Skin intrinsic fluorescence scores are a predictor of all-cause mortality risk in type 1 diabetes: The Epidemiology of Diabetes Complications study.

AIMS: We assessed the association of skin intrinsic fluorescence (SIF) scores, as a measure of advanced glycation end-products (AGE), with all-cause mortality in type 1 diabetes (T1D). METHODS: This is an observational retrospective study of a convenience sample from the Epidemiology of Diabetes Complications (EDC) study. AGEs were measured with a SIF score between 2007 and 2014; vital status was assessed in 2020. RESULTS: Among 245 participants, mean age was 48.6 ±â€¯7.4 years, median diabetes duration was 39.5 years (IQR: 34.2, 44.9), and 53.5% were female. Compared to survivors, the deceased (n = 20) were older, with higher SIF scores, longer diabetes duration, lower body mass index (BMI), and an adverse risk factor profile (all p≤0.05). Univariate Cox regression showed a marginal association between SIF score and mortality (HR: 1.1, 95% CI 0.9-1.2, p = 0.06), which persisted after adjustment for multiple daily insulin shots/pump (MDI) use (HR: 1.1, 95% CI 1.0-1.2, p = 0.04). This association was attenuated after adjustment for T1D duration, A1c months, or estimated glomerular filtration rate (eGFR). CONCLUSIONS: In individuals with long duration T1D, SIF scores adjusted for MDI predicted all-cause mortality, although this association was attenuated after adjustments. Given the nature of sampling and small number of events, our findings require replication.

Perfluoroalkyl substances and likelihood of stroke in persons with and without diabetes.

OBJECTIVE: The main objective of this study is to evaluate the relationship of perfluoroalkyl substances with stroke and any modifying influence of diabetes. METHODS: Data on 3921 adults aged ⩾20 years with and 44,285 without diabetes were drawn from the C8 Health Project. Four perfluoroalkyl substances were investigated: perfluorohexane sulphate, C8 - perfluorooctanoic acid, perfluoroctane sulfonate and perfluorononaoic acid. RESULTS: There were 238 cases of stroke among those with and 643 among those without diabetes. In analyses controlled for age, sex, race, diabetes duration, body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein, kidney function and a history of smoking, a history of stroke was significantly inversely associated with serum perfluorohexane sulphate (odds ratio = 0.75, 0.64-0.88) and perfluoroctane sulfonate (odds ratio = 0.81, 0.70-0.90), but not perfluorooctanoic acid (odds ratio = 1.04, 0.94-1.15) or perfluorononaoic acid (odds ratio = 0.89, 0.70-1.14) among those with diabetes. Perfluoroalkyl substances demonstrated no association with stroke among those without diabetes (p interaction = 0.006 and 0.01 for perfluorohexane sulphate and perfluorooctanoic acid, respectively). CONCLUSION: In this large cross-sectional study, serum levels of perfluorohexane sulphate and perfluoroctane sulfonate were inversely associated with stroke among those with diabetes. Although mechanisms and implications for this diabetes-specific inverse relationship need to be further explored, our data suggest that perfluoroalkyl substances do not increase risk of stroke among persons with or without diabetes.

Perfluoroalkyl substances are inversely associated with coronary heart disease in adults with diabetes.

AIMS: Perfluoroalkyl substances (PFAS) are environmentally and biologically persistent synthetic environmental contaminants linked to adverse health outcomes. Though null to modest inverse relationships between PFAS and coronary heart disease (CHD) have been reported, studies regarding relationships in high risk populations such as those with diabetes are sparse. We investigated the relationship of PFAS with CHD in persons with diabetes. METHODS: Data on 5270 adults, aged ≥20 years, with diabetes were obtained from the C8 Health Project. Four PFAS were investigated separately: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA). RESULTS: In logistic regression analyses adjusting for age, sex, diabetes duration, BMI, smoking, lipids, WBC, CRP, eGFR, uric acid, hemoglobin and iron, all PFAS were inversely associated with CHD, ORs (95% CIs): PFHxS; 0.72 (0.65-0.79), PFOA; 0.90 (0.81-0.96), PFOS; 0.90 (0.81-0.99), PFNA; 0.88 (0.76-1.02). Stratification by chronic kidney disease status revealed similar inverse relationships for those with and without chronic kidney disease. CONCLUSIONS: In this cross-sectional study of over 5000 adults with diabetes, PFAS showed inverse associations with CHD. These findings may, if confirmed in future studies, provide new physiologic understanding of CHD prevention strategies.

Perfluoroalkyl substances and kidney function in chronic kidney disease, anemia, and diabetes.

BACKGROUND: Anemia often complicates chronic kidney disease (CKD), leading to insufficient tissue oxygenation and hypoxic injury, the factor thought to underlie progression from CKD to renal failure. Perfluorocarbons are potent oxygen transporters used in organ preservation and synthetic blood development. Data are scarce on their relationship with kidney function, especially in diabetes where anemia and hypoxia are more prevalent. We investigated the relationship of perfluoroalkyl acids (PFAS) with kidney function and variation by diabetes and anemia status. METHODS: Data on 53,650 adults (5,210 with diabetes) were obtained from the C8 Health Project. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorooctane sulfonate, and perfluorononanoic acid. FINDINGS: Each PFAS was positively associated with eGFR among those with CKD or anemia; this was the strongest among those with both CKD and anemia, followed by those with CKD uncomplicated by anemia. These relationships were more pronounced among those with diabetes (all P<0.01). In the absence of both CKD and anemia, PFAS was inversely associated with eGFR. Among persons with both anemia and diabetes, when further stratified by CKD stage, compared to an eGFR <30, ORs (95% CI) for being in the eGFR ≥ 90, 60-89, 45-59, and 30-45 range, respectively, were 3.20 (2.00-5.13), 2.64 (1.83-3.80), 3.18 (2.17-4.67), and 1.99 (1.38-2.86) for each ng/dL increase in PFHxS. Results were similar for each PFAS. INTERPRETATION: PFAS are inversely associated with kidney function in CKD and diabetes, with a stronger relation observed when anemia is present.

Increased risk of respiratory diseases in adults with Type 1 and Type 2 diabetes.

AIMS: Diabetes is linked with decreases in lung elasticity and in capacity to transfer carbon monoxide. Systemic inflammation, a common concern with diabetes, may contribute to airflow obstruction. We examined the association of self-reported diabetes with self-reported respiratory diseases (RDs) among 53,146 adults from the C8 Health Project. METHODS: Participants were categorized into three groups: Type 1 (T1D, n = 781), Type 2 (T2D, n = 4277), or no diabetes (n = 48,088). ORs (95% CIs) for the association of diabetes with four RDs were computed: emphysema, chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), and asthma. Covariates controlled for were age, sex, estimated glomerular filtration rate, C-reactive protein, smoking history, BMI, and perfluorooctonaoic acid (C8). RESULTS: RDs were present in 26%, 21% and 13% of persons with T1D, T2D, and no diabetes, respectively. In multivariable analyses, persons with T1D were 62% more likely to have any RD (OR: 1.62, CI: (1.36-1.93)), while those with T2D were 1.3 times as likely (OR: 1.26, CI: 1.15-1.37)). Compared to those without diabetes, in those with T1D and T2D diabetes respectively, ORs (CIs) for COPD were 1.89 (1.38-2.57), 1.45 (1.23-1.71), asthma: 1.51 (1.21-1.87), 1.38 (1.24-1.53), CB: 1.96 (1.57-2.45), 1.35 (1.20-1.52) and emphysema: 1.25 (0.85-1.82), 1.31 (1.10-1.56). Population attributable risks for any RDs associated with a history of smoking were 19%, 30%, and 26% for those with Type 1, Type 2, and no diabetes respectively. CONCLUSIONS: Diabetes, more so in T1D, appears to increase RD risk. Smoking is an important risk factor, but not as informative in Type 1 diabetes.

The obesity epidemic and rising diabetes incidence in a low-income racially diverse southern US cohort.

