OBJECTIVE -To explain the stronger effect of type 2 diabetes on the risk of coronary heart disease (CHD) in women compared with men. RESEARCH DESIGN AND METHODS -The study population consisted of 1,296 nondiabetic subjects and 835 type 2 diabetic subjects aged 45-64 years without cardiovascular disease. The end points were CHD death and a major CHD event (CHD death or nonfatal myocardial infarction). The follow-up time was 13 years.RESULTS -Major CHD event rate per 1,000 person-years was 11.6 in nondiabetic men, 1.8 in nondiabetic women, 36.3 in diabetic men, and 31.6 in diabetic women. The diabetes-related hazard ratio for a major CHD event from the Cox model, adjusted for age and area of residence, was 2.9 (95% CI 2.2-3.9) in men and 14.4 (8.4 -24.5) in women, and after further adjustment for cardiovascular risk factors, 2.8 (2.0 -3.7) and 9.5 (5.5-16.9), respectively. The burden of conventional risk factors in the presence of diabetes was greater in women than in men at baseline. Prospectively, elevated blood pressure, low HDL cholesterol, and high triglycerides contributed to diabetes-related CHD risk more in women than in men. However, after adjusting for conventional risk factors, a substantial proportion of diabetes-related CHD risk remained unexplained in both genders.CONCLUSIONS -The stronger effect of type 2 diabetes on the risk of CHD in women compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in diabetic women. Diabetes Care 27:2898 -2904, 2004T ype 2 diabetes increases the risk of coronary heart disease (CHD) more markedly in women than in men. However, the reported magnitudes of the diabetes-related CHD risk in men and women vary widely between different studies (1-5). The greater relative risk of CHD in diabetic women still remains incompletely understood, but several explanations can be offered. First, adverse changes induced by type 2 diabetes in some cardiovascular risk factors, such as HDL cholesterol, triglycerides, LDL particle size, and blood pressure, have been found to be more pronounced in women than in men (6 -8). Second, it is possible that gender may alter the effect of some cardiovascular risk factors for CHD in diabetic subjects, leading to a stronger risk effect in women. Third, diabetes in women may interfere more with protective mechanisms in the vascular wall and thereby lead to enhanced atherogenesis and/or thrombogenesis (9).In the present study, based on 13 years of follow-up of 1,296 nondiabetic and 835 type 2 diabetic subjects, we evaluated possible explanations for the stronger effect of type 2 diabetes on the risk of CHD in women than in men.RESEARCH DESIGN AND METHODS -Altogether, 1,059 subjects (581 men and 478 women) with type 2 diabetes aged 45-64 years and born and living in the Turku University Hospital district in West Finland and in the Kuopio University Hospital district in East Finland were identified through a national drug reimbursement register. A random sample of nondiab...

OBJECTIVE -The purpose of this study was to investigate the hypothesis that coronary heart disease (CHD) mortality in diabetic subjects without prior evidence of CHD is equal to that in nondiabetic subjects with prior myocardial infarction or any prior evidence of CHD.RESEARCH DESIGN AND METHODS -During an 18-year follow-up total, cardiovascular disease (CVD) and CHD deaths were registered in a Finnish population-based study of 1,373 nondiabetic and 1,059 diabetic subjects.RESULTS -Adjusted multivariate Cox hazard models indicated that diabetic subjects without prior myocardial infarction, compared with nondiabetic subjects with prior myocardial infarction, had a hazard ratio (HR) of 0.9 (95% CI 0.6 -1.5) for the risk of CHD death. The corresponding HR was 0.9 (0.5-1.4) in men and 1.9 (0.6 -6.1) in women. Diabetic subjects without any prior evidence of CHD (myocardial infarction or ischemic electrocardiogram [ECG] changes or angina pectoris), compared with nondiabetic subjects with prior evidence of CHD, had an HR of 1.9 (1.4 -2.6) for CHD death (men 1.5 [1.0 -2.2]; women 3.5 [1.8 -6.8]). The results for CVD and total mortality were quite similar to those for CHD mortality.CONCLUSIONS -Diabetes without prior myocardial infarction and prior myocardial infarction without diabetes indicate similar risk for CHD death in men and women. However, diabetes without any prior evidence of CHD (myocardial infarction or angina pectoris or ischemic ECG changes) indicates a higher risk than prior evidence of CHD in nondiabetic subjects, especially in women. Diabetes Care 28:2901-2907, 2005T ype 2 diabetes increases the risk of coronary heart disease (CHD) events at least by two-to threefold in type 2 diabetic subjects compared with nondiabetic subjects (1). In type 2 diabetic women the relative risk is even greater (2). The reasons for this increased risk are largely unknown but could be related at least in part to more adverse changes in cardiovascular risk factors among diabetic women compared with diabetic men. Although the incidence of CHD events in nondiabetic subjects has considerably decreased during the last decades, this is not true for type 2 diabetic patients, particularly for women (3).We previously reported that type 2 diabetic patients without a history of prior myocardial infarction have the same risk of CHD death as nondiabetic subjects with a history of prior myocardial infarction (4). This observation has led to the conclusion that type 2 diabetes is a CHD equivalent and has had a profound effect, particularly on the recommendations for treatment of dyslipidemia (5).During recent years other studies have investigated the same question in different populations and study settings. Contradictory results have been obtained, with some studies confirming our original findings (6 -10) and some studies reporting opposite results, especially among men (11-18). The conclusion of these studies is that type 2 diabetes might be a CHD equivalent, but only among women.Our original study population included 1,059 patients ...

OBJECTIVE -To investigate the association of retinopathy with the risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in type 2 diabetic subjects in a population-based 18-year follow-up study with particular emphasis on sex differences.RESEARCH DESIGN AND METHODS -Our study cohort comprised 425 Finnish type 2 diabetic men and 399 type 2 diabetic women who were free of CVD at baseline. The findings were classified based on standardized clinical ophthalmoscopy to categories of no retinopathy, background retinopathy, and proliferative retinopathy. The study end points were all-cause, CVD, and CHD mortality.RESULTS -Adjusted Cox model hazard ratios (95% CIs) of all-cause, CVD, and CHD mortality in men were 1.34 (0.98 -1.83), 1.30 (0.86 -1.96), and 1.18 (0.74 -1.89), respectively, for background retinopathy and 3.05 (1.70 -5.45), 3.32 (1.61-6.78), and 2.54 (1.07-6.04), respectively, for proliferative retinopathy and in women 1.61 (1.17-2.22), 1.71 (1.17-2.51), and 1.79 (1.13-2.85), respectively, for background retinopathy and 2.92 (1.41-6.06), 3.17 (1.38 -7.30), and 4.98 (2.06 -12.06), respectively, for proliferative retinopathy.CONCLUSIONS -Proliferative retinopathy in both sexes and background retinopathy in women predicted all-cause, CVD, and CHD death. These associations were independent of current smoking, hypertension, total cholesterol, HDL cholesterol, glycemic control of diabetes, duration of diabetes, and proteinuria. This suggests the presence of common background pathways for diabetic microvascular and macrovascular disease other than those included in the conventional risk assessment of CVD. The sex difference observed in the association of background retinopathy with macrovascular disease warrants closer examination. Diabetes Care 30:292-299, 2007H yperglycemia is the major determinant of the risk of microvascular complications of diabetes (1), whereas the evidence that hyperglycemia is a major risk factor for macrovascular complications of this disease is more limited (2,3). Population-based studies have shown that microvascular complications predict cardiovascular disease (CVD) mortality not only in type 1 (3,4) and type 2 (5-10) diabetic subjects but even in nondiabetic subjects (10) and in general population samples, controlling for the effect of glucose status (11)(12)(13)(14). These observations suggest similar underlying pathogenic processes in microvascular complications and in atherosclerotic CVD in diabetes.It has been suggested that microvascular processes might be especially important in the development of coronary heart disease (CHD) in women (11,13). However, epidemiological data are largely missing with respect to possible sex differences in the association of diabetic retinopathy with CVD. We have performed an 18-year follow-up study of 824 Finnish subjects with type 2 diabetes (425 men and 399 women) who were free of CVD at baseline to evaluate the predictive value of retinopathy for all-cause, CVD, and CHD mortality by sex. RESEARCH DESIGN ANDMET...

Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p=0.002) and CVD mortality (p=0.021) in women, but not in men. Serum levels of AGEs in the highest sexspecific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14-1.99; p=0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p=0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p=0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation

OBJECTIVE -To compare the risk of cardiovascular disease (CVD) death and the impact of hyperglycemia on the risk of CVD mortality associated with type 1 diabetes to that associated with type 2 diabetes.RESEARCH DESIGN AND METHODS -The study comprised 173 participants with type 1 diabetes, 834 participants with type 2 diabetes, and 1,294 nondiabetic participants, aged 45-64 years at baseline and free of CVD. The age of onset of diabetes was Ͼ30 years in both diabetic groups.RESULTS -During an 18-year follow-up, 86 participants with type 1 diabetes, 567 participants with type 2 diabetes, and 252 nondiabetic participants died. CVD mortality rates per 1,000 person-years were 23.1 (95% CI 16.9 -31.9) in type 1 diabetic, 35.3 (30.8 -40.4) in type 2 diabetic, and 4.6 (3.8 -5.7) in nondiabetic participants. Adjusted hazard ratios for CVD mortality in participants with type 1 diabetes versus no diabetes was 3.6 (95% CI 2.2-5.7) in men and 13.3 (6.9 -22.5) in women and in participants with type 2 diabetes versus no diabetes 3.3 (2.5-4.5) in men and 10.1 (6.7-17.4) in women. An increment of 1 unit (%) of GHb increased CVD mortality by 52.5% (95% CI 28.4 -81.3) in type 1 diabetic subjects and by 7.5% (4.3-10.8) in type 2 diabetic participants.CONCLUSIONS -The impact of type 1 and type 2 diabetes on CVD mortality was similar. The effect of increasing hyperglycemia on the risk of CVD mortality was more profound in type 1 than in type 2 diabetic subjects.

Background-Advanced glycation end products (AGEs), modification products of glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes as well as in nondiabetic subjects.

The risk of death due to infectious causes after kidney transplantation in Finland dropped by one half since the 1990s. Common bacterial infections remained the most frequent cause of infection-related mortality, whereas opportunistic viral, fungal, or unconventional bacterial infections rarely caused deaths after kidney transplantation.

Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4CXCR5 follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D. We demonstrate that the frequency of CXCR5PD-1ICOS-activated circulating Tfh cells is increased both in children with newly diagnosed T1D and in autoantibody-positive at-risk children with impaired glucose tolerance. Interestingly, this increase was only evident in children positive for two or more biochemical autoantibodies. No alterations in the circulating B-cell compartment were observed in children with either prediabetes or diabetes. Our results demonstrate that Tfh activation is detectable in the peripheral blood close to the presentation of clinical T1D but only in a subgroup of children identifiable by positivity for multiple autoantibodies. These findings suggest a role for Tfh cells in the pathogenesis of human T1D and carry important implications for targeting Tfh cells and/or B cells therapeutically.