Basal and exercise-induced skeletal muscle blood flow is augmented in type I diabetes mellitus

Hyperaemia occurs early in the renal and retinal microcirculation of patients with type I (insulin-dependent) diabetes mellitus, and may be critical in the development of nephropathy and retinopathy. We therefore sought to determine whether resting and exercise-induced hyperaemia was also apparent in the skeletal muscle circulation of young subjects with type I diabetes. Blood flow was assessed by venous occlusion plethysmography in 18 diabetic (DM) subjects and 20 matched controls. Exercise entailed 2 min of isotonic exercise against no load. Endothelium-dependent and -independent vasodilator function was assessed following intra-arterial infusion of acetylcholine and sodium nitroprusside respectively. Forearm blood flow (FBF) was higher in DM subjects than in controls (3.3+/-0.3 and 2.2+/-0.2 ml x min(-1) x 100 ml(-1) forearm respectively; P<0.005). This was not due to differences in forearm or body size, blood pressure, heart rate, lipid status or glycaemic control. Peripheral insulin levels were higher in DM subjects than in controls (48.5+/-8 and 15.5+/-1.5 micro-units/ml respectively; P<0.005). Resting FBF was closely correlated with insulin levels (r(2)=0.4; P<0.005). Parameters of exercise-induced hyperaemia [including peak flow (16.4+/-1.4 and 12.0+/-0.7 ml x min(-1) x 100 ml(-1) forearm in DM and control subjects respectively; P<0.01) and the volume repaid to the forearm at 5 min post-exercise (32.1+/-3.1 and 23.1+/-1.4 ml x 100 ml(-1) forearm respectively; P<0.05)] were also significantly greater in DM subjects, even when differences in resting FBF were taken into account. Peak hyperaemic blood flow and the volume repaid at 5 min were also related to insulin levels (r(2)=0.16; P<0.05 and r(2)=0.27; P<0.005 respectively). The vasodilator response to acetylcholine was reduced in DM subjects (P<0.05; analysis of variance), and the slope of this dose-flow relationship was inversely related to insulin levels (r(2)=0.2; P<0.05). These data show that both resting and exercise-induced skeletal muscle blood flow are augmented in young patients with type I diabetes, possibly due to the vasodilatory effect of increased insulin levels. Diminished vasodilator responses to acetylcholine may also, in part, be a consequence of insulin-augmented resting muscle blood flow.     

Reduced skeletal muscle oxygen uptake and reduced beta-cell function: two early abnormalities in normal glucose-tolerant offspring of patients with type 2 diabetes

OBJECTIVE: Studies on insulin sensitivity and insulin secretion in subjects with a familial predisposition for type 2 diabetes mellitus (T2DM) traditionally produce inconsistent results. This may be due to small sample size, subject selection, matching procedures, and perhaps lack of a measure of physical fitness. RESEARCH DESIGN AND METHODS: In the present study, we specifically tested the hypothesis that a family history of T2DM is associated with reduced VO(2max), measured by incremental bicycle ergometry, independent of insulin sensitivity estimated from an oral glucose tolerance test (OGTT; n = 424) and measured by a euglycemic-hyperinsulinemic clamp (n = 185). Subjects included in the study were young (34 +/- 10 years), healthy, and normal glucose tolerant with either a first-degree relative (FDR) with T2DM (n = 183), a second-degree relative with T2DM (n = 94), or no family history of T2DM (control subjects, n = 147). BMI, percent body fat, waist-to-hip ratio (WHR), and habitual physical activity (HPA; standard questionnaire) were comparable among groups. FDRs had significantly lower VO(2max) than control subjects: 40.5 +/- 0.6 vs. 45.2 +/- 0.9 ml O(2)/kg lean body mass, P = 0.01 after adjusting for sex, age, BMI, HPA, and insulin sensitivity (euglycemic-hyperinsulinemic clamp). RESULTS: BMI, percent body fat, waist-to-hip ratio (WHR), and habitual physical activity (HPA; standard questionnaire) were comparable among groups. FDRs had significantly lower VO(2max) than control subjects: 40.5 +/- 0.6 vs. 45.2 +/- 0.9 ml O(2)/kg lean body mass, P = 0.01 after adjusting for sex, age, BMI, HPA, and insulin sensitivity (euglycemic-hyperinsulinemic clamp). Insulin sensitivity per se was not affected by family history of T2DM after adjusting for age, sex, BMI, and percent body fat (P = 0.76). The appropriateness of beta-cell function for the individual insulin sensitivity (disposition index: product of a validated secretion parameter [OGTT] and sensitivity [clamp]) was significantly lower in FDRs (87 +/- 4 units) versus control subjects (104 +/- 6 units, P = 0.02 after adjusting for sex, age, and BMI). Analyses of the larger OGTT group produced essentially the same results. CONCLUSIONS: In conclusion, these data are compatible with the hypothesis that familial predisposition for T2DM impairs maximal oxygen consumption in skeletal muscle. Because habitual physical activity was not different, genetic factors may be involved. Conceivably, reduced VO(2max) precedes skeletal muscle insulin resistance, providing a partial explanation for discrepancies in the literature.     

