Improvement of early-phase insulin secretion is an independent factor for achieving glycaemic control: A pooled analysis of SEED and DAWN study.

AIM: To investigate the effect of improving early phase insulin secretion function for glycaemic control in patients with type 2 diabetes mellitus treated with a new class of antidiabetic drug dorzagliatin. MATERIALS AND METHODS: Early insulin secretion function was studied in 726 participants of which 414 were treated with dorzagliatin in the SEED and DAWN study. The early insulinogenic index (IGI30min ) and disposition index (DI) were used to assess early-phase insulin secretion function in this study. Logistic regression analysis was performed to verify the importance of IGI30min and DI indices for achieving effective glycaemic control. RESULTS: The reduction in HbA1c has a significant correlation with the improvement of IGI30min for patients that received 24 weeks of dorzagliatin treatment (p < .001), and this correlation was not observed in the placebo group (p = .364). In the dorzagliatin treatment group, the responders showed significant improvements in homeostasis model assessment 2-ß, IGI30min and DI compared with the non-responders. Logistic regression analysis revealed that the odds ratio (OR) for achieving glycaemic control was 1.28 (95% CI 1.14-1.43) for baseline IGI30min , and 1.24 (95% CI 1.14-1.35) for the 24-week incremental IGI30min from baseline. The OR for baseline DI and 24-week changes in DI from baseline were 1.39 (95% CI 1.2-1.6) and 1.30 (95% CI 1.19-1.43) respectively. The timing of insulin secretion analysis showed the significant contribution of early-phase insulin secretion, rather than late-phase insulin secretion, to postprandial glucose control with the OR for the incremental IGI30min and IGI2h to postprandial glucose control were 1.3 (95% CI 1.19-1.42) and 1 (95% CI 1-1.01) respectively. CONCLUSIONS: Restoring the impaired early-phase insulin secretion function in patients with type 2 diabetes mellitus is a critical factor for improving the glycaemic control by dorzagliatin treatment.

Morning Mastication Enhances Postprandial Glucose Metabolism in Healthy Young Subjects.

Postprandial glucose concentration is dependent on the time of day and its concentration in the morning is lower than in the evening. However, whether it is dependent on mastication at different times of the day has not been studied before. We hypothesized that mastication affects insulin-mediated glucose metabolism differently in the morning and evening in healthy individuals. Firstly, nine healthy male volunteers (22.0 ± 0.7 SEM years, body mass index 22.0 ± 1.0 kg/m2) performed a 75-g oral glucose tolerance test (OGTT). One week after the OGTT, they participated in a high-carbohydrate food (rice) consumption test with 10 or 40 chews per mouthful. Each experiment was conducted in the morning (0800 h) and evening (2000 h) on the same day. Blood samples were collected before and at 30-min intervals for 120 min after glucose or rice consumption. The incremental area under the curve (iAUC) for glucose in the OGTT was significantly lower in the morning than in the evening, whereas the iAUC for insulin was similar at both times. In participants who chewed 40 times, the iAUC for glucose after rice consumption was significantly lower in the morning than in the evening but was similar at both times in individuals who chewed 10 times. Chewing 40 times in the morning (but not the evening) significantly increased insulin secretion at 30 min. This suggests that morning mastication improves early-phase insulin secretion after rice consumption. This novel finding may aid in reducing the incidence of obesity and type 2 diabetes mellitus.

The correlation between serum uric acid level and early-phase insulin secretion in subjects with normal glucose regulation / 中华内科杂志

Objective To investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR).Methods Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled.The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively.The subjects were divided into 4 groups according to the SUA level quartiles.Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups.Results Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin (30 minINS), 2 hours postprandial insulin(2hlNS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P ＜ 0.01).The SUA level was positively correlated with age (r =0.157, P ＜ 0.01), BMI (r =0.262, P ＜ 0.01), waist circumference(r =0.372, P ＜ 0.01), systolic blood pressure (r =0.200, P ＜ 0.01), diastolic blood pressure(r =0.254,P ＜ 0.01) , 30 minutes postprandial plasma glucose(r =0.118 ,P =0.023), FINS(r =0.249, P ＜ 0.01), 30minlNS (r =0.189, P ＜ 0.01) ,2hlNS (r =0.206, P ＜ 0.01), glycosylated hemoglobin (HbAlc, r=0.106,P =0.042), HOMA-IR(r =0.244,P ＜0.01), TG(r =0.350,P ＜0.01), ΔI30/ΔG30 (r =0.144, P ＜ 0.01), and negatively correlated with HDL-C level (r =-0.321, P ＜ 0.01).Multiple stepwise regression analysis showed that SUA (β =0.292, P ＜ 0.01) and HOMA-IR (β3 =29.821, P ＜ 0.01)were positively associated with ΔI30/ΔG30.Conclusion SUA level is closely related with the early-phase insulin secretion in NGR subjects.

Intraportal GLP-1 stimulates insulin secretion predominantly through the hepatoportal-pancreatic vagal reflex pathways.

We previously reported that glucagon-like peptide-1 (GLP-1) appearance in the portal vein facilitates hepatic vagal afferent activity, and this further augments reflexively the pancreatic vagal efferents in anesthetized rats, suggesting a neuroincretin effect of GLP-1. To determine whether the GLP-1-induced vagal pathways lead to a neuronal-mediated component (NMC) of insulin secretion, we infused GLP-1 at a physiological or pharmacological dose (1 or 3 pmol·kg(-1)·min(-1), respectively) into the portal vein in conscious rats with selective hepatic vagotomy (Vagox) or sham operation (Sham). The experiments consisted of two sequential 10-min intraportal infusions (P1 and P2): glucose at a physiological rate (56 µmol·kg(-1)·min(-1)) in P1 and the glucose plus GLP-1 or vehicle in P2. Under arterial isoglycemia across the groups, the physiological GLP-1 infusion in Sham augmented promptly and markedly arterial insulin levels, approximately twofold the levels in glucose alone infusion (P < 0.005), and insulin levels in Vagox diminished apparently (P < 0.05). Almost 60% of the GLP-1-induced insulin secretion (AUC) in Sham met the NMC, i.e., difference between insulin secretion in Sham and Vagox, (AUC 976 ± 65 vs. 393 ± 94 pmol·min/l, respectively, P < 0.005). Intraportal pharmacological GLP-1 infusion further augmented insulin secretion in both groups, but the NMC remained in 46% (NS; Sham vs. Vagox). In contrast, "isoglycemic" intravenous GLP-1 infusion (3 pmol·kg(-1)·min(-1)) evoked an equal insulin secretion in both groups. Thus, the present results indicate that GLP-1 appearing in the portal vein evokes a powerful neuronal-mediated insulinotropic effect, suggesting the neuroincretin effect.

Metabolic Characteristics of Insulin Secretion and Insulin Sensitivity in Isolated Postchallenge Hyperglycemia / 上海第二医科大学学报

Objective To evaluate the metabolic characteristics of insulin secretion and insulin sensitivity in isolated postchallenge hyperglycemia(IPH) and to clarify the factors responsible for the development of IPH. Methods(Eight hundred) and fifty subjects were classified into the following three groups based on the results of a 75-g oral glucose tolerance test(OGTT): normal glucose tolerance(NGT),n=557;isolated impaired glucose tolerance(iIGT),n=146;and IPH,n=147.Insulin secretion(insulinogenic index) and insulin sensitivity(insulin sensitivity index) were identified in the three groups. Results From NGT to iIGT and IPH in these subjects,the insulinogenic index and insulin sensitivity index were gradually decreased(P

Contribution of basal and early phase insulin secretion to plasma glucose level in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective To investigate the effects of basal and early phase insulin secretion on plasma glucose level in type 2 diabetes. Methods Plasma glucose and true insulin levels were measured at 0, 30, 60, 120 min during standard meal test in 81 patients with type 2 diabetes. Insulin sensitivity index (ISI) and insulin secretion index (?I 30 /?G 30 ) were calculated for evaluating the insulin sensitivity. Contributions of basal and early insulin secretion to plasma glucose level were evaluated by multivariate regression analysis with SAS software. Results ISI and ?I 30 /?G 30 showed nearly equal effects on plasma glucose levels by multivariate regression analysis. Among insulin levels of different time points during standard meal test, basal and postprandial 60 min insulin levels played important roles in changes of plasma glucose levels. The effect of fasting insulin on the area under plasma glucose curve was stronger than that of ?I 30 /?G 30 . Conclusion Both basal and early insulin secretions greatly contribute to glycemic control.