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Li XN, Kan YS, Liu HY, Pang J, He YY, Liu L, Zou Y, Zhang N, Zhang Y. Prevalence and contributing factors of impaired awareness of hypoglycemia in patients with type 2 diabetes: a meta-analysis. Acta Diabetol 2023; 60:1155-1169. [PMID: 37199797 DOI: 10.1007/s00592-023-02102-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/18/2023] [Indexed: 05/19/2023]
Abstract
AIMS To conduct a systematic review to summarize the definition, measurement tools, prevalence, and contributing factors of impaired awareness of hypoglycemia (IAH) in type 2 diabetes mellitus (T2DM). METHODS A reproducible search strategy was used to identify factors affecting IAH in T2DM in PubMed, MEDLINE, EMBASE, Cochrane, PsycINFO, and CINAHL from inception until 2022. Literature screening, quality evaluation, and information extraction were performed independently by 2 investigators. A meta-analysis of prevalence was performed using Stata 17.0. RESULTS The pooled prevalence of IAH in patients with T2DM was 22% (95%CI:14-29%). Measurement tools included the Gold score, Clarke's questionnaire, and the Pedersen-Bjergaard scale. IAH in T2DM was associated with sociodemographic factors (age, BMI, ethnicity, marital status, education level, and type of pharmacy patients visited), clinical disease factors (disease duration, HbAlc, complications, insulin therapy regimen, sulfonylureas use, and the frequency and severity of hypoglycemia), and behavior and lifestyle (smoking and medication adherence). CONCLUSION The study found a high prevalence of IAH in T2DM, with an increased risk of severe hypoglycemia, suggesting that medical workers should take targeted measures to address sociodemographic factors, clinical disease, and behavior and lifestyle to reduce IAH in T2DM and thus reduce hypoglycemia in patients.
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Affiliation(s)
- Xiang-Ning Li
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Yin-Shi Kan
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Hong-Yuan Liu
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China
| | - Juan Pang
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Yu-Ying He
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Lin Liu
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Yan Zou
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Ning Zhang
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China
| | - Yu Zhang
- School of Nursing, Yangzhou University, Jiangyang Road 136, Yangzhou, China.
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China.
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Kijprasert W, Tarudeeyathaworn N, Loketkrawee C, Pimpaporn T, Pattarasettaseranee P, Tangsuwanaruk T. Predicting hypoglycemia after treatment of hyperkalemia with insulin and glucose (Glu-K60 score). BMC Emerg Med 2022; 22:179. [DOI: 10.1186/s12873-022-00748-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Background
Hyperkalemia can lead to fatal cardiac arrhythmias. Ten units of intravenous (IV) regular insulin with 25 g of glucose is the mainstay for treating hyperkalemia. However, the most important complication of this treatment is hypoglycemia. We aimed to develop a scoring model to predict hypoglycemia after the treatment of hyperkalemia.
Methods
A retrospective study was conducted at a university-based hospital between January 2013 and June 2021. We included the hyperkalemic patients (> 5.3 mmol/L) who were ≥ 18 years old and treated with 10 units of IV regular insulin with 25 g of glucose. Incomplete data on posttreatment blood glucose, pregnancy, and diabetes mellitus were excluded. Endpoint was posttreatment hypoglycemia (≤ 70 mg/dL or ≤ 3.9 mmol/L). Multivariable logistic regression was used to establish a full model and a subsequently reduced model using the backward elimination method. We demonstrated the model performance using the area under the receiver operating characteristic curve (AuROC), calibration plot, and Hosmer–Lemeshow goodness-of-fit test. Internal validation was done with a bootstrap sampling procedure with 1000 replicates. Model optimism was estimated.