PKC-theta knockout mice are protected from fat-induced insulin resistance

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-theta are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-theta KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40-50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated PI3K activity. In contrast, PKC-theta inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the treatment of type 2 diabetes.     

肥胖的2型糖尿病患者血中白细胞介素-6含量与胰岛素抵抗

目的　探讨肥胖的 2型糖尿病 (T2DM )患者血浆白细胞介素 6 (IL 6 )水平及其与胰岛素敏感性的关系。方法　受试者分为肥胖的T2DM组 (4 2例 )、非肥胖的T2DM组 (4 0例 )和正常体质量对照组 (37例 ) ;除体质量指数、腰臀比值外 ,各组间在年龄、性别、种族等方面均具有可比性 ;禁食 12～ 14小时 ,空腹静脉取血 ,测定血浆IL 6、血脂、空腹血糖 (FPG)、空腹血浆胰岛素 (FPI) ,并计算胰岛素敏感性指数 (ISI)。结果　肥胖组血浆IL 6水平 (199.10±4 2 .18)ng/L明显高于非肥胖组 (12 1.4 5± 39.4 0 )ng/L(P <0 .0 5 )和正常体质量对照组 (119.91± 34.12 )ng/L(P<0 .0 1) ;血浆IL 6水平与ISI呈显著负相关 (r =- 0 .4 8,P <0 .0 1) ;与空腹三酰甘油水平呈正相关 (r =0 .36 ,P<0 .0 5 )。结论　血浆IL 6水平可能与肥胖的T2DM发生有关 ,血浆中IL 6含量升高可能加重肥胖的T2DM患者的胰岛素抵抗     

Long–echo time MR spectroscopy for skeletal muscle acetylcarnitine detection

Animal models suggest that acetylcarnitine production is essential for maintaining metabolic flexibility and insulin sensitivity. Because current methods to detect acetylcarnitine involve biopsy of the tissue of interest, noninvasive alternatives to measure acetylcarnitine concentrations could facilitate our understanding of its physiological relevance in humans. Here, we investigated the use of long–echo time (TE) proton magnetic resonance spectroscopy (¹H-MRS) to measure skeletal muscle acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE ¹H-MRS to measure acetylcarnitine in endurance-trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE ¹H-MRS protocol was implemented for successful detection of skeletal muscle acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS (³¹P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle acetylcarnitine concentration showed a reciprocal distribution, with mean acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring acetylcarnitine concentrations with ¹H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of acetylcarnitine, possibly underlying decreased insulin sensitivity.     

Effect of resistance exercise on insulin sensitivity of skeletal muscle

Insulin resistance (IR) is the common pathophysiological basis of many metabolic diseases. IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue, especially in skeletal muscle. Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation. Glucose uptake by skeletal muscle is complex, and it is controlled by many pathways. The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose. From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle, a series of signal transduction processes is completed, any of which potentially affects the physiological effects of insulin and leads to IR. Resistance exercise (RT) can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus (T2DM). However, the exact mechanism by which RT improves skeletal muscle IR remains unclear. Therefore, this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR. In conclusion, RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass, microvascular blood flow, and glucose transporter-4 expression in skeletal muscle, as well as by reducing lipid accumulation and inflammation in skeletal muscle. Thus, it is potentially useful in the prevention and treatment of T2DM.     

Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography.

Patients with coronary artery disease or heart failure have been shown to be insulin resistant. Whether in these patients heart muscle participates in the insulin resistance, and whether reduced blood flow is a mechanism for such resistance is not known. We measured heart and skeletal muscle blood flow and glucose uptake during euglycemic hyperinsulinemia (insulin clamp) in 15 male patients with angiographically proven coronary artery disease and chronic regional wall motion abnormalities. Six age- and weight-matched healthy subjects served as controls. Regional glucose uptake was measured by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose (FDG), blood flow was measured by the H2(15)O method. Myocardial glucose utilization was measured in regions with normal perfusion and wall motion as assessed by radionuclide ventriculography. Whole-body glucose uptake was 37+/-4 micromol x min(-1) x kg(-1) in controls and 14+/-2 mciromol x min(-1) x kg(-1) in patients (P = 0.001). Myocardial blood flow (1.09+/-0.06 vs. 0.97+/-0.04 ml x min(-1) x g(-1), controls vs. patients) and skeletal muscle (arm) blood flow (0.046+/-0.012 vs. 0.043+/-0.006 ml x min(-1) x g(-1)) were similar in the two groups (P = NS for both). In contrast, in patients both myocardial (0.38+/-0.03 vs. 0.70+/-0.03 micromol x min(-1) x g(-1), P = 0.0005) and muscle glucose uptake (0.026+/-0.004 vs. 0.056+/-0.006 micromol x min(-1) x g(-1), P = 0.005) were markedly reduced in comparison with controls. In the whole dataset, a direct relationship existed between insulin-stimulated glucose uptake in heart and skeletal muscle. Patients with a history of myocardial infarction and a low ejection fraction are insulin resistant. This insulin resistance affects both the myocardium and skeletal muscle and is independent of blood flow.     

Increased plasma amylin in type 1 diabetic patients after kidney and pancreas transplantation: A sign of impaired beta-cell function?

OBJECTIVE: In response to hyperglycemia, beta-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all beta-cell hormones. RESEARCH DESIGN AND METHODS: Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1 kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT). RESULTS: PKT patients had higher fasting amylin (19 +/- 3 vs. control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10 +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (-64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell sensitivity to glucose (r = -0.543, P < 0.004). CONCLUSIONS: After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired beta-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired beta-cell function in type 1 diabetic patients after PKT.     

糖尿病患者胰高血糖素样肽-1在糖耐量试验前后的变化及意义

目的探讨2型糖尿病患者胰高血糖素样肽-1(glucagon-like peptical-1,GLP-1)水平与血糖、胰岛素及胰岛素抵抗的关系。方法 2型糖尿病患者50例(糖尿病组)及体检健康者30例(对照组),2组均禁食10h后行糖耐量试验,采集空腹及餐后2h血标本,分别检测血浆葡萄糖、胰岛素、GLP-1水平。结果糖尿病组空腹及餐后2h血糖明显高于对照组(P<0.05),餐后2hGLP-1水平明显低于对照组(P<0.05),空腹和餐后2h胰岛素水平及空腹GLP-1水平与对照组比较差异无统计学意义(P>0.05)。结论 2型糖尿病患者餐后2hGLP-1水平较正常人明显降低;餐后GLP-1分泌水平可反映2型糖尿病患者胰岛功能受损程度。     

Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus

BACKGROUND: A prospective evaluation of the relationship between insulin secretion and insulin sensitivity, derived from the fasting state, is needed in clinical practice in order to identify the worsening of glucose metabolism. In this study the authors examine whether the product of insulin sensitivity and insulin secretion, assessed from the fasting state, predicts progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were followed up over a 5-year period. Insulin sensitivity was calculated using the Belfiore index (B) and insulin secretion by the homeostasis model analysis beta-cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0) pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] - 3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to IGT and T2DM, respectively. The product B-beta predicts the progression from NGT to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3, CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of insulin secretion to compensate for decreased insulin sensitivity during transition to IGT and T2DM can be successfully assessed with simple measures derived from the fasting state. The product B-beta predicts the development to IGT and T2DM.     

Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans.

Uncoupling protein-2 and -3 (UCP2 and UCP3) are mitochondrial proteins that show high sequence homology with the brown adipocyte-specific UCP1. UCP1 induces heat production by uncoupling respiration from ATP synthesis. UCP2 is widely expressed in human tissues, whereas UCP3 expression seems restricted to skeletal muscle, an important site of thermogenesis in humans. We have investigated the regulation of UCP2 and UCP3 gene expression in skeletal muscle and adipose tissue from lean and obese humans. UCP2 and -3 mRNA levels were not correlated with body mass index (BMI) in skeletal muscle, but a positive correlation (r = 0.55, P < 0.01, n = 22) was found between UCP2 mRNA level in adipose tissue and BMI. The effect of fasting was investigated in eight lean and six obese subjects maintained on a hypocaloric diet (1,045 kJ/d) for 5 d. Calorie restriction induced a similar 2-2.5-fold increase in UCP2 and -3 mRNA levels in lean and obese subjects. To study the effect of insulin on UCP gene expression, six lean and five obese subjects underwent a 3-h euglycemic hyperinsulinemic clamp. Insulin infusion did not modify UCP2 and -3 mRNA levels. In conclusion, the similar induction of gene expression observed during fasting in lean and obese subjects shows that there is no major alteration of UCP2 and -3 gene regulation in adipose tissue and skeletal muscle of obese subjects. The increase in UCP2 and -3 mRNA levels suggests a role for these proteins in the metabolic adaptation to fasting.     

2型糖尿病合并非酒精性脂肪性肝病肝纤维化与骨密度的相关性

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)合并非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)肝纤维化与骨密度的关系。方法:筛选T2DM患者539例,依据腹部超声分为T2DM组(n=234)、T2DM+NAFLD组(n=305),再依据非酒精性脂肪肝肝纤维化评分(non-alcoholic fatty liver disease fibrosis score,NAFLDFS)分为<-1.455排除纤维化亚组、-1.455~0.676可疑纤维化亚组、>0.676诊断纤维化亚组,行骨密度检查并测定空腹血糖(fasting blood glucose,FBG)、空腹C肽(fasting C-peptide,F-CP)、空腹胰岛素(fasting insulin,FINS)、糖化血红蛋白(HbA1c)、肝功能及血脂等血清学指标。结果:与T2DM组相比,T2DM+NAFLD组股骨颈、Ward’s三角、大粗隆、股骨干及全部股骨的骨密度及T值下降(P<0.05)。与-1.455~0.676亚组及<-1.455亚组相比,>0.676亚组股骨颈、Ward’s三角的骨密度及T值下降(P<0.05)。T2DM组和T2DM+NAFLD组骨量异常(骨量减少和骨质疏松)发生率存在差异(48.29%vs 65.90%,P<0.01);<-1.455亚组,-1.455~0.676亚组,>0.676亚组骨量异常发生率存在差异(48.39%vs 67.98%vs 82.5%,两两比较均P<0.01)。相关性分析示:NAFLDFS与股骨颈、Ward’s三角的骨密度及T值呈负相关(P<0.05)。Logistic回归分析示:在控制年龄、性别、BMI、病程、FBG、ALT、HDLC、HbA1C及载脂蛋白B(APOB)后,NAFLDFS评分是骨量减少的独立危险因素。-1.455~0.676亚组相对于<-1.455亚组骨量减少的风险增加(OR=2.235,95%CI 1.040~4.803,P<0.05);>0.676亚组相对于<-1.455亚组骨量减少的风险增加(OR=4.463,95%CI 1.221~16.308,P<0.05)。结论:T2DM合并NAFLD肝纤维化患者骨密度减低,两者具有相关性,进展性肝纤维化是骨量减少的危险因素。     

