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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
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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.
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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.
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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.
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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.
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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.
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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).