Public health burden of pre-diabetes and diabetes in Luxembourg: finding from the 2013-2015 European Health Examination Survey.

OBJECTIVE: The aim of this study was to determine the burden and risk factors of prediabetes and diabetes in the general adult population of Luxembourg. DESIGN: Cross-sectional survey between 2013 and 2015. SETTING: Data were collected as part of the European Health Examination Survey in Luxembourg (EHES-LUX). PARTICIPANTS: 1451 individuals were recruited in a random sample of the 25-64-year-old population of Luxembourg. OUTCOMES: Diabetes was defined by a glycaemic biomarker (fasting plasma glucose (FPG) ≥7.0 mmol/L), self-reported medication and medical diagnosis; prediabetes by a glycaemic biomarker (FPG 5.6-6.9 mmol/L), no self-reported medication and no medical diagnosis. Undiagnosed diabetes was defined only from the glycaemic biomarker; the difference between total and undiagnosed diabetes was defined as diagnosed diabetes. Odds of diabetes and prediabetes as well as associated risk factors were estimated. RESULTS: The weighted prevalence of prediabetes and diabetes was 25.6% and 6.5%, respectively. Nearly 4.8% (men: 5.8%; women: 3.8%) were diagnosed diabetes and 1.7% (men: 2.6%; women: 0.7%) were undiagnosed diabetes. The multivariable-adjusted OR (MVOR) for diabetes risk were: age 1.05 (95% CI 1.01 to 1.09), family history of diabetes 3.24 (1.95-5.38), abdominal obesity 2.63 (1.53-4.52), hypertension 3.18 (1.76-5.72), one-unit increase of triglycerides 1.16 (1.10-1.22) and total cholesterol 0.74 (0.64-0.86). The MVOR for prediabetes risk were: age 1.04 (95% CI 1.02 to 1.06), male sex 1.84 (1.30-2.60), moderate alcohol consumption 1.38 (1.01-1.89), family history of diabetes 1.52 (1.13-2.05), abdominal obesity 1.44 (1.06-1.97), second-generation immigrants 0.61 (0.39-0.95) and a one-unit increase of serum high-density lipoprotein cholesterol 0.70 (0.54-0.90). CONCLUSIONS: In Luxembourg, an unexpectedly high number of adults may be affected by prediabetes and diabetes. Therefore, these conditions should be addressed as a public health priority for the country, requiring measures for enhanced detection and surveillance, which are currently lacking, especially in primary care settings.

Dietary Intake of Lutein and Diabetic Retinopathy in the Atherosclerosis Risk in Communities Study (ARIC).

PURPOSE: We tested the hypothesis that dietary intake of lutein is inversely associated with prevalence of diabetic retinopathy (DR) due to its antioxidant and anti-inflammatory properties and location within the retina. METHODS: We used logistic regression to examine the association between prevalent DR and energy-adjusted lutein intake by quartile (Q) using data collected from 1430 Atherosclerosis Risk in Communities Study (ARIC) participants with diabetes (n = 994 white, n = 508 black). DR was assessed from 45° non-mydriatic retinal photographs of one randomly chosen eye taken at visit 3 (1993-1995). Dietary lutein intake was estimated using a 66-item food frequency questionnaire at visit 1 (1987-1989). RESULTS: Median estimated daily lutein intake was 1370 µg/1000 kcals and prevalence of DR was ~21%. We found a crude association between lutein and DR (odds ratio, OR, 2.11, 95% confidence interval, CI, 1.45-3.09 for Q4, high intake, vs. Q1, low intake; p for trend <0.0001), which was attenuated after adjustment for ethnicity, duration of diabetes, glycosylated hemoglobin levels, field center and energy intake (OR 1.41, 95% CI 0.87-2.28; p for trend = 0.01). In analyses limited to persons with short diabetes duration (<6 years), the association no longer persisted (OR 0.94, 95% CI 0.31-2.16; p for trend =0.72) compared to the association in those with longer diabetes duration (≥6 years; OR 1.58, 95% CI 0.91-2.75; p for trend = 0.01). CONCLUSION: Contrary to our hypothesis, we found that the odds of higher lutein intake were greater among those with DR than those without DR. However, after adjusting for confounders, intake of lutein was not associated with DR.

Health-related quality of life and risk of hypertension in the community: prospective results from the Western New York Health Study.

OBJECTIVES: Measures of health-related quality of life (HRQL) are strong predictors of health outcomes including cardiovascular disease (CVD). However, prospective evidence on the potential impact of these measures on hypertension risk is scant. We therefore examined the independent role of HRQL on the risk of hypertension in a 6-year longitudinal investigation among 979 women and men (mean age 54.3 years) from the community, who were free of hypertension, CVD and diabetes at the baseline examination. METHODS: Baseline variables included socio-demographics, anthropometrics, blood pressure, behavioural risk factors and measures of HRQL, such as the physical and mental health component summaries of the short form-36 questionnaire (SF-36). Incident hypertension was defined as blood pressure at least 140/90  mmHg or on antihypertensive medication at the follow-up visit. RESULTS: The cumulative 6-year incidence of hypertension was 21.9% (214/979). In bivariate analyses, there were several baseline correlates of incident hypertension, including age, abdominal height, BMI and baseline blood pressure levels in both sexes, whereas impaired fasting glucose, family history of hypertension and the SF-36 physical score were all significantly associated with hypertension among women only. After multivariate adjustment, the SF-36 physical scores [odds ratio (OR) 0.97, 0.94-0.99 for unit change] were still significant predictors of hypertension in women only, independent of age, anthropometrics, baseline SBP levels, behavioural risk factors and other covariates. CONCLUSION: Measures of HRQL may represent independent predictors of hypertension risk, at least among women, above and beyond the role of traditional risk factors, such as age, anthropometrics and genetic predisposition.

Evaluating the prognostic value of positron-emission tomography myocardial perfusion imaging using automated software to calculate perfusion defect size.

BACKGROUND: Myocardial perfusion imaging by positron-emission tomography (PET MPI) is regarded as a valid technique for the diagnosis of coronary artery disease (CAD), but the incremental prognostic value of PET MPI among individuals with known or suspected CAD is not firmly established. HYPOTHESIS: Myocardial perfusion defect sizes as measured by PET MPI using automated software will provide incremental prognostic value for cardiac and all-cause mortality. METHODS: This study included 3739 individuals who underwent rest-stress rubidium-82 PET MPI for the evaluation of known or suspected CAD. Rest, stress, and stress-induced myocardial perfusion defect sizes were determined objectively by automated computer software. Study participants were followed for a mean of 5.2 years for cardiac and all-cause mortality. Cox proportional hazards models were developed to evaluate the incremental prognostic value of PET MPI. RESULTS: A strong correlation was observed between perfusion defect sizes assessed visually and by automated software (r = 0.76). After adjusting for cardiac risk factors, known CAD, noncoronary vascular disease, and use of cardioprotective medications, stress perfusion defect size was strongly associated with cardiac death (P < 0.001). Rest perfusion defects demonstrated a stronger association with cardiac death (P < 0.001) than stress-induced perfusion defects (P = 0.01), yet both were highly significant. Similar patterns held for all-cause death. CONCLUSIONS: The current study is the largest to date demonstrating PET MPI provides incremental prognostic value among individuals with known or suspected CAD. Automated calculation of perfusion defect sizes may provide valuable supplementary information to visual assessment.

Cross-cultural comparison of correlates of quality of life and health status: the Whitehall II Study (UK) and the Western New York Health Study (US).