Results
Three hundred and eighty-five patients were included, with 97 posttreatment hypoglycemia (25.2%). The predictive model comprised the following three criteria: age > 60 years old, pretreatment blood glucose ≤ 100 mg/dL (≤ 5.6 mmol/L), and pretreatment potassium > 6 mmol/L. The AuROC of this model was 0.671 (95% confidence interval [CI] 0.608 to 0.735). The calibration plot demonstrated consistency with the original data. Hosmer–Lemeshow goodness-of-fit test showed no evidence of lack-of-fit (p 0.792); therefore, the model was also fit to the original data. Internal validation via bootstrap sampling showed a consistent AuROC of 0.670 (95% CI 0.660 to 0.670) with minimal model optimism. A high risk for posttreatment hypoglycemia was indicated if the patient met at least one of those criteria. Sensitivity and specificity were 95.9% and 14.9%, respectively.
Conclusion
High risk was indicated when at least one of the criteria was met: age > 60 years old, pretreatment blood glucose ≤ 100 mg/dL (≤ 5.6 mmol/L), and pretreatment potassium > 6 mmol/L. Blood glucose levels should frequently check in the high-risk group.
Trial registration
TCTR20210225002 (www.thaiclinicaltrials.org).
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A comprehensive health education plus monitoring support program for older adults with knee osteoarthritis coexisting with overweight and type 2 diabetes. Int J Nurs Sci 2022; 9:512-520. [PMID: 36285081 PMCID: PMC9587398 DOI: 10.1016/j.ijnss.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 12/03/2022] Open
Abstract
Objectives To examine the patient outcomes of a comprehensive health education plus village health volunteer monitoring support program on older adults with knee osteoarthritis who are overweight and have type 2 diabetes. Methods Quasi-experimental, two-group, pretest-posttest design was applied. Using random geographic cluster sampling, older adults who met the inclusion criteria were assigned to two groups, 62 in the intervention group and 71 in the control group. The intervention group received the comprehensive health education plus village health volunteer monitoring support program. The control group received only the comprehensive health education program. Study outcomes, including blood glucose level, knee pain and range of motion, body weight, physical ability (Timed Up and Go Test), fatigue, depressive symptoms, quality of sleep, and quality of life, were assessed at baseline, 3 months, and 6 months after enrollment and analyzed using descriptive statistics and multivariate analysis of variance. Results One hundred and ten participants completed the study (55 participants in each group). Most patient outcomes in the two groups showed general improvement with statistical significance (P ≤ 0.001): pain decreased, physical ability improved, less depressive symptoms and fatigue, quality of life and sleep improved. The interaction effect (the group and time) demonstrated statistically significant differences between the intervention and control groups on pain, knee range of motion, and fatigue according to each time follow-up (P < 0.001). Conclusions The comprehensive health education plus village health volunteer monitoring support program promotes good patient outcomes in this population. The integrated health education resource and support for older adults with knee osteoarthritis and type 2 diabetes is an effective, non-surgical treatment that highlights professional nursing roles and non-professional roles—village health volunteers. Nurses should consider implementing a health education plus monitoring support program to mitigate the effects of chronic diseases and improve patients’ quality of life.
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Association between Dietary Magnesium Intake and Glycemic Markers in Ghanaian Women of Reproductive Age: A Pilot Cross-Sectional Study. Nutrients 2021; 13:nu13114141. [PMID: 34836395 PMCID: PMC8619971 DOI: 10.3390/nu13114141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 01/03/2023] Open
Abstract
Low magnesium intake has been shown to be associated with an increased risk of type 2 diabetes mellitus (T2DM) in several studies conducted in high-income countries. However, very few studies have been performed in Africa, where many countries have a growing rate of T2DM. We conducted a pilot cross-sectional study among 63 women in Ghana to investigate the association between magnesium intake and glycemic markers. We assessed dietary magnesium using a food frequency questionnaire and glycemic markers using fasting blood glucose and glycated hemoglobin A1c (HbA1c). Our findings showed that the mean magnesium intake was 200 ± 116 mg/day. The prevalence of T2DM was 5% by measuring fasting blood glucose and 8% by measuring HbA1c. Unadjusted linear regression models revealed that higher magnesium intake significantly predicted higher fasting blood glucose levels (β = 0.31; 95% CI: 0.07, 0.55; p = 0.01) and HbA1c levels (β = 0.26; 95% CI: 0.01, 0.51; p = 0.04). In adjusted analyses, magnesium intake was no longer significantly associated with either fasting blood glucose levels (β = 0.22; 95% CI: −0.03, 0.46; p = 0.08) or HbA1c levels (β = 0.15; 95% CI: −0.08, 0.39; p = 0.20). In conclusion, our study did not show a significant association between magnesium intake and glycemic markers in women of reproductive age in Ghana. The results of this study need to be further substantiated because this was the first study to examine magnesium intake and glycemic markers in this population in Africa.
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Tanaka K, Higuchi R, Mizusawa K, Nakamura T, Nakajima K. Fasting biochemical hypoglycemia and related-factors in non-diabetic population: Kanagawa Investigation of Total Check-up Data from National Database-8. World J Diabetes 2021; 12:1131-1140. [PMID: 34326960 PMCID: PMC8311474 DOI: 10.4239/wjd.v12.i7.1131] [Citation(s) in RCA: 1] [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: 02/08/2021] [Revised: 04/28/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In healthy people, the lowest daily blood glucose concentration is usually observed in the early morning, after overnight fasting. However, the clinical relevance and the prevalence of fasting biochemical hypoglycemia (FBH) are poorly understood in people who do not have diabetes, although the clinical implications of such hypoglycemia have been extensively studied in patients with diabetes. FBH can be influenced by many factors, including age, sex, body mass, smoking, alcohol drinking, exercise levels, medications, and eating behaviors, such as breakfast skipping and late-night eating. AIM To determine the prevalence of FBH and investigated its association with potential risk factors in a population without diabetes. METHODS Clinical parameters and lifestyle-related factors were assessed in a cross-sectional study of 695613 people aged 40-74 years who had undergone a health check-up (390282 men and 305331 women). FBH was defined as fasting plasma glucose < 70 mg/dL (3.9 mmol/L) after overnight fasting, regardless of any symptoms. The absence of diabetes was defined as HbA1c < 6.5%, fasting plasma glucose < 126 mg/dL (7.0 mmol/L), and no pharmacotherapy for diabetes. Multivariate logistic regression analysis, with adjustment for confounding factors, was used to identify associations. RESULTS FBH was present in 1842 participants (0.26%). There were significantly more women in the FBH group (59.1%) than in the non-FBH group (43.9%). Values of most of the clinical parameters, but not age, were significantly lower in the FBH group than in the non-FBH group. Logistic regression analysis showed that a body mass index of ≤ 20.9 kg/m2 (reference: 21-22.9 kg/m2) and current smoking were significantly associated with FBH, and this was not altered by adjustment for age, sex, and pharmacotherapy for hypertension or dyslipidemia. Female sex was associated with FBH. When the data were analyzed according to sex, men in their 60s or 70s appeared more likely to experience FBH compared with their 40s, whereas men in their 50s and women aged ≥ 50 years appeared less likely to experience FBH. The relationships of FBH with other factors including alcohol drinking and pharmacotherapies for hypertension and dyslipidemia also differed between men and women. CONCLUSION FBH occurs even in non-diabetic people, albeit at a very low frequency. FBH is robustly associated with low body mass and smoking, and its relationship with lifestyle factors varies according to sex.
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Affiliation(s)
- Kotone Tanaka
- Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki 210-0821, Japan
| | - Ryoko Higuchi
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka 238-8522, Japan
| | - Kaori Mizusawa
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka 238-8522, Japan
| | - Teiji Nakamura
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka 238-8522, Japan
| | - Kei Nakajima
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka 238-8522, Japan
- Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, Japan
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Abdelhafiz AH, Emmerton D, Sinclair AJ. Impact of frailty metabolic phenotypes on the management of older people with type 2 diabetes mellitus. Geriatr Gerontol Int 2021; 21:614-622. [PMID: 34151494 DOI: 10.1111/ggi.14214] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 05/08/2021] [Accepted: 05/27/2021] [Indexed: 12/25/2022]
Abstract
AIMS To provide a pathophysiological basis for distinguishing metabolic variants of the frailty phenotype in older adults with type 2 diabetes. METHODS We have made an in-depth review of the possible mechanisms in diabetes, ageing and frailty that will alter allow us to describe phenotypic changes which might assist in predicting responses to particular glucose-lowering therapy. RESULTS Our review has enable us to describe with some confidence a sarcopenic obese phenotype and an anorexic malnourished phenotype. CONCLUSIONS By identifying these two phenotypes we can predict which would be most responsive to certain classes of therapy and where therapies may be ill-advised. This represents the first novel approach in this area. Further work is being planned to develop this hypothesis. Geriatr Gerontol Int 2021; 21: 614-622.
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Affiliation(s)
- Ahmed H Abdelhafiz
- Department of Geriatric Medicine, Rotherham General Hospital, Rotherham, UK
| | - Demelza Emmerton
- Department of Geriatric Medicine, Rotherham General Hospital, Rotherham, UK
| | - Alan J Sinclair
- Foundation for Diabetes Research in Older People, Diabetes Frail Ltd, Droitwich Spa, UK
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Emmerton D, Abdelhafiz A. Newer anti-diabetic therapies with low hypoglycemic risk-potential advantages for frail older people. Hosp Pract (1995) 2021; 49:164-175. [PMID: 33729898 DOI: 10.1080/21548331.2021.1905414] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The prevalence of diabetes is increasing due to increasing aging of the population. Hypoglycemia is a common diabetes-related complication in old age especially in patients with multiple comorbidities and frailty. Hypoglycemia and frailty appear to have a bidirectional relationship reenforcing each other in a negative downhill spiral that leads to an increased risk of adverse events including disability and mortality. The incidence of hypoglycemia in this age group is usually underestimated due to its atypical clinical presentation and difficult recognition by health care professionals. Guidelines generally recommend a relaxed glycemic control in frail older people with diabetes mainly due to the fear of anti-diabetic medications-induced hypoglycemia. The new anti-diabetic therapies of sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA) have consistently shown a cardio-renal protective effect independent of their glycemic control. Contrary to the traditional hypoglycemic agents that either increase insulin stimulation or insulin sensitization with a potential hypoglycemic risk especially sulfonylureas, the new therapies have a novel anti-diabetic mechanisms of action that have a negligible risk of hypoglycemia. The new therapies appear to be both effective and well tolerated in old age. With appropriate patients' selection, most older people will be eligible for the new therapies if well tolerated and no contraindications. In frail older people, we suggest a pragmatic approach of the use of the new therapies based on the concept of the weight status rather than the frailty status. Frail patients with normal or excess weight are likely to gain most from the new therapies due to its favorable metabolic properties in this group, while the use in the underweight frail patients should be largely avoided especially in those with persistent anorexia and weight loss.
