Background The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly‐onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima‐media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta‐analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM. Methods PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration ≥3 months) to insulin treatment alone in T1DM. Data were expressed as weighted/standardized mean differences (MDs/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence. Results Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima‐media thickness (MD −0.06 mm [95% CI −0.88, −0.28], P < .001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI −1.88, 6.29], P = .29), the total daily insulin dosage (SMD −0.81 [95% CI −1.25, −0.36], P < .001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events. Conclusions Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.

We explored potential biomarkers and molecular mechanisms regarding multiple benefits after bariatric surgery. Differentially expressed genes (DEGs) for subcutaneous adipose tissue (AT) after bariatric surgery were identified by analyzing two expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs and gene-TFs networks were interrogated to identify hub genes and associated pathways. Co-expressed DEGs included one that was up-regulated and 22 that were down-regulated genes. The enrichment analyses indicated that down-regulated DEGs were significantly involved in inflammatory responses. GSEA provided comprehensive evidence that most genes enriched in pro-inflammation pathways, while gene-sets after surgery enriched in metabolism. We identified nine hub genes in the PPI network, most of which were validated as highly expressed and hypomethylated in obesity by Attie Lab Diabetes and DiseaseMeth databases, respectively. DGIdb was also applied to predict potential therapeutic agents that might reverse abnormally high hub gene expression. Bariatric surgery induces a significant shift from an obese pro-inflammatory state to an anti-inflammatory state, with improvement in adipocyte metabolic function-representing key mechanisms whereby AT function improves after bariatric surgery. Our study deepens a mechanistic understanding of the benefits of bariatric surgery and provides potential biomarkers or treatment targets for further research.

AimThis study aimed to investigate the role of nerve conduction studies (NCS) and sympathetic skin response (SSR) in evaluating diabetic cardiac autonomic neuropathy (DCAN).MethodsDCAN was diagnosed using the Ewing test combined with heart rate variability analysis. NCS and SSR were assessed by electrophysiological methods. The association between NCS/SSR and DCAN was assessed via multivariate regression and receiver-operating characteristic analyses.ResultsThe amplitude and conduction velocity of the motor/sensory nerve were found to be significantly lower in the DCAN+ group (all P &lt; 0.05). A lower amplitude of peroneal nerve motor fiber was found to be associated with increased odds for DCAN (OR 2.77, P &lt; 0.05). The SSR amplitude was lower while the SSR latency was longer in the DCAN+ group than in the DCAN– group. The receiver-operating characteristic analysis revealed that the optimal cutoff points of upper/lower limb amplitude of SSR to indicate DCAN were 1.40 mV (sensitivity, 61.9%; specificity, 66.3%, P &lt; 0.001) and 0.85 mV (sensitivity, 66.7%; specificity, 68.5%, P &lt; 0.001), respectively. The optimal cutoff points of upper/lower limb latency to indicate DCAN were 1.40 s (sensitivity, 61.9%; specificity, 62%, P &lt; 0.05) and 1.81 s (sensitivity, 69.0%; specificity, 52.2%, P &lt; 0.05), respectively.ConclusionsNCS and SSR are reliable methods to detect DCAN. Abnormality in the peroneal nerve (motor nerve) is crucial in predicting DCAN. SSR may help predict DCAN.

Aims/Introduction: Diabetic cardiovascular autonomic neuropathy (DCAN) seriously threatens the prognosis and quality of life of patients with type 2 diabetes mellitus, associated with increased mortality. The present study aimed to investigate the relevant risk factors of DCAN. Materials and Methods: The present study enrolled a total of 109 patients with type 2 diabetes mellitus. DCAN was defined as a score of at least 2 points in Ewing tests. The updated homeostasis model assessment of insulin resistance (HOMA2-IR) based on fasting C-peptide was calculated to reflect insulin resistance. Logistic regression analysis, interaction and stratified analyses were used to investigate the relationship between HOMA2-IR or other indicators and DCAN. Receiver operating characteristic analysis was carried out to estimate the discriminative value of the variables independently associated with DCAN and to determine the optimal cut-off point of these models to screen DCAN. Results: The HOMA2-IR levels were significantly higher in patients with DCAN, and tended to be worsened with the progression of the DCAN. Logistic regression analysis showed an independent association between HOMA2-IR (odds ratio 39.30, 95% confidence interval 7.17-215.47) and DCAN. HOMA2-IR (area under the curve 0.878, 95% confidence interval 0.810-0.946; cut-off value 1.735) individually predicted DCAN significantly higher than the other independent risk factors individually used, whereas models combining HOMA2-IR and other risk factors did not significantly boost the diagnostic power. Conclusions: Insulin resistance is independently associated with DCAN. HOMA2-IR presents to be a highly accurate and parsimonious indicator for DCAN screening. Patients with HOMA2-IR >1.735 are at a high risk of DCAN; thus, priority diagnostic tests should be carried out for these patients for timely integrated intervention.