; 31:138-46. [PMID: 25044633 DOI: 10.1002/dmrr.2574] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 06/17/2014] [Indexed: 12/14/2022]
Abstract
AIMS The main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34 years). METHODS All 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19 years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. RESULTS After median 17 years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1 kg/m²), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p = 0.041), BMI (p = 0.012) and HbA1c (p < 0.001) were significant predictors of developing diabetic nephropathy between 9 and 17 years of diabetes. At 17 years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1 mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.05 1.12 per 1 mmHg increase) were associated with DN. CONCLUSIONS Patients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9 years of follow-up was a risk marker for later development of diabetic nephropathy.
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Affiliation(s)
- M K Svensson
- Department of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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Do DV, Wang X, Vedula SS, Marrone M, Sleilati G, Hawkins BS, Frank RN. Blood pressure control for diabetic retinopathy. Cochrane Database Syst Rev 2015; 1:CD006127. [PMID: 25637717 PMCID: PMC4439213 DOI: 10.1002/14651858.cd006127.pub2] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. OBJECTIVES The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes. SEARCH METHODS We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data. SELECTION CRITERIA We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo. DATA COLLECTION AND ANALYSIS Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost-effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials. MAIN RESULTS We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti-hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government-sponsored grants and institutional support.Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants.For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow-up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4- to 5-year follow-up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review.The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings.The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials. AUTHORS' CONCLUSIONS Hypertension is a well-known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy.
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Affiliation(s)
- Diana V Do
- Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Xue Wang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | - Michael Marrone
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | - Barbara S Hawkins
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Robert N Frank
- Department of Ophthalmology, Kresge Eye Institute, Detroit, Michigan, USA
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Wilmot E, Idris I. Early onset type 2 diabetes: risk factors, clinical impact and management. Ther Adv Chronic Dis 2014; 5:234-44. [PMID: 25364491 DOI: 10.1177/2040622314548679] [Citation(s) in RCA: 170] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities', in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic.
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Affiliation(s)
- Emma Wilmot
- Department of Diabetes & Endocrinology, Royal Derby Hospital, Uttoxeter Road, Derby, UK
| | - Iskandar Idris
- Royal Derby Hospital and Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Nottingham, UK
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Fekete A, Vannay Á. [Importance of diabetic nephropathy in childhood. Clinical findings and basic research in recent decades]. Orv Hetil 2014; 155:141-50. [PMID: 24440726 DOI: 10.1556/oh.2014.29814] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Over the past decades diabetes mellitus is becoming a global pandemic affecting more than 371 million people worldwide. Parallel with the increasing prevalence of type 1 diabetes, there is a growing number of type 2 diabetes cases among children and adolescents that poses new challenges to pediatricians. Diabetic nephropathy is one of the major causes of end stage renal disease, developing in approximately 30% of diabetic patients. However, overt nephropathy is rare in childhood; screening and ongoing assessment for the earliest manifestation of renal injury is extremely important in this young population, as well. Although in the past decades intensive research activity focused on understanding of the pathomechanism of diabetic nephropathy and invention of new therapeutic approaches, prevention and definitive care are still urgently needed. The clinical section of the article summarizes the present state of epidemiology, diagnosis and current therapies of childhood diabetic nephropathy. Then, the authors discuss the state of basic research and show a few promising targets for drug development.
