Haemoglobin A1c measurement for diabetes among subjects with a previous history of impaired glucose tolerance

Haemoglobin A_1c (HbA_1c) measurement for diagnosis of diabetes and impaired glucose tolerance (IGT) was assessed during a prospective study of subjects with IGT; 183 of the 207 IGT persons underwent the second oral glucose tolerance tests (OGTT) 2.1 years, on the average, after the first tests. HbA_1c was administered to every participant before the second OGTTs. The results of HbA_1c were compared with those of the second OGTTs. The sensitivity of HbA_1c test was 71% for diabetes and 41% for IGT, when the specificity was 93% at a cutoff point of 4.81%. The conclusion is that the HbA_1c test is moderately sensitive for diabetes but insensitive for IGT, when it is specific. However, it may be useful for selecting and reducing the total number of subjects referred to 2-h OGTTs in a follow-up study of subjects with IGT, if the rate of progression to diabetes is not high.     

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.     

Platelet activation in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT), a prediabetic state, is associated with an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk factor for atherothrombosis. This study was designed to answer the following questions: (i) Do MPV levels change in IGT? (ii) Is there any relation between MPV levels and 2 h plasma glucose levels after 75 g oral glucose tolerance test. We selected 48 subjects with IGT, and 48 healthy subjects with normal glucose tolerance matched for age, gender, and body mass index. MPV was significantly higher in IGT group than in control group (9.06 ± 1.5 fl vs. 8.28 ± 0.8 fl, p = 0.002). Also, MPV was positively correlated with 2 h plasma glucose concentration in IGT group (r = 0.39, p = 0.006). In conclusion, our results suggest that subjects with IGT tend to have increased platelet activation. Increased platelet activity could contribute to increasing the risk of cardiovascular disease in IGT.     

Lessons learned from the 1‐hour post‐load glucose level during OGTT: Current screening recommendations for dysglycaemia should be revised

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1‐hour post‐load glucose level during the 75‐g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1‐hour post‐load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β‐cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA_1c or 2‐hour post‐load glucose values. An elevated 1‐hour post‐load glucose level was a better predictor of type 2 diabetes than isolated 2‐hour post‐load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1‐hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2‐hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1‐hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1‐hour post‐load level. Measurement of the 1‐hour PG level would increase the likelihood of identifying a larger, high‐risk group with the additional practical advantage of potentially replacing the conventional 2‐hour oral glucose tolerance test making it more acceptable in a clinical setting.     

Relationship between HbA1c and indices of glucose tolerance derived from a standardized meal test in newly diagnosed treatment naive subjects with Type 2 diabetes.

AIMS: To determine the relationship between HbA1c and other indices of glycaemic status derived during a standardized meal tolerance test (MTT) in newly diagnosed treatment-naive subjects with Type 2 diabetes (T2DM). METHODS: T2DM subjects (n = 262) consumed a standard MTT in the morning after a 10-h overnight fast. Frequent samples for plasma glucose (PG) were collected over the 4-h test period. The relationship between HbA1c and other glycaemic indices derived from the MTT were explored. The postprandial glucose exposure was calculated as the area under the incremental plasma glucose curve above the fasting level for the test period (AUC1). Excess hyperglycaemia was calculated as the AUC0-4 h above the arbitrary PG concentrations of 6.0 mmol/l (AUC2) and 5.5 mmol/l (AUC3), respectively [upper limit of fasting normoglycaemia according to World Health Organization (WHO) and American Diabetes Association (ADA), respectively]. Fasting hyperglycaemia was also estimated, being the difference between each of the above and the postprandial excursion. The participants were divided into three subgroups according to HbA1c (Group 1, 9.0%) and the relative contribution calculated of the postprandial glucose and fasting hyperglycaemia to the excess hyperglycaemia above the designated international thresholds for fasting plasma glucose. RESULTS: HbA1c was more strongly correlated with the fasting plasma glucose (r = 0.85, P < 0.001) than the overall postprandial glucose exposure (r = 0.539, P = 0.003). The contribution of fasting hyperglycaemia to excess hyperglycaemia using the WHO criteria for normal fasting plasma glucose for the three groups (Groups 1, 2 and 3) was 50.4%, 54.3% and 69.8%, respectively, and 57.8%, 58.8% and 71.4% using the ADA criteria. CONCLUSIONS: The contribution of fasting hyperglycaemia to excess hyperglycaemia increases as glycaemic control deteriorates, becoming dominant with an HbA1c in excess of 7.0%. These findings indicate which therapeutic approach needs to be adopted based on the HbA1c of the person with T2DM.     

Haemostatic effects of simvastatin in subjects with impaired glucose tolerance

Background: Very little is known about extra‐lipid effects of statins in prediabetic subjects. Aim: Our study has assessed the effect of simvastatin on coagulation and fibrinolysis in patients with impaired glucose tolerance (IGT), comparing this effect with that exhibited by simvastatin in isolated hypercholesterolaemia. Methods: Lipid profile, fasting and 2‐h post‐glucose challenge plasma glucose levels, the homeostatic model assessment (HOMA) ratio, glycated haemoglobin, the prothrombin and partial thromboplastin time, plasma fibrinogen, plasminogen activator inhibitor‐1 (PAI‐1), von Willebrand factor (vWF), factor X levels and factor VII coagulant activity were assessed at baseline, and after 30 and 90 days of simvastatin treatment (20 mg daily) in 28 patients with IGT and 28 subjects with primary isolated hypercholesterolaemia. The control group included 26 age‐, sex‐ and weight‐matched dyslipidaemia‐free individuals with normal glucose tolerance. The experiments comply with the current law of Poland. Results: Compared to the control subjects, hypercholesterolaemic and IGT patients exhibited increased baseline plasma levels of fibrinogen, PAI‐1 and vWF, and increased factor VII activity, with no difference between the two groups of patients. All these haemostatic abnormalities were alleviated or normalized after simvastatin treatment, which was accompanied by a prolongation of the prothrombin and partial thromboplastin time. In both treatment groups simvastatin reduced total and low‐density lipoprotein (LDL)‐cholesterol, oxidized LDL and apoprotein B but did not affect glucose metabolism marker levels. Conclusions: Our study shows that haemostasis is disturbed to a similar degree in IGT and isolated hypercholesterolaemia. Simvastatin exhibits a multidirectional, lipid‐independent favourable action on coagulation and fibrinolysis in IGT patients, which may play a role in the prevention of initiation and progression of atherosclerosis in this prediabetic state.     

Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance1

Aims We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. Methods The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan–Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social–psychological factors. Results Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow‐up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1–6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white‐collar worker (HR = 0.34, P = 0.033), non‐smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). Conclusions In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white‐collar worker, a non‐smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT.     

HbA1c对中老年人糖尿病及糖调节受损诊断价值的探讨

目的 探讨HbA1c诊断中老年人糖尿病、糖调节受损的最佳切点.方法 采用整群随机抽样方法选取贵阳市云岩区40岁及以上,且居住5年以上的中老年人共8 803名.所有研究对象进行口服葡萄糖耐量试验(OG'TT)及检测HbA1c等指标.对HbA1c诊断糖尿病、糖调节受损的切点进行分析;按年龄分层分析HbA1c诊断糖尿病在不同年龄段的切点.结果 HbA1c诊断新发现糖尿病的切点为6.4％的特异性较高(86.8％),相应的敏感性为68.0％.HbA1c诊断糖调节受损的受试者工作曲线下面积偏低(0.558).40 ～49岁年龄组HbA1c诊断糖尿病的切点值最低,为6.1％;而70～岁年龄组HbA1c诊断糖尿病切点值最高,为6.6％.结论 中老年人群中HbA1c 6.4％为诊断糖尿病的最佳切点,HbA1 c不适合作为诊断糖调节受损的指标.     

Detection of impaired glucose tolerance and undiagnosed type 2 diabetes in UK South Asians: an effective screening strategy

Aim:  We tested a stepwise, community-based screening strategy for glucose intolerance in South Asians using a health questionnaire in conjunction with body mass index (BMI). Anthropometric measurements (waist and hip circumference, sagittal diameter and percentage body fat) were then conducted in a hospital setting followed by an oral glucose tolerance test (OGTT) to identify subjects at the highest risk and analyse the factors predicting that risk.
Methods:  A health questionnaire was administered to 435 subjects in a community setting and BMI was measured. Subjects were graded by a risk score based on the health questionnaire as high, medium and low. Subjects with high and medium risk scores and a representative sample of those with low scores had anthropometric measurements in hospital followed by an OGTT. In total, 205 (47%) of the subjects had an OGTT performed.
Results:  In total, 48.7% of the subjects tested with an OGTT had evidence of glucose dysregulation: 20% had diabetes and 28.7% had impaired glucose tolerance (IGT). Logistic regression model explained 49.1% of the total variability. The significant predictors of diabetes and IGT were Blood Glucose Monitoring Strips (BMI), random blood glucose (BM), sibling with diabetes and presence of diagnosed hypertension or ischaemic disease. Most of these predictors along with other heredity diabetes factors create a composite score, with high predictability, as the receiver operating curve analysis shows.
Conclusion:  We describe a simple, stepwise strategy in a community setting, based on a health questionnaire and anthropometric measurements, to explain about 50% of cases with IGT and diabetes and diagnose about 50% of cases from the population screened. We have also identified factors that predict the risk.     

Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.

AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.     

Gender differences in the prevalence of impaired fasting glycaemia and impaired glucose tolerance in Mauritius. Does sex matter?

OBJECTIVE: To examine gender differences in the characteristics and prevalence of various categories of glucose tolerance in a population study in Mauritius. RESEARCH DESIGN AND METHODS: In 1998, a community-based cross-sectional survey was conducted in Mauritius. Categories of glucose metabolism were determined in 5388 adults, with an oral glucose tolerance test given to those who did not have previously diagnosed diabetes (n=4036). Other cardiovascular risk factors were assessed among those without known diabetes. RESULTS: For men and women the prevalence of diabetes (22.0 vs. 21.8%, respectively) and the prevalence of coexisting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (3.2 vs. 2.9%) were similar. However, men were twice as likely as women to have isolated IFG [5.1% (4.2-6.0) vs. 2.9% (2.3-3.5)], despite being younger, thinner and with lower plasma insulin but higher lipids. Conversely, the prevalence of isolated IGT was lower in men [9.0% (7.9-10.2) vs. 13.9% (12.6-15.1)]. Among non-diabetic individuals, fasting glucose was higher in men than women, whereas 2-h glucose was higher in women. In people without diabetes, women had significantly higher body mass index, beta cell function (HOMA-B), fasting and 2-h insulin than men and significantly lower waist-hip ratios, waist circumference, insulin sensitivity (HOMA-S) and triglycerides. CONCLUSION: In Mauritius, the distribution of impaired glucose metabolism differs by sex. The observation that IFG is more prevalent in men and IGT more prevalent in women raises important questions about their underlying aetiology and the ability of the current glucose thresholds to equally identify men and women at high-risk of developing diabetes. IFG should be seen as a complimentary category of abnormal glucose tolerance, rather than a replacement for IGT.     

Impaired glucose tolerance in first‐episode drug‐naïve patients with schizophrenia

Aims To determine whether there is an association between Type 2 diabetes mellitus and schizophrenia, independent of medication. Methods In this cross‐sectional study we performed an oral glucose tolerance test on 38 non‐obese white Caucasians who fulfilled the criteria for first‐episode drug‐naïve schizophrenia, 38 control subjects (matched for age, gender, smoking status, alcohol intake and ethnicity) and 44 first‐degree relatives of the patients. Results The frequency of impaired glucose tolerance (IGT), defined by World Health Organization criteria, was 10.5% (n = 4) in patients with schizophrenia, 18.2% (n = 8) in unaffected relatives and 0.0% in healthy control subjects (χ² = 4.22, d.f. = 2, P < 0.05). Conclusions The high point prevalence of IGT in never‐treated patients and relatives supports either shared environmental or genetic predisposition to IGT. Both patients and their relatives present an ideal cost‐effective opportunity to screen for Type 2 diabetes mellitus, as they are both easily identifiable.     

A simple way to estimate mean plasma glucose and to identify Type 2 diabetic subjects with poor glycaemic control when a standardized HbA1c assay is .

AIMS: To evaluate the relationship between HbA(1c) and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels, and to estimate the mean plasma glucose (mPG) derived from FPG and PPG that would predict Type 2 diabetic subjects with poor glycaemic control. METHODS: FPG, PPG and HbA(1c) values from 565 Type 2 diabetic patients (247 men and 318 women) were recorded. Linear regression analysis and Pearson's correlation was used to determine the relationship between HbA(1c), FPG and PPG. FPG and PPG were included as explanatory variables of HbA(1c) in linear regression analysis. RESULTS: The American Diabetes Association's objective of achieving an HbA(1c) level < 7.0% was obtained in 26.2% of the patients. The coefficients of FPG and PPG which determined HbA(1c) were similar. Therefore, mPG was calculated using the equation (FPG + PPG)/2. Pearson's correlation coefficient for HbA(1c) and FPG, PPG and mPG were 0.723 (P < 0.0001), 0.734 and 0.761 (P < 0.0001), respectively. A mPG cut-off value of 10 mmol/l predicted an HbA(1c) > 7% in the whole population, with a sensitivity of 84.2% and specificity of 80.4%. The area was high (0.90) in receiver-operating characteristic (ROC) curve analysis performed to examine the performance of mPG to predict HbA(1c) > 7%. CONCLUSIONS: The mPG derived from FPG and PPG correlates strongly with HbA(1c). We therefore suggest that using a cut-off of 10 mmol/l for mPG may be appropriate in diabetes management in the primary-care setting, where most management of Type 2 diabetes occurs.