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Affiliation(s)
- Demelza Emmerton
- Department of Geriatric Medicine, Rotherham General Hospital, Rotherham, United Kingdom of Great Britain and Northern Ireland
| | - Ahmed Abdelhafiz
- Department of Geriatric Medicine, Rotherham General Hospital, Rotherham, United Kingdom of Great Britain and Northern Ireland
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Zhao MJY, Prentice JC, Mohr DC, Conlin PR. Association between hemoglobin A1c variability and hypoglycemia-related hospitalizations in veterans with diabetes mellitus. BMJ Open Diabetes Res Care 2021; 9:9/1/e001797. [PMID: 33431600 PMCID: PMC7802724 DOI: 10.1136/bmjdrc-2020-001797] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/10/2020] [Accepted: 12/14/2020] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION To study the impact of hemoglobin A1c (A1c) variability on the risk of hypoglycemia-related hospitalization (HRH) in veterans with diabetes mellitus. RESEARCH DESIGN AND METHODS 342 059 veterans with diabetes aged 65 years or older were identified for a retrospective cohort study. All participants had a 3-year baseline period from January 1, 2005 to December 31, 2016, during which they had at least four A1c tests. A1c variability measures included coefficient of variation (A1c CV), A1c SD, and adjusted A1c SD. HRH was identified during a 2-year follow-up period from Medicare and the Veterans Health Administration through validated algorithms of International Classification of Diseases (ICD)-9 and ICD-10 codes. Logistic regression modeling was used to evaluate the relationship between A1c variability and HRH risk while controlling for relevant clinical covariates. RESULTS 2871 patients had one or more HRH in the 2-year follow-up period. HRH risk increased with greater A1c variability, and this was consistent across A1c CV, A1c SD, and adjusted A1c SD. Average A1c levels were also independently associated with HRH, with levels <7.0% (53 mmol/mol) having lower risk and >9% (75 mmol/mol) with greater risk. The relationships between A1c variability remained significant after controlling for average A1c levels and prior HRH during the baseline period. CONCLUSION Increasing A1c variability and elevated A1c levels are associated with a greater risk of HRH in older adults with diabetes. Clinicians should consider A1c variability when assessing patients for risk of severe hypoglycemia.
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Affiliation(s)
- Molly J Y Zhao
- Center for Healthcare Organization and Implementation Research (CHOIR), VA Boston Health Care System, Boston, Massachusetts, USA
- Boston University School of Medicine, Boston, Massachusetts, USA
| | - Julia C Prentice
- Center for Healthcare Organization and Implementation Research (CHOIR), VA Boston Health Care System, Boston, Massachusetts, USA
- Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA
| | - David C Mohr
- Center for Healthcare Organization and Implementation Research (CHOIR), VA Boston Health Care System, Boston, Massachusetts, USA
- Health Law, Policy and Management, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Paul R Conlin
- Medical Service (111), VA Boston Healthcare System, West Roxbury, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Abdelhafiz AH, Sinclair AJ. Cognitive Frailty in Older People with Type 2 Diabetes Mellitus: the Central Role of Hypoglycaemia and the Need for Prevention. Curr Diab Rep 2019; 19:15. [PMID: 30806826 DOI: 10.1007/s11892-019-1135-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
PURPOSE OF REVIEW To highlight the central role of hypoglycaemia in the causation of cognitive frailty and explore ways of recognition and prevention of hypoglycaemia. RECENT FINDINGS Cognitive frailty is an emerging new concept defined as the concomitant presence of physical frailty and cognitive impairment. In older people with diabetes, cognitive frailty is associated with an increased risk of mortality greater than from either physical frailty or cognitive impairment alone. Hypoglycaemia is directly associated with increased risk of cognitive impairment and physical frailty which are the two components of cognitive frailty. The incidence of hypoglycaemia in older people with diabetes is rising and hypoglycaemia-related hospitalisation has overtaken that of hyperglycaemia. Recognition of hypoglycaemic episodes in old age remains challenging which leads to misdiagnoses and under-reporting. Therefore, hypoglycaemia prevention strategies are needed. Research is still required to investigate whether prevention of hypoglycaemia would lead to a reduction in the incidence of cognitive frailty.
