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Park Y, Ko KS, Rhee BD. New Perspectives in Studying Type 1 Diabetes Susceptibility Biomarkers. Int J Mol Sci 2025; 26:3249. [PMID: 40244115 PMCID: PMC11989529 DOI: 10.3390/ijms26073249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/26/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
Type 1 diabetes (T1D) is generally viewed as an etiologic subtype of diabetes caused by the autoimmune destruction of the insulin-secreting β-cells. It has been known that autoreactive T cells unfortunately destroy healthy β-cells. However, there has been a notion of etiologic heterogeneity around the world implicating a varying incidence of a non-autoimmune subgroup of T1D related to insulin deficiency associated with decreased β cell mass, in which the β-cell is the key contributor to the disease. Beta cell dysfunction, reduced mass, and apoptosis may lead to insufficient insulin secretion and ultimately to the development of T1D. Interestingly, Korean as well as other ethnic genetic results have also suggested that genes related with insulin deficiency, let alone those of immune regulation, were associated with the risk of T1D in the young. Genes related with insulin secretion may influence the phenotype of diabetes differentially and different genes may be working on different steps of T1D development. Although we admit the consensus that islet autoimmunity is an essential component in the pathogenesis of T1D, however, dysfunction might occur not only in the immune system but also in the β-cells, the defect of which may induce further dysfunction of the immune system. These arguments stem from the fact that the β-cell might be the trigger of an autoimmune response. This emergent view has many parallels with the fact that by their nature and function, β-cells are prone to biosynthetic stress with limited measures for self-defense. Beta cell stress may induce an immune attack that has considerable negative effects on the production of a vital hormone, insulin. If then, both β-cell stress and islet autoimmunity can be harnessed as targets for intervention strategies. This also may explain why immunotherapy at best delays the progression of T1D and suggests the use of alternative therapies to expand β-cells, in combination with immune intervention strategies, to reverse the disease. Future research should extend to further investigate β-cell biology, in addition to studies of immunologic areas, to find appropriate biomarkers of T1D susceptibility. This will help to decipher β-cell characteristics and the factors regulating their function to develop novel therapeutic approaches.
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Affiliation(s)
- Yongsoo Park
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul 01757, Republic of Korea; (K.S.K.); (B.D.R.)
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Mori JI, Miyakoshi T, Yuzuriha H, Kondo T, Nishimori E, Naka M, Sato A, Komatsu M, Yamashita K, Aizawa T. Snap diagnosis of fulminant type 1 diabetes by the normalized glucose/HbA1c ratio. Endocr J 2024; 71:1093-1096. [PMID: 39135233 PMCID: PMC11778347 DOI: 10.1507/endocrj.ej24-0226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 07/09/2024] [Indexed: 11/06/2024] Open
Abstract
Elevated Fulminant Index (FI), [plasma glucose (PG)/glycosylated hemoglobin A1c (HbA1c)], was reportedly a sensitive index to differentiate fulminant type 1 diabetes (FT1D) from non-fulminant T1D (nFT1D). Aim of this study was to describe a better, but simpler index of FT1D. 49 and 52 patients with FT1D and nFT1D, respectively, were registered, and the discriminating ability of the rounded, normalized ratio, [PG (mmol/L) - 5.0]/[HbA1c (%) - 5.0], and the original ratio, [PG (mmol/L)]/[HbA1c (%)], was compared. Normalizing the ratio significantly raised its accuracy: area under the curve for receiver operating curve, AUROC (95%CI), 0.927 (0.858-0.964) and 0.851 (0.763-0.910), respectively, with and without the normalization (p < 0.01). Rounding of the figure into [PG (mmol/L) - 5.0]/[HbA1c (%) - 5.0] did not significantly sacrifice the discriminating ability of the index. Namely, the optimal cut point of rounded and normalized GAR, 10.0, showed 89.8% sensitivity. In conclusion, rounded, normalized (rn) GAR ≥10 (the rounded optimal cut-off) could be used for the snap diagnosis of FT1D.
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Affiliation(s)
- Jun-Ichiro Mori
- Department of Medical Education, Shinshu University, Matsumoto 390-8621, Japan
| | | | - Hanae Yuzuriha
- Resident of Internal Medicine, Aizawa Hospital, Matsumoto 390-8510, Japan
| | - Teruki Kondo
- Diabetes, Endocrinology and Metabolism, Nagano Chuo Hospital, Nagano 380-0814, Japan
| | - Eita Nishimori
- Department of Diabetes Medicine, Asama Central Hospital, Nagano 385-8558, Japan
| | - Motoji Naka
- Department of Diabetes Medicine, Asama Central Hospital, Nagano 385-8558, Japan
| | - Ai Sato
- Diabetes Center, Okaya City Hospital, Okaya 394-0028, Japan
| | - Mitsuhisa Komatsu
- Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University Hospital, Matsumoto 390-8621, Japan
| | - Koh Yamashita
- Diabetes Center, Aizawa Hospital, Matsumoto 390-8510, Japan
| | - Toru Aizawa
- Diabetes Center, Aizawa Hospital, Matsumoto 390-8510, Japan
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Wu D, Zheng R, Kan X, Hao L, Wei Y, Cao J. Early change of retinal nerve fiber layer in children with type 1 diabetes mellitus in northern China. J Pediatr Endocrinol Metab 2024; 37:341-346. [PMID: 38487852 DOI: 10.1515/jpem-2023-0446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 02/18/2024] [Indexed: 04/11/2024]
Abstract
OBJECTIVES This study aimed to identify discrepancies in the retinal nerve fiber layer (RNFL) between type 1 diabetes mellitus (T1DM) children without retinopathy and healthy subjects in northern China. METHODS This was a cross-sectional hospital-based study carried out from Jan 2019 until Jul 2021 at the department of pediatrics in Tianjin medical university general hospital. Children with T1DM but no retinal disease were screened. RNFL thickness was obtained via spectral domain optical coherence tomography. Disease duration, HbA1c, 25-hydroxyvitamin D level, insulin regimen, and diet control status were also collected. RESULTS A total of 20 children with T1DM and 20 matched health participants were enrolled. The mean age in the T1DM group was 10.3 ± 2.8 years, and the median duration of diabetes was 1 (range 1-3) year. Children with T1DM had thinner average RNFL than control subjects (105 ± 6 vs. 110 ± 11 μm, p=0.008), especially in temporal and nasal parts. There was a significant negative association between HbA1c levels and the RNFL thickness in the T1DM group (B (95 % confidence interval): -4.313 (-7.055 to -1.571); p=0.005). CONCLUSIONS In our study, the decreased thickness of RNFL was negatively associated with elevated HbA1c in children with early stages of T1DM.
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Affiliation(s)
- Dejing Wu
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, P.R. China
| | - Rongxiu Zheng
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, P.R. China
| | - Xuan Kan
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, P.R. China
| | - Liping Hao
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, P.R. China
| | - Ying Wei
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, P.R. China
| | - Jie Cao
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, P.R. China
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Waernbaum I, Lind T, Möllsten A, Dahlquist G. The incidence of childhood-onset type 1 diabetes, time trends and association with the population composition in Sweden: a 40 year follow-up. Diabetologia 2023; 66:346-353. [PMID: 36264296 PMCID: PMC9807495 DOI: 10.1007/s00125-022-05816-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 08/24/2022] [Indexed: 01/07/2023]
Abstract
AIMS/HYPOTHESIS During the 1980s and 1990s, the incidence of childhood-onset type 1 diabetes more than doubled in Sweden, followed by a plateau. In the present 40 year follow-up, we investigated if the incidence remained stable and whether this could be explained by increased migration from countries reporting lower incidences. METHODS We used 23,143 incident cases of childhood-onset type 1 diabetes reported between 1978 and 2019 to the nationwide, population-based Swedish Childhood Diabetes Registry and population data from Statistics Sweden. Generalised additive models and ANOVA were applied to analyse the effects of onset age, sex, time trends and parental country of birth and interaction effects between these factors. RESULTS The flattening of the incidence increase seems to remain over the period 2005-2019. When comparing the incidence of type 1 diabetes for all children in Sweden with that for children with both parents born in Sweden, the trends were parallel but at a higher level for the latter. A comparison of the incidence trends between individuals with Swedish backgrounds (high diabetes trait) and Asian backgrounds (low diabetes trait) showed that the Asian subpopulation had a stable increase in incidence over time. CONCLUSIONS/INTERPRETATION In Sweden, the increase in incidence of childhood-onset type 1 diabetes in the late 20th century has been approaching a more stable albeit high level over the last two decades. Increased immigration from countries with lower incidences of childhood-onset type 1 diabetes does not provide a complete explanation for the observed levelling off.
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Affiliation(s)
| | - Torbjörn Lind
- Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden
| | - Anna Möllsten
- Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden
| | - Gisela Dahlquist
- Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden
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Qiu J, Luo S, Yin W, Guo K, Xiang Y, Li X, Liu Z, Zhou Z. Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin. Front Immunol 2022; 13:968798. [PMID: 36451831 PMCID: PMC9702060 DOI: 10.3389/fimmu.2022.968798] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 10/07/2022] [Indexed: 12/05/2023] Open
Abstract
OBJECTIVE Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD). RESEARCH DESIGN AND METHODS We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin. RESULTS Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD. CONCLUSIONS IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.
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Affiliation(s)
- Junlin Qiu
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Shuoming Luo
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Wenfeng Yin
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Keyu Guo
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yufei Xiang
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Li
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhenqi Liu
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, United States
| | - Zhiguang Zhou
- Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China
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Diabetes Prevalence and Associated Risk Factors among Women in a Rural District of Nepal Using HbA1c as a Diagnostic Tool: A Population-Based Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19127011. [PMID: 35742264 PMCID: PMC9223207 DOI: 10.3390/ijerph19127011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/30/2022] [Accepted: 06/04/2022] [Indexed: 11/17/2022]
Abstract
Given the scarcity of data on diabetes prevalence and associated risk factors among women in rural Nepal, we aimed to examine this, using glycated hemoglobin (HbA1c) as a diagnostic tool. A cross-sectional survey addressing reproductive health and non-communicable diseases was conducted in 2012–2013 among non-pregnant, married women in Bolde, a rural district of Nepal. HbA1c ≥ 6.5% (48 mmol/mol) was used as diagnostic criterion for diabetes, a cut-off of 7.0% (53 mmol/mol) was used to increase the specificity. HbA1c was measured in 757 women (17–86 years). The prevalence of diabetes and prediabetes was 13.5% and 38.5%, respectively. When using 7.0% as a cut-off, the prevalence of diabetes was 5.8%. Aging, intake of instant noodles and milk and vegetarian food (ns) were associated with increased risk for diabetes. Waist circumference was higher among women with diabetes, although not significant. The women were uneducated (87.6%), and only 12% had heard about diabetes. In conclusion, we observed a higher prevalence of diabetes and prediabetes than anticipated among rural, Nepalese women. The increased risk was mainly attributed to dietary factors. In contrast to most previous studies in Nepal, we used HbA1c as diagnostic criterion.
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Rittiphairoj T, Owais M, Ward ZJ, Reddy CL, Yeh JM, Atun R. Incidence and prevalence of type 1 diabetes and diabetic ketoacidosis in children and adolescents (0–19 years) in Thailand (2015–2020): A nationwide population-based study. THE LANCET REGIONAL HEALTH - WESTERN PACIFIC 2022; 21:100392. [PMID: 35169761 PMCID: PMC8829760 DOI: 10.1016/j.lanwpc.2022.100392] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Background There is a lack of published studies on incidence of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) in Thailand. We aimed to estimate the national prevalence and incidence of T1D and DKA. Methods Using Thailand's nationwide population-based longitudinal data covering 69 million individuals, we included the entire children and adolescents recorded in the database. Diseases were identified using ICD-10 codes. We investigated the prevalence of T1D and cumulative incidence of T1D, T1D referral, DKA, and mortality risk of DKA in five years from 2015 to 2020. T1D and DKA annual incidence were also estimated. We present findings for the total population and by sex, age, and urban-rural residencies. Findings A total of 19,784,781 individuals aged less than 20 years were identified in 2015. The crude T1D prevalence in 2015 was 17·6 per 100,000 and crude T1D incidence rate was 5·0 per 100,000. T1D prevalence and cumulative incidence were significantly higher in older children (p < 0·001) and females (p < 0·001) than their counterparts. Among those with T1D, cumulative incidence of T1D referral was 42·4%. It was highest amongst children aged 5–14 years and was significantly higher among females (all p < 0·05). The crude DKA incidence rate at any point after diagnosis was 10·8%. The cumulative incidence of DKA was significantly higher in females and peaked in individuals aged 5–14 years (all p < 0·001). The DKA mortality risk was 258·2 per 100,000. Interpretation Older children and females had higher T1D prevalence. The DKA cumulative incidence and mortality risk were relatively low, and such incidence was peak in individuals aged 5–14 years. Funding Harvard University.