BACKGROUND: Obesity is known to be a major risk factor for diabetes, but the magnitude of risk and variation between blacks and whites are less well documented in populations heavily affected by obesity. Herein we assess rates and risks of incident diabetes in a diverse southern population where obesity is common. METHODS: A total of 24,000 black and 14,064 white adults aged 40-79 in the Southern Community Cohort Study with no self-reported diabetes at study enrollment during 2002-2009 was followed for up to 10 (median 4.5) years. Incidence rates, odds ratios (OR) and accompanying 95% confidence intervals (CI) for medication-treated incident diabetes were determined according to body mass index (BMI) and other characteristics, including tobacco and alcohol consumption, healthy eating and physical activity indices, and socioeconomic status (SES). RESULTS: Risk of incident diabetes rose monotonically with increasing BMI, but the trends differed between blacks and whites (pinteraction < .0001). Adjusted ORs (CIs) for diabetes among those with BMI≥40 vs 20-25 kg/m2 were 11.9 (8.4-16.8) for whites and 4.0 (3.3-4.8) for blacks. Diabetes incidence was more than twice as high among blacks than whites of normal BMI, but the racial difference became attenuated as BMI rose, with estimated 5-year probabilities of developing diabetes approaching 20% for both blacks and whites with BMI≥40 kg/m2. Diabetes risk was also associated with low SES, significantly (pinteraction≤.02) more so for whites, current cigarette smoking, and lower healthy eating and physical activity indices, although high BMI remained the predominant risk factor among both blacks and whites. From baseline prevalence and 20-year projections of the incidence trends, we estimate that the large majority of surviving cohort participants with BMI≥40 kg/m2 will be diagnosed with diabetes. CONCLUSIONS: Even using conservative criteria to ascertain diabetes incidence (i.e., requiring diabetes medication use and ignoring undiagnosed cases), rates of obesity-associated diabetes were exceptionally high in this low-income adult population. The findings indicate that effective strategies to halt the rising prevalence of obesity are needed to avoid substantial increases in diabetes in coming years.

Effect of high density lipoprotein cholesterol on the relationship of serum iron and hemoglobin with kidney function in diabetes.

Findings of increased hemoglobin inside the HDL proteome among persons with diabetes who have haptoglobin 2-2 genotype suggest that iron-induced lipid peroxidation may be involved in diabetic kidney disease. We investigated the relationships of serum hemoglobin and iron with kidney function, and whether this varied by level of HDLc, in 5296 adults with and 49,161 without diabetes. Estimated eGFR was our marker of kidney function. Hemoglobin was positively associated with eGFR among those with diabetes and inversely among those without diabetes (interaction p-value <0.0001). Iron was inversely associated with eGFR regardless of diabetes status. When stratified by median HDLc and median hemoglobin, among persons with diabetes mean eGFR was highest in those with high hemoglobin and low HDLc and lowest in those with both low hemoglobin and low HDLc. This divergent relationship was not observed in the non-diabetic population. In contrast to hemoglobin, high iron and low HDLc were associated with a lower mean eGFR regardless of diabetes status. Our data suggest that among persons with diabetes, both hemoglobin and iron are harmful to kidney function at high levels. Our data also suggest that HDLc may play a role in the relationship of high hemoglobin in kidney function in diabetes.

Validating the extract, transform, load process used to populate a large clinical research database.

BACKGROUND: Informaticians at any institution that are developing clinical research support infrastructure are tasked with populating research databases with data extracted and transformed from their institution's operational databases, such as electronic health records (EHRs). These data must be properly extracted from these source systems, transformed into a standard data structure, and then loaded into the data warehouse while maintaining the integrity of these data. We validated the correctness of the extract, load, and transform (ETL) process of the extracted data of West Virginia Clinical and Translational Science Institute's Integrated Data Repository, a clinical data warehouse that includes data extracted from two EHR systems. METHODS: Four hundred ninety-eight observations were randomly selected from the integrated data repository and compared with the two source EHR systems. RESULTS: Of the 498 observations, there were 479 concordant and 19 discordant observations. The discordant observations fell into three general categories: a) design decision differences between the IDR and source EHRs, b) timing differences, and c) user interface settings. After resolving apparent discordances, our integrated data repository was found to be 100% accurate relative to its source EHR systems. CONCLUSION: Any institution that uses a clinical data warehouse that is developed based on extraction processes from operational databases, such as EHRs, employs some form of an ETL process. As secondary use of EHR data begins to transform the research landscape, the importance of the basic validation of the extracted EHR data cannot be underestimated and should start with the validation of the extraction process itself.

Perfluoroalkyl substances and beta cell deficient diabetes.

AIMS: Perfluoroalkyl substances (PFAS) are synthetic hydrocarbons shown to preserve pancreatic islet cell viability and reduce islet cell hypoxia and apoptosis. We investigated the relationship of serum PFAS with diabetes, and whether this varied by diabetes type. METHODS: 6,460 individuals with and 60,439 without diabetes from the C8 Health Project, were categorized into three groups: type 1 (n=820), type 2 (n=4,291), or uncategorized diabetes (n=1,349, missing data on diabetes type or diabetes based on blood sugar at study entry). Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononaoic acid (PFNA). RESULTS: PFAS levels were significantly lower in those with diabetes, and lowest in those with type 1 diabetes. In age and sex adjusted analyses, ORs (CI) for type 1, type 2, and uncategorized diabetes compared to no diabetes were 0.59 (0.54-0.64), 0.74 (0.71-0.77), 0.84 (0.78-0.90), respectively for PFHxS; 0.69 (0.65-0.74), 0.87 (0.89-0.91), 0.92 (0.88-0.97), respectively for PFOA; 0.65 (0.61-0.70), 0.86 (0.82-0.90), 0.93 (0.86-1.03), respectively for PFOS; and 0.65 (0.57-0.74), 0.94 (0.88-1.00), 0.95 (0.85-1.06), respectively for PFNA. Further adjustment for eGFR and other covariates did not eliminate these inverse associations. CONCLUSIONS: PFAS levels were negatively associated with diabetes. This inverse relationship was strongest for type 1 diabetes, suggesting the relationship with serum PFAS may vary with the severity of islet cell deficiency.

Glycemic control and fracture risk in elderly patients with diabetes.

AIMS: Elderly patients with diabetes are at increased fracture risk. Although long exposure to hyperglycemia may increase fracture risk via adverse effects on bone metabolism, tight glycemic control may increase risk via trauma subsequent to hypoglycemia. We tested the prospective relationship between glycemic control and fracture risk in 10,572 elderly patients (age ≥65) with diabetes. METHODS: Geriatric patients with diabetes were drawn from Vanderbilt University Medical Center's Electronic Health Record. Baseline was defined as age at first HbA1c after the latter of age 65 or ICD 9 code for diabetes. Cox analysis was used to test the relationship of updated mean HbA1c (average HbA1c over follow-up) with time to first fracture since baseline. HbA1c was categorized as follows: <6.5% [<48mmol/mol]; 6.5-6.9% [48-52mmol/mol]; 7-7.9% [53-63mmol/mol]; 8-8.9% [64-74 mmol-mol]; ≥9% [≥75mmol/mol]. The number of BMI measurements was used as a surrogate for relative frequency of outpatient visits, i.e. patient-provider contacts. RESULTS: During follow-up, there were 949 fracture events. HbA1c demonstrated a cubic relationship with fracture risk (p<0.05). In analyses accounting for age, sex, race, and number of BMI measures (a surrogate for patient-provider interaction), compared to an HbA1c of 7-7.9%, HRs (95% CIs) were: HbA1c<6.5% HR=0.97 (0.82-1.14), 6.5-6.9% HR=0.80 (0.66-0.97), 8-8.9% HR=1.13 (0.92-1.40), ≥9% HR=1.19 (0.93-1.54). CONCLUSIONS: An HbA1c of 6.5-6.9% is associated with the lowest risk of fracture in elderly patients with diabetes. Risk associated with an HbA1c ≥9% may be a marker of infrequent patient-provider interaction.

Effect of BMI on cardiovascular and metabolic syndrome risk factors in an Appalachian pediatric population.

