Detecting impaired glucose tolerance or type 2 diabetes mellitus by means of an oral glucose tolerance test in HIV‐infected patients

Objective

As a proactive diagnosis of diabetes mellitus (DM) may prevent the onset of severe complications, we used an oral glucose tolerance test (OGTT) to check for impaired glucose tolerance (IGT) and DM in patients with long‐standing HIV infection and long durations of exposure to antiretroviral drugs with normal fasting plasma glucose (FPG) levels.

Methods

This was a cross‐sectional, single‐centre study. The homeostatic model assessment for insulin resistance (HOMA‐IR) and 2‐h post‐load glucose levels were used to evaluate patients with known HIV‐1 infection since before 1988 and no previous diagnosis of DM for whom data on hepatitis C virus (HCV) and hepatitis B virus (HBV) infection were available.

Results

Eighty‐four Caucasian patients [67 (80%) male; median age 45.7 years; range 43.8–49.1 years] were able to be evaluated; 65 (77%) were coinfected with HCV, and seven (8%) were coinfected with HBV. Median (interquartile range [IQR]) exposure to antiretrovirals was 12.8 (10.4–16.5) years. Fifteen patients (18%) had a previous AIDS‐defining event, 64 (76%) had HIV RNA<50 copies/mL, and the median (IQR) CD4 count was 502 (327–628) cells/μL. The median [IQR] FPG was 81 mg/dL (4.5 mmol/L) [75–87 mg/dL (4.2–4.8 mmol/L)], and the median (IQR) HOMA‐IR was 2.82 (1.89–4.02). After OGTT, nine patients (11%) were diagnosed as having IGT (6) or DM (3). A first multivariable analysis showed that CD4 cell count (P=0.038) and HOMA‐IR (P=0.035) were associated with IGT or DM, but a second model including only the variables with a P‐value of <0.2 in the univariable analysis (CD4 cell count, HBV coinfection, and HOMA‐IR) found that only HOMA‐IR independently predicted IGT or DM.

Conclusions

In patients with long‐standing HIV infection and normal FPG levels, an OGTT can reveal IGT or DM.     

Assessment of insulin sensitivity and secretion with the labelled intravenous glucose tolerance test: improved modelling analysis

Summary A new modelling analysis was developed to assess insulin sensitivity with a tracer-modified intravenous glucose tolerance test (IVGTT). IVGTTs were performed in 5 normal (NGT) and 7 non-insulin-dependent diabetic (NIDDM) subjects. A 300 mg/kg glucose bolus containing [6,6-²H₂]glucose was given at time 0. After 20 min, insulin was infused for 5 min (NGT, 0.03; NIDDM, 0.05 U/kg). Concentrations of tracer, glucose, insulin and C-peptide were measured for 240 min. A circulatory model for glucose kinetics was used. Glucose clearance was assumed to depend linearly on plasma insulin concentration delayed. Model parameters were: basal glucose clearance (Cl_b), glucose clearance at 600 pmol/l insulin concentration (Cl₆₀₀), basal glucose production (P_b), basal insulin sensitivity index (BSI = Cl_b/basal insulin concentration); incremental insulin sensitivity index (ISI = slope of the relationship between insulin concentration and glucose clearance). Insulin secretion was calculated by deconvolution of C-peptide data. Indices of basal pancreatic sensitivity (PSI_b) and first (PSI₁) and second-phase (PSI₂) sensitivity were calculated by normalizing insulin secretion to the prevailing glucose levels. Diabetic subjects were found to be insulin resistant (BSI: 2.3 ± 0.6 vs 0.76 ± 0.18 ml · min^–1· m^–2· pmol/l^–1, p < 0.02; ISI: 0.40 ± 0.06 vs 0.13 ± 0.05 ml · min^–1· m^–2· pmol/l^–1, p < 0.02; Cl₆₀₀: 333 ± 47 vs 137 ± 26 ml · min^–1· m^–2, p < 0.01; NGT vs NIDDM). P_b was not elevated in NIDDM (588 ± 169 vs 606 ± 123 μmol · min^–1· m^–2, NGT vs NIDDM). Hepatic insulin resistance was however present as basal glucose and insulin were higher. PSI₁ was impaired in NIDDM (67 ± 15 vs 12 ± 7 pmol · min^–1· m^–2· mmol/l^–1, p < 0.02; NGT vs NIDDM). In NGT and in a subset of NIDDM subjects (n = 4), PSI_b was inversely correlated with BSI (r = 0.95, p < 0.0001, log transformation). This suggests the existence of a compensatory mechanism that increases pancreatic sensitivity in the presence of insulin resistance, which is normal in some NIDDM subjects and impaired in others. In conclusion, using a simple test the present analysis provides a rich set of parameters characterizing glucose metabolism and insulin secretion, agrees with the literature, and provides some new information on the relationship between insulin sensitivity and secretion. [Diabetologia (1998) 41: 1029–1039] Received: 17 September 1997 and in final revised form: 28 April 1998     

