Baqiyyah Conway

Temporal patterns in overweight and obesity in Type 1 diabetes.

Diabet. Med. 27, 398–404 (2010)

Adiposity and mortality in type 1 diabetes.

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 20 years of follow-up.Methods:Individuals were categorized as underweight (body mass index (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 variation (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 by 47% and obesity increased sevenfold. There were 146 deaths. In unadjusted models, BMI (modeled continuously) showed 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, whereas the baseline model showed no differences by BMI category. In both the updated mean and time-varying models, the underweight were at greater risk than were the normal weight (P<0.0001 both models). The nonlinear relationship of adiposity with mortality remained after adjustment for diabetes complications and for biological or socioeconomic/lifestyle risk factors, with the exception of baseline socioeconomic/lifestyle risk factors, in which a linear association emerged. Adjustment for waist circumference eliminated risk in the obese. Finally, weight gain during follow-up was protective.Conclusion:The relationship of adiposity with mortality in T1D now seems to resemble that of the general population, albeit with a marked increased risk in those who are underweight.

Polycyclic aromatic hydrocarbon biomarkers and serum markers of inflammation. A positive association that is more evident in men

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.

Urinary polycyclic aromatic hydrocarbon biomarkers and diabetes mellitus

Objective The aim of the current study is to investigate the association of polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants, with diabetes mellitus. Animal studies link PAHs to inflammation and subsequent development of diabetes mellitus. In addition, occupational studies suggest that exposure to other aromatic hydrocarbons such as dioxins may be associated with diabetes risk in humans. Design We examined participants from the merged National Health and Nutrition Examination Survey 2001–2002, 2003–2004 and 2005–2006. Exposures of interest were eight urinary monohydroxy-PAHs. Our outcome was diabetes mellitus defined as a glycohemoglobin level (HbA1c) ≥6.5%, a self-reported physician diagnosis of diabetes or use of oral hypoglycaemic medication or insulin. Analyses were adjusted for age, sex, body mass index, race, alcohol consumption, poverty–income ratio, total cholesterol and serum cotinine. Results We observed a positive association between urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed low molecular weight (LMW) PAH biomarkers, and diabetes mellitus. Compared with participants with summed LMW PAH biomarkers in the lowest quartile, the multivariable-adjusted OR of diabetes mellitus among those in the highest quartile was 3.1 (95% CI 1.6 to 5.8). Conclusions Urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed LMW PAH biomarkers are associated with diabetes mellitus in US adults 20–65 years of age. The association of a one-time biomarker of PAH exposure has limitations commonly associated with cross-sectional studies, yet is consistent with experimental animal data and is worthy of additional consideration.

Age at menarche, the leg length to sitting height ratio, and risk of diabetes in middle-aged and elderly Chinese men and women.

Aims To 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 Methods Information from 69,385 women and 55,311 men, aged 40–74 years from the Shanghai Womens Health Study and Shanghai Mens 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. Results There 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. Conclusions Our 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.

Skin Intrinsic Fluorescence Correlates With Autonomic and Distal Symmetrical Polyneuropathy in Individuals With Type 1 Diabetes

OBJECTIVE To determine whether skin intrinsic fluorescence (SIF) was associated with autonomic neuropathy and confirmed distal symmetrical polyneuropathy (CDSP) in 111 individuals with type 1 diabetes (mean age 49 years, mean diabetes duration 40 years). RESEARCH DESIGN AND METHODS SIF was measured using the SCOUT DM device. Autonomic neuropathy was defined as an electrocardiographic abnormal heart rate response to deep breathing (expiration-to-inspiration ratio <1.1). CDSP was defined using the Diabetes Control and Complications Trial clinical exam protocol (the presence of two or more of the following: symptoms, sensory and/or motor signs, and/or reduced/absent tendon reflexes consistent with DSP) confirmed by the presence of an abnormal age-specific vibratory threshold (using a Vibratron II tester). RESULTS The prevalence of autonomic neuropathy and CDSP were 61 and 66%, respectively. SIF was higher in those with autonomic neuropathy (P < 0.0001). In multivariable analyses controlling for age and updated mean (18-year average) HbA1c, and allowing for other univariately and clinically significant correlates of autonomic neuropathy, each SD change in SIF was associated with a 2.6-greater likelihood of autonomic neuropathy (P = 0.006). Receiver operating characteristic (ROC) analyses revealed that SIF and updated mean HbA1c accounted for 80 and 57%, respectively, of the area under the curve (AUC) for autonomic neuropathy. SIF also was higher in those with CDSP (P < 0.0001) and remained so in multivariable analyses (odds ratio 2.70; P = 0.005). ROC analyses revealed that SIF and updated mean HbA1c accounted for 78 and 59%, respectively, of the AUC for CDSP. CONCLUSIONS SIF, a marker of dermal advanced glycation end products, appears to be more strongly associated with the presence of both CDSP and autonomic neuropathy than mean HbA1c.

Skin Intrinsic Fluorescence Is Associated With Coronary Artery Disease in Individuals With Long Duration of Type 1 Diabetes

OBJECTIVE Skin intrinsic fluorescence (SIF) reflects many factors, including the presence of certain advanced glycation end products. We investigated whether SIF was associated with coronary artery disease (CAD) in type 1 diabetes and whether this relationship was independent of renal disease. RESEARCH DESIGN AND METHODS SIF was measured in 112 subjects from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study and 60 from MedStar Health Research Institute when mean age and diabetes duration were 48 and 36 years, respectively. Cumulative glycemic exposure (updated mean A1C) represented a mean of 18 years’ follow-up in EDC and 10.3 in MedStar. RESULTS Of the 172 participants, 30 had CAD (15 male and 15 female). SIF levels were higher in those with CAD (P < 0.0001). SIF was strongly associated with CAD (odds ratio [OR] 3.5 [95% CI 2.1–6.1]). After age, duration, and updated mean A1C were controlled for, SIF remained associated with CAD (2.4 [1.3–4.4]), more strongly in men (5.6 [2.1–14.6]) than in women (1.4 [0.61–3.3]). As there was no significant sex interaction, further analyses were conducted combining the sexes. Further accounting for sex and nephropathy status did not improve the model fit, though with nephropathy in the model, the OR for SIF was reduced to 1.7 (95% CI 0.89–3.4). CONCLUSIONS SIF has a significant cross-sectional association with CAD. This association is strongly linked to age and duration and, to a lesser degree, to mean A1C and renal disease. SIF therefore may be a useful overall marker of CAD risk in type 1 diabetes.

Double-edged relationship between adiposity and coronary artery calcification in type 1 diabetes.

Coronary artery disease (CAD), a leading cause of death in type 1 diabetes (T1D), often occurs two or more decades earlier in this population compared to the population without diabetes. Although CAD generally increases with adiposity, this association is unclear in T1D. In this study, we examined associations of adiposity with coronary artery calcium (CAC) in 315 individuals with T1D. Mean age and diabetes duration were 42 and 34 years, respectively, at study entry. CAC, visceral adiposity (VAT) and subcutaneous adiposity (SAT) were determined by electron beam tomography; and BMI and waist circumference (WC) were determined. The presence of CAC was positively associated with VAT, SAT and BMI in men (p<0.05) and with all four adiposity measures in women (p<0.05) after adjustment for age and other traditional cardiovascular risk factors. However, after adjustment, the degree of CAC was not associated with any of the four adiposity measures, with the exception of SAT in women. Women in the lowest tertile of SAT had more CAC than those in the second tertile (p<0.016). Adiposity was positively associated with the presence of CAC, but the relationship with its severity was either inverse or non-existent. This double-edged association emphasises the complex relationship between adiposity and cardiovascular risk in diabetes.

Cross-sectional evaluation of noninvasively detected skin intrinsic fluorescence and mean hemoglobin a1c in type 1 diabetes.

BACKGROUND This study evaluated the relationship between skin intrinsic fluorescence (SIF) and long-term mean hemoglobin A1c (HbA1c) in individuals with type 1 diabetes. SUBJECTS AND METHODS We undertook a cross-sectional analysis of 172 individuals with type 1 diabetes followed longitudinally with HbA1c data available over an average of 16.6 years. SIF was evaluated cross-sectionally using the SCOUT DS device (VeraLight Inc., Albuquerque, NM) and correlated with most recent HbA1c and long-term mean HbA1c. Potential determinants of this relationship, including age, gender, smoking status, duration of diabetes, and renal function, were also evaluated. RESULTS Age-adjusted skin intrinsic fluorescence significantly correlated with long-term mean HbA1c (R=0.44, P<0.0001). In contrast, there was no significant relationship between SIF and most recent HbA1c (R=0.14, P=0.075). The best-fit model describing the relationship between SIF and mean HbA1c controlled for factors of age, duration of disease, renal function, and site of study conduct. Controlling for these factors was also important in understanding the relationship between most recent HbA1c and SIF. Evaluating longer-term HbA1c data also strengthened the relationship between SIF and mean HbA1c. In the presence of renal dysfunction or damage, as indicated by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or presence of gross proteinuria, there was no significant correlation between SIF and mean HbA1c. CONCLUSIONS Noninvasive detection of SIF significantly correlates with long-term mean HbA1c, providing insight into long-term glycemic exposure. Age, duration of diabetes, and renal function are potential contributors to this relationship.

Mortality Among Low-Income African Americans and Whites With Diabetes

OBJECTIVE To estimate mortality rates and risk factors for mortality in a low-socioeconomic status (SES) population of African Americans and whites with diabetes. RESEARCH DESIGN AND METHODS We determined mortality among African Americans and whites aged 40–79 years with (n = 12,498) and without (n = 49,914) diabetes at entry into a cohort of participants recruited from government-funded community health centers. Multivariable Cox analysis was used to estimate mortality hazard ratios (HRs) (95% CI) among those with versus those without diabetes and among those with diabetes according to patient characteristics. RESULTS During follow-up (mean 5.9 years), 13.5% of those with and 7.3% of those without diabetes died. All-cause mortality risk was higher among those with versus without diabetes for both African Americans (HR 1.84 [95% CI 1.71–1.99]) and whites (1.80 [1.58–2.04]), although among those with diabetes, mortality was lower among African Americans than whites (0.78 [0.69–0.87]). Mortality risk increased with duration of diabetes and was greater among patients on insulin therapy and reporting histories of cardiovascular disease (CVD), hypertension, and stroke. The HRs associated with these multiple risk factors tended to be similar by sex and race, with the exception of a differentially higher impact of prevalent CVD on mortality among African Americans (interaction P value = 0.03), despite a lower baseline prevalence of CVD. CONCLUSIONS In this population with similarly low SES and access to health care, strong and generally similar predictors of mortality were identified for African Americans and whites with diabetes, with African Americans at a moderately but significantly lower mortality risk.