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Affiliation(s)
- A H Abdelhafiz
- Department of Geriatric Medicine, Rotherham General Hospital, Moorgate Road, Rotherham, S60 2UD, UK.
| | - A J Sinclair
- Foundation for Diabetes Research in Older People, Diabetes Frail Ltd, Droitwich Spa, WR9 0QH, UK
- Kings College, London, SE1 9NH, UK
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Zhou Z, Wang L, Wen Z, Zheng S, Ye X, Liu D, Wu J, Zou X, Liu Y, Wang Y, Dong S, Huang X, Du X, Zhu K, Chen X, Huang S, Zeng C, Han Y, Zhang B, Nie L, Yang G, Jing C. Association Analysis of NLRP3 Inflammation-Related Gene Promotor Methylation as Well as Mediating Effects on T2DM and Vascular Complications in a Southern Han Chinese Population. Front Endocrinol (Lausanne) 2018; 9:709. [PMID: 30555415 PMCID: PMC6281743 DOI: 10.3389/fendo.2018.00709] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 11/09/2018] [Indexed: 12/19/2022] Open
Abstract
Objective: To explore the association between the methylation levels in the promoter regions of the NLRP3, AIM2, and ASC genes and T2DM and its vascular complications in a Southern Han Chinese population and further analyze their interaction and mediating effects with environmental factors in T2DM. Methods: A case-control study was used to determine the association between population characteristics, the methylation level in the promoter region of the NLRP3, AIM2, and ASC genes and T2DM and vascular complications. A mediating effect among genes-environment-T2DM and the interaction of gene-gene or gene-environment factors was explored. Results: In the logistic regression model with adjusted covariants, healthy people with lower total methylation levels in the AIM2 promoter region exhibited a 2.29-fold [OR: 2.29 (1.28~6.66), P = 0.011] increased risk of developing T2DM compared with higher-methylation individuals. T2DM patients without any vascular complications who had lower methylation levels (<methylation median) in NLRP3 CpG2 and AIM2 total methylation had 6.45 (OR: 6.45, 95% CI: 1.05~39.78, P = 0.011) and 9.48 (OR: 9.48, 95% CI: 1.14~79.00, P = 0.038) times higher risks, respectively, of developing diabetic microvascular complications than T2DM patients with higher methylation. Similar associations were also found between the lower total methylation of the NLRP3 and AIM2 promoter regions and macrovascular complication risk (NLRP3 OR: 36.03, 95% CI: 3.11~417.06, P = 0.004; AIM2 OR: 30.90, 95% CI: 2.59~368.49, P = 0.007). Lower NLRP3 promoter total methylation was related to a 17.78-fold increased risk of micro-macrovascular complications (OR: 17.78, 95% CI: 2.04~155.28, P = 0.009). Lower ASC CpG1 or CpG3 methylation levels had significant partial mediating effects on T2DM vascular complications caused by higher age (ASC CpG1 explained approximately 52.8% or 32.9% of the mediating effect of age on macrovascular or macro-microvascular complications; ASC CpG3 explained approximately 38.9% of the mediating effect of age on macrovascular complications). No gene-gene or gene-environment interaction was identified in T2DM. Conclusion: Lower levels of AIM2 promoter total methylation might increase the risk of T2DM. NLRP3, AIM2, and ASC promoter total methylation or some CpG methylation loss might increase the risk of T2DM vascular complications, which merits further study to support the robustness of these findings.
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Affiliation(s)
- Zixing Zhou
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Lijun Wang
- Department of Nutriology, School of Medicine, Jinan University, Guangzhou, China
| | - Zihao Wen
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Shaoling Zheng
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiaohong Ye
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Dandan Liu
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Jing Wu
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiaoqian Zou
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Yumei Liu
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Yao Wang
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Shirui Dong
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiuxia Huang
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiuben Du
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Kehui Zhu
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiaojing Chen
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Shiqi Huang
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Chengli Zeng
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Yajing Han
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Baohuan Zhang
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
| | - Lihong Nie
- Department of Endocrine, The First Affiliated Hospital of Jinan University, Guangzhou, China
- *Correspondence: Lihong Nie
| | - Guang Yang
- Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou, China
- Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, China
- Guang Yang
| | - Chunxia Jing
- Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China
- Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, China
- Chunxia Jing
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