Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients.

AIM: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes. METHODS: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m2), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose (n = 25) or 1 mg t.i.d. glibenclamide (n = 27) or one t.i.d. placebo (n = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test. RESULTS: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0]. CONCLUSIONS: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.

Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level.

OBJECTIVE: To observe the relationship of fasting plasma glucose (FPG), postchallenge plasma glucose (PG) (30, 60, 90, and 120 min during an oral glucose tolerance test [OGTT], as well as maximal PG during an OGTT, postchallenge glucose spikes [PGS], and glucose under the OGTT curve), and HbA1c to intima-media thickness (IMT) as a marker of atherosclerosis. RESEARCH DESIGN AND METHODS: OGTT, ultrasound measurement of carotid IMT, and various atherosclerosis risk factors, such as family history of diabetes, obesity, and/or hyperlipoproteinemia, but without known diabetes, were analyzed in 582 individuals aged 40-70 years and at risk for type 2 diabetes. RESULTS: In univariate analysis, all examined glycemic parameters were significantly correlated to IMT. The 2-h postchallenge plasma glucose showed the strongest odds ratio (OR) of 1.88 (1.34-2.63) in relation to abnormal IMT. All PG variables, except for 30-min glucose in OGTT, showed a significant OR, whereas the OR for HbA1c and FPG was not significant. In logistic regression analysis, 2-h PG was identified as the strongest determinant of IMT from all glycemic parameters. The 2-h PG and PGS, but not FPG, were associated with a significant rise of IMT in tertiles of HbA1c. Glycemic parameters were strongly related to each other and to many atherosclerosis risk factors. In multivariate analysis including a variety of atherosclerosis risk factors, 2-h PG was a significant independent determinant of IMT. CONCLUSIONS: PG and PGS are more strongly associated with carotid IMT than FPG and HbA1c level and modify substantially the risk for atherosclerosis, estimated by HbA1c alone, in a cohort at risk for diabetes and in the early diabetes stage.

Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD Study. Risk Factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes.

AIMS: Only scarce information exists on the distribution and atherosclerosis risk in different types of hyperglycaemia at diabetes detection. This study aimed to analyse the occurrence of isolated fasting (IFH), isolated post-challenge (IPH) and combined hyperglycaemia (FH/PH) among subjects detected to have diabetes and the association of these types of hyperglycaemia with cardiovascular risk factors and carotid intima-media thickness (IMT). METHODS: A total of 785 middle-aged subjects of the Risk Factors in Impaired Glucose Tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study underwent a 75-g oral glucose tolerance test and examination of various atherosclerosis risk factors. IMT was measured by B-mode ultrasound. RESULTS: One hundred and nineteen (15.2%) asymptomatic diabetic subjects were detected: of these, 35.3% with IFH, 26% with IPH and 38.7% with FH/PH. The level of risk factors was higher in diabetic vs. non-diabetic subjects. HbA1c and cardiovascular risk factors were in the same range for IFH and IPH except for active plasminogen activator inhibitor (PAI)-1 which was significantly higher in IFH. A higher risk burden was found in the FH/PH group vs. both IFH and IPH. IMT was as follows: non-diabetic subjects 0.85 +/- 0.18 mm, IFH 0.91 +/- 0.20 mm, IPH 0.94 +/- 0.18 mm, FH/PH 0.98 +/- 0.17 mm (P < 0.05 vs. non-diabetes). 2 h post-challenge glucose (2hPG) correlated more closely (r = 0.23, P < 0.001) to IMT than fasting plasma glucose (FPG) (r = 0.14, P = 0.004). The importance of 2hPG was confirmed by the direct comparison of FPG and 2hPG in a three dimensional analysis. A significant increase of IMT was only observed in the subgroups with abnormal post-challenge hyperglycaemia for both combinations with normal FPG and IFG. FPG category did not significantly add to IMT in either group of post-challenge hyperglycaemia. Regression analysis in the whole sample revealed 2hPG but not FPG as a significant determinant of IMT. Further significant risk factors were age, male sex, total cholesterol, HDL-cholesterol and hypertension. CONCLUSIONS: The RIAD study population at high risk for Type 2 diabetes mellitus, post-challenge hyperglycaemia was found to relate more strongly than fasting hyperglycaemia with carotid IMT.

Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals.

Postprandial (pp) hyperglycemia--frequently associated with an increase in cardiovascular risk factors--may be damaging for the endothelium. So far, little information exists how glucose, insulin and lipids may affect atherosclerosis in the pp state. Therefore, we evaluated the relationship of pp hyperglycemia, insulin secretion and coronary risk factors to intima-media thickness (IMT) in a non-diabetic risk population. In 403 subjects (147 males, 256 females), aged 40-70 years, in the majority relatives of index cases with type 2 diabetes--a 75 g oral glucose tolerance test was performed together with measurement of insulin fractions, various risk factors and IMT of the common carotid artery. We found a continuous rise of 2h pp insulin fractions along the quintiles of 2h pp plasma glucose. A significant increase of body mass index, waist to hip ratio, triglycerides and decrease of HDL-cholesterol was observed in the top quintile of 2h pp plasma glucose (8.24 > or = pp plasma glucose < 11.1 mmol/l). Albuminuria was significantly enhanced in the 5th quintile. In parallel, IMT was significantly increased in the 5th quintile versus the bottom quintile of 2 h and maximal glucose (range 11.7-15.3 mmol/l) postprandially. After age and sex adjustment pp glucose and C-peptide, total cholesterol, triglycerides and HDL-cholesterol but not fasting plasma glucose were significantly correlated to IMT. In multivariate analysis age, male sex, pp plasma glucose, total and HDL-cholesterol were found to be independent risk factors for increased IMT. In conclusion, our data in a non-diabetic European risk population show that the two top quintiles of pp plasma glucose are associated with a clustering of standard risk factors. Corresponding to this clustering of risk factors IMT was significantly increased in the top quintile of 2 h and maximal pp plasma glucose. These data show that pp hyperglycemia may exert a noxious impact on the arterial wall together with a cluster of anomalies typical for the metabolic syndrome.

Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals.

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, pro-insulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia.