Jeanette Kuhl

Characterisation of subjects with early abnormalities of glucose tolerance in the Stockholm Diabetes Prevention Programme: the impact of sex and type 2 diabetes heredity

Aims/hypothesisWe evaluated the impact of sex and type 2 diabetes heredity on the prevalence and pathogenesis of early abnormalities of glucose homeostasis in subjects participating in the Stockholm Diabetes Prevention Programme.MethodsA sample of 3,128 men and 4,821 women, of whom approximately half had a family history of type 2 diabetes (FHD) was categorised according to an OGTT: NGT, IFG, IGT, combined glucose intolerance and type 2 diabetes. The homeostasis model assessment was used to determine insulin sensitivity and beta cell function.ResultsPrevalence of early abnormalities of glucose metabolism was two to three times higher in subjects with FHD and two to three times higher in men compared to women. Both maternal and paternal heredity of type 2 diabetes were associated with an increased risk of having early abnormalities of glucose metabolism. However, in women with type 2 diabetes heredity on the father’s side seems to have less impact on an increased risk of having type 2 diabetes. Both waist circumference and systolic blood pressure were increased in subjects with abnormalities of glucose homeostasis, whereas insulin sensitivity and beta cell function were decreased. Subjects with IFG had more pronounced impairment of beta cell function and insulin sensitivity than subjects with IGT.Conclusion/interpretationAn FHD and male sex increased the prevalence of abnormalities of glucose homeostasis. Subjects with IFG had more pronounced defects of insulin secretion and action than subjects with IGT.

The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers

Background Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. Materials and Methods 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. Results Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. Conclusion Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.

Long-term prognosis in patients with type 1 and 2 diabetes mellitus after coronary artery bypass grafting.

BACKGROUND Patients with diabetes mellitus (DM) have an increased risk of adverse outcomes after coronary artery bypass grafting (CABG). Previous studies have reported prognosis in relation to treatment with or without insulin, and not to the type of diabetes. OBJECTIVES This study investigated long-term survival in patients with type 1 DM (T1DM) and type 2 DM (T2DM) following CABG. METHODS We included all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent primary isolated CABG in Sweden during 2003 through 2013. We identified patients with T1DM or T2DM in the Swedish National Diabetes Register. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause mortality in patients with T1DM or T2DM. RESULTS In total, 39,235 patients were included, of whom 725 (1.8%) had T1DM and 8,208 (21%) had T2DM. Patients with TDM1 were younger (59 vs. 67 years), had reduced kidney function (31% vs. 24%), and had peripheral vascular disease (21% vs. 11%) more often than patients with TDM2 or no diabetes. During a mean follow-up of 5.9±3.2 years (230,085 person-years), 6,765 (17%) patients died. Among patients with T1DM, 152 (21%) died, and among patients with T2DM, 1,549 (19%) died. Adjusted hazard ratio (95% confidence interval) for death in patients with T1DM and T2DM, compared with patients without diabetes, were 2.04 (1.72 to 2.42), and 1.11 (1.05 to 1.18), respectively. CONCLUSIONS Patients with T1DM had more than double the long-term risk of death after CABG compared with patients without diabetes. The long-term risk of death in patients with T2DM was only slightly increased.

Relationship between preoperative hemoglobin A1c levels and long-term mortality after coronary artery bypass grafting in patients with type 2 diabetes mellitus.

BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have an increased risk of coronary heart disease and death. We aimed to investigate the association between preoperative hemoglobin A1c (HbA1c) levels and long-term mortality after coronary artery bypass grafting (CABG) among patients with T2DM. METHODS All patients with T2DM who underwent CABG in Sweden from 2003 to 2013 were included from the SWEDEHEART register. Information about diabetes was retrieved from the Swedish National Diabetes Register. We used Cox regression to calculate hazard ratios (HR) with 95% confidence intervals (CI) for all-cause mortality and also a combination of death or a major cardiovascular event (MACE). RESULTS In total, 6313 patients were included. During a mean follow-up time of 5.5 (±3.8) years, (34,482 person-years), 1630 (26%) patients died. After multivariable adjustment, HbA1c was associated with an increased risk of death in patients with HbA1c levels 9.1-10%, and >10% (HR (95% CI): 1.26 (1.04-1.53), and 1.33 (1.05-1.69), respectively). There was an increased risk for death or MACE at HbA1c levels 8.1-9%, 9.1-10%, and >10% (HR (95% CI): 1.17 (1.04-1.33), 1.44 (1.22-1.70), and 1.50 (1.22-1.84), respectively). In patients with insulin-treatment there was no association between HbA1c levels and death. CONCLUSIONS In patients with T2DM who underwent CABG we found an increased risk of death at HbA1c levels above 9.0%, and also for the combination of death or MACE at HbA1c levels above 8.1%. There was no association between HbA1c levels and death in T2DM patients who were insulin-treated.