Differences in insulin resistance and pancreatic B‐cell function in obese subjects with isolated impaired glucose tolerance and isolated impaired fasting glucose

Aims To investigate changes in insulin action and insulin secretion in obese subjects with different categories of impaired glucose regulation (IGR): impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG/IGT (CGI). Methods A total of 222 subjects underwent an oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test (FSIGTT); 100 had normal glucose tolerance (subdivided into 32 lean NGT, 68 obese NGT), and 122 were obese with IGR (82 IGT, 14 IFG and 26 CGI). The insulin sensitivity index (S_I) was assessed by Bergman's minimal model method with FSIGTT; insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S_I, was used to determine whether AIRg was adequate to compensate for insulin resistance. Results S_I was similar in NGT and IGR obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT, significantly reduced in IGT, and further reduced in IFG and CGI subjects as compared with obese NGT subgroups. DI was reduced in NGT obese individuals. Within the obese IGR subgroups, IFG and CGI subjects had even lower DI value than IGT subjects. Conclusions Obese Chinese subjects with IGR have a similar degree of insulin resistance but differ in insulin secretion. Subjects with IFG and CGI have a more prominent deficiency in insulin secretion than subjects with IGT.     

空腹血糖异常、糖耐量减低患者血清胰岛素水平的变化及其意义

目的 观察空腹血糖异常(IFG)、糖耐量减低(IGT)患者血清胰岛素水平的变化。方法 对50例空腹血糖和糖耐量正常者(NGT)、40例IFC和80例IGT患者行口服葡萄糖耐量试验(0GTT)，用氧化酶法检测血糖，用放免法测定血清空腹及餐后2小时胰岛素。结果 IFG、IGT组空腹血糖、空腹胰岛素水平及胰岛素敏感指数较NGT组明显升高(P＜0.05或P＜0．01)，IFG组胰岛素敏感指数与IGT组比较无显著性差异(P＞0．05)。结论 在IFG、IGT状态下已经存在胰岛素抵抗，而且在程度上两者间并没有显著性差异，应早期干预治疗。     

Diurnal triglyceridaemia and insulin resistance in mildly obese subjects with normal fasting plasma lipids

OBJECTIVE: A novel method has been developed to study diurnal triglyceride (TG) profiles using repeated capillary self-measurements in an 'out-of-hospital' situation. We assessed the diurnal capillary TG (TGc) profile in males with mild obesity and evaluated the use of plasma and capillary TG as markers of insulin resistance. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Fifty-four lean (body mass index, BMI < 25 kg m-2) and 27 mildly obese (25 < BMI < 30 kg m-2), normolipidaemic males measured capillary TG concentrations on six fixed time-points over a 3-day period in an 'out-of-hospital' situation. MAIN OUTCOME MEASURES: The total area under the TGc curve (TGc-AUC) and incremental area under the TGc curve (TGc-IAUC) were used as estimation of diurnal triglyceridaemia. Fasting blood samples were obtained once. Food intake was recorded by all participants. RESULTS: Obese and lean subjects had comparable fasting capillary TG concentrations (1.37 +/- 0.40 mmol L-1 and 1.32 +/- 0.53 mmol L-1, respectively). However, during the day, obese subjects showed a greater TG increase, resulting in significantly higher TGc-AUC (27.1 +/- 8.4 and 23.0 +/- 6.3 mmol h-1 l-1, respectively; P < 0.05) and TGc-IAUC (7.9 +/- 5.8 and 4.6 +/- 6.6 mmolh-1 L-1, respectively; P < 0.05). The total group of 81 males was divided into quartiles based on fasting plasma TG, fasting capillary TG, TGc-AUC and TGc-IAUC. Amongst these variables, TGc-AUC was the only significant discriminator of subjects with high homeostasis model assessment (HOMA) (insulin resistance) compared with low HOMA (insulin sensitive). Overall, BMI was the strongest determinant of HOMA. CONCLUSIONS: Diurnal TG profiles can be used to investigate postprandial lipaemia in both lean and mildly obese subjects and may help to detect subjects with an underlying disposition for hypertriglyceridaemia related to insulin resistance, i.e. the metabolic syndrome.     