BACKGROUND: The purpose of this study was to characterize cardiovascular risk factors in a rural pediatric population by body mass index (BMI) category and the presence of the metabolic syndrome. METHODS: Data on 13,018 children and adolescents (aged younger than 20 years) from West Virginia and Ohio in 2005-2006 were obtained from the C8 Health Project to determine the prevalence of overweight/obesity and the metabolic syndrome, which was then compared with National Health and Nutrition Examination Survey 2005-2006 data. Cardiovascular risk factors were assessed by age-standardized and sex-standardized BMI category (<85th, 85th-95th, >95th percentiles) and the presence of metabolic syndrome, defined as the presence of three or more of the following criteria: BMI >97th percentile, triglycerides >110 mg/dL, high-density lipoprotein cholesterol <40 mg/dL, and fasting blood glucose >110 mg/dL. RESULTS: The population was 51% male and 95% white. The prevalence of overweight/obesity was 38% and metabolic syndrome was 4.6% in the C8 population, compared with a prevalence of 30% and 3.4%, respectively, within the National Health and Nutrition Examination Survey population. In our Appalachian population, a significant adverse trend across BMI categories was observed for lipids, insulin, inflammatory markers, white blood cell count, and C-reactive protein. Significant differences in these risk factors were seen among those with metabolic syndrome compared with those without metabolic syndrome. CONCLUSION: The increased prevalence of overweight/obesity and the metabolic syndrome along with the increase in cardiovascular risk factors in Appalachian children and adolescents, suggests a cohort that may develop earlier onset and possibly increased severity of cardiovascular disease and other complications associated with metabolic syndrome and obesity.

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.

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.

Mortality by race among low-income adults with early-onset insulin-treated diabetes.

OBJECTIVE: To determine if long-term mortality rates in early-onset insulin-treated diabetes differ by race among adults of similar socioeconomic status. RESEARCH DESIGN AND METHODS: A total of 391 (299 African Americans, 92 whites) mostly low-income adults 40-79 years of age with insulin-treated diabetes diagnosed before 30 years of age were recruited from community health centers in the southeast U.S. Cox models were used to estimate hazard ratios (HRs) of all-cause mortality among African Americans compared with whites. Additionally, standardized mortality ratios (SMRs) were used to compare the mortality experience of the individuals with diabetes with both national and general community health center sex- and race-specific population norms. RESULTS: Mean age at diabetes diagnosis and cohort entry, respectively, was 21 and 50 years in African Americans and 19 and 51 years in whites. During an average of 6.7 years of follow-up, 29% of African Americans and 35% of whites died. In multivariable analysis, no significant mortality difference was observed among African Americans compared with whites (HR 0.83 [95% CI 0.53-1.30]; P=0.51). Compared with the race-specific U.S. general population, SMRs for those with diabetes were 5.7 in African Americans and 11.7 in whites. However, when compared with the same source population (i.e., the community health center population), SMRs were 3.5 and 3.7 in African Americans and whites, respectively. CONCLUSIONS: Elevated mortality persists in men and women with long duration of early-onset insulin-treated diabetes, but given survival to 40 years of age and similarly low economic status and access to health care, our data do not suggest a racial disparity in mortality.

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.

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.

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.

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 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. 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.

Mortality experience of a low-income population with young-onset diabetes.

OBJECTIVE: In young-onset diabetes, insulin therapy status is a rough marker of diabetes type. We describe the mortality experience of a low-income, predominantly minority population with diabetes diagnosed before age 30 years, stratified by insulin therapy. RESEARCH DESIGN AND METHODS: A total of 1,098 adults aged 40-79 years (median 49) diagnosed with diabetes before age 30 years and 49,914 without diabetes were recruited from community health centers. Individuals with diabetes were categorized by insulin therapy at baseline: group A, insulin therapy only; group B, insulin therapy and an oral hypoglycemic agent; and group C, no insulin therapy. Cox models were used to compute hazard ratios (HRs) and 95% CI for cause-specific mortality based on both underlying and contributing causes of death from death certificates. RESULTS: During follow-up (mean 3.9 years), 15.0, 12.5, and 7.3% of groups A, B, and C, respectively, and 4.6% without diabetes died. Compared with individuals without diabetes, HRs (CI) for all-cause mortality were 4.3 (3.4-5.6), 4.2 (2.8-6.3), and 2.0 (1.4-2.8) in groups A, B, and C, respectively. The leading cause of death was renal failure (end-stage renal disease [ESRD]) in group A, ESRD and coronary artery disease (CAD) in group B, and CAD in group C and individuals without diabetes. HRs for these conditions were at least twice as high as the HRs for all-cause mortality, reaching 17.3 (10.2-29.3), 17.9 (8.3-38.7), and 5.1 (2.3-11.7) in groups A, B, and C, respectively, for ESRD. CONCLUSIONS: Excess mortality persists among people with young-onset diabetes of long duration, with ESRD and CAD as the leading contributors to mortality.