Relationship between glucose tolerance,insulin secretion,and insulin action in non-obese individuals with varying degrees of glucose tolerance

Summary Plasma glucose and insulin concentration following a 75 g oral glucose challenge and glucose uptake during a hyperinsulinaemic glucose clamp study were determined in 50 non-obese individuals. The study population was divided into five groups on the basis of their glucose tolerance: normal, impaired glucose tolerance, Type 2 (non-insulin-dependent) diabetes mellitus with fasting plasma glucose of less than 8 mmol/l, between 8–15 mmol/l, and more than 15 mmol/l. The plasma insulin response was significantly greater (p<0.001) than normal in those with either impaired glucose tolerance or Type 2 diabetes and a fasting plasma glucose concentration less than 8 mmol/l. In contrast, the plasma insulin response was similar to normal in the other two groups of patients with Type 2 diabetes, i.e. fasting plasma glucose concentration 8–15 mmol/l or greater than 15 mmol/l. Glucose uptake rates were significantly lower (p<0.001) than normal in subjects with impaired glucose tolerance and all three groups of patients with Type 2 diabetes. Although glucose uptake rates during the glucose clamp studies were relatively similar in all four groups of glucose intolerant subjects, the values were significantly lower in those patients with Type 2 diabetes who had a fasting plasma glucose concentration greater than 8 mmol/l (p<0.01), These data indicate that a significant degree of insulin resistance exists in patients with impaired glucose tolerance or Type 2 diabetes, relatively independent of fasting plasma glucose concentration. Indeed, glucose uptake during glucose clamp studies fell 8-fold over a range in fasting plasma glucose concentration of from 4.5 to 6.5 mmol/l. In contrast, the plasma insulin response increased over the same range of fasting plasma glucose concentrations. The fact that this defect in insulin action can be seen in patients who are hyperinsulinaemic, not hypoinsulinaemic, and only modestly hyperglycaemic, is consistent with the hypothesis that resistance to insulin-stimulate glucose uptake is a basic characteristic of patients with impaired glucose tolerance or Type 2 diabetes.     

Revisiting the oral glucose tolerance test criterion for the diagnosis of diabetes

OBJECTIVE: The Expert Committee on the Diagnosis and Classification of Diabetes retained the 2-hour glucose concentration on an oral glucose tolerance test of ≥11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated hemoglobin levels have emerged as the best measure of long-term glycemia and an important predictor of microvascular and neuropathic complications, we evaluated the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had undergone an oral glucose tolerance test to determine how well 2-hour values could identify those with normal versus increased Hb A1C levels. DESIGN: A cross-sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour glucose concentrations on an oral glucose tolerance test separated into 4 intervals (<7.8 mmol/L [140 mg/dL], 7.8–11.0 mmol/L [140–199 mg/dL], 11.1–13.3 mmol/L [200–239 mg/dL], and ≥13.3 mmol/L [240 mg/dL]) with Hb A1C levels separated into 3 intervals (normal; <1% above the upper limit of normal; and greater than or equal to the upper limit of normal +1%). RESULTS: Approximately two thirds of patients in both data sets with 2-hour glucose concentrations of 11.1 to 13.3 mmol/L (200–239 mg/dL) had normal Hb A1C levels. In contrast, 60% to 80% of patients in both data sets with 2-hour glucose concentrations ≥13.3 mmol/L (240 mg/dL) had elevated Hb A1C levels. CONCLUSION: Since Hb A1C levels are the best measures presently available that reflect long-term glycemia, we conclude that the 2-hour glucose concentration criterion on an oral glucose tolerance test for the diagnosis of diabetes should be raised from ≥11.1 mmol/L (200 mg/dL) to ≥13.3 mmol/L (240 mg/dL) to remain faithful to the concept that diagnostic concentrations of glucose should predict the subsequent development of specific diabetic complications (e.g., retinopathy). Presented at the American Diabetes Association meeting, San Diego, Calif, June 1999.     

Potential impact of a change in the diagnostic criteria for diabetes mellitus on the prevalence of abnormal glucose tolerance in a local community at risk of diabetes: impact of new diagnostic criteria for diabetes mellitus.

AIMS: To compare the prevalence of diabetes and abnormal glucose metabolism using conventional and suggested new WHO and new ADA criteria in a group of people with symptoms of diabetes. METHODS: We examined retrospectively the results of 154 consecutive OGTTs in such patients performed using capillary whole blood. RESULTS: With the 1985 WHO criteria. Forty-four point eight per cent of subjects (69 subjects, with 95% confidence intervals, 37-52.6%) had diabetes, 47.8% (33 subjects, 36-59.6%) had a normal fasting glucose, 31.2% (48 subjects, 23.9-38.5%) had impaired glucose tolerance (IGT) and 76% (117 subjects, 69.3-82.7%) had abnormal glucose tolerance. Applying the ADA criteria (fasting capillary whole blood only), 33.1% (51 subjects, 25.7-40.5%) had diabetes (a 26% relative reduction) and 11% (17 subjects, 6.1-15.9%) IFG, with 44.1% (68 subjects, 36.3-51.9%) having abnormal glucose metabolism (a 42% relative reduction). If the proposed 1998 WHO criteria were used, the number with diabetes increase to 48% (74 subjects, 40.1-55.9%) a 7.2% increase on the old criteria. 27.9% (43 subjects, 20.8-35%) had IGT, so the number with some degree of abnormal glucose metabolism remains unchanged. Use of the ADA criteria, considering only the fasting glucose as suggested, will result in a significant reduction in the diagnosis of diabetes and those with abnormal glucose metabolism.     

正常糖耐量者口服葡萄糖-胰岛素释放试验的胰岛素分泌曲线特点的研究

目的研究口服葡萄糖一胰岛素释放试验（OGIRT）的胰岛素（Ins）分泌曲线特点,初步探讨适用于I临床评价个体胰岛素敏感性和8细胞分泌功能的方法。方法对12例正常糖耐量者行OGIRT和静脉糖耐量试验（IVGTT）,观察OGIRT、IVGTT血浆Ins分泌峰值时间分布频数,分析胰岛素敏感性和B细胞功能各指标相关指数。结果OGIRT血浆Ins分泌高峰出现于35-45min,无明显第二分泌峰。经多因素线性回归分析表明20、30、35minIns增值与葡萄糖增值的比值（ΔI20／ΔG20、ΔI30／ΔG30、ΔI35／ΔG35）与第一相（1PH）胰岛素分泌、葡萄糖及胰岛素曲线下面积比值（SGI）、胰岛素作用指数（IAI）、HOMA—IR、胰岛素分泌指数均不相关（P〉0．05）,ΔI40／ΔG40与SGI、IAI、HOMA-IR显著相关（P均〈0．01）。结论OGIRT可能不能反映1PH;OGIRTΔI40／ΔG40比I20／ΔG20、△I30／ΔG30能更好地评估β细胞功能。     