空腹血糖异常人群胰岛素分泌功能及胰岛素抵抗状态的探讨

目的　探讨空腹血糖异常人群的胰岛素分泌及胰岛素抵抗状态。　方法　选择包钢糖尿病普查中复查口服葡萄糖耐量试验 (OGTT) 3985例 ,分为 6组 :正常糖耐量 (NGT)组 2 5 88例 ,异常空腹血糖 (IFG)组 2 72例 ,糖耐量减低 (IGT)组 4 4 9例 ,空腹血糖异常伴糖耐量减低 (IFG/ IGT)组116例 ,新诊断糖尿病 (DM1)组 338例 ,已知糖尿病 (DM2 )组 2 2 2例。测腰围、体重指数、血压、血脂及血浆胰岛素 ,应用稳态模式胰岛素抵抗指数 (HOMA- IR)作为胰岛素抵抗指标 ,稳态模式胰岛 β细胞功能指数 (HBCI)及胰岛素分泌指数 (IS)作为胰岛素分泌指标 ,并对 6组患者的这些指标及临床特征 ,进行对比分析。　结果　与 NGT组比较 ,IFG组 HOMA- IR(1.4 6± 0 .6 0 ,1.0 6± 0 .6 4 ,t=- 6 .716 ,P<0 .0 0 1)、空腹胰岛素 (FINS) (17.90± 10 .0 6 ,15 .79± 10 .94 ,t=- 2 .0 71,P=0 .0 39)增高 ,HB-CI(4.6 5± 0 .6 0 ,5 .2 7± 0 .76 ,t=3.399,P<0 .0 0 1)及 IS(0 .86± 0 .6 0 ,0 .99± 0 .6 2 ,t=2 .36 6 ,p=0 .0 18)降低 ;IGT组 HOMA- IR(1.39± 0 .5 8,t=4 .6 98) ,FINS(2 1.2 7± 15 .39,t=4 .4 93)、2 - h胰岛素(6 0 .84± 37.86 ,t=8.4 82 )、HBCI(5 .4 7± 0 .79,t=2 .6 98)、IS(1.2 5± 0 .6 1,t=4 .0 34,P值均 <0     

Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus

Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 ± 0.15 at baseline to 0.43 ± 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (ΔI_0-30/ΔG_0-30) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = −0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in 11 healthy subjects; but neither serum total nor HMW adiponectin changed. In conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly after glucose loading in subjects with NGT or IFG; and the decrease of HMW adiponectin may be associated with an increase of serum insulin at 30 minutes.     

Adipocytes in subjects with impaired fasting glucose and impaired glucose tolerance are resistant to the anti-lipolytic effect of insulin

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two intermediate states in the transition from normal glucose metabolism to type 2 diabetes. Insulin clamp studies have shown that subjects with IGT have increased insulin resistance in skeletal muscle, while subjects with IFG have near normal muscle insulin sensitivity. Because of the central role of altered free fatty acid (FFA) metabolism in the pathogenesis of insulin resistance, we have examined plasma free fatty acid concentration under fasting conditions, and during OGTT in subjects with IGT and IFG. Seventy-one NGT, 70 IGT and 46 IFG subjects were studied. Fasting plasma FFA in IGT subjects was significantly greater than NGT, while subjects with IFG had similar fasting plasma FFA concentration to NGT. However, fasting plasma insulin concentration was significantly increased in IFG subjects compared to NGT while subjects with IGT had near normal fasting plasma insulin levels. The adipocyte insulin resistance index (product of fasting plasma FFA and FPI) was significantly increased in both IFG and IGT subjects compared to NGT. During the OGTT both IFG and IGT subjects suppressed their plasma FFA concentration similarly to NGT subjects, but the post-glucose loads were significantly increased in both IFG and IGT subjects. These data suggest that both subjects with IFG and IGT have increased resistance to the antilipolytic action of insulin. However, under basal conditions, fasting hyperinsulinemia in IFG subjects is sufficient to offset the adipocyte insulin resistance and maintain normal fasting plasma FFA concentration while the lack of increase in FPI in IGT subjects results in an elevated fasting plasma FFA.     

Effects of miglitol taken just before or after breakfast on plasma glucose,serum insulin,glucagon and incretin levels after lunch in men with normal glucose tolerance,impaired fasting glucose or impaired glucose tolerance

Aims/Introduction: One of the reasons for the poor adherence to α‐glucosidase inhibitor (αGI) treatment is the need to take medication three times a day. We hypothesized that the administration of miglitol might be effective for the next meal if the miglitol‐induced inhibition of α‐glucosidase activity persists until the next meal. In the present study, we evaluated whether the administration of miglitol just before or after breakfast was effective for postprandial glucose excursion after lunch without taking miglitol at lunch. Materials and Methods: We measured the plasma glucose, serum insulin and glucagon, plasma active glucagon‐like peptide‐1 (GLP‐1), and total glucose‐dependent insulinotropic polypeptide levels in non‐diabetic men. Miglitol was given to each patient according to four different intake schedules (control: no drug; intake 1: drug given just before breakfast [50 mg]; intake 2: drug given 30 min after the start of breakfast [50 mg]; intake 3: drug given at the same time as intake 2, but without eating breakfast [50 mg]). Results: Both intake 1 and intake 2 had a smaller area under the curve (AUC) for plasma glucose excursion after lunch, compared with the control. Intake 2 had a larger AUC for active GLP‐1 after lunch, compared with intake 1. Conclusions: Intake 1 and intake 2 can improve postprandial hyperglycemia after lunch. The results of the present study raise the possibility that the administration of miglitol twice a day might be effective and might help to improve treatment adherence among diabetic patients. This trial was registered with UMIN Clinical Trial Registry (no. UMIN000002896). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00129.x, 2011)     

Evaluation of insulin resistance in non-obese subjects with impaired glucose tolerance

Insulin resistance was estimated in nine subjects with impaired glucose tolerance (IGT) and eleven healthy, age and body-weight matched controls. Glucose tolerance and insulin response were evaluated by means of a 2h-glucose infusion test. Insulin resistance was determined by measuring the steady state plasma glucose response (SSPG) to a continuous infusion of glucose (6 mg . kg-1 . min-1 or 12 mg . kg-1 . min-1), insulin, epinephrine and propranolol for 150 minutes as described previously by other authors. The endogenous insulin secretion (C-peptide) was inhibited by epinephrine and propranolol in controls and subjects with IGT irrespective of a low (6 mg . kg-1 . min-1) or high (12 mg . kg-1 . min-1) glucose infusion. Steady-state plasma levels of exogenous insulin were virtually identical in all groups studied. There were no significant differences in the pancreatic glucagon, growth hormone, FFA and glycerol response during the SSPG period between controls and subjects with IGT. In comparison to controls the mean SSPG was significantly higher in subjects with IGT (during low and high glucose infusion) suggesting the existence of insulin resistance in these subjects. A higher glucose dose as described earlier by other investigators does not provide a better discrimination of controls and subjects with IGT concerning their degree of insulin resistance. Finally, there was a direct correlation between the SSPG and glucose tolerance in the total group. In conclusion, our results have confirmed the validity of an infusion technique of glucose, insulin, epinephrine and propranolol for evaluation of insulin sensitivity in vivo. In addition, our findings have added further support for insulin resistance in subjects with IGT which is directly proportional to the degree of glucose intolerance.     

