Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action

Aims/hypothesis The impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic and peripheral insulin action, and glucagon and incretin hormone secretion in individuals with i-IFG (n = 18), i-IGT (n = 28) and normal glucose tolerance (NGT, n = 20). Methods Glucose tolerance status was confirmed by a repeated OGTT, during which circulating insulin, glucagon, glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels were measured. A euglycaemic–hyperinsulinaemic clamp with [3–³H]glucose preceded by an IVGTT was performed. Results Absolute first-phase insulin secretion during IVGTT was decreased in i-IFG (p = 0.026), but not in i-IGT (p = 0.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p ≥ 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion×insulin sensitivity) during IVGTT (DI_IVGTT)) was reduced in both i-IFG and i-IGT (p < 0.005 vs NGT). In contrast, the DI during OGTT (DI_OGTT) was decreased only in i-IGT (p < 0.001), but not in i-IFG (p = 0.143) compared with NGT. Decreased levels of GIP in i-IGT (p = 0.045 vs NGT) vs increased levels of GLP-1 in i-IFG (p = 0.013 vs NGT) during the OGTT may partially explain these discrepancies. Basal and post-load glucagon levels were significantly increased in both i-IFG and i-IGT individuals (p ≤ 0.001 vs NGT). Conclusions/interpretation We propose that differentiated preventive initiatives in prediabetic individuals should be tested, targeting the specific underlying metabolic defects.     

不同状态的糖调节受损患者胰岛素分泌和胰岛素敏感性的差异

目的评估初发的单纯空腹血糖受损（IFG）和单纯糖耐量受损（IGT）患者的胰岛素分泌以及胰岛素敏感性（IS）特征。方法北京市东城区既往无糖尿病史的2388名受试者行葡萄糖耐量试验,同时行胰岛素释放试验,本文纳入2244例,其中糖耐量正常（NGT）1608例,IFG240例,IGT243例,IFG＋IGT 153例。比较各组胰岛素抵抗指数（HOMA-IR）、IS指数（Matsudaindex）、B细胞功能指数（1相Stumvoll index、△I30／△G30）。结果与NGT组比较,其余三组HOMA-IR显著升高,Matsuda指数及B细胞功能指数均显著降低（P均〈0．01）;IFG组HOMA-IR及Matsuda指数均高于IGT组;IFG组△I30／△G30高于IGT组,而Stumvoll指数低于IGT组（P〈0．01）;与IFG组、IGT组比较,IFG＋IGT组HOMA-IR显著升高,Matsuda指数、1相Stumvoll指数显著降低（P均〈0．01）。结论糖尿病前期人群存在不同程度的胰岛素分泌缺陷和IR,IFG组肝IR较重,而IGT组肌肉IR较重。     

空腹血糖异常、糖耐量减低患者血清胰岛素水平的变化及其意义

目的 观察空腹血糖异常(IFG)、糖耐量减低(IGT)患者血清胰岛素水平的变化。方法 对50例空腹血糖和糖耐量正常者(NGT)、40例IFC和80例IGT患者行口服葡萄糖耐量试验(0GTT)，用氧化酶法检测血糖，用放免法测定血清空腹及餐后2小时胰岛素。结果 IFG、IGT组空腹血糖、空腹胰岛素水平及胰岛素敏感指数较NGT组明显升高(P＜0.05或P＜0．01)，IFG组胰岛素敏感指数与IGT组比较无显著性差异(P＞0．05)。结论 在IFG、IGT状态下已经存在胰岛素抵抗，而且在程度上两者间并没有显著性差异，应早期干预治疗。     

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.     

The effect of defective early phase insulin secretion on postload glucose intolerance in impaired fasting glucose

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk groups for type 2 diabetes. Type 2 diabetes is characterized by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycemia may differ due to heterogeneity of the disease. Combined glucose intolerance (CGI), on the other hand, seems to represent a more advanced stage of prediabetes that bears a distinctly higher risk of progression to diabetes and its comorbidities. This study has the aim to compare isolated IFG and CGI categories with respect to the degree of early phase insulin secretion abnormalities and insulin resistance. Subjects who had IFG (fasting glucose: 110-126 mg/dl) were included in the study. A 75-g oral glucose tolerance test (OGTT) with insulin response was done and subjects were classified according to the WHO criteria. Six subjects were excluded because they had diabetic glucose tolerance. A total of 66 patients (53.4 +/- 11.1 years, female/male: 48/18) were divided into two groups according to their glucose tolerance in OGGT (Group 1: isolated IFG and group 2: CGI). Early phase insulin secretion was measured by intravenous glucose tolerance test (IVGTT) and OGTT. Insulin resistance was assessed by the R value of the homeostasis model assessment (HOMA). We did not find any statistically significant difference between groups according to age, gender, body mass index (BMI), fasting glucose, fasting insulin, insulin-AUC (0-180 min) and HOMA-R values. In OGGT there was no statistically significant difference between 0', 30', 60' and 90' insulin levels of the groups; only 120' and 180' insulin levels were higher in CGI than in IFG group (p<0.05). In IVGTT, there was no statistically significant difference between glucose levels of the groups. Furthermore, insulin response to intravenous glucose was higher in IFG than in CGI (p<0.05). Our data demonstrate that isolated IFG and CGI are similar with respect to the degree of insulin resistance, and that subjects with CGI had a more prominent deficit in early phases of insulin secretion.     

新疆汉、维民族糖调节受损人群胰岛素分泌功能和胰岛素作用功能的研究

目的 评估新疆汉、维民族在IFG,IGT及IGR阶段的胰岛素分泌功能和胰岛素作用功能。 方法 采用多中心研究进行横断面调查,行OGTT试验。用胰岛素抵抗指数（HOMA-IR）评估IR,胰岛β细胞功能指数（HOMA-β）评估基础胰岛素分泌;ΔI30/ΔG30评价胰岛素早相分泌,ΔI30/ΔG30/HOMA-IR评估葡萄糖处置指数（DI）。 结果 WC、BMI、血脂、FIns、2 hIns在汉、维民族不同糖代谢组差异有统计学意义。IFG组与NGT、IGT组比较,汉、维族人群的HOMA-IR差异有统计学意义。在汉族中NGT组与IGT、IGR组比较,HOMA-β差异有统计学意义（P=0.030、0.044）,而在维族只有IFG组与NGT组比较差异有统计学意义（P=0.001）。ΔI30/ΔG30、DI在两民族不同糖代谢组差异均无统计学意义。 结论 汉族人群IR在IFG阶段,胰岛素分泌功能在IGT阶段起主要作用。IR和胰岛素分泌功能在维族人群IFG阶段起重要作用。胰岛素早相分泌及葡萄糖处置功能在糖调节受损阶段作用不显著。     

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.     

空腹血糖受损与糖耐量减低的概念及表现谱的差异和对策

1997年美国糖尿病学会(ADA)提出空腹血糖受损(IFG)的概念,2003年11月ADA提出IFG下限诊断标准从6.1mmol/L下调到5.6mmol/L。IFG与糖耐量减低(IGT)人群进展为2型糖尿病的危险均较正常血糖人群高,但两者的表现谱却存在许多差异,如两者的患病率具有性别及种族差异;胰岛素分泌及胰岛素抵抗状况也不同;两者与血管病变的关系及血管病变的发生率和病死率也有差异。因此,基于IFG、IGT的病理生理学应对其采取相应的干预措施。     

Adipocytes in subjects with impaired fasting glucose and impaired glucose tolerance are resistant to the anti-lipolytic effect of insulin

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two intermediate states in the transition from normal glucose metabolism to type 2 diabetes. Insulin clamp studies have shown that subjects with IGT have increased insulin resistance in skeletal muscle, while subjects with IFG have near normal muscle insulin sensitivity. Because of the central role of altered free fatty acid (FFA) metabolism in the pathogenesis of insulin resistance, we have examined plasma free fatty acid concentration under fasting conditions, and during OGTT in subjects with IGT and IFG. Seventy-one NGT, 70 IGT and 46 IFG subjects were studied. Fasting plasma FFA in IGT subjects was significantly greater than NGT, while subjects with IFG had similar fasting plasma FFA concentration to NGT. However, fasting plasma insulin concentration was significantly increased in IFG subjects compared to NGT while subjects with IGT had near normal fasting plasma insulin levels. The adipocyte insulin resistance index (product of fasting plasma FFA and FPI) was significantly increased in both IFG and IGT subjects compared to NGT. During the OGTT both IFG and IGT subjects suppressed their plasma FFA concentration similarly to NGT subjects, but the post-glucose loads were significantly increased in both IFG and IGT subjects. These data suggest that both subjects with IFG and IGT have increased resistance to the antilipolytic action of insulin. However, under basal conditions, fasting hyperinsulinemia in IFG subjects is sufficient to offset the adipocyte insulin resistance and maintain normal fasting plasma FFA concentration while the lack of increase in FPI in IGT subjects results in an elevated fasting plasma FFA.     

糖调节受损个体胰岛β细胞功能和胰岛素抵抗观察

评价152例人选者[正常糖耐量、空腹血糖受损和(或)糖耐量受损]胰岛β细胞功能和胰岛素抵抗.结果 显示空腹血糖受损者主要表现胰岛素早期分泌功能缺陷和基础分泌不足,胰岛素抵抗严重;糖耐量受损者则胰岛素早期和晚期分泌功能显著下降伴轻度胰岛素抵抗.     

Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects with IGT and we also examined this interrelation in relation to the 2 main incretins, glucagon-like peptide (GLP-1) and gastric inhibitory polypeptide (GIP). To that end, 13 women with IGT and 17 women with normal glucose tolerance (NGT) underwent an oral glucose tolerance test (OGTT) with measurements of glucose, insulin, C-peptide, GLP-1, and GIP. Insulin secretion (TIS) and insulin sensitivity (OGIS) were assessed using models describing the relationship between glucose, insulin and C-peptide data. These models allowed estimation also of the hepatic extraction of insulin. The age (54.2 +/- 9.7 [mean +/- SD] years) and body mass index (BMI; 26.0 +/- 4.0 kg/m(2)) did not differ between the groups. Subjects with IGT displayed lower TIS during the initial 30 minutes after oral glucose (0.97 +/- 0.17 [mean +/- SEM] v 1.75 +/- 0.23 nmol/L in NGT; P =.018) and lower OGIS (397 +/- 21 v 463 +/- 12 mL/min/m(2); P =.005). The incremental 30-minute TIS times OGIS (reflecting insulin secretion in relation to insulin sensitivity) was significantly reduced in IGT (359 +/- 51 v 774 +/- 91 nmol/min/m(2), P =.001). This measure correlated inversely to the 2-hour glucose level (r = -0.71; P <.001). In contrast, TIS over the whole 180-minute period was higher in IGT (26.2 +/- 2.4 v 20.0 +/- 2.0 nmol/L; P =.035). Hepatic insulin extraction correlated linearly with OGIS (r = 0.71; P <.001), but was not significantly different between the groups although there was a trend with lower extraction in IGT (P =.055). Plasma levels of GLP-1 and GIP increased after oral glucose. Total secretion of these incretin hormones during the 3-hour test did not differ between the 2 groups. However, the 30-minute increase in GLP-1 concentrations was lower in IGT than in NGT (P =.036). We conclude that also in non-obese subjects with IGT, when adiposity is controlled for in relation to NGT, defective early insulin secretion after oral glucose is a key factor. This defective beta-cell function is associated with, and may be caused by, a reduced early GLP-1 response.     

Impaired fasting glucose and impaired glucose tolerance in urban population in India.

AIMS: To study prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in urban Indians and their demographic and anthropometric characteristics. METHODS: Data on capillary blood glucose (OGTT), anthropometric and demography details were available in 10 025 subjects (M : F 4711 : 5314) aged > or = 20 years. Glucose tolerance was categorized as normal, isolated IFG, isolated IGT, IFG + IGT and diabetes using the fasting and 2-h blood glucose (2hBG; 75-g glucose load) values. Subjects with known diabetes were excluded. RESULTS: Age-standardized prevalences of IFG, IGT and newly detected diabetes were 8.7%, 8.1% and 13.9%, respectively. IFG was more prevalent in women (9.8%) than in men (7.4%) (chi2 = 13.62, P = 0.0002), while the gender differences in IGT (men 8.4%, women 7.9%) and diabetes (men 13.3%, women 14.3%) were not significant. Body mass index and waist circumference were higher in glucose-intolerant groups than in normal glucose tolerance (NGT). Prevalence of diabetes, IGT and IFG + IGT increased with age. Among the IFG, 4% had diabetes and 27.1% had IGT using 2hBG criteria. In IFG, the fasting and 2hBG values were not correlated. CONCLUSIONS: Prevalences of IFG and IGT were similar in urban Indians and an overlap occurred in only less than half of these subjects. IFG was more common in women. Subjects with IFG were older and had more adverse anthropometric characteristics in comparison with NGT. IFG did not show an increasing trend with age.     

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.     

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.     

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.     

Endothelial dysfunction in impaired fasting glycemia, impaired glucose tolerance, and type 2 diabetes mellitus

The aim of this study was to evaluate whether abnormal endothelial function is present in early stages of diabetes, such as impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Endothelial function was assessed by measuring flow-mediated dilatation and nitrate-induced dilatation of the brachial artery using high-resolution ultrasound. Fasting serum lipid levels were determined, and glucose and insulin values in response to a 75-g oral glucose load were also measured. The results showed the following new findings: (1) compared with subjects with normal glucose tolerance, those with IFG and IGT had impaired flow-mediated dilatation, more remarkable in subjects with type 2 diabetes mellitus than those with IFG and IGT, and (2) flow-mediated dilatation was inversely and strongly related to the extent of hyperglycemia. In conclusion, endothelial dysfunction is present in subjects with IGT and IFG, indicating endothelial damage in these stages.     

Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents

OBJECTIVE: The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth. RESEARCH DESIGN AND METHODS: We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups. RESULTS: Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r(2) = 25.9%). CONCLUSIONS: IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion.     

Differences in insulin resistance and pancreatic B‐cell function in obese subjects with isolated impaired glucose tolerance and isolated impaired fasting glucose

Aims To investigate changes in insulin action and insulin secretion in obese subjects with different categories of impaired glucose regulation (IGR): impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG/IGT (CGI). Methods A total of 222 subjects underwent an oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test (FSIGTT); 100 had normal glucose tolerance (subdivided into 32 lean NGT, 68 obese NGT), and 122 were obese with IGR (82 IGT, 14 IFG and 26 CGI). The insulin sensitivity index (S_I) was assessed by Bergman's minimal model method with FSIGTT; insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S_I, was used to determine whether AIRg was adequate to compensate for insulin resistance. Results S_I was similar in NGT and IGR obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT, significantly reduced in IGT, and further reduced in IFG and CGI subjects as compared with obese NGT subgroups. DI was reduced in NGT obese individuals. Within the obese IGR subgroups, IFG and CGI subjects had even lower DI value than IGT subjects. Conclusions Obese Chinese subjects with IGR have a similar degree of insulin resistance but differ in insulin secretion. Subjects with IFG and CGI have a more prominent deficiency in insulin secretion than subjects with IGT.     

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。     

Undiagnosed diabetes and impaired glucose regulation in adult Ghanaians using the ADA and WHO diagnostic criteria

Fasting glucose and oral glucose tolerance test (OGTT) criteria for glucose homeostasis were compared in a cross-sectional cluster, community study in Accra, Ghana. A total of 4636 subjects without prior diagnosis of diabetes had fasting plasma glucose, 2-hour OGTT and measurement of cardiovascular risk factors. Mean age of subjects was 44.2 years; 39.1% of subjects were males. The overall prevalence of undiagnosed diabetes ascertained with both criteria was 4.5% (n=209). The prevalence of undiagnosed diabetes by fasting (3,2%) and OGTT (3.1%) criteria were similar (p>0.05). The prevalence of impaired glucose tolerance (IGT) (15.8%) was higher than that of impaired fasting glucose (IFG) (10.7%). Only 56.5% (n=83) of subjects with diabetes by fasting criteria also had diabetes by OGTT criteria. Sixty-two subjects (42.8%) with diabetes by OGTT had normal or impaired fasting glucose. There was poor agreement between the two diagnostic criteria (kappa=0.31). The concordant normoglycaemic group was the youngest and had the lowest body-mass indey (BMI), waist girth, waist-hip ratio (WHR), total cholesterol, and systolic and diastolic blood pressures. The concordant diabetic group, in contrast, had the highest BMI, waist girth, WHR, total cholesterol and triglyceride levels. Both systems gave similar undiagnosed diabetes rates bur dissimilar IFG and IGT rates. There was poor agreement between the two diagnostic criteria. Diagnostic criteria influenced cardiovascular risk factors. A case may be made for using both criteria in order to ascertain all “diabetes” and all “at-risk” subjects. Received: 4 January 2001 / Accepted in revised form: 18 January 2002