The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study

Summary Although an increased plasma non-esterified fatty acid (NEFA) concentration has been shown to increase insulin resistance (Randle cycle), decrease insulin secretion and increase hepatic gluconeogenesis, the effect of NEFA on the deterioration of glucose tolerance has not been studied prospectively in Caucasian subjects. Therefore, we investigated whether plasma NEFA may be regarded as predictors of deterioration of glucose tolerance in subjects with normal (NGT, n = 3671) or impaired (IGT, n = 418) glucose tolerance who were participants in the Paris Prospective study. The subjects were first examined between 1967 and 1972 and underwent two 75-g oral glucose tolerance tests 2 years apart with measurements of plasma glucose, insulin and NEFA concentrations. Glucose tolerance deteriorated from NGT to IGT or non-insulin-dependent diabetes (NIDDM) in 177 subjects and from IGT to NIDDM in 32 subjects. In multivariate analysis, high fasting plasma NEFA in NGT subjects and high 2-h plasma NEFA and low 2-h plasma insulin concentrations in IGT subjects were significant independent predictors of deterioration along with older age, high fasting and 2-h plasma glucose concentrations and high iliac to thigh ratio. When subjects were divided by tertiles of plasma NEFA concentration at baseline, there was an increase in 2-h glucose concentration with increasing NEFA in the subjects who did not deteriorate, but no effect of plasma NEFA in those who deteriorated. In subjects with IGT who deteriorated compared with those who did not 2-h plasma insulin concentration was lower but there was no evidence that this resulted from an effect of plasma NEFA. Our data suggest that a high plasma NEFA concentration is a risk marker for deterioration of glucose tolerance independent of the insulin resistance or the insulin secretion defect that characterize subjects at risk for NIDDM. [Diabetologia (1997) 40: 1101–1106] Received: 11 March 1997 and in revised form: 20 May 1997     

Insulin secretion and action in different stages of glucose tolerance in Asian Indians.

AIMS: To evaluate the sequence of changes in insulin secretion and action in different stages of glucose tolerance and the effect of obesity on insulin profile in South Indian adults. Blood samples from 260 consecutive cases with no known history of diabetes were collected. Plasma insulin levels were measured during a 75-g oral glucose tolerance test. Insulin resistance (IR) was calculated, using the homeostasis model assessment (HOMA). An index of insulin secretion was derived as the ratio of incremental insulin at 30 min divided by 30 minute plasma glucose (delta I/G). RESULTS: Normoglycaemia was present in 164, impaired glucose tolerance (IGT) in 60 and diabetes in 36 subjects. Fasting and 2 h insulin secretion showed bell shaped curves with increasing plasma glucose. The peak values corresponded to the cut-off values used for the diagnosis of clinical diabetes. IR was higher in obese than in nonobese, nondiabetic subjects but the effect of obesity on IR was not found in subjects with diabetes. IGT was associated with higher IR, but not with evidence of a beta-cell defect. CONCLUSIONS: Evaluation of insulin resistance and beta-cell function in different stages of glucose tolerance indicate that insulin resistance is manifested in the early stage of glucose intolerance in South Indians, i.e. IGT. A beta-cell defect was mostly found in people with diabetes. The beta-cell defect is more common in diabetes among the nonobese.     

Effects of the new oral hypoglycaemic agent nateglinide on insulin secretion in Type 2 diabetes mellitus.

AIMS: The new non-sulphonylurea oral hypoglycaemic agent nateglinide has been shown to enhance insulin secretion in animals and in healthy human volunteers and thus offers a potential advance in the treatment of Type 2 diabetes mellitus. This study examined whether nateglinide can enhance insulin secretion, and particularly the first phase insulin response, in patients with Type 2 diabetes. METHODS: A double-blind, placebo-controlled trial, examining the effects of a single oral dose of 60 mg nateglinide, given 20 min prior to an intravenous glucose tolerance test (IGTT), on insulin secretion in 10 otherwise healthy Caucasian men with recently diagnosed Type 2 diabetes (duration since diagnosis 0-44 months). RESULTS: Insulin secretion (both overall and first phase) was significantly increased by nateglinide (P < 0.001), as were C-peptide (P < 0.001) and proinsulin (P < 0.001) secretion. Overall glucose concentrations following glucose challenge were lower after nateglinide than after placebo (P = 0.05). CONCLUSIONS: Nateglinide significantly increases insulin secretion in Type 2 diabetic patients, in particular restoring the first phase insulin response. Further study is necessary to determine the effects of chronic administration on insulin secretion and blood glucose concentration.     

Early and late C-peptide responses during oral glucose tolerance testing are oppositely predictive of type 1 diabetes in autoantibody-positive individuals

We examined whether the timing of the C-peptide response during an oral glucose tolerance test (OGTT) in relatives of patients with type 1 diabetes (T1D) is predictive of disease onset. We examined baseline 2-h OGTTs from 670 relatives participating in the Diabetes Prevention Trial-Type 1 (age: 13.8 ± 9.6 years; body mass index z-score: 0.3 ± 1.1; 56% male) using univariate regression models. T1D risk increased with lower early C-peptide responses (30–0 min) (χ² = 28.8, P < 0.001), and higher late C-peptide responses (120–60 min) (χ² = 23.3, P < 0.001). When both responses were included in a proportional hazards model, they remained independently and oppositely associated with T1D, with a stronger overall association for the combined model than either response alone (χ² = 41.1; P < 0.001). Using receiver operating characteristic curve analysis, the combined early and late C-peptide response was more accurately predictive of T1D than area under the curve C-peptide (P = 0.005). Our findings demonstrate that lower early and higher late C-peptide responses serve as indicators of increased T1D risk.     

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AimsThe clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.MethodsWe recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3–6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7–6.4%, 39–46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.ResultsEighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥165 mg/dL and a 30-min C-peptide <5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98–26.16) of developing diabetes than other prediabetic subjects.ConclusionsIn Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.     

Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population

Abstract. Rolandsson O, Hägg E, Nilsson M, Hallmans G, Mincheva‐Nilsson L, Lernmark Å (Umeå University, Sweden; and University of Washington, Seattle, WA, USA). Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population. J Intern Med 2001; 249: 279–288. Objective. Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA‐2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. Design. A population‐based follow‐up cohort study. Setting. Participants visited the primary health care centre in Lycksele, Sweden in 1988–92. Participants. A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow‐up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main outcome measurements. A clinically diagnosed diabetes at follow‐up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies. Results. At follow‐up, 42/2278 (1.8%, 95% CI 1.2–2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow‐up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3–18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8–12.6) in the fourth quartile of 2‐h plasma glucose (>7.5 mmol L^?1) and 7.2 (95% CI 4.8–11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L^?1). Conclusion. Islet cell autoantibodies did not predict diabetes at follow‐up. BMI measured at base line was as effective as 2‐h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.     

Decreased insulin action and insulin secretion predict the development of impaired glucose tolerance

Summary The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of impaired glucose tolerance (IGT) is controversial. Few prospective data are available on metabolic precursors of IGT. We examined the relation of fasting serum insulin level (as a marker of insulin resistance) and change in insulin/glucose ratio (ΔI ₃₀/ΔG₃₀) over the first 30 min after glucose ingestion (as a marker of insulin secretion) as predictors of the 7-year development of IGT in 839 Mexican Americans and non-Hispanic whites with normal glucose tolerance at baseline from the San Antonio Heart Study. IGT eventually developed in 148 subjects. When modelled separately, fasting serum insulin (odds ratio (OR)=2.60,95 % confidence interval (CI)=1.58,4.28,p<0.005), but not ΔI ₃₀/ΔG₃₀ (OR=0.80, 95 % CI=0.50,1.27,p=0.339) predicted the development of IGT. However, when both variables were included in the same logistic regression model, fasting serum insulin (OR=3.50, 95 % CI=1.97,6.21,p<0.001) and low ΔI ₃₀/ΔG₃₀ (OR=0.48, 95 % CI=0.28,0.82,p=0.008) both predicted IGT. These results were basically unchanged after further adjustment for obesity, body fat distribution and fasting plasma glucose level. We conclude that both decreased insulin secretion (as assessed by low ΔI ₃₀/ΔG₃₀) and increased insulin resistance (as assessed by fasting serum insulin) predict the development of IGT and are thus early precursors of non-insulin-dependent diabetes mellitus; further studies of insulin secretion should take into account the level of basal insulin resistance.     

Elevated glucose concentrations during an oral glucose tolerance test are associated with the presence of metabolic syndrome in childhood obesity

Aims To investigate whether changes in glucose concentrations during an OGTT in obese children reflect the presence of peripheral insulin resistance and/or cardiovascular risk factors more closely than single measurements of fasting plasma glucose (FPG). Methods One hundred and twenty‐two obese children attending our Paediatric Obesity Service underwent formal OGTTs, following the measurement of blood pressure and fasting levels of insulin, glucose and lipid profiles in the majority. Fasting insulin was used as a surrogate measure of insulin sensitivity. Three different child‐specific definitions for metabolic syndrome were used to identify clustering of cardiovascular risk factors in 65 of these children. Results In the whole group, 10.7% had IGT but changes in glucose during the OGTT were not influenced by age, sex, pubertal status or raw (or age‐ and sex‐adjusted) body mass index (BMI). During the OGTT, FPG, glucose at 60 min and area under the glucose curve correlated highly with fasting insulin. Children with metabolic syndrome (defined using any of three definitions) had comparable FPG levels to those without metabolic syndrome, but they demonstrated significantly elevated glucose levels at 60 min. On sub‐group analysis, obese children with normal carbohydrate metabolism were significantly more likely to have a 1 h glucose level ≥ 7.8 mmol/l if they had metabolic syndrome (P = 0.026). Conclusions These data suggest that an elevated 1 h post‐load glucose measurement is seen in obese children who have a coexistent clustering of cardiovascular risk factors.     

Height and glucose tolerance in adult subjects

Summary In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulindependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentration and age and body mass index were observed in both sexes and between 120-min plasma glucose and waist/hip ratio in male subjects. An unexpected negative correlation was found between 120-min plasma glucose and height in both sexes (r = – 0.23, (95% confidence interval, – 0.38– – 0.07) p<0.007 for male subjects and r = – 0.24, (– 0.37– – 0.11) p<0.006 for female subjects). These negative associations with height remained significant after controlling for age and body mass index in male subjects but not in female subjects. In the latter a highly significant negative relationship of height with age was recorded (r = – 0.33, (– 0.45– – 0.20) p<0.0001). Comparison between individuals with impaired glucose tolerance and control subjects matched for sex, age and body mass index showed that subjects with impaired glucose tolerance are significantly shorter. Mean (± SEM) height in the male subjects with impaired glucose tolerance (n = 29) was 173.4 ± 1.1 cm vs 176.9 ± 1.3 cm in control subjects, p = 0.02. In the female subjects(n = 39)mean(±SEM)height was 159.4±1.0 cm vs 162.4±1.0 cm in control subjects, p = 0.02. The negative relationship between height and glucose tolerance is a new epidemiological observation which has not been previously reported. One possible reason for this is that the most commonly used anthropometric index, body mass index, eliminates height as an independent analytical variable.     

Fasting proinsulin and 2-h post-load glucose levels predict the conversion to NIDDM in subjects with impaired glucose tolerance: The Hoorn Study

Summary The aims of the present study were to observe the natural history of impaired glucose tolerance and to identify predictors for development of non-insulin-dependent diabetes mellitus (NIDDM). A survey of glucose tolerance was conducted in subjects aged 50–74 years, randomly selected from the registry of the middle-sized town of Hoorn in the Netherlands. Based on the mean values of two oral glucose tolerance tests subjects were classified in categories of glucose tolerance according to the World Health Organization criteria. All subjects with impaired glucose tolerance (n=224) were invited to participate in the present study, in which 70% (n=158) were subsequently enrolled. During follow-up subjects underwent a repeated paired oral glucose tolerance test. The mean follow-up time was 24 months (range 12–36 months). The cumulative incidence of NIDDM was 28.5% (95% confidence interval 15–42%). Age, sex, and anthropometric and metabolic characteristics at baseline were analysed simultaneously as potential predictors of conversion to NIDDM using multiple logistic regression. The initial 2-h post-load plasma glucose levels and the fasting proinsulin levels were significantly (p<0.05) related to the incidence of NIDDM. Anthropometric characteristics, the 2-h post-load specific insulin levels and the fasting proinsulin/fasting insulin ratio were not related to the incidence of NIDDM. These results suggest that beta-cell dysfunction rather than insulin resistance plays the most important role in the future development of diabetes in a high-risk Caucasian population.Abbreviations IGT Impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - OGTT oral glucose tolerance test - CI confidence interval - W/H ratio waist/hip ratio - BMI body mass index - OR odds ratio     

Serum retinol-binding protein 4 is associated with insulin secretion in Chinese people with normal glucose tolerance

Background:  Serum levels of retinol‐binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on β‐cell function. Thus, the present study investigated the relationship between serum RBP4 and insulin secretion in Chinese people with and without T2DM. Methods:  A 75 g oral glucose tolerance test was administered to all 867 subjects and serum RBP4 concentrations were determined. Insulin secretion was assessed by ΔI/ΔG (increment in plasma insulin concentration/plasma glucose concentration 30 min after the oral administration of 75 g glucose) and the total area under the curve for insulin over 180 min (AUC‐I). Magnetic resonance imaging was used to measure visceral fat area (VFA) at L4–L5; subjects with VFA ≥80 cm² were considered to have visceral obesity (VO). Results:  Serum RBP4 concentrations were significantly higher in subjects with VO than without, regardless of the presence of T2DM. In addition, in the entire group with normal glucose tolerance (NGT), serum RBP4 was positively correlated with ΔI/ΔG (r = 0.152; P < 0.01) and AUC‐I (r = 0.218; P < 0.01) after adjustment for gender. The correlation between RBP4 and ΔI/ΔG (r = 0.162; P < 0.05) and AUC‐I (r = 0.195; P < 0.01) remained in NGT non‐VO subjects. No correlation was found between serum RBP4 and ΔI/ΔG or AUC‐I in T2DM patients. Stepwise multiple regression analysis showed that serum RBP4 is an independent factor that contributes to ΔI/ΔG (β = 0.176) and AUC‐I (β = 0.204) in NGT non‐VO subjects. Conclusions:  Serum RBP4 is correlated with glucose‐stimulated insulin secretion in NGT non‐VO subjects, but not in NGT VO subjects and T2DM patients.     

Post-partum reclassification of glucose tolerance in women previously diagnosed with gestational diabetes mellitus.

AIMS: To re-evaluate post-partum screening; fasting plasma glucose (FPG) vs. oral glucose tolerance test (OGTT) in Caucasian women with previous gestational diabetes mellitus (GDM). METHODS: Once breast-feeding had finished, an OGTT was performed in 120 women with previous GDM. They were classified according to World Health Organization (WHO) 1985 and American Diabetes Association (ADA) 1997 criteria. The kappa-statistic measure of agreement was used to compared both diagnostic categories. A receiver-operating characteristic (ROC) curve studied the FPG as a test to detect abnormal glucose tolerance. RESULTS: Identical diabetes prevalence (2%) but quite different intermediate categories (12% impaired glucose tolerance vs. 3% impaired fasting glucose) were observed with both criteria. The kappa-statistic (scaled from 0 to 1) was 0.38 (fair agreement), P = 0.000. The ROC curve area of the FPG was 0.65. CONCLUSIONS: FPG is an unsatisfactory method of evaluating the glucose tolerance of Caucasian women with previous GDM. OGTT may be a better test for such a purpose.     

Differences in height explain gender differences in the response to the oral glucose tolerance test— the AusDiab study

Aim To determine the extent of gender‐related differences in the prevalence of glucose intolerance for the Australian population and whether body size may explain such differences. Methods Cross‐sectional data were collected from a national cohort of 11 247 Australians aged ≥ 25 years. Glucose tolerance status was assessed according to both fasting plasma glucose (FPG) and 2‐h plasma glucose (2hPG) levels following a 75‐g oral glucose tolerance test (OGTT). Anthropometric and glycated haemoglobin measurements were also made. Results Undiagnosed diabetes and non‐diabetic glucose abnormalities were more prevalent among men than women when based only on the FPG results (diabetes: men 2.2%, women 1.6%, P = 0.02; impaired fasting glycaemia: men 12.3%, women 6.6%, P < 0.001). In contrast 16.0% of women and 13.0% of men had a 2hPG abnormality (either diabetes or impaired glucose tolerance, P = 0.14). Women had a mean FPG 0.3 mmol/l lower than men (P < 0.001), but 2hPG 0.3 mmol/l higher (P = 0.002) and FPG‐2hPG increment 0.5 mmol/l greater (P < 0.001). The gender difference in mean 2hPG and FPG‐2hPG increment disappeared following adjustment for height. For both genders, those in the shortest height quartile had 2hPG levels 0.5 mmol/l higher than the tallest quartile, but height showed almost no relationship with the FPG. Conclusions Men and women had different glycaemic profiles; women had higher mean 2hPG levels, despite lower fasting levels. It appeared that the higher 2hPG levels for women related to lesser height and may be a consequence of using a fixed glucose load in the OGTT, irrespective of body size.