新诊断2型糖尿病患者血清miR-126、VEGF水平与胰岛素抵抗的相关性分析

目的分析新诊断2型糖尿病(T2DM)患者血清微小核糖核酸-126(miR-126)、血管内皮生长因子(VEGF)水平与胰岛素抵抗的相关性。方法选取该院2018年2月至2019年4月收治的T2DM患者86例设为观察组,另选取同期体检健康者86例设为对照组。检测两组空腹血清miR-126、VEGF、总胆固醇(TC)、三酰甘油(TG)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹血胰岛素(FIns)水平,计算体质量指数(BMI)、胰岛β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)。分析新诊断T2DM患者miR-126、VEGF水平与胰岛素抵抗的相关性。结果两组性别、年龄比较,差异无统计学意义(P>0.05);两组BMI、血清TC、TG、FPG、HbA1c、FIns水平及HOMA-IR、HOMA-β、ISI比较,差异有统计学意义(P<0.05);观察组血清VEGF水平[(523.48±145.36)ng/L]明显高于对照组[(295.45±94.46)ng/L],血清miR-126水平明显[(0.08±0.01)ng/μL]低于对照组[(0.18±0.02)ng/μL],差异有统计学意义(P<0.05);Pearson相关分析发现:VEGF与BMI、TC、TG、FPG、HbA1c、FIns、HOMA-IR呈正相关,与HOMA-β、ISI呈负相关(P<0.05);miR-126与BMI、TC、TG、FPG、HbA1c、FIns、HOMA-IR呈负相关,与HOMA-β、ISI呈正相关(P<0.05);经多因素逐步回归分析得出:影响血清VEGF表达的因素为ISI,影响血清miR-126水平表达的因素为ISI、HbA1c(P<0.05)。结论新诊断T2DM患者VEGF水平升高、miR-126水平降低,二者可能参与了胰岛素抵抗及T2DM的发生、发展。     

Effect of acarbose on insulin sensitivity in elderly patients with diabetes

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.     

2型糖尿病患者体质量指数、血脂与胰岛β细胞功能的相关性研究

目的探讨2型糖尿病(T2DM)患者体质量指数(BMI)、血脂与胰岛β细胞功能的相关性。方法选取2018年12月至2019年12月于该院内分泌科门诊就诊的334例T2DM患者作为研究对象,收集年龄、病程等基线资料,计算BMI,检测空腹血糖(FBG)、空腹胰岛素(FINS)、血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C),计算胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(HOMA-ISI)及胰岛素抵抗指数(HOMA-IR)。结果相关性分析显示,HOMA-IR与BMI呈正相关(P<0.05),HOM A-ISI与HDL-C呈正相关(P<0.05)。根据BMI将患者分为正常组、超重组和肥胖组,3组FBG、HOMA-IR差异有统计学意义(P<0.05);以HDL-C=1.1 mmol/L为界值将患者分为两组,两组年龄、病程、FINS、HOMA-ISI差异有统计学意义(P<0.05)。多元线性回归分析示,BMI是T2DM患者HOMA-IR的独立影响因素(P<0.05);HDL-C是T2DM患者HOMA-ISI的独立影响因素(P<0.05)。结论T2DM患者BMI、HDL-C与胰岛β细胞功能存在一定相关性,对T2DM合并胰岛素抵抗的诊断及指导治疗具有重要参考价值。     

卡格列净联合阿卡波糖对2型糖尿病患者miR-144、NLRP3 mRNA及MCP-1水平的影响

目的 探讨卡格列净联合阿卡波糖对2型糖尿病患者微小RNA(miR)-144、NOD样受体3炎性小体(NLRP3)mRNA及单核细胞趋化蛋白-1(MCP-1)水平的影响.方法 选取2019年7月至2020年7月该院收治的2型糖尿病患者186例,依据随机数字表法分为单药治疗组、联合治疗组,每组93例.比较两组患者治疗前后血...     

Effects of glimepiride on insulin secretion and sensitivity in patients with recently diagnosed type 2 diabetes mellitus

BACKGROUND: The exact mechanism of the efficacy of glimepiride in the achievement of glycemic control has not yet been clearly defined. OBJECTIVE: This study was conducted to examine the influence of glimepiride on insulin secretion and sensitivity in patients with type 2 diabetes mellitus (DM) of recent onset. METHODS: This 24-week, open-label, controlled trial was conducted at the Division of Endocrinology and Metabolism, Veterans Affairs Medical Center (Phoenix, Arizona). Study participants were aged 32 to 75 years and had recent-onset (established by a short duration of symptoms 6 weeks to 6 months prior to the study) type 2 DM, or were age-matched healthy volunteers (control group). In the diabetic patients, glimepiride tablets were administered orally, initially at 2 mg once daily in the morning, with the dosage increased by 1 mg every 2 weeks until fasting plasma glucose (FPG) decreased to 6.7 mmol/L; the dosage was then maintained for the remainder of the 24-week study period. Oral glucose tolerance tests (OGTTs) were conducted in the control group and before treatment and at 24 weeks after the achievement and maintenance of glycemic control (glycosylated hemoglobin <7.0%) in the diabetic group. For OGTT, plasma insulin and glucose levels were determined after the subjects fasted overnight and then at every 15 minutes for 2 hours after glucose challenge. RESULTS: Fourteen diabetic men (mean [SEM] age, 50 [6] years; range, 32-75 years) and 10 male healthy controls (mean [SD] age, 48 [5] years; range, 30-68 years) were enrolled. In the DM group, FPG decreased significantly after treatment ( P<0.001); fasting plasma insulin was markedly elevated before treatment (P<0.001 vs controls) and decreased after treatment ( P<0.01) but did not normalize; first-phase insulin secretion was markedly inhibited before treatment ( P<0.001 vs controls) and normalized after treatment ( P<0.001) total insulin secretion significantly improved after treatment ( P<0.01) but did not normalize. Finally, the pretreatment insulin sensitivity index decreased significantly (P<0.01) after treatment and normalized in 6 of 14 patients (42.9%) with type 2 DM. CONCLUSIONS: In this study, glimepiride achieved desirable glycemic control in patients with recent-onset type 2 DM through improvement in insulin secretion and sensitivity.     

白细胞介素-6在2型糖尿病患者腹部皮下和网膜脂肪组织中的表达及其与胰岛素抵抗的关系

目的探讨白细胞介素石（IL-6）基因在2型糖尿病（T2DM）患者腹部皮下和网膜脂肪组织中的表达情况，及其与胰岛素抵抗的关系。方法用半定量RT-PCR方法检测22例正常人（对照组）和20例T2DM（糖尿病组）患者的大网膜与皮下脂肪组织IL-6mRNA的表达水平，并测量体重、血压、腰围、臀围、血糖、空腹胰岛素、血脂和胰岛素敏感指数（IAI）。结果①糖尿病组网膜和皮下脂肪的IL-6mRNA表达量均高于对照组（P〈0．05）；对照组网膜组织的IL-6mRNA表达量高于皮下脂肪组织（P〈0．05）．而糖尿病组网膜和皮下脂肪组织差异无显著性（P〉0．05）。②将两组数据合并，网膜和皮下脂肪的IL-6mRNA表达量与腰臀比、胰岛素抵抗指数（HOMA-IR）呈正相关（P〈0．05），与血浆IAI呈负相关（P〈0．05），与其他因素均无相关性（均P〉0．05）。③多元逐步回归分析发现，皮下脂肪IL-6mRNA表达量与HOMA—IR、腰臀比相关（P〈0．05），网膜IL-6mRNA表达量与HOMA—IR相关（P〈0．05）。结论，12DM患者网膜和皮下脂肪组织IL-6mRNA表达水平升高，可以作为胰岛素抵抗的一个重要参数。