Insulin resistance and ß-cell function in smokers: results from the EGIR-RISC European multicentre study.

AIMS: Tobacco smoking is known to increase the long-term risk of developing Type 2 diabetes mellitus, but the mechanisms involved are poorly understood. This observational, cross-sectional study aims to compare measures of insulin sensitivity and ß-cell function in current, ex- and never-smokers. METHODS: The study population included 1246 people without diabetes (mean age 44 years, 55% women) from the EGIR-RISC population, a large European multicentre cohort. Insulin sensitivity was measured using a hyperinsulinaemic, euglycaemic clamp and the homeostatic model assessment - insulin resistance (HOMA-IR) index. Two ß-cell function parameters were derived from measures during an oral glucose tolerance test: the early insulin response index and ß-cell glucose sensitivity. Additionally, the areas under the curve during the oral glucose tolerance test were calculated for glucose, insulin and C-peptide. RESULTS: According to smoking habits, there were differences in insulin sensitivity, which was lower in women who smoked, and in ß-cell glucose sensitivity, which was lower in men who smoked, but these associations lost significance after adjustment. However, after adjustment, the areas under the glucose and the C-peptide curves during the oral glucose tolerance test were significantly higher in men who smoked. CONCLUSIONS: Smoking habits were not independently associated with insulin sensitivity or ß-cell function in a healthy middle-aged European population. Health-selection bias, methodological shortcomings or a true lack of causal links between smoking and impaired insulin sensitivity/secretion are possible explanations. The mechanisms behind the observed increased glucose and C-peptide areas under the curve during the oral glucose tolerance test in male smokers need to be further evaluated.

Associations between sleep duration and sleep debt with insulin sensitivity and insulin secretion in the EGIR-RISC Study.

AIM: Extremes in sleep duration play an important role in the development of type 2 diabetes. We examined the associations between sleep duration and sleep debt with estimates of insulin sensitivity and insulin secretion. METHODS: Data were derived from the European multi-centre EGIR-RISC study. Sleep duration and sleep debt were derived from a sleep questionnaire asking about sleeping time during the week and during the weekend. Insulin sensitivity and insulin secretion were estimated from a 2-hour Oral Glucose Tolerance Test, with samples every 30 minutes. Associations between sleep duration and sleep debt with insulin sensitivity and insulin secretion, were analysed by multiple linear regression models corrected for possible confounders. RESULTS: Sleep data were available in 1002 participants, 46% men, mean age 48 ± 8 years, who had an average sleep duration of 7 ± 1 hours [range 3-14] and an average sleep debt (absolute difference hours sleep weekend days minus weekdays) of 1 ± 1 hour [range 0-8]. With regard to insulin sensitivity, we observed an inverted U-shaped association between sleep duration and the Stumvoll MCR in (mL/kg/min), with a corrected ß (95% CI) of 2.05 (0.8; 3.3) and for the quadratic term -0.2 (-0.3; -0.1). Similarly, a U-shaped association between sleep duration and log HOMA-IR in (µU/mL), with a corrected ßs of -0.83 (-1.4; -0.24) and 0.06 (0.02; 0.10) for the quadratic term. Confounders showed an attenuating effect on the associations, while BMI mediated 60 to 91% of the association between sleep duration and insulin sensitivity. No significant associations were observed between sleep duration with insulin secretion or between sleep debt with either insulin sensitivity or insulin secretion. CONCLUSIONS: Short and long sleep duration are associated with a lower insulin sensitivity, suggesting that sleep plays an important role in insulin resistance and may provide the link with development of type 2 diabetes.

Predictive markers of abdominal aortic stiffness measured by echo-tracking in subjects with varying insulin sensitivity.

Arterial stiffness is influenced by advancing age and vascular disease and is an independent risk factor for cardiovascular events and death. Using ultrasound measurements, arterial stiffness in a specific arterial segment can be assessed. The aim of this observational study was to explore the prospective and cross-sectional associations between arterial stiffness measured by ultrasound locally in the abdominal aorta and cardiovascular risk factors/markers including insulin resistance measured by the homeostatic model assessment-insulin resistance (HOMA-IR), lipids and abdominal obesity. This study includes 335 subjects from Malmö, Sweden, examined in 1991-1994 and again at follow-up in 1998-2000 (mean age 64 years, 42% men). Ultrasound measurement of the abdominal aorta was performed at follow-up investigation. In the female subgroup, there was a positive association between HOMA-IR at baseline and abdominal aortic stiffness at follow-up (ß = 0.18, P = 0.03) and a negative association between high-density lipoprotein and aortic stiffness (ß = -0.23, P = 0.005), independently of classical cardiovascular risk factors. These associations were not found among men. The results suggest a greater or different role of impaired glucose metabolism in the pathophysiology of arterial stiffness in women than in men.

Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study.

AIMS/HYPOTHESIS: This study analysed cause-specific mortality in Type II (non-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin. METHODS: Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood glucose at inclusion. RESULTS: We included 169 patients taking sulphonylurea and metformin in combination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortality was 1.63 (95% confidence interval 1.27-2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95% confidence interval 1.17-2.55) and 2.33 (95% confidence interval 1.17-4.63), respectively. CONCLUSION/INTERPRETATION: There was a higher cardiovascular mortality in Type II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro- or macrovascular disease than sulphonylurea or metformin alone.

Differences in pharmacotherapy and in glucose control of type 2 diabetes patients in two neighbouring towns: a longitudinal population-based study.

AIM: To compare prescribing, dosage and blood glucose levels in patients with type 2 diabetes in two communities with differences in anti-hyperglycaemic drug utilization. METHODS: A retrospective longitudinal (1984-1994) population-based study in two neighbour towns in southern Sweden. The mean prescribed daily dose was expressed as a fraction of the Defined Daily Dose (DDD) for each drug. RESULTS: In town A, prescribing of oral agents and insulin was predominantly made by one specialized diabetes clinician, while in town B it was spread among several different general practitioners and one specialist. Altogether 44 636 medical visits by 2348 patients were identified. In each town, about 40% of the patients were treated without anti-hyperglycaemic drugs, about 40% with oral agents and about 20% with insulin. However, there were pronounced between-town differences in dosage and glucose control. The mean prescribed daily dose of sulphonylurea monotherapy decreased gradually from approximately 0.7 to approximately 0.5 DDD in town B but remained approximately 0.8 DDD in town A. The proportion of patients on both sulphonylurea and metformin increased substantially in town A but not in town B. In these patients, the mean prescribed daily dose of sulphonylurea exceeded 1.0 DDD in both towns, although it decreased with time in town B. The mean prescribed daily dose of insulin increased from 1.05 to 1.2 DDD in town A but remained virtually unchanged at 0.95 DDD in town B. The mean fasting blood glucose was lower in town A than in town B both overall (7.7 vs. 8.8 mmol/l), in those treated without any anti-hyperglycaemic drugs (7.2 vs. 8.1 mmol/l), in those on sulphonylurea monotherapy (8.3 vs. 9.7 mmol/l) and in those treated with insulin (8.1 vs. 10.2 mmol/l). CONCLUSIONS: Glucose control in routine care was better when most patients were treated by a diabetes specialist and were exposed to more intense pharmacotherapy.