Distinguishing between persistent and transient impaired glucose tolerance using a prediction model.

Screening for impaired glucose tolerance (IGT) and Type 2 (non-insulin dependent) diabetes was carried out in 777 people and those with high blood glucose levels completed three 2-h oral glucose tolerance tests (OGTT). Blood lipid levels, fasting and 2-h insulin levels, body mass index, and blood pressure were also measured and family history of Type 2 diabetes recorded. Fifty people were identified with IGT and of these 21 were found to have persistent IGT and 29 transient IGT. A model including the variables body mass index, fasting and 2-h insulin levels, fasting triglycerides and family history of Type 2 diabetes was developed using the Speigelhalter-Knill-Jones weighting method to predict subjects with persistent IGT. This model could be useful in identifying people with persistent IGT and therefore eliminate the need for repeat OGTTs which are time consuming and expensive.     

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.     

Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance

AIMS: To assess the efficacy and long-term effects of glipizide treatment on glucose and insulin metabolism in individuals with impaired glucose tolerance (IGT). METHODS: Thirty-seven first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT were randomized to treatment with either glipizide 2.5 mg once daily or matching placebo for 6 months. A 75 g, 2-h oral (OGTT) and 60 min intravenous glucose tolerance test (IVGTT) were performed at baseline and after 6 months. The subjects were followed up for another 12 months after discontinuation of treatment and a repeat OGTT was performed at 18 months. RESULTS: Thirty-three subjects fulfilled the study. Markers of insulin sensitivity - i.e. fasting insulin and HOMA(IR)-index - improved in the glipizide group (P = 0.04 and 0.02 respectively) as well as HDL cholesterol (P = 0.05) compared with placebo group after 6 months. At 18 months, both fasting and 2 h glucose concentrations were significantly lower in the glipizide group compared with the placebo group (P = 0.04 and 0.03 respectively). The prevalence of type 2 diabetes was 29.4% in the placebo group and 5.9% in the glipizide group at 18 months. This equals an 80% relative risk reduction in the active treatment group. CONCLUSIONS: Short-term treatment with glipizide improves glucose and insulin metabolism in subjects with IGT primarily by improving insulin sensitivity mediated by lowering glucose toxicity, thereby providing the beta cells rest. Larger studies are needed to establish whether these effects are sufficient to prevent progression to manifest type 2 diabetes and associated cardiovascular morbidity in subjects at increased risk of developing type 2 diabetes.     

Subscapular skinfold thickness distinguishes between transient and persistent impaired glucose tolerance: Study on Lifestyle-Intervention and Impaired Glucose Tolerance Maastricht (SLIM).

AIMS: To assess whether adding anthropometric measurements to an oral glucose tolerance test (OGTT) can help to distinguish between transient and persistent impaired glucose tolerance (IGT). METHODS: From the SLIM project (Study on Lifestyle-Intervention and IGT Maastricht), a study designed to evaluate whether diet and physical activity intervention can improve glucose tolerance in subjects at risk for diabetes, 108 subjects with IGT underwent a repeated OGTT 2-4 months after the initial OGTT. Following the second test, subjects were classified as transient IGT, or persistent IGT. Anthropometric measurements, including body mass index, waist and hip circumference, sagittal and transverse abdominal diameters and skinfold thickness measurements, were done during the second OGTT. RESULTS: Persistent IGT was diagnosed in 47 subjects (44%), transient IGT in 40 (37%), impaired fasting glucose in eight subjects (7%), and diabetes in 13 cases (12%). Two-hour blood glucose levels at the initial OGTT and subscapular skinfold thickness were significantly higher in subjects with persistent IGT (2-h blood glucose 9.8+/-0.1 mmol/l vs. 10.2+/-0.1 mmol/l for transient IGT and persistent IGT, respectively; subscapular skinfold thickness 25.4+/-1.4 mm vs. 29.8+/-1.2 mm for transient IGT and persistent IGT, respectively). After adjustment for age, sex and family history of diabetes mellitus, logistic regression indicated that 2-h blood glucose level during the initial OGTT represented the strongest predictor of persistent IGT (P<0.02), followed by subscapular skinfold thickness (P<0.05). After adjustment for 2-h blood glucose levels during the first OGTT, subscapular skinfold thickness remained significantly associated with persistent IGT (odds ratio 1.84; P<0.05). CONCLUSIONS: In addition to the 2-h blood glucose level, subscapular skinfold thickness was the best predictor of persistent IGT, suggesting that adding simple anthropometric measures to oral glucose tolerance testing may improve the distinction between persistent and transient glucose intolerance.     

Metabolic effects of metformin in patients with impaired glucose tolerance.

AIMS: To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). METHODS: Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. RESULTS: Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 +/- 13 to 34.4 +/- 10.7 micromol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 +/- 3.6 to 19.1 +/- 4.4 micromol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. CONCLUSIONS: Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578-583 (2001)     

High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non-obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p less than 0.05, Student's t-test) in offspring of parents with IGT (718 +/- 71 pmol l-1 h) than in the subjects whose parents had normal glucose tolerance (524 +/- 47 pmol l-1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17 +/- 0.11 vs 0.92 +/- 0.08 mmol l-1, 0.10 greater than p greater than 0.05), as were both systolic (132 +/- 5 vs 118 +/- 3 mmHg, p less than 0.05) and diastolic (79 +/- 3 vs 70 +/- 2 mmHg, p less than 0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.     

Impaired glucose tolerance and fasting hyperglycaemia have different characteristics.

AIMS: Use of the oral glucose tolerance test (OGTT) to define glucose intolerance in the general population may bias towards selection of those with insulin resistance. Beta cell function and insulin resistance markers were analysed in four groups: controls (n = 101); fasting hyperglycaemia (FH, n 45); impaired glucose tolerance; (IGT, n = 16) and those with features of both FH and IGT ('Both', n = 30). METHODS: Subjects underwent an OGTT. Plasma glucose, fasting lipid profiles, fasting, 30 and 120 min insulin were measured and beta cell function (% B) and insulin sensitivity (% S) assessed by homeostatic model assessment (HOMA) RESULTS: The FH group compared to controls had a significantly lower % B. The IGT group compared to controls had features of insulin resistance (higher body mass index (BMI), systolic blood pressure and 2 h insulin concentration). Subjects with 'both' IGT and FH had features of insulin resistance (higher BMI, systolic and diastolic blood pressure and triglyceride concentration) as well as beta cell dysfunction with a lower % B and 30 min insulin-glucose ratio compared to controls. There was a preponderance of males in this group. In all, 192 subjects' 30-min insulin concentration and incremental insulin response showed only a significantly negative correlation with fasting glucose concentration. In a linear regression analysis, a low 30-min insulin-glucose ratio was only a significant factor in the fasting glucose model. Thus, higher fasting glucose concentrations appear to be associated with beta cell dysfunction. However, HbA1 only showed a significant correlation with 120-min glucose, not fasting glucose concentration. CONCLUSIONS: In those with milder degrees of glucose intolerance, FH is associated with beta cell dysfunction and those with IGT and a relatively 'normal' fasting glucose have features of the insulin resistance syndrome.     

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.     

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.     

Does impaired glucose tolerance predict hypertension?

