Influence of insulin on growth hormone secretion, level and growth hormone signalling / 生理学报

Growth hormone (GH), as a vital hormone, has to experience a series of processes to fulfill its function including secretion, entering the circulation to reach target tissues (pre-receptor process), binding on the GH receptor (GHR) and triggering signaling inside cells (post-GHR process). Insulin can directly or indirectly influence part of these processes. GH secretion from pituitary somatotropes is regulated by GH-releasing hormone (GHRH) and somatostatin (SS) from hypothalamus. Insulin may exert positive or negative effects on the neurons expressing GHRH and SS and somatotropes under healthy and pathological conditions including obesity and diabetes. Glucose and lipid levels in circulation and dietary habits may influence the effect of insulin on GH secretion. Insulin may also affect GHR sensitivity and the level of insulin-like growth factor 1 (IGF-1), thus influence the level of GH. The GH signaling is also important for GH to play its role. GH signaling involves GHR/JAK2/STATs, GHR/JAK2/SHC/MAPK and GH/insulin receptor substrate (IRS)/PI3K/Akt pathways. These pathways may be shared by insulin, which is the basis for the interaction between insulin and GH, and insulin may attenuate or facilitate the GH signal by influencing molecules in the pathways. Many factors are related to the effect of insulin, among them the most important ones are duration of action and amount of insulin. The tendency of insulin-reduced GH signaling becomes obvious with increased dose and acting time of insulin. The participation of suppressor of cytokine signaling (SOCS), the interaction between JAK2 and IRS, and GHR sensitivity should also be considered when discovering GH signal. The involvement of SS in response to insulin is not clear yet. The details of how GH secretion, level and signaling change in response to time and dose of insulin treatment warrant further studies.

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.</p><p><b>METHODS</b>This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.</p><p><b>RESULTS</b>At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.</p><p><b>CONCLUSIONS</b>Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.</p><p><b>REGISTRATION NUMBER</b>ChiCTR-TRC-13003776.</p>

Management status of type 2 diabetes mellitus in tertiary hospitals in Beijing: gap between guideline and reality / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetes has become one of the most common chronic diseases and the third leading cause of death in China. Many programs have been initiated at national and local levels to address the illness. However, the effect of these programs in daily outpatient clinics is still unclear. The objective of this study was to investigate the management status of type 2 diabetes mellitus (T2DM) and factors associated with it in diabetes clinics of tertiary hospitals in Beijing.</p><p><b>METHODS</b>A cross-sectional survey was conducted in six tertiary hospitals in Beijing. Control criteria were defined based on 2007 China guideline for type 2 diabetes (CGT2D).</p><p><b>RESULTS</b>A sample of 1151 patients, age (60.8 ± 9.2) years, and with a median disease duration of 7.3 years was included. The hemoglobin A1c (HbA1c) mean level was (7.15 ± 1.50)%, the percentage of patients achieving the targets for HbA1c was 37.8%, blood pressure 65.6%, triglyceride (TG) 48.8%, high-density lipoprotein (HDL) 59.2%, low-density lipoprotein (LDL) 34.0%, and total cholesterol (TC) 42.0%. The factors independently associated with glycemic control were diabetes duration (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.919 - 0.982, P < 0.01), body mass index (BMI) (OR = 0.914, 95%CI: 0.854 - 0.979, P = 0.01) and smoking (OR = 0.391, 95%CI: 0.197 - 0.778, P < 0.01). The factors independently associated with blood pressure control were BMI (OR = 0.915, 95%CI: 0.872 - 0.960, P < 0.01) and male gender (OR = 0.624, 95%CI: 0.457 - 0.852, P < 0.01). The factor independently associated with LDL control was education level (OR = 1.429, 95%CI: 1.078 - 1.896, P = 0.013).</p><p><b>CONCLUSIONS</b>The management status of T2DM patients in tertiary hospitals in Beijing has improved remarkably. However, there is still room for further improvement to reach the guideline target. Long diabetes duration, high BMI, smoking, male gender and low education level were independently associated with poor metabolic control.</p>