Effect of glucagon-like peptide-1 receptor agonists in subjects with type 2 diabetes mellitus: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: We performed a meta-analysis to evaluate the effects of glucagon-like peptide-1 receptor agonists compared to placebo on cardiovascular, kidney-related, and eye-related disease outcomes or on mortality in subjects with type 2 diabetes mellitus. METHODS: A systematic literature search up to April 2021 was performed, and 8 studies included 61,661 subjects with type 2 diabetes mellitus at the start of the study, 29,034 of them were using glucagon-like peptide-1 receptor agonists and 32,627 were given a placebo. They reported on relationships between the effects of glucagon-like peptide-1 receptor agonists compared to placebo on mortality rates, cardiovascular, renal and ophthalmic outcomes in subjects with type 2 diabetes mellitus. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to assess the effects of glucagon-like peptide-1 receptor agonists compared to placebo on the listed outcomes on subjects with type 2 diabetes mellitus, using the dichotomous method with a random or fixed-effect model. RESULTS: The use of glucagon-like peptide-1 receptor agonists was associated with significantly lowered all-cause mortality (OR, 0.76; 95% CI, 0.65-0.89, p < 0.001), cardiovascular deaths (OR, 0.87; 95% CI, 0.81-0.94, p < 0.001), myocardial infarctions (OR, 0.92; 95% CI, 0.85-0.98, p = 0.01), strokes (OR, 0.81; 95% CI, 0.74--0.90, p < 0.001), hospital admissions owing to heart failure (OR, 0.91; 95% CI, 0.83-1.00, p = 0.04) and renal events (OR, 0.83; 95% CI, 0.77-0.89, p < 0.001) compared to placebo in subjects with type 2 diabetes mellitus. However, glucagon-like peptide-1 receptor agonists had significantly higher ophthalmic events (OR, 1.15; 95% CI, 1.04-1.29, p = 0.009) compared to placebo in subjects with type 2 diabetes mellitus. WHAT IS NEW AND CONCLUSION: Glucagon-like peptide-1 receptor agonists may have a lower risk of all-cause mortality, cardiovascular death, myocardial infarction, stroke, hospital admission owing to heart failure and renal events compared to placebo in subjects with type 2 diabetes mellitus. However, they have significantly higher ophthalmic events compared to placebo in subjects with type 2 diabetes mellitus. Further studies are required to validate these findings.

Reduced circulating oxytocin and High-Molecular-Weight adiponectin are risk factors for metabolic syndrome.

The neurohypophysial hormone, oxytocin, is involved in the regulation of energy metabolism. Adiponectin (APN) is an adipose tissue-specific serum protein that inversely associates with metabolic syndrome (MetS). High-molecular-weight adiponectin (HMW APN) is considered the active form. In the present study, we aimed to determine the relationships of oxytocin and HMW APN to MetS and investigate whether or not the combination of oxytocin and HMW APN is associated with further metabolic abnormalities compared to each of them alone. A total of 170 subjects (75 with MetS and 95 non-MetS) were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT), blood lipids, hs-CRP, oxytocin and HMW APN levels were measured. Compared with non-MetS subjects, serum oxytocin and HMW APN levels were significantly lower in subjects with MetS (P<0.01). We then classified the subjects into three groups: high oxytocin and high HMW APN levels (high score group), low oxytocin and low HMW APN levels (low score group) and others. Participants in low score group showed the worst metabolic profiles and were more likely to have MetS compared to the other two group. In Spearman rank correlation coefficient, the classification by the combination of oxytocin and HMW APN was significantly correlated with a larger number of metabolic risk factors compared with classification by each of them alone. Individuals with low circulating oxytocin levels coupled with low HMW APN levels were at significantly increased risk of MetS. The combination of both markers would be useful for identifying MetS high risk patients.

Fibroblast growth factor 1 levels are elevated in newly diagnosed type 2 diabetes compared to normal glucose tolerance controls.

Fibroblast growth factor 1 (FGF1) has been recently characterized as a potent insulin sensitizer that regulates adipose tissue remodeling, but the physiological role of FGF1 remains unclear. This study measured serum FGF1 levels for the first time in patients with newly diagnosed type 2 diabetes mellitus (T2DM), and further explored the correlations between FGF1 levels and various metabolic parameters in T2DM. Serum FGF1 levels were determined using ELISA in age-, sex- and BMI- matched subjects with normal glucose tolerance (NGT) (n=80) and newly diagnosed T2DM (n=80). Oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1C), blood lipids, and insulin secretion were also measured. Insulin resistance and pancreatic ß-cell function were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta cell function (HOMA-ß), respectively. Serum FGF1 levels were significantly higher in T2DM patients than in normal glucose tolerance subjects (74.52 [55.91∼101.34] vs. 60.31 [48.99∼83.91] pg/mL; P<0.05). In addition, serum FGF1 level positively correlated with body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), fasting plasma glucose (FPG), 2-h post-OGTT glucose (2h PG), and HbA1C (all P values <0.05) in T2DM subjects. Multivariate regression analyses showed that BMI and HbA1C were the independent factors influencing serum FGF1 levels. Logistic regression analyses demonstrated that serum FGF1 was significantly associated with type 2 diabetes (P<0.01). Circulating concentrations of FGF1 are significantly increased in T2DM patients. Our results suggest that FGF1 may play a role in the pathogenesis of T2DM.

Improvement of ß-cell function ameliorated glycemic variability in patients with newly diagnosed type 2 diabetes after short-term continuous subcutaneous insulin infusion or in combination with sitagliptin treatment: a randomized control trial.

Glycemic variability (GV) has been proposed as contributor to diabetes-related macrovascular complications. This randomized control trial evaluated a new combination therapy with continuous subcutaneous insulin infusion (CSII) plus sitagliptin (CSII + sitagliptin) vs. CSII only in terms of metabolic control, GV and ß-cell function in patients with newly diagnosed type 2 diabetes (T2DM). 217 patients were randomized to two weeks of CSII (n = 108) or CSII + sitagliptin (n = 109) therapy. As a measure of GV, the coefficient of variation (CV) was computed from capillary blood glucose during the first and second week, respectively. ß-cell function before and after treatment was determined with the Insulin Secretion-Sensitivity Index-2 (ISSI-2). Good metabolic controls were established with both therapies. CSII + sitagliptin therapy resulted in greater improvements in CV and ISSI-2 than CSII alone (all P = 0.000). For each group, change in CV was inversely correlated with change in ISSI-2 (r = -0.529, P = 0.000 and r = -0.433, P = 0.000, respectively). The multivariate regression analysis demonstrated that improved ISSI-2 was the only independent contributor to reduced CV in both groups (standardized ß = -0.388, P = 0.004 and standardized ß = -0.472, P = 0.000, respectively). Correction of ß-cell function in newly diagnosed T2DM patients via use of either CSII or CSII + sitagliptin therapy was feasible in controlling GV to prevent secondary complications of T2DM. Moreover, CSII + sitagliptin therapy was superior to CSII monotherapy in terms of GV.

Safety and efficacy of sitagliptin in combination with transient continuous subcutaneous insulin infusion (CSII) therapy in patients with newly diagnosed type 2 diabetes.

Sitagliptin was used as monotherapy or in combination with metformin, thiazolidinedione or sulfonylurea. It is not clear whether effects are enhanced or unique when in combination with transient continuous subcutaneous insulin infusion (CSII) therapy. The aim of this study was to assess the safety and efficacy of sitagliptin in combination with transient CSII therapy in patients with newly diagnosed type 2 diabetes. Eighty patients with newly diagnosed type 2 diabetes from July 2011 to May 2013 were recruited into the study. These patients were randomly divided into a CSII monotherapy group (group A, n = 40) or a sitagliptin in combination with CSII therapy group (group B, n = 40) and received insulin intensive therapy. Treatments were maintained for 2 weeks. 75g oral glucose tolerance test (OGTT) was performed before and after treatments, and the levels of glucose, insulin and C-peptide were examined. The results indicated that, compared with CSII therapy group, the level of plasma glucose significantly decreased, the levels of insulin and C-peptide strikingly increased and homeostasis model assessment for beta-cell function (HOMA-ß) and Insulinogenic index (Ins index) were improved in the group of sitagliptin in combination with CSII therapy. Above all, the incidence of hypoglycemia was lower, insulin doses were less and the rate of recovery to normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) determined by 75gOGTT was higher in the latter. So, Sitagliptin in combination with CSII therapy can be a new safe and effective therapy in patients with newly diagnosed type 2diabetes.

Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients.

OBJECTIVE: Betatrophin, a newly identified hormone, has been recently characterized as a potent stimulator that increases the production and expansion of insulin-secreting ß-cells in mice, but the physiological role of betatrophin remains poorly understood. This study measured for the first time serum betatrophin levels in newly diagnosed patients with type 2 diabetes (T2DM) and explored the correlations between its serum levels and various metabolic parameters in T2DM. RESEARCH DESIGN AND METHODS: We analyzed the concentrations of betatrophin by ELISA in blood samples of 166 well-characterized individuals in whom anthropometric parameters, oral glucose tolerance test (OGTT), glycosylated hemoglobin, blood lipids, insulin sensitivity (1/homeostasis model assesment of insulin resistance [1/HOMA-IR] and Matsuda index [ISIM]), and insulin secretion were measured. The participants were divided into newly diagnosed T2DM patients (n = 83) and age-, sex- and BMI-matched healthy control subjects (n = 83). RESULTS: Serum betatrophin levels were significantly higher in T2DM patients than in healthy control subjects (613.08 [422.19-813.08] vs. 296.57 [196.53-509.46] pg/mL; P < 0.01). Serum betatrophin positively correlated with age, 2-h post-OGTT glucose (2hPG), and postprandial serum insulin (PSI), but negatively with 1/HOMA-IR and ISIM in T2DM patients. In the control group, betatrophin was only positively associated with age. In T2DM subjects, multivariate regression analyses showed that age, 2hPG, and PSI were independent factors influencing serum betatrophin levels. CONCLUSIONS: Circulating concentrations of betatrophin are significantly increased in T2DM patients. Our results suggest that betatrophin may play a role in the pathogenesis of T2DM.

Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients.

CONTEXT AND OBJECTIVE: Oxytocin can affect energy homeostasis and has interesting potential as a metabolic disease therapeutic. We detected serum oxytocin levels in obese (OB) and type 2 diabetes mellitus (T2DM) subjects and investigated the relationships between serum oxytocin levels and glycolipid metabolism, insulin resistance, pancreatic ß-cell function, and inflammation. PATIENTS AND METHODS: A total of 176 subjects were enrolled in the study, including 88 patients with newly diagnosed T2DM and 88 subjects with normal glucose tolerance (NGT). NGT and T2DM groups were divided into normal-weight (NW) and OB subgroups. We analyzed the concentrations of oxytocin by ELISA. Oral glucose tolerance testing was done, and hemoglobin A1c (HbA1c), blood lipids, and highly sensitive C-reactive protein (hs-CRP) were also measured. Insulin resistance and pancreatic ß-cell function were assessed by homeostasis model assessment (HOMA). RESULTS: Serum oxytocin levels were lower in the T2DM group than in the NGT group (P < .01). The levels of serum oxytocin in OB subjects were also lower than those in NW subjects (P < .01). Serum oxytocin levels were negatively correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), HbA1c, fasting plasma glucose (FPG), 2-hour plasma glucose, fasting insulin (FINS), 2-h insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), HOMA of insulin resistance (HOMA-IR), and hs-CRP and positively correlated with HOMA of ß-cell function (HOMA-ß) (P < .05). Multiple stepwise regression analysis showed that 2-hour plasma glucose, BMI, and TC were associated with serum oxytocin levels (P < .05). Logistic regression analyses demonstrated that serum oxytocin was significantly associated with T2DM (P < .01). CONCLUSIONS: Serum oxytocin levels were decreased in T2DM as well as OB subjects.