[show abstract][hide abstract] ABSTRACT: Lower adiponectin levels are associated with higher risk of incident type 2 diabetes. Most analyses have been adjusted for confounding factors, but few have taken into account insulin resistance per se. We tested the hypothesis that the association of adiponectin levels with incident type 2 diabetes differs between insulin-resistant and insulin-sensitive individuals.
We studied two prospective cohorts: the Framingham Offspring Study (n = 2,023) and the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study (n = 887) cohorts. Insulin resistance was estimated by HOMA-insulin resistance (HOMA-IR). We used logistic regression analysis to test the association between adiponectin and incident type 2 diabetes overall and in insulin-resistant vs insulin-sensitive individuals (defined by ≥ vs <75th percentile of HOMA-IR).
At baseline, Framingham's participants were 60 ± 9 years old and 56% were women; KORA's participants were 63 ± 5 years old and 49% were women. Type 2 diabetes incidence was 5.4% over 6.5 years (n = 109) in Framingham and 10.5% over 8 years (n = 93) in KORA. Lower adiponectin levels were associated with type 2 diabetes incidence in both cohorts. In insulin-resistant individuals, lower adiponectin levels were associated with higher risk of type 2 diabetes incidence (OR 1.60 [95% CI 1.10-2.31] per SD decrease in Framingham, p = 0.01; and OR 2.34 [95% CI 1.16-4.73] in KORA, p = 0.02); while this was not observed in insulin-sensitive individuals (OR 1.10 [95% CI 0.73-1.67] in Framingham, p = 0.64; and OR 1.34 [95%CI: 0.88-2.03] in KORA, p = 0.18).
We conclude that lower adiponectin levels are associated with higher risk of type 2 diabetes in insulin-resistant but not in insulin-sensitive individuals. This suggests that some level of insulin resistance is needed to see deleterious effects of low adiponectin.
[show abstract][hide abstract] ABSTRACT: To review published data on vascular disease- and diabetes-related outcomes related to adiposity and metabolic risk factors.
Community cohort study with cross-sectional and prospective data.
Middle-aged Caucasian adults in a suburban environment.
Traditional risk factors for cardiovascular disease and the type 2 diabetes mellitus, as well as measures of insulin resistance, left ventricular hypertrophy and vascular calcification.
The cardiometabolic risk factors cluster in the population and a common core that includes adiposity (both waist and body mass index), abnormal lipids (both HDL cholesterol and triglycerides), and abnormal glucose and insulin metabolism was found to be present in Framingham participants. Increased insulin resistance was also found to be associated with coronary artery calcification and left ventricular hypertrophy in women. Analyses of the metabolic syndrome risk factors showed that a greater burden of risk factors was associated with greater risk of both cardiovascular disease and diabetes mellitus. An equation to estimate risk of developing type 2 diabetes mellitus has been developed from the Framingham experience, and the risk factors included in the metabolic syndrome are key components, including increased waist girth, elevated blood pressure, low HDL cholesterol, high triglycerides and impaired fasting glucose.
Cardiometabolic factors and insulin resistance are important contributors to the development of type 2 diabetes mellitus, subclinical cardiovascular disease and clinical cardiovascular disease.
International journal of obesity (2005) 06/2008; 32 Suppl 2:S17-20. · 4.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bony proliferation (exostoses) and vascular calcification are common in elderly men and women, but it is unclear whether they have a common etiology. Lateral lumbar and hand radiographs were obtained (1967-1970) in 777 men and 1,241 women (mean age 59, range 47-80 years) from the Framingham Heart Study. Each group of hand exostoses, specifically apiostoses (tufting), enthesophytes, and osteophytes, was graded on a scale of 0-3 (absent to severe) and summed across phalanges of digits 2-5. Anterior lumbar osteophytes were assessed in intervertebral spaces T12-L5 and abdominal aortic calcification (AAC) at lumbar segments L1-L4. Information on age, sex, body mass index, smoking, alcohol consumption, physical activity, systolic blood pressure, total cholesterol level, diabetes, and estrogen replacement therapy in women was obtained at the time of radiography and adjusted for in multivariate analyses. We used multivariable logistic regression models to assess the relationship between AAC (dependent variable) and exostoses for each sex. Multivariable adjusted logistic regression revealed a significant association between increased anterior lumbar osteophytes and prevalent AAC in men [odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.1-1.3 per unit increase in osteophytes] and in women (OR = 1.25, 95% CI 1.1-1.4). There also was an inverse association between enthesophytes and AAC in women only (OR = 0.82, 95% CI 0.73-0.92). Apiostoses were weakly associated with AAC in men only. Hand osteophytes were not associated with AAC. In conclusion, in this cross-sectional study, anterior lumbar osteophytes and AAC occurred in the same individuals after adjustment for age and other covariates. In general, hand exostoses were not associated with aortic calcification.
Calcified Tissue International 02/2006; 78(1):1-8. · 2.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the -174 IL-6 gene polymorphism as a risk factor for type 2 diabetes mellitus in a family-based analysis.
We tested for associations between the -174 IL-6 G/C promoter polymorphism and fasting plasma glucose (FPG) and type 2 diabetes in a sample of 1,428 individuals from the largest 182 families in the National Heart, Lung and Blood Institute's Framingham Heart Study population.
A significant association was found with FPG (p=0.01) and log (FPG) (p=0.005) using a modified family-based transmission disequilibrium test, the family-based association test (FBAT). The association between IL-6 genotype and FPG (p=0.035) and log (FPG) (p=0.03) was also found in the subset of families that were informative in FBAT using a mixed-effects regression model and strengthened after adjustment for potential confounders (p=0.008 for log [FPG]). The mean glucose level estimated from models with log (FPG) as the dependent variable for the GG genotype in the informative families was significantly lower (5.20+/-0.06 mmol/l) than for the GC (5.41+/-0.06 mmol/l) and CC (5.38+/-0.06 mmol/l) genotypes (p=0.03 for contrast between GG and GC genotypes). In the subset of informative families, the risk of type 2 diabetes associated with the GG genotype was lower relative to the GC and CC genotypes combined (potential confounder-adjusted, mixed-effects odds ratio 0.35, 95% CI 0.14-0.88, p=0.026, unaffected n=391, affected n=32).
These results are consistent with a protective role for the -174 IL-6 G allele against type 2 diabetes and warrant further analysis of this polymorphism.
[show abstract][hide abstract] ABSTRACT: To evaluate the contributions of socioeconomic, lifestyle, and body weight factors to predicted risk of coronary heart disease (CHD) in the population and thus provide a focus for policies on prevention.
Prospective study and cross-sectional population health survey.
In all, 3090 men in the Framingham study and 2571 men in the 1998 Health Survey for England (HSE) aged 35-74 y with no history of cardiovascular disease participated in the study.
Data on sex, age, systolic blood pressure and antihypertensive medication, total and high-density lipoprotein cholesterol levels, diabetes, and their association with the incidence of myocardial infarction and fatal CHD in the Framingham study population were used to derive functions for predicting individual 10-y risk of CHD. These functions were applied to the same data on participants in the HSE. High risk was defined as 10-y CHD risk > or = 15%. The proportion of high risk in the English population attributable to each of the risk factors examined was assessed.
In all, 32% of men in England had predicted 10-y CHD risk > or =15%. Such high risk was significantly associated with body mass index (BMI, kg/m2), waist:hip ratio (WHR), smoking, and levels of physical activity, educational attainment, and income (all P < or = 0.007). In this population, 47% of high CHD risk was attributable to excess body weight--BMI > or = 25 kg/m2 and/or WHR > or = 0.95--and 31% to the sum of the four other significant factors: lack of educational qualifications, low income, smoking, and physical inactivity.
Overweight and obesity now dominate the standard risk factors of CHD in men and should be the focus of national policies for prevention.
International Journal of Obesity 03/2005; 29(3):317-23. · 5.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1-3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4-5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.
American Journal of Transplantation 02/2004; 4 Suppl 7:13-53. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyperinsulinaemia and insulin resistance usually precede clinical hyperglycaemia and Type 2 diabetes. Thus, plasma insulin concentrations and insulin resistance are important quantitative traits associated with risk of Type 2 diabetes, and represent key measures for genetic analysis of the syndrome.
We carried out a genome-wide search for loci related to plasma insulin concentrations and insulin resistance in 330 extended, community-based pedigrees from the Framingham Heart Study. Normalized deviates of the standardized residuals of plasma insulin concentrations in the fasting state, 2 h after oral glucose challenge and as a measure of insulin resistance were used in linkage analysis with the variance components model implemented in the computer program SOLAR.
The results suggest susceptibility loci influencing plasma concentrations of fasting insulin and insulin resistance on chromosomes 11 (LOD 2.43 at 85 cM close to D11S2002) and 17 (LOD 1.8 at 60 cM, close to D17S784); and susceptibility loci influencing 2-h plasma insulin concentrations on chromosomes 9 (LOD 2.8 at 80 cM, close to D9S922) and 19 (LOD 1.8 at 66 cM, close to D19S245). The results of the analysis of 1000 simulations of the trait and an unlinked marker suggest that in a genome scan of 401 markers fewer than one LOD score over 1 would be due to Type 1 error, and be a false positive.
We conclude that these suggestive regions for quantitative pre-diabetic insulin traits could contain major loci in the pathogenesis of Type 2 diabetes.
[show abstract][hide abstract] ABSTRACT: Insulin-like growth factor-1 (IGF-I) plays a central role in the maintenance of bone mass. To test whether two major IGF-I binding proteins, IGFBP-4 and IGFBP-5, are related to bone mineral density (BMD), we studied a sample of the Framingham Offspring Cohort participants (99 men and 101 women, ages 60-87). Serum levels of IGF-I, IGFBP-4, and IGFBP-5 were measured by previously validated radioimmunoassays (CVs approximately 10%). BMDs of the proximal femur and lumbar spine were measured using a Lunar DPX-L densitometer. In males, but not females, IGF-I and IGFBP-5 were inversely associated with age (r = 0.34 and r = -0.28, respectively; P <0.01), while IGFBP-4 levels were positively associated with age (P <0.01). Multivariate means for BMD (adjusted for age, body mass index, height, smoking, and in women, estrogen use) were computed across quartiles of IGFBP-4 and IGFBP-5 and IGFBP-4/IGFBP-5 ratio. In women, but not men, IGFBP-5 was positively associated with femoral neck BMD (P = 0.03), however, after statistical adjustment for IGF-I, this association was no longer significant. No other associations were observed for BMD at any other site. Further study is necessary for elucidation of the gender differences in the possible influence of IGF system components on bone mass.
Calcified Tissue International 10/2002; 71(4):323-8. · 2.50 Impact Factor