Relationship between hyperinsulinemia and remnant lipoprotein concentrations in patients with impaired glucose tolerance

This study was performed to explore further the association between insulin resistance and plasma remnant lipoprotein (RLP) concentration. For this purpose we used the sum of the plasma insulin concentrations before and 30, 60, 90, 120, and 180 min after a 75-g oral glucose load (sigmaIRI) as a surrogate measure of insulin resistance in 61 subjects with impaired glucose tolerance. SigmaIRI was determined on 2 occasions, before and 16 weeks after initiation of a diet and exercise program. At baseline, sigmaIRI correlated with the sum of the plasma glucose concentrations in response to the 75-g oral glucose load (r = 0.26; P < 0.04) as well as plasma concentrations of triglyceride (r = 0.21; P = 0.09), RLP-cholesterol (r = 0.41; P < 0.001), and RLP-triglyceride (r = 0.46; P < 0.001). In contrast, neither total (r = 0.07) nor high density lipoprotein (HDL) cholesterol (r = 0.04) concentrations correlated with sigmaIRI. SigmaIRI was lower in 42 subjects following life-style intervention, associated with significant (P < 0.005) reductions in sigmaglucose, and fasting glucose, insulin, triglyceride, RLP-cholesterol, and RLP-triglyceride concentrations. However, none of these variables decreased in the 19 subjects whose sigmaIRI did not fall. Finally, the change in sigmaIRI following intervention with diet and exercise was significantly associated with differences in sigmaglucose (r = 0.63; P < 0.001) and fasting glucose (r = 0.26; P < 0.05), insulin (r = 0.79; P < 0.001), triglyceride (r = 0.29; P < 0.03), RLP-cholesterol (r = 0.71; P < 0.001), and RLP-triglyceride (r = 0.49; P < 0.001) concentrations. These results demonstrate that variations in concentrations of RLPs are highly correlated with changes in sigmaIRI, consistent with the possibilities that 1) RLP measurements are useful estimates of insulin resistance; and 2) an increase in RLP concentrations may provide the mechanistic link between insulin resistance and coronary heart disease.     

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.     

Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia

This study examined the prevalence of both basal and glucose-stimulated hyperinsulinemia and acanthosis nigricans (AN) as well as the relationship between insulin and androgen levels in hyperandrogenic women. Sixty-two women who had an elevation of 1 or more plasma androgen levels were studied. The results in these women, grouped for analysis on the basis of obesity and ovulatory status, were compared to those in 36 control women of similar ages and weights. The anovulatory hyperandrogenic women had the clinical and biochemical features of the polycystic ovary syndrome (PCO). Oral glucose tolerance tests were performed with measurement of glucose, insulin, sex hormone-binding globulin (SHBG), and total and non-SHBG-bound sex steroid levels. AN was present in 29% of the hyperandrogenic women, the majority of them obese. Fifty percent of obese PCO women had AN, but they did not otherwise differ from PCO women lacking this dermatological change. Only women with PCO had significant hyperinsulinemia independent of obesity, and obese PCO women with AN had the highest serum insulin levels. Plasma glucose values during the oral glucose tolerance test were significantly increased in obese PCO women independent of the presence of AN, and 20% of these women had frank impairment of glucose tolerance. Ovulatory hyperandrogenic women had normal insulin levels and glucose tolerance. Obese and nonobese women had different relationships between sex steroid and insulin levels; obese women had significant correlations between insulin and non-SHBG testosterone levels (r = 0.30; P less than 0.05), whereas nonobese women had significant correlations between insulin and FSH (r = 0.40; P less than 0.01), dehydroepiandrosterone sulfate (r = 0.33; P less than 0.05), and SHBG (r = 0.37; P less than 0.05) levels, suggesting that the mechanisms underlying the association between sex steroid and insulin levels are complex. These findings suggest that 1) only women with PCO have hyperinsulinemia independent of obesity; hyperinsulinemia is not a feature of hyperandrogenic states in general; 2) AN is a common finding in obese hyperandrogenic women, particularly those with PCO; 3) only obese PCO women are at risk for impairment of glucose tolerance, independent of the presence of AN, suggesting that the negative impact of PCO and obesity on insulin action is additive; and 4) PCO women with AN can be considered as a subgroup of PCO and do not appear to have a distinct endocrine disorder.     

Metformin decreases plasma resistin concentrations in pediatric patients with impaired glucose tolerance: a placebo-controlled randomized clinical trial

The objective was to determine the effect of metformin on the concentrations of resistin and other markers of insulin resistance or inflammation (C-reactive protein, cytokines, body weight, HbA1c, among others) in minors with glucose intolerance. Patients aged 4 to 17 years with glucose intolerance were studied. They were randomized to receive 850 mg of either metformin or placebo twice daily for 12 weeks, during which all followed an iso-caloric diet and an exercise program. High sensitivity C-reactive protein, TNF-alpha, IL-6, IL1-beta, resistin, leptin, adiponectin, glucose, insulin, HbA1c, lipid profile and transaminases were measured at the beginning and at the end of the period. Fifty-two patients were included, 11.9 ± 2.6 years old; 28 (12 males/16 females) received metformin and 24 placebo (11 males/13 females). Baseline characteristics were similar between groups (except for body mass index, which in the metformin group was slightly higher). Percentage weight loss was greater in the metformin group (?5.86% vs 2.75%, P < .05). At study end, there were statistically significant differences in resistin concentrations, even after adjusting for confounding variables (F = 7.714; P < .006). Also, metformin was associated with a significant decrease in HOMA-IR index (P = .032) and HbA1c levels (P = .001), but no change was observed in the concentration of other markers of inflammation. Metformin resulted in significant reductions of plasma resistin levels in minors with glucose intolerance. This change is independent of its effects on body weight. In contrast, metformin did not alter the concentration of inflammatory markers.     

Syndrome W: a new model of hyperinsulinemia, hypertension and midlife weight gain in healthy women with normal glucose tolerance

To characterize a new insulin resistance syndrome in euglycemic midlife women and the relationship of its features (including hypertension and dyslipidemia), with hyperinsulinemia (AUC insulin > or = 100 microU/mL), retrospective cohort analysis was conducted in 278 consecutive women who presented to a Menopausal Health Program. Of 67 women with midlife weight gain "greater than 20 pounds since their twenties" and body mass indices (BMIs) between 25 and 32 kg/m(2), none of the subjects met criteria for Type 2 diabetes, 5 women had impaired glucose tolerance, and 36 women were hyperinsulinemic. Hyperinsulinemia was a highly statistically significant determinant of hypertension, dyslipidemia, and truncal obesity (Odds Ratios 10.6, 4.0, and 13.7; P values < or = 0.0001, < or = 0.007, and < or = 0.0001) in cross-tabulations. AUC insulin was the best predictor variable of hypertension and dyslipidemia in univariate and multivariate logistic regression models (univariate P values 0.0004 and 0.0088). After adjustment for BMI, age, and estrogen use, the final models, correctly classified, respectively, 74% and 69% of all cases in the dataset (model P values: < or = 0.0001 and < or = 0.0067) and AUC insulin had a log-linear (i.e., dose-dependent) relationship with hypertension and dyslipidemia, which suggests causality. We propose that the constellation of symptoms that includes midlife weight gain, "waist-gain," hypertension, dyslipidemia, and appetite dysregulation in euglycemic women with hyperinsulinemia be titled Syndrome W and suggest that the highly statistically significant relationship of hyperinsulinemia with the characteristic features are evidence of a causal role for insulin in its etiology. The identification of Syndrome W before the onset of overt impaired glucose tolerance, diabetes, or manifestations of coronary artery disease could have important clinical and public health implications for midlife women.     

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。     

Fetal growth and impaired glucose tolerance in men and women

Summary A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p < 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p < 0.004), as did 2-h plasma insulin concentrations (p < 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition.     

High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non-obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p less than 0.05, Student's t-test) in offspring of parents with IGT (718 +/- 71 pmol l-1 h) than in the subjects whose parents had normal glucose tolerance (524 +/- 47 pmol l-1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17 +/- 0.11 vs 0.92 +/- 0.08 mmol l-1, 0.10 greater than p greater than 0.05), as were both systolic (132 +/- 5 vs 118 +/- 3 mmHg, p less than 0.05) and diastolic (79 +/- 3 vs 70 +/- 2 mmHg, p less than 0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.     

高血压合并糖耐量减低患者血清脂联素水平的研究

非高血压(HT)者43例,其中糖耐量正常者(NGT)30例,糖耐量减低者(IGT)13例。HT者45例,其中17例伴NGT,28例伴IGT,研究显示:脂联素水平(mg/L)HT伴NGT组低于非HT的NGT组(4.3±1.7vs7.1±3.6),HT伴IGT组低于非HT的IGT组(4.0±2.1vs6.6±1.4)(P均<0.05);NGT与IGT组脂联素水平的差异无统计学意义;IGT组脂联素与DBP、TG、C肽负相关;NGT组脂联素水平与BMI、SBP负相关。     

Fasting plasma glucose and glycated haemoglobin in the screening of diabetes and impaired glucose tolerance

Abstract. The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA_1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA_1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG 7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA_1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA_1C is effective in the screening of IGT; although combined FPG and HbA_1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.     

Incidence of diabetes mellitus in women following impaired glucose tolerance in pregnancy is lower than following impaired glucose tolerance in the non-pregnant state

Summary Impaired glucose tolerance (IGT), which is asymptomatic and requires a glucose tolerance test for detection, is a well-known risk factor for diabetes mellitus. Outside the research setting it is rarely identified in people who lack specific risk factors for diabetes except during pregnancy, at which time screening with an oral glucose challenge is a routine procedure. A 75-g oral glucose tolerance test was performed during the latter part of pregnancy or during a routine epidemiology survey in 15–39-year-old Pima Indian women with no history of abnormal glucose tolerance. Those with IGT by World Health Organization criteria were included in this study. Diabetes incidence in women was compared between those whose IGT was first detected during pregnancy and those who were not pregnant when IGT was first recognized. Seventeen of 73 pregnant women and 114 of 244 non-pregnant women developed diabetes within 10 years. When controlled for plasma glucose concentration, age, body mass index, parity and duration of follow-up, those who were not pregnant were at higher risk of developing diabetes than those who were pregnant (hazard rate ratio = 1.71, 95 % confidence interval = 1.01–2.91). Previous studies had reported that women with IGT during pregnancy are at higher risk of diabetes than women with normal glucose tolerance. This study suggests that women with IGT during pregnancy are at lower risk than non-pregnant women with a similar plasma glucose concentration who, in the clinical setting, are likely to remain unrecognized. [Diabetologia (1996) 39: 1334–1337] Received: 15 February 1996 and in revised form: 8 May 1996     

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。     

Clustering of impaired glucose tolerance, hyperinsulinemia and dyslipidemia in young north Indian patients with coronary heart disease: a preliminary case-control study

Metabolic insulin resistance syndrome is a critical factor in the pathogenesis of atherosclerosis and coronary heart disease in Indians. In a preliminary case-control study, 44 young patients (age < 40 years) with coronary heart disease (angina, myocardial infarction), not previously diagnosed to have diabetes mellitus, were recruited seven days to six weeks after the cardiac event (group I), and compared to 20 healthy subjects (group II). After recording history and anthropometric data, they were subjected to oral glucose tolerance test. Each group was divided into A and B subgroups according to the magnitude of impaired glucose tolerance. Hypertension was recorded in 11 (25%) patients in group I, while all the subjects in group II were normotensive (p < 0.05). Groups IB and IIB, consisting of subjects with impaired glucose tolerance displayed significantly high post-load blood glucose values. After excluding patients with the family history of diabetes mellitus, there were 13 (39%) and 3 (17%) patients with impaired glucose tolerance in groups I and II, respectively. Total cholesterol and low-density lipoprotein cholesterol levels were higher in group I as compared to group II (p < 0.01). Group IB showed highest mean values of total cholesterol, triglycerides, low-density lipoprotein cholesterol and lowest level of high-density lipoprotein cholesterol as compared to other subgroups. Serum insulin levels at 30 and 90 minutes were significantly higher in group I (p < 0.05). Group IB and IIB showed higher insulin values at 90 minutes when compared to group IA (p < 0.05) and IIA (p < 0.05). Elevated serum insulin values at 90 minutes during oral glucose tolerance test could differentiate among both groups and subgroups, except IB versus IIB. The study demonstrates significantly high prevalence of hypertension, obesity, impaired glucose tolerance, hyperinsulinemia and dyslipidemia, suggesting fully developed metabolic insulin resistance syndrome in young north Indian patients with manifest coronary heart disease.     

Association between impaired glucose tolerance and carotid atherosclerosis: A study in 64-year-old women and a meta-analysis

Background and aimsImpaired glucose tolerance (IGT) is regarded as a transient metabolic state leading to type-2 diabetes, and is known to predict future risk of cardiovascular disease. This study was designed to investigate if IGT is associated with subclinical atherosclerosis.Methods and resultsIn a population-based cohort of 64-year-old women, a group with IGT determined by repeated oral glucose tolerance tests (n = 205) was compared with healthy women with normal glucose tolerance (NGT, n = 188). Intima-media thickness (IMT) and plaques in the common carotid arteries (CCA) and bulbs were measured by ultrasound. The 95% confidence interval (CI) of the difference between the IGT and NGT groups was −0.03 to 0.03 mm. There was no difference in carotid bulb IMT or in the occurrence, size, and characteristics of plaques between the IGT and NGT groups. A meta-analysis was used to calculate summary measures of 12 reviewed studies showing a difference of 0.030 (95% CI 0.012–0.048) mm in carotid IMT between IGT and NGT groups. Heterogeneity in IMT differences between studies was shown.ConclusionsIn our population-based cohort of 64-year-old women, IGT was not associated with increased occurrence of subclinical atherosclerosis. However, a meta-analysis of 12 studies, including our current study, showed that IGT was associated with a small increase in the CCA IMT.     

人血浆瘦素水平与肥胖及血糖、胰岛素的关系

目的　探讨人血浆瘦素水平与肥胖程度、血糖、胰岛素浓度的关系。方法　免疫放射法测定171例检查者(2型DM84例,IGT36例,NGT51例;男90例,女81例)的空腹血浆瘦素水平,并行口服葡萄糖耐量试验,测定血浆胰岛素和葡萄糖浓度,同时测量身高、体重,计算体重指数(BMI)。结果　空腹血浆瘦素水平与体重指数呈正相关(男r=0.6772,P＜0.01;女r=0.7191,P＜0.01),但性别差异显著(P＜0.001),女性是男性的2～3倍。采用多元逐步回归法分析,去除体重指数等因素的影响后,瘦素与胰岛素曲线下面积呈正相关,与血糖浓度无相关性。结论　肥胖者空腹血浆瘦素升高,血浆高瘦素水平与高胰岛素血症的相关性提示瘦素可能在2型糖尿病的发病中起一定作用。     

Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance

Aims/hypothesis. We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT). Methods. Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f_b, f_d, f_s, T_up, T_down ), and insulin sensitivity (Si). Results. ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f_b) and stimulated (f_d, f_s) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T_up) and -down (T_down) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR × Si (10^–5·min^–2× l) was lower in Obese-IGT compared to Controls, both during step-up (919 ± 851 vs 3192 ± 1185, p < 0.05) and step-down (1455 ± 1203 vs 3625 ± 691, p < 0.05) phases. Consistently, the product f_s× Si (10^–14·min^–2· pmol^–1× l) was lower in Obese-IGT than in control subjects (27.6 ± 25.4 vs 103.1 ± 20.2, p < 0.05). Conclusion/interpretation. Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling. [Diabetologia (2002) 45: ▪–▪] Received: 30 July 2001 and in revised form: 21 November 2001