新疆汉、维民族糖调节受损人群胰岛素分泌功能和胰岛素作用功能的研究

目的 评估新疆汉、维民族在IFG,IGT及IGR阶段的胰岛素分泌功能和胰岛素作用功能。 方法 采用多中心研究进行横断面调查,行OGTT试验。用胰岛素抵抗指数（HOMA-IR）评估IR,胰岛β细胞功能指数（HOMA-β）评估基础胰岛素分泌;ΔI30/ΔG30评价胰岛素早相分泌,ΔI30/ΔG30/HOMA-IR评估葡萄糖处置指数（DI）。 结果 WC、BMI、血脂、FIns、2 hIns在汉、维民族不同糖代谢组差异有统计学意义。IFG组与NGT、IGT组比较,汉、维族人群的HOMA-IR差异有统计学意义。在汉族中NGT组与IGT、IGR组比较,HOMA-β差异有统计学意义（P=0.030、0.044）,而在维族只有IFG组与NGT组比较差异有统计学意义（P=0.001）。ΔI30/ΔG30、DI在两民族不同糖代谢组差异均无统计学意义。 结论 汉族人群IR在IFG阶段,胰岛素分泌功能在IGT阶段起主要作用。IR和胰岛素分泌功能在维族人群IFG阶段起重要作用。胰岛素早相分泌及葡萄糖处置功能在糖调节受损阶段作用不显著。     

Plasma glucagon suppressibility after oral glucose in obese subjects with normal and impaired glucose tolerance

Blood glucose, plasma insulin, and glucagon responses after a 75 g oral glucose-tolerance test were assessed in 9 normal controls, 5 obese nondiabetics (ON), 5 obese nondiabetics with fasting hyperinsulinemia (obese “resistant” nondiabetics—OR), 9 obese with impaired glucose tolerance (O-IGT), and 9 nonobese insulin-dependent diabetics (IDD). Fasting plasma glucagon concentrations were significantly higher in all groups of patients in comparison to the normal controls. Insulin secretion, evaluated in all but the IDD, was similar to normal in the ON and increased in the OR and O-IGT. Normal glucagon suppression was observed in the lean controls and ON but not in OR, O-IGT, and IDD. We suggested that the resistance to glucagon suppression after glucose load in the OR and O-IGT in the presence of increased insulin response could be an indication that the A cell participates in the relative insulin insensitivity of these subjects.     

Skeletal muscle potassium increases after diet and weight reduction in obese subjects with normal and impaired glucose tolerance

Body composition calculated from total body potassium and skeletal muscle potassium were studied in middle-aged obese men and women with normal and impaired glucose tolerance as well as Type II diabetes before and after advice on calorie reduction during twelve months. The subjects were compared with healthy lean men and women. Mean weight loss was 6.6 kg (P less than 0.05). Lean body mass and body fat decreased 2.0 kg (P less than 0.05) and 4.6 kg (P less than 0.05), respectively. Total body potassium decreased by a mean of 146 +/- 49 mmol (P less than 0.01). Obese men with Type II diabetes and impaired glucose tolerance had lower total body potassium and muscle potassium levels than obese healthy men. After dieting, the obese men and women increased their muscle potassium levels with a mean of 2.8 mmol/100 fat-free dry weight to 42.6 +/- 2.6 mmol/100 g fat-free dry weight (P less than 0.05), but they were still below the levels of the lean controls, 44.4 +/- 1.3 MMOL/100 g fat-free dry weight, (P less than 0.01). Increase in skeletal muscle potassium was correlated to decrease in body weight, r = 0.55 (P less than 0.01) and to decrease in fasting blood glucose, r = 0.42 (P less than 0.05).     

肥胖和非肥胖糖耐量受损患者胰岛素敏感性和1相胰岛素分泌研究

目的研究肥胖和非肥胖糖耐量受损(IGT)患者的胰岛素敏感性和β细胞1相胰岛素分泌功能,以探讨在IGT患者中肥胖对胰岛素抵抗和1相胰岛素分泌的影响。方法共有99位受试者(包括正常对照者32名,肥胖IGT44例,非肥胖IGT23例)接受了口服75 g葡萄糖耐量试验(OGTT)和胰岛素改良的减少样本数(采血样12次)的Bergman微小模型技术结合静脉葡萄糖耐量试验(FSIGTT)。胰岛素抵抗由FSIGTT中胰岛素敏感性指数(SI)加以评估,而OGTT中糖负荷后30 min胰岛素增值与血糖增值之比值[ΔI30/ΔG30=(I30 min-I0 min) /(G30 min-G0 min)]和FSIGTT中急性胰岛素分泌反应(AIRg)则用以评价胰岛β细胞分泌功能。处理指数(DI =AIRg×SI)用于评价AIRg是否代偿机体的胰岛素抵抗。结果与正常对照组[(7.52±10.89)×10-4]相比,二组IGT患者之SI明显降低,而肥胖IGT组的SI[(1.72±1.11)×10-4]较非肥胖组[(3.15±1.49)×10-4]更低(均P<0.01); AIRg和ΔI30/ΔG30在正常组(412±191,14.45±8.47)和肥胖IGT组(378±235,17.02±11.30)之间差异无统计学意义,但均大于非肥胖组(196±160,8.93±6.69,均P<0.01);与正常组(2 851±1 180)相比,DI指数在二组IGT显著降低(595±485,584±517),但后二组间此值差异无统计学意义。SI与2 h胰岛素、体重指数、尿酸和胆固醇呈显著的负相关性(校正r2=0.603,P<0.01);而AIRg与ΔI30/ΔG30显著正相关,与空腹血糖负相关(校正r2=0.479,P<0.01)。结论IGT患者存在胰岛素抵抗和β细胞功能异常。与非肥胖IGT患者相比,肥胖IGT患者胰岛素抵抗程度更为严重,但胰岛β细胞胰岛素1相分泌相对充分。     

Are insulin resistance,impaired fasting glucose and impaired glucose tolerance all equally strongly related to age?

BACKGROUND: Insulin resistance (IR) has been considered an underlying cause of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Whether IR increases with age has been debated. We investigated the age-associated deterioration in the homeostasis model assessment (HOMA) of IR and in glucose metabolism. METHODS: Ten (nine including women) European studies contributed data on 6314 men and 6393 women aged 30-88 years. The cohort- and sex-specific top 25% of HOMA of IR in non-diabetic subjects was used to define HOMA-IR. RESULTS: Compared with subjects aged 50-59 years, the cohort- and body mass index-adjusted odds ratio (95% confidence interval) for HOMA-IR was 0.83 (0.64, 1.08), 0.87 (0.74, 1.03), 1.20 (1.02, 1.42) and 1.45 (1.10, 1.92) in men and 0.84 (0.62, 1.14), 0.91 (0.77, 1.09), 1.38 (1.19, 1.62) and 1.71 (1.35, 2.17) in women, respectively, aged 30-39, 40-49, 60-69 and > or = 70 years (P < 0.0001 for trend test). The same increasing trend was also observed for IFG. In contrast, the corresponding odds ratios for IGT increased linearly and more strongly with age, being 0.37 (0.22, 0.63), 0.67 (0.52, 0.87), 1.55 (1.24, 1.92) and 2.96 (2.13, 4.13) in men and 0.51 (0.31, 0.85), 0.66 (0.52, 0.86), 1.92 (1.57, 2.35) and 3.85 (2.89, 5.12) in women, respectively. CONCLUSIONS: Age is more strongly associated with IGT than with HOMA-IR or IFG in non-diabetic European populations.     

Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance

OBJECTIVE: This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, beta-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). METHODS: Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) < or = 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. RESULTS: After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4.25 +/- 0.22 vs 4.80 +/- 0.17 mmol/l, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (1.25 +/- 0.07 vs 1.43 +/- 0.06 mmol/l, P < 0.05), and low-density lipoprotein cholesterol (LDL-C) (2.70 +/- 0.15 vs 3.37 +/- 0.17 mmol/l, P < 0.05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic beta-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0.38 +/- 0.06 vs 0.54 +/- 0.09 x 10(-5) min(-1)/pmol, P < 0.05; 0.017 +/- 0.002 vs 0.021 +/- 0.001 min(-1), P < 0.05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0.05). CONCLUSION: Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on beta-cell secretory function.     

艾塞那肽对糖调节受损肥胖者血胰岛素及胰岛素抵抗的影响

目的探讨艾塞那肽对糖调节受损（IGR）肥胖者血胰岛素及血糖的影响。方法选取2011年5月至2012年11月在福建医科大学附属泉州第一医院就诊的75例糖调节受损（IGR）肥胖者为研究对象,其中62例受试者符合入选条件,按基线胰岛素水平分为高胰岛素血症（HIns,32例）与非高胰岛素血症（NHIns,30例）2组,HIns以空腹胰岛素≥15mU／L和（或）口服葡萄糖耐量试验（OGTr）2h胰岛素≥80mU儿作为切点。测定基线及应用艾塞那肽5d及14d时的空腹与OGTF2h血浆血糖、胰岛素、C肽、体重等指标。以稳态模型评估的胰岛素抵抗指数（HOMA-IR）及Gutt胰岛素敏感指数评估胰岛素抵抗及敏感性。同一组治疗前后比较采用配对t检验,组间均数比较采用单因素方差分析,率的比较采用x。检验。结果两组的空腹及OGTr2h血糖在用药5d时较基线下降（t=4．42、9．78、4．00、8．66,均P〈0．05）,HIns组空腹胰岛素在用药5d时较基线下降（t=2．07,P〈0．05）,OGTr2h胰岛素在用药5d较基线时下降,用药14d较5d时进一步下降（F=24．17,P〈0．05）。HIns组HOMA—IR在用药5d时较基线下降（t=3．27,只〈0．05）。NHIns组HOMA—IR在用药5d及14d时较基线均无下降（均P〉0．05）,HIns组Gutt胰岛素敏感指数在用药5d时较基线升高（t=-9．84,P〈0．05）,14d时较5d时进一步升高（F=55．96,P、遗0．05）。NHIns组Gutt胰岛素敏感指数在用药5d时较基线升高（t=-4．27,P〈0．05）。HIns组与NHIns组体重在5d时较基线无下降,14d时均较5d时明显下降（t=14．13、12．00,均P〈0．05）。结论IGR肥胖人群短期应用艾塞那肽即可获益调节血糖、改善胰岛素抵抗、控制体重。     

Effects of hyperglycaemia and hyperinsulinaemia on plasma amino acid levels in obese subjects with normal glucose tolerance

OBJECTIVE: To investigate the effects of hyperglycaemia and hyperinsulinaemia on amino acid disposal in human obesity. DESIGN: Four sequential experimental conditions: (1) overnight fasting; (2) hyperglycaemia with hyperinsulinaemia (2 h hyperglycaemic clamp at 11 mmol/l); (3) hyperglycaemia with basal insulin (1 h hyperglycaemic clamp during somatostatin infusion), (4) hyperglycaemia with resuming hyperinsulinaemia (1 h hyperglycaemic clamp after somatostatin discontinuation). SUBJECTS: Seven non-obese and seven obese non-diabetic, normo-insulinaemic subjects. MEASUREMENTS: Glucose infused to maintain steady-state hyperglycaemia. Plasma insulin, glucagon, free fatty acid and amino acid concentrations in the last 20 min of the four experimental conditions. Net rates of plasma amino acid disappearance and appearance (micromol/l per hour), calculated as the slopes of the regression of amino acid concentration on time. RESULTS: The amount of glucose infused to maintain hyperglycaemia was reduced by nearly 50% in obese subjects. During hyperinsulinaemia, FFA suppression was lower in obese subjects. In all experimental conditions plasma amino acid levels were slightly, non-significantly higher in obese than in non-obese subjects. In both groups plasma amino acids decreased slightly with ongoing fasting, decreased remarkably during hyperglycaemia-hyperinsulinaemia, rose promptly when insulin concentration was suppressed by somatostatin infusion, and declined again after somatostatin discontinuation. Also the time-course of plasma branched-chain amino acids, which paralleled that of total amino acids, was similar in the two groups. The net rates of amino acid disappearance from plasma did not differ in obese and non-obese subjects both at fasting and during hyperglycaemia-hyperinsulinaemia. Also plasma amino acid appearance during hyperglycaemia with basal insulin was not different in the two groups. CONCLUSION: The net traffic of amino acids to and from plasma in relation to insulin drive and prevailing glucose is not impaired in obese subjects with normal glucose tolerance, in spite of a decreased insulin sensitivity of glucose and lipid metabolism.     

A pilot study to examine the feasibility of insulin glargine in subjects with impaired fasting glucose, impaired glucose tolerance or new-onset type 2 diabetes.

OBJECTIVE: People with early type 2 diabetes and pre-diabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) are at risk of hyperglycaemia-related complications, including cardiovascular disease. Insulin, traditionally reserved as late treatment in type 2 diabetes, may also be a useful therapy in this population. We examined the short-term efficacy and tolerability of insulin glargine (glargine) in individuals with early or pre-type 2 diabetes. RESEARCH DESIGN AND METHODS: In this multicentre, double-blind, placebo-controlled, randomized, parallel group, 12-day study, subjects with IGT/IFG (n=9), newly diagnosed type 2 diabetes (n=9) or normal glucose tolerance (n=3) (confined to a clinical research unit taking a prescribed diet) were randomized to once-daily glargine (n=16) or placebo (saline; n=5) at bedtime. Dose was titrated to achieve target fasting blood glucose (FBG) 80-95 mg/dL. RESULTS: Over the treatment period, mean FBG decreased in glargine-treated subjects (from 100.0+/-18.8 to 85.6+/-18.4 mg/dL), but was unchanged in placebo-treated subjects (from 112.5+/-10.6 to 111.3+/-17.5 mg/dL). Mean eight-point blood glucose value decreased by 9.7 mg/dL in the glargine group, but increased by 8.1 mg/dL in the placebo group. Mean post-exercise blood glucose was similar before and after glargine treatment, but increased after placebo treatment. Five subjects receiving glargine experienced 16 mild symptomatic hypoglycaemia episodes; however, no hypoglycaemia occurred during exercise. Mean body weight decreased in both the glargine (-0.44 kg) and placebo (-0.25 kg) groups, in line with dietary restrictions. CONCLUSIONS: The results of this pilot study suggest that glargine can be used by people with IFG, IGT or new-onset type 2 diabetes for management of hyperglycaemia with low risk of hypoglycaemia. However titration of insulin in people on dietary restrictions should be more cautious as they may be more prone to hypoglycaemia. Further studies are warranted to determine the clinical benefits of this approach.     

The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study

Aim:  Acarbose, a glucose oxidase inhibitor, delays the absorption of glucose thus reducing post-prandial blood glucose level, haemoglobin A1c (HbA1c) and insulin resistance in patients with diabetes mellitus and in subjects with impaired glucose tolerance. The effect of acarbose in subjects with normal glucose tolerance (NGT) has hitherto not been examined. The aim of the present study was to examine the effect of acarbose in obese hypertensive subjects with NGT.
Methods:  A double-blinded, parallel group study was performed on 56 male subjects with hypertension, body mass index (BMI) 27–35 kg/m², fasting blood glucose ≤ 6 mmol/l and a normal oral glucose tolerance test. Blood pressure, HbA1c, lipid profile and insulin resistance [homeostasis model assessment (HOMA) index] were determined initially and following 24 weeks of acarbose, 150 mg/day or placebo. The primary end point was the change in insulin resistance. Anti-hypertensive treatment and diet were kept constant during the study.
Results:  Insulin resistance decreased in acarbose users but not on placebo. HOMA index declined from 5.36 ± 1.7 to 4.10 ± 1.6 (p = 0.001) on acarbose, the corresponding values on placebo were 5.44 ± 1.9 and 5.53 ± 1.7. A decrease in serum triglyceride values (2.16 ± 0.16 mmol/l to 1.76 ± 0.15 mmol/l, p = 0.02) took place on acarbose with no change on placebo. There was no change in BMI, low-density lipoprotein or high-density lipoprotein values in either group. Blood pressure declined equally in both the groups, probably due to better patient compliance.
Conclusions:  Acarbose may reduce insulin resistance and triglycerides also in obese hypertensive subjects with normal glucose tolerance.