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.     

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.     

Thiazolidinedione therapy in the prevention/delay of type 2 diabetes in patients with impaired glucose tolerance and insulin resistance

AIM: The second-generation thiazolidinediones (TZDs), rosiglitazone and pioglitazone, significantly decrease fasting plasma glucose and glycosylated haemoglobin (HbA(1c)) levels in patients with diabetes. Recent studies suggest that early treatment with TZDs may prevent the progression from insulin resistance (IR) to type 2 diabetes mellitus (T2DM). This prospective analysis examined the effect of early TZD treatment in the prevention or delay of T2DM in a multiethnic population with impaired glucose tolerance (IGT) and IR. METHODS: The analysis included 172 patients (aged 29-86 years) with IGT and IR (normal or borderline HbA(1c), C-peptide levels > 2 mg/ml, fasting blood sugar 100-125 mg/dl, and 2-h postprandial blood glucose levels 140-200 mg/dl). Patients in the active treatment group (n = 101) had received troglitazone for an average of 10 months before being randomly switched to rosiglitazone (4 mg/day) or pioglitazone (30 mg/day). Patients were switched when troglitazone was withdrawn from the US market because of liver toxicity concerns. Patients with IGT and IR who received no antidiabetic medication served as a control group (n = 71). HbA(1c) and C-peptide levels were measured at baseline (2 years) and study end point (3 years). Kaplan-Meier testing, using time to outcome as the main outcome variable, determined risk reduction in the TZD group relative to the control group. RESULTS: Mean HbA(1c) and C-peptide levels decreased for patients receiving either TZD at the 2-year assessment, and reductions were maintained at study end point. After 2 years, none of the patients receiving TZD therapy progressed to T2DM; three patients progressed to T2DM by study end point. In the control group, 11 patients became diabetic after 2 years and 19 patients became diabetic by the end of the study. The incidence (risk reduction) of diabetes after 3 years was 88.9% lower in the TZD group compared with the control group (p < 0.001). CONCLUSIONS: The TZDs, rosiglitazone and pioglitazone, were effective in reducing HbA(1c) and C-peptide levels in patients with IGT/IR. Progression of IR/IGT to T2DM appears to be significantly delayed or prevented with early TZD treatment.     

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.     

Rosiglitazone improves insulin sensitivity in nonobese subjects with impaired glucose tolerance: the role of adiponectin and C-reactive protein

To evaluate the effects of rosiglitazone (ROS) on serum adiponectin and C-reactive protein (CRP) in nonobese subjects with impaired glucose tolerance (IGT), we enrolled 21 patients with body mass index < or =24 kg/m(2) to receive ROS 4 mg daily for 12 weeks. Fifteen age-, sex-, and body mass index-matched healthy subjects were recruited as controls. A 75-g oral glucose tolerance test (OGTT), hemoglobin A(1c), fasting glucose, insulin, C-peptide, lipid profiles, adiponectin, and CRP levels were determined before initiation and at the end of the 12-week ROS treatment. Insulin resistance and beta-cell function were calculated using the homeostasis model assessment method (HOMA-IR and HOMA-beta, respectively). Compared with healthy controls, the ROS-treated subjects had significantly higher glycemic indices, HOMA-IR, CRP, and glucose and insulin concentrations in response to OGTT, and lower HOMA-beta level. After 12 weeks of ROS therapy, the results showed statistically significant changes from baseline in 2-hour plasma glucose during OGTT (9.4 +/- 0.3 vs 8.3 +/- 0.4 mmol/L, P < .05), HOMA-IR (2.6 +/- 0.2 vs 1.9 +/- 0.3, P < .05), HOMA-beta (63.4 +/- 12.5 vs 90.1 +/- 13.0, P < .05), and glucose and insulin concentrations during OGTT in nonobese subjects with IGT. In addition, elevation of serum adiponectin and decrease in CRP levels were significantly found after ROS treatment. Of 21 patients treated with ROS, 5 subjects were converted to normal (converter), 1 progressed to diabetes, and 15 remained in IGT status (nonconverter). There was a significant amelioration in HOMA-IR (-2.10 +/- 1.03 vs -0.07 +/- 0.33, P < .05) without significant changes in adiponectin and CRP levels in converter compared with nonconverter. We conclude that ROS effectively enhanced insulin sensitivity and beta-cell function to improve adiponectin and CRP levels in nonobese patients with IGT. The amelioration of insulin resistance may be a major determinant to predict the conversion of IGT independent of the changes in adiponectin and CRP.     

