Ag Tabak

Moving to an A1C-Based Diagnosis of Diabetes Has a Different Impact on Prevalence in Different Ethnic Groups

OBJECTIVE To compare screen-detected diabetes prevalence and the degree of diagnostic agreement by ethnicity with the current oral glucose tolerance test (OGTT)-based and newly proposed A1C-based diagnostic criteria. RESEARCH DESIGN AND METHODS Six studies (1999–2009) from Denmark, the U.K., Australia, Greenland, Kenya, and India were tested for the probability of an A1C ≥6.5% among diabetic case subjects based on an OGTT. The difference in probability between centers was analyzed by logistic regression adjusting for relevant confounders. RESULTS Diabetes prevalence was lower with the A1C-based diagnostic criteria in four of six studies. The probability of an A1C ≥6.5% among OGTT-diagnosed case subjects ranged widely (17.0–78.0%) by study center. Differences in diagnostic agreement between ethnic subgroups in the U.K. study were of the same magnitude as between-country comparisons. CONCLUSIONS A shift to an A1C-based diagnosis for diabetes will have substantially different consequences for diabetes prevalence across ethnic groups and populations.

Validating the Framingham Hypertension Risk Score. Results From the Whitehall II Study

A promising hypertension risk prediction score using data from the US Framingham Offspring Study has been developed, but this score has not been tested in other cohorts. We examined the predictive performance of the Framingham hypertension risk score in a European population, the Whitehall II Study. Participants were 6704 London-based civil servants aged 35 to 68 years, 31% women, free from prevalent hypertension, diabetes mellitus, and coronary heart disease. Standard clinical examinations of blood pressure, weight and height, current cigarette smoking, and parental history of hypertension were undertaken every 5 years for a total of 4 times. We recorded a total of 2043 incident (new-onset) cases of hypertension in three 5-year baseline follow-up data cycles. Both discrimination (C statistic: 0.80) and calibration (Hosmer-Lemeshow &khgr;2: 11.5) of the Framingham hypertension risk score were good. Agreement between the predicted and observed hypertension incidences was excellent across the risk score distribution. The overall predicted:observed ratio was 1.08, slightly better among individuals >50 years of age (0.99 in men and 1.02 in women) than in younger participants (1.16 in men and 1.18 in women). Reclassification with a modified score on the basis of our study population did not improve the prediction (net reclassification improvement: −0.5%; 95% CI: −2.5% to 1.5%). These data suggest that the Framingham hypertension risk score provides a valid tool with which to estimate near-term risk of developing hypertension.

Personality and risk of diabetes in adults: Pooled analysis of 5 cohort studies

OBJECTIVE Diabetes is an increasingly important public health concern, but little is known about the contribution of psychological factors on diabetes risk. We examined whether personality is associated with risk of incident diabetes and diabetes-related mortality. METHOD An individual-participant meta-analysis of 34,913 adults free of diabetes at baseline (average age 53.7 years, 57% women) from 5 prospective cohort studies from the United States and United Kingdom. Personality dimensions included extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience based on the Five Factor Model. RESULTS During an average follow-up of 5.7 years, 1845 participants became diabetic. Of the 5 personality dimensions, only low conscientiousness was associated with an elevated diabetes risk (OR = 0.87, 95% CI = 0.82-0.91 per 1 standard deviation increment in conscientiousness). This association attenuated by 60% after adjustment for obesity and by 25% after adjustment for physical inactivity. Low conscientiousness was also associated with elevated risk of diabetes mortality (HR = 0.72, CI = 0.53-0.98 per 1 standard deviation increment in conscientiousness). Other personality traits were not consistently associated with diabetes incidence or mortality. CONCLUSIONS Low conscientiousness-a cognitive-behavioral disposition reflecting careless behavior and a lack of self-control and planning-is associated with elevated risk of diabetes and diabetes-related mortality. The underlying mechanisms are likely to involve health behaviors, such as poor weight management, physical inactivity, and adherence to medical management recommendations.

Adiposity, Obesity, and Arterial Aging Longitudinal Study of Aortic Stiffness in the Whitehall II Cohort

We sought to determine whether adiposity in later midlife is an independent predictor of accelerated stiffening of the aorta. Whitehall II study participants (3789 men; 1383 women) underwent carotid-femoral applanation tonometry at the mean age of 66 and again 4 years later. General adiposity by body mass index, central adiposity by waist circumference and waist:hip ratio, and fat mass percent by body impedance were assessed 5 years before and at baseline. In linear mixed models adjusted for age, sex, ethnicity, and mean arterial pressure, all adiposity measures were associated with aortic stiffening measured as increase in pulse wave velocity (PWV) between baseline and follow-up. The associations were similar in the metabolically healthy and unhealthy, according to Adult Treatment Panel-III criteria excluding waist circumference. C-reactive protein and interleukin-6 levels accounted for part of the longitudinal association between adiposity and PWV change. Adjusting for chronic disease, antihypertensive medication and risk factors, standardized effects of general and central adiposity and fat mass percent on PWV increase (m/s) were similar (0.14, 95% confidence interval: 0.05–0.24, P=0.003; 0.17, 0.08–0.27, P<0.001; 0.14, 0.05–0.22, P=0.002, respectively). Previous adiposity was associated with aortic stiffening independent of change in adiposity, glycaemia, and lipid levels across PWV assessments. We estimated that the body mass index–linked PWV increase will account for 12% of the projected increase in cardiovascular risk because of high body mass index. General and central adiposity in later midlife were strong independent predictors of aortic stiffening. Our findings suggest that adiposity is an important and potentially modifiable determinant of arterial aging.

Low serum adiponectin predicts 10-year risk of type 2 diabetes and HbA1c independently of obesity, lipids and inflammation –Whitehall II study

Our aim of the present work was to study the effect of serum adiponectin on incident diabetes and HbA1c values. We measured baseline serum adiponectin levels in a nested case-control selection (n=140) of the Whitehall II Cohort. Participants (mean [SD] age 50.9 [6.3] years) had no prevalent diabetes or CHD at baseline. Cases (n=55) had incident diabetes according to an oral glucose tolerance test during follow-up (mean: 11.5+/-3.0 years). Adiponectin levels were lower among cases (9.3 microg/ml, 3.2 [median; IQR] vs. 10.5; 3.6, p=0.01). The risk of incident diabetes decreased by 11% (p=0.03) for 1 microg/ml higher adiponectin levels. Higher adiponectin levels were associated with lower HbA1c at follow-up (p<0.05). Both associations were stable to adjustment for age, sex, body mass index, systolic blood pressure, and serum lipids, and for the case of HbA1c, also for C-reactive protein (all p<0.05). The observed robust, prospective associations support that adiponectin is an independent predictor of diabetes and the degree of glycaemic impairment.

Generalizability of occupational cohort study findings

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Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: The Whitehall II study

OBJECTIVE Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. DESIGN AND METHODS We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. RESULTS Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. CONCLUSIONS Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.

Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up.

BACKGROUND Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure. AIMS To examine lifetime blood pressure as a predictor of brain structure in old age. METHOD A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985-2013). In 2012-2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities. RESULTS Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy. CONCLUSIONS Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose-response pattern.

Myocardial infarction is associated with Sp1 binding site polymorphism of collagen type 1A1 gene

Objective — Human atherosclerotic lesions contain collagen type 1, which plays a pivotal role in atherosclerotic plaque stability. In contrast, the normal coronary arteries do not express this type of collagen. Data have shown that the collagen type 1A1 (COL1A1) gene Sp1 binding site (-1245 G/T) polymorphism is associated with disturbed collagen protein production. Methods — In our study, COL1A1 gene Sp1 polymorphism was investigated in 136 patients with myocardial infarction (MI) 5 months after the acute phase, and 212 age-matched control subjects in association with any cardiovascular risk factors (such as serum adiponectin levels, hyperinsulinaemic status, hyperlipaemia). Results — The “SS” genotype of the COL1A1 gene was found to occur significantly more frequently in patients surviving a MI, as compared to the control group and the “Ss” and “ss” genotype frequencies (the presence of the s allele) were lower in our patients, than in control group. However, the occurrence of cardiovascular risk factors was significantly higher among the “s” allelic carriers as compared to patients carrying the “S” allele of the COL1A1 gene. Conclusion — Our results raise the possibility that COL1A1 gene Sp1 polymorphism might have an impact on the development of MI.

Serum erythropoietin level and mortality in kidney transplant recipients

BACKGROUND AND OBJECTIVES Posttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 ± 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk. RESULTS During the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 ± 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P = 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR(1SD increase) 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR(1SD increase) 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups. CONCLUSIONS In this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.