Effect of insulin secretagogues on major cardiovascular events and all-cause mortality: A meta-analysis of randomized controlled trials

Background and aimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs) and all-cause mortality as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin secretagogues (sulfonylureas and glinides) with this respect.Methods and resultsA MEDLINE database search was performed to identify all RCTs, up to January 1st, 2020, with duration≥52 weeks, in which insulin secretagogues (glibenclamide, gliclazide, glimepiride, glipizide, chlorpropamide, repaglinide, nateglinide) were compared with either placebo or active comparators. The principal endpoints were MACE (restricted for RCT reporting MACEs within their outcomes) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Fourteen RCTs were included in the analysis for MACEs (919 in insulin secretagogues and 1,087 in control group). Insulin secretagogues were not significantly associated with an increased risk of MACEs in comparison with controls (MH–OR 1.08 [95% CI 0.96, 1.22], p = 0.20). When considering the 48 RCTs fulfilling criteria for inclusion in the analysis on all-cause mortality, insulin secretagogues were associated with a significantly increased risk of all-cause mortality (MH–OR 1.11 [1.00, 1.23], p = 0.04).ConclusionsThis meta-analysis suggests that insulin secretagogues are associated with an increased risk of all-cause mortality when compared with placebo or other anti-hyperglycaemic drugs.     

Carbohydrate restriction in midlife is associated with higher risk of type 2 diabetes among Australian women: A cohort study

Background and aimsLow-carbohydrate diets (LCDs) are increasingly popular but may be nutritionally inadequate. We aimed to examine if carbohydrate restriction in midlife is associated with risk of developing type 2 diabetes (T2DM), and if this association differs by previous gestational diabetes (GDM) diagnosis.Methods and resultsDietary intake was assessed for 9689 women from the Australian Longitudinal Study on Women's Health in 2001 (aged 50–55) and 2013 (aged 62–67) via validated food frequency questionnaires. Average long-term carbohydrate restriction was assessed using a low-carbohydrate diet score (highest quartile (Q4) indicating lowest proportion of energy from carbohydrates). Incidence of T2DM between 2001 and 2016 was self-reported at 3-yearly surveys. Log-binomial regression was used to estimate relative risks (RR) and 95% CIs. During 15 years of follow-up, 959 women (9.9%) developed T2DM. Carbohydrate restriction was associated with T2DM after adjustment for sociodemographic factors, history of GDM diagnosis and physical activity (Q4 vs Q1: RR 1.27 [95% CI 1.10, 1.48]), and this was attenuated when additionally adjusted for BMI (1.10 [0.95, 1.27]). Carbohydrate restriction was associated with lower consumption of fruit, cereals and high-fibre bread, and lower intakes of these food groups were associated with higher T2DM risk. Associations did not differ by history of GDM (P for interaction >0.15).ConclusionCarbohydrate restriction was associated with higher T2DM incidence in middle-aged women, regardless of GDM history. Health professionals should advise women to avoid LCDs that are low in fruit and grains, and to consume a diet in line with current dietary recommendations.     

WJD 5~(th) Anniversary Special Issues(2): Type 2 diabetes Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.     

Self-reported use of diabetes healthcare services in a Quebec community-based sample: impact of depression status

Objectives

To ascertain the impact of minor and major depression on self-reported use of and access to diabetes healthcare services, and the care components received in a community-based Quebec sample with type 2 diabetes.

Study design

Adults with type 2 diabetes who took part in baseline and 1-year follow-up telephone interviews for the Diabetes Health Study were assessed (n = 1175).

Methods

Information was collected regarding depression status (i.e. minor or major depression), use of and access to diabetes healthcare services, sociodemographic and diabetes characteristics, treatment, diabetes complications, disability, body mass index, residential area and depression.

Results

People with major depression were more likely to be high users or non-users of diabetes healthcare services. The high users reported more diabetes complications. People with major depression also reported more problems with accessing diabetes healthcare services, specifically having to wait too long between making their appointment and their visit, specialist care not being available in their area, general health deterioration, being unable to leave their house due to their health and problems with transportation. People with major depression were less likely to report having their feet checked by their doctor, and were more likely to report problems with getting advice from their doctor.

Conclusions

People with diabetes need to use healthcare services in order to receive recommended care components. People with major depression and no complications are less likely to report using healthcare services; conversely, people with major depression and complications are more likely to be high users of healthcare services. People with major depression perceive more problems with the health care they receive.     

Immunomodulation therapy of diabetes by oral administration of a surfactin lipopeptide in NOD mice

Type 1 diabetes mellitus (T1DM) is considered an autoimmune disease, which can be attenuated by modulation of immune pathway from Th1- to Th2-type through vaccination. WH1fungin surfactin is a Bacillus-produced natural immunomodulator. NOD mice were orally treated with 5 mg/kg or 25 mg/kg WH1fungin once a week for total 4 weeks. After the final administration, the diabetes incidence and the anti-inflammatory roles of WH1fungin were investigated by immunohistochemistry, FACS and ELISA. The results showed oral WH1fungin obviously resulted in a WH1fungin-unspecific suppression of T1DM. Diabetes incidence was significantly reduced when compared to phosphate buffered saline (PBS) control. Mice in the control group began to be onset of diabetes at week 15, following with an increased mortality from week 16 to 28. At the end of observation, the diabetes incidence reached to 81% at week 30, while only 25% in WH1fungin groups. The splenocytes assay showed oral WH1fungin could suppress T cells proliferation, down-regulate amounts of activated CD8⁺ T cells with the production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and increase CD4⁺CD25⁺FOXP3⁺ regulator T cells (Tregs). The serum assay revealed oral WH1fungin down-regulated TNF-α and IgG2a but increased interleukin (IL)-10 and IgG1 in mice. All of these data showed oral WH1fungin tended to switch the immune response from Th1- to Th2-type. The further surveys revealed that less IFN-γ but more transfer growth factor (TGF)-β were found in the islets of mice with oral WH1fungin when compared to that in the control group. As a result, the normal islet architecture and slight inflammatory cells infiltration was observed with a slight insulitis in the oral WH1fungin groups. These results demonstrate that oral WH1fungin might be a novel therapeutic approach for the prevention of T1DM.     

阿托伐他汀联合替米沙坦治疗2型糖尿病肾病的疗效观察

目的：观察阿托伐他汀联合替米沙坦治疗2型糖尿病肾病的疗效。方法将收治的80例2型糖尿病肾病患者随机分为观察组和对照组,每组各40例,两组患者均严格执行糖尿病饮食及常规降糖药物和（或）降压药物治疗,对照组予替米沙坦80mg/d,口服,观察组同时联合阿托伐他汀20mg/d,口服,疗程4个月。比较两组患者治疗前后TG、TC、BUN、UAER、Scr值。结果观察组患者治疗后TG、TC、BUN、UAER、Scr水平较对照组降低更明显,差异具有显著性（P＜0.05或P＜0.01）。结论阿托伐他汀联合替米沙坦治疗2型糖尿病肾病能够显著改善血脂水平及肾功能,且不良反应发生率低,值得临床广泛推广和应用。     

Antidiabetic effect of Lactobacillus casei CCFM0412 on mice with type 2 diabetes induced by a high-fat diet and streptozotocin

ObjectiveThe aim of this study was to evaluate the antidiabetic effects of Lactobacillus casei CCFM0412 on mice with type 2 diabetes induced by a high-fat diet and streptozotocin.MethodsThirty-two male C57 BL/6 J mice were assigned to four groups in this study. Type 2 diabetes was induced by feeding of a high-fat diet and injection of streptozotocin. L. casei CCFM0412 was administered to mice at a dose of 10⁹ cfu/d per mouse for 12 wk. Body weight, fasting and postprandial 2-h blood glucose, oral glucose tolerance, glycosylated hemoglobin, insulin, and glycogen in liver were measured. Endotoxin, tumor necrosis factor-α, and interleukin-10 levels were determined. Lipid metabolic parameters including triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were also measured. The activities of glutathione peroxides, reactive oxygen species, and superoxide dismutase, and the levels of glutathione and malondialdehyde in the liver also were determined. Pancreas injury was evaluated by histologic analysis.ResultsAt 13 wk, L. casei CCFM0412 significantly decreased fasting and postprandial 2-h blood glucose, glycosylated hemoglobin, endotoxin, tumor necrosis factor-α, triglycerides, total cholesterol, low-density lipoprotein cholesterol, reactive oxygen species, and malondialdehyde levels compared with the control group (P < 0.05). The values for insulin, interleukin-10, high-density lipoprotein cholesterol, glutathione peroxides, superoxide dismutase, glutathione, and glycogen were significantly increased at 13 wk (P < 0.05). Islets of Langerhans in the L. casei CCFM0412 group were substantially protected from destruction compared with those in the control group.ConclusionL. casei CCFM0412 significantly improved glucose intolerance, dyslipidemia, immune-regulatory properties, and oxidative stress in mice with type 2 diabetes induced by a high-fat diet and streptozotocin. The results provide a sound rationale for future clinical trials of oral administration of L. casei CCFM0412 for the primary prevention of type 2 diabetes.