Measures of quality of life (QoL) have been found to be predictors of mortality and morbidity; however, there is still limited understanding of the multifaceted nature of these measures and of potential correlates. Using two large populations from the UK and US, we aimed to evaluate and compare measured levels of QoL and the key factors correlated with these levels. Participants were 6,472 white subjects (1,829 women) from the Whitehall II Study (mean age 55.8 years) and 3,684 white subjects (1,903 women) from the Western New York Health Study (mean age 58.7 years). QoL was assessed in both using the physical and mental health component summaries of the short form-36 questionnaire (SF-36). Analysis of covariance was used to compare gender-specific mean scores for the two populations across several potential correlates (including socio-demographic, lifestyle and co-morbidity factors). Levels of reported physical QoL tended to be higher in the UK population (51.2 vs. 48.6) while mental QoL was higher in the US group (53.1 vs. 51.1). Age, sleep duration and depressive symptoms were the main factors correlated with both physical and mental QoL in both samples. Increasing age was associated with poorer physical health but higher mental health scores in both populations (P<0.001). Sleep duration below 6 or above 8 h was associated with lower levels of QoL. Depressive symptoms were strongly associated with poorer mental health scores (P<0.001) while higher BMI, lower physical activity levels and presence of cardiovascular disease were associated with poorer physical health in both samples and gender (P<0.05). There were consistent findings for correlates of QoL in this cross-cultural comparison of two populations from the UK and US. Strongest associations were between lifestyle and co-morbidity factors and the physical health component of the SF-36 rather than the mental health component. This is a novel finding which warrants further consideration.

Short sleep duration is associated with the development of impaired fasting glucose: the Western New York Health Study.

PURPOSE: To examine whether sleep duration was associated with incident-impaired fasting glucose (IFG) over 6 years of follow-up in the Western New York Health Study. METHODS: Participants (N = 1,455, 68% response rate) who were free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001) were reexamined in the period 2003-2004. A nested case-control study was conducted. Cases had fasting plasma glucose (FPG) less than 100 mg/dL at baseline and 100 to 125 mg/dL at follow-up: controls (n = 272) had FPG less than 100 mg/dL at both exams. Cases (n = 91) were individually matched to three controls (n = 272) on sex, race, and year of study enrollment. Average sleep duration was categorized as short (<6 hours), mid-range (6 to 8 hours), and long (>8 hours). RESULTS: In multivariate conditional logistic regression after adjustment for several diabetes risk factors, the odds ratio (OR) of IFG among short sleepers was 3.0 (95% confidence limit [CL]: 1.05, 8.59) compared to mid-range sleepers. There was no association between long sleep and IFG: OR 1.6 (95% CL: 0.45, 5.42). Adjustment for insulin resistance attenuated the association only among short sleepers: OR 2.5 (95% CL: 0.83, 7.46). CONCLUSIONS: Short sleep duration was associated with an elevated risk of IFG. Insulin resistance appears to mediate this association.

A population-based study of reduced sleep duration and hypertension: the strongest association may be in premenopausal women.

OBJECTIVES: Recent evidence indicates that reduced sleep duration may be associated with an increased risk of hypertension with possibly stronger effects among women than men. We therefore examined cross-sectional sex-specific associations of sleep duration with hypertension in a large population-based sample from the Western New York Health Study (1996<2001). METHODS: Participants were 3027 white men (43.5%) and women (56.5%) without prevalent cardiovascular disease (median age 56 years). Hypertension was defined as blood pressure at least 140 or at least 90&mmHg or regular use of antihypertensive medication. Multivariate logistic regression analyses were performed to estimate odds ratios (ORs) of hypertension comparing less than 6&h of sleep per night versus the reference category (&6&h) while accounting for a number of potential confounders. RESULTS: In multivariate analyses, less than 6&h of sleep was associated with a significant increased risk of hypertension compared to sleeping at least 6&h per night, only among women [OR&=&1.66 (1.09 to 2.53)]. No significant association was found among men [OR&=&0.93 (0.62 to 1.41)].In subgroup analyses by menopausal status, the effect was stronger among premenopausal women [OR&=&3.25 (1.37 to 7.76)] than among postmenopausal women [OR&=&1.49 (0.92 to 2.41)]. CONCLUSION: Reduced sleep duration, by increasing the risk of hypertension, may produce detrimental cardiovascular effects among women. The association is independent of socioeconomic status, traditional cardiovascular risk factors, and psychiatric comorbidities, and is stronger among premenopausal women. Prospective and mechanistic evidence is necessary to support causality.

Vitality and recurrent event risk in acute myocardial infarction survivors.

BACKGROUND: Low vitality, characterized by fatigue and lack of energy, is common among survivors of acute myocardial infarction (AMI) and has been shown to be associated with increased risk of primary and secondary cardiac events. The goal of this study was to determine whether an association between vitality and recurrent cardiac events (nonfatal MI, cardiac death) among acute MI survivors persists after controlling for possible physiological and psychological confounders. DESIGN AND METHODS: Incident AMI survivors (n = 1328) from Erie and Niagara (New York) county hospitals were enrolled and followed up to 9 years. Vitality was measured by the Short Form-36 on a 0-100 scale approximately 4 months post-AMI. Cox proportional hazards models were developed to assess the vitality-recurrent event association controlling for traditional cardiovascular disease risk factors, index MI severity, and psychological correlates of vitality. RESULTS: Low-vitality individuals at baseline were more likely females, of higher BMI, smoking, diabetic, less physically active, and to have worse depression scores. Vitality was not strongly associated with MI severity markers. Lower vitality scores were associated with increased risk of recurrent cardiac events: adjusted hazard ratios (95% CI) for vitality scores 51-79, 21-50, and < or =20 (compared with > or =80) were 1.2 (0.8, 1.8), 1.4 (0.9, 2.2), and 2.9 (1.5, 5.4), respectively (Ptrend = 0.005). CONCLUSION: Low vitality was associated with increased risk of recurrent cardiac events among AMI survivors after controlling for physiological and psychological confounders. Mechanistic links with vitality should be sought as interventional targets.

Cigarette smoking is associated with conversion from normoglycemia to impaired fasting glucose: the Western New York Health Study.

PURPOSE: To determine whether cigarette smoking is associated with the conversion from normoglycemia to impaired fasting glucose (IFG). METHODS: During the years 2003 and 2004, 1,455 participants (mean age, 56.5 years; range, 35-79 years) from the Western New York Health Study who were free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001) were reexamined (68% response rate). Incident IFG was defined as a subject whose baseline fasting plasma glucose was <100mg/dL (normoglycemic) and between 100 and 125 mg/dL at follow-up. Prevalent IFG (n=528) was excluded. Baseline smoking status was categorized as never, former, or current. RESULTS: Of the 1,455 participants, 924 were normoglycemic at baseline: 101/924 converted to IFG over 6 years. Compared with those who remained normoglycemic, converters to IFG were at baseline older, had a larger body mass index, more likely to be hypertensive, currently smoke, and have a family history of type 2 diabetes mellitus (all p<0.05). Multivariate logistic regression demonstrated that compared with subjects who remained normoglycemic, the odds ratio of incident IFG among former and current smokers (vs. never) was 1.68 (95% confidence interval: 0.99-2.80) and 2.35 (95% confidence interval: 1.17-4.72) (p trend=0.008), respectively. CONCLUSION: Smoking was positively associated with incident IFG after accounting for several putative risk factors.

Correlates of short and long sleep duration: a cross-cultural comparison between the United Kingdom and the United States: the Whitehall II Study and the Western New York Health Study.

The authors examined sociodemographic, lifestyle, and comorbidity factors that could confound or mediate U-shaped associations between sleep duration and health in 6,472 United Kingdom adults from the Whitehall II Study (1997-1999) and 3,027 US adults from the Western New York Health Study (1996-2001). Cross-sectional associations between short (<6 hours) and long (>8 hours) durations of sleep across several correlates were calculated as multivariable odds ratios. For short sleep duration, there were significant, consistent associations in both samples for unmarried status (United Kingdom: adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI): 1.15, 1.94; United States: AOR = 1.49, 95% CI: 1.10, 2.02), body mass index (AORs were 1.04 (95% CI: 1.01, 1.07) and 1.02 (95% CI: 1.00, 1.05)), and Short Form-36 physical (AORs were 0.96 (95% CI: 0.95, 0.98) and 0.97 (95% CI: 0.96, 0.98)) and mental (AORs were 0.95 (95% CI: 0.94, 0.96) and 0.98 (95% CI: 0.96, 0.99)) scores. For long sleep duration, there were fewer significant associations: age among men (AORs were 1.08 (95% CI: 1.01, 1.14) and 1.05 (95% CI: 1.02, 1.08)), low physical activity (AORs were 1.75 (95% CI: 0.97, 3.14) and 1.60 (95% CI: 1.09, 2.34)), and Short Form-36 physical score (AORs were 0.96 (95% CI: 0.93, 0.99) and 0.97 (95% CI: 0.95, 0.99)). Being unmarried, being overweight, and having poor general health are associated with short sleep and may contribute to observed disease associations. Long sleep may represent an epiphenomenon of comorbidity.

Young women with type 1 diabetes have lower bone mineral density that persists over time.

OBJECTIVE: Individuals with type 1 diabetes have decreased bone mineral density (BMD), yet the natural history and pathogenesis of osteopenia are unclear. We have previously shown that women with type 1 diabetes (aged 13-35 years) have lower BMD than community age-matched nondiabetic control subjects. We here report 2-year follow-up BMD data in this cohort to determine the natural history of BMD in young women with and without diabetes. RESEARCH DESIGN AND METHODS: BMD was measured by dual-energy X-ray absorptiometry at baseline and 2 years later in 63 women with type 1 diabetes and in 85 age-matched community control subjects. A1C, IGF-1, IGF binding protein-3, serum osteocalcin, and urine N-teleopeptide were measured at follow-up. RESULTS: After adjusting for age, BMI, and oral contraceptive use, BMD at year 2 continued to be lower in women >or=20 years of age with type 1 diabetes compared with control subjects at the total hip, femoral neck, and whole body. Lower BMD values were observed in cases <20 years of age compared with control subjects; however, the differences were not statistically significant. Lower BMD did not correlate with diabetes control, growth factors, or metabolic bone markers. CONCLUSIONS: This study confirms our previous findings that young women with type 1 diabetes have lower BMD than control subjects and that these differences persist over time, particularly in women >or=20 years of age. Persistence of low BMD as well as failure to accrue bone density after age 20 years may contribute to the increased incidence of osteoporotic hip fractures seen in postmenopausal women with type 1 diabetes.

Oxidation, type 2 diabetes, and coronary heart disease: a complex interaction: findings from a population-based study.

OBJECTIVE: The purpose of this study was to analyze the interrelationship among oxidation, myocardial infarction (MI), and type 2 diabetes in a population-based case-control study of MI. RESEARCH DESIGN AND METHODS: Participants were 1,709 individuals from western New York: 257 women and men with incident MI and 1,452 healthy control subjects (aged 35-70 years). Lipid peroxidation was measured by plasma levels of thiobarbituric acid reactive substances (TBARS). History of type 2 diabetes was determined by self-reported history of medical diagnosis. RESULTS: In multivariate analyses, there was no significant difference in TBARS levels between case and control subjects in both sexes. In subgroup analyses by diabetes status, diabetic subjects, regardless of MI status, exhibited significantly higher TBARS values than nondiabetic subjects. For diabetic women, TBARS values were 1.84 and 1.83 nmol/ml for case and control subjects, respectively. Values for nondiabetic women were 1.29 and 1.31 nmol/ml, respectively. In diabetic men, values were 1.65 and 1.97 nmol/ml for case and control subjects, respectively. Values for nondiabetic men were 1.36 and 1.36 nmol/ml, respectively. CONCLUSIONS: Whereas type 2 diabetes may be an important correlate of lipid peroxidation, clinical coronary heart disease may not.

