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.     

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.     

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。     

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.     

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。     

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

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

Reduced attenuation of bone resorption after oral glucose in type 2 diabetes

Objective  To investigate the effect of oral glucose on bone resorption and osteoprotegerin (OPG) in subjects with varying degrees of glucose tolerance.
Design and Patients  In a cross-sectional study, 163 postmenopausal women aged 50–88 years without previous history of diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were recruited. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and were then classified as having normal glucose tolerance (NGT), IFG, IGT or diabetes according to American Diabetes Association (ADA) criteria.
Measurements  Plasma glucose, serum insulin, C-terminal telopeptide of type I collagen (CTX-I) and OPG were measured.
Results  Fasting insulin levels increased progressively from subjects with NGT, IFG/IGT to diabetes. After adjusted for age and body mass index (BMI), there was no significant difference in fasting CTX-I and OPG levels across the various degrees of glucose tolerance. After oral glucose, there was a significant decrease in serum CTX-I and OPG ( P <  0·001) except for serum OPG in diabetic subjects. In addition, the percentages of change from baseline for both serum CTX-I and OPG were significantly less in diabetic subjects when compared to those in NGT subjects (–40·9% and 0·6% for diabetes and –50·2% and –10·6% for NGT, respectively).
Conclusions  Oral glucose intake causes suppression of serum CTX-I and OPG in postmenopausal women. The effect is attenuated in women with type 2 diabetes.     

2型糖尿病患者非糖尿病后代心率变异性与血清脂联素水平的相关性研究

目的旨在探讨血清脂联素浓度降低是否与2型糖尿病(T2DM)患者非糖尿病后代心率变异性(heart rate variability,HRV)改变有关.方法31例(男16例,女15例)T2DM患者,所有子女(91例)排除已进行药物治疗的T2DM患者14例,其余空腹静脉取血测定血浆葡萄糖,排除≥7.0 mmol/L者3例,排除5.6~7.0 mmol/L之间者7例.选择其空腹血糖≤5.6 mmol/L后代行口服葡萄糖耐量试验,均未达到T2DM诊断标准,分为正常葡萄糖耐量组(NGT,n=32),葡萄糖耐量异常组(IGT,n=35),对照组(n=32)为无糖尿病家族史的健康查体者.行24 h动态心电图检查测定HRV,指标包括:全部正常窦性R-R间期值的标准差(SDNN);全程按5 min分成连续的时间段,先计算每5 min正常R-R间期的平均值,再计算所有平均值的标准差(SDANN);全部相邻R-R间期差的均方根(rMSSD);总功率(TP);低频功率(LF);高频功率(HF).ELISA法测定血清脂联素.结果T2DM非糖尿病后代血清脂联素水平与其体重指数(BMI)、空腹胰岛素负相关,与高密度脂蛋白胆固醇(HDL-c)、SDNN、SDANN、rMSSD、TP、LF、HF正相关.对照组、NGT组、IGT组之间血清脂联素逐渐降低、空腹胰岛素、SDNN、SDANN、rMSSD、TP、LF、HF逐渐升高.IGT组BMI、血清三酰甘油高于HDL-c,低于对照组和NGT组.结论自主神经平衡的改变与胰岛素抵抗和血清脂联素水平改变具有相关性.     

Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin secretion in high-risk African Americans with impaired glucose tolerance test and type 2 diabetes

We examined the metabolic effects of rosiglitazone therapy on glucose control, insulin sensitivity, insulin secretion, and adiponectin in first-degree relatives of African Americans with type 2 diabetes (DM) with impaired glucose tolerance (IGT) and DM for 3 months. The study was comprised of 12 first-degree relatives with IGT, 17 newly diagnosed DM, and 19 healthy relatives with normal glucose tolerance (NGT). Oral glucose tolerance test (OGTT) was performed before and after 3 months of rosiglitazone therapy (4 to 8 mg/d) in patients with IGT and DM. Serum glucose, insulin, C-peptide, and adiponectin levels were measured before and 2 hours during OGTT in the NGT and patients with IGT and DM. Insulin resistance index (HOMA-IR) and beta-cell function (HOMA-%B) were calculated in each subject using homeostasis model assessment (HOMA). Rosglitazone improved the overall glycemic control in the IGT and DM groups. Following rosiglitazone, the beta-cell secretion remained unchanged, while HOMR-IR was reduced in DM by 30% (4.12 +/- 1.95 v 6.33 +/- 3.54, P < .05) and the IGT group (3.78 +/- 2.45 v 4.81 +/- 3.49, P = not significant [NS]). Mean plasma adiponectin levels were significantly (P < .05) lower in the DM (6.74 +/- 1.95 microg/mL) when compared with the NGT group(9.61 +/- 5.09). Rosiglitazone significantly (P < .001) increased adiponectin levels by 2-fold in patients with IGT (22.2 +/- 10.97 microg/mL) and 2.5-fold greater in DM (15.68 +/- 8.23 microg/mL) at 3 months when compared with the 0 month. We conclude that adiponectin could play a significant role (1) in the pathogenesis of IGT and DM and (2) the beneficial metabolic effects of thiazolidinediones (TZDs) in high-risk African American patients.     

Characteristics of Japanese subjects who progress from normal to impaired glucose tolerance. Longitudinal study excluding changes in body weight

In this retrospective longitudinal study, we focused on the clinical characteristics of Japanese individuals with recent onset impaired glucose tolerance (IGT) who have been followed up for insulin secretory function and 75-gram oral glucose tolerance test (OGTT) for more than 3 years annually before they progressed from normal glucose tolerance (NGT) to IGT. Subjects whose body weight did not show significant change for the period were selected and labeled as either NGT (no change in OGTT over 3 years) or IGT (progressors from NGT to IGT) groups (n = 24, each). We compared the basal biochemical data and response of plasma glucose and serum insulin after OGTT of the two groups. In the IGT progressors, significant increase of plasma glucose at 30 to 120 minutes during OGTT and significant decrease of HDL-cholesterol were observed since 3 years before onset of IGT. In addition to increase of serum glucose and decrease of HDL-cholesterol, serum insulin at 120 minutes during OGTT were significantly and remarkably high at onset and 3 years before onset of IGT. Plasma glucose at 30-120 minutes and serum insulin level at 120 minutes after glucose load are potentially significant predictors of progression from NGT to IGT even in subjects who do not show increase of body weight.     

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     

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。     

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.     

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.     

Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus

Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 ± 0.15 at baseline to 0.43 ± 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (ΔI_0-30/ΔG_0-30) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = −0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in 11 healthy subjects; but neither serum total nor HMW adiponectin changed. In conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly after glucose loading in subjects with NGT or IFG; and the decrease of HMW adiponectin may be associated with an increase of serum insulin at 30 minutes.     

Increased visceral fat and impaired glucose tolerance predict the increased risk of metabolic syndrome in Japanese middle-aged men.

BACKGROUND: Impaired glucose tolerance (IGT) represents a stage of pre-diabetes and is a risk factor for future cardiovascular disease (CVD) which is a major cause of death in type 2 diabetes. The metabolic risk factors such as elevated blood pressure (elevated BP), abdominal obesity, dyslipidemia (elevated levels of total triglycerides [TG] and low levels of HDL cholesterol), and hyperglycemia precede the onset of the metabolic syndrome that increases the risk for CVD. This clustering is commonly associated with pre-diabetic hyperinsulinemia and it reflects peripheral insulin resistance. The present study documented that a visceral fat area (VFA) >/= 100 cm (2) can replace waist-to-hip ratios (WHR) associated with IGT or IFG/IGT as a critical risk for the development of the metabolic syndrome in Japanese middle-aged men. MATERIALS AND METHODS: A total of 575 middle-aged Japanese men with fasting plasma glucose levels of 6.1 - 6.9 mmol/l (impaired fasting glucose; IFG) were enrolled in the study. After a 75-g oral glucose tolerance test (OGTT), blood samples were collected 0 - 2 h later for determination of plasma glucose, insulin concentrations and other variables. Based on the results of an OGTT, the subjects were subgrouped into categories of glucose tolerance for further study. RESULTS: Subjects with IGT or IFG/IGT had significantly higher levels of metabolic abnormalities such as high BMI, increased AUC glucose, elevated HbA1c, high VFA, elevated BP, and increased TG levels when compared to NGT (normal glucose tolerance) (p < 0.001). Compensatory hyper-secretion of insulin was seen in all pre-diabetic subjects, and was higher in IFG/IGT subjects (681 +/- 33 pmol . h/l) than NGT (480 +/- 22 pmol . h/l) (p < 0.01). The metabolic clustering including abnormal VFA, TG, HDL-C, and BP was strongly associated with the development of metabolic syndrome. Interestingly, VFA >/= 100 cm (2) adjusted for the Japanese correlates strongly with the development of the metabolic syndrome in preclinical IGT or IFG/IGT subjects, with odds ratios of 2.7 and higher. CONCLUSION: VFA >/= 100 cm (2) strongly correlates with prediabetic IGT or IFG/IGT which is possibly associated with underlying insulin resistance, and is a critical risk factor linked to the development of metabolic syndrome in Japanese middle-aged subjects with IGT or IFG/IGT.     

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。     

Impaired fasting glucose is not a risk factor for atherosclerosis.

AIM: To determine a new category of dysfunctional glucose homeostasis - impaired fasting glucose (IFG) - introduced by the American Diabetes Association (ADA) and the World Health Organization (WHO) defining those with abnormal but nondiabetic fasting glucose values and with a possible risk for developing diabetes. It is not known whether IFG is a risk factor for atherosclerosis, as is impaired glucose tolerance (IGT). METHODS: In this case-control cross-sectional study in which the oral glucose tolerance (75-g OGTT) and the carotid intima-media thickness (IMT) with B mode ultrasound, as a marker of atherosclerosis, were measured, together with HbA1c, lipids, plasminogen activator (PAI), insulin and proinsulin concentrations in blood plasma. Out of 788 subjects of the risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study we found 104 IFG cases that were compared to 104 controls with fasting plasma glucose (FPG)<6.1 mmol/l, matched for age, sex and body mass index. Subjects with 2h postprandial (pp) plasma glucose > or = 11.1 mmol/l were excluded. The rest were subdivided into those with 2h plasma glucose < 7.8 mmol/l (63 pairs, NGT) and those with plasma glucose > 7.8 mmol/l and < 11.1 mmol/l (41 pairs, IGT). RESULTS: The case and control groups showed no significant differences in the major risk factors except for waist-to-hip ratio (WHR) which was higher in the IFG with NGT. IFG with NGT exhibited significantly higher levels of HbA1c, true insulin and proinsulin. In IFG with IGT, only HbA1c and proinsulin were significantly increased vs. controls. IMT was in the same range for cases and controls in both subgroups. However, IMT mean and IMTmax were significantly increased in IFG with IGT vs. IFG with NGT (0.95 mm vs. 0.80 mm and 1.10 mm vs. 0.90 mm). Cumulative distribution analysis of IMT illustrates that IMT in IFG with IGT is more shifted to higher artery wall thickness than in IFG with NGT. CONCLUSIONS: In our case-control study IFG alone was not related to increased IMT. Only IFG in a combination with IGT exhibited atherosclerotic changes of the carotid arteries. IFG is not analogous to IGT as a risk factor for atherosclerosis.     

Plasma interleukin-6 levels are increased in subjects with impaired glucose tolerance but not in those with impaired fasting glucose in a cohort of Italian Caucasians

BACKGROUND: While the relationship between impaired glucose tolerance (IGT) and circulating interleukin-6 (IL-6) is well established, there is no information whether IL-6 levels are elevated in impaired fasting glucose (IFG). METHODS: To this end, we examined the relationship between plasma IL-6 concentration and different degrees of glucose homeostasis in a cohort of 470 Italian Caucasian subjects comprising 236 normal glucose tolerant (NGT), 49 IFG, 51 IGT, and 134 type 2 diabetic subjects. RESULTS: We observed that IL-6, CRP and fibrinogen levels were higher in subjects with IGT or type 2 diabetes as compared with NGT and IFG subjects. Univariate correlations between IL-6 concentrations and metabolic variables in the whole cohort showed that IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, CRP, fibrinogen, and negatively correlated with insulin sensitivity, IGF-I and HDL. In a subgroup analysis including NGT, IFG and IGT (n = 336), IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, triglycerides, CRP, fibrinogen, fasting insulin, 2 h post-load glucose, and negatively correlated with insulin sensitivity, IGF-I and HDL. Stepwise linear regression analysis in a model including gender, age, BMI, waist, glucose tolerance status, fasting plasma glucose, 2 h post-load glucose, triglycerides, HDL, fasting insulin, and insulin sensitivity revealed that waist was the only independent variable associated with IL-6 levels accounting for 21.0% of its variation (P < 0.0001). CONCLUSIONS: These data show that IGT and type 2 diabetes, but not IFG, are associated with elevated plasma IL-6 levels.