No abstract

Background Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in type 1 diabetes (T1D) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, a cohort of childhood onset T1D. Methods Participants were first seen in 1986–1988, when mean age and diabetes duration were 29 and 20 years, respectively, and biennially thereafter for 18 years. Overweight was defined as 25≤BMI<30 kg/m2. Obese was defined as a BMI≥30 kg/m2. Results At baseline, the prevalence of overweight and obesity were 28.6% and 3.4%, respectively. After 18 years of follow-up, the prevalence of overweight increased by 47% while the prevalence of obesity increased 7-fold. Seven percent were on intensive insulin therapy (≥3 insulin injections per day or on insulin pump) at baseline; by 2004–2007, this was 82%. Predictors of weight change were a higher baseline HbA1c, symptomatic autonomic neuropathy (inversely), overt nephropathy (inversely), and going onto intensive insulin therapy during follow-up. Conclusion These data demonstrate dramatic weight gain in T1D and underscore the complexity of weight change in this disease.

The epidemic rise in obesity has fuelled the current debate over its classification as a disease. Contrary to just being a medical condition or risk factor for other diseases, obesity is a complex disease of multifaceted aetiology, with its own disabling capacities, pathophysiologies and comorbidities. It meets the medical definition of disease in that it is a physiological dysfunction of the human organism with environmental, genetic and endocrinological aetiologies. It is a response to environmental stimuli, genetic predisposition and abnormalities, and has a characteristic set of signs and symptoms with consistent anatomical alterations. Excess adipose tissue increases the work of the heart and leads to anatomical changes in this organ. It alters pulmonary, endocrine and immunological functions, all with adverse effects on health. Some of the complications of obesity include cardiovascular disease, non-insulin-dependent diabetes mellitus, obstructive pulmonary disease, arthritis and cancer. Given the excess mortality, substantial morbidity and the economic toll of obesity, this is a disease that warrants serious attention by the medical community. Obesity's status and acceptance as a disease is pivotal in determining its treatment, reimbursement for treatment and the development of widespread interventions.

Background-Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in type 1 diabetes (T1D) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, a cohort of childhood onset T1D.

Background In the general population, adiposity exhibits a J- or U-shaped relationship with mortality; however, in catabolic states this relationship is often inversely linear. We have recently documented an age-independent increase in overweight/obesity in the Pittsburgh Epidemiology of Diabetes Complications study (EDC) of type 1 diabetes (T1D). As intensified insulin therapy (IIT) may promote weight gain, the impact of weight gain in T1D is of importance. We therefore assessed the association of adiposity with mortality in 655 EDC participants during twenty years of follow-up. Methods Individuals were categorized as underweight (BMI <20), normal (20≤BMI<25), overweight (25≤BMI<30), or obese (BMI≥30). Cox models were constructed using BMI and covariates at baseline, updated means during follow-up, time-varying (reflecting most recent status), and change during adulthood as predictors of mortality. Results The prevalence of IIT (3+ insulin shots daily and/or pump) increased from 7% to 82%. Overweight increased 47%; obesity increased 7-fold. There were 146 deaths. In unadjusted models BMI (modeled continuously) demonstrated a quadratic relationship with mortality (p=0.002, <0.0001, <0.0001 for baseline, updated mean, and time-varying models, respectively). However, only in the time-varying model were the obese significantly different from the normal weight. while the baseline model revealed no differences by BMI category, in both the updated mean and time varying models, the underweight were at greater risk than the normal weight (p<0.0001 both models). The nonlinear relationship of adiposity with mortality remained after adjustment for diabetes complications, biological, or socioeconomic/lifestyle risk factors, with the exception of baseline socioeconomic/lifestyle risk factors where a linear association emerged. Adjustment for waist circumference eliminated the risk in the obese. Finally, weight gain during follow-up was protective. Conclusion The relationship of adiposity with mortality in T1D now appears to resemble that of the general population, albeit with a marked increased risk in those underweight.

Background Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric pollutants, occurring from anthropogenic and natural sources. Several animal studies have reported a positive association of PAHs with inflammation. However, it is not clear if lower background exposure to PAHs is associated with inflammation in humans, independent of smoking, a major source of PAHs. Methods We examined participants from the National Health and Nutrition Examination Survey 2001– 2002, 2003–2004, and 2005–2006. Our exposures of interest were eight urinary monohydroxy polycyclic aromatic hydrocarbon biomarkers. Our outcomes were serum markers of inflammation; C-reactive protein (CRP) (≤10 mg/L) and total white blood cell (WBC) count (4000–12,000 cells/µL). Results Compared to participants with summed biomarkers of low-molecular weight (LMW) PAHs in the lowest quartile, the multivariable odds ratios (95% confidence interval) of high serum CRP (≥3 mg/L) and high total WBC count (defined as at or above the 95 percentile of total WBC distribution) among participants in the highest exposure quartile were 1.77 (1.13, 2.76) and 1.34 (1.12, 1.60) respectively. Urinary 1-hydroxypyrene, the biomarker of the higher molecular weight pyrene, was positively associated with total WBC count, and to lesser extent with serum CRP. In subsequent analyses, the positive association between LMW PAHs and serum CRP and total WBC count was found to be present within the stratified subgroups, independent of smoking and other potential confounders. The positive association was more evident among adult males when compared to females. Conclusions Urinary PAH biomarkers were found to be positively associated with serum CRP and total WBC count independent of smoking and other potential confounders. The association was more evident in men.

Background: Coronary artery calcification (CAC) is more severe and occurs at an earlier age in type 1 diabetes. Risk factors for this subclinical marker of atherosclerotic burden, like coronary artery disease (CAD) itself, are not fully identified. One postulated mechanism for the increased CAC observed in type 1 diabetes is the accumulation of advanced glycation end products (AGEs). As certain collagen AGEs fluoresce, skin intrinsic fluorescence (SIF) can act as a novel marker of levels of collagen AGEs. We thus sought to determine the relationship between skin intrinsic fluorescence and CAC in type 1 diabetes. Methods: One hundred five participants in the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset (age <17 years) type 1 diabetes who had previously undergone electron beam tomography scanning for CAC (80 of whom had follow-up data) had SIF measurements taken using the SCOUT DM Ò (VeraLight, Inc., Albuquerque, NM). Mean age and diabetes' duration were 49 and 40 years, respectively, at the time of SIF measurement. Results: Seventy-one percent of the study participants had some measurable CAC that was univariately (but not after age adjustment) cross-sectionally associated with SIF (odds ratio ¼ 2.51, 1.37-4.59). However, for CAC severity using natural logarithmically transformed scores, SIF was both univariately (P < 0.0001) and multivariably (P ¼ 0.03) associated with CAC. This relationship was independent of age, a history of CAD, renal function, or renal damage. Receiver operator characteristic analyses revealed that the discriminative ability of SIF to detect CAC went from an area under the curve of 71% for the presence of any CAC to 85% for those with a CAC score >400. Conclusions: The relationship between SIF and CAC appears stronger with more severe calcification. Given the strong relationship of CAC with CAD this finding has important implications and suggests that SIF maybe a useful marker of CAC=CAD risk and potentially a therapeutic target.

AimsTo evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.Materials and MethodsInformation from 69,385 women and 55,311 men, aged 40–74 years from the Shanghai Women's Health Study and Shanghai Men's Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.ResultsThere were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92–0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80–0.97 for men; HR = 0.91, 0.86–0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96–1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91–1.10 for men; HR = 1.01, 0.96–1.07 for women) with diabetes risk.ConclusionsOur study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity.