Abnormal glucose regulation and gender-specific risk of fatal coronary artery disease in the HUNT 1 study.

OBJECTIVES: To assess fatal coronary artery disease (CAD) by gender and glucose regulation status. DESIGN: 47,951 people were followed up according to fatal CAD identified in the National Cause of Death Registry. Gender-effects of fatal CAD in people with impaired glucose regulation (IGR), newly diagnosed diabetes (NDM) or known diabetes (KDM) compared with people with normal glucose regulation (NGR) were calculated using Cox regression. RESULTS: Using NGR as reference, the hazard ratios (HR, 95% confidence intervals) associated with IGR was 1.2 (0.8-1.9) for women and 1.2 (0.9-1.6) for men. The corresponding HRs were 1.6 (1.2-2.2) and 1.4 (1.1.-1.9) for NDM, and 2.5 (2.1-2.8) and 1.8 (1.6-2.1) for KDM. The gender-difference in mortality varied by category (P(interaction) = 0.003). Using women as the reference, the HRs for men were 2.1 (2.0-2.3) for NGR, 1.8 (1.0-3.3) for IGR, 1.6 (1.0-2.5) for NDM, and 1.2 (1.0-1.5) for KDM. CONCLUSIONS: Diabetes mellitus, but not IGR, was associated with fatal CAD in both genders. The known gender-difference in CAD mortality was attenuated in people with abnormal glucose regulation, evident already in people with IGR.

Glycaemic control in newly diagnosed diabetes patients and mortality from ischaemic heart disease: 20-year follow-up of the HUNT Study in Norway.

AIMS: To assess the influence of glycaemic control on long-term mortality from ischaemic heart disease (IHD) in patients with newly diagnosed diabetes. METHODS AND RESULTS: In a large population study in Norway, people > or =40 years with non-fasting glucose > or =8 mmol/L were invited to a fasting glucose test, and if the fasting value was <7 mmol/L, an oral glucose tolerance test was also performed. Among people who were diagnosed with diabetes, 205 patients were followed with annual measurements of HbA1c in order to monitor glycaemic control. Stratified Cox regression analysis was used to compare IHD mortality rates during 20 years of follow-up, with comparison of newly diagnosed diabetes patients and a matched group of 205 individuals without diabetes. Among patients, we also assessed the relation of HbA1c with IHD mortality. After adjustment for potentially confounding factors, IHD mortality in the total diabetes group was substantially higher (HR 1.8, 95% CI, 1.0-3.4) compared with the comparison group. However, the increased risk was particularly high in patients with HbA1c in the highest quartile (HR 4.2, 95% CI, 2.1-8.1). Analysing HbA1c as a continuous time-varying variable showed 30% (HR 1.3, CI 1.1-1.5) higher risk per increment of HbA1c among diabetes patients without known CVD at baseline. CONCLUSION: Poor long-term glycaemic control is associated with a substantial increase in the risk of dying from IHD in patients with diabetes, whereas in patients with reasonably good control, risk of dying from IHD may not substantially differ from that of people without diabetes.

Lactoferrin is a novel predictor of fatal ischemic heart disease in diabetes mellitus type 2: long-term follow-up of the HUNT 1 study.

OBJECTIVES: The pathogenesis of diabetes and atherosclerosis is linked through inflammation. Neutrophils contribute to atherosclerotic plaque development, and are dysfunctional in diabetes. The aim of this study was to compare the predictive values of two neutrophil degranulation products, myeloperoxidase and lactoferrin, on long-term risk for fatal ischemic heart disease in persons with newly diagnosed diabetes and controls. DESIGN: Prospective population-based cohort study. SETTING AND PATIENTS: In 1984-1986, a large population study, HUNT 1, was conducted in Norway. Previously unknown diabetes was diagnosed in 205 persons. A matched control group without diabetes was selected from the HUNT 1. MAIN OUTCOME MEASURES: Fatal ischemic heart disease was registered until 2004. Baseline serum was analysed for myeloperoxidase and lactoferrin. Cox regression analysis with adjustments for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios for fatal ischemic heart disease. RESULTS: In the diabetes group (200 subjects), the two highest tertiles of lactoferrin predicted fatal ischemic heart disease, hazard ratio 2.54 (95% CI, 1.00-6.45) and 4.06 (1.72-9.60). Myeloperoxidase did not predict death from ischemic heart disease in subjects with diabetes. In the controls (198 subjects), none of the biomarkers predicted fatal ischemic heart disease. CONCLUSION: Increased baseline concentration of lactoferrin strongly predicted the long-term risk for fatal ischemic heart disease in patients with newly diagnosed diabetes. Based on the literature, we hypothesize that the increased concentrations may reflect neutrophil priming caused by hyperglycemia.

Neopterin predicts the risk for fatal ischemic heart disease in type 2 diabetes mellitus: long-term follow-up of the HUNT 1 study.

AIMS: Neopterin has emerged as a novel predictor of coronary events. The study aim was to compare the predictive value of neopterin and C-reactive protein (CRP) on long-term risk for fatal ischemic heart disease (IHD) in persons with newly diagnosed diabetes compared to persons without diabetes. METHODS AND RESULTS: In 1984-1986 a large population study, HUNT 1, was conducted in Norway. During the study, 205 patients were diagnosed with formerly unknown diabetes. A matched control group without diabetes was selected from the HUNT 1 population. Fatal IHD was registered until 2004. Blood samples were drawn at baseline and serum was analysed for neopterin and CRP. Cox regression analysis with correction for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios (HR) for fatal IHD. In the diabetes group, neopterin and CRP were independent predictors of fatal IHD, HR 2.59 (1.11-6.01) and 2.45 (1.05-5.69), respectively. Neither CRP nor neopterin were significant predictors of fatal IHD in the control group. CONCLUSION: In subjects with diabetes, both neopterin and CRP were independent predictors of fatal IHD, suggesting that these two markers reflect different aspects of the pathogenesis underlying fatal coronary events.

Secular decline in mortality from coronary heart disease in adults with diabetes mellitus: cohort study.

OBJECTIVE: To examine trends in fatal coronary heart disease in adults with and without diabetes. DESIGN: Cohort study. SETTING: Two surveys of the Nord-Trøndelag health study (HUNT), a population based study in Norway. PARTICIPANTS: 74 914 men and women from the first survey (1984-6) and 64 829 from the second survey (1995-7). MAIN OUTCOME MEASURE: Age specific mortality from coronary heart disease among adults with and without diabetes during two consecutive nine year follow-up periods. RESULTS: A total of 2623 men and 1583 women died from coronary heart disease. Mortality rates were substantially lower during the most recent follow-up period: among men aged 70-79 without diabetes, deaths per 1000 person years declined from 16.38 to 8.79 (reduction 48%, 95% confidence interval 39% to 55%) and among women aged 70-79 from 6.84 to 2.68 (62%, 52% to 70%). Among the same age group with diabetes, deaths per 1000 person years in men declined from 38.97 to 17.89 (54%, 32% to 69%) and in women from 28.15 to 11.83 (59%, 37% to 73%). The reduction was more noticeable in age groups younger than 70 at baseline, and less pronounced among people aged 80 or more. Mortality from coronary heart disease was more than twofold higher in people with than without diabetes, with a slightly stronger association in women. The difference in mortality by diabetes status remained almost unchanged from the first to the second survey. CONCLUSION: The strong general reduction in mortality rates from coronary heart disease from the first to the second follow-up period also benefited people with diabetes, but the more than twofold higher mortality from coronary heart disease associated with diabetes persisted over time.

Diabetes mellitus and risk of fatal ischaemic heart disease by gender: 18 years follow-up of 74,914 individuals in the HUNT 1 Study.

AIM: To study long-term mortality from ischaemic heart disease (IHD) in subjects with and without diabetes and how the association between diabetes and fatal IHD is influenced by gender and established cardiovascular disease (CVD). METHODS AND RESULTS: In 1984-86, all inhabitants aged 20 years or older in Nord-Trøndelag County, Norway were invited to the HUNT Study. A total of 74,914 participated in our study, 2100 of them with prevalent diabetes. During 18 years of follow-up, 19,967 persons died. Among people without diabetes or CVD at baseline, men had twice (HR 2.20, CI 2.00-2.41) the rate of fatal IHD compared with women. With diabetes present, the gender gap was substantially reduced (HR 1.25, CI 0.9-1.72), and if both diabetes and CVD were present, IHD mortality in men and women was identical (HR 1.1, CI 0.79-1.64). Gender specific analyses showed a stronger association of diabetes with IHD mortality in women (HR 2.71, CI 2.33-3.16) compared with men (HR 1.98, CI 1.70-2.30, test for interaction, P < 0.01). CONCLUSION: Diabetes is a stronger predictor for IHD mortality in women than in men, and diabetes attenuates the usual gender gap in IHD mortality. With both diabetes and established CVD present, the gender gap is fully attenuated.