Summary This study evaluates prospectively the relationship between impaired glucose tolerance (IGT) and blood pressure. From a population of 1376 men and women aged 40–59 years, all those with IGT (n=54) plus 133 age- weight- and sex-matched nor-moglycaemic control subjects were selected after excluding treated hypertensive patients. Blood pressure, fasting and postload blood glucose and plasma insulin were measured. At 11.5 years after the first visit 76% of the IGT patients and 80% of the control subjects were re-examined. At baseline blood pressure was significantly higher in IGT patients than in control subjects (systolic 135.5±2.3 vs 127.9±1.4mm Hg, p<0.001; and diastolic 88.0±1.5 vs 84.7±0.7 mmHg, p<0.05) independent of age, gender, weight, antihypertensive medication and insulin-aemia. Accordingly, hypertension was more frequent in subjects with IGT (odds ratio 2.1, 95% confidence, interval (CI) 0.9–4.9). Postload insulin was significantly associated with hypertension — both at univariate and multivariate analysis — in normoglycaemic subjects, but not in those with IGT. At follow-up systolic blood pressure increased in both groups; the increase was smaller in patients with IGT (6.0±2.4 vs 12.3±1.6 mmHg p<0.05). Likewise, the 11.5 years' cumulative incidence of hypertension was not significantly different in subjects with baseline IGT or normoglycaemia; if anything it was lower in the IGT group (odds ratio 0.36, 95% CI 0.1–1.2). In multivariate analysis incidence of hypertension was associated positively with baseline blood pressure (p<0.0003) and negatively with IGT status p<0.03), while no significant association was found with insulin. In conclusion, the findings of this study question IGT as a risk factor for hypertension. Furthermore, these data do not indicate a major role for hyperglycaemia and hyperinsulinaemia per se in the aetiology of hypertension and suggest that IGT and hypertension share one or more pathogenetic factor(s) (i.e., insulin resistance, hyperactivity of the sympathetic nervous system, etc.), which induce deterioration of blood pressure control first, and hyperglycaemia later.Abbreviations IGT Impaired glucose tolerance - CI confidence interval - BMI body mass index     

Plasma interleukin-6 levels are increased in subjects with impaired glucose tolerance but not in those with impaired fasting glucose in a cohort of Italian Caucasians

BACKGROUND: While the relationship between impaired glucose tolerance (IGT) and circulating interleukin-6 (IL-6) is well established, there is no information whether IL-6 levels are elevated in impaired fasting glucose (IFG). METHODS: To this end, we examined the relationship between plasma IL-6 concentration and different degrees of glucose homeostasis in a cohort of 470 Italian Caucasian subjects comprising 236 normal glucose tolerant (NGT), 49 IFG, 51 IGT, and 134 type 2 diabetic subjects. RESULTS: We observed that IL-6, CRP and fibrinogen levels were higher in subjects with IGT or type 2 diabetes as compared with NGT and IFG subjects. Univariate correlations between IL-6 concentrations and metabolic variables in the whole cohort showed that IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, CRP, fibrinogen, and negatively correlated with insulin sensitivity, IGF-I and HDL. In a subgroup analysis including NGT, IFG and IGT (n = 336), IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, triglycerides, CRP, fibrinogen, fasting insulin, 2 h post-load glucose, and negatively correlated with insulin sensitivity, IGF-I and HDL. Stepwise linear regression analysis in a model including gender, age, BMI, waist, glucose tolerance status, fasting plasma glucose, 2 h post-load glucose, triglycerides, HDL, fasting insulin, and insulin sensitivity revealed that waist was the only independent variable associated with IL-6 levels accounting for 21.0% of its variation (P < 0.0001). CONCLUSIONS: These data show that IGT and type 2 diabetes, but not IFG, are associated with elevated plasma IL-6 levels.     

糖耐量异常对心室重塑的影响

目的 探讨糖耐量异常对心室重塑的影响及可能的机制,从而预防心室重塑的发生和发展.方法 入选患者均接受葡萄糖耐量试验(OGTT)和心脏彩色超声检查,测定E波与A波流速比值(E/A)、计算左室心肌重量(LVM)、左室心肌指数(LVMI),行24 h动态血压检测,分析糖耐量异常与心室重塑相关指标的关系.结果 合并糖耐量异常高血压组左室舒张功能减低发生率(74%)高于单纯高血压组(39%)(x2=6.5,P＜0.05),糖耐量异常组左室舒张功能减低(34%)发生率高于对照组(10%)(x2=5.2,P＜0.05).合并糖耐量异常高血压组左室肥厚发生率(24%)明显高于高血压组、糖耐量异常组及正常组(分别为7%、0、0)(x2=4.561,P＜0.05).多因素逐步回归分析显示,年龄和餐后2 h血糖值是E/A比值的独立危险因素.结论 糖耐量异常是导致左室肥厚和舒张功能减低的一个危险因素和病理基础之一,且导致左室舒张功能减低发生率高于左室肥厚.     

糖耐量受损转化为正常糖耐量或演变为糖尿病者血压均下降——来自大庆糖尿病研究的新发现

目的 分析大庆糖尿病预防研究中糖耐量受损(IGT)人群随访6年期间的糖耐量演变及其与血压变化的关联.方法 大庆糖尿病预防研究中有334例IGT患者未曾服用任何降血压药物,其中264例基线血压≥130/80 mm Hg(1mm Hg=0.133kPa).随机分配在对照、饮食、运动及饮食加运动干预4个组.从1986年随访到1992年.根据研究结束时口服葡萄糖耐量试验(OGTY)2h血糖水平(2hPG)分为<7.8、7.8～8.8、8.9～9.9、10.0～11.0、11.1～13.8、13.9～16.6和≥16.7mmol/L7个亚组,探讨各组血压水平的变化及其与血糖变化的关联.结果 经多因素分析调整了年龄、性别、基线体重指数及随访期体重变化等因素的影响后,1986至1992年间各组的收缩压改变分别为-2.4、0.6、7.7、4.3、1.7、-2.9、和-6.9 mm Hg,舒张压变化为-3.2、3.0、3.3、1.7、-0.7、-1.3和-3.7 mm Hg.收缩压和舒张压在演变为糖耐量正常或糖尿病者比那些仍然保持为IGT且2hPG在8.9～9.9mmol/L者显著下降(均P<0.05).264 例基线血压≥130/80 mm Hg者中血压变化更为显著.在上述各组,收缩压变化分别为-5.2、-2.6、5.2、2.3、-2.3、-4.2、-7.6 mm Hg,舒张压变化分别为-5.0、-3.7、1.5、-2.9、-4.3、-4.0和-6.0mm Hg.结论 大庆6年研究中IGT人群中血糖水平仍保持为IGT者血压有所升高.相反,IGT转化为正常糖耐量或糖尿病组血压明显下降.     

The abbreviated glucose tolerance test in screening for diabetes: the Islington Diabetes Survey

The World Health Organization has recommended a single 2-h post-glucose load blood glucose level as a screening test for diabetes mellitus in epidemiological surveys. We have assessed its characteristics, when compared with a full supervised glucose tolerance test (OGTT), in estimating prevalence, and in diagnosing diabetes in the individual patient. A stratified sample of 223 of 1040 subjects who had participated in a diabetic survey that utilized a single capillary 2-h blood glucose estimation as a screening test were recalled for formal glucose tolerance testing. The numbers of subjects with diabetes at screening and at recall were similar (14/212, 6.6%; 13/216, 6.0%) but only 9 subjects were so classified on both occasions. Thirty-five subjects (16.5%) were suspected of having impaired glucose tolerance (IGT) at screening, and 52 (24.1%) at recall. There was substantial reclassification from screening IGT, with 3/35 worsening to diabetes, and 10/35 returning to normal. Capillary 2-h glucose levels gave an accurate assessment of the prevalence of diabetes but underestimated that of IGT. On the full OGTT, little difference in classification was found when the values of fasting and 1-h blood glucose were used in addition to those of the 2-h blood glucose used alone. The 2-h glucose had a within-subject coefficient of variation of 32.4% which produced substantial reclassification of subjects with levels close to the diagnostic levels for diabetes, and this implies that such individuals should not be classified as having diabetes on the basis of a single glucose tolerance test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Loss of the First Phase Insulin Response to Intravenous Glucose in Subjects with Persistent Impaired Glucose Tolerance

Loss of the first phase insulin response to intravenous glucose is one of the earliest detectable defects of beta cell dysfunction in Type 2 diabetes mellitus. Impaired glucose tolerance (IGT) is considered a prediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early lesion in the development of Type 2 diabetes. Three groups of subjects were studied, 7 subjects with persistent IGT (classified as having IGT at two 75 g oral glucose tolerance tests (OGTT) done 6 months apart), 6 subjects with transient IGT (IGT at the first OGTT, but normal glucose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucose tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two-site immunoradiometric assay). The fasting insulin was similar in all three groups, however the 3 min insulin response was significantly lower in those with persistent impaired glucose tolerance (p < 0.02). Thus subjects with persistent impaired glucose tolerance demonstrated loss of the first phase insulin response as an early indicator of beta cell dysfunction while subjects with transient IGT had a normal insulin response to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different (p = 0.1) but the 30 min insulin to glucose ratio was significantly lower in subjects with persistent IGT (p < 0.03). In the whole group the 30 min insulin to glucose ratio during the OGTT showed a significant correlation with the peak insulin response during the IVGTT (r = 0.76, p < 0.001). This study suggests that beta cell dysfunction with impaired early insulin release is present before the development of Type 2 diabetes.     

Insulin secretion and insulin sensitivity in Japanese subjects with impaired fasting glucose and isolated fasting hyperglycemia

Impaired fasting glucose (IFG) is a subgroup of impaired glucose regulation exhibiting an elevated fasting glucose levels without elevated 2-h glucose levels on oral glucose tolerance test (OGTT). Diabetes mellitus with isolated fasting hyperglycemia (DM/IFH) is a similar subgroup of diabetes having higher fasting glucose levels with 2-h glucose levels within the non-diabetic range. The aim of this study is to profile the characteristics of these subgroups to estimate the factors involved in the development from normal glucose tolerance (NGT) via IFG to DM/IFH. Five hundred and sixty seven Japanese males were classified on the basis of 75 g OGTT into four groups, NGT, IFG, DM/IFH, and isolated impaired glucose tolerance (isolated IGT). Insulin secretion was evaluated by insulinogenic index, insulin sensitivity was evaluated by ISI composite, and insulin secretory patterns were compared additionally. IFG and DM/IFH subjects exhibited both lower insulin secretion and lower insulin sensitivity than NGT subjects. There was an insulin peak in NGT, IFG, and DM/IFH at 60 min, which did not occur in isolated IGT. Impaired early-phase and basal insulin secretion and decreased insulin sensitivity both are estimated as factors in progression from NGT via IFG to DM/IFH in these subjects. IFG and DM/IFH subjects have definite fasting hyperglycemia in contrast to isolated IGT subjects, 2-h glucose levels being maintained within the non-diabetic range partly by the insulin peak at 60 min.     

Pioglitazone prevents reactive hypoglycemia in impaired glucose tolerance

A 42-year-old woman with hypoglycemic symptoms that occurred several hours after a meal visited our hospital. The hypoglycemic symptoms appeared when she was 37 years old, and her plasma glucose level had been assessed as less than 60 mg/dL when she experienced the symptoms. One year before, she had been diagnosed with reactive hypoglycemia by 75 g-oral glucose tolerance test (OGTT), which showed a normal glucose tolerance (NGT) pattern, and had begun taking an alpha-glucosidase inhibitor and nutritional treatment. A 75 g-OGTT on admission showed hypoglycemia at 240 min after glucose loading, excessive insulin secretion and an impaired glucose tolerance (IGT) pattern. A euglycemic-hyperinsulinemic clamp study demonstrated decreased insulin sensitivity. Therefore, we suspected that she had reactive hypoglycemia associated with insulin resistance and treated her with 15 mg/day pioglitazone. Her hypoglycemic symptoms completely disappeared after treatment with pioglitazone; insulin sensitivity in a euglycemic-hyperinsulinemic clamp study improved. Another 75 g-OGTT revealed that the excessive insulin secretion and hypoglycemia at 240 min after glucose loading had disappeared, and glucose tolerance was normalized from an IGT pattern to an NGT pattern. Thus, we believe that pioglitazone is effective for reactive hypoglycemia and aggravated glycemic metabolism associated with insulin resistance.     

胰岛素增敏剂罗格列酮抗高血压作用探讨

目的　观察胰岛素增敏剂马来酸罗格列酮在超重和 (或 )肥胖的轻、中度高血压患者的降血压作用及其影响因素 ,探讨胰岛素增敏剂用于原发性高血压治疗或辅助治疗的可能性。方法　超重及肥胖 (体重指数≥ 2 5kg/m2 )的非糖尿病轻、中度原发性高血压 [14 0mmHg <收缩压 <190mmHg ,(1mmHg =0 133kPa) ]患者 89例。测定口服葡萄糖耐量试验各时点血糖及胰岛素浓度 ,排除糖尿病。原服用降血压药物者停用药物 2周后进入试验 ,原生活方式不变。仅服用胰岛素增敏剂马来酸罗格列酮 8mg/d ,疗程 4周。分析血压下降情况及影响因素。 结果　 (1)治疗 4周后收缩压平均降低了 17mmHg ,舒张压平均降低了 11mmHg。 (2 )治疗后比治疗前空腹、糖负荷后 1h及 2h血胰岛素水平分别下降 2 7%、35 %、4 1% (P <0 0 0 0 1)。胰岛素敏感性改善了 30 % (P <0 0 0 0 1)。(3)在基线血压水平较高、胰岛素抵抗程度较严重及无高血压家族史的患者中罗格列酮的降压幅度更大。结论　马来酸罗格列酮对超重或肥胖非糖尿病人群显示了良好的抗高血压效能 ,提示此类胰岛素增敏剂可能在某些人群原发高血压治疗或辅助治疗中有一定价值。     

Relationship between blood pressure and glucose tolerance in acromegaly

BACKGROUND: Hypertension represents a well-known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown. OBJECTIVE: The aim of the present study was to evaluate the impact of glucose metabolism abnormalities on BP values in a series of patients with active acromegaly. DESIGN: An open multicentre prospective study. PATIENTS: Sixty-eight patients with active disease, aged 47.5 +/- 11.7 years, have been studied. Thirty-nine had normal glucose tolerance (NGT), 16 impaired glucose tolerance (IGT) and 13 suffered from diabetes mellitus (DM). MEASUREMENTS: Mean clinical BP values were calculated as the mean of BP values obtained by sphygmomanometric measurement in three separate occasions and mean 24-h, diurnal and nocturnal systolic (SBP) and diastolic (DBP) values were obtained by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Patient's age and the degree of glucose tolerance abnormalities were found to significantly and independently influence BP values. All clinical and ABPM SBP and DBP values significantly increased with age by linear regression (P < 0.02 for all BP values, 0.30 < or = R < or = 0.43), and the independent influence of this parameter on BP values was confirmed by mutivariate analysis. Similarly, the independent influence of glucose tolerance abnormalities on BP values was confirmed when introducing age as a covariable in a multivariate analysis, and patients with DM presented significantly higher clinical SBP and 24-h, diurnal and nocturnal SBP and DBP than patients with NGT (P < 0.02 for clinical SBP, P < 0.015 for all ABPM values, respectively). In addition, patients with DM showed significantly higher 24-h, diurnal and nocturnal DBP than those with IGT (P < 0.05 in all cases). In contrast, no significant difference was found between NGT and IGT patients. No significant influence of disease duration, BMI, GH, IGF-I, or fasting and 2-h post glucose load insulinaemia on BP values was observed. CONCLUSIONS: Abnormalities of glucose metabolism significantly contribute to increase systolic blood pressure and especially diastolic blood pressure in acromegalic patients. Careful control of blood pressure and of risk factors for developing systemic hypertension, with special reference to glucose tolerance, is mandatory to decrease cardiovascular morbidity and mortality in such patients.     

Metformin treatment leads to an increase in basal, but not insulin-stimulated, glucose disposal in obese patients with impaired glucose tolerance.

AIMS: This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations. METHODS: Nineteen obese patients with impaired glucose tolerance (IGT) were treated with either metformin or placebo in a randomized, double-blind, placebo-controlled, cross-over study. Insulin secretion and insulin resistance were quantified using the homeostasis model assessment (HOMA) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose (SSPG). RESULTS: The average benefit of metformin was 0.6 mmol/l for glucose (95% confidence interval (CI) 0.2-0.9 P = 0.002), 2.8 pmol/l for insulin (95% CI 0.2-5.4, P = 0.019). Insulin resistance, as quantified by HOMA, was improved by 1.1 (95% CI 0.2-2.0, P = 0.004), without any change in insulin secretion. Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period, as was the SSPG concentration. However, both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo. CONCLUSIONS: These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure. In contrast, neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia.