-
1.
Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.
Vujkovic, M, Keaton, JM, Lynch, JA, Miller, DR, Zhou, J, Tcheandjieu, C, Huffman, JE, Assimes, TL, Lorenz, K, Zhu, X, et al
Nature genetics. 2020;(7):680-691
-
-
Free full text
-
Abstract
We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.
-
2.
The prevalence of comorbid depression in patients with type 2 diabetes: an updated systematic review and meta-analysis on huge number of observational studies.
Khaledi, M, Haghighatdoost, F, Feizi, A, Aminorroaya, A
Acta diabetologica. 2019;(6):631-650
Abstract
AIMS: Depression is a common co-morbidity in patients with type 2 diabetes mellitus (T2DM). Untreated depression in these patients adversely affects self-care activities and other diabetes complications. The aim of this study is to estimate the prevalence of depression among patients with T2DM by conducting a meta-analysis of observational studies. METHODS MEDLINE, Web of Science, Science Direct, and Google Scholar databases were searched for all observational studies that assessed depression in T2DM. Relevant articles were searched using the combination of Medical Subject Heading (MeSH) terms of "depression", "depressive disorder", and "diabetes mellitus" published between January 2007 and July 2018. Random effects model was used to estimate the weighted prevalence rates and 95% CI using "metaprop program in STATA 11". RESULTS In total, the 248 included studies (with 273 reported prevalence) identified 83,020,812 participants; of them, 23,245,827 (28%; 95% CI 27, 29) suffered from different severity levels of depressive disorders. The prevalence of depression was separately reported in 137,372 males and 134,332 females. Of them, 31,396 males (23%, 95% CI: 20, 26) and 45,673 females (34%, 95% CI: 31, 38) were depressed. Compared with global estimate, depression prevalence was lower in Europe (24%) and Africa (27%), but higher in Australia (29%) and Asia (32%). The prevalence in America was equal to the estimated prevalence in the world (28%). Depression was more common in subjects younger than 65 compared with elderlies (31% vs. 21%). CONCLUSION Our findings demonstrated that almost one in four adults with T2DM experienced depression. Given the high prevalence of depressive disorders in diabetic patients, screening these patients for co-morbid depression and its relevant risk factors is highly recommended.
-
3.
Evidence and potential mechanisms of traditional Chinese medicine for the treatment of type 2 diabetes: A systematic review and meta-analysis.
Tian, J, Jin, D, Bao, Q, Ding, Q, Zhang, H, Gao, Z, Song, J, Lian, F, Tong, X
Diabetes, obesity & metabolism. 2019;(8):1801-1816
Abstract
Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as limited intervention duration, small sample sizes and inconsistent efficacy evaluations, the role of TCM in the treatment of diabetes cannot be fully elucidated. In this review, we evaluate randomized controlled trials of prediabetes, diabetes and diabetic complications published in the past decade. We found that TCM could significantly improve glucose control and clinical indices in patients with diabetes and effectively delay the progression of diabetes. We also summarize potential pharmacological mechanisms underlying the efficacy of TCM medication/herbs and their active ingredients for treating diabetes. More rigorously designed experiments and long-term evaluation of TCM for diabetes will allow for more effective diabetes management.
-
4.
Effects of sodium-glucose cotransporter (SGLT) inhibitors in addition to insulin therapy on glucose control and safety outcomes in adults with type 1 diabetes: A meta-analysis of randomized controlled trials.
Lu, J, Tang, L, Meng, H, Zhao, J, Liang, Y
Diabetes/metabolism research and reviews. 2019;(7):e3169
Abstract
Sodium-glucose cotransporter (SGLT) inhibitors added to insulin therapy have been proposed as treatment strategy for type 1 diabetes (T1D). We thus conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of this combination in T1D. We searched the PubMed, EMBASE, and Cochrane Library databases and ClinicalTrials.gov for RCTs. Statistical analyses were performed using STATA 15. Ten eligible placebo-controlled trials involving 5961 patients were included. Compared with placebo, SGLT inhibitors were associated with a reduction in HbA1c of -0.39% (95% CI, -0.43 to -0.36), an improved mean amplitude of glucose excursion (MAGE) of -14.81 mg/dL (95% CI, -19.08 to -10.54), and a reduction in body weight of -3.47% (95% CI, -3.78 to -3.16), as well as no increased relative risk of hypoglycaemia (1.01; 95% CI, 0.99-1.02) or severe hypoglycaemia (0.91; 95% CI, 0.77-1.07). SGLT inhibitors decreased fasting plasma glucose and insulin requirement but increased the risk of genital infection (3.57; 95% CI, 2.97-4.29) and diabetic ketoacidosis (3.11; 95% CI, 2.11-4.58). However, the very low dose empagliflozin (2.5 mg) did not increase the risk of diabetic ketoacidosis (risk ratio [RR] 0.67; 95% CI, 0.11-3.95). SGLT inhibitors had no effect on overall adverse events, urinary tract infection, or bone fracture but slightly increased the risk of serious adverse events (1.35; 95% CI, 1.16-1.58), severe adverse events (1.84; 95% CI, 1.20-2.84), adverse events leading to discontinuation (1.50; 95% CI, 1.22-1.84), drug-related adverse events (1.78; 95% CI, 1.44-2.19), and diarrhoea (1.54; 95% CI, 1.15-2.05). Although adverse events exist, the available data provide evidence that the combination of SGLT inhibitors with basal insulin treatment is beneficial in patients with T1D.
-
5.
Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies.
,
The lancet. Diabetes & endocrinology. 2018;(7):538-546
Abstract
BACKGROUND Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. METHODS In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. RESULTS Individual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97-2·24) and tripled risk among women (3·00, 2·71-3·33; χ2 test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2·60, 2·30-2·94) than in older individuals (aged 70-89 years: 2·01, 1·85-2·19; p=0·0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5·55, 4·15-7·44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0·05% (95% CI 0·03-0·07) per year in women compared with 0·08% (0·05-0·10) per year in men; the corresponding excess at ages 70-89 years was 1·08% (0·84-1·32) per year in women and 0·91% (0·77-1·05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. INTERPRETATION Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained. FUNDING UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health).
-
6.
Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †.
Zhang, P, Lu, J, Jing, Y, Tang, S, Zhu, D, Bi, Y
Annals of medicine. 2017;(2):106-116
Abstract
Diabetic foot is a severe public health issue, yet rare studies investigated its global epidemiology. Here we performed a systematic review and meta-analysis through searching PubMed, EMBASE, ISI Web of science, and Cochrane database. We found that that global diabetic foot ulcer prevalence was 6.3% (95%CI: 5.4-7.3%), which was higher in males (4.5%, 95%CI: 3.7-5.2%) than in females (3.5%, 95%CI: 2.8-4.2%), and higher in type 2 diabetic patients (6.4%, 95%CI: 4.6-8.1%) than in type 1 diabetics (5.5%, 95%CI: 3.2-7.7%). North America had the highest prevalence (13.0%, 95%CI: 10.0-15.9%), Oceania had the lowest (3.0%, 95% CI: 0.9-5.0%), and the prevalence in Asia, Europe, and Africa were 5.5% (95%CI: 4.6-6.4%), 5.1% (95%CI: 4.1-6.0%), and 7.2% (95%CI: 5.1-9.3%), respectively. Australia has the lowest (1.5%, 95%CI: 0.7-2.4%) and Belgium has the highest prevalence (16.6%, 95%CI: 10.7-22.4%), followed by Canada (14.8%, 95%CI: 9.4-20.1%) and USA (13.0%, 95%CI: 8.3-17.7%). The patients with diabetic foot ulcer were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot ulceration. Our results provide suggestions for policy makers in deciding preventing strategy of diabetic foot ulceration in the future. Key messages Global prevalence of diabetic foot is 6.3% (95%CI: 5.4-7.3%), and the prevalence in North America, Asia, Europe, Africa and Oceania was 13.0% (95%CI: 10.0-15.9%), 5.5% (95%CI: 4.6-6.4%), 5.1% (95%CI: 4.1-6.0%), 7.2% (95%CI: 5.1-9.3%), and 3.0% (95% CI: 0.9-5.0%). Diabetic foot was more prevalent in males than in females, and more prevalent in type 2 diabetic foot patients than in type 1 diabetic foot patients. The patients with diabetic foot were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot.
-
7.
Dietary sugars versus glucose tablets for first-aid treatment of symptomatic hypoglycaemia in awake patients with diabetes: a systematic review and meta-analysis.
Carlson, JN, Schunder-Tatzber, S, Neilson, CJ, Hood, N
Emergency medicine journal : EMJ. 2017;(2):100-106
Abstract
BACKGROUND While glucose tablets have been advocated for treating symptomatic hypoglycaemia in awake patients, dietary sugars may be more convenient. We performed a systematic review to compare the impact of these treatment options on the relief of symptomatic hypoglycaemia, time to resolution of symptoms, blood glucose levels, complications and hospital length of stay. METHOD We searched PubMed, Embase and the Cochrane Library through 28 June 2016 and assessed the quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Reference lists from a subset of the resulting articles were mined for additional, potentially eligible papers. We calculated the risk ratio (RR) of each treatment option for the preselected outcomes of interest. RESULTS Of the 1774 identified papers, four studies met the inclusion criteria; three randomised controlled trials totalling 502 hypoglycaemic events treated with dietary sugars and 223 with glucose tablets and one observational study with 13 events treated with dietary sugars and 9 with glucose tablets. The dietary forms of sugar included sucrose, fructose, orange juice, jelly beans, Mentos, cornstarch hydrolysate, Skittles and milk. In the pooled analysis, patients treated with dietary sugars had a lower resolution of symptoms 15 min after treatment compared with glucose tablets (RR 0.89, 95% CI 0.83 to 0.95). CONCLUSIONS When compared with dietary sugars, glucose tablets result in a higher rate of relief of symptomatic hypoglycaemia 15 min after ingestion and should be considered first, if available, when treating symptomatic hypoglycaemia in awake patients.
-
8.
Distribution of Esophageal Motor Disorders in Diabetic Patients With Dysphagia.
George, NS, Rangan, V, Geng, Z, Khan, F, Kichler, A, Gabbard, S, Ganocy, S, Fass, R
Journal of clinical gastroenterology. 2017;(10):890-895
Abstract
BACKGROUND Diabetes mellitus can cause various gastrointestinal symptoms. Assessment of esophageal dysmotility in diabetic patients has been scarcely studied. The aim of this study was to determine the esophageal motor characteristics of diabetic versus nondiabetic patients who present with dysphagia. METHODS High-resolution esophageal manometries (HREMs) of 83 diabetic patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2 medical centers were included in this study. Demographic information, medical comorbidities, and medication usage were recorded for each patient in a single registry. HREM of each patient was evaluated and the different functional parameters were recorded. KEY RESULTS Overall, 46% of diabetic patients were found to have an esophageal motor disorder. Diabetic patients with dysphagia were more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared with nondiabetic patients. Among diabetic patients, those being treated with insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5% vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin. Among diabetic patients, those with abnormal manometry were more likely to demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend toward increased incidence of esophagogastric junction outflow obstruction in diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic patients. CONCLUSIONS Nearly half of diabetic patients with dysphagia have some type of an esophageal motility disorder. Diabetic retinopathy and the use of insulin are predictive of esophageal motor abnormalities among diabetic patients.
-
9.
Association of Helicobacter pylori infection with diabetic complications: a meta-analysis.
Wang, F, Fu, Y, Lv, Z
Endocrine research. 2014;(1):7-12
Abstract
UNLABELLED BACKGROUND. Helicobacter pylori (HP) infects more than half of the world's population. The aim of the study was to quantify the association between HP and the risk of diabetic complications. METHODS A literature search was performed to identify studies published between 1998 and 2012 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for ischemic heart disease, retinopathy, neuropathy and nephropathy. RESULTS Eight studies were included. HP was associated with an increase risk of nephropathy and neuropathy (relative risk [RR]: 1.35, 95% CI: 1.06-1.73, p = 0.45 and RR: 1.20, 95% CI: 1.03-1.40, p = 0.29). We also discovered significant associations between bacterial infection and nephropathy risk in Oriental people (RR: 1.73, 95% CI: 1.19-2.50, p = 0.82) and in type 2 diabetic patients (RR: 1.50, 95% CI: 1.11-2.02, p = 0.29). CONCLUSIONS Our meta-analyses suggest a possible relationship between HP and the risk of nephropathy and neuropathy. Our results also suggest that the effect of HP on the risk of nephropathy is stronger in Oriental people and in type 2 DM patients.
-
10.
Associations study of vitamin D receptor gene polymorphisms with diabetic microvascular complications: a meta-analysis.
Liu, Z, Liu, L, Chen, X, He, W, Yu, X
Gene. 2014;(1):6-10
Abstract
BACKGROUND Emerging evidence from preclinical and clinical studies has shown that vitamin D plays an important role in the pathogenesis of diabetic microvascular complications (DMI). Several potentially functional polymorphisms (ApaI, BsmI, FokI and TaqI) of vitamin D receptor (VDR) gene have been implicated in DMI risk, but individually published studies showed inconclusive results. The aim of this study was to quantitatively summarize the association between VDR polymorphisms and DMI risk. METHODS We searched all the publications about the associations mentioned as above from PubMed and ISI database updated in December 2013. Meta-analysis of the overall odds ratios (ORs) with 95% confidence intervals (CIs) was calculated with the fixed or random effect model. RESULTS Eight studies involving 2734 subjects were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests that no significant association was observed among the ApaI, BsmI, FokI and TaqI variants and DMI risk in diabetic patients (all P values >0.05). In the stratified analysis, significant association was observed with diabetic nephropathy (DN) for VDR gene FokI polymorphism under a dominant model (OR 1.35, 95% CI 1.05-1.74, P=0.02) in Caucasians. CONCLUSIONS This meta-analysis indicated that the FokI polymorphism in VDR gene might affect individual susceptibility to DN in Caucasians. Further investigations are needed to confirm our results.