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Affiliation(s)
- Thanitsara Rittiphairoj
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA
- Division of Health Systems Management, Department of Community Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Corresponding author at: Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA.
| | - Maira Owais
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA
- Amherst College, Amherst, USA
| | - Zachary J. Ward
- Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, USA
| | - Ché L. Reddy
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA
| | - Jennifer M. Yeh
- Division of General Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Rifat Atun
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA
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James S, Maniam J, Cheung PT, Urakami T, von Oettingen J, Likitmaskul S, Ogle G. Epidemiology and phenotypes of diabetes in children and adolescents in non-European-origin populations in or from Western Pacific region. World J Clin Pediatr 2022; 11:173-195. [PMID: 35433305 PMCID: PMC8985498 DOI: 10.5409/wjcp.v11.i2.173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/09/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) incidence varies substantially between countries/ territories, with most studies indicating increasing incidence. In Western Pacific region (WPR), reported rates are much lower than European-origin populations. In contrast, there are reports of substantial numbers of young people with type 2 diabetes (T2D). A deeper understanding of T1D and T2D in the WPR may illuminate factors important in pathogenesis of these conditions. Furthermore, with varying resources and funding for diabetes treatment in this region, there is a need to more clearly determine the current burden of disease and also any gaps in knowledge. AIM To compile and summarise published epidemiologic and phenotypic data on childhood diabetes in non-European populations in and from WPR. METHODS Research articles were systematically searched from PubMed (MEDLINE), Embase, Cochrane library, and gray literature. Primary outcome measures were incidence and prevalence, with secondary measures including phenotypic descriptions of diabetes, including diabetes type categorization, presence of diabetic ketoacidosis (DKA) at onset, autoantibody positivity, C-peptide levels, and human leucocyte antigen phenotype. Extracted data were collected using a customized template. Three hundred and thirty relevant records were identified from 16 countries/territories, with analysis conducted on 265 (80.3%) records published from the year 2000. RESULTS T1D incidence ranged from < 1-7.3/100000 individuals/year, rates were highest in emigrant/ mixed populations and lowest in South-East Asia, with most countries/territories (71.4%) having no data since 1999. Incidence was increasing in all six countries/territories with data (annual increases 0.5%-14.2%, highest in China). Peak age-of-onset was 10-14 years, with a female case excess. Rate of DKA at onset varied from 19.3%-70%. Pancreatic autoantibodies at diagnosis were similar to European-origin populations, with glutamic acid decarboxylase-65 autoantibody frequency of 44.1%-64.5%, insulinoma-associated 2 autoantibody 43.5%-70.7%, and zinc transporter-8 autoantibody frequency 54.3% (one study). Fulminant T1D also occurs. T2D was not uncommon, with incidence in Japan and one Chinese study exceeding T1D rates. Monogenic forms also occurred in a number of countries. CONCLUSION T1D is less common, but generally has a classic phenotype. Some countries/ territories have rapidly increasing incidence. T2D is relatively common. Registries and studies are needed to fill many information gaps.
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Affiliation(s)
- Steven James
- School of Nursing, Midwifery and Paramedicine, University of the Sunshine Coast, Petrie 4502, Queensland, Australia
| | - Jayanthi Maniam
- Life for a Child Program, Diabetes NSW & ACT, Glebe 2017, New South Wales, Australia
| | - Pik-To Cheung
- Department of Paediatric Endocrinology, Genetics and Metabolism, Virtus Medical Group, Hong Kong, China
| | - Tatsuhiko Urakami
- Department of Pediatrics, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Julia von Oettingen
- Research Institute, McGill University Health Centre, Montreal H4A 3JI, Quebec, Canada
| | - Supawadee Likitmaskul
- Siriraj Diabetes Center, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Graham Ogle
- Life for a Child Program, Diabetes NSW & ACT, Glebe 2017, New South Wales, Australia
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Moon MK, Lee I, Lee A, Park H, Kim MJ, Kim S, Cho YH, Hong S, Yoo J, Cheon GJ, Choi K, Park YJ, Park J. Lead, mercury, and cadmium exposures are associated with obesity but not with diabetes mellitus: Korean National Environmental Health Survey (KoNEHS) 2015-2017. ENVIRONMENTAL RESEARCH 2022; 204:111888. [PMID: 34403664 DOI: 10.1016/j.envres.2021.111888] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/27/2021] [Accepted: 08/12/2021] [Indexed: 05/24/2023]
Abstract
BACKGROUND Associations of heavy metal exposures with obesity and obesity-related traits have been suggested, while those with nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are often inconsistent. METHODS This study included 3787 adults aged ≥19 years who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of toxic heavy metals with metabolic diseases. Lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine (uHg, uCd) or total blood (bPb, bHg). Body mass index (BMI) was calculated, and DM cases were identified through a self-answered medication history. Hepatic Steatosis Index (HSI) as a surrogating index of NAFLD, was calculated using hepatic enzyme measurements, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS Adults in the highest quartile of bPb, bHg, and uHg showed significantly elevated odds of obesity (BMI ≥25 kg/m2), compared to the lowest quartile (OR 1.58 for bPb, 1.92 for bHg, and 1.81 for uHg). HSI was positively correlated with bHg, uHg, and uCd concentrations. The odds of NAFLD (HSI ≥36) were also increased with increasing quartile of bHg, uHg, and uCd concentrations. For DM, bPb showed a significant negative association, while bHg and uCd exhibited non-monotonic and inconclusive associations. CONCLUSIONS Among the general adult population of Korea, both Pb and Hg exposures were associated with an increased risk of obesity. In addition, both Hg and Cd exposures were associated with increased odds of NAFLD. These metals, however, were not associated with an increased risk of DM.
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Affiliation(s)
- Min Kyong Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Inae Lee
- School of Public Health, Seoul National University, Seoul, South Korea
| | - Aram Lee
- Department of Environmental Health Sciences, Soonchunhyang University, Asan, South Korea
| | - Hyunwoong Park
- Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Min Joo Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Sunmi Kim
- School of Public Health, Seoul National University, Seoul, South Korea; Chemical Safety Research Center, Korea Research Institute of Chemical Technology, Daejeon, South Korea
| | - Yoon Hee Cho
- Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA
| | - Sooyeon Hong
- Environmental Health Research Division, National Institute of Environmental Research, Ministry of Environment, Incheon, Republic of Korea
| | - Jiyoung Yoo
- Environmental Health Research Division, National Institute of Environmental Research, Ministry of Environment, Incheon, Republic of Korea
| | - Gi Jeong Cheon
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyungho Choi
- School of Public Health, Seoul National University, Seoul, South Korea
| | - Young Joo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
| | - Jeongim Park
- Department of Environmental Health Sciences, Soonchunhyang University, Asan, South Korea.
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Wu H, Patterson CC, Zhang X, Ghani RBA, Magliano DJ, Boyko EJ, Ogle GD, Luk AOY. Worldwide estimates of incidence of type 2 diabetes in children and adolescents in 2021. Diabetes Res Clin Pract 2022; 185:109785. [PMID: 35189261 DOI: 10.1016/j.diabres.2022.109785] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/21/2022] [Accepted: 02/14/2022] [Indexed: 12/19/2022]
Abstract
AIMS We aimed to conduct a systematic review of published studies on the incidence of type 2 diabetes in children and adolescents aged under 20 years and provide worldwide incidence estimates for 2021. METHODS We used MEDLINE and EMBASE to identify studies reporting type 2 diabetes incidence in children and adolescents published between Jan 2000 and April 2021. We used a negative binomial regression model to develop a prediction equation to estimate incidence rates from country characteristics. We applied the resulting incidence predictions to country population data to estimate numbers of incident cases in children and adolescents by International Diabetes Federation (IDF) region and World Bank income classification group. RESULTS We estimate that there are approximately 41,600 new cases of diagnosed type 2 diabetes among children and adolescents in 2021 worldwide. Around 30% and 40% of the worldwide total incident cases are in IDF Western Pacific region and in World Bank upper-middle-income countries, respectively. The three countries with the highest estimated number of incident cases are China, India, and United States of America. CONCLUSIONS The number of newly diagnosed type 2 diabetes in children and adolescents is substantial. More reliable data are needed to track the incidence of type 2 diabetes in children and adolescents.
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Affiliation(s)
- Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | | | - Xinge Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Ruhina Binta A Ghani
- Centre for Public Health, Queen's University Belfast, United Kingdom; Health, Nutrition and Population Programme, BRAC, Bangladesh
| | | | - Edward J Boyko
- Seattle Epidemiologic Research and Information Center, VA Puget Sound, and Department of Medicine, University of Washington, Seattle, WA, USA
| | - Graham D Ogle
- Life for a Child Program, Diabetes NSW & ACT, 26 Arundel St., Glebe NSW 2037, Australia
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
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11
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Exposure to polycyclic aromatic hydrocarbons and volatile organic compounds is associated with a risk of obesity and diabetes mellitus among Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017. Int J Hyg Environ Health 2021; 240:113886. [PMID: 34864598 DOI: 10.1016/j.ijheh.2021.113886] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 11/23/2021] [Accepted: 11/23/2021] [Indexed: 01/06/2023]
Abstract
Environmental pollutants have been known to increase the risks of not only respiratory and cardiovascular disease but also metabolic diseases such as obesity and diabetes mellitus (DM). Polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) such as benzene and toluene are major constituents of environmental pollution. In the present study, we employed the population of the Korean National Environmental Health Survey (KoNEHS) Cycle 3 conducted between 2015 and 2017, and assessed the associations of urinary biomarkers for PAHs and VOCs exposure with obesity and DM. A total of 3787 adult participants were included and the urinary concentrations of four PAH metabolites and two VOC metabolites were measured. For correcting urine dilution, a covariate-adjusted standardization method was used. The highest quartiles of urinary 2-hydroxynaphthalene (2-NAP) [OR (95% confidence interval (CI)) = 1.46 (1.13, 1.87)] and sum of PAH metabolites [OR (95% CI) = 1.45 (1.13, 1.87)] concentrations were associated with a higher risk of obesity [body mass index (BMI)≥25 kg/m2]. BMI was positively associated with urinary 2-NAP [β (95% CI) = 0.25 (0.09, 0.41), p = 0.003] and sum of PAH metabolites [β (95% CI) = 0.29 (0.08, 0.49), p = 0.006] concentrations. The risk of DM was increased with increasing quartile of 2-hydroxyfluorene (2-OHFlu) and trans, trans-muconic acid (t,t-MA) (p for trend<0.05 and < 0.001, respectively). The highest quartile of t,t-MA showed a significantly higher risk of DM [OR (95% CI) = 2.77 (1.74, 4.42)] and obesity [OR (95% CI) = 1.42 (1.06, 1.90)]. Urinary t,t,-MA level was positively associated with BMI [(β (95% CI) = 0.51 (0.31, 0.71), p < 0.001] and non-alcoholic fatty liver disease index [(β (95% CI) = 0.09 (0.06, 0.12), p < 0.001]. In conclusion, the benzene metabolites t,t-MA and PAH metabolite 2-OHFlu were associated with an increased risk of DM. Urinary biomarkers for PAHs and VOCs were positively associated with BMI in the Korean adult population. Further studies to validate these observations in other populations are warranted.
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12
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Zainal Abidin Z, Zainuren ZA, Noor E, Mohd Nor NS, Mohd Saffian S, Abdul Halim R. Periodontal health status of children and adolescents with diabetes mellitus: a systematic review and meta-analysis. Aust Dent J 2021; 66 Suppl 1:S15-S26. [PMID: 33864280 DOI: 10.1111/adj.12845] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 04/03/2021] [Accepted: 04/08/2021] [Indexed: 01/02/2023]
Abstract
Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycaemia resulted from defects in insulin secretion or action, or both. Various studies have reported on the bidirectional relationship between DM and periodontal disease. A systematic search of the literature was performed in several databases, EBSCO Medline Complete, PubMed, Science Direct and a manual search for articles from 2000 until 2019. Literature that fulfilled the inclusion criteria were identified, and data measuring plaque index (PI), gingival index (GI), clinical attachment loss (CAL) and periodontal probing depth (PPD) were extracted and subjected to Random-effects meta-analysis. From 947 titles and abstracts screened, 11 articles were included for meta-analysis. It was found that PI, GI, CAL and PPD were significantly higher in DM children than in non-DM children according to the Standardized Mean different (SMD) and 95% confidence intervals (CI) (SMD 0.54, 95% CI 0.20-0.87, P = 0.002; SMD 0.63, 95% CI 0.39-0.87, P < 0.001; SMD 0.79, 95% CI 0.52-1.05, P < 0.001, SMD 0.67, 95% CI 0.23-1.11, P = 0.003, respectively). The meta-analysis showed significant differences in PI, GI, PD and CAL between the two groups, favouring non-DM children. Therefore, early detection of DM children with periodontal disease is crucial to prevent periodontal disease.
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Affiliation(s)
- Z Zainal Abidin
- Centre of Paediatric Dentistry and Orthodontic Studies, Faculty of Dentistry, UniversitiTeknologi Mara (UiTM), Sungai Buloh, Malaysia
| | - Z A Zainuren
- Centre of Paediatric Dentistry and Orthodontic Studies, Faculty of Dentistry, UniversitiTeknologi Mara (UiTM), Sungai Buloh, Malaysia
| | - E Noor
- Centre of Periodontology Studies, Faculty of Dentistry, Universiti Teknologi Mara (UiTM), Sungai Buloh, Malaysia
| | - N S Mohd Nor
- Paediatric Department, Faculty of Medicine and Institute for Pathology, Laboratory and Forensic Medicine (IPPerForM), Universiti Teknologi MARA (UiTM), Sungai Buloh, Malaysia
| | - S Mohd Saffian
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - R Abdul Halim
- Centre of Paediatric Dentistry and Orthodontic Studies, Faculty of Dentistry, UniversitiTeknologi Mara (UiTM), Sungai Buloh, Malaysia
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13
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Lee I, Park YJ, Kim MJ, Kim S, Choi S, Park J, Cho YH, Hong S, Yoo J, Park H, Cheon GJ, Choi K, Moon MK. Associations of urinary concentrations of phthalate metabolites, bisphenol A, and parabens with obesity and diabetes mellitus in a Korean adult population: Korean National Environmental Health Survey (KoNEHS) 2015-2017. ENVIRONMENT INTERNATIONAL 2021; 146:106227. [PMID: 33152652 DOI: 10.1016/j.envint.2020.106227] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 10/15/2020] [Accepted: 10/15/2020] [Indexed: 05/08/2023]
Abstract
Phthalates and bisphenol A (BPA) have been suspected as risk factors for obesity and diabetes mellitus (DM) among humans. However, associations between phthalates and environmental phenols are often inconsistent across different populations. In this study, we recruited the adult population (n = 3782) of the Korean National Environmental Health Survey (KoNEHS) 2015-2017 (Cycle 3) and assessed the associations between urinary biomarkers of phthalate, BPA, and paraben exposure with obesity and DM. A potential collider issue with the use of urinary creatinine (Cr) or specific gravity (SG) exists when adjusting urinary dilution; therefore, a covariate-adjusted standardization (CAS) was employed for adjustment, and the results were compared. In the present population, the direction of the association often varied depending on the choices made to adjust urinary dilution. When using CAS, the direction of association resembled those of previously reported experimental observations. With Cr or SG adjustment, ORs for obesity decreased in the highest quartiles of monocarboxyoctyl phthalate (MCOP) [OR (95% CI) = Cr: 0.71 (0.54, 0.93); SG: 0.68 (0.52, 0.90)], monocarboxy-isononyl phthalate (MCNP) [OR (95% CI) = Cr: 0.67 (0.52, 0.87); SG: 0.68 (0.52, 0.89)], and mono(3-carboxylpropyl) phthalate (MCPP) in the urine [OR (95% CI) = Cr: 0.60 (0.47, 0.76); SG: 0.61 (0.48, 0.77)]; however, with CAS, these negative associations disappeared. Instead, mono-benzyl phthalate (MBzP) [OR (95% CI) = 1.31 (1.03, 1.66)], BPA [OR (95% CI) = 1.62 (1.27, 2.06)], or ethyl paraben (EtP) [OR (95% CI) = 1.51 (1.19, 1.91)] concentrations in the highest quartile showed positive associations with a higher risk of obesity. On the other hand, for DM, an overall decrease in ORs was observed for phthalate metabolites and BPA following SG adjustment and disappeared with CAS adjustment. In addition, the highest quartiles of BPA, methyl paraben (MeP), and ethyl paraben (EtP) showed a significantly higher risk of DM than those in the lowest quartiles following CAS [OR (95% CI) = BPA: 1.65 (1.06, 2.59); MeP: 1.68 (1.08, 2.60); and EtP: 2.74 (1.77, 4.24), respectively]. The present observations outline the importance of using an appropriate adjustment method for urinary dilution in association studies on obesity and DM. In addition, several phthalates, BPA, and parabens were identified as potential chemical risk factors for these outcomes. Further studies are warranted in other populations to confirm these observations.
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Affiliation(s)
- Inae Lee
- School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Young Joo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Min Joo Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sunmi Kim
- School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Sohyeon Choi
- College of Natural Science, Soonchunhyang University, Asan, Republic of Korea
| | - Jeongim Park
- College of Natural Science, Soonchunhyang University, Asan, Republic of Korea
| | - Yoon Hee Cho
- Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA
| | - Sooyeon Hong
- Environmental Health Research Division, National Institute of Environmental Research, Ministry of Environment, Incheon, Republic of Korea
| | - Jiyoung Yoo
- Environmental Health Research Division, National Institute of Environmental Research, Ministry of Environment, Incheon, Republic of Korea
| | - Hyunwoong Park
- Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Gi Jeong Cheon
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyungho Choi
- School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Devision of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
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14
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Guo Y, Luo R, Corsi DJ, Retnakaran R, Walker MC, Wen SW. Caucasian and Asian difference in role of type 1 diabetes on large-for-gestational-age neonates. BMJ Open Diabetes Res Care 2020; 8:8/2/e001746. [PMID: 33214189 PMCID: PMC7678233 DOI: 10.1136/bmjdrc-2020-001746] [Citation(s) in RCA: 0] [Impact Index Per Article: 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: 07/01/2020] [Revised: 09/10/2020] [Accepted: 10/26/2020] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Racial differences in the association between type 1 diabetes mellitus (T1DM) and large-for-gestational-age (LGA) neonates remain unclear. The objective of this study was to compare the effect of T1DM on LGA neonates between Caucasian and Asian women. RESEARCH DESIGN AND METHODS A population-based retrospective cohort study was conducted among Caucasian and Asian women who had prenatal screening and gave a singleton live birth in an Ontario hospital between April 2015 and March 2018. Multivariable log-binomial regression models were used to estimate the adjusted relative risks (aRRs) and 95% CIs of T1DM on LGA for Caucasian and Asian women. Relative contribution of T1DM to LGA was examined by multivariable logistic regression model, stratified by Caucasian and Asian women. RESULTS A total of 232 503 women (69.4% Caucasians and 30.6% Asians) were included in the final analysis. The rate of T1DM was higher in Caucasians (0.5%) than in Asians (0.2%), and the rate of LGA neonates was also higher in Caucasians (11.0%) than in Asians (5.0%). The association between T1DM and LGA in Caucasians (aRR 4.18, 95% CI (3.84 to 4.55)) was more robust than that in Asians (aRR 2.11, 95% CI (1.24 to 3.59)). T1DM was the fourth strongest contributor to LGA in Caucasians, while T1DM was the seventh contributor to LGA in Asians. CONCLUSIONS T1DM plays a more substantial role in LGA among Caucasians than Asians. Clinicians should be aware of the Caucasian-Asian differences of effects of T1DM on LGA when developing pregnancy management strategies.
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Affiliation(s)
- Yanfang Guo
- Better Outcomes Registry & Network Ontario, Ottawa, Ontario, Canada
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
- OMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
| | - Rong Luo
- OMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
| | - Daniel J Corsi
- Better Outcomes Registry & Network Ontario, Ottawa, Ontario, Canada
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
- OMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
| | - Ravi Retnakaran
- Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Mark C Walker
- Better Outcomes Registry & Network Ontario, Ottawa, Ontario, Canada
- OMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Department of Obstetrics, Gynecology, and Newborn Care, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
| | - Shi Wu Wen
- OMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Department of Obstetrics, Gynecology, and Newborn Care, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
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15
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Ke C, Stukel TA, Luk A, Shah BR, Jha P, Lau E, Ma RCW, So WY, Kong AP, Chow E, Chan JCN. Development and validation of algorithms to classify type 1 and 2 diabetes according to age at diagnosis using electronic health records. BMC Med Res Methodol 2020; 20:35. [PMID: 32093635 PMCID: PMC7038546 DOI: 10.1186/s12874-020-00921-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 02/10/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Validated algorithms to classify type 1 and 2 diabetes (T1D, T2D) are mostly limited to white pediatric populations. We conducted a large study in Hong Kong among children and adults with diabetes to develop and validate algorithms using electronic health records (EHRs) to classify diabetes type against clinical assessment as the reference standard, and to evaluate performance by age at diagnosis. METHODS We included all people with diabetes (age at diagnosis 1.5-100 years during 2002-15) in the Hong Kong Diabetes Register and randomized them to derivation and validation cohorts. We developed candidate algorithms to identify diabetes types using encounter codes, prescriptions, and combinations of these criteria ("combination algorithms"). We identified 3 algorithms with the highest sensitivity, positive predictive value (PPV), and kappa coefficient, and evaluated performance by age at diagnosis in the validation cohort. RESULTS There were 10,196 (T1D n = 60, T2D n = 10,136) and 5101 (T1D n = 43, T2D n = 5058) people in the derivation and validation cohorts (mean age at diagnosis 22.7, 55.9 years; 53.3, 43.9% female; for T1D and T2D respectively). Algorithms using codes or prescriptions classified T1D well for age at diagnosis < 20 years, but sensitivity and PPV dropped for older ages at diagnosis. Combination algorithms maximized sensitivity or PPV, but not both. The "high sensitivity for type 1" algorithm (ratio of type 1 to type 2 codes ≥ 4, or at least 1 insulin prescription within 90 days) had a sensitivity of 95.3% (95% confidence interval 84.2-99.4%; PPV 12.8%, 9.3-16.9%), while the "high PPV for type 1" algorithm (ratio of type 1 to type 2 codes ≥ 4, and multiple daily injections with no other glucose-lowering medication prescription) had a PPV of 100.0% (79.4-100.0%; sensitivity 37.2%, 23.0-53.3%), and the "optimized" algorithm (ratio of type 1 to type 2 codes ≥ 4, and at least 1 insulin prescription within 90 days) had a sensitivity of 65.1% (49.1-79.0%) and PPV of 75.7% (58.8-88.2%) across all ages. Accuracy of T2D classification was high for all algorithms. CONCLUSIONS Our validated set of algorithms accurately classifies T1D and T2D using EHRs for Hong Kong residents enrolled in a diabetes register. The choice of algorithm should be tailored to the unique requirements of each study question.
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Affiliation(s)
- Calvin Ke
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Department of Medicine, University of Toronto, Toronto, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - Thérèse A. Stukel
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- ICES, Toronto, Canada
| | - Andrea Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Asia Diabetes Foundation, Prince of Wales Hospital, Shatin, Hong Kong
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Baiju R. Shah
- Department of Medicine, University of Toronto, Toronto, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- ICES, Toronto, Canada
- Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Prabhat Jha
- Centre for Global Health Research, St. Michael’s Hospital, and Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
| | - Eric Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Asia Diabetes Foundation, Prince of Wales Hospital, Shatin, Hong Kong
| | - Ronald C. W. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Wing-Yee So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Alice P. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Juliana C. N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Asia Diabetes Foundation, Prince of Wales Hospital, Shatin, Hong Kong
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
- Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
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16
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Głowińska-Olszewska B, Szabłowski M, Panas P, Żoła̧dek K, Jamiołkowska-Sztabkowska M, Milewska AJ, Kadłubiska A, Polkowska A, Łuczyński W, Bossowski A. Increasing Co-occurrence of Additional Autoimmune Disorders at Diabetes Type 1 Onset Among Children and Adolescents Diagnosed in Years 2010-2018-Single-Center Study. Front Endocrinol (Lausanne) 2020; 11:476. [PMID: 32849272 PMCID: PMC7424019 DOI: 10.3389/fendo.2020.00476] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 06/17/2020] [Indexed: 12/18/2022] Open
Abstract
Objectives: The prevalence of type 1 diabetes mellitus (T1D) in children is growing, but its relation to other autoimmune disorders that coexist since the onset of diabetes is not recognized. The objective of this study was to assess the incidence of T1D and the prevalence of autoimmune illnesses additionally coexisting since the diabetes mellitus onset in children during a period of 9 years' observation. Methods: In this retrospective study, the incidence rate (IR) of the T1D was calculated as the total number of all cases that were newly diagnosed per 100,000 population people between 0 and 18 years of age. The selected age groups (0-4, 5-9, 10-14, and 15-18 years) were examined, respectively. The studied group included 493 children (264 [53.55%] boys) between 0 and 18 years old newly diagnosed with T1D in one of the Polish centers in the years 2010-2018. Other autoimmune illnesses diagnoses were obtained from medical records taken from the first hospital treatment, when T1D was recognized. Results: The annual standardized IR of T1D increased from 19.2/100,000 in year 2010 to 31.7/100,000 in 2018 (1.7-fold over 9 years' observation), with an increase in the incidence rate ratio (IRR) by 4% per year. The highest growth in IR was recorded in 5- to 9-year-olds (from 19.61 in 2010 to 43.45 in 2018). In 61 (12.4%) of the studied group, at least one additional autoimmune disease was diagnosed. The prevalence doubled from 10.4% in the year 2010 to 20.8% in the year 2018. Autoimmune thyroid illnesses were found in 37 children (7.5%); their incidence increased from 6.3% to almost 2-fold, 12.5%, in 2018. In 26 children (5.3%), celiac disease was recognized; the prevalence increased from 4.2 to 9.8% in the study period. The prevalence of additional autoimmune thyroid disease was higher in glutamic acid decarboxylase-positive antibodies (χ2 = 3.4, p = 0.04) patients, the oldest age group (15-18 years) (χ2 =7.1, p = 0.06), and in girls (χ2 =7.1, p = 0.007). Conclusions:The standardized IR of T1D in children increased 1.7-fold over the 9-year observation period, and IRR increased 4% per year. Additional autoimmunity represents a significant comorbidity in patients with new-onset T1D. The number of children diagnosed with additional autoimmune diseases that accompany T1D is rapidly growing in all age groups throughout recent years.
