Plasma gastric inhibitory polypeptide and glucagon‐like peptide‐1 levels after glucose loading are associated with different factors in Japanese subjects

Aims/Introduction: Gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are major incretins that potentiate insulin secretion from pancreatic β‐cells. The factors responsible for incretin secretion have been reported in Caucasian subjects, but have not been thoroughly evaluated in Japanese subjects. We evaluated the factors associated with incretin secretion during oral glucose tolerance test (OGTT) in Japanese subjects with normal glucose tolerance (NGT). Materials and Methods: We measured plasma GIP and GLP‐1 levels during OGTT in 17 Japanese NGT subjects and evaluated the factors associated with GIP and GLP‐1 secretion using simple and multiple regression analyses. Results: GIP secretion (AUC‐GIP) was positively associated with body mass index (P < 0.05), and area under the curve (AUC) of C‐peptide (P < 0.05) and glucagon (P < 0.01), whereas GLP‐1 secretion (AUC‐GLP‐1) was negatively associated with AUC of plasma glucose (P < 0.05). The insulinogenic index was most strongly associated with GIP secretion (P < 0.05); homeostasis model assessment β‐cell was the most the strongly associated factor in GLP‐1 secretion (P < 0.05) among the four indices of insulin secretion and insulin sensitivity. Conclusions: Several distinct factors might be associated with GIP and GLP‐1 secretion during OGTT in Japanese subjects. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00078.x, 2011)     

Predictors of deterioration of glucose tolerance and effects of lifestyle intervention aimed at reducing visceral fat in normal glucose tolerance subjects with abdominal obesity

Aims/Introduction: The aim of the present study was to determine the predictors of deterioration of glucose tolerance in individuals with normal glucose tolerance (NGT) and abdominal obesity, and whether a lifestyle intervention to reduce visceral fat is effective in these individuals. Materials and Methods: The study subjects were 251 individuals who had abdominal obesity with certain risk factors (hypertension, high fasting plasma glucose (FPG), elevated hemoglobin A_1c (HbA_1c), dyslipidemia and hyperuricemia) and underwent oral glucose tolerance test (OGTT) in 2004 and 2005. Results: Using the area under the receiver operating characteristic curve, we found that PG at 0 min, 60 min, and area under the curve (AUC) of glucose from 0 to 120 min (AUC [glucose_0–120]) in OGTT were significant predictors of deterioration of glucose tolerance, with optimal cut‐off values of 95 mg/dL, 158 mg/dL and 271 mg h/dL, respectively. Although the rate of deterioration of glucose tolerance didn’t decrease with reductions in visceral fat area (VFA) over the 1‐year period in subjects with NGT, the rate tended to decrease with reductions in VFA in high‐risk NGT subjects (PG at 0 min > 95 or at 60 min > 158, or AUC [glucose_0–120] > 271). Conclusions: These results suggest that reduction of visceral fat over 1 year might not be beneficial in all subjects with NGT, but is beneficial in high‐risk NGT. We propose that individuals with values of the aforementioned predictors higher than the cut‐off levels, even those with NGT, should receive a lifestyle intervention program aimed at reducing visceral fat to prevent deterioration of glucose tolerance. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00080.x, 2011)     

The response of Gastric Inhibitory Polypeptide (GIP) and insulin to glucose in duodenal ulcer patients

Summary The response of Gastric Inhibitory Polypeptide (GIP) and insulin to a 50 g oral glucose tolerance test (OGTT) and an intravenous glucose infusion (IVGI), which copied the changes in plasma glucose concentrations during the OGTT, were measured in 10 patients with duodenal ulcer and in 10 healthy control subjects. The mean responses of GIP and insulin to OGTT were significantly increased in the ulcer patients. During IVGI the responses were normal. The degree of increased GIP response in the patients was positively correlated with the plasma glucose increase during the OGTT. It is postulated that the increased GIP secretion is related to a faster glucose absorption due to rapid gastric emptying in duodenal ulcer patients. No correlation was found between basal and peak gastric acid output and the GIP response in the patients. The data demonstrate that GIP secretion is not defective in duodenal ulcer patients.     

Insulin‐secretion capacity in normal glucose tolerance,impaired glucose tolerance,and diabetes in obese and non‐obese Japanese patients

Aims/Introduction: Pronounced reduction of insulin secretion in response to a rise in glucose level has been reported in Japanese patients compared with Caucasian patients, but the mean body mass index (BMI) is also lower in Japanese patients. As BMI is a determinant of insulin secretion, we examined insulin‐secretion capacity in obese and non‐obese Japanese patients. Materials and Methods: Using the oral glucose tolerance test (OGTT), we estimated the insulin‐secreting capacity in obese (BMI ≥ 25) and non‐obese (BMI < 25) Japanese patients, including 1848 patients with normal glucose tolerance (NGT), 321 patients with impaired glucose tolerance (IGT) and 69 diabetes (DM) patients. Results: The insulinogenic index (I.I.), calculated by dividing the increment in serum insulin by the increment in plasma glucose from 0 to 30 min during OGTT, decreased from NGT to IGT and to DM in patients with and without obesity. In patients with NGT, IGT and DM, the I.I. values of obese patients were higher than those of the non‐obese patients. The peak of insulin concentration in OGTT appeared at 60 min in NGT and at 120 min in IGT in both obese and non‐obese patients, but in DM it was observed at 120 min in obese patients and at 60 min in non‐obese patients. Conclusions: These results show that early‐phase insulin secretion in obese Japanese patients is higher than in non‐obese patients in all stages of glucose tolerance, and delayed insulin‐secretion capacity is also conserved in obese Japanese patients, even in IGT and DM, which is similar to Caucasian patients. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00180.x , 2011)     

Serum retinol-binding protein 4 is associated with insulin secretion in Chinese people with normal glucose tolerance

Background:  Serum levels of retinol‐binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on β‐cell function. Thus, the present study investigated the relationship between serum RBP4 and insulin secretion in Chinese people with and without T2DM. Methods:  A 75 g oral glucose tolerance test was administered to all 867 subjects and serum RBP4 concentrations were determined. Insulin secretion was assessed by ΔI/ΔG (increment in plasma insulin concentration/plasma glucose concentration 30 min after the oral administration of 75 g glucose) and the total area under the curve for insulin over 180 min (AUC‐I). Magnetic resonance imaging was used to measure visceral fat area (VFA) at L4–L5; subjects with VFA ≥80 cm² were considered to have visceral obesity (VO). Results:  Serum RBP4 concentrations were significantly higher in subjects with VO than without, regardless of the presence of T2DM. In addition, in the entire group with normal glucose tolerance (NGT), serum RBP4 was positively correlated with ΔI/ΔG (r = 0.152; P < 0.01) and AUC‐I (r = 0.218; P < 0.01) after adjustment for gender. The correlation between RBP4 and ΔI/ΔG (r = 0.162; P < 0.05) and AUC‐I (r = 0.195; P < 0.01) remained in NGT non‐VO subjects. No correlation was found between serum RBP4 and ΔI/ΔG or AUC‐I in T2DM patients. Stepwise multiple regression analysis showed that serum RBP4 is an independent factor that contributes to ΔI/ΔG (β = 0.176) and AUC‐I (β = 0.204) in NGT non‐VO subjects. Conclusions:  Serum RBP4 is correlated with glucose‐stimulated insulin secretion in NGT non‐VO subjects, but not in NGT VO subjects and T2DM patients.     

Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women

Background High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. Objective To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). Methods We studied normal glucose‐tolerant (NGT), age‐matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2‐h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC‐HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC‐insulin was correlated positively with AUC‐visfatin, and negatively with AUC‐HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC‐visfatin, and negative correlation with basal and AUC‐HMWA. Conclusion In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter‐regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.     

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     

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.     

Comparison of incretin immunoassays with or without plasma extraction: Incretin secretion in Japanese patients with type 2 diabetes

Aims/Introduction: The effectiveness of incretin‐based therapies in Asian type 2 diabetes requires investigation of the secretion and metabolism of glucose‐dependent insulinotropic polypepide (GIP) and glucagon‐like peptide 1 (GLP‐1). Plasma extractions have been suggested to reduce variability in intact GLP‐1 levels among individuals by removing interference that affects immunoassays, although no direct demonstration of this method has been reported. We have evaluated the effects of ethanol and solid‐phase extractions on incretin immunoassays. We determined incretin levels during meal tolerance tests in Japanese patients with type 2 diabetes and characterized predictors for incretin secretion. Materials and Methods: Japanese patients with type 2 diabetes (23 anti‐diabetic drug‐naïve and 18 treated with sulfonylurea [SU] alone) were subjected to meal tolerance tests, and incretin levels were determined by immunoassays with or without extraction. Results: Intact GLP‐1 levels determined by an intact GLP‐1 immunoassay with ethanol and solid‐phase extractions were lower than those determined without extraction. Intact GLP‐1 levels determined by the extractions were highly correlated with each other, much more so than the levels with and without extraction. Total GLP‐1 was unaffected by extractions, showing that extractions remove interference only in the case of intact GLP‐1. Incretin secretion after meal ingestion was similar between drug‐naïve and SU‐treated patients. Fasting and postprandial GLP‐1 levels were correlated positively with fasting free fatty acids and negatively with dipeptidyl peptidase‐4 activity. Conclusions: Ethanol and solid‐phase extractions remove interference for intact GLP‐1 immunoassay. SU showed little effect on incretin secretion. GLP‐1 and GIP secretion were predicted by different factors. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00141.x, 2012)     

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.     

单纯空腹血糖受损和单纯空腹高血糖型糖尿病的代谢特征

目的评估初发的单纯空腹血糖受损（iIFG）和单纯空腹高血糖型糖尿病（IFH）患者的胰岛素分泌及胰岛素敏感性特征,进一步探讨进展为IFH的相关因素。方法2004—2005年瑞金医院内分泌科门诊初诊病人,隔夜空腹10h后行口服葡萄糖耐量试验,其中同时行胰岛素释放试验1852例。其中糖耐量正常（NGT）557例;iIFG221例;IFH81例。比较各组的代谢指标及胰岛素分泌和胰岛素敏感性指数。结果对1852例接受者操作特征曲线（ROC）分析确定的糖耐量异常（除外糖尿病）发生的最佳空腹血糖切点为5．590mmol／L,2型糖尿病发生的最佳空腹血糖切点为6．695mmol／L。从NGT→iIFD→IFH,早期相胰岛素分泌和胰岛素敏感性指数均逐渐降低。结论初发的iIFG和IFH均有显著的早期相胰岛素分泌缺陷和胰岛素敏感性降低。B细胞胰岛素分泌缺陷和胰岛素抵抗均是从NGT向iIFG向IFH的进展过程中的重要因素。     

Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus

Background: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC). Aims: The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV. Methods: This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance. Results: Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and γ‐glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis. Conclusions: A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.     

新诊断2型糖尿病患者葡萄糖耐量试验与糖化血红蛋白水平的相关分析

目的 对比分析新诊断2型糖尿病及糖尿病前期患者口服葡萄糖耐量试验(OGTT)与糖化血红蛋白(HbAIc)水平变化的特点及影响因素. 方法 按照OGTT结果将受检者分为糖耐量正常组(正常组):31例,年龄29～75岁,平均(48.4±15.3)岁;空腹血糖受损组(血糖受损组):33例.年龄38～72岁,平均(50.8±9.8)岁;糖耐量受损组:34例,年龄33～74岁,平均(54.5±11.4)岁;2型糖尿病组(T2DM组):117例,年龄29～75岁,平均(54.3±14.1)岁.采用OGTT试验、HbAlc结果评价糖代谢状态,胰岛β细胞功能指数(HOMA-E)、OGTT 30 min胰岛素分泌增值与血糖增值比值(△I30/△G330)、胰岛素分泌曲线下面积(AUCINS)及胰岛素抵抗指数(HOMA-IR)分别反映胰岛β细胞分泌功能和胰岛素抵抗情况. 结果 (1)T2DM、糖耐量受损组和正常组HbAlc分别为7.41%、5.85%和5.21%,差异有统计学意义(P<0.01),T2DM、糖耐量受损组和血糖受损组HOMA-β指数与正常组比较,分别下降了53.1%(P<0.01)、29.3%(P<0.01)和23.4%(P<0.05),T2DM组HOMA-IR分别是正常组的1.66倍(P<0.01)、血糖受损组的1.29倍(P<0.001)和糖耐量受损组的1.44倍(P<0.05);(2)HbAIc与糖负荷后3 h血糖水平相关性最高(r=0.71,P<0.01),且独立相关;△I30/△G330与糖负荷后1 h和2 h血糖水平独立负相关(P<0.01);AUCINS只与糖负荷后3 h血糖水平独立负相关(P<0.01);HOMA-β与2 h以外的其他各点血糖独立负相关(P<0.01);HOMA-IR与OGTT各点血糖水平均呈正相关(P<0.01或P<0.05);三酰甘油与空腹血糖独立正相关(P<0.05),腰围与1/2 h血糖独立正相关(P<0.01).OGTT试验血糖水平变化的独立相关因素依次为△I30/△G330、AUCINS、HOMA-β、HOMA-IR和腰围.HbAlc水平的独立相关因素是OGTT 3 h血糖变化. 结论 在2型糖尿病、糖耐量低减及正常等不同糖代谢状态人群中,HbAlc水平存在差异,当HbAlc>8.0%时,OGTT试验、血糖、胰岛素水平或曲线下面积均不能反映出病情差别和变化的显著性.     

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。     

Strong association of C-reactive protein with body mass index and 2-h post-challenge glucose in non-diabetic, non-smoker subjects without hypertension.

AIMS: Increases in C-reactive protein (CRP) levels have been shown to be associated with cardiovascular diseases as well as asymptomatic atherosclerosis and to be closely related to traditional cardiovascular risk factors. The aim of this study was to determine the clinical and biochemical characteristics associated with CRP in non-diabetic, non-smoker subjects without hypertension. METHODS: A 75-g oral glucose tolerance test was performed on 305 Japanese subjects aged 40-70 years who were undergoing health examinations. We recruited non-diabetic, non-smoker subjects without hypertension. Subjects with known cardiovascular diseases, chronic or acute inflammation, malignant diseases, or autoimmune disorders were excluded. Plasma high-sensitivity CRP was measured in 125 subjects who satisfied the admission criteria. RESULTS: Plasma CRP levels were significantly higher in the 28 subjects with impaired glucose tolerance (IGT) than that in the 97 subjects with normal glucose tolerance (NGT) (median 0.53, range 0.18-1.10 mg/l vs. median 0.32, range 0.17-0.49 mg/l; P = 0.032). There was a positive correlation of CRP with body mass index (BMI), triglycerides, uric acid, fasting glucose, oral glucose tolerance test (OGTT) 1-h glucose, OGTT 2-h glucose, and a negative correlation with HDL cholesterol. Multivariate regression analysis identified BMI (F = 8.57, P = 0.004) and OGTT 2-h glucose (F = 5.96, P = 0.016) as independent predictors for CRP. CONCLUSIONS: BMI and OGTT 2-h glucose are the most important predictors for plasma CRP in non-diabetic, non-smoker subjects without hypertension.     

Pancreatic beta-cell function and insulin sensitivity in japanese subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes mellitus

To clarify whether pancreatic beta-cell function and/or insulin resistance contributes to development of glucose intolerance in Japanese subjects, we investigated 551 subjects who underwent a 75-g oral glucose tolerance test (OGTT). Subjects were divided into 3 groups: normal glucose tolerance (NGT, n = 238), impaired glucose tolerance (IGT, n = 211), and newly diagnosed type 2 diabetes mellitus (n = 102). The diabetics were subdivided into 3 subgroups as follows: diabetes with normal fasting glucose (fasting plasma glucose [FPG] < 110 mg/dL), diabetes with impaired fasting glucose (FPG 110 to 125 mg/dL), and diabetes with diabetic fasting glucose (FPG >or= 126 mg/dL). Insulinogenic index as early-phase insulin secretion, homeostasis model assessment (HOMA-beta and HOMA-resistance), and 4 different formulas of insulin sensitivity index were assessed by plasma glucose and insulin concentrations obtained at fasting or during a 75-g OGTT. Both early-phase insulin secretion and insulin sensitivity were low even in the IGT stage compared with NGT. The transition from IGT to diabetes was accompanied by a progressive deterioration of insulin reserve as well as insulin resistance. During the further progression in diabetes, insulinogenic index decreased additionally, whereas declines in insulin sensitivity were relatively small. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of glucose intolerance in Japanese subjects.     

Oral glucose tolerance testing but not intravenous glucose administration uncovers hyper-responsiveness of hypothalamo-pituitary-adrenal axis in patients with adrenal incidentalomas

OBJECTIVE: Modern imaging techniques are detecting adrenal incidentalomas with increasing frequency. Recent data suggests food-dependent hypercortisolism in a subgroup of patients with bilateral macronodular hyperplasia due to aberrant adrenal responsiveness to gastric inhibitory polypeptide (GIP). We studied the putative influence of food intake on the hypothalamo-pituitary-adrenal (HPA) axis in patients with adrenal incidentalomas and possible mediation by GIP. PATIENTS AND MEASUREMENTS: We examined 15 mildly obese patients with adrenal incidentalomas, eight healthy, lean subjects, and seven obese patients with the metabolic syndrome, who were matched for body weight and age. Each individual underwent oral glucose tolerance testing (OGTT, 75 g glucose), i.v. glucose administration (IVGTT, 30 g glucose over 1 h) and i.v. glucose plus GIP infusion (body weight adapted leading to physiological postprandial GIP serum levels) on three occasions. Plasma glucose, ACTH and cortisol were measured from blood samples taken every 15 minutes from time - 30 minutes to + 75 minutes. RESULTS: OGTT, i.v. glucose administration and GIP infusion led to comparable glucose values within the groups. In contrast to normal subjects and patients with the metabolic syndrome, patients with adrenal incidentalomas had significantly higher mean cortisol values after oral glucose intake as compared to i.v. glucose administration or GIP infusion. The increase in cortisol levels was preceded by a corresponding ACTH increase. No significant effect of GIP administration on cortisol or on ACTH secretion could be detected. CONCLUSIONS: Patients with adrenal incidentalomas showed an abnormal responsiveness of the pituitary-adrenal axis to oral glucose administration. The cortisol peaks in these patients seemed to be ACTH-mediated and were not induced by GIP.     

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.     

Insulin secretion and computed tomography values of the pancreas in the early stage of the development of diabetes

Aims/Introduction: The computed tomography (CT) value of the pancreas was examined across the range of glucose tolerance, and the relationships between pancreatic CT values and factors responsible for glucose intolerance were analyzed. Materials and Methods: A total of 167 health‐check examinees were classified into normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) according to 75 g oral glucose tolerance test (OGTT). Pancreatic and hepatic CT values were estimated at decreasing stages of glucose tolerance. The association of CT values of the pancreas and the indices of glucose tolerance were analyzed. Results: Insulinogenic index (II) was decreased from NGT through IGT to DM. Mean pancreatic CT value was decreased significantly from NGT through IGT to DM. Mean area under the curves of glucose (AUC‐G) was significantly associated with II and insulin sensitivity index (ISI) composite in univariate analysis. In multiple regression analysis, II was most strongly inversely correlated with mean AUC‐G, suggesting that II is the strongest determinant of glucose tolerance in Japanese. In addition, II was significantly associated with mean pancreatic CT value in univariate analysis. In multiple regression analysis, mean pancreatic CT value was strongly correlated with II. Conclusions: Pancreatic CT values were significantly decreased from NGT through IGT to DM. II was the strongest determinant of glucose tolerance, and was significantly influenced by pancreatic CT values. Thus, pancreatic fat deposition might impair insulin secretion in the early stage of development of type 2 diabetes, before overt deterioration of glucose tolerance. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00212.x, 2012)