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Affiliation(s)
- Andrea Fekete
- Semmelweis Egyetem, Általános Orvostudományi Kar I. Gyermekgyógyászati Klinika, MTA-SE Lendület Diabétesz Kutatócsoport Budapest Bókay J. u. 53. 1083
| | - Ádám Vannay
- MTA-SE Gyermekgyógyászati és Nephrologiai Kutatócsoport Budapest
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Panagiotopoulos C, Nguyen D, Smith J. Cardiovascular risk factors and health behaviours in elementary school-age Inuvialuit and Gwich'in children. Paediatr Child Health 2014; 19:256-60. [PMID: 24855429 PMCID: PMC4029239 DOI: 10.1093/pch/19.5.256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2014] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES To determine cardiovascular risk factors and health behaviours in Aboriginal children from the Beaufort-Delta region (Northwest Territories). METHODS A total of 91 elementary school-age children underwent a cross-sectional assessment of body mass index, waist circumference, blood pressure and aerobic fitness. Healthy living knowledge and behaviours, including frequency of self-reported physical activity (PA) and dietary intake, were also evaluated. RESULTS A total of 49.5% of children were obese/overweight and 31.9% had elevated blood pressure. The percentages having one, two or three cardiovascular risk factor(s) were 64.4%, 42.2% and 15.6%, respectively, with no significant difference between boys and girls. Overall, the students obtained higher mean scores in the areas of healthy PA, body image, self-esteem and nutritious beverage knowledge (89%, 85%, 79% and 71% of the maximum scores, respectively). The lowest scores were in nutritious food consumption and healthy PA frequency (46% and 56% of the maximum scores, respectively). On average, children consumed 2.7 L of sugar-sweetened beverages weekly and <2 servings of fruits or vegetables daily. Children spent approximately 2 h per day watching television, playing games or using a computer. CONCLUSION There is an urgent need for community-based approaches to address the high rates of obesity and related cardiovascular risk factors among these Aboriginal children. Given the disconnect between healthy living knowledge and behaviour, it is important that future treatment programs address other barriers faced by Aboriginal populations living in rural and remote regions, including the high cost and limited access to high-quality nutritious foods and beverages, and limited access to indoor recreational programs over the long winter season.
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Affiliation(s)
- Constadina Panagiotopoulos
- Department of Pediatrics, University of British Columbia
- Child & Family Research Institute
- British Columbia Children’s Hospital, Vancouver, British Columbia
| | - Duc Nguyen
- Department of Pediatrics, University of British Columbia
| | - Jane Smith
- Beaufort-Delta Health and Social Services Authority, Northwest Territories
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Rajalakshmi R, Amutha A, Ranjani H, Ali MK, Unnikrishnan R, Anjana RM, Narayan KMV, Mohan V. Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset type 1 and type 2 diabetes. J Diabetes Complications 2014; 28:291-7. [PMID: 24512748 DOI: 10.1016/j.jdiacomp.2013.12.008] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 11/29/2013] [Accepted: 12/23/2013] [Indexed: 11/22/2022]
Abstract
AIM To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). METHODS T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. RESULTS The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. CONCLUSION Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR.
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Affiliation(s)
- Ramachandran Rajalakshmi
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, India
| | - Anandakumar Amutha
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, India
| | - Harish Ranjani
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, India
| | - Mohammed K Ali
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Ranjit Unnikrishnan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, India
| | - Ranjit Mohan Anjana
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, India
| | - K M Venkat Narayan
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, India.
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Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care 2014; 37:436-43. [PMID: 24130346 DOI: 10.2337/dc13-0954] [Citation(s) in RCA: 192] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate the risk of complications in youth with type 2 diabetes. RESEARCH DESIGN AND METHODS Population-based cohorts of 342 youth (1-18 years of age) with prevalent type 2 diabetes, 1,011 youth with type 1 diabetes, and 1,710 nondiabetic control youth were identified between 1986 and 2007 from a clinical registry and linked to health care records to assess long-term outcomes using ICD-9CM and ICD-10CA codes. RESULTS Youth with type 2 diabetes had an increased risk of any complication (hazard ratio 1.47 [95% CI 1.02-2.12]). Significant adverse clinical factors included age at diagnosis (1.08 [1.02-2.12]), HbA1c (1.06 [1.01-1.12]), and, surprisingly, renin-angiotensin-aldosterone system (RAAS) inhibitor use (1.75 [1.27-2.41]). HNF-1α G319S polymorphism was protective in the type 2 diabetes cohort (0.58 [0.34-0.99]). Kaplan-Meier statistics revealed an earlier diagnosis of renal and neurologic complications in the type 2 diabetes cohort, manifesting within 5 years of diagnosis. No difference in retinopathy was seen. Cardiovascular and cerebrovascular diseases were rare; however, major complications (dialysis, blindness, or amputation) started to manifest 10 years after diagnosis in the type 2 diabetes cohort. Youth with type 2 diabetes had higher rates of all outcomes than nondiabetic control youth and an overall 6.15-fold increased risk of any vascular disease. CONCLUSIONS Youth with type 2 diabetes exhibit complications sooner than youth with type 1 diabetes. Younger age at diagnosis is potentially protective, and glycemic control is an important modifiable risk factor. The unexpected adverse association between RAAS inhibitor use and outcome is likely a confounder by indication; however, further evaluation in young people is warranted.
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