Prediction of coronary heart disease risk in a general, pre-diabetic, and diabetic population during 10 years of follow-up: Accuracy of the Framingham, SCORE, and UKPDS risk functions - The Hoorn Study

OBJECTIVE - To test the validity of the Framingham, Systematic Coronary Risk Evaluation (SCORE), and UK Prospective Diabetes Study (UKPDS) risk function in the prediction of risk of coronary heart disease (CHD) in populations with normal glucose tolerance (NGT), intermediate hyperglycemia, and type 2 diabetes. RESEARCH DESIGN AND METHODS - Calibration and discrimination of the three prediction models were tested using prospective data for 1,482 Caucasian men and women, 50-75 years of age, who participated in the Hoorn Study. All analyses were stratified by glucose status. RESULTS - During 10 years of follow-up, a total of 197 CHD events, of which 43 were fatal, were observed in this population, with the highest percentage of first CHD events in the diabetic group. The Framingham and UKPDS prediction models overestimated the risk of first CHD event in all glucose tolerance groups. Overall, the prediction models had a low to moderate discriminatory capacity. The SCORE risk function was the best predictor of fatal CHD events in the group with NGT (area under the receiver operating characteristic curve 0.79 [95% CI 0.70-0.87]), whereas the UKPDS performed better in the intermediate hyperglycemia group (0.84 [0.74-0.94]) in the estimation of fatal CHD risk. After exclusion of known diabetic patients, all prediction models had a higher discriminatory ability in the group with diabetes. CONCLUSIONS - The use of the Framingham function for prediction of the first CHD event is likely to overestimate an individual's absolute CHD risk. In CHD prevention, application of the SCORE and UKPDS functions might be useful in the absence of a more valid tool. © 2009 by the American Diabetes Association

Impact of Communicating Familial Risk of Diabetes on Illness Perceptions and Self-Reported Behavioral Outcomes: A randomized controlled trial

OBJECTIVE: To assess the potential effectiveness of communicating familial risk of diabetes on illness perceptions and self-reported behavioral outcomes. RESEARCH DESIGN AND METHODS: Individuals with a family history of diabetes were randomized to receive risk information based on familial and general risk factors (n = 59) or general risk factors alone (n = 59). Outcomes were assessed using questionnaires at baseline, 1 week, and 3 months. RESULTS: Compared with individuals receiving general risk information, those receiving familial risk information perceived heredity to be a more important cause of diabetes (P <0.01) at 1-week follow-up, perceived greater control over preventing diabetes (P <0.05), and reported having eaten more healthily (P = 0.01) after 3 months. Behavioral intentions did not differ between the groups. CONCLUSIONS: Communicating familial risk increased personal control and, thus, did not result in fatalism. Although the intervention did not influence intentions to change behavior, there was some evidence to suggest it increases healthy behavio

Endothelial Dysfunction Plays a Key Role in Increasing Cardiovascular Risk in Type 2 Diabetes The Hoorn Study

In the pathogenesis of cardiovascular events, interaction between risk factors has seldom been identified. However, endothelial dysfunction on the one hand and type 2 diabetes mellitus, impaired glucose metabolism (IGM), and insulin resistance on the other may act synergistically (ie, interact) in the development of cardiovascular disease. We therefore investigated the interaction between endothelial dysfunction and type 2 diabetes mellitus, IGM, and insulin resistance with regard to risk of cardiovascular events. In a prospective population-based cohort (n=445; 69 years; 55% women; 23% type 2 diabetes mellitus, 28% IGM [by design]), endothelial dysfunction (brachial artery flow-mediated dilatation), glucose tolerance (oral glucose tolerance test), and insulin sensitivity (homeostasis model assessment for insulin resistance [HOMA2-IR]) were determined. After a median follow-up of 7.6 years, 106 participants had had a cardiovascular event. After adjustments, 1 SD less flow-mediated dilatation was associated with cardiovascular events in type 2 diabetes mellitus (hazard ratio 1.69 [95% confidence interval, 1.14-2.52]) and IGM (1.50 [0.95-2.37]) and among those in the highest HOMA2-IR tertile (1.92 [1.42-2.60]), but not in normal glucose metabolism (0.85 [0.63-1.16]) or among those in the lower 2 HOMA2-IR tertiles combined (0.85 [0.65-1.12]). Interaction between flow-mediated dilatation and type 2 diabetes mellitus, IGM, or insulin resistance was present on an additive (relative excess risk caused by interaction &gt;0) and on a multiplicative scale (P interactio

Local Stiffness of the Carotid and Femoral Artery Is Associated With Incident Cardiovascular Events and All-Cause Mortality The Hoorn Study

ObjectivesThis study sought to investigate the association of local and segmental arterial stiffness with incident cardiovascular events and all-cause mortality.BackgroundThe association of different stiffness indices, in particular of carotid, brachial, and femoral stiffness, with cardiovascular disease and mortality is currently unknown.MethodsIn a population-based cohort (n = 579, mean age 67 years, 50% women, 23% with type 2 diabetes [by design]), we assessed local stiffness of carotid, femoral, and brachial arteries (by ultrasonography), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index, and systemic arterial compliance.ResultsAfter a median follow-up of 7.6 years, 130 participants had a cardiovascular event and 96 had died. The hazard ratios (HRs) (95% confidence intervals [CIs]) per 1 SD for cardiovascular events and all-cause mortality, respectively, were HR: 1.22 (95% CI: 0.95 to 1.56) and 1.51 (95% CI: 1.11 to 2.06) for lower carotid distensibility; HR: 1.19 (95% CI: 1.00 to 1.41) and 1.28 (95% CI: 1.07 to 1.53) for higher carotid elastic modulus; HR: 1.08 (95% CI: 0.88 to 1.31) and 1.43 (95% CI: 1.10 to 1.86) for lower carotid compliance; HR: 1.39 (95% CI: 1.06 to 1.83) and 1.27 (95% CI: 0.90 to 1.79) for lower femoral distensibility; HR: 1.25 (95% CI: 0.96 to 1.63) and 1.47 (95% CI: 1.01 to 2.13) for lower femoral compliance; and HR: 1.56 (95% CI: 1.23 to 1.98) and 1.13 (95% CI: 0.83 to 1.54) for higher cfPWV. These results were adjusted for age, sex, mean arterial pressure, and cardiovascular risk factors. Mutual adjustments for each of the other stiffness indices did not materially change these results. Brachial stiffness, augmentation index, and systemic arterial compliance were not associated with cardiovascular events or mortality.ConclusionsCarotid and femoral stiffness indices are independently associated with incident cardiovascular events and all-cause mortality. The strength of these associations with events may differ per stiffness parameter

Quantitative models for reverse logistics

This article surveys the recently emerged field of reverse logistics. The management of return flows induced by the various forms of reuse of products and materials in industrial production processes has received growing attentio

Genetic factors and insulin secretion: gene variants in the IGF genes

IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes-related parameters were not significantly different for both the IGF-I and IGF-II gene variant. We conclude that gene variants in the IGF-I and IGF-II genes are not associated with detectable variations in glucose-stimulated insulin secretion in these three independent populations. Further studies are needed to examine the exact contributions of the IGF-I CA repeat alleles to variations in ISI and DI

Homocysteine, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study

A B S T R A C T The aim of the present study was to investigate the relationship between homocysteine and homocysteine metabolism components and retinal microvascular disorders in subjects with and without Type 2 diabetes. In this population-based study of 256 participants, aged 60-85 years, we determined total plasma homocysteine, SAM (S-adenosylmethionine) and SAH (S-adenosylhomocysteine) in plasma and erythrocytes, total folate in serum and erythrocytes, 5-MTHF (5-methyltetrahydrofolate), and vitamins B12 and B6. Participants were examined ophthalmologically by means of indirect funduscopy and two-field 45 • fundus photography, and were graded for retinopathy and retinal sclerotic vessel abnormalities. A computer-assisted method was used to measure retinal vessel diameters. Total plasma homocysteine was inversely associated with retinal arteriolar diameters {standardized β, − 0.20 [95 % CI (confidence interval), − 0.33 to − 0.07]} or a decrease of 3.78 μm CRAEs (central retinal arteriolar equivalents) per 1 S.D. increase in homocysteine level (= 4.6 μmol/l). In addition, the SAM/SAH ratio in plasma was inversely associated with retinal sclerotic vessel abnormalities and retinopathy [odds ratios, 0.61 (95 % CI, 0.39-0.96) and 0.50 (95 % CI, 0.30-0.83) per 1 S.D. respectively]. The associations were independent of age, sex, glucose tolerance status, other homocysteine metabolism components and cardiovascular risk factors. In conclusion, the results of the present study support the concept that total plasma homocysteine and a low SAM/SAH ratio in plasma, which may reflect reduced transmethylation reactions, may contribute to the pathogenesis of (retinal) microangiopathy