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.     

Factors responsible for elevation of 1-h postchallenge plasma glucose levels in Japanese men

The 1-h postchallenge plasma glucose (1-h PG) level is considered to be a good index of the development of glucose intolerance and type 2 diabetes as well as of diabetic complications. In some cases, in Japanese, 1-h PG is elevated despite normal fasting glucose during oral glucose tolerance test (OGTT), but the factors responsible remain unclear. In the present study, subjects with normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), and isolated impaired glucose tolerance (IGT) were divided into subgroups at 1-h PG of 10.0 mM, and the four indices of insulin secretion and insulin sensitivity were compared. In all three categories, the insulinogenic index in subjects with elevated 1-h PG was remarkably lower than in those without elevated 1-h PG. In addition, the insulinogenic index was the strongest factor in elevated 1-h PG according to the multiple regression analysis. Interestingly, one third of the NGT subjects enrolled in this study had elevated 1-h PG. These subjects showed significantly elevated area under the curve of glucose (G-AUC) compared to NGT subjects without 1-h PG elevation. Thus, elevated 1-h PG in Japanese subjects indicates mildly impaired glucose tolerance due to decreased early-phase insulin secretion.     

Pancreatic polypeptide response to oral glucose load in patients with liver cirrhosis--interrelationship between PP and other pancreatic endocrine hormones

The purpose of the present study was to elucidate the interrelationship between pancreatic polypeptide (PP) and other pancreatic endocrine hormones. For this purpose, a radioimmunoassay (RIA) system of plasma PP was established and the changes in plasma PP, plasma immunoreactive insulin (IRI), plasma C-peptide reactivity (CPR) and plasma immunoreactive glucagon (IRG) following oral administration of glucose were examined in ten normal subjects and twenty-five patients with liver cirrhosis. Patients with liver cirrhosis were classified into a normal glucose tolerance group (NGT), an impaired glucose tolerance group (IGT), and a diabetes mellitus group (DM) on the basis of the glucose tolerance curves obtained after the oral administration of glucose. In the IGT and DM groups, fasting plasma PP levels were significantly elevated when compared with those in the control and NGT groups. Also oral administration of 75g glucose elicited an exaggerated rise in plasma PP in the IGT and DM groups when compared with the response in the control and NGT groups. On the other hand, PP response to glucose in the NGT group was similar to that in the control group. Plasma IRI increased markedly before and after oral administration of glucose in the IGT and DM groups when compared with the control groups. In these patients, plasma levels of CPR almost paralleled those of IRI. No significant difference was noted between the NGT group and the control group with regard to plasma IRI and CPR levels before and after oral glucose loading. Accordingly, insufficient insulin action was considered to exist in the IGT and DM groups. This insufficiency in insulin action was expressed in terms of the indices of increase in plasma IRI and CPR, delta IRI/delta BS and delta CPR/delta BS, which corresponded to the elevated blood glucose levels, being significantly lower in the IGT and DM groups than in the control and NGT groups 30 minutes after oral administration of glucose. No significant difference was noticeable between the NGT group and control group with regard to these indices. In the patients with liver cirrhosis, the delta PP value, obtained by subtracting the plasma PP level during fasting from the PP level 30 minutes after oral glucose loading, was inversely correlated with the values of both delta IRI/delta BS and delta CPR/delta BS.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hyperbolic correlation between insulin sensitivity and insulin secretion fades away in lean subjects with superb glucose regulation

The relationship between insulin sensitivity (Si) and insulin secretion (β) was analyzed in 533 health examinees. The subjects underwent a 75 g oral glucose tolerance test, with plasma glucose (PG) and immunoreactive insulin (IRI) determined at fasting, 30 min and 120 min, and were classified according to the current criteria as normal glucose tolerance (NGT, n=328), non-diabetic hyperglycemia (NDH, n=113) including impaired fasting glucose and impaired glucose tolerance, and diabetes mellitus (DM, n=72). NGT was subdivided by fasting PG (FPG) tertile, ≤4.9, 5.0-5.4 and 5.5-6.0 mM, into NGT(FPG1), NGT(FPG2) and NGT(FPG3), or by body mass index (BMI) tertile, ≤21.8, 21.9-24.4 and ≥24.5 kg/m2, into NGT(BMI1), NGT(BMI2) and NGT(BMI3). As an index of Si and β, Matsuda index=10,000/sqrt[FPG·FIRI·2hPG·2hIRI] and δIRI????/δPG????, were employed respectively: FIRI, 2hPG and 2hIRI denote fasting IRI, 2h-post glucose PG and IRI, respectively. Correlation between Si and β was evaluated by Spearman's rank correlation and the parameters for [β]=a·[Si](b) were obtained by standardized major axis (SMA) regression. Si-β correlation was strongest in NDH (Spearman's rho=-0.546, SMA regression r2=0.277), intermediate in DM (rho=-0.432, r2=0.193) and weakest in NGT (rho=-0.201, r2=0.039). Spearman's rho for the Si-β correlation was significantly lower in NGT than in NDH (p=0.003). Si-β correlation was significant in NGT(FPG3), NGT(FPG2) and NGT(BMI3), but not in NGT(FPG1), NGT(BMI2) and NGT(BMI1). The slope, b, was -1.184?-1.530 without significant differences between any groups. In conclusion, the hyperbolic Si-β correlation was weaker in NGT than in NDH and absent in NGT subjects belonging to the lowest FPG or BMI tertile.     

肥胖症患者和新诊断的2型糖尿病患者真胰岛素和前胰岛素的改变

目的 了解真胰岛素（ｔｒｕｅ ｉｎｓｕｌｉｎ，ＴＩ）和前胰岛素（ｐｒｏｉｎｓｕｌｉｎ，ＰＩ）在肥胖症和２型糖尿病患者中的改变，了解免疫活性胰岛素（ｉｍｍｕｎｏｒｅａｃｔｉｖｅ ｉｎｓｕｌｉｎ，ＩＲＩ）能否准确反映ＴＩ。方法 ３３例糖耐量正常（ＮＧＴ），２４例糖耐量减低（ＩＧＴ）和５３例新诊断的２型糖尿病患者行口服葡萄糖耐量实验，并根据体重指数（ＢＭＩ）分为肥胖和非肥胖组；采用ＥＬＩＳＡ方法（其单克     

Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus

Glucagon is the physiological antagonist of insulin. Postprandial (pp) hyperglycemia in impaired glucose tolerance (IGT) and in type 2 diabetes mellitus (T2DM) may also depend on irregularities in glucagon secretion. This study investigated the glucagon excursion after a lipid-glucose-protein tolerance test in subjects with different stages of glucose intolerance. We also analyzed the relationship between pp glucagon secretion and hyperglycemias. A total of 64 men (27 healthy subjects with normal glucose tolerance [NGT], 15 with IGT, and 22 with T2DM) were examined. Plasma glucose (PG), insulin, proinsulin, free fatty acids, and triglycerides were measured in the fasting state and at 30 minutes and 2, 3, 4, and 6 hours after the intake of the test meal, which contained 126 g carbohydrates, 92 g fat, and 17 g protein. Postprandial concentrations of metabolic parameters were calculated as area under the curve (AUC). Glucagon was measured in the fasting state and at 30 minutes and 2 and 4 hours pp. Early glucagon increment was defined as glucagon at 30 minutes minus fasting glucagon. The insulin response was quantified as insulin increment divided by PG increment in the corresponding time. Insulin resistance was calculated using lomeostasis model assessment (HOMA). Fasting glucagon was significantly increased in IGT vs NGT (P<.05), and early glucagon increment was significantly higher in T2DM vs NGT and IGT (P<.05). The 2-hour glucagon concentration after the load (AUC) was increased in IGT and T2DM vs NGT (P<.05). Early glucagon increment and the 2-hour AUC of glucagon were strongly correlated to pp glycemia (r=0.494 and P=.001, and r=0.439 and P=.003, respectively). An inverse correlation was observed between early glucagon increment and insulin response at 30 minutes and 2 hours after the meal load (r=-0.287 and P=.026, and r=-0.435 and P=.001, respectively). The 2-hour AUC of glucagon was significantly associated with insulin resistance (r=0.354, P=.020). Multivariate analysis revealed 2-hour insulin response and early glucagon increment as significant independent determinants of the AUC of PG in IGT (R=0.787). In T2DM, 2-hour insulin response, insulin resistance, and early glucagon increment were significant determinants of the AUC of PG (R=0.867). Our study suggests an important role for the irregularities in glucagon response in the pp glucose excursion after a standardized oral mixed meal in IGT and in T2DM. According to our data, a bihormonal imbalance starts before diabetes is diagnosed. Prospective studies are needed to evaluate the impact of glucagon on the progression of glucose intolerance and the possible effects of medicinal suppression of glucagon increment to prevent the progression of glucose tolerance.     

Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese

The aim of this study was to assess the changes in insulin secretion and insulin sensitivity in relation to fasting and 2-hour plasma glucose (PG) levels and to assess the independent contributions of their impairments to non-diabetic hyperglycemia. A total of 2157 Japanese workers (mean age 52.6±7.3 years and mean BMI 23.9±3.2 kg/m(2)) underwent an oral glucose tolerance test (OGTT). Of these subjects, 1125 had normal glucose tolerance (NGT), 525 subjects had isolated impaired fasting glucose (IFG), 159 subjects had isolated impaired glucose tolerance (IGT), 263 subjects had combined IFG and IGT, and 85 subjects had newly diagnosed type 2 diabetes. Insulinogenic index and Matsuda insulin sensitivity index (ISI) were significantly attenuated in subjects with normal but slightly elevated fasting PG, or in subjects with normal but slightly elevated 2-hour PG. Whereas, InsAUC(120)/GluAUC(120) was not significantly decreased in those subjects, and significant decrease of it was observed exclusively in subjects with abnormal fasting PG (≥ 106 mg/dL) or abnormal 2-hour PG (≥ 221 mg/dL). Using multiple regression analyses, both Matsuda ISI and insulinogenic index were independently correlated with PG concentrations in subjects with IFG and/or IGT, while Matsuda ISI alone was independently correlated with fasting PG concentrations in normoglycemic subjects. In conclusion, both insulinogenic index and Matsuda ISI were significantly attenuated in subjects with normal but slightly elevated PG. Lowering of Matsuda ISI was likely to be a strong contributor to 'elevation of fasting PG within the normal range' in this population.     

不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗

目的　研究不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗 (IR)之间的关系。方法　将受试者根据口服葡萄糖耐量试验 (OGTT)结果分为正常糖耐量组 (NGT) ,糖耐量受损组 (IGT )及 2型糖尿病组(DM )。采用毛细血管气相色谱法测定血浆脂肪酸谱 ,用胰岛素敏感指数 (IAI)评估IR。结果　DM组及IGT组血浆软脂酸 (C16:0 )、硬脂酸 (C18:0 )、二十二烷酸 (C2 2 :0 )、二十四烷酸 (C2 4:0 )和饱和脂肪酸浓度较NGT组明显升高 (P <0 .0 5～P <0 .0 1) ;花生四烯酸 (C2 0 :4)分别从NGT、IGT和DM组依次升高 ,差异有显著性 (P <0 .0 5～P <0 .0 1) ;血浆饱和脂肪酸 (SFA)从NGT、IGT、DM亚组依次升高 (P <0 .0 5～P <0 .0 1) ;NGT组的多不饱和脂肪酸 (PUFA)与饱和脂肪酸 (SFA)的比率高于IGT组和DM组 (均P <0 .0 5 ) ;血浆C16:0、C2 0 :4、C2 2 :0、SFA与IAI呈负相关 (P均 <0 .0 1)、PUFA/SFA与IAI呈正相关 (P <0 .0 1)。结论　不同糖耐量者血浆脂肪酸谱不同 ,糖耐量减低与 2型糖尿病患者SFA浓度升高 ,PUFA/SFA下降 ,且与胰岛素抵抗密切相关     

空腹和餐后高血糖患者的胰岛素敏感性和胰岛β细胞功能的研究

目的通过比较不同的空腹和负荷后血糖状态下患者的胰岛素分泌功能和胰岛素敏感性状态,分析空腹和负荷后血糖逐渐升高的影响因素,探讨空腹和餐后血糖的调节机制。方法北京地区研究对象1787人,按照不同的糖代谢紊乱情况分组：（1）根据空腹血糖（PG。）情况将人群分为PG。正常组（NFG,PG0〈6．1mmol／L）,PG0受损组（IFG,6．1mmol／L≤PG0〈7．0mmol／L）和空腹高血糖型糖尿病组（IFH,PG0≥7．0mmol／L）三大组。然后将IFG和IFH大组分别按照OGTT中PG120细分为IFG[糖负荷后血糖正常（ngt,PG120〈7．8mmol／L）]组,IFG[糖耐量减低（igt,7．8mmol／L≤PG120〈11．1mmol／L）]组;IFH（ngt）组,IFH（igt）组和IFH[糖负荷后高血糖型糖尿病（iph,PG120≥11．1mmol／L）]组。（2）同理,根据OGTT中PG120将人群分为NGT,IGT和IPH三大组。然后根据PG0细分为IGT（nfg）组,IGT（ifg）组;IPH（nfg）组,IPH（ifg）组和IPH（ifh）组。用胰岛素抵抗指数（HOMA—IR）反映胰岛素敏感性,用胰岛素初期分泌功能指数（△I30／△G30）评价糖负荷早期胰岛β细胞的分泌功能。结果（1）从NFG（ngt）→IFG（ngt）→IFH（ngt）组,HOMA-IR逐渐增加,△I10／△G30逐渐减小（P均〈0．05）。（2）从NGT（nfg）→IGT（nfg）→IPH（nfg）组△I30／△G30逐渐减小,而HOMA-IR三组相似。结论负荷后血糖升高过程中,其早时相胰岛素分泌功能减退是主要决定因素;而在空腹血糖的升高过程中,胰岛素分泌缺陷和胰岛素抵抗都起重要作用。     

Ten-year follow-up of Japanese overweight subjects with impaired glucose tolerance: identification of a diabetes-prone subpopulation.

Ninety-four overweight subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) were followed for 10 years. No one from the NGT group developed diabetes, however 32% of the IGT subjects did develop diabetes. Initial data of the IGT subjects who developed diabetes were significantly different from those who did not develop diabetes. Fasting, peak and/or sigma plasma glucose (PG), IRI and CPR at 180 minutes and CPR/IRI at 0 and 180 minutes were increased, and the peak time of PG was delayed; also the prevalence of a positive family history was higher, and the body weight heavier. Seventy-nine percent of IGT subjects with the initial sigma PG of greater than or equal to 40 mM or a positive family history developed diabetes whereas only 3% of those with sigma PG of less than 40 mM and a negative family history developed diabetes. Therefore, it might be considered that among the overweight adults with IGT, those with sigma PG of greater than or equal to 40 mM or a positive family history are diabetes prone and those with sigma PG of less than 40 mM and a negative family history are diabetes resistant.     

Effects of thorough mastication on postprandial plasma glucose concentrations in nonobese Japanese subjects

Thorough mastication has the potential to affect postprandial plasma glucose concentrations by improving digestibility and absorption of nutrients. To evaluate the effects of mastication on postprandial plasma glucose concentration, we compared usual and thorough mastication in subjects with normal glucose tolerance (NGT group, n = 16) and subjects predisposed to type 2 diabetes (first-degree relatives of type 2 diabetic patients, subjects with impaired glucose tolerance, and type 2 diabetic patients) (predisposed group, n = 10) in a crossover trial of 52 test meals. Plasma glucose and serum insulin concentrations were measured for 3 hours postprandially, and the insulinogenic index (the ratio of incremental serum insulin to plasma glucose concentration during the first 30 minutes after meal) was calculated. In the NGT group, thorough mastication reduced the postprandial plasma glucose concentration at 90 minutes (5.8 +/- 0.3 vs 6.5 +/- 0.4 mmol/L, P < .05) and 120 minutes (5.4 +/- 0.2 vs 6.3 +/- 0.4 mmol/L, P < .05) and the area under the curve (AUC) from -15 to 180 minutes (19.1 +/- 0.6 vs 20.6 +/- 0.8 [mmol . L]/h, P < .05) without an increase in the AUC for insulin. In the predisposed group, thorough mastication significantly augmented plasma glucose and serum insulin concentrations and the AUCs compared with usual mastication. Thorough mastication elicited a significantly higher insulinogenic index than usual mastication in the NGT group (205.0 +/- 27.6 vs 145.6 +/- 17.7 pmol/mmol, P < .05), whereas the predisposed group showed significantly less early-phase insulin secretion than the NGT group. In the NGT group the postprandial plasma glucose concentration upon thorough mastication of meal was significantly lower, most probably because of the potentiation of early-phase insulin secretion. In the subjects predisposed to type 2 diabetes, thorough mastication did not potentiate early-phase insulin secretion and elicited a higher postprandial plasma glucose concentration.     

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.     

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。     

Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in each type of impaired glucose tolerance in man

For this study we enrolled 1,615 males who were admitted to our hospital for a general health check-up. Plasma glucose (PG) and insulin were measured during 75 g OGTT, and abdominal obesity was assessed by ultrasonography in all subjects. We divided them into several groups: normal glucose tolerance (NGT), high-normal glucose tolerance (h-NGT) who showed >10.0 nmol/l at 1 hr PG among those with NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and DM, according to the results of 75 g OGTT. The aim of the present study was to clarify the clinical characteristics of pre-diabetic disorders relating to metabolic syndrome by comparing various parameters including body mass index (BMI), blood levels of various lipids and abdominal wall fat index (AFI) calculated from the thickness of preperitoneal (Pmax) and subcutaneous (Smin) fat layer in the abdomen estimated by ultrasonography with insulin sensitivity determined by homeostatic model assessment (HOMA-IR) in each type of abnormal glucose regulation as classified by PG changes in 75 g OGTT. We also investigated the relationship between insulin secretion capability and insulin sensitivity to delineate the characteristics of each type of abnormal glucose regulation, and compared the area under the insulin curve (AUCins) and the time axis, and the ability of early insulin secretion by glucose loading (insulinogenic index: I.I.) in each type of abnormal glucose regulation. There was a significant positive correlation between HOMA-IR and Smin or Pmax, suggesting that Smin and Pmax may reflect insulin sensitivity. Abdominal obesity, which was diagnosed from the data of AFI, was present in the h-NGT and IFG + IGT groups, suggesting that those groups belong to the clinical entity of metabolic syndrome. HOMA-IR was higher in IFG than in IGT, although I.I. was reduced and AUCins was increased in IFG as well as in IGT. h-NGT demonstrated a slightly lower I.I. and higher AUCins, compared with IGT. IFG demonstrated much stronger insulin resistance than IGT, although I.I. was reduced and AUCins was increased in IFG and IGT. Thus, it is suggested that insulin sensitivity may partly account for the difference in pathogenesis between IFG and IGT; and that h-NGT, which showed abdominal obesity assessed as AFI by ultrasonography, should be recognized as a disease state of metabolic syndrome with impaired glucose regulation.     

Pathophysiologic heterogeneity in the development of type 2 diabetes mellitus in Korean subjects

OBJECTIVE: To investigate the clinical characteristics and predisposing metabolic abnormalities in the development of glucose intolerance and diabetes mellitus in obese and non-obese Korean subjects. METHODS: Four hundred Korean subjects were classified into five groups according to degree of glucose tolerance by OGTT: NGT, IGT alone, IFG alone, IFG+IGT, and DM. The groups were also subdivided into obese and non-obese group according to body mass index. Insulin resistance was assessed by using homeostasis model assessment of insulin resistance (HOMA-R), and insulinogenic index was used as an index of early-phase insulin secretion. RESULTS: Impaired early-phase insulin secretion was seen in non-obese IGT alone, IFG alone, and IFG+IGT, though more profound secretory defects were noted in IFG+IGT and DM. No significant difference were found in HOMA-R among non-obese IGT alone, IFG alone, or IFG+IGT, or in terms of early-phase insulin secretion in obese IGT alone, IFG alone, or IFG+IGT. However, the magnitude of insulin resistance differed in the obese group, IFG+IGT and DM being more insulin resistant than IGT alone or IFG alone. CONCLUSIONS: These results suggest that the predisposing metabolic abnormality in non-obese subjects with IGT alone or IFG alone and in progression to IFG+IGT might be deterioration of early phase insulin secretion, whereas insulin resistance might be the major contributory factor in obese subjects. The predisposing metabolic abnormality leading to diabetes in both obese and non-obese groups was deterioration of early-phase insulin secretion.     

The interplay of insulin resistance and beta-cell dysfunction involves the development of type 2 diabetes in Chinese obeses

Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of β-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S _I) was assessed by the reduced sample number (n = 12) of Bergman’s minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I _{30 min} − I _{0 min})/(G _{30 min} − G _{0 min}) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S _I was used to determine whether AIR was adequate to compensate for insulin resistance. The S _I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population.     

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.     

High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia

High serum concentrations of soluble adhesion molecules are present in diabetics, but whether similar levels are present in patients with impaired glucose tolerance (IGT) is unclear. We measured serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin in 128 nondiabetic Japanese subjects. The concentrations of sICAM-1, sVCAM-1, and sE-selectin in IGT patients (n=47) were not different from those in subjects with normal glucose tolerance (NGT; n=81). IGT patients were subdivided into two groups by the results of 75 g OGTT, those with low- (hypoinsulinemia; n=23) or high-insulin (hyperinsulinemia; n=24). The levels of sICAM-1 and sVCAM-1 were not different among NGT and IGT with high-insulin or with low-insulin. However, sE-selectin concentrations were significantly higher in IGT patients with high-insulin than in NGT and IGT with low-insulin (61.1+/-3.4, 47.1+/-1.8 and 43.7+/-3.9 ng/ml, respectively, P<0.001). Adjustment for age and gender did not influence the results. Serum sE-selectin concentrations correlated significantly with the area under the curve of insulin (AUC(insulin)), AUC(glucose), diastolic blood pressure, and triglyceride levels (r=0.35, 0.26, 0.18 and 0.21, respectively), and negatively with HDL-cholesterol levels (r=-0.20). Multiple regression analysis showed that AUC(insulin) was the only independent factor that correlated with sE-selectin levels (P<0.001). Our results indicate that hyperinsulinemia/insulin resistance may be responsible for the elevation of sE-selectin levels.     

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.