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OBJECTIVES: Urinary tract infections (UTIs) are common, but overdiagnosed, in children with spina bifida. We sought to evaluate the diagnostic test characteristics of urinalysis (UA) findings for symptomatic UTI in children with spina bifida. METHODS: Retrospective cross-sectional study using data from 2 centers from January 1, 2016, to December 31, 2021. Children with myelomeningocele aged <19 years who had paired UA (and microscopy, when available) and urine culture were included. The primary outcome was symptomatic UTI. We used generalized estimating equations to control for multiple encounters per child and calculated area under the receiver operating characteristics curve, sensitivity, and specificity for positive nitrites, pyuria ($10 white blood cells/high-powered field), and leukocyte esterase (more than trace) for a symptomatic UTI. RESULTS: We included 974 encounters from 319 unique children, of which 120 (12.3%) met our criteria for UTI. Pyuria had the highest sensitivity while nitrites were the most specific. Comparatively, nitrites were the least sensitive and pyuria was the least specific. When the cohort was limited to children with symptoms of a UTI, pyuria remained the most sensitive parameter, whereas nitrites remained the least sensitive. Nitrites continued to be the most specific, whereas pyuria was the least specific. Among all encounters, the overall area under the receiver operating characteristics curve for all components of the UA was lower in children who use clean intermittent catheterizations compared with all others. CONCLUSIONS: Individual UA findings have moderate sensitivity (leukocyte esterase or pyuria) or specificity (nitrites) but overall poor diagnostic accuracy for symptomatic UTIs in children with spina bifida. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that there is heterogeneity in long-term patterns of glycemic control with respect to cardiovascular disease (CVD) development in type 1 diabetes and that risk factors for CVD differ by glycemic control pattern. Thus, we estimated associations between data-derived latent HbA1c trajectories and 30-year CVD risk in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset (<17 years old) type 1 diabetes.Research Design and Methods: Participants (n = 536 with two or more HbA1c measurements [median 6] and CVD-free at baseline; mean age 27 and diabetes duration 18 years) were followed from 1986 to 1988 to 2016 to 2018 to ascertain CVD incidence (CVD death, myocardial infarction, stroke, coronary revascularization or blockage ≥50%, ischemic electrocardiogram, or angina). Latent HbA1c trajectories and their association with time-to-CVD incidence were simultaneously assessed using joint latent class mixed models.Results: Two HbA1c trajectories with respect to differential CVD risk were identified: low (HbA1c ∼8% [64 mmol/mol] and improving over follow-up, 76% of cohort) and high (HbA1c ∼10% [86 mmol/mol] and stable, 24%). Overall, 30-year CVD incidence was 47.4% (n = 253); major adverse cardiovascular event incidence was 31.0% (n = 176). High HbA1c was associated with threefold increased CVD risk versus low HbA1c. Both groups had similar age and diabetes duration. Non-HDL cholesterol and estimated glomerular filtration rate were associated with CVD risk only in low HbA1c; albumin excretion rate was associated with CVD risk only in high HbA1c.Conclusions: These risk factor differences suggest that pathways to CVD may differ by glycemic control, potentially resulting in important implications for prognosis in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims: We aimed to identify long‐term HbA1c trajectories and examine associated characteristics in an observational, childhood‐onset (<17 years) type 1 diabetes cohort. Methods: Data are from the Epidemiology of Diabetes Complications study, comprising 405 participants with ≥2 of seven possible HbA1c measurements over follow‐up (1988–2013) and available DNA (baseline mean diabetes duration 21 years, 53% men). HbA1c trajectories were estimated using latent class growth models. Baseline and change in participant characteristics were compared across trajectories. Results: Five HbA1c trajectories were identified: low (51%), intermediate stable (22%), improved (19%), high stable (6%), and worsened (2%; not included in analyses). Age, diabetes duration, diabetes onset age, and sex did not differ across trajectories. Characteristics did not differ significantly between intermediate stable and low trajectories at baseline, though albumin excretion rate (AER, p = 0.0002) and estimated glomerular filtration rate (eGFR, p = 0.001) worsened slightly more in intermediate stable over time. Improved and high stable trajectories had higher baseline LDL‐c (p = 0.002 and 0.003, respectively). Improved trajectory increased median self‐monitoring of blood glucose from <1 to 3.5 times/day (p < 0.0001) and had larger LDL‐c improvement (p = 0.004) but greater worsening of AER (p < 0.0001) and eGFR (p < 0.0001) than low. The A allele of rs12970134 (near MC4R) was associated with improved (p = 0.0003) or high stable (p = 0.001) HbA1c trajectory, both patterns with high baseline HbA1c. Conclusions: Long‐term HbA1c trajectories were primarily associated with modifiable factors in this type 1 diabetes cohort. The intermediate stable pattern had a risk factor profile that suggests some protection against adverse metabolic effects of chronic hyperglycaemia, warranting further study. [ABSTRACT FROM AUTHOR]

Aim: To determine the effect of hydroxychloroquine (HCQ) on skeletal muscle and liver insulin sensitivity, insulin clearance, inflammation and adipokines. Methods: Insulin‐resistant adults without rheumatic disease were randomized to 13 weeks of HCQ (400 mg/day) versus placebo (double‐blinded). Primary outcomes were changes in skeletal muscle and liver insulin sensitivity assessed by hyperinsulinaemic‐euglycaemic clamp and stable‐isotope tracer methods. Secondary outcomes included insulin clearance, inflammation biomarkers and adipokines. Results: Compared with placebo, HCQ significantly improved skeletal muscle insulin sensitivity by 26% (p =.019) and enhanced systemic glucose clearance (p =.025). By contrast, HCQ had no effect on hepatic insulin sensitivity. HCQ did not affect insulin clearance but decreased circulating IL‐6 (p =.01) and increased adiponectin (p =.045). There were no effects on leptin, RBP‐4, FGF‐21 or C‐reactive protein. Conclusions: HCQ selectively enhances insulin sensitivity and glucose disposal in skeletal muscle, without affecting hepatic insulin sensitivity or insulin clearance. These findings offer a mechanistic explanation for the antidiabetic properties of HCQ and suggest that this medication might be useful in conditions linked to insulin resistance such as type 2 diabetes. [ABSTRACT FROM AUTHOR]

The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA1c (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed. [ABSTRACT FROM AUTHOR]

Aim: To assess the role of periodontal disease (PD) as a predictor of coronary artery disease (CAD) and mortality in a prospective type 1 diabetes (T1D) cohort and to evaluate the role of smoking in this relationship.Methods: Data were based on 320 participants of the Pittsburgh Epidemiology of Diabetes Complications study of T1D who, during 1992-94, received a partial mouth periodontal exam, and who were followed for up to 19 years to ascertain complication incidence. PD was defined as clinical attachment loss of ≥4 mm for at least 10% of the examined sites. Predictors of all-cause mortality; Hard CAD (CAD death, myocardial infarction or revascularization), and Total CAD (Hard CAD, angina, ischemic ECG) were assessed using Cox models.Results: During 19 years of follow-up, 33.7% (97/288) developed CAD, 27.3% (83/304) developed Hard CAD, and 16.9% (54/320) died. Among current smokers, 46.4% (26/56) developed CAD, 42.7% (24/56) developed Hard CAD and 29.5% (18/61) died. PD was not associated with all-cause mortality, although it was a significant predictor of both CAD (HR = 1.12, CI = 1.01-1.23) and Hard CAD (HR = 1.30, CI = 1.11-1.51). As smoking modified the PD-CAD and PD-Hard CAD associations, analyses were stratified by smoking status. PD was associated with an increased risk of CAD (HR = 1.25, CI = 1.03-1.50) and Hard CAD (HR = 1.85, CI = 1.17-2.93) only among smokers.Conclusion: PD was a significant predictor of CAD and Hard CAD among current smokers with T1D. [ABSTRACT FROM AUTHOR]

In a recent Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study report, mean HbA1c was the strongest predictor of cardiovascular disease (CVD) after age. In DCCT/EDIC, mean diabetes duration was 6 years (median 4) at baseline and those with high blood pressure or cholesterol were excluded. We now replicate these analyses in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (at <17 years of age) type 1 diabetes, with similar age (mean 27 years in both studies) but longer diabetes duration (mean 19 years and median 18 years) and no CVD risk factor exclusion at baseline. CVD incidence (CVD death, myocardial infarction (MI), stroke, revascularization, angina, or ischemic electrocardiogram) was associated with diabetes duration, most recent albumin excretion rate (AER), updated mean triglycerides, baseline hypertension, baseline LDL cholesterol, and most recent HbA1c Major atherosclerotic cardiovascular events (CVD death, MI, or stroke) were associated with diabetes duration, most recent AER, baseline systolic blood pressure, baseline smoking, and updated mean HbA1c Compared with findings in DCCT/EDIC, traditional risk factors similarly predicted CVD; however AER predominates in EDC and HbA1c in DCCT/EDIC. Thus, the relative impact of HbA1c and kidney disease in type 1 diabetes varies according to diabetes duration. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is associated with increased risk of cardiovascular disease (CVD), but hyperglycemia (measured by hemoglobin A1c (HbA1c) level), which characterizes T1D, has itself been an inconsistent predictor of CVD incidence. However, only baseline HbA1c or a summary measure (e.g., mean level over follow-up) is usually analyzed. Joint models allow simultaneous modeling of repeatedly measured longitudinal covariates, using random effects, and time-to-event data. We evaluated data from the Pittsburgh Epidemiology of Diabetes Complications Study, an ongoing prospective cohort study of childhood-onset T1D that has followed participants since 1986-1988 and has repeatedly found little association between baseline HbA1c or mean follow-up HbA1c and coronary artery disease incidence. Of 561 participants without CVD at baseline, 263 (46.9%) developed CVD over a period of 25 years (1986-2014). In joint models, each 1% unit increase in HbA1c trajectory was associated with a 1.26-fold increased risk of CVD (95% confidence interval: 1.07, 1.45), after adjustment for baseline levels of other CVD risk factors, and a 1.13-fold increased risk (95% confidence interval: 0.99, 1.32) after adjustment for updated mean levels of other CVD risk factors. These findings, which support the need for good glycemic control to prevent CVD in persons with T1D, underscore the importance of utilizing methods incorporating within-subject variation over time when analyzing and interpreting longitudinal cohort study data. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess association between abnormal LVEF, in the absence of coronary artery disease (CAD), and 25-year incidence of major outcomes of diabetes (MOD) in a cardiology substudy of the Pittsburgh Epidemiology of Diabetes Complications cohort of childhood-onset type 1 diabetes.Methods: 115 normotensive type 1 diabetes individuals without known CAD, underwent a baseline exercise radionuclide ventriculography. Abnormal LVEF was defined as a resting ejection fraction <50% or a failure to increase ejection fraction with exercise by >5% (men) or a fall in ejection fraction with exercise (women). Cox proportional hazards models were used to predict the composite endpoint of MOD (first instance of major CAD, stroke, end-stage renal disease, blindness, amputation or diabetes-related death).Results: Mean baseline age was 28 and diabetes duration 19 years. In a mean follow-up of 19 years, 50 MOD events were identified. Allowing for established risk factors at baseline, abnormal LVEF (n = 22) independently predicted MOD incidence (HR = 2.12, 95% CI: 1.12-4.00, p = 0.022) but not major CAD (HR = 1.33, 95% CI: 0.53-3.33, p = 0.539).Conclusions: An abnormal LVEF may identify diabetic cardiomyopathy and predict long term risk of MOD (but not CAD alone) in type 1 diabetes individuals, consistent with it reflecting microvascular disease. [ABSTRACT FROM AUTHOR]

Objective: The degree to which mortality and cardiovascular disease (CVD) incidence remains elevated in young U.S. adults with type 1 diabetes (T1DM) is unclear. We determined contemporary rates for adults <45 years old with long-standing, childhood-onset T1DM from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study.Research Design and Methods: Members of the EDC Study cohort <45 years old during the 1996-2012 follow-up period (n = 502) were studied. Mortality and CVD rates were calculated for those aged 30-39 and 40-44 years. Data from the background Allegheny County, Pennsylvania, population were used to calculate age- and sex-matched standardized mortality (SMR) and incidence rate ratios (IRR).Results: In both age groups, the SMR for total mortality was ∼5 (95% CIs: 30-39-year-olds, 2.8, 7.2; 40-44-year-olds, 3.4, 7.8). CVD mortality SMRs ranged from 19 (95% CI 11, 32) to 33 (95% CI 17, 59). Hospitalized CVD IRR was ∼8 (95% CIs: 30-39-year-olds, 2.5, 18.9; 40-44-year-olds, 4.5, 12.8); revascularization procedures account for much of the increased risk. For all outcomes, the relative risk was larger in women. Participants aged 30-39 years had 6.3% (95% CI 3.8, 9.8) absolute 10-year CVD risk, approaching the American College of Cardiology/American Heart Association-recommended cut point of 7.5% for initiation of statin therapy in older adults.Conclusions: Total and CVD mortality and hospitalized CVD are all significantly increased in this contemporary U.S. cohort of young adults with long-standing T1DM. These findings support more aggressive risk factor management in T1DM, especially among women. [ABSTRACT FROM AUTHOR]

Objective: The incidence of type 1 diabetes complications appears to be decreasing, but relative contributions of risk factors are unclear. We thus estimated the effect of modifiable risk factors on the incidence of a composite end point, major outcomes of diabetes (MOD).Research Design and Methods: The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study was used to derive two cohorts based on diabetes diagnosis year (1960-1969 and 1970-1980). Baseline exam data in the current analysis for the 1960s group were collected in 1986-1988 and for the 1970s in 1996-1998. Each group was followed for 8 years for MOD incidence (diabetes-related death, myocardial infarction, revascularization procedure/blockage ≥50%, stroke, end-stage renal disease, blindness, and amputation). Assessed risk factors include the following: HbA1c, hypertension, microalbuminuria, BMI, hypercholesterolemia, and smoking. Accelerated failure time models were used to estimate the acceleration factor.Results: MOD incidence decreased in the 1970s cohort (15.8% [95% CI 11.6-21.4]) compared with the 1960s (22.6% [17.0-29.1]) over the 8-year follow-up (P = 0.06). Hypertension and microalbuminuria were associated with significantly accelerated MOD incidence in both cohorts (P < 0.01 for both). High HbA1c (P = 0.0005), hypercholesterolemia (P = 0.01), and current smoking (P = 0.003) significantly accelerated the incidence of MOD in the 1960s but not 1970s cohort. BMI was not associated with MOD in either cohort.Conclusions: These results suggest that hypertension and microalbuminuria remain important predictors of complications that are not being adequately addressed. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The incidence of type 1 diabetes complications appears to be decreasing, but relative contributions of risk factors are unclear. We thus estimated the effect of modifiable risk factors on the incidence of a composite end point, major outcomes of diabetes (MOD). RESEARCH DESIGN AND METHODS--The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study was used to derive two cohorts based on diabetes diagnosis year (1960-1969 and 1970-1980). Baseline exam data in the current analysis for the 1960s group were collected in 1986-1988 and for the 1970s in 1996-1998. Each group was followed for 8 years for MOD incidence (diabetes-related death, myocardial infarction, revascularization procedure/blockage $50%, stroke, end-stage renal disease, blindness, and amputation). Assessed risk factors include the following: HbA1c, hypertension, microalbuminuria, BMI, hypercholes-terolemia, and smoking. Accelerated failure time models were used to estimate the acceleration factor. RESULTS--MOD incidence decreased in the 1970s cohort (15.8% [95% CI 11.6-21.4]) compared with the 1960s (22.6% [17.0-29.1]) over the 8-year follow-up (P = 0.06). Hypertension and microalbuminuria were associated with significantly accelerated MOD incidence in both cohorts (P, 0.01 for both). High HbA1c (P = 0.0005), hypercholesterolemia (P = 0.01), and current smoking (P = 0.003) significantly accelerated the incidence of MOD in the 1960s but not 1970s cohort. BMI was not associated with MOD in either cohort. CONCLUSIONS--These results suggest that hypertension and microalbuminuria remain important predictors of complications that are not being adequately addressed. [ABSTRACT FROM AUTHOR]

Introduction Diabetes and obesity pose a significant burden for the U.S. military beneficiary population, creating a great need to provide evidence-based diabetes and obesity prevention services for military personnel, retirees, and their dependents. Despite increasing dissemination of the Diabetes Prevention Program (DPP) lifestyle intervention nationwide, formal evaluation of implementation of this highly successful program is limited in the military setting. The purpose of this study is to prospectively evaluate delivery of a direct adaptation of a 1-year DPP lifestyle intervention at a U.S. Air Force medical facility, Wright-Patterson Medical Center (WPMC), to determine the feasibility of delivery of the program in a group of at-risk active duty military, retirees, and family members, as well as assess effectiveness in improving weight and other risk factors for type 2 diabetes. Materials and Methods A pre/post study design was utilized to evaluate feasibility and effectiveness of the DPP Group Lifestyle Balance (GLB), an up-to-date, 22-session direct adaptation of the DPP curriculum, at WPMC. Participants chose to complete the 1-year program either in coach-led face-to-face groups or via DVD with weekly telephonic coach contact. The study was approved by the University of Pittsburgh and WPMC Institutional Review Boards. Results A total of 99 individuals enrolled in the study, with 83 (84%) and 77 (78%) completing 6- and 12-month follow-up assessments, respectively. The mean age of participants at baseline was 57 (range 20-85 years), with 63% being female. The group was comprised of individuals who were non-Hispanic White (73.7%), non-Hispanic Black (18.2%), and other race or Hispanic ethnicity (8.1%). Within this group, there were 10 active duty military, 37 retirees, and 52 family members. The DPP-GLB program was shown to be feasible to implement in this military healthcare setting as demonstrated by the high engagement over the course of the year-long program. Significant improvements were shown in the two main behavioral goals: mean weight (−12.8 lbs, −6.3%, P  < .001) and mean physical activity (PA) (+18.9 Met-hrs/wk, P  < .001). In addition, significant improvements in other diabetes and cardiovascular risk factors including low-density lipoprotein cholesterol, fasting insulin, diastolic blood pressure, and waist circumference were noted, as well as improvement in health-related quality of life. Conclusions These results demonstrate that the DPP-GLB program delivered via face-to-face groups or DVD was feasible and effective in improving weight, PA levels, and diabetes and cardiovascular risk factors in this group of active and retired military personnel and their family members. The program was well received by the program participants as well as the WPMC team. These findings offer a model for provision of the DPP-GLB program throughout the Military Health System. [ABSTRACT FROM AUTHOR]

Aims: Higher HbA1c has been associated with dyslipidemia in type 1 diabetes, but it is unknown whether there is heterogeneity in this association. Thus we assessed the longitudinal association between HbA1c and lipids over 30 years in a type 1 diabetes cohort and examined whether variation in such longitudinal patterns was associated with total and cause-specific mortality.Methods: Data were from the Pittsburgh Epidemiology of Diabetes Complications study (n = 581 with ≥2 visits, 51% male, baseline mean age 27, diabetes duration 19 years). Longitudinal associations between HbA1c and lipids were assessed in mixed models. Group-based multi-trajectory models identified simultaneous trajectories of HbA1c and lipids.Results: Longitudinal HbA1c was associated with Non-HDLc (p < 0.0001) and triglycerides (p < 0.0001), but not HDLc (men: p = 0.72, women: p = 0.76). There was heterogeneity in the HbA1c-Non-HDLc association only, with five HbA1c-Non-HDLc groups identified. One group (20%) had an unexpected combination of high HbA1c but normal Non-HDLc and had only moderately increased cardiovascular mortality (rate ratio [RR] = 2.80, 95% CI 1.31-6.00) and kidney disease mortality (RR = 2.30, 95% CI 0.97-5.50) compared to Low HbA1c-Normal Non-HDLc.Conclusions: These results suggest there is a subgroup with type 1 diabetes who, despite poor glycemic control, has a relatively good prognosis, perhaps related to good Non-HDLc. [ABSTRACT FROM AUTHOR]

Survival in type 1 diabetes has improved, but the impact on life expectancy in the U.S. type 1 diabetes population is not well established. Our objective was to estimate the life expectancy of the Pittsburgh Epidemiology of Diabetes Complications (EDC) study cohort and quantify improvements by comparing two subcohorts based on year of diabetes diagnosis (1950-1964 [n = 390] vs. 1965-1980 [n = 543]). The EDC study is a prospective cohort study of 933 participants with childhood-onset (aged < 7 years) type 1 diabetes diagnosed at Children's Hospital of Pittsburgh from 1950 to 1980. Mortality ascertainment was censored 31 December 2009. Abridged cohort life tables were constructed to calculate life expectancy. Death occurred in 237 (60.8%) of the 1950-1964 subcohort compared with 88 (16.2%) of the 1965-1980 subcohort. The life expectancy at birth for those diagnosed 1965-1980 was ∼15 years greater than participants diagnosed 1950-1964 (68.8 [95% CI 64.7-72.8] vs. 53.4 [50.8-56.0] years, respectively) (P< 0.0001); this difference persisted regardless of sex or pubertal status at diagnosis. This improvement in life expectancy emphasizes the need for insurance companies to update analysis of the life expectancy of those with childhood-onset type 1 diabetes because weighting of insurance premiums is based on outdated estimates. [ABSTRACT FROM AUTHOR]

Purpose: To examine the relationship between retinal vessel diameter and coronary artery disease (CAD) incidence in type 1 diabetes (T1D) using data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. Design: Prospective cohort study of childhood-onset T1D. Methods: Data are from 448 participants who had retinal photographs taken at baseline examination (May 1986 to November 1988) and no history of laser photocoagulation. Computer-assisted grading was used to measure retinal arteriolar and venular caliber. CAD incidence (CAD death, myocardial infarction, revascularization/stenosis ≥50%, ischemic electrocardiogram, or physician-diagnosed angina) was ascertained over a median follow-up time of 18 years (range, 2 months to 20.5 years). Results: Mean baseline arteriolar and venular caliber were 180.0 μm (standard deviation [SD], 15.2 μm) and 273.3 μm (SD, 28.0 μm), respectively; 80 (17.9%) CAD events occurred during follow-up. After covariate adjustment for T1D duration, gender, hypertension, serum lipids, and smoking status, smaller arteriolar caliber was significantly associated with CAD (hazard ratio [HR], 1.42; P = .03), but larger venular caliber was not. A vessel diameter-gender interaction term was significant for arteriolar caliber (P = .006). Stratified by gender, smaller arteriolar caliber was significantly associated with the incidence of CAD in women (HR, 1.92; P = .004), but not men. Venular caliber was not associated with CAD in either gender. Conclusion: Smaller arteriolar caliber may indicate an increased risk of CAD in women, but not men, with T1D. Additional studies are needed to further examine the role of microvascular disease in the pathogenesis of CAD in women with T1D. [Copyright &y& Elsevier]

Aims: Dietary intake provides a potential intervention target to reduce the high risk for coronary artery disease (CAD) in type 1 diabetes. This effort aimed to identify patterns of nutrient intake in young/middle-aged adults with type 1 diabetes and to examine associations between those patterns and development of CAD.Methods: Principal component analysis was used to derive nutrient intake patterns among 514 individuals with childhood-onset (<17 years old) type 1 diabetes aged 18+ years and free of CAD (defined as CAD death, myocardial infarction, revascularization, ischemia, or study physician diagnosed angina). Cox models were used to assess the association between nutrient patterns and CAD incidence over 30-years of follow-up.Results: Three nutrient principal components (PC) were identified: PC1 (high caffeine and saccharin intake), PC2 (high alcohol and caffeine, lower intake of essential nutrients) and PC3 (higher fiber/micronutrients, low alcohol). In unadjusted Cox models, only PC1 (negatively) and PC2 (positively) were associated with CAD risk. These associations were no longer significant after adjusting for diabetes duration.Conclusions: Important dietary components underlying the three patterns identified may have been influenced by diabetes duration or age. Future research can continue to explore patterns of nutrient intake over time and CAD development in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Nearly 50% of US adults >60 years have metabolic syndrome (MetS), which is linked to heart disease and diabetes. We evaluated if changes in cardiometabolic measures during a behavioral weight loss intervention for older adults differed by baseline MetS status (+ vs. -). The Pitt Retiree Study (PRS) was a 1-year lifestyle intervention trial adapted from DPP for adults 65+ years at high cardiometabolic risk. Participants attended 12 in-person group sessions, then were randomized to a monthly follow-up mode (phone or newsletter). Goals included 7% weight loss by 4 months via reduced calorie/fat intake, increased lean protein, and aerobic/strength training. Analyses include women only as 77% of PRS was female and sex differences in lipid metabolism exist. Participants (n=238) were mean (SD) age 71.1 (4.2), BMI 33.8 (5.4), and 67% had MetS at baseline. Regression models were used to compare change in cardiometabolic measures at 12 months in -MetS vs. +MetS (Table). Mean triglycerides (TG) decreased more in +MetS than -MetS while changes in other cardiometabolic measures did not differ between groups. -MetS had normal mean TG at baseline with little scope to improve, while +MetS had controlled blood pressure (BP) and LDL due to greater use of BP and lipid-lowering drugs. Nevertheless, both groups showed favorable cardiometabolic changes following lifestyle intervention. Disclosure: H. J. Stern: None. R. G. Miller: None. T. J. Orchard: None. T. Costacou: None. E. M. Venditti: None. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R18DK096405) [ABSTRACT FROM AUTHOR]

Physical function, health-related quality of life (HRQoL), and depressive symptoms are key outcomes for older adults (≥65y) enrolled in behavioral weight management, but less is known about relationships among these variables. We evaluated associations between changes in these measures after a 1-year DPP-based lifestyle program. Participants (N=322) were M±SD age 71.2y±4.3, BMI 33.8±5.1, 77% women, 13% Black, averaged 4 chronic conditions, and 31% had prediabetes. Most took blood pressure (67%) and lipid (52%) medications. Participants attended 12 in-person weekly groups, then were randomized to continued monthly contact by phone or newsletter, losing 7.4% (CI) (-8.9, -5.9) and 6.1% (-8.6, -3.6) of weight at 1 year, respectively. Goals included reducing calorie/fat intake, increasing lean protein, ≥150 minutes aerobic activity/week, and strength training. Physical function was measured via Short Physical Performance Battery (SPPB) gait speed, chair rise, and balance tests, perceived HRQoL via SF-12 Physical and Mental Component Summary (PCS and MCS), and mood via Center for Epidemiologic Studies Depression Scale (CES-D) at pre- and post-intervention. Associations between baseline-12 month changes in SPPB, HRQoL and CES-D were estimated in mixed-effect models. SPPB improved by 0.3±1.4 (p=0.001) in phone and 0.3±1.7 (p=0.02) in newsletter. Increased SPPB was associated with improved PCS (β=1.18, SE=0.20, p<0.001) and CES-D (β=-0.50, SE=0.17, p=0.002) in all participants, and improved MCS in phone (β=0.19, SE=0.28, p=0.049) and decreased MCS in newsletter (β=-0.37, SE=0.22, p=0.049). After weight loss, regardless of follow-up mode, modestly improved physical function relates to greater perceived physical HRQoL and mood, but less change in perceived mental HRQoL. Future weight loss trials in high risk elders should evaluate how to optimize physical function and subjective well-being outcomes. Disclosure: H. J. Stern: None. R. G. Miller: None. R. P. K. Conlon: None. M. D. Levine: None. M. D. Marcus: Advisory Panel; Self; Weight Watchers International, Inc. E. M. Venditti: None. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R18DK096405) [ABSTRACT FROM AUTHOR]

Patients with type 1 diabetes (T1D) exhibit a dramatically increased CAD risk compared with the general population. This risk is thought to be similar by sex. However, whether these patterns are maintained with long disease duration is unknown. We thus examined the 50 yr cumulative CAD risk in a childhood onset T1D cohort diagnosed in 1950-80 (n=932; mean baseline age 29 and duration 19 yrs). Participants included 146 who died prior to the baseline exam (1986-88) and 788 who were followed with periodic surveys (n=130) or biennial surveys and a maximum of 10 exams (n=658) for 30 yrs. CAD was defined as CAD death, myocardial infarction confirmed by Q-waves on electrocardiogram (Minnesota codes 1.1 or 1.2) or hospital records, or revascularization. Participants were divided into calendar years of T1D onset and cumulative incidence was estimated at 5 yr intervals between 20 and 50 yrs duration (Figure 1). Although the cumulative incidence of both CAD and CAD mortality declined in those with a more recent T1D diagnosis, stronger trends were observed for mortality than morbidity, potentially due to an increasing number of revascularizations in more recent cohorts. These trends were similar by sex. Disclosure: T. Costacou: None. R. G. Miller: None. T. J. Orchard: None. Funding: National Institutes of Health (DK34818) [ABSTRACT FROM AUTHOR]

Higher HbA1c is associated with worse average lipid trajectory in T1D. It is unknown if there is heterogeneity in this association. Thus we assessed the 30-yr association between HbA1c and both Non-HDLc and HDLc in a T1D cohort, examining varying longitudinal patterns in association with mortality. Data are from the Pittsburgh Epidemiology of Diabetes Complications study (n=658, 51% male, baseline mean age 27 yrs, T1D duration 19 yrs). Longitudinal associations between HbA1c and Non-HDLc were assessed in mixed models. The same analysis was performed for HDLc separately by sex. Group based multi-trajectory models identified simultaneous trajectories of HbA1c and each lipid. Over 30 yr each 1% higher HbA1c was associated with 6.6±0.4 mg/dl greater Non-HDLc (p<0.001). There was no association between HbA1c and HDLc (men: p=0.72, women: p=0.76). Five HbA1c - Non-HDLc combined groups were identified (Figure 1). Group 1 had the best HbA1c and Non-HDLc trajectories. Group 2 had an unexpected combination of high HbA1c but normal Non-HDLc and was characterized by better baseline systolic blood pressure (p=0.03) and estimated glomerular filtration rate (p<0.001) compared to Group 1. Group 2 had moderately elevated total and cardiovascular (CVD) mortality, but not end-stage renal disease (ESRD) mortality. These results suggest there is a subgroup with T1D who, despite high HbA1c, is at relatively low renal risk, perhaps related to good Non-HDLc. Disclosure: R. G. Miller: None. T. J. Orchard: None. T. Costacou: None. Funding: American Diabetes Association (1-19-JDF-109 to R.G.M.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034818) [ABSTRACT FROM AUTHOR]

Aims: To examine candidate insulin resistance single nucleotide polymorphisms (SNPs) for associations with glycemic control, insulin resistance, BMI, and complications in an observational type 1 diabetes (T1D) cohort: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study.Methods: In 422 European-ancestry participants, we assessed associations using additive models between 15 candidate SNPs and 25-year mortality, cardiovascular disease, microalbuminuria, overt nephropathy and proliferative retinopathy, and 25-year mean HbA1c, estimated glucose disposal rate (eGDR, inverse measure of insulin resistance), and BMI.Results: The A allele of rs12970134 was associated with higher mean HbA1c (β = +0.34 ± 0.09, p = 0.00009) and nominally associated with worse eGDR (p = 0.02). Further analyses suggest the HbA1c association may be modified by diabetes therapy regimen: rs12970134 AA genotype was associated with higher HbA1c under non-intensive therapy conditions (<3 insulin injections/day or monitoring blood glucose<3 times/day [p = 0.004]), but not under intensive therapy (≥3 injections/day or insulin pump and monitoring glucose≥3 times/day [p = 0.71]). There were no significant associations between any SNPs and BMI or complications.Conclusions: rs12970134, near MC4R, is strongly associated with HbA1c in this cohort. Further exploration of this genomic region is warranted, as it may hold promise for discovering new therapeutic targets to improve glycemic control in T1D. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- While lower hemoglobin is generally associated with adverse events in diabetes, we have recently observed in type 1 diabetes that those with overt nephropathy had hemoglobin levels as high as 18.8 g/dl. We thus explored whether hemoglobin concentrations are generally higher in type 1 diabetes. RESEARCH DESIGN AND METHODS -- Baseline (1986-1988) hemoglobin levels from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of type 1 diabetes were compared with general population data from the National Health and Nutrition Examination Survey (NHANES) III in the same age range as the EDC population (aged 8-48 years). RESULTS -- Both male and female EDC study participants had significantly higher hemoglobin levels than their NHANES III counterparts (men: 16.0 vs. 15.1 g/dl, P < 0.0001; women: 14.1 vs. 13.3 g/dl, P < 0.0001). The difference between the two populations was greatest in adolescent female subjects. CONCLUSIONS -- Hemoglobin levels may be higher in type 1 diabetes than in the general population, which may have important clinical implications. [ABSTRACT FROM AUTHOR]

The article presents a response by the authors to a comment published within the issue on their article which raised the issue of metabolic memory. Topics covered include their agreement with the commentary that intensive therapy should be started as early as possible after the onset of type 1 diabetes, and their confusion to the commentary's claim that they failed to recognize that cumulative glycemic exposure includes long-term effects, such as metabolic memory.

The DPP lifestyle intervention showed that meeting weight loss (WL) and activity goals can prevent/delay T2D. The success of community translated versions of it (e.g., Group Lifestyle Balance, DPP-GLB) has led to Medicare reimbursement based on session attendance (at 6 and 12 months) and participant success at meeting a 5% WL goal at 12 months. Although attendance has been suggested to be related to WL success, the impact of the 6 monthly maintenance sessions (mos 7-12) after the more frequent 16 core sessions (mos 0-6) on one-year WL is not known. This effort examines how maintenance session attendance and WL goal status at 6 months in DPP-GLB affects achievement of the 12-month 5% WL goal. Data were combined from two identical intervention trials that delivered the 12-month DPP-GLB in a community setting to overweight/obese adults (mean age 62 years, 76% women) with prediabetes and/or metabolic syndrome. Participants who attended ≥4 core sessions during the first 6 months and had complete data on maintenance attendance and WL were included (n=238). Meeting the 6-month WL goal was associated with greater odds of meeting the 12-month WL goal (p<.0001). Odds of meeting the 12-month 5% WL goal were significantly greater for those who attended ≥4 maintenance sessions vs. those who did not (OR=6.0, 95% CI: 2.4-15.0). When stratified by achieving the 5% WL goal at 6 months, those who attended ≥4 maintenance sessions and met the 6-month WL goal were more likely to meet the WL goal at 12 months (OR=11.4, CI: 3.2- 40.7) compared to those who failed to meet the WL goal at 6 months (OR=1.5, CI: 0.3-7.5). Adjustment for age, gender and 6-month physical activity yielded similar results. Attending DPP-GLB maintenance sessions and meeting the 6-month WL goal increased the odds of meeting ≥5% WL at 12 months. For those who failed to meet the 6-month WL goal, attending maintenance sessions did not significantly improve their chance of 12-month WL success. Disclosure: J. Napoleone: None. R.G. Miller: None. S. Devaraj: None. B. Rockette-Wagner: None. V.C. Arena: None. E.M. Venditti: None. K. Kramer: None. A. Kriska: None. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R18DK100933, R18DK081323) [ABSTRACT FROM AUTHOR]

Adherence to a Mediterranean (Med) diet pattern, characterized by increased intake of fruits, nuts/seeds, vegetables, legumes, whole grains, seafood, yogurt and vegetables, and decreased intake of red/processed meats, refined grains, starches and added sugars, is associated with reduced cardiometabolic risk independent of total calorie intake or single nutrients. We examined whether adherence to Med diet was associated with risk factor change in the context of a behavioral weight management trial for U.S. community-dwelling older adults at elevated diabetes and cardiovascular risk. The Pitt Retiree Study (n=322) examined the impact of 12 weekly group lifestyle sessions on weight and cardiometabolic risk (BMI, waist, glucose, lipids, and blood pressure) in older adults (age 65-80 yrs). Dietary goals included calorie reduction, <30% of total calories from fat, lean protein at most meals, and following USDA MyPlate guidelines but not a Med diet. Adherence to a Med diet pattern (0-14 score) was assessed at baseline, 4, 12, and 24 months and categorized as low (0-5), moderate (6-9), or high (≥10). The baseline median Med diet score was 6 (range 0-13), with 45% categorized as low, 50% moderate, 5% high. Women were more adherent than men (p<0.01). Adjusting for sex, higher scores were correlated with older age (p=0.02), lower baseline BMI (p=0.01) and smaller waist (p=0.01). Median [IQR] scores improved at 4 months (+1 [0, +2] p<.001) with 27% low, 63% moderate, 10% high. Each 1-unit Med diet increase was associated with -0.1 kg/m2 BMI (SE=0.04, p=.006) and -1.0 mmHg Systolic BP (SE=0.47, p=0.03) at 4 months. Med diet improvement was maintained at 12 (+1, [0, +2] p<.001) and 24 months (n=299, +1 [0, +2] p<.001). Adherence to a food pattern consistent with a Med diet improves after lifestyle intervention, even when not specifically prescribed, and is associated with weight and blood pressure benefits. Importantly, older adults sustain change in dietary quality over 2 years. Disclosure: R.G. Miller: None. E.M. Venditti: None. M.D. Marcus: None. L.J. Germeroth: None. R.P.K. Conlon: None. M.D. Levine: None. T. Costacou: None. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R18DK096404) [ABSTRACT FROM AUTHOR]

While poor glycemic control is a well-established risk factor for mortality and MACE in T1D, specific patterns of control over time have not been well-studied. Thus, we sought to identify long-term trajectories of HbA1c and examine associated participant characteristics, mortality, and MACE incidence in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective observational cohort with childhood-onset (<17 years) T1D. These data were analyzed as part of a DNA methylation sub-study (currently in progress), where n=422 (baseline mean T1D duration 21 yrs, 53% male) have been followed for outcomes, including 28-year mortality and MACE. Beginning in 1988, HbA1c was measured at baseline, 2, 4, 6, 8, 15, and 22 yrs. HbA1c trajectories were identified using latent class growth modeling. Five HbA1c trajectories were identified (Figure). There were no significant differences in age, T1D duration, age at T1D onset, sex, education, or insulin dose between groups. Both mortality and MACE were significantly increased in IMPROVED (p<0.02) and even more so in HIGH (p<.0001) compared to LOW. MODERATE and WORSENED did not have increased risk of either outcome compared to LOW. These results demonstrate that, despite improvement, past high HbA1c remains associated with increased long-term mortality and MACE risk in this T1D cohort. Disclosure: R.G. Miller: None. T. Costacou: None. T.J. Orchard: None. Funding: American Diabetes Association (1-19-JDF-109 to R.G.M.) [ABSTRACT FROM AUTHOR]

Aims: We compared risk factors for three CVD manifestations and a composite outcome over 25 years' follow-up in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (<17 years) type 1 diabetes (n = 658).Methods: First CVD manifestations examined were: (1) major atherosclerotic cardiovascular event (MACE, i.e. CVD death, myocardial infarction, stroke), (2) coronary revascularization, (3) soft coronary artery disease (CAD, i.e. ischemia ECG, angina), and a (4) composite (MACE + revascularization) outcome. Baseline and time-varying mean and current risk factors, including medication use, were assessed, in diabetes duration-adjusted models.Results: MACE (n = 107) was predicted by ln(albumin excretion rate) (AER, HR = 1.3, p < 0.0001), systolic BP (SBP, HR = 1.03, p < 0.0001), white blood cell count (WBC, HR = 1.2, p < 0.0001), HbA1c (HR = 1.2p = 0.03), LDLc (HR = 1.01, p = 0.03). Soft CAD (n = 91) was predicted by ln(AER) (HR = 1.2, p = 0.004), SBP (HR = 1.03, p = 0.0002), WBC (HR = 1.2, p = 0.0003), HbA1c (HR = 1.2, p = 0.005). Revascularization (n = 38) was predicted by LDLc (HR = 1.03, p < 0.0001), eGFR (HR = 0.98, p = 0.002), HbA1c (HR = 1.3, p = 0.03). Adding revascularization to MACE enhanced the role of LDLc, while diminishing that of HbA1c, compared to MACE alone.Conclusions: Important risk factor associations may be affected by examining composite CVD outcomes. More research is needed to determine how to best incorporate revascularization into composite CVD definitions. [ABSTRACT FROM AUTHOR]

Background: The Diabetes Prevention Program (DPP) behavioral lifestyle intervention was effective among a diverse sample of adults with prediabetes. Demonstrated effectiveness in translated versions of the DPP lifestyle intervention (such as Group Lifestyle Balance, DPP-GLB) led to widescale usage with national program oversight and reimbursement. However, little is known about the success of these DPP-translation programs across subgroups of sociodemographic factors. This current effort investigated potential disparities in DPP-translation program primary goal achievement (physical activity and weight) by key sociodemographic factors.Methods: Data were combined from two 12-month community-based DPP-GLB trials among overweight/obese individuals with prediabetes and/or metabolic syndrome. We evaluated change in weight (kilograms and percent) and activity (MET-hrs/week) and goal achievement (yes/no; ≥5% weight loss and 150 min per week activity) after 6 and 12 months of intervention within and across subgroups of race/ethnicity (non-Hispanic white, non-Hispanic black), employment status, education, income, and gender.Results: Among 240 participants (85%) with complete data, most sociodemographic subgroups demonstrated significant weight loss. However, non-Hispanic white lost more weight at both 6 and 12 months compared to non-Hispanic black participants [median weight loss (IQR), 6 months: 5.7% (2.7-9.0) vs. 1.5% (1.2-7.5) p = .01 and 12 months: 4.8% (1.1-9.6) vs. 1.1% (- 2.0-3.7) p = .01, respectively]. In addition, a larger percentage of non-Hispanic white demonstrated a 5% weight loss at 6 and 12 months. Employment was significantly related to 12-month weight loss, with retired participants being the most successful. Men, participants with graduate degrees, and those with higher income were most likely to meet the activity goal at baseline and 12 months. Differences in physical activity goal achievement across gender, education, and income groups were significant at baseline, attenuated after 6 months, then re-emerged at 12 months.Conclusions: The DPP-GLB was effective in promoting weight loss and helped to alleviate disparities in physical activity levels after 6 months. Despite overall program success, differences in weight loss achievement by race/ethnicity were found and disparities in activity re-emerged after 12 months of intervention. These results support the need for intervention modification providing more tailored approaches to marginalized groups to maximize the achievement and maintenance of DPP-GLB behavioral goals.Trial Registration: NCT01050205 , NCT02467881 . [ABSTRACT FROM AUTHOR]

The MC4R gene (18q21.32) plays a role in regulating appetite and energy homeostasis and is consistently linked with obesity. A variant near MC4R (rs12970134) has also been associated with IR and type 2 diabetes, independent of BMI. We examined the association of rs12970134 with HbA1c, IR, and BMI in the Pittsburgh Epidemiology of Diabetes Complications study, a prospective T1D cohort (mean age 27, T1D duration 18 years at baseline, 1986-88). In 422 EDC participants of European ancestry with available DNA, we assessed associations between 16 published IR SNPs, including rs12970134, and longitudinal measures of HbA1c, estimated glucose disposal rate (eGDR, an inverse measure of IR), and BMI over 18 years of follow-up (1986-88 to 2004-06). General additive mixed models were adjusted for sex, T1D duration, and principal components of ancestry. The rs12970134 SNP was associated with longitudinal HbA1c (β=0.33, p=5x10-5, see Figure) and eGDR (β=-0.31, p=0.008) trajectories, but not BMI (β=0.21, p=0.38). The associations remained significant after adjusting for BMI and insulin dose. There was no evidence for a SNP x time interaction (p>0.25 for both); all groups showed a similar fall in HbA1c after publication of the DCCT results. Thus, the rs12970134 SNP near MC4R is associated with glycemic control and insulin resistance, despite no association with BMI, in this T1D cohort. Disclosure: R.G. Miller: None. T. Costacou: None. S. Onengut-Gumuscu: None. W. Chen: None. S.S. Rich: None. T.J. Orchard: Consultant; Self; Boehringer Ingelheim International GmbH. Funding: National Institutes of Health; Rossi Memorial Fund; JDRF [ABSTRACT FROM AUTHOR]

Many SNPs in multiple loci are associated with IR in the general population. IR itself is associated with increased complication and mortality risk in T1D. We thus assessed whether a genetic risk score derived from IR SNPs (IR_GRS) is associated with mortality in the T1D prospective Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. In 422 participants of European ancestry, with available DNA, a weighted IR_GRS based on 16 published IR-associated SNPs was calculated. First, for each SNP, the effect size of the association between each SNP and estimated glucose disposal rate (eGDR, an inverse measure of insulin resistance) was estimated using a general additive linear model. This effect size was then multiplied by the risk allele count to obtain the IR-weighted count. The IR_GRS was calculated as the sum of the 16 weighted counts. All deaths were classified by a physician committee yielding underlying and contributing causes. IR_GRS was related to 25-year total, any mention of cardiovascular disease (CVD), and any end-stage renal disease (ESRD) mortality in Cox models adjusted for sex, principal components for ancestry, and T1D duration and baseline (1986-88) clinical risk factors, including HbA1c, lipids, blood pressure, albumin excretion rate (AER), estimated glomerular filtration rate, and white blood cell count. IR_GRS was associated with increased risk of mortality outcomes: total (99 deaths, p=0.003), any CVD (71 deaths, p=0.01), and any ESRD (49 deaths, p=0.01). Adjustment for clinical risk factors attenuated these associations: total mortality (p=0.04), CVD mortality (p=0.17), ESRD mortality (p=0.10), largely as a result of adjustment for log-transformed AER, which was significantly associated with the IR_GRS (p=0.0003). These results, while needing validation in other cohorts, suggest that an IR_GRS may help to identify individuals with T1D who are at increased risk of mortality and vascular damage (i.e., AER) due to IR. Disclosure: R.G. Miller: None. T. Costacou: None. S. Onengut-Gumuscu: None. W. Chen: None. S.S. Rich: None. T.J. Orchard: Consultant; Self; Boehringer Ingelheim International GmbH. Funding: National Institutes of Health; Rossi Memorial Fund; JDRF [ABSTRACT FROM AUTHOR]

The study was aimed to determine optimal blood pressure (BP) goals for minimizing coronary artery disease (CAD) risk in adults with childhood-onset type 1 diabetes (T1D). The Pittsburgh Epidemiology of Diabetes Complications study participants without known baseline CAD (n=605) were recruited and then followed for 25 years. The associations of time-updated cumulative (mmHg-year) and time-weighted (mmHg) BP measures (systolic [SBP], diastolic [DBP], and mean artery pressure [MAP]) with incident CAD were examined using Cox proportional hazard models. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were summarized by different cut-points of time-weighted BPs. Risk stratification analyses were then undertaken based on time-weighted BP (< vs. ≥ 120/80 mmHg) and time-weighted HbA1c (< vs. ≥ 8%). All time-updated cumulative BP measures independently predicted incident CAD over the follow-up period. A dose-gradient association was observed for categorized time-weighted SBP, DBP and MAP in their association with CAD risk. According to both Cox models and AUCs, the optimal cut-points for SBP, DBP and MAP were approximately 120, 80 and 90 mmHg, respectively. Participants with a BP ≥120/80 mmHg, compared to <120/80 mmHg, were associated with 1.9 (95% CI: 1.4, 2.6) times greater risk of developing CAD. Compared to participants with good control of both BP (<120/80 mmHg) and HbA1c (<8%), the high BP only group (HR: 2.0 [1.1, 3.9]) carried a similar risk as compared to high HbA1c only group (HR: 1.6 [0.97, 2.8]). These findings support that lower BP goals (i.e., 120/80 mmHg) than 2018 ADA recommendations (140/90 mmHg) may be needed for young adults with T1D. Lowering BP may further reduce cardiovascular risk in addition to maintaining good glycemic control in these individuals. Disclosure: J. Guo: None. R.G. Miller: None. T. Costacou: None. T.J. Orchard: Consultant; Self; Boehringer Ingelheim International GmbH. Funding: National Institutes of Health [ABSTRACT FROM AUTHOR]

Background: Group lifestyle sessions with phone maintenance could improve weight, health, and function in vulnerable older adults.Methods: Community-dwelling adults (N = 322) with body mass index (BMI, kg/m2) ≥27 and additional risk factors received 12 one-hour in-person behavioral weight management group sessions then were randomized to 8 half-hour telephone sessions (n = 162) or newsletter control (n = 160) from 4 to 12 months with no treatment contact thereafter. Primary outcome was 0- to 12-month weight change. Cardiometabolic, short physical performance battery (SPPB), and self-reported activity changes were assessed at 12 and 24 months.Results: At baseline, the mean (SD) age was 71.2 (4.3) and BMI was 33.8 (5.1). Participants were 77% women, 13% Black, 85% retired, averaging 4 medical conditions, and taking blood pressure (67.4%) and lipid-lowering (51.6%) medications. At 12 months, a greater proportion of the phone group (66.0%) achieved ≥5% weight loss compared with newsletter control (53.2%; p = .02). Mean (95% CI) weight loss was greater for phone (-6.6 kg [-7.5, -5.8]) than newsletter (-5.1 kg [-7.2, -3.0]); p = .01. Modest lipid, glucose, and blood pressure improvements were found, but did not differ significantly between groups. Small SPPB and activity improvements were maintained at 12 and 24 months in both groups.Conclusions: Brief phone contacts compared to newsletters enhanced weight loss maintenance among older high-risk adults at 1 year, but not cardiometabolic outcomes. Modest functional improvements were observed in both. Lower-intensity maintenance contacts (phone or newsletter) for weight, health, and physical function in older adults warrant further study.Clinical Trials Registration Number: NCT03192475. [ABSTRACT FROM AUTHOR]

It has previously been shown that baseline estimates of IR, assessed by estimated glucose disposal rate (eGDR, a regression equation derived from euglycemic clamp studies), predict overt nephropathy (ON, albumin excretion rate (AER)>200ug/min) in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) cohort of childhood onset T1D. As increasing evidence suggests renal function decline (eg. creatinine clearance) is not always preceded by albuminuria, the current analyses aim to assess the relationship eGDR and 24-hour creatinine clearance (CRCL). Patients with ON or worse at baseline were excluded. Data are from 487 patients (238 men, means: T1D duration=17.7, age=23.6 yrs, and 249 women, means: T1D duration= 18.3, age=26.7 yrs) at baseline. Measures of kidney function, CRCL and AER, were obtained biennially over 10 years. The association of the natural log of each measure with eGDR was assessed separately for men and women using mixed models, with random coefficients for the intercept and time variable, and adjusting for T1D duration, serum lipids, BMI, smoking, blood pressure medication, ACE/ARB, and white blood cell count. Alternative models using the individual components of eGDR (HbA1, hypertension (HTN), and waist-hip ratio (WHR) were fit to examine the relative importance of each component. eGDR was associated with ln(AER) in both men (p=0.01) and women (p<0.0001) after covariate adjustment. There was a marginally significant interaction between eGDR and time with respect to ln(AER) in men only (p=0.08), suggesting an increasing association over time. In the alternate models, HbA1 was marginally associated with In(AER) in women (p=0.06) and HTN was significantly associated in men(p=0.01) and women (p<.0001). Significant positive interactions were observed between HbA1 and time in both sexes (men:p=0.02, women:p=0.002), as was a marginal interaction between WHR and time in men(p=0.08). In contrast, eGDR was associated with In(CRCL) only in women (p=0.01) and no interaction with time was observed in either sex. Likewise, none of the components of eGDR were associated with In(CRCL) in men; HTN was associated in women (p=0.001) and a marginal interaction with time was observed (p=0.06). These results suggest that IR is more strongly related to albuminuria than creatinine clearance, further confirming the hypothesis that these markers of renal disease may not always be reflecting the same pathologic process. [ABSTRACT FROM AUTHOR]

Strategies for management of pre-diabetes within the community setting are needed. An adaptation of the successful Diabetes Prevention Program lifestyle intervention delivered by trained diabetes educators was evaluated. Results indicate that trained diabetes educators offer an important community resource for health care providers for their patients with pre-diabetes. [ABSTRACT FROM AUTHOR]

Background: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. Methods: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010–2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. Results: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. Conclusion: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions. [ABSTRACT FROM AUTHOR]

Caloric restriction prolongs lifespan in model organisms and improves metrics of aging-related diseases in humans, but daily compliance is challenging. Intermittent fasting improves metrics of lipid and glucose metabolism in the setting of weight loss but whether these metrics are improved independent of weight loss is not known. We seek to address this gap with IFAST, a single-center, three-arm, prospective, randomized, controlled clinical trial. Eligible study participants are adults with no chronic medical conditions beyond prediabetes or overweight but who are at high risk for type 2 diabetes mellitus (T2D), defined as having a history of gestational diabetes or a first-degree relative with T2D. Participants will be randomized in a 1:2:2 schema to either a control group, a fasting group, or a fasting/weight maintenance group. The fasting groups will complete a 24-h fast one day per week for 12 weeks. The key mechanistic endpoint is change in triglyceride composition (defined by carbon content and degree of saturation) as measured by longitudinal metabolomics. The key safety endpoint is percent change from baseline in bone volume fraction (BV/TV; high-resolution peripheral quantitative CT) at the radius in the fasting group. Secondary endpoints include measures of insulin sensitivity (hyperinsulinemic-euglycemic clamp), clinical lipid profiling, systemic inflammation markers, hunger assessment, bone density, and bone microarchitecture with high-resolution peripheral quantitative CT. IFAST will investigate intrinsic metabolic benefits of intermittent fasting beyond weight loss. ClinicalