Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin secretion in high-risk African Americans with impaired glucose tolerance test and type 2 diabetes

We examined the metabolic effects of rosiglitazone therapy on glucose control, insulin sensitivity, insulin secretion, and adiponectin in first-degree relatives of African Americans with type 2 diabetes (DM) with impaired glucose tolerance (IGT) and DM for 3 months. The study was comprised of 12 first-degree relatives with IGT, 17 newly diagnosed DM, and 19 healthy relatives with normal glucose tolerance (NGT). Oral glucose tolerance test (OGTT) was performed before and after 3 months of rosiglitazone therapy (4 to 8 mg/d) in patients with IGT and DM. Serum glucose, insulin, C-peptide, and adiponectin levels were measured before and 2 hours during OGTT in the NGT and patients with IGT and DM. Insulin resistance index (HOMA-IR) and beta-cell function (HOMA-%B) were calculated in each subject using homeostasis model assessment (HOMA). Rosglitazone improved the overall glycemic control in the IGT and DM groups. Following rosiglitazone, the beta-cell secretion remained unchanged, while HOMR-IR was reduced in DM by 30% (4.12 +/- 1.95 v 6.33 +/- 3.54, P < .05) and the IGT group (3.78 +/- 2.45 v 4.81 +/- 3.49, P = not significant [NS]). Mean plasma adiponectin levels were significantly (P < .05) lower in the DM (6.74 +/- 1.95 microg/mL) when compared with the NGT group(9.61 +/- 5.09). Rosiglitazone significantly (P < .001) increased adiponectin levels by 2-fold in patients with IGT (22.2 +/- 10.97 microg/mL) and 2.5-fold greater in DM (15.68 +/- 8.23 microg/mL) at 3 months when compared with the 0 month. We conclude that adiponectin could play a significant role (1) in the pathogenesis of IGT and DM and (2) the beneficial metabolic effects of thiazolidinediones (TZDs) in high-risk African American patients.     

Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes

To evaluate the factors causing glucose intolerance in type 2 diabetes in Japan, insulin secretion and insulin sensitivity were compared across the range of glucose tolerance. Subjects were divided into 3 groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (DM) according to the criteria of the World Health Organization (WHO). We examined insulin secretion and insulin sensitivity using fasting blood glucose and insulin levels and 75 g oral glucose tolerance test (OGTT). We used homeostasis model assessment (HOMA) beta-cell and insulinogenic index (30 minutes) to estimate insulin secretion and HOMA-insulin resistance (IR) and insulin sensitivity index (ISI) composite for insulin sensitivity. Although insulin resistance plays an important role in the development of diabetes in many ethnic populations, the differences in insulin sensitivity between NGT and IGT and between IGT and DM are small in Japanese patients. On the other hand, as glucose intolerance increases, insulin secretion decreases most remarkably both between NGT and IGT and between IGT and DM in Japanese patients. Decreasing insulin secretion and decreasing insulin sensitivity both occur in developing type 2 diabetes in Japanese patients, but decreased basal and early-phase insulin secretion had more pronounced contribution to glucose tolerance than the indices of insulin sensitivity. Japanese type 2 diabetic patients are characterized by a larger decrease in insulin secretion and show less attribution of insulin resistance.     

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

OBJECTIVE: To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. METHODS: A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic beta-cell function (HOMA-derived beta-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. RESULTS: Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (P<0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P=0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.9+/-6.5 vs 89.2+/-10.6 mg/dl, P<0.05), higher 2-h post-OGGT insulin levels (101.2+/-74.0 vs 207.6+/-129.7 microU/ml, P<0.001), a lower QUICKI (0.323+/-0.031 vs 0.309+/-0.022, P<0.05), and higher fasting triglyceride levels (117.4+/-53.1 vs 156.9+/-68.9, P=0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes.CONCLUSIONS:Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.     

Diabetes and impaired glucose tolerance prevalences in Turkish patients with impaired fasting glucose

Impaired fasting glucose (IFG) like impaired glucose tolerance (IGT) has increased risk of progressing to diabetes mellitus (DM). The aim of the study was to evaluate prevalance of IGT and type 2 DM with oral glucose tolerance test (OGTT) in Turkish patients who had fasting glucose of 110 and 125 mg/dl. Hundred and forty-eight (67.3%) women and 72 (32.7%) men (30-65 years old with mean age of 51.3 +/- 8.7 year) who had fasting glucose range 110-125 mg/dl were evaluated with OGTT. Seventy-two patients had IGT (32.8%), 74 (33.6%) patients had type 2 diabetes and 74 (33.6%) patients had normal glucose tolerance (NGT). Mean fasting glucose and insulin levels were higher in the IGT group than in the NGT group. Mean level of total cholesterol was higher in DM than that in NGT and IGT groups. Mean triglyceride (TG) (P = 0.476), high-density lipoprotein (HDL) (P = 0.594), low-density lipoprotein (LDL) (P = 0.612), Apoproteine A (P = 0.876), Apoproteine B (P = 0.518), uric acid (P = 0.948) and ferritin (P = 0.314) were found higher in diabetic patients. Lipoproteine a (P = 0.083), fibrinogen (P = 0.175) and hsCRP (P = 0.621) levels were higher in IGT. Mean HOMA S% levels of NGT, IGT and DM were found to be 65.0 +/- 13.0%, 60.9 +/- 16.0% and 50.1 +/- 11.1%, respectively. HOMA B% levels were measured to be 80.4 +/- 29.1% in NGT, 85.3 +/- 14.59% in IGT and 60.1 +/- 10.1% in DM. Significant difference was found between IFG and DM (P = 0.043) groups. The prevalences of diabetes and IGT were found to be 33.63 and 32.7% in IFG, respectively.     

beta-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis

The nature of the progressive beta-cell failure occurring as normal glucose tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and insulin secretion rate (by deconvolution of plasma C-peptide levels during an oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass index [BMI] 相似文献   

Thiazolidinediones increase hepatic insulin extraction in African Americans with impaired glucose tolerance and type 2 diabetes mellitus. A pilot study of rosiglitazone

Peripheral insulin levels are determined by beta-cell secretion, insulin sensitivity, and hepatic insulin extraction (HIE). We have previously shown that whereas sulfonylureas reduce insulin extraction, metformin enhances HIE. However, the effects of thiazolidinediones (TZDs) on HIE remain uncertain. Thus, we investigated the potential contribution of hepatic insulin clearance to peripheral insulin levels during rosiglitazone therapy in African Americans with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). The study was composed of 12 first-degree relatives with IGT and 17 patients with newly diagnosed type 2 DM. Nineteen healthy relatives with normal glucose tolerance served as controls. Serum glucose, insulin, and C-peptide, and HIE (C-peptide-insulin molar ratios) were measured at t = 0 and 120 minutes during oral glucose tolerance test (OGTT) in all the subjects. The OGTT was performed before and after 3 months of rosiglitazone therapy (4 mg/d x 4 weeks and >8 mg/d x 8 weeks) in patients with IGT and type 2 DM. Insulin resistance index and beta-cell function were calculated in each subject using homeostasis model assessment (HOMA). Rosiglitazone therapy improved but did not normalize the overall glycemic control in the IGT and type 2 DM groups. After rosiglitazone therapy, the mean serum insulin and C-peptide levels at fasting remained unchanged. However, the 2-hour serum glucose and insulin were lower, whereas serum C-peptide was unchanged during 3 months of rosiglitazone treatment. Mean insulin resistance index of HOMA was reduced by 30% (4.12 +/- 1.95 vs 6.33 +/- 3.54, P < .05) in the type 2 DM group and by 21% (3.78 +/- 2.45 vs 4.81 +/- 3.49, P = NS) in the IGT group. Mean HIE values were significantly lower (70%) in the type 2 DM and IGT groups when compared with the normal glucose tolerance group. At 3 months, basal HIE was not significantly changed by rosiglitazone therapy in IGT and type 2 DM groups when compared with the baseline (0 month). However, rosiglitazone therapy was associated with increased HIE at 2 hours during OGTT by 40% and 30% in the IGT and type 2 DM groups, respectively, from the baseline (0 month) values. Furthermore, HIE inversely correlated with the insulin resistance index of HOMA (r = -.46, P < .05). We conclude that rosiglitazone therapy improved overall glucose tolerance and enhanced insulin sensitivity in patients with IGT and type 2 DM. Although basal HIE remained unchanged, rosiglitazone therapy increased postglucose challenge HIE in African Americans with IGT and type 2 DM. We speculate that TZDs increase insulin clearance or HIE after oral glucose challenge. This study suggests that in addition to insulin sensitization, rosiglitazone may be involved in insulin metabolism. The significance of the increased insulin clearance by TZD therapy remains uncertain and deserves further investigation in patients with insulin resistance and glucose intolerance.     

肥胖者胰岛素分泌功能对糖耐量低减及糖尿病发生的影响

目的　探讨肥胖者胰岛素分泌变化对糖耐量低减 (IGT)及糖尿病 (DM)发生的影响。　方法　对 30例单纯性肥胖 [体重指数 (BMI) >2 7]患者进行血糖和胰岛素测定 ,并观察胰岛细胞分泌指数 (HOMA- IS)及胰岛素敏感性指数 (IAI) ,并对这些患者进行 15年随访。　结果　肥胖者空腹胰岛素 (FINS)水平明显高于正常人 (P <0 .0 1) ,与 HOMA - IS明显的正相关 (P <0 .0 1) ;空腹血糖(FPG)与 HOMA- IS及 IAI呈明显的负相关 (P<0 .0 1)。15年内 6 3.3%的肥胖者发展成 IGT,5 0 .0 %的肥胖者及发展成 IGT者发展为 2型 DM。　结论　肥胖对 IGT及糖尿病的发生、发展有着明显的影响 ,控制体重是减少 IGT发生的重要环节。     

Effects of low intensity exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance and type 2 diabetes mellitus

This study was designed to evaluate effects of exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). The subjects consisted of overweight subjects with normal glucose tolerance (NGT, n=10), IGT (n=10) and DM (n=10) (age: 51.1+/-8.2, 56.3+/-8.8 and 58.5+/-6.2 years, respectively). All of these patients performed exercise therapy at lactate threshold intensity for 12 weeks. Before intervention, area under the glucose curve (AUC(PG)) was higher in DM, IGT and NGT groups, and area under the insulin curve (AUC(IRI)) and the early phase insulin secretion as calculated by insulinogenic index was higher in the NGT group than in either the IGT or DM groups (p<0.05). After exercise therapy, the insulin sensitivity, AUC(PG) and AUC(IRI) improved in three groups (p<0.05, respectively). The insulinogenic index increased in IGT and DM groups (p<0.05, respectively), but the changes in the insulinogenic index showed no significant differences between IGT and DM groups. These results suggest that the ss-cell function in subjects with IGT and DM could therefore improve after exercise therapy. Moreover, AUC(PG), AUC(IRI) and insulin sensitivity were also improved no relation to NGT, IGT and DM.     

不同糖耐量水平人群血清真胰岛素和胰岛素原水平的临床意义

目的 探讨不同糖耐量者血清真胰岛素（ＴＩ）及胰岛素原（ＰＩ）水平的变化及临床意义。方法 用特异的单克隆抗体夹心放大酶联免疫分析法（ＢＡ－ＥＬＩＳＡ）检测１３５例正常糖耐量（ＮＧＴ）、８６例糖耐量低减（ＩＧＴ）及１０１例Ⅱ型糖尿病（ＤＭ）者口服葡萄糖耐量试验（ＯＧＴＴ）各点血清ＴＩ及ＰＩ水平。结果 ３组血清空腹ＴＩ差异无显著性（Ｐ〉０．０５）,免疫反应胰岛素（ＩＲＩ）Ⅱ型ＤＭ组明显升高（Ｐ〈０．０１     

Impaired beta-cell function in human aging: response to nicotinic acid-induced insulin resistance

CONTEXT: Glucose tolerance declines with age and may involve impaired beta-cell sensitivity to glucose and beta-cell compensation for insulin resistance. OBJECTIVE: We investigated beta-cell sensitivity to glucose and beta-cell compensation for nicotinic acid-induced insulin resistance in young (age <35 yr) people with normal glucose tolerance (NGT) and old (age >60 yr) people with NGT and impaired glucose tolerance (IGT). DESIGN/PATIENTS/SETTING/INTERVENTION: Fifteen young NGT, 16 old NGT, and 14 old IGT were randomized to 2-wk treatment with nicotinic acid or placebo in a double-blind, crossover study in a university medical setting. At the end of each treatment period, participants had a frequently sampled iv glucose tolerance test and ramp clamp, in which insulin secretion rates (ISR) were determined in response to a matched 5-10 mm glucose stimulus. MAIN OUTCOME MEASURES: Insulin sensitivity (S(I)), acute insulin response to iv glucose (AIRg), and disposition index (AIRg x S(I), or beta-cell compensation for insulin resistance) from frequently sampled iv glucose tolerance testing, and ISR area under the curve (or beta-cell sensitivity to glucose) from ramp clamp were determined. RESULTS: Progressive impairments in insulin secretion as assessed by AIRg, disposition index, and ISR area under the curve were identified in older people with NGT, with more marked defects in older people with IGT. Nicotinic acid treatment significantly reduced S(I) in all groups. beta-Cell compensation for nicotinic acid-induced insulin resistance was incomplete in all three groups, with greater defects in the two older groups. CONCLUSIONS: Human aging is associated with impaired beta-cell sensitivity to glucose and impaired beta-cell compensation to insulin resistance.     

Differences in insulin sensitivity, pancreatic beta cell function and circulating adiponectin across glucose tolerance status in Thai obese and non-obese women

Although adiponectin levels are associated with obesity and insulin insensitivity, the role of adiponectin in the progression to diabetes in non-obese subjects is unclear. Therefore, 289 women aged 50–80 years without previous history of diabetes or impaired glucose tolerance (IGT) were studied. They were classified as normal glucose tolerance (NGT), IGT or diabetes based on WHO criteria. Insulin sensitivity (S) and beta cell function (B) indices were calculated using homeostasis model assessment (HOMA). In obese women with BMI ≥ 25 kg/m² (n = 161), there were declines in HOMA-%S (P < 0.001), HOMA-%B (P < 0.05) and circulating adiponectin (P < 0.001) across glucose tolerance status. In non-obese women with BMI < 25 kg/m² (n = 128), there was no significant change in HOMA-%S in women with IGT and diabetes as compared to women with NGT. However, HOMA-%B (P < 0.05) and serum adiponectin levels (P < 0.001) were significantly decreased across glucose tolerance. Serum adiponectin levels were correlated to HOMA-%S in both obese and non-obese women while negative correlations between circulating adiponectin and HOMA-%B were demonstrated only in obese women. We have demonstrated in the present study the predominant role of beta cell dysfunction as compared to that of insulin resistance in the deterioration of glucose tolerance in non-obese women. Circulating adiponectin appears to be inversely related to beta cell dysfunction in addition to insulin resistance only in obese women.     

Prevalence of glucose intolerance in primary hyperparathyroidism and the benefit of parathyroidectomy

BACKGROUND: Increased prevalence of diabetes mellitus (DM) in primary hyperparathyroidism (PHPT) is established, but not glucose intolerance (GI), nor benefit from parathyroidectomy on GI. We determined these during management of a continuous series of patients with PHPT routinely followed after surgery. PATIENTS AND METHODS: WHO criteria classified 75 g oral glucose tolerance tests (OGTT) in 51/54 consecutively proven PHPT patients, into normal glucose tolerance (NGT), DM, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG); GI was derived by adding those with DM and IGT/IFG. OGTT were repeated after parathyroidectomy (mean follow up 2.4 +/- SD 1.6 years). Paired student t tests were used to compare fasting and 2-h plasma glucose (PG). RESULTS: At presentation 32/54 patients (59%) had NGT, 10 IGT/IFG (19%) and 12 type 2 DM (22%), nine newly diagnosed. Before parathyroidectomy 17/35 patients had NGT (49%), 18 GI (51%), 12 DM (34%) and 6 IGT/IFG (17%). Five out of six patients with IGT/IFG had NGT, one with NGT developed IGT. At completion 23 patients (66%) had NGT, 12 GI (34%), 4 IGT/IFG (11%) and 8 DM (23%). After parathyroidectomy fasting and 2-h. PG fell in 30/34 normocalcaemic patients not on hypoglycaemic agents, 5.6 +/- 1.0 to 5.4 +/- 0.8 mmol/l, 7.2 +/- 3.0 to 6.3 +/- 3.1 mmol/l (p < 0.05, p < 0.01). CONCLUSIONS: 1.At presentation with PHPT, OGTT commonly identifies Type 2 DM and GI.2.After successful parathyroidectomy fasting and 2-h. PG fall significantly (p < 0.05, p < 0.01). DM and IGT/IFG often ameliorates to IGT or NGT, persistently.     

Tumor necrosis factor alpha and insulin resistance in obese type 2 diabetic patients

The relationship between basal serum tumor necrosis factor alpha (TNFalpha) levels and peripheral tissue (muscle) sensitivity to insulin was examined in 63 subjects with normal glucose tolerance (NGT), 18 subjects with impaired glucose tolerance (IGT), and 123 patients with type 2 diabetes mellitus (T2DM). The BMI was similar in NGT (28.8+/-0.7 kg/m(2)), IGT (31.1+/-1.0), and T2DM (30.0+/-0.4) groups. The fasting serum TNFalpha concentration in T2DM (4.4+/-0.2 pg/ml) was significantly higher than in NGT (3.1+/-0.2) and IGT (3.4+/-0.2; both P<0.05). In T2DM the fasting plasma glucose (FPG=183+/-5 mg/dl) and insulin (FPI=17+/-1 micro U/ml) concentrations were significantly higher than in NGT (FPG=95+/-1; FPI=10+/-1) and IGT (FPG=100+/-2; FPI=13+/-1; all P<0.01). The rate of total body insulin-mediated glucose disposal (Rd; 40 mU/m(2) min euglycemic insulin clamp in combination with (3)H-glucose) was reduced in T2DM (102+/-3 mg/m(2) min) compared with NGT (177+/-10) and IGT (151+/-14; both P<0.01). The serum TNFalpha concentration was inversely correlated with Rd (r=-0.47, P<0.0001) and positively correlated with both FPG (r=0.32, P=0.004) and FPI (r=0.32, P=0.004) in NGT plus IGT. No correlation was observed between serum TNFalpha and Rd (r=-0.02), FPG (r=0.15), or FPI (r=0.15) in T2DM. In stepwise multiple regression analysis using age, sex, BMI, FPG, FPI and serum TNFalpha concentration as independent variables, only BMI and serum TNFalpha concentration were significant and independent predictors of Rd (r(2)=0.29, P<0.0001) in the NGT plus IGT group, while FPG and FPI were significant and independent predictors of Rd (r(2)=0.13, P<0.0001) in T2DM. These results suggest that: (i) an increase in circulating TNFalpha concentration is associated with peripheral insulin resistance and increased plasma glucose and insulin levels prior to the onset of type 2 diabetes; and (ii) the further deterioration in peripheral insulin resistance in T2DM (compared with NGT and IGT) is unrelated to the increase in serum TNFalpha concentration.     

Limitation of the homeostasis model assessment to predict insulin resistance and beta-cell dysfunction in older people

CONTEXT: Studies in older people have shown inconsistent agreement between homeostasis model assessment of insulin resistance (HOMA-IR) and dynamic measures of insulin action and have not evaluated HOMA beta-cell. OBJECTIVE: We compared measures of insulin sensitivity and beta-cell function from the frequently sampled iv glucose tolerance test (FSIGT) to HOMA models. DESIGN/PATIENTS/SETTING/INTERVENTION: Two hundred fourteen young and old with normal glucose tolerance (NGT) and old with impaired glucose tolerance (IGT) participated in a retrospective analysis of FSIGT data in a university medical setting. MAIN OUTCOME MEASURE: Sensitivity to insulin (S(I)) and acute insulin response to glucose (AIRg) from FSIGT were compared with HOMA models. RESULTS: S(I) and HOMA-IR measures identified similar patterns of increasing insulin resistance in the two older groups, compared with younger people with NGT, with the greatest degree of insulin resistance in older people with IGT (P < 0.05 vs. young and old NGT for both S(I) and HOMA-IR). Agreement between HOMA-IR and S(I) was moderate (weighted kappa = 0.51). AIRg was similar in young and old NGT but was markedly decreased in old IGT (P < 0.05 vs. young and old NGT). HOMA-beta-cell was similar in the three groups. Agreement between HOMA beta-cell and AIRg was weak (weighted kappa = 0.35). CONCLUSIONS: HOMA-IR may detect age-related insulin resistance when comparing large populations of older people. However, dynamic testing appears to be necessary to quantitate diminished insulin secretion in older people.     

In middle-aged siblings of patients with type 2 diabetes mellitus normal glucose tolerance is associated with insulin resistance and with increased insulin secretion. The SPIDER study

OBJECTIVES: To evaluate the frequency of impaired glucose tolerance (IGT) and of Type 2 diabetes mellitus (Type 2 DM) in siblings of patients with Type 2 DM, and to assess insulin release and insulin sensitivity in siblings with normal glucose tolerance (NGT), compared with NGT spouses of probands without family history of Type 2 DM. DESIGN AND METHODS: We evaluated 87 families including 103 Type 2 DM patients (87 probands), and we carried out an oral glucose tolerance test (OGTT) in 130 siblings and in 60 spouses. Among NGT subjects, 12 siblings and 16 spouses underwent a low-dose insulin-glucose infusion test (LDIGIT) to evaluate C-peptide release and insulin sensitivity. RESULTS: After the OGTT, 24 siblings were classified as having Type 2 DM, 31 as IGT, and only 14 spouses as IGT (P=0.0012 vs siblings). NGT siblings (n=75) showed higher insulin levels at 120 min than NGT spouses (n=46) at OGTT, in spite of identical blood glucose levels; at LDIGIT, NGT siblings secreted more C-peptide and showed a lower insulin sensitivity than NGT spouses. CONCLUSIONS: These data indicate that middle-aged siblings of probands with Type 2 DM have a high frequency of IGT and Type 2 DM, and that NGT siblings have increased insulin resistance and increased insulin secretion when compared with adequate controls.     

1193例住院高血压病患者胰岛素分泌和敏感性情况

目的用口服葡萄糖耐量试验中各点血糖和胰岛素的值来计算反映胰岛素敏感性及β细胞功能的参数,回顾性研究住院高血压病人糖代谢情况。方法根据WHO和美国糖尿病协会标准计算血糖分布情况,去除新诊断的糖尿病病人后,分成正常血糖(NGT)、单纯性空腹血糖升高(IFG)、单纯性餐后血糖升高(IGT)和空腹、餐后血糖均升高(IFG,／IGT)组进行比较。再分别以口服75g葡萄糖后30min或60min血糖正常值为标准对NGT组和IGT组进行分组。用HOMA-IR和Composite胰岛素敏感性指数(ISI)计算胰岛素敏感性,HOMA-B和△I／AG计算β细胞功能。结果1193例住院的原发性高血压病人中,新诊断的糖尿病病人为11．1％,其中57．9％仅有餐后血糖升高。IGT、和IFG／ICT组的HOMA-IR高于NGT组,Composite ISI和AI／AG低于NGT组。无论是否30min或60min血糖升高,IGT组的Composite ISI均低于30min和60min血糖正常的NGT组。30min和(或)60min血糖升高的NGT组△I／AG低于30min和60min血糖正常的NGT组。结论IGT或IFG／IGT的高血压患者同时存在空腹和总体胰岛素敏感性的下降和糖负荷后早期β细胞分泌功能的受损。30min和(或)60min血糖升高的NGT高血压病人存在糖负荷后早期β细胞分泌功能的受损。     

Blood pressure increase with impaired glucose tolerance in young adult american blacks

Hypertension and non-insulin-dependent diabetes mellitus are more prevalent in blacks than whites. The convergence of these 2 disorders augments the expression and severity of cardiovascular disease. The purpose of this study was to determine whether alterations in glucose metabolism are related to an increase in blood pressure (BP). This study was conducted on 304 nondiabetic blacks (mean age=32 years). Measurements in all subjects included BP, anthropometric measures, oral glucose tolerance test, insulin clamp to measure insulin sensitivity, and plasma lipids. The sample was stratified according to plasma glucose on oral glucose tolerance test to normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM). A 2-way ANOVA was performed to determine differences between the metabolic groups. With the use of American Diabetic Association criteria, 20.4% of the samples were classified as IGT and 5.9% were diabetic. A significant increase in BP existed from NGT to IGT to DM, which was stronger in women than men (systolic blood pressure in women: NGT=122, IGT=127, and DM=140 mm Hg, P<0.001) with a significant linear trend (P<0.001). With the use of body mass index as a covariate, the group difference in BP remained significant (P=0.006). Measures of insulin sensitivity demonstrated significant metabolic group differences (P<0.001) with a linear trend (P<0.001) of decreasing insulin sensitivity from NGT to DM. These results indicate that early alterations in glucose metabolism effects an upward shift in BP. The higher BP in IGT and DM may be due to vascular endothelial cell resistance to insulin action.     

Insulin secretory dysfunction and insulin resistance in the pathogenesis of korean type 2 diabetes mellitus

Although insulin resistance has been shown to be a primary defect causing type 2 (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes. We undertook a study to investigate the initial abnormality of glucose intolerance in Koreans. A total of 370 Korean subjects were classified into 5 groups according to their degree of glucose intolerance (normal fasting glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68; diabetes, n = 118). Insulinogenic index was used as an index of early-phase insulin secretion. Insulin resistance was assessed by the R value of the homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT. However, there was no significant difference in HOMA(R) between subjects with NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased significantly with the increase of plasma glucose 120-minute value at the earlier stage of glucose intolerance compared with HOMA(R). These results suggest that early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes in Korean subjects.     

Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment

OBJECTIVE: Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism. DESIGN: Prospective study. PATIENTS: We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50.7 +/- 12.7 years, body mass index (BMI) 30.1 +/- 4.8 (kg/m2). MEASUREMENTS: All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy. RESULTS: Acromegalic patients showed low M-values in respect to the control group at baseline (P<0.05), followed by a significant improvement after 6 months of therapy (P<0.005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P<0.05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P<0.05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4.7 +/- 0.6% and 5.1 +/- 0.5%, basal and after six months, respectively, P<0.005). CONCLUSION: In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.     

Fibrinolytic dysfunction after gestation is associated to components of insulin resistance and early type 2 diabetes in latino women with previous gestational diabetes

Among patients with metabolic syndrome (MS), atherosclerosis and abnormal fibrinolytic function are frequently present, mostly owing to an increase in plasminogen activator inhibitor-1(PAI-1). We analyze PAI-1 in pregnant women, both normal and with gestational diabetes (GDM) and postpartum regarding its correlation to MS surrogates. Clinical characteristics, glucose tolerance (100g-OGTT), lipids, PAI-1 antigen, insulin sensitivity (HOMA-S), and pancreatic beta-cell function (HOMA-B) were investigated in 34 women. Eleven had normal glucose tolerance (NGT) during pregnancy and 23 had GDM (all GAD antibodies-negative). All patients were studied at 28-34 weeks of gestation and 16-24 weeks after delivery (75 g-OGTT). Parameters of interest were determined using commercial test systems. During pregnancy, PAI-1 was not statistically different between NGT and GDM (47+/-25 ng/ml versus 47+/-28 ng/ml, p=0.9). After gestation, 19 (56%) women had NGT (11 of them from previous NGT group) and 15 (44%) had impaired glucose tolerance (IGT) or DM. The IGT (IGT+DM) group had higher PAI-1 (p=0.01), which did not decreased after delivery NGT-NGT before and after delivery (47+/-25 ng/ml versus 6+/-5 ng/ml; p<0.001), GDM-NGT (62+/-36 ng/ml versus 14+/-15 ng/ml; p=0.001) and GDM-IGT (39+/-20 ng/ml versus 27+/-23 ng/ml; p=0.15). PAI-1 levels were positively correlated (p<0.05) to total cholesterol (r(s)=0.37), triglycerides (r(s)=0.48), fasting plasma glucose (r(s)=0.52), 2-h plasma glucose in the OGTT (r(s)=0.58) and were negatively correlated (p<0.05) with HOMA-S (r(s)=-0.42) and HOMA-B (r(s)=-0.38). Fibrinolytic dysfunction is still present in GDM women and is associated with early development of IGT or T2DM. PAI correlated with surrogate markers of MS levels and may identify a group of women at risk for macroangiopathy.