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.     

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.     

Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.

AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.     

Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease

Objective: The association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and metabolic syndrome has been documented for obese men and middle‐aged men. This study was designed to determine the relationship between NAFLD and the oral glucose tolerance test (OGTT) to predict preclinical diabetes in nondiabetic young male patients (<30 years old). Methods: A total of 75 male patients who had elevated liver enzymes and who were diagnosed with NAFLD were enrolled in this study. A standard 75 g OGTT was carried out on all patients. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined as a fasting plasma glucose (FPG) level ≥100 mg/dl but <126 mg/dl, and a 2‐h post‐load glucose on the OGTT of ≥140 mg/dl, but <200 mg/dl respectively. Results: According to the OGTT results, 24 (32%) patients were diagnosed as having IGT and 12 (16%) patients were diagnosed as having diabetes. Among the 48 patients with normal fasting glucose, 18 (37.6%) patients showed abnormal glucose tolerance (15 had IGT and three had diabetes). The NAFLD patients with abnormal glucose tolerance showed significant differences in age, weight, body mass index, waist–hip ratio, alanine aminotransferase, total bilirubin, total cholesterol, low‐density lipoprotein cholesterol, triglyceride, insulin, FPG and homeostasis model for insulin resistance (HOMA‐IR). Multiple regression analysis showed that age, FPG and HOMA‐IR were independent predictors of abnormal glucose tolerance. Conclusions: Although the patients were young men, an OGTT should be recommended for NAFLD patients with elevated liver enzymes and IFG to predict the risk of type 2 diabetes.     

Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients

OBJECTIVE: Abnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and beta-cell function in acromegalic patients. DESIGN: Twenty-four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and beta-cell function, we used correct homeostasis model assessment (HOMA) model, a computer-solved model. We also investigated the effects of surgical success on both parameters. RESULTS: HOMA insulin sensitivity (HOMA-%S) in the acromegalic patients was 74 +/- 51 (SD)%, significantly lower than that in 24 healthy controls (144 +/- 49%). HOMA-%S in 12 normal glucose tolerance (NGT) patients was 54 +/- 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 +/- 60%). By contrast, HOMA beta-cell function (HOMA-%beta) in the NGT acromegalic patients was 163 +/- 67%, significantly higher than the IGT/DM acromegalic patients (89 +/- 34%) and the healthy controls (72 +/- 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA-%S significantly increased to control ranges (from 76 +/- 26 to 159 +/- 61%) within 2 weeks after the surgical success. CONCLUSIONS: We conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of beta-cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.     

Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation

Background Both beta‐cell dysfunction and decreased insulin sensitivity are involved in the pathogenesis of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), while their relative contribution in the progression to type 2 diabetes still remains controversial. The aim of the present study is to clarify this process in Chinese subjects by using cross‐sectional method. Methods 2975 Chinese subjects were classified into: normal glucose tolerance (NGT), impaired glucose regulations (IGR), and diabetes mellitus (DM) based on oral glucose tolerance test (OGTT). The IGR group was sub‐classified as isolated IFG, isolated IGT and combined glucose intolerance (CGI). The DM group was sub‐classified as normal fasting plasma glucose and 2‐hour hyperglycemia (N0D2), fasting hyperglycemia and normal 2‐hour plasma glucose (D0N2), and both fasting and 2‐hour hyperglycemia (D0D2). Results As far as insulinogenic index (IGI) was concerned, there was no difference between IFG and IGT in either gender, however, HOMA2‐B% (homeostasis model assessment for beta‐cell function) of IGT was higher than that of IFG and CGI in both male and female (P < 0.05). In the diabetic sub‐groups, IGI of N0D2 was higher than that of D0N2, and both deteriorated compared with those of IGT and IFG, respectively. HOMA2‐B% of N0D2 was still higher than that of D0N2 and D0D2. No significant difference was detected in OGIS and HOMA2‐S% (homeostasis model assessment for insulin sensitivity) between IFG and IGT, and this was the case between N0D2 and D0N2. OGIS and HOMA‐IR of IGR sub‐groups were not different from those of their diabetic counterparts. Conclusion Failure of beta‐cell function might be the main reason for both IGT and IFG developing into diabetes instead of aggravated insulin resistance. Copyright © 2008 John Wiley & Sons, Ltd.     

Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose

Subjects with impaired fasting glucose (IFG) are at increased risk for type 2 diabetes. We recently demonstrated that IFG subjects have increased hepatic insulin resistance with normal insulin sensitivity in skeletal muscle. In this study, we quantitated the insulin secretion rate from deconvolution analysis of the plasma C-peptide concentration during an oral glucose tolerance test (OGTT) and compared the results in IFG subjects with those in subjects with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). One hundred and one NGT subjects, 64 subjects with isolated IGT, 24 subjects with isolated IFG, and 48 subjects with combined (IFG + IGT) glucose intolerance (CGI) received an OGTT. Plasma glucose, insulin, and C-peptide concentrations were measured before and every 15 min after glucose ingestion. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide concentration. Inverse of the Matsuda index of whole body insulin sensitivity was used as a measure of insulin resistance; 56 subjects also received a euglycemic hyperinsulinemic clamp. The insulin secretion/insulin resistance (disposition) index was calculated as the ratio between incremental area under the ISR curve (∆ISR[AUC]) to incremental area under the glucose curve (∆G[AUC]) factored by the severity of insulin resistance (measured by Matsuda index during OGTT or glucose disposal during insulin clamp). Compared to NGT, the insulin secretion/insulin resistance index during first 30 min of OGTT was reduced by 47, 49, and 74% in IFG, IGT, and CGI, respectively (all < 0.0001). The insulin secretion/insulin resistance index during the second hour (60–120 min) of the OGTT in subjects with IFG was similar to that in NGT (0.79 ± 0.6 vs. 0.72 ± 0.5, respectively, P = NS), but was profoundly reduced in subjects with IGT and CGI (0.31 ± 0.2 and 0.19 ± 0.11, respectively; P < 0.0001 vs. both NGT and IFG). Early-phase insulin secretion is impaired in both IFG and IGT, while the late-phase insulin secretion is impaired only in subjects with IGT.     

Insulin action and insulin secretion in newly diagnosed type 2 diabetic patients

To clarify the insulin action and insulin secretion in newly diagnosed type 2 diabetic subjects, we investigated insulin and C-peptide response to an oral glucose tolerance test (OGTT) in 15 newly diagnosed type 2 diabetic patients and 17 healthy subjects. For insulin action, we found fasting hyperinsulinemia (8.4 +/- 0.8 vs. 6.0 +/- 0.5 microIU/ml, p = 0.014), higher insulin resistance by homeostasis model assessment (HOMA) (4.33 +/- 0.2 vs. 1.34 +/- 0.1 microIU/ml.mmol/l, p < 0.001), and lower insulin sensitivity index (ISI) (51.0 +/- 0.7 vs. 104.0 +/- 0.8, p < 0.001) in newly diagnosed diabetic patients compared to normal subjects. For insulin secretion, the increments of AUCI (area under curve of insulin) and AUCC-P (area under curve of C-peptide) (increment of AUCI: 26.1 +/- 1.4 vs. 82.8 +/- 4.5 microIU/ml.hour, p < 0.001; increment of AUCC-P: 3.9 +/- 0.2 vs. 11.4 +/- 0.6 ng/ml.hour, p < 0.001), insulin secretion by HOMA model (20.7 +/- 1.2 vs. 79.1 +/- 3.8 IU/mol, p < 0.001), and ratio of 30 min increment of fasting insulin to glucose during OGTT (1.14 +/- 0.1 vs. 13.1 +/- 0.5 IU/mol, p < 0.001) were significantly lower in the newly diagnosed diabetic patients than normal subjects. In addition, body mass index (BMI) in our type 2 diabetes is relatively lower (24 +/- 0.65 kg/m2) than those in western countries. These findings revealed poor insulin action and decreased insulin secretion in relatively less obese Taiwanese with newly diagnosed type 2 diabetes.     

不同糖耐量者血清超敏C-反应蛋白表达及与胰岛素抵抗的相关性研究

目的探讨不同糖耐量者血清超敏C-反应蛋白(hs-CRP)的表达及与胰岛素抵抗的相关性。方法对2004年10月至2005年4月中国医科大学附属第一医院体检中心90名体检者(男53名,女37名),根据标准75g口服葡萄糖耐量试验(OGTT)分为正常糖耐量(NGT)组、单纯空腹血糖受损(IFG)组、单纯糖耐量异常(IGT)组、同时合并IFG/IGT组及2型糖尿病(T2DM)组,采用酶联免疫吸附(ELISA)法分别检测各组血清hs-CRP,并与稳态模型胰岛素抵抗指数(HOMA-IR)作相关分析。结果IFG组、IFG/IGT组及T2DM组hs-CRP均明显高于NGT组,并与糖代谢指标及HOMA-IR呈正相关。结论T2DM患者早在IFG阶段就已经存在炎症状态,炎症可能参与了T2DM的发生与发展。     

High prevalence of glucose metabolism disturbance in patients with lichen planus

AIM: To establish the prevalence of diabetes mellitus (DM) and insulin resistance in patients with lichen planus (LP), and to examine whether diabetic status showed any relation with the type of LP. PATIENTS AND METHODS: Thirty patients with LP and 30 age, weight, and sex matched volunteers were included. Serum fasting glucose, insulin, hemoglobin A1c levels were determined, a standard oral glucose tolerance test (OGTT) was performed. RESULTS: Of patients with LP, eight (26.7%) had DM (four newly diagnosed), however, only one (3.33%) diagnosed as DM in control group (p=0.007). Six patients (20.0%) with LP and four healthy persons (13.3%) had IGT (p>0.05). Glucose metabolism disturbance (DM+IGT) was detected in 14 (46.7%) of the patients and in 5 (16.7%) of the controls (p=0.026). HbA1c, fasting serum glucose, and insulin resistance (HOMA) were statistically higher in patients compared to controls. CONCLUSION: Our finding documented that approximately one half of the patients with LP had glucose metabolism disturbance, and one fourth had DM. We believe that further studies are needed to explain this close relationship between DM and LP.     

Recovery of BMIPP uptake and regional wall motion in insulin resistant patients following angioplasty for acute myocardial infarction.

The effect of insulin resistance (IR) on the fatty acid metabolism of myocardium, and therefore on the recovery of left ventricular (LV) wall motion, has not been established in patients with acute myocardial infarction (AMI). A total of consecutive 58 non-diabetic AMI patients who had successfully undergone emergency coronary angioplasty were analyzed retrospectively. They were categorized into 2 groups, normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), based on a 75-g oral glucose tolerance test (OGTT). The parameters of OGTT, myocardial scintigraphy (n=58) (thallium-201 (Tl) and iodine-123-beta-methyl-iodophenylpentadecanoic acid (BMIPP)) and left ventriculography (n=24) were compared in the 2 groups after reperfusion (acute phase) and 3-4 weeks after the AMI (chronic phase). The insulin resistance (IR), estimated by the serum concentration of insulin at 120 min (IRI 120') of the OGTT and by the HOMA (the homeostasis model assessment) index, was higher in the IGT group than in NGT group. An inverse correlation was found between the recovery of regional LV wall motion in the ischemic lesion and the IRI 120' and HOMA index. Although the recovery of BMIPP uptake from the acute to the chronic phase was higher in the IGT group, it was only correlated with the degree of IRI 120', not with the HOMA. IR accompanied by IGT can negatively influence the recovery of regional LV wall motion.     

不同糖耐量状态者血清SICAM-1和SVCAM-1水平与炎症相关性研究

按口服葡萄糖耐量试验结果,将研究对象分为正常糖耐量(NGT)组、单纯空腹血糖受损(IFG)组、单纯糖耐量受损(IGT)组、IFG与IGT并存(IFG/ICT)组及2型糖尿病(DM)组。采用酶联免疫吸附法(ELISA)分别检测上述人群的血清可溶性细胞间黏附分子1(SICAM-1)、可溶性血管细胞黏附分子1(SVCAM-1)和超敏C反应蛋白水平(hr-CRP),并与糖脂代谢指标和稳态模型胰岛素抵抗指数(HOMA- IR)作相关性分析。结果显示,血清SICAM-1、SVCAM-1和hs-CRP水平按分组顺序逐组升高,提示2型DM的发病过程与内皮细胞损伤和炎症状态有关。     

The prevalence of prediabetes,diabetes, and insulin resistance among urban obese children of south Andhra Pradesh in India

Obesity is increasing rapidly in developing countries undergoing rapid nutrition and lifestyle transition. Obesity and associated insulin resistance are considered the main risk factors for developing type 2 diabetes mellitus, regardless of genetic predisposition. The aim of this study is to analyze the prevalence of prediabetes (impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT)), diabetes, and insulin resistance in obese children/adolescents. In this prospective study, a total of 224 obese children/adolescents were recruited. All patients underwent oral glucose tolerance test (OGTT) with blood samples at 0 and 2 h. Fasting insulin and lipid profiles were also estimated in each case. The prevalence of IFG, IGT, and type 2 DM in obese children was found to be 8.33 % (6/72), 9.72 % (7/72), and 1.38 % (1/72), respectively. Similarly, the prevalence of IFG, IGT, and type 2 DM in obese adolescents was found to be 9.86 % (15/152), 15.78 % (24/152), and 1.97 % (3/152), respectively. The prevalence of insulin resistance in obese children was 33.33 % (24/72) and adolescents was 47.36 (72/152). Also, 2-h plasma glucose (P = 0.014) was significantly elevated in the insulin-resistant group compared to the group without insulin resistance in obese children/adolescents. IGT and insulin resistance are highly prevalent in obese children/adolescents. Therefore, obese children/adolescents are more prone to prediabetes and type 2 DM is to be screened by OGTT.     

Glucose metabolism after normalization of markers of iron overload by venesection in subjects with hereditary hemochromatosis

Hereditary hemochromatosis (HH) is associated with abnormal glucose metabolism (AGM). We investigated the effect on glucose metabolism of normalization of the markers of iron overload by phlebotomy in subjects with HH. We prospectively studied 11 newly diagnosed subjects with HH and AGM using a standard 75-g oral glucose tolerance test. Basal quantitative insulin sensitivity check index (QUICKI) and stimulated oral glucose insulin sensitivity index (OGIS) insulin sensitivity was calculated from glucose and insulin data, whereas β-cell function was assessed using C-peptide concentration after adjusting for ambient insulin sensitivity. After normalization of ferritin and transferrin saturations by venesection for 12 (range, 8-16) months, subjects were studied again using the same methods. From 11 subjects with AGM at the time that HH was diagnosed, 7 had impaired glucose tolerance (IGT) and 4 had type 2 diabetes mellitus (T2DM). Normalization of the iron stores (ferritin and transferrin) improved the glucose tolerance status of 4 patients with IGT (to normal glucose tolerance), whereas 2 of those with IGT progressed to T2DM. In 5 patients, glucose tolerance status did not change (4 T2DM and 1 IGT). The area under the insulin and the C-peptide curve during the oral glucose tolerance test and the hepatic insulin extraction increased (P = .05), whereas no statistically significant changes occurred in insulin sensitivity. However, the disposition index, a measure of the ability of insulin release to compensate for insulin resistance, improved significantly (P = .02). Normalization of ferritin and transferrin saturation by venesection in subjects with HH and AGM led to improvements in some, but not all, measures of insulin secretion and action. Most patients with AGM had an improvement in glucose tolerance status, probably due to the augmented action of insulin in peripheral tissues.