Additional contribution of emerging risk factors to the prediction of the risk of type 2 diabetes: evidence from the Western New York Study.

OBJECTIVE: To examine whether several biomarkers of endothelial function and inflammation improve prediction of type 2 diabetes over 5.9 years of follow-up, independent of traditional risk factors. METHODS AND PROCEDURES: A total of 1,455 participants from the Western New York Study, free of type 2 diabetes at baseline, were selected. Incident type 2 diabetes was defined as fasting glucose exceeding 125 mg/dl or on antidiabetic medication at the follow-up visit. Sixty-one people who met the case definition (8/1,000 person years) were identified and individually matched with up to three controls on gender, race, year of study enrollment, and baseline fasting glucose (<110 or 110-125 mg/dl). Biomarkers were measured from frozen baseline samples. RESULTS: In conditional logistic regression analyses accounting for traditional risk factors (age, family history of diabetes, smoking, drinking status, and BMI), E-selectin was positively related (3rd vs. 1st tertile: odds ratio 2.77, 95% confidence interval (CI) 1.13-6.79, P for linear trend = 0.023) and serum albumin was inversely related (3rd vs. 1st tertile: odds ratio 0.36, 95% CI 0.14-0.93, P for linear trend = 0.032) to type 2 diabetes incidence. The addition of E-selectin, serum albumin, and leukocyte count to a basic risk factor model including only traditional risk factors significantly increased the area under the receiver operating characteristic curve (AUC) (from 0.646 to 0.726, P value = 0.04). DISCUSSION: These results support the role of endothelial dysfunction and subclinical inflammation as important mechanisms in the etiopathogenesis of type 2 diabetes; moreover, they indicate that novel biomarkers may improve the prediction of type 2 diabetes beyond the use of traditional risk factors alone.

Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial.

BACKGROUND: Findings from animal models suggest that selenium supplementation improves glucose metabolism. OBJECTIVE: To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Areas of low selenium consumption of the eastern United States. PATIENTS: 1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline. INTERVENTION: Oral administration of selenium, 200 microg/d, or placebo. MEASUREMENTS: Incidence of type 2 diabetes. RESULTS: During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]). LIMITATIONS: Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white. CONCLUSIONS: Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. Click here for related information on selenium.

Elevated cystatin C concentration and progression to pre-diabetes: the Western New York study.

OBJECTIVE: We conducted a nested case-control investigation to examine whether elevated baseline concentrations of cystatin C predicted progression from normoglycemia to pre-diabetes over 6 years of follow-up from the Western New York Health Study. RESEARCH DESIGN AND METHODS: In 2002-2004, 1,455 participants from the Western New York Health Study, who were free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001), were reexamined. An incident case of pre-diabetes was defined as an individual with fasting glucose < 100 mg/dl at the baseline examination and > or = 100 and < or = 125 mg/dl at the follow-up examination, thereby eliminating individuals with prevalent pre-diabetics. All case patients (n = 91) were matched 1:3 to control participants based on sex, race/ethnicity, and year of study enrollment. All control subjects had fasting glucose levels < 100 mg/dl at both baseline and follow-up examinations. Cystatin C concentrations and the urinary albumin-to-creatinine ratio were measured from frozen (-196 degrees C) baseline blood and urine samples. Serum creatinine concentrations were available from the baseline examination only. RESULTS: Multivariate conditional logistic regression analyses adjusted for age, baseline glucose level, homeostasis model assessment of insulin resistance, BMI, hypertension, estimated glomerular filtration rate, cigarette smoking, and alcohol use revealed a significantly increased risk of progression to pre-diabetes among those with elevated baseline concentrations of cystatin C (odds ratio 3.28 [95% CI 1.43-7.54]) (upper quintile versus the remainder). Results of secondary analyses that considered high-sensitivity C-reactive protein, interleukin-6, E-selectin, or soluble intercellular adhesion molecule-1 did not alter these results. CONCLUSIONS: These results suggest that cystatin C was associated with a threefold excess risk of progression to pre-diabetes in this population.

Sex differences in endothelial function markers before conversion to pre-diabetes: does the clock start ticking earlier among women? The Western New York Study.

OBJECTIVE: We examined whether biomarkers of endothelial function, fibrinolysis/thrombosis and adiponectin, predict the progression from normal to pre-diabetes more strongly among women than men over 6 years of follow-up from the Western New York Health Study. RESEARCH DESIGN AND METHODS: In 2002-2004, 1,455 participants from the Western New York Health Study, who were free of type 2 diabetes and cardiovascular disease at baseline (1996-2001), were selected for reexamination. An incident case of pre-diabetes was defined as fasting glucose <100 mg/dl at the baseline examination and > or =100 and <126 mg/dl at the follow-up examination. Biomarkers of endothelial function (E-selectin and soluble intracellular adhesion molecule-1 [sICAM-1]), fibrinolysis/thrombosis (plasminogen activator inhibitor-1 [PAI-1]), and fasting insulin, adiponectin, and inflammation (high-sensitivity C-reactive protein) were measured in frozen (-190 degrees C) baseline samples. RESULTS: Multivariate analyses revealed higher adjusted mean values of biomarkers of endothelial dysfunction (E-selectin and sICAM-1) and fibrinolysis (PAI-1) and lower mean values of adiponectin only among women who developed pre-diabetes compared with control subjects. Formal tests for interaction between sex and case/control status were statistically significant for E-selectin (P = 0.042), PAI-1 (P = 0.001), sICAM-1 (P = 0.011), and frequency of hypertension (P < 0.001). CONCLUSIONS: These results support the concept that women who progressed from normoglycemia to pre-diabetes have greater endothelial dysfunction than men as well as more hypertension and a greater degree of fibrinolysis/thrombosis. Whether this relates to the higher risk of heart disease among diabetic women awaits further study.

Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease.

To determine if non-high-density lipoprotein (HDL) cholesterol is a more useful predictor of coronary heart disease (CHD) risk than low-density lipoprotein (LDL) cholesterol and if very-low-density lipoprotein (VLDL) cholesterol is an independent predictor of CHD risk, data from the Framingham Heart Study (2,693 men, 3,101 women) were used for this analysis. All subjects were aged > or =30 years and free of CHD at baseline, and incident CHD was the end point (618 men, 372 women). Cox proportional-hazards models were used to assess the risk for CHD (relative risks and 95% confidence intervals) on the basis of the joint distribution of LDL cholesterol and non-HDL cholesterol (in milligrams per deciliter), as well as LDL cholesterol, non-HDL cholesterol, and VLDL cholesterol as continuous variables. After multivariate adjustment, within non-HDL cholesterol level, no association was found between LDL cholesterol and the risk for CHD, whereas within LDL cholesterol levels, a strong positive and graded association between non-HDL cholesterol and risk for CHD was observed. When the analysis was repeated within triglyceride levels (<200 vs > or =200 mg/dl), the risk pattern did not change significantly. Also, VLDL cholesterol was found to be a significant predictor of CHD risk after adjusting for LDL cholesterol at triglyceride levels of > or =200 or <200 mg/dl. In conclusion, these results suggest that non-HDL cholesterol level is a stronger predictor of CHD risk than LDL cholesterol; that is, VLDL cholesterol may play a critical role in the development of CHD.

Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial.

Despite the documented antioxidant and chemopreventive properties of selenium, studies of selenium intake and supplementation and cardiovascular disease have yielded inconsistent findings. The authors examined the effect of selenium supplementation (200 microg daily) on cardiovascular disease incidence and mortality through the entire blinded phase of the Nutritional Prevention of Cancer Trial (1983-1996) among participants who were free of cardiovascular disease at baseline (randomized to selenium: n = 504; randomized to placebo: n = 500). Selenium supplementation was not significantly associated with any of the cardiovascular disease endpoints during 7.6 years of follow-up (all cardiovascular disease: hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.37; myocardial infarction: HR = 0.94, 95% CI: 0.61, 1.44; stroke: HR = 1.02, 95% CI: 0.63, 1.65; all cardiovascular disease mortality: HR = 1.22, 95% CI: 0.76, 1.95). The lack of significant association with cardiovascular disease endpoints was also confirmed when analyses were further stratified by tertiles of baseline plasma selenium concentrations. These findings indicate no overall effect of selenium supplementation on the primary prevention of cardiovascular disease in this population.

Body fat distribution, liver enzymes, and risk of hypertension: evidence from the Western New York Study.

Gamma-glutamyltransferase (GGT) has been associated with hypertension (HTN); however, the nature of this association remains unclear. GGT is a marker of alcohol consumption, but it is also related to the infiltration of fat in the liver (fatty liver). The association between GGT and HTN was examined in a 6-year longitudinal investigation among 1455 men and women who returned for the follow-up visit. Baseline variables included serum GGT, blood pressure, and anthropometric measures. Incident HTN was defined as blood pressure > or =140/90 or on antihypertensive medication at the follow-up visit. To eliminate individuals with potential liver pathology, analyses focused only on individuals with GGT within its normal range (n=897). Participants were divided in quintiles (Q) based on their baseline GGT levels. Multiple logistic regression analyses [odds ratio (95% confidence intervals)] revealed a significant association of GGT with incident hypertension [2.1 (1.1 to 4.0) Q5 versus Q1]. In subgroup analyses, GGT and HTN were significantly associated among both noncurrent and current drinkers, but only for participants above the median of anthropometric measures [eg, body mass index >26.4, 2.3 (0.9 to 5.7), waist circumference >86.1 cm, 3.7 (1.4 to 9.9), and abdominal height >19.8 cm, 3.1 (1.2 to 8.5), for Q5 versus Q1, in fully adjusted models]. These findings suggest that the association between GGT and hypertension is not caused solely by alcohol consumption and indicate that serum GGT, within its normal range, may predict hypertension among individuals with increased central fat distribution, suggesting that fatty liver may represent an important underlying mechanism for this association.

Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes.

OBJECTIVE: To assess coronary heart disease (CHD) risk within levels of the joint distribution of non-HDL and LDL cholesterol among individuals with and without diabetes. RESEARCH DESIGN AND METHODS: We used four publicly available data sets for this pooled post hoc analysis and confined the eligible subjects to white individuals aged > or = 30 years and free of CHD at baseline (12,660 men and 6,721 women). Diabetes status was defined as either "reported by physician-diagnosed and on medication" or having a fasting glucose level > or = 126 mg/dl at the baseline examination. The primary end point was CHD death. Within diabetes categories, risk was assessed based on lipid levels (in mg/dl): non-HDL <130 and LDL <100 (group 1); non-HDL <130 and LDL > or = 100 (group 2); non-HDL > or = 130 and LDL <100 (group 3); and non-HDL > or = 130 and LDL > or = 100 (group 4). Group 1 within those without diabetes was the overall reference group. RESULTS: Of the subjects studied, approximately 6% of men and 4% of women were defined as having diabetes. A total of 773 CHD deaths occurred during the average 13 years of follow-up time. A Cox proportional hazard model was used to estimate the relative risk (RR) of CHD death. Those with diabetes had a 200% higher RR than those without diabetes. In a multivariate model, CHD risk in those with diabetes did not increase with increasing LDL, whereas it did increase with increasing non-HDL: RR (95% confidence interval) for group 1: 5.7 (2.0-16.8); group 2: 5.7 (1.6-20.7); group 3: 7.2 (2.6-19.8); and group 4: 7.1 (3.7-13.6). CONCLUSIONS: Non-HDL is a stronger predictor of CHD death among those with diabetes than LDL and should be given more consideration in the clinical approach to risk reduction among diabetic patients.