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Affiliation(s)
- Barbara Głowińska-Olszewska
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
- *Correspondence: Barbara Głowińska-Olszewska
| | - Maciej Szabłowski
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
| | - Patrycja Panas
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
| | - Karolina Żoła̧dek
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
| | - Milena Jamiołkowska-Sztabkowska
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
- Department of Pediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, Białystok, Poland
| | - Anna Justyna Milewska
- Department of Statistics and Medical Informatics, Medical University of Bialystok, Białystok, Poland
| | - Anna Kadłubiska
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
| | - Agnieszka Polkowska
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
| | - Włodzimierz Łuczyński
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
- Department of Medical Simulations, Medical University of Bialystok, Białystok, Poland
| | - Artur Bossowski
- Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Białystok, Poland
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17
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Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2018; 19 Suppl 27:7-19. [PMID: 30226024 PMCID: PMC7521365 DOI: 10.1111/pedi.12773] [Citation(s) in RCA: 368] [Impact Index Per Article: 52.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 07/27/2018] [Indexed: 12/16/2022] Open
Affiliation(s)
- Elizabeth J. Mayer-Davis
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Craig Jefferies
- Starship Children’s Hospital, Auckland District Health Board, Auckland, New Zealand
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colorado
| | - Naby Balde
- Department of Endocrinology, University Hospital, Conakry, Guinea
| | - Chun X. Gong
- Beijing Children’s Hospital, Capital Medical University, Beijing, China
| | | | - Maria E. Craig
- The Children’s Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia,School of Women’s and Children’s Health, University of NSW, Sydney, New South Wales, Australia
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18
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Tung YC, Fann CSJ, Chang CC, Chu CC, Yang WS, Hwu WL, Chen PL, Tsai WY. Comprehensive human leukocyte antigen genotyping of patients with type 1 diabetes mellitus in Taiwan. Pediatr Diabetes 2018; 19:699-706. [PMID: 29383806 DOI: 10.1111/pedi.12645] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/11/2017] [Accepted: 12/27/2017] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) mellitus is an autoimmune disorder involving both complex genetic and environmental factors. The incidence rates are low in Asian countries, and the specific, explanatory genetic factors underlying this have been investigated. The aim of this study was to elucidate the association of human leukocyte antigen (HLA) alleles/haplotypes with T1D in Taiwan. METHODS We performed direct comprehensive genotyping of 6 classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) to 4-digit resolution in 104 unrelated T1D patients and 504 controls. Twenty-four of the 104 patients also exhibited thyroid autoimmunity. RESULTS Three major susceptibility haplotypes were identified: DRB1*03:01-DQB1*02:01 (odds ratio [OR] = 5.39 under the dominant model, P = 2.3 × 10-13 ), DRB1*04:05-DQB1*04:01 (OR = 2.44, P = 5.0 × 10-4 ), and DRB1*09:01-DQB1*03:03 (OR = 2.02, P = 1.4 × 10-3 ); one protective haplotype was identified: DRB1*08:03-DQB1*06:01 (OR = 0.10, P = 1.6 × 10-3 ). DRB1*03:01-DQB1*02:01, the major T1D susceptibility haplotype, was found at a lower frequency in T1D patients with thyroid autoimmunity. The T1D protective allele DRB1*12:02 was shown to be protective against Graves' disease in our previous report. CONCLUSION In addition to clarifying the roles of several known T1D HLA alleles and haplotypes, we discovered that the DRB1*08:03-DQB1*06:01 haplotype is protective against T1D. The DRB1*12:02 allele protected against both T1D and Graves' disease.
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Affiliation(s)
- Yi-Ching Tung
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cathy S-J Fann
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | | | - Chen-Chung Chu
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wuh-Liang Hwu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Lung Chen
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Yu Tsai
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
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19
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Park Y, Wintergerst KA, Zhou Z. Clinical heterogeneity of type 1 diabetes (T1D) found in Asia. Diabetes Metab Res Rev 2017; 33. [PMID: 28544229 DOI: 10.1002/dmrr.2907] [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: 12/31/2016] [Revised: 04/26/2017] [Accepted: 05/02/2017] [Indexed: 12/17/2022]
Abstract
Diabetes mellitus among young patients in Asia is caused by a complex set of factors. Although type 1 diabetes (T1D) remains the most common form of diabetes in children, the recent unabated increase in obesity has resulted in the emergence of type 2 diabetes (T2D) as a new type of diabetes among adolescents and young adults. In addition to the typical autoimmune type 1 diabetes (T1aD) and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1bD). Additional forms have been described, including fulminant T1D (FT1D). Although most diagnoses of T1D are classified as T1aD, fulminant T1D exists as a hyper-acute subtype of T1D that affects older children, without associated autoimmunity. Patient with this rare aetiology of diabetes showed a complete loss of β-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults is a form of autoimmune-mediated diabetes, usually diagnosed during the insulin-dependent stage that follows a non-insulin requiring phase, which can be diagnosed earlier based on anti-islet autoantibody positivity. Some reports discuss T1bD. Others are elaborating on the presence of "atypical T1b diabetes," such as Flatbush diabetes. The prevalence of diabetes mellitus in young adults continues to rise in Asian populations as T2D increases. With improved characterization of patients with diabetes, the range of diabetic subgroups will become even more diverse in the future. Distinguishing T1D, T2D, and other forms of diabetes in young patients is challenging in Asian populations, as the correct diagnosis is clinically important and has implications for prognosis and management. Despite aetiological heterogeneity in the usual clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds as well as measuring islet autoantibodies and fasting plasma C-peptide could provide a possible viable method to minimize complications.
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Affiliation(s)
- Yongsoo Park
- Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY, USA
- College of Medicine and Engineering, Hanyang University, Seoul, South Korea
| | - Kupper A Wintergerst
- Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY, USA
- Department of Pediatrics, Division of Endocrinology, University of Louisville, Louisville, KY, USA
- Wendy Novak Diabetes Care Center, Kosair Children's Hospital, University of Louisville, Louisville, KY, USA
| | - Zhiguang Zhou
- Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China
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20
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Larizza D, De Amici M, Klersy C, Albanesi M, Albertini R, Badulli C, Torre C, Calcaterra V. Anti-Zinc Transporter Protein 8 Antibody Testing Is Not Informative in Routine Prediabetes Screening in Young Patients with Autoimmune Thyroiditis and Celiac Disease. Horm Res Paediatr 2017; 86:100-105. [PMID: 27487045 DOI: 10.1159/000448003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 06/24/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Patients with type 1 diabetes mellitus (T1DM), autoimmune thyroiditis (ATD), and celiac disease (CD) are at increased risk for developing other autoimmune diseases. We evaluated zinc transporter 8 (ZnT8) prevalence in patients with ATD and/or CD in order to define the usefulness of ZnT8 autoantibodies for prediabetes screening. METHODS Eighty-one young patients with ATD and/or CD were included in the study; 32 subjects with clinical onset of T1DM were enrolled as a control group. GAD65, IA-2, and ZnT8 antibodies were measured. An intravenous glucose tolerance test, C-peptide, glycosylated hemoglobin levels, and genomic analysis of HLA-DQA1* and -DQB1* were also considered in patients positive for autoantibodies. RESULTS The ZnT8 prevalence was higher in T1DM patients than in patients with other autoimmune diseases (p < 0.001); positive ZnT8 detection was found in 2 ATD (p = 0.004) and 3 ATD + CD (p = 0.04) patients. Positive ZnT8 was associated with GAD65 (p = 0.01) but not with IA-2 positivity. No correlation between ZnT8 detection and the number of T1DM-susceptible HLA-DQ heterodimers was found. Pathological C-peptide levels and insulin response were found in subjects with islet autoimmunity and genetic susceptibility. CONCLUSION ZnT8 autoantibodies detection in ATD and/or CD patients is low, and routine ZnT8 screening is not justified. ZnT8 evaluation may be recommended in subjects with autoimmune diseases as a marker for predicting compromised insulin secretion.
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Affiliation(s)
- Daniela Larizza
- Department of Internal Medicine, University of Pavia, Pavia, Italy
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21
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Ayabe T, Fukami M, Ogata T, Kawamura T, Urakami T, Kikuchi N, Yokota I, Ihara K, Takemoto K, Mukai T, Nishii A, Kikuchi T, Mori T, Shimura N, Sasaki G, Kizu R, Takubo N, Soneda S, Fujisawa T, Takaya R, Kizaki Z, Kanzaki S, Hanaki K, Matsuura N, Kasahara Y, Kosaka K, Takahashi T, Minamitani K, Matsuo S, Mochizuki H, Kobayashi K, Koike A, Horikawa R, Teno S, Tsubouchi K, Mochizuki T, Igarashi Y, Amemiya S, Sugihara S. Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21. Diabet Med 2016; 33:1717-1722. [PMID: 27352912 DOI: 10.1111/dme.13175] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 05/08/2016] [Accepted: 06/27/2016] [Indexed: 12/11/2022]
Abstract
AIMS The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. METHODS We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. RESULTS Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. CONCLUSIONS The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood.
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Affiliation(s)
- T Ayabe
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
| | - M Fukami
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
| | - T Ogata
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
- Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - T Kawamura
- Department of Pediatrics, Osaka City University Hospital, Osaka, Japan
| | - T Urakami
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - N Kikuchi
- Department of Pediatrics, Yokohama City Minato Red Cross Hospital, Yokohama, Japan
| | - I Yokota
- Department of Clinical Laboratory, Shikoku Medical Center for Children and Adults, Zentsuji, Japan
- Department of Pediatrics, Graduate School of Medical Sciences Tokushima University, Tokushima, Japan
| | - K Ihara
- Department of Pediatrics, Kyushu University Hospital, Fukuoka, Japan
- Department of Pediatrics, Oita University Hospital, Yufu, Japan
| | - K Takemoto
- Department of Pediatrics, Ehime University Hospital, Toon, Japan
- Department of Pediatrics, Sumitomo Besshi Hospital, Niihama, Japan
| | - T Mukai
- Department of Pediatrics, Asahikawa Medical University Hospital, Asahikawa, Japan
- Department of Pediatrics, Asahikawa-Kosei General Hospital, Asahikawa, Japan
| | - A Nishii
- Department of Pediatrics, JR Sendai Hospital, Sendai, Japan
| | - T Kikuchi
- Department of Pediatrics, Saitama Medical University Hospital, Saitama, Japan
- Department of Pediatrics, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - T Mori
- Department of Pediatrics, Nagano Red Cross Hospital, Nagano, Japan
- Department of Pediatrics, Shinshu Ueda Medical Center, Ueda, Japan
| | - N Shimura
- Department of Pediatrics, Dokkyo Medical University Hospital, Shimotsuga, Japan
| | - G Sasaki
- Department of Pediatrics, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan
| | - R Kizu
- Department of Pediatrics, Yokosuka Kyosai Hospital, Yokosuka, Japan
| | - N Takubo
- Department of Pediatrics, Kitasato University Hospital, Sagamihara, Japan
- Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - S Soneda
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - T Fujisawa
- Department of Pediatrics, National Mie Hospital, Tsu, Japan
| | - R Takaya
- Department of Pediatrics, Osaka Medical College, Takatsuki, Japan
| | - Z Kizaki
- Department of Pediatrics, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - S Kanzaki
- Department of Pediatrics, Tottori University Faculty of Medicine, Yonago, Japan
| | - K Hanaki
- Department of Pediatrics, Tottori Prefectural Kousei Hospital, Kurayoshi, Japan
| | - N Matsuura
- Department of Pediatrics, Teine Keijinkai Hospital, Sapporo, Japan
- Department of Early Childhood Care and Education, Seitoku University Junior College, Matsudo, Japan
| | - Y Kasahara
- Department of Pediatrics, Kanazawa University, Kanazawa, Japan
| | - K Kosaka
- Department of Pediatrics, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | | | - K Minamitani
- Department of Pediatrics, Teikyo University Chiba Medical Center, Ichihara, Japan
| | - S Matsuo
- Matsuo Kodomo Clinic, Kyoto, Japan
| | - H Mochizuki
- Department of Metabolism and Endocrinology, Saitama Children's Medical Center, Saitama, Japan
| | - K Kobayashi
- Department of Pediatrics, University of Yamanashi Hospital, Chuo, Japan
| | - A Koike
- Miyanosawa Koike Child Clinic, Sapporo, Japan
| | - R Horikawa
- Division of Endocrinology and Metabolism, Department of Medical Subspecialties, National Medical Center for Children and Mothers, Tokyo, Japan
| | - S Teno
- Teno Clinic, Izumo, Japan
| | - K Tsubouchi
- Department of Pediatrics, Chuno Kosei Hospital, Seki, Japan
| | - T Mochizuki
- Department of Pediatrics, Osaka City General Hospital, Osaka, Japan
- Department of Pediatrics, Osaka Police Hospital, Osaka, Japan
| | - Y Igarashi
- Igarashi Children's Clinic, Sendai, Japan
| | - S Amemiya
- Department of Pediatrics, Saitama Medical University Hospital, Saitama, Japan
| | - S Sugihara
- Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
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22
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A comparison of IDeg + IAsp versus IDet + IAsp in subjects with type 1 diabetes: subgroup analysis of Japanese subjects. Diabetol Int 2016; 7:404-412. [PMID: 30603293 DOI: 10.1007/s13340-016-0267-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 03/17/2016] [Indexed: 10/22/2022]
Abstract
Objective Efficacy and safety were compared between insulin degludec (IDeg) once daily (OD) in combination with mealtime insulin aspart (IAsp) and insulin detemir (IDet) OD or twice daily (BID) in combination with mealtime IAsp in Japanese subjects with type 1 diabetes mellitus (T1DM). Materials and methods This was a post hoc analysis of a multinational, controlled, open-label, parallel-group, treat-to-target trial that randomised adults [aged ≥18 years (≥20 years for Japan)] with T1DM for ≥12 months to basal IDeg OD (n = 124) or IDet (n = 62), both with mealtime bolus IAsp. The IDet dosing was adjusted to BID if required at ≥8 weeks. Results The estimated mean change in HbA1c from baseline to week 26 (the primary outcome measure) was -1.03 % in the IDeg + IAsp group and -0.94 % in the IDet + IAsp group (mean estimated treatment difference [ETD] -0.09; 95 % confidence interval [CI] -0.29, 0.10). Significantly greater reductions in fasting plasma glucose were observed in the IDeg + IAsp group (mean ETD -39.36 mg/dL; 95 % CI -56.04, -22.68). Both groups had similar rates of confirmed hypoglycaemia (59.9 and 59.2 per patient-year of exposure [PYE] with IDeg + IAsp and IDet + IAsp, respectively). Rates of nocturnal confirmed hypoglycaemia were significantly lower with IDeg + IAsp than with IDet + IAsp (5.2 vs 9.5 episodes per PYE; estimated ratio 0.48; 95 % CI 0.31, 0.75). Adverse event profiles were similar. Conclusion The findings were consistent with those of the global trial population. IDeg + IAsp may represent an improvement on current standard treatments for Japanese patients with T1DM.
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23
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Ong SC, Lee VTW, Lim JFY, Chow WL, Tong SC, Kee TYS, Madhavan K. Is simultaneous pancreas kidney transplant the most cost-effective strategy for type 1 diabetes patients with renal failure? PROCEEDINGS OF SINGAPORE HEALTHCARE 2015. [DOI: 10.1177/2010105815610137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Introduction: Simultaneous pancreas kidney transplant (SPK) has shown beneficial outcomes in type 1 diabetes patients with renal failure (IDDM-RF). The objective of this study was to assess its cost-effectiveness compared with other treatment strategies for IDDM-RF. Methods: A decision analytic model was developed for IDDM-RF treatment with four possible strategies: deceased donor kidney transplant (DDKT), living donor kidney transplant (LDKT), SPK and dialysis. A cost-utility analysis from the healthcare provider perspective was conducted based on a five-year model. Local data were used whenever possible except for SPK survival variables, wherein data from United Network for Organ Sharing and Scientific Registry of Transplant Recipients were used. Sensitivity analyses were performed to evaluate the impact of uncertainties around key variables. Results: In the baseline analysis, LDKT was the most cost-effective strategy with the lowest cost per quality-adjusted life year gained, i.e. SGD77,068, followed by SPK (SGD82,991), DDKT (SGD92,432) and dialysis (SGD181,192). The DDKT was extended dominated by dialysis and LDKT strategies. Incremental cost-effectiveness ratios with dialysis as a reference for LDKT and SPK strategies were SGD43,094 and SGD56,201, respectively. Both strategies are considered highly cost-effective under World Health Organization (WHO) guidelines. In the sensitivity analysis, a 6% increase in both SPK kidney graft survival and patient survival would make SPK the most cost-effective strategy. Conclusions: Both LDKT and SPK are highly cost-effective strategies in the treatment of IDDM-RF. SPK is potentially the most cost-effective strategy if a 6% increase in both SPK kidney graft survival and patient survival is achieved.
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Affiliation(s)
- Siew Chin Ong
- Department of Pharmacostatistics, Info Kinetics Ptd. Ltd., Penang, Malaysia
| | - Victor Tswen-Wen Lee
- Division of Hepatobiliary & Pancreatic Surgery, National University Hospital, Singapore
- National University of Singapore, Department of Surgery, Yong Loo Lin School of Medicine, Singapore
| | | | - Wai Leng Chow
- Health Services Research, Eastern Health Alliance, Singapore
| | - Shao Chuen Tong
- Health Services Research, Eastern Health Alliance, Singapore
| | | | - Krishnakumar Madhavan
- Division of Hepatobiliary & Pancreatic Surgery, National University Hospital, Singapore
- National University of Singapore, Department of Surgery, Yong Loo Lin School of Medicine, Singapore
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24
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Gutierrez-Achury J, Romanos J, Bakker SF, Kumar V, de Haas EC, Trynka G, Ricaño-Ponce I, Steck A, Chen WM, Onengut-Gumuscu S, Simsek S, Rewers M, Mulder CJ, Liu E, Rich SS, Wijmenga C. Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity. Diabetes Care 2015; 38 Suppl 2:S37-44. [PMID: 26405070 PMCID: PMC4582914 DOI: 10.2337/dcs15-2007] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) versus those with only one. We hypothesized that double autoimmunity individuals carry more of the genetic risk markers that are shared between the two diseases independently. SNPs were genotyped in loci associated with T1D (n=42) and CeD (n=28) in 543 subjects who developed double autoimmunity, 2,472 subjects with T1D only, and 2,223 CeD-only subjects. For identification of loci that were specifically associated with individuals developing double autoimmunity, two association analyses were conducted: double autoimmunity versus T1D and double autoimmunity versus CeD. HLA risk haplotypes were compared between the two groups. The CTLA4 and IL2RA loci were more strongly associated with double autoimmunity than with either T1D or CeD alone. HLA analyses indicated that the T1D high-risk genotype, DQ2.5/DQ8, provided the highest risk for developing double autoimmunity (odds ratio 5.22, P=2.25×10(-29)). We identified a strong HLA risk genotype (DQ2.5/DQ8) predisposing to double autoimmunity, suggesting a dominant role for HLA. Non-HLA loci, CTLA4 and IL2RA, may also confer risk to double autoimmunity. Thus, CeD patients who carry the DQ2.5/DQ8 genotype may benefit from periodic screening of autoantibodies related to T1D.
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Affiliation(s)
- Javier Gutierrez-Achury
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Jihane Romanos
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Sjoerd F Bakker
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, the Netherlands
| | - Vinod Kumar
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Esther C de Haas
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Gosia Trynka
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Isis Ricaño-Ponce
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Andrea Steck
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO
| | | | - Wei-Min Chen
- Center for Public Health Genomics and Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA
| | - Suna Onengut-Gumuscu
- Center for Public Health Genomics and Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA
| | - Suat Simsek
- Department of Internal Medicine, Medical Center Alkmaar, Alkmaar, the Netherlands
| | | | - Marian Rewers
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO
| | - Chris J Mulder
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, the Netherlands
| | - Ed Liu
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO
| | - Stephen S Rich
- Center for Public Health Genomics and Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA
| | - Cisca Wijmenga
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
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25
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Hong SW, Linton JA, Shim JY, Kang HT. High-risk drinking is associated with a higher risk of diabetes mellitus in Korean men, based on the 2010-2012 KNHANES. Alcohol 2015; 49:275-81. [PMID: 25920001 DOI: 10.1016/j.alcohol.2015.02.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 01/31/2015] [Accepted: 02/24/2015] [Indexed: 01/14/2023]
Abstract
We examined the association between alcohol-drinking pattern and diabetes mellitus (DM) in Korean adults. This cross-sectional study included 12,486 participants (5551 men and 6935 women) who participated in the 2010-2012 Korean National Health and Nutrition Examination Survey. We categorized alcohol-drinking pattern into three groups based on the alcohol-use disorders identification test (AUDIT): low-risk (score: 0-7), intermediate-risk (score: 8-14), and high-risk (score: ≥15). DM was defined as having fasting plasma glucose ≥126 mg/dL or taking glucose-lowering medication, including insulin therapy. In the study population, 25.2% of men and 4.7% of women were high-risk drinkers. DM prevalence was 9.2% in men and 5.4% in women. DM prevalence was 9.0% and 5.7% in the low-risk drinking group, 7.6% and 4.1% in the intermediate-risk drinking group, and 11.2% and 3.5% in the high-risk drinking group in men and women, respectively. Compared to the low-risk drinking group, odds ratios (95% confidence intervals) of men and women in the intermediate-risk drinking group for DM were 1.043 (0.779-1.396) and 1.139 (0.712-1.824), respectively, and 1.480 (1.133-1.933) and 0.827 (0.296-2.311) in the high-risk drinking group, after adjusting for age and other confounding factors. In conclusion, high-risk drinking appears to be associated with a higher risk of DM in men, but not in women.
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Affiliation(s)
- Sung-Won Hong
- Health Promotion Center, Chung-Ang University Medical Center, Seoul, Republic of Korea; Department of Medicine, Graduate School, Yonsei University, Seoul, Republic of Korea
| | - John A Linton
- International Health Care Center, Severance Hospital, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Jae-Yong Shim
- Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hee-Taik Kang
- Department of Medicine, Graduate School, Yonsei University, Seoul, Republic of Korea; Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
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26
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Kiani AK, John P, Bhatti A, Zia A, Shahid G, Akhtar P, Wang X, Demirci FY, Kamboh MI. Association of 32 type 1 diabetes risk loci in Pakistani patients. Diabetes Res Clin Pract 2015; 108:137-142. [PMID: 25661663 DOI: 10.1016/j.diabres.2015.01.022] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 11/15/2014] [Accepted: 01/03/2015] [Indexed: 12/16/2022]
Abstract
AIM To identify risk alleles contributing towards type 1 diabetes in Pakistani patients. INTRODUCTION Type 1 diabetes (T1D) is an autoimmune disease which is caused by destruction of insulin producing β cells by immune system. Genetic predisposition as well as environmental factors contribute to its etiology. To date more than 40 risk loci have been identified for T1D. METHODOLOGY A total of 191 family-based and unrelated T1D cases and controls were recruited. DNA was extracted and 32 genome-wide significant single nucleotide polymorphisms (SNPs) previously reported in Europeans were genotyped. Genotyping was performed using TaqMan SNP genotyping assays and the data was analyzed using FamCC software. RESULTS Our results showed significant association of 10 single nucleotide polymorphisms (SNPs) with T1D at p<0.01, including HLA-DQA1/rs9272346, ERBB3/rs2292239, SIRPG/rs2281808, IL2-KIAA1109/rs4505848, GLIS3/rs7020673, CD226/rs763361, PTPN2/rs478582, IKZF1/rs10272724, BACH2/rs11755527, C6orf173/rs9388489, whereas 5 more SNPs showed their association at 0.01 CONCLUSION We have replicated many of the T1D loci established among Europeans in a Pakistani population.
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Affiliation(s)
- Aysha Karim Kiani
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
| | - Peter John
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
| | - Attya Bhatti
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Asima Zia
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Gulbin Shahid
- Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan
| | | | - Xingbin Wang
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
| | - F Yesim Demirci
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
| | - M Ilyas Kamboh
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
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Ke C, Sohal P, Qian H, Quan H, Khan NA. Diabetes in the young: a population-based study of South Asian, Chinese and White people. Diabet Med 2015; 32:487-96. [PMID: 25472769 DOI: 10.1111/dme.12657] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/01/2014] [Indexed: 12/16/2022]
Abstract
AIMS Rates of diabetes mellitus in the young have not been quantified on a population level, particularly in South Asian and Chinese populations, which bear high rates of diabetes. We determined the incidence of diabetes (Type 2 diabetes and diabetes using insulin only) and rates of hospitalizations among South Asian, Chinese and White people aged 5-29 years with newly diagnosed diabetes. METHODS People with newly diagnosed diabetes (1997-2006) in British Columbia, Canada were identified using population-based administrative data and pharmacy databases. Age-standardized incidence rates were calculated for people with diabetes prescribed insulin only and those with Type 2 diabetes. They were followed for up to 8 years for all hospitalizations and diabetes-related complications. RESULTS There were 712 South Asians, 498 Chinese and 6176 White people aged 5-29 years with diabetes. Most youth with diabetes had Type 2 diabetes (South Asian 86.4%; Chinese 87.1% and White 61.8%). The incidence of diabetes on insulin only was highest in White people compared with the other groups. The incidence of Type 2 diabetes was highest in South Asians, particularly in 20-29-year-olds, with rates 2.2 times that of White people and 3.1 times that of Chinese people. Hospitalization and diabetes-related complications were uncommon in all groups. CONCLUSION The incidence of Type 2 diabetes is higher than previously estimated among youth and is now surpassing diabetes on insulin only. Significant reductions in Type 2 diabetes screening ages in South Asians need to be considered and prevention efforts are urgently required in childhood and adolescence. Global estimates need to consider the epidemic of Type 2 diabetes in the young.
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Affiliation(s)
- C Ke
- Department of Medicine, University of British Columbia, Vancouver, Canada
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Lee BS, Park EC, Park SW, Nam CM, Roh J. Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A case-control study in Korea. World J Gastroenterol 2015; 21:502-510. [PMID: 25593465 PMCID: PMC4292281 DOI: 10.3748/wjg.v21.i2.502] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 07/04/2014] [Accepted: 07/30/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To identify possible risk factors and their synergism for cholangiocarcinoma development.
METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma (ECC) and 83 intrahepatic cholangiocarcinoma (ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, respectively.
RESULTS: There was an association between cholangiocarcinoma and hepatitis B virus (HBV) infection, diabetes mellitus (DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios (AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM (AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC (AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC (AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM (OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.
CONCLUSION: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanisms for such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.
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Craig ME, Jefferies C, Dabelea D, Balde N, Seth A, Donaghue KC. ISPAD Clinical Practice Consensus Guidelines 2014. Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2014; 15 Suppl 20:4-17. [PMID: 25182305 DOI: 10.1111/pedi.12186] [Citation(s) in RCA: 177] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 06/16/2014] [Indexed: 12/20/2022] Open
Affiliation(s)
- Maria E Craig
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead and University of Sydney, Sydney, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, Australia
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Gloria-Bottini F, Saccucci P, Meloni GF, Manca-Bitti ML, Coppeta L, Neri A, Magrini A, Egidio B. Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia. World J Diabetes 2014; 5:557-561. [PMID: 25126401 PMCID: PMC4127590 DOI: 10.4239/wjd.v5.i4.557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 03/06/2014] [Accepted: 06/20/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes (T1D) in Continental Italy and Sardinian populations.
METHODS: Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032 healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age at conception and age at onset of disease were obtained from clinical records. χ2 test of independence, student t test for differences between means and odds ratio analysis were carried out by SPSS programs. Three way contingency table analysis was carried out according to Sokal and Rohlf.
RESULTS: The pattern of association between PTPN22 and T1D is similar in Continental Italy and Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in controls. The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy: the proportion of newborn from mother aging more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P < 10-6) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive newborns (P = 0.005). This points to an important role of ethnicity. A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia. PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia. Maternal age does not influence significantly age at onset in Italy (8.2 years in T1D infants from mothers aging 32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants from mothers aging more than 32 years: P = 0.062). No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males (8.07 years in males vs 6.3 years in females: P = 0.002).
CONCLUSION: The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.
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Kim TN, Lee JE, Lee EJ, Won JC, Noh JH, Ko KS, Rhee BD, Kim DJ. Prevalence of and factors associated with lens opacities in a Korean adult population with and without diabetes: the 2008-2009 Korea National Health and Nutrition Examination Survey. PLoS One 2014; 9:e94189. [PMID: 24718421 PMCID: PMC3981769 DOI: 10.1371/journal.pone.0094189] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 03/10/2014] [Indexed: 11/18/2022] Open
Abstract
Objective We examined the prevalence of and factors associated with lens opacities in a Korean adult population with and without diabetes. Research Design and Methods Among the 11,163 adults (≥19 years old) from the fourth Korea National Health and Nutrition Examination Survey in 2008–2009, the data from laboratory tests, nutritional surveys, and slit-lamp examinations of 10,248 persons (4,397 men, 5,851 women) were examined. Cataract was defined as the presence of any nuclear, cortical, subcapsular, or mixed cataract in at least one eye, using the Lens Opacities Classification System III. Results The weighted prevalence of cataracts were 23.5% [95% confidence interval (CI), 21.7–25.4] in a Korean adult population (19–39 years old, 1.8% [1.3–2.5], 40–64 years old, 25.2% [22.5–28.1],≥65 years old, 87.8% [85.4–89.9])and 54.7% [50.1–59.2] in a diabetic population(19–39 years old, 11.6% [4.5–26.5], 40–64 years old, 41.1% [35.4–47.0], ≥65 years old, 88.3% [83.5–91.8]). In a logistic regression analysis, age, myopia, and the presence of diabetes were independent risk factors. For young (age 19–39 years) and middle aged (age 40–65 years) adults with diabetes, the OR of having a lens opacity is 5.04 [1.41–17.98] and 1.47 [1.11–1.94], respectively, as those without diabetes, whereas for adults aged 65 and older, there was no difference in the prevalence of cataract. Conclusions According to these national survey data, ∼ 24% of Korean adults and ∼ 55% of people with diabetes have cataracts. The presence of diabetes was independently associated with cataracts in young and middle aged adults.
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Affiliation(s)
- Tae Nyun Kim
- Department of Internal Medicine, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Korea
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea
| | - Joo Eun Lee
- Department of Ophthalmology, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Korea
| | - Eun Ju Lee
- Department of Internal Medicine, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Korea
| | - Jong Chul Won
- Department of Internal Medicine, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea
| | - Jung Hyun Noh
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea
- Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University, Koyang, Korea
| | - Kyung Soo Ko
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea
- Department of Internal Medicine, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea
| | - Byoung Doo Rhee
- Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea
- Department of Internal Medicine, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea
| | - Dong-Jun Kim
- Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University, Koyang, Korea
- * E-mail:
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Pei Z, Chen X, Sun C, Du H, Wei H, Song W, Yang Y, Zhang M, Lu W, Cheng R, Luo F. A novel single nucleotide polymorphism in the protein tyrosine phosphatase N22 gene (PTPN22) is associated with Type 1 diabetes in a Chinese population. Diabet Med 2014; 31:219-26. [PMID: 24117662 DOI: 10.1111/dme.12331] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 08/09/2013] [Accepted: 09/19/2013] [Indexed: 11/29/2022]
Abstract
AIMS To examine single nucleotide polymorphisms in the protein tyrosine phosphatase N22 gene (PTPN22) and to study their association with Type 1 diabetes in a Chinese cohort. METHODS Three hundred and sixty-four young patients with Type 1 diabetes and 719 healthy children were included in this case-controlled study. The genotypes of rs1217385, rs2488457 (-1123C>G), rs1217414, rs1217419, rs3765598 and rs2476601 (1858C>T) in the PTPN22 gene were determined using the SNaPshot method. Alleles, genotypes and haplotype frequencies were compared between patients with Type 1 diabetes and healthy control subjects. The association between single nucleotide polymorphisms and clinical traits/autoantibody status was also analysed. RESULTS The single nucleotide polymorphism, rs1217419, located in the second intron of the PTPN22 gene was associated with Type 1 diabetes (odds ratio 1.5, 95% CI 1.14-1.97, P = 0.003). An additional single nucleotide polymorphism, rs1217385, was also associated with Type 1 diabetes; however, the association was secondary to that of rs1217419. The previously reported single nucleotide polymorphism that is associated with Type 1 diabetes (-1123G>C) had only marginal association with Type 1 diabetes in our study. A marginal association was also identified between -1123G>C and glutamic acid decarboxylase autoantibody positivity in patients with Type 1 diabetes. There was no association between the single nucleotide polymorphism 1858C>T and Type 1 diabetes in our studied cohort. CONCLUSIONS Our study confirmed that PTPN22 is a gene that contributes to Type 1 diabetes susceptibility. The primary association occurs with single nucleotide polymorphism rs1217419 and there is clear heterogeneity of the association between PTPTN22 polymorphisms and Type 1 diabetes in a Chinese population compared with other populations.
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Affiliation(s)
- Z Pei
- Department of Pediatric Endocrinology and Inborn Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
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Asanghanwa M, Gorus FK, Weets I, der Auwera BV, Aminkeng F, Mbunwe E, Goubert P, Verhaeghen K, Sobngwi E, Wenzlau JM, Hutton JC, Pipeleers DG, Keymeulen B, Mbanya JCN, van Schravendijk C. Clinical and biological characteristics of diabetic patients under age 40 in Cameroon: relation to autoantibody status and comparison with Belgian patients. Diabetes Res Clin Pract 2014; 103:97-105. [PMID: 24332797 PMCID: PMC4120294 DOI: 10.1016/j.diabres.2013.11.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 10/04/2013] [Accepted: 11/12/2013] [Indexed: 12/18/2022]
Abstract
AIMS We investigated the prevalence of diabetes autoantibodies (Abs) in Cameroonian patients and controls, assessed their contribution in disease classification and compared results with data from Belgium. METHODS Abs against GAD (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A) were assessed in 302 recently diagnosed Cameroonian patients with diabetes and 184 control subjects without diabetes aged below 40 years. RESULTS Only 27 (9%) Cameroonian patients were younger than 15 years. Overall, 29% of patients presented at least one diabetes-associated antibody vs 9% in healthy controls (24% vs 7% for GADA (p<0.001), 10% vs 3% for IA-2A (p<0.006), 4% vs 2% for ZnT8A). Ab(+) patients had lower C-peptide levels (p<0.001), were more often insulin-treated (p<0.002) and were as frequently diagnosed with type 1 diabetes as Ab(-) patients. Only 43% of Ab(+) patients aged 15-39 years were clinically classified as having type 1 diabetes in Cameroon vs 96% in Belgium (p<0.001). Not one Ab(+) Cameroonian patient carried HLA-DQ2/DQ8 genotype vs 23% of Belgian Ab(+) patients (p<0.001). Younger age at diagnosis and antibody positivity were independent predictors of insulin therapy. Ab(+) Cameroonian patients were older (p<0.001), had higher BMI (p<0.001) and lower Ab titers than Belgian Ab(+) patients. In ketonuric patients, prevalence of autoantibodies was similar as in non-ketonuric patients. CONCLUSIONS In Cameroonian patients with diabetes aged under 40 years, antibody-positivity is not clearly related to disease phenotype, but may help predict the need for insulin treatment.
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Affiliation(s)
- Milca Asanghanwa
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium
| | - Frans K Gorus
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium; Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels Free University - UZ Brussel, Brussels, Belgium
| | - Ilse Weets
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium; Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels Free University - UZ Brussel, Brussels, Belgium
| | - Bart V der Auwera
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium
| | - Folefac Aminkeng
- The Canadian Pharmacogenomics Network for Drug Safety, University of British Columbia, Canada
| | - Eric Mbunwe
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium
| | - Patrick Goubert
- Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels Free University - UZ Brussel, Brussels, Belgium
| | - Katrijn Verhaeghen
- Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels Free University - UZ Brussel, Brussels, Belgium
| | - Eugene Sobngwi
- Faculty of Medicine and Biomedical Sciences, Department of Medicine and Specialties, Laboratory for Molecular and Metabolic Medicine, The Biotechnology Centre, University of Yaoundé 1, Yaoundé, Cameroon
| | - Janet M Wenzlau
- Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, CO, United States
| | - John C Hutton
- Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, CO, United States
| | - Daniel G Pipeleers
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium
| | - Bart Keymeulen
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium; Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels Free University - UZ Brussel, Brussels, Belgium
| | - Jean-Claude N Mbanya
- Faculty of Medicine and Biomedical Sciences, Department of Medicine and Specialties, Laboratory for Molecular and Metabolic Medicine, The Biotechnology Centre, University of Yaoundé 1, Yaoundé, Cameroon
| | - Chris van Schravendijk
- Diabetes Research Center, Brussels Free University - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium.
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Status and trends of diabetes in Chinese children: analysis of data from 14 medical centers. World J Pediatr 2013; 9:127-34. [PMID: 23677831 DOI: 10.1007/s12519-013-0414-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Accepted: 11/26/2012] [Indexed: 01/14/2023]
Abstract
BACKGROUND Childhood diabetes has become a growing concern. We conducted a study to evaluate the status and trend of diabetes from 14 medical centers in China. Pre-diabetic status among obese children was also noted. METHODS Hospital medical records were reviewed, and data of diabetes were collected from 1995 through 2010. We took every five years as a calculation unit to analyze the trend of new-onset diabetes. Data on obesity were collected in the recent five years. RESULTS A total of 4 337 836 patients aged 0-18 years were discharged from the 14 centers. The prevalence (per 100 000 persons) of new-onset type 1 diabetes, type 2 diabetes and other types of diabetes were 96.8, 8.0, and 3.3, respectively. The prevalence of type 1 diabetes increased from 90.9 to 92.9 and 101.4, while type 2 diabetes increased from 4.1 to 7.1 and 10.0 in every five years (P<0.0001). The increasing trend was significant from Southwest to East and North China (type 1 diabetes from 59.76 to 80.02 and 120.45, type 2 diabetes from 2.52 to 3.77 and 15.64 (per 100 000 persons) (all P<0.0001). Well developed areas in China had a higher prevalence compared to less developed areas [type 1 diabetes: 151.51 vs. 32.2 (per 100 000 persons); type 2 diabetes: 15.16 vs. 1.64 and others: 7.54 vs. 0.42 (per 100 000 persons)]. Of the 3153 obese children, 18.24% had impaired fasting glucose (IFG), 5.99% had impaired gulose tolerance (IGT), and 4% had combined IFG and IGT. CONCLUSIONS The prevalence of childhood diabetes in China has increased dramatically, with type 2 diabetes exceeding type 1 diabetes. The incidence rate of abnormal glucose metabolism in obese children has reached 28.26%.
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Nakashima K, Narukawa M, Kanazu Y, Takeuchi M. Differences Between Japan and the United States in Dosages of Drugs Recently Approved in Japan. J Clin Pharmacol 2013; 51:549-60. [DOI: 10.1177/0091270010375958] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Mishra PK, Patel N, Wu W, Bleich D, Gause WC. Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response. Mucosal Immunol 2013; 6:297-308. [PMID: 22806101 DOI: 10.1038/mi.2012.71] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Helminth infection can prevent type 1 diabetes (T1D); however, the regulatory mechanisms inhibiting disease remain largely undefined. In these studies, nonobese diabetic (NOD) IL-4(-/-) mice were infected with the strictly enteric nematode parasite, Heligmosomoides polygyrus. Short-term infection, 5-7 weeks of age, inhibited T1D onset, as late as 40 weeks of age. CD4(+) T-cell STAT6 phosphorylation was inhibited, while suppressed signal transducer and activator of transcription 1 phosphorylation was sustained, as were increases in FOXP3(-), CD4(+) T-cell interleukin (IL)-10 production. Blockade of IL-10 signaling in NOD-IL-4(-/-), but not in NOD, mice during this short interval abrogated protective effects resulting in pancreatic β-cell destruction and ultimately T1D. Transfer of CD4(+) T cells from H. polygyrus (Hp)-inoculated NOD IL-4(-/-) mice to NOD mice blocked the onset of T1D. These studies indicate that Hp infection induces non-T-regulatory cells to produce IL-10 independently of STAT6 signaling and that in this Th2-deficient environment IL-10 is essential for T1D inhibition.
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Affiliation(s)
- P K Mishra
- Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA
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Ko SH, Kwon HS, Song KH, Ahn YB, Yoon KH, Yim HW, Lee WC, Park YM. Long-term changes of the prevalence and control rate of hypertension among Korean adults with diagnosed diabetes: 1998-2008 Korean National Health and Nutrition Examination Survey. Diabetes Res Clin Pract 2012; 97:151-7. [PMID: 22609056 DOI: 10.1016/j.diabres.2012.04.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2011] [Revised: 03/10/2012] [Accepted: 04/03/2012] [Indexed: 11/17/2022]
Abstract
AIMS We investigated the long-term changes in the prevalence and the control rate of hypertension among Korean adults diagnosed with diabetes. METHODS Using data from the Korean National Health and Nutrition Examination Survey (1998-2008), including 1384 adults diagnosed with diabetes, we analyzed changes in the prevalence of hypertension (mean SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or use of antihypertensive medication) and the control rate of hypertension (BP < 130/80 mmHg). RESULTS The prevalence of hypertension in diabetic adults was 50.9% in 1998 and 51.7% in 2008 (P = 0.563). The mean blood pressure decreased from 138.1 ± 1.1/80.0 ± 0.6 mmHg to 124.7 ± 0.8/76.0 ± 0.5 mmHg (P < 0.001); awareness (37.4 to 85.2%, P < 0.001), treatment (37.4 to 81.8%, P < 0.001), and the control rate (20.1 to 34.7%, P = 0.001) steadily increased. The prevalence of hypertension increased significantly more in the obese group compared with the non-obese group (53.3% vs. 49.0% in 1998, P = 0.784; 64.3% vs. 42.0% in 2008, P < 0.0001, respectively, P for trend = 0.0001). CONCLUSIONS Although the rates of hypertension treatment have significantly improved, the control rate remains inadequate, and intensive intervention is urgently needed.
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Affiliation(s)
- Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea
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Ling F, Zhuo M, Ni C, Zhang GQ, Wang T, Li W, Wei LQ, Du HL, Wang JF, Wang XN. Comprehensive identification of high-frequency and co-occurring Mafa-B, Mafa-DQB1, and Mafa-DRB alleles in cynomolgus macaques of Vietnamese origin. Hum Immunol 2012; 73:547-553. [PMID: 22365968 PMCID: PMC7115533 DOI: 10.1016/j.humimm.2012.02.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Revised: 01/24/2012] [Accepted: 02/01/2012] [Indexed: 11/13/2022]
Abstract
High-frequency alleles and/or co-occurring human leukocyte antigen (HLA) alleles across loci appear to be more important than individual alleles, because they might be markers of disease risk that have clinical value as biomarkers for targeted screening or the development of new therapies. To better elucidate the major histocompatibility complex background and to facilitate the experimental use of cynomolgus macaques, Mafa-B, Mafa-DQB1, and Mafa-DRB alleles were characterized and their combinations were investigated from 30 macaques of Vietnamese origin by cloning and sequencing. A total of 48 Mafa-B, 22 Mafa-DQB1, and 42 Mafa-DRB alleles, were detected in this study, respectively. In addition, two Mafa-DQB1 and eight Mafa-DRB alleles represented novel sequences that had not been documented in earlier studies. Our results also showed that the macaque from Vietnam might be valuable because >30% of the test animals possessed Mafa-DRB*w304 (30%) and -DQB1*0616 (30%). We report that the combination of major histocompatibility complex (MHC) class I and II alleles, including the combination of DRB3*0403-DRB*w304, DRB1*1013-DRB*w304, and Mafa-B*007:01:01-DRB*w304, which was in 17%, 13%, and 13% of the animals, respectively. Interesting, more than two Mafa-DQB1 alleles detected in one animal in this study suggest that Mafa-DQB1, like Mafa-DRB, might be a duplication in the chromosome, which have ever been documented in cynomolgus monkeys but has not yet been observed in rhesus macaques or other primates. Our results for the high frequency of commonly co-occurring MHC alleles across loci in a cohort of the Vietnamese cynomolgus macaque emphasized the value of this species as a model for biomedical research.
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Affiliation(s)
- Fei Ling
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, P.R. China
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Hsu WC, Boyko EJ, Fujimoto WY, Kanaya A, Karmally W, Karter A, King GL, Look M, Maskarinec G, Misra R, Tavake-Pasi F, Arakaki R. Pathophysiologic differences among Asians, native Hawaiians, and other Pacific Islanders and treatment implications. Diabetes Care 2012; 35:1189-98. [PMID: 22517940 PMCID: PMC3329855 DOI: 10.2337/dc12-0212] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- William C Hsu
- Asian American Diabetes Initiative, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
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Sayad A, Akbari MT, Pajouhi M, Mostafavi F, Zamani M. The influence of the HLA-DRB, HLA-DQB and polymorphic positions of the HLA-DRβ1 and HLA-DQβ1 molecules on risk of Iranian type 1 diabetes mellitus patients. Int J Immunogenet 2012; 39:429-36. [PMID: 22494469 DOI: 10.1111/j.1744-313x.2012.01116.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Type 1 Diabetes mellitus (T1D) is an autoimmune and multifactorial disease. HLA-DRB1 and DQB1 loci have the strongest association with T1D. This study aimed at investigating (i) susceptibility or protection of alleles, genotypes and haplotypes of HLA-DRB1 and DQB1 loci; and (ii) highly polymorphic amino acid residues of HLA-DRβ1 and DQβ1 in 105 Iranian T1D patients and 100 controls. The results indicated that DRB1*04:01, 03:01, DQB1*03:02, 02:01 alleles, DRB1*03:01/04:01, 03:01/13:03, DQB1*02:01/03:02 genotypes, DRB1*04:01-DQB1*03:02, DRB1*03:01-DQB1*02:01, DRB1*07:01-DQB1*03:03 haplotypes had positive association with T1D. In contrast, HLA-DRB1*15:01, 13:01, DQB1*03:01, 06:01 alleles, DRB1*11:01/15:01, DQB1*03:01/06:01, 03:01/05:01 genotypes and DRB1*15:01-DQB1*06:01, DRB1*11:01-DQB1*03:01 haplotypes had negative association with T1D. Analysis of amino acid sequence of HLA-DRβ1 and DQβ1 revealed that DRβ1(Lys71+) and DQβ1(Asp57-) were significantly more frequent in patients than in controls and had a positive effect in the development of T1D. Haplotype analysis demonstrated that HLA-DRB1(Lys71+) allele provided major susceptibility for T1D, and DQβ1(Asp57-) had an additive effect. We designed an allele-specific primer to develop an easy, quick and cost-benefit method to detect the DRβ1(Lys71+) . This method can identify all 114 DRB1 alleles encoding DRβ1(Lys71+) by three PCR reactions. The PcPPV and PcNPV were also calculated to determine the impact of HLA genotype testing at amino acid positions. It showed that the DRβ1(Lys71+/+) genotype carrier had 1% absolute risk of developing T1D.
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Affiliation(s)
- A Sayad
- Department of Neurogenetics, Iranian Centre of Neurological Research, Tehran
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Alves LI, Davini E, Correia MR, Fukui RT, Santos RF, Cunha MR, Rocha DM, Volpini WMG, Silva MER. Autoantibodies and high-risk HLA susceptibility markers in first-degree relatives of Brazilian patients with type 1 diabetes mellitus: a progression to disease based study. J Clin Immunol 2012; 32:778-85. [PMID: 22402866 DOI: 10.1007/s10875-012-9673-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2012] [Accepted: 02/15/2012] [Indexed: 01/21/2023]
Abstract
PURPOSE The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes (T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives. METHODS IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM. RESULTS Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes. CONCLUSIONS The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.
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Affiliation(s)
- L I Alves
- Laboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School, São Paulo, Brazil
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Kim JW, Cheong JH, Hyung WJ, Choi SH, Noh SH. Outcome after gastrectomy in gastric cancer patients with type 2 diabetes. World J Gastroenterol 2012; 18:49-54. [PMID: 22228970 PMCID: PMC3251805 DOI: 10.3748/wjg.v18.i1.49] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Revised: 04/15/2011] [Accepted: 04/22/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the prognosis of type II diabetes mellitus (T2DM) after gastrectomy and related factors in gastric cancer patients.
METHODS: 403 gastric cancer patients with T2DM were studied, who underwent gastrectomy between May 2003 and September 2009. A review of medical records and telephone interviews was performed in this cross-sectional study. The factors included in the statistical analysis were as follows: gender, age, type of surgery, preoperative body mass index (BMI), current BMI, BMI reduction ratio, preoperative insulin or oral diabetic medicine requirement, follow-up duration, and current state of diabetes. Assessment of diabetes status after surgery was classified into four categories according to the change in hypoglycemic agents after surgery and present status of T2DM: resolution, improvement, same, and worse.
RESULTS: The mean follow-up duration was 33.7 mo (± 20.6 mo), preoperative BMI was 24.7 kg/m2 (± 3.0 kg/m2), and BMI reduction ratio was 9.8% (± 8.6%). After surgery, T2DM was cured in 58 patients (15.1%) and was improved in 117 patients (30.4%). According to the type of surgery, the BMI reduction ratio was significantly higher in the total gastrectomy and Roux-en-Y reconstruction group [14.2% ± 9.2% vs 9.2% ± 7.7% (Billroth II group), P < 0.001] and significantly lower in the subtotal gastrectomy and Billroth I reconstruction group [7.6% ± 8.0%, 9.2% ± 7.7% (Billroth II group), P < 0.001]. The BMI reduction ratio, follow-up duration after surgery, type of surgery, extent of gastrectomy, and performance of duodenal bypass were significantly correlated to the course of T2DM (P < 0.05). The BMI reduction ratio was the most influential factor on T2DM status. In a subgroup analysis of patients with a BMI reduction ratio of 10% or less (n = 206), T2DM was cured in 15 (7.6%) patients and was improved in 57 (28.8%) patients after surgery, and only the duration of surgery was significantly correlated to T2DM status (P = 0.022).
CONCLUSION: The course of T2DM was significantly correlated to the BMI reduction ratio but not to the type of surgery without a significant change in BMI.
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Park Y, Lee HS, Park Y, Min D, Yang S, Kim D, Cho B. Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population. Diabetes Metab Res Rev 2011; 27:867-71. [PMID: 22069275 DOI: 10.1002/dmrr.1263] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Recently, the association of a common STAT4 haplotype with type 1 diabetes (T1D) as well as rheumatoid arthritis has been documented in Caucasians and Koreans. STAT4 is involved in the signalling of interleukin-12 and γIFN, as well as interleukin-23. To discover genes affecting the susceptibility of common autoimmune diseases, we studied the association of polymorphisms in STAT4 with autoimmune thyroid disease (AITD) as well as T1D in the Korean population. SUBJECTS AND METHODS Four single-nucleotide polymorphisms on the chromosome 2q (rs11889341, rs7574865, rs8179673, and rs10181656), which were found to associate with rheumatoid arthritis were examined for association in a Korean sample of 428 AITD, 418 T1D patients, and 1060 controls. RESULTS The minor alleles of all four single-nucleotide polymorphisms and the reconstructed STAT4 haplotypes conferred significant degree of risk for AITD (p=10(-2) to 10(-4)). Although we found a weak association of rs11889341 with T1D (p<0.05), the same haplotypes were not associated with T1D susceptibility. When we stratified T1D patients according to the age of onset, the minor alleles of all four single-nucleotide polymorphisms and the same haplotypes showed significant association with the susceptibility of T1D in the early-onset subgroup (p<0.01), not in the late-onset subgroup. CONCLUSION STAT4 alleles and the same haplotypes might influence cytokine signalling, and therefore the development of AITD as well as T1D. These results reinforce the influence of STAT4 gene as a general autoimmune gene.
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Affiliation(s)
- Yongsoo Park
- Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, and Hanyang University Hospital, Seoul, Korea.
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Lee HS, Kang J, Yang S, Kim D, Park Y. Susceptibility influence of a PTPN22 haplotype with thyroid autoimmunity in Koreans. Diabetes Metab Res Rev 2011; 27:878-82. [PMID: 22069277 DOI: 10.1002/dmrr.1265] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Considerable amount of evidences in the Caucasians have suggested the association of a missense single-nucleotide polymorphism (SNP) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene (rs2476601) with several autoimmune diseases including autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). As the SNP was reported to be non-polymorphic in Asians, we attempt to explore an association of PTPN22 without restricting to the rs2476601 with AITD or T1D in Korean population. METHODS We studied 389 T1D, 212 AITD (84 Graves' disease and 128 Hashimoto's thyroiditis) patients and 225 controls. In addition to the rs2476601, we selected five testing SNPs spanning 58 kb over the PTPN22 gene using the previous resequencing data and International HapMap Project. RESULTS We found that neither alleles, genotypes among all five SNPs, nor reconstructed haplotypes of five SNPs were associated with T1D. Interestingly, a minor allele of a SNP (rs12730735) and a haplotype (GGCTT) showed significant association with the susceptibility of AITD, especially with that of Hashimoto's thyroiditis (p<0.01). CONCLUSIONS These results indicate that the PTPN22 gene polymorphism independent of the SNP rs2476601 might be a supplementary risk factor to AITD, but not in T1D in Koreans, contradicting a major contributory influence of the PTPN22 gene in explaining common mechanism underlying multiple autoimmune diseases.
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Affiliation(s)
- Hye-Soon Lee
- Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, and Hanyang University Hospital, Seoul, Korea
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Jirapongsananuruk O, Pongpreuksa S, Sangacharoenkit P, Visitsunthorn N, Vichyanond P. Identification of the etiologies of chronic urticaria in children: a prospective study of 94 patients. Pediatr Allergy Immunol 2010; 21:508-14. [PMID: 19555353 DOI: 10.1111/j.1399-3038.2009.00912.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The etiologies of chronic urticaria (CU) in childhood remains incompletely understood because of limited data in children. The objective of this study was to examine some of the possible etiologies of CU in children by focusing on the functional autoantibody to FcepsilonRIalpha and IgE, thyroid autoimmunity, urticarial vasculitis, parasitic infestation and food allergy. Children 4-15 yr of age with CU were investigated for complete blood count, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), CH(50), free-T4 (FT(4)), thyroid stimulating hormone (TSH), anti-thyroglobulin and anti-microsomal antibody, autologous serum skin test (ASST), skin prick tests (SPT) for foods, food challenges, and stool examination for parasites. Ninety-four children who met the criteria for CU were recruited. Patients with physical urticaria were excluded. Eosinophilia and elevated ESR were found in 23% and 13%, respectively. High ANA titers were found in 2%. None of these patients had clinical features of urticarial vasculitis, abnormal CH(50) level, abnormal TSH and FT(4). Anti-thyroglobulin and anti-microsomal antibodies were not detected. Positive ASST was found in 38%. There were no differences in medication requirement and CU remission between patients with positive and negative ASST. Parasites were found in 5% without clinical correlation. SPT to foods was positive in 35%. Positive food challenges were found in six/nine patients with positive history of food allergy and two/seven patients with negative history. Food avoidance was beneficial to the subgroup of patients with positive history of food allergy only.
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Beta-cell autoantibodies and their function in Taiwanese children with type 1 diabetes mellitus. J Formos Med Assoc 2010; 108:856-61. [PMID: 19933029 DOI: 10.1016/s0929-6646(09)60417-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND/PURPOSE To understand the importance of autoimmunity in the development of type 1 diabetes in Taiwanese children, we evaluated the presence of beta-cell autoantibodies and their correlation with residual beta-cell function. METHODS From 1989 to 2006, 157 Taiwanese children with newly diagnosed type 1 diabetes were enrolled in this study. We determined the presence of beta-cell autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), insulinoma antigen 2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs). A 6-minute glucagon test was also performed at diagnosis. RESULTS At diagnosis, 73% of children tested positive for GADAs, 76% for IA-2As and 21% for IAAs. Ninety-two percent of them had at least one of the beta-cell autoantibodies detected. Positivity for IAAs was more frequent in patients younger than 5 years than in those older than 5 years (45% vs. 13%). Using multiple regression analysis, the presence of GADAs or IAAs, or age of onset of these patients was an independent factor for residual beta-cell function. Younger patients and those with GADAs had less residual beta-cell function at disease onset, whereas those with IAAs had more insulin reserve. CONCLUSION Autoimmunity plays an important role in the pathogenesis of type 1 diabetes in Taiwanese children, and the presence of IAAs tends to be more common in younger children.
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Raha O, Chowdhury S, Dasgupta S, Raychaudhuri P, Sarkar BN, Raju PV, Rao VR. Approaches in type 1 diabetes research: A status report. Int J Diabetes Dev Ctries 2010; 29:85-101. [PMID: 20142874 PMCID: PMC2812756 DOI: 10.4103/0973-3930.53126] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2008] [Accepted: 05/29/2009] [Indexed: 12/18/2022] Open
Abstract
Type 1 diabetes is a multifactorial disease with an early age of onset, in which the insulin producing beta cell of the pancreas are destroyed because of autoimmunity. It is the second most common chronic disease in children and account for 5% to 10% of all diagnosed cases of diabetes. India is having an incidence of 10.6 cases/year/100,000, and recent studies indicate that the prevalence of type 1 diabetes in India is increasing. However in view of poor health care network, there is no monitoring system in the country. Of the 18 genomic intervals implicated for the risk to develop type 1 diabetes, the major histocompatibility complex (MHC) region on chromosome 6p21.31 has been the major contributor estimated to account for 40-50%, followed by 10% frequency of INS-VNTR at 5' flanking region of the insulin gene on chromosome 11p15.5. However, population studies suggest that > 95% of type 1 diabetes have HLA-DR3 or DR4, or both, and in family studies, sibling pairs affected with type 1 diabetes have a non-random distribution of shared HLA haplotypes. As predisposing genetic factors such as HLA alleles are known, immunological interventions to prevent type 1 diabetes are of great interest. In the present study we have reviewed the status of molecular genetics of the disease and the approaches that need to be adopted in terms of developing patient and suitable control cohorts in the country.
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Affiliation(s)
- Oindrila Raha
- Anthropological Survey of India, 27-Jawaharlal Nehru Road, Kolkata, West-Bengal - 700 016, India
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Lee HS, Park H, Yang S, Kim D, Park Y. STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes. Ann N Y Acad Sci 2009; 1150:93-8. [PMID: 19120275 DOI: 10.1196/annals.1447.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
In an effort to discover non-HLA genes affecting susceptibility to type 1 diabetes (T1D), we have investigated the association of polymorphisms in STAT4, an important signaling molecule of IL-12, gammaIFN, and IL-23, in a sample of 389 T1D patients and 152 nondiabetic controls in Korea. Four SNPs on chromosome 2q, which were recently found to be associated with rheumatoid arthritis, were examined for association and linkage disequilibrium. We found that neither alleles or genotypes among all four SNPs nor reconstructed haplotypes of the three SNPs within the same LD block (rs7574865, rs8179673, and rs10181656) were associated with susceptibility to T1D. When we stratified T1D patients into early-onset and late-onset subgroups on the basis of fewer or more than 7.8 years of age at diagnosis, however, the minor alleles of three SNPs (rs7574865, rs8179673, and rs10181656) showed a significant association with susceptibility to T1D in the early-onset subgroup (i.e., rs7574865, OR = 1.44 [1.03-2.01], P < 0.05), but not in the late-onset subgroup, suggesting that STAT4 is related to earlier development of T1D. The analysis of genotypes and haplotypes of the same SNPs (rs7574865, rs8179673, and rs10181656) showed very comparable degrees of risk for T1D. The age at diagnosis is lowest in the patients carrying the homozygotes of a minor allele, middle in the heterozygotes, and highest in the homozygotes of a major allele, suggesting the dosage effects of risk alleles on the age of onset of disease. Recognizing that only the early-onset cases might represent the true autoimmune T1D in Asian populations, we see that STAT4 alleles and haplotype might influence cytokine signaling and, therefore, development of T1D.
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Affiliation(s)
- Hye-Soon Lee
- Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, Seoul, Korea
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Shin HD, Yang SW, Kim DH, Park Y. Independent association of tumor necrosis factor polymorphism with type 1 diabetes susceptibility. Ann N Y Acad Sci 2009; 1150:76-85. [PMID: 19120272 DOI: 10.1196/annals.1447.059] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The contribution of SNPs in TNF genes to type 1 diabetes (T1D) is not well established and may be confounded by the linkage disequilibrium within the HLA genes. Seven SNPs in the TNF genes (TNFA and TNFB) were genotyped in a Korean cohort (398 T1D patients and 1422 nondiabetic controls), along with HLA DRB1, DQB1, and MICA (MHC class I chain-related genes). Among them, three SNPs (TNFB+318, TNFA-857, and TNFA-308) and two common TNF haplotypes showed significant association with the risk of T1D (P= 5 x 10(-3)-10(-5)). T1D patients were more often heterozygous for the alleles at the TNFB+318 (OR = 1.7, P= 10(-3)) and TNFA-308 (OR = 1.7, P < 10(-5)) than were the controls. Genetic association analyses of the DRB1, DQB1, and MICA alleles with the risk of T1D revealed dramatic associations in several alleles as expected. Independent analyses to discern the genetic effects of TNF polymorphisms on the risk of T1D suggested that these genetic influences might be not totally dependent on the nearby HLA genes. Our results support the hypothesis that two susceptibility loci in the MHC (one in the HLA class II and another in the central MHC region) act epistatically to increase susceptibility to T1D.
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Affiliation(s)
- Hyoung Doo Shin
- Department of Genetic Epidemiology, SNP Genetics, Gasan-Dong, Geumcheon-Gu, Seoul, Korea
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Thai AC, Mohan V, Khalid BAK, Cockram CS, Pan CY, Zimmet P, Yeo JP. Islet autoimmunity status in Asians with young-onset diabetes (12-40 years): association with clinical characteristics, beta cell function and cardio-metabolic risk factors. Diabetes Res Clin Pract 2008; 80:224-30. [PMID: 18207602 DOI: 10.1016/j.diabres.2007.12.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2007] [Accepted: 12/04/2007] [Indexed: 10/22/2022]
Abstract
In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.
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Affiliation(s)
- A C Thai
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore, Singapore
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