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.     

Insulin sensitivity and first-phase insulin secretion in obese Chinese with hyperglycemia in 30 and/or 60 min during glucose tolerance tests

The purpose of this study was to investigate insulin sensitivity and first-phase insulin secretion in obesity with hyperglycemia in 30 and/or 60 min during oral glucose tolerance (OGTT, glucose > or = 11.1 mmol/l, post-loading hyperglycemia, PLH) in Chinese population. A total of 196 nondiabetic subjects were included in the present study, among them 99 had normal glucose tolerance (NGT, subdivided into 32 lean NGT and 67 obese NGT), 74 had obesity with impaired glucose tolerance (IGT) and 23 had obesity with PLH. A standard 75-g oral glucose tolerance test was performed after fasting and at 30 min, 1, 2 and 3 h. Insulin sensitivity index (S(I)) was assessed by the Bergman's minimal model method with frequently sampled intravenous glucose tolerance test (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. S(I) was significantly equally lower in three obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT controls, and reduced to the same extent in IGT and PLH subjects. There was no significant difference among lean NGT, IGT and PLH subjects. DI value was reduced from obese NGT individuals, IGT and PLH subjects had a similar lower level of DI. In conclusion, our present results demonstrated that the pathophysiological basis of obese subjects with PLH were clearly insulin resistance and defective in first-phase insulin secretion as that in IGT subjects in Chinese population.     

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。     

2型糖尿病患者血管紧张素Ⅱ与胰岛β细胞分泌功能的关系探讨

目的 探讨不同糖耐量状态下血管紧张素Ⅱ与胰岛β细胞分泌功能的关系.方法 新诊断2型糖尿病患者42例(DM组)、空腹血糖受损/糖耐量受损者38例(IFG/IGT组)、正常对照者40名(NGT组)行静脉葡萄糖耐量试验,ELISA法测定空腹血管紧张素Ⅱ(AngⅡ)及脂联素水平.计算急性胰岛素分泌反应(AIR3-10)、第一时相(0～10min)胰岛素分泌曲线下面积(AUCⅠ)及峰值浓度、第二时相(10～120min)胰岛素分泌曲线下面积(AUCⅡ)、稳态模型评估胰岛β细胞功能指数(HOMA-β)及胰岛素抵抗指数(HOMA-IR).探讨AngⅡ与AIR3-10、AUCⅠ及峰值浓度、AUCⅡ、脂联素、HOMA-β及HOMA-IR的关系.结果 (1)DM组和IFG/IGT组AngⅡ显著高于NGT组(P＜0.05);DM组和IFG/IGT组AIR3-10、AUCⅠ及峰值浓度、AUCⅡ、脂联素显著低于NGT组(P＜0.05),DM组降低更为显著;(2)AngⅡ与AIR3-10、AUCⅠ及峰值浓度、AUCⅡ、脂联素、HOMA-β呈显著负相关(P＜0.01),与空腹血糖、糖负荷后2 h血糖、空腹胰岛素、HOMA-IR呈正相关(P＜0.05);(3)多元逐步回归分析,AngⅡ与AUCⅠ、AUCⅡ独立相关.结论 AngⅡ为胰岛β细胞分泌功能的独立影响因素.排除血压、体位、药物等因素的影响,高AngⅡ水平可预测2型糖尿病患者胰岛β细胞功能受损及胰岛素抵抗.

Abstract：

Objective To investigate the relationship between angiotensin Ⅱ and pancreatic islet β cell secretion function under different glucose tolerance statuses. Method Forty-two patients with newly diagnosed type 2diabetes mellitus ( DM group), 38 subjects with impaired fasting glucose/impaired glucose tolerance ( IFG/IGTgroup) ,and 40 normal control subjects (NGT group) underwent intravenous glucose tolerance test. Fasting plasma angiotensin Ⅱ ( Ang Ⅱ ) and adiponectin were assayed by ELISA. Acute insulin response from 3 to 10 min( AIR3-10 ),the area under the curve( AUCⅠ ) and the peak concentration of the first-phase ( 0-10 min) insulin secretion, the area under the curve of the second-phase( 10-120 min) insulin secretion( AUCⅡ), homeostasis model assessment for β cell function index(HOMA-β) and homeostasis model assessment for insulin resistance index(HOMA-IR) were calculated to explore the relationship with Ang Ⅱ. Result ( 1 ) The levels of Ang Ⅱ in DM group and IFG/IGT group were significantly higher than that in NGT group( P＜0.05 ). The AIR3-10, AUCⅠ and peak concentration, AUCⅡ ,adiponectin in DM group and IFG/IGT group were significantly lower than those in the NGT group ( P＜0. 05), and these results were more significantly reduced in DM group compared with those in IFG/IGT group. (2) Ang Ⅱ was negatively correlated with AIR3-10, AUCⅠ and the peak concentration, AUCⅡ, adiponectin, HOMA-β ( P＜0. 01 ), and positively correlated with fasting blood glucose,2 h blood glucose after glucose loading, fasting insulin, HOMA-IR (P＜0. 05 ). (3)Multiple stepwise regression analysis showed that Ang Ⅱ was independently associated with AUCⅠ and AUCⅡ.Conclusion Ang Ⅱ was an independent factor that affected the insulin secretion function of pancreatic islet βcells. Ruling out the effect of blood pressure, body position, drugs, and other factors, high levels of Ang Ⅱ could predict the dysfunction of pancreatic islet β cell as well as insulin resistance in patients with type 2 diabetes.     

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

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

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。     

Insulin secretory dysfunction and insulin resistance in the pathogenesis of korean type 2 diabetes mellitus

Although insulin resistance has been shown to be a primary defect causing type 2 (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes. We undertook a study to investigate the initial abnormality of glucose intolerance in Koreans. A total of 370 Korean subjects were classified into 5 groups according to their degree of glucose intolerance (normal fasting glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68; diabetes, n = 118). Insulinogenic index was used as an index of early-phase insulin secretion. Insulin resistance was assessed by the R value of the homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT. However, there was no significant difference in HOMA(R) between subjects with NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased significantly with the increase of plasma glucose 120-minute value at the earlier stage of glucose intolerance compared with HOMA(R). These results suggest that early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes in Korean subjects.     

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.     

Different contributions of insulin resistance and beta-cell dysfunction in overweight Israeli Arabs with IFG and IGT

BACKGROUND: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are both intermediate stages that exist between normal glucose tolerance and overt type 2 diabetes. Epidemiological studies demonstrated that the two categories define distinct populations. In this study, we examined the contributions of insulin resistance and beta-cell dysfunction to both states in overweight subjects of Arab origin. METHODS: Twelve subjects with isolated IFG, 10 with isolated IGT, and 20 with IFG and IGT (combined glucose in tolerance-CGT) were compared with 30 subjects with normal glucose tolerance (NGT) subjects; all were of Arab origin and were overweight or obese. Different indices for insulin resistance and beta-cell function were calculated from oral glucose tolerance (OGTT) values. RESULTS: Subjects with isolated IFG and CGT were more obese and had significantly higher values of insulin resistance than subjects with isolated IGT and NFG. There was no significant difference between the insulin resistance in subjects with isolated IGT and that in subjects with NGT. Indices of beta cell function were severely reduced among subjects with isolated IGT and CGT when compared with those with both isolated IFG and NGT, while subjects with isolated IFG had similar beta-cell indices to subjects with NGT. CONCLUSION: These data demonstrate that beta-cell dysfunction and insulin resistance contribute differently to the pathogenesis of IFG and IGT among overweight Arab subjects.     

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.     

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 sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

Aims/hypothesis We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. Methods Non-diabetic offspring (n = 874; mean age 40 ± 10.4 years; BMI 26.6 ± 4.9 kg/m²) of type 2 diabetic patients from five different European Centres (Denmark, Finland, Germany, Italy and Sweden) were examined with regard to insulin sensitivity (euglycaemic clamps), insulin release (IVGTT) and glucose tolerance (OGTT). The levels of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) were measured during the OGTT in 278 individuals. Results Normal glucose tolerance was found in 634 participants, while 110 had isolated IFG, 86 had isolated IGT and 44 had both IFG and IGT, i.e. about 28% had a form of reduced glucose tolerance. Participants with isolated IFG had lower glucose-corrected first-phase (0–10 min) and higher second-phase insulin release (10–60 min) during the IVGTT, while insulin sensitivity was reduced in all groups with abnormal glucose tolerance. Similarly, GLP-1 but not GIP levels were reduced in individuals with abnormal glucose tolerance. Conclusions/interpretation The primary mechanism leading to hyperglycaemia in participants with isolated IFG is likely to be impaired basal and first-phase insulin secretion, whereas in isolated IGT the primary mechanism leading to postglucose load hyperglycaemia is insulin resistance. Reduced GLP-1 levels were seen in all groups with abnormal glucose tolerance and were unrelated to the insulin release pattern during an IVGTT.     

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。     

糖尿病前期人群的胰岛β细胞功能和胰岛素抵抗的探讨

目的评价糖调节受损（IGR）不同组分的胰岛素抵抗（IR）和胰岛β细胞功能状况。方法OGTT筛查北京地区无DM史中老年人群，据2003年ADA标准，分为正常糖耐量（NGT）组、空腹血糖受损（IFG）组、糖耐量减低（IGT）组、及IFG合并IGT（IFG＋IGT）组，检测各组胰岛素抵抗指数（HO-MA-IR）、胰岛素敏感指数（ISI-Stumvoll）、β细胞功能指数（HBCI/IR）及第一、二时相胰岛素分泌指数。结果（1）IFG组：HOMA-IR显著高于NGT组和IGT组，ISI-Stumvoll高于IGT组（P均〈0.05），HBCI/IR显著低于NGT组和IGT组（P〈0.05）；（2）IGT组：HOMA-IR和HBCI/IR均位于NGT组和IFG组之间，ISI-Stumvoll、第一时相和第二时相胰岛素分泌指数显著低于NGT组和IFG组（P均〈0.05）；（3）IFG＋IGT组：HOMA-IR高于NGT组、IFG组和IGT组，ISI-Stumvoll显著低于NGT组和IFG组（P均〈0.05），HBCI/IR显著低于NGT组和IGT组（P均〈0.05）；（4）在非糖尿病人群中，随着FPG及2hPG的升高，HOMA-IR有递增趋势，ISI-Stumvoll、第一时相和第二时相胰岛素分泌指数有递减趋势（P均〈0.05）。结论IFG主要是肝脏IR和基础状态时的胰岛β细胞分泌功能受损。IGT的肌肉IR较重，其糖负荷后的胰岛β细胞分泌功能受损较重。在非糖尿病人群，FPG和2hPG的升高与IR呈正相关，与胰岛β细胞功能呈负相关。     

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.     

A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and improves β-cell function in individuals with impaired fasting glucose

The objective was to examine the effects of diet macronutrient composition on insulin sensitivity, fasting glucose, and β-cell response to glucose. Participants were 42 normal glucose-tolerant (NGT; fasting glucose <100 mg/dL) and 27 impaired fasting glucose (IFG), healthy, overweight/obese (body mass index, 32.5 ± 4.2 kg/m(2)) men and women. For 8 weeks, participants were provided with eucaloric diets, either higher carbohydrate/lower fat (55% carbohydrate, 18% protein, 27% fat) or lower carbohydrate/higher fat (43:18:39). Insulin sensitivity and β-cell response to glucose (basal, dynamic [PhiD], and static) were calculated by mathematical modeling using glucose, insulin, and C-peptide data obtained during a liquid meal tolerance test. After 8 weeks, NGT on the higher-carbohydrate/lower-fat diet had higher insulin sensitivity than NGT on the lower-carbohydrate/higher fat diet; this pattern was not observed among IFG. After 8 weeks, IFG on the higher-carbohydrate/lower-fat diet had lower fasting glucose and higher PhiD than IFG on the lower-carbohydrate/higher-fat diet; this pattern was not observed among NGT. Within IFG, fasting glucose at baseline and the change in fasting glucose over the intervention were inversely associated with baseline PhiD (-0.40, P < .05) and the change in PhiD (-0.42, P < .05), respectively. Eight weeks of a higher-carbohydrate/lower-fat diet resulted in higher insulin sensitivity in healthy, NGT, overweight/obese individuals, and lower fasting glucose and greater glucose-stimulated insulin secretion in individuals with IFG. If confirmed, these results may have an impact on dietary recommendations for overweight individuals with and without IFG.     

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。     

Factors determining normalization of glucose intolerance in middle‐aged Swedish men and women: a 8–10‐year follow‐up

Aims To examine factors in middle‐aged Swedish men and women predicting the conversion from a state of abnormal glucose regulation to normal glucose tolerance (NGT) after 8–10 years. Methods At baseline 3128 men and 4821 women, aged 35–56 years, without previously diagnosed diabetes underwent an oral glucose tolerance test and completed a questionnaire. At follow‐up, 2383 men and 3329 women were re‐examined. The study group consisted of 156 men and 124 women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both at baseline. Results The rate of reversal to NGT from IFG or IGT was similar regardless of gender. In participants having IFG or IGT, reversal to NGT was predicted by low fasting and 2‐h insulin, homeostasis model assessment of insulin resistance and of pancreatic β cell function, body mass index and waist circumference without differences between gender and baseline glucose tolerance group. Low 2‐h glucose, however, predicted reversal to NGT in men with IFG at baseline, but not in men with IGT at baseline, or in women with either IFG or IGT at baseline. Men reverting to NGT had higher coffee consumption and women had higher baseline leisure‐time physical activity. In multiple logistic regression, including all participants, low fasting and 2‐h glucose remained independent predictors of reverting to NGT. Conclusions Factors predicting reversal to NGT were measures correlated with low insulin resistance, but also lower insulin secretion, perhaps indicating a lower pancreatic β cell workload in those who reverted. In men, but not in women, low 2‐h glucose was of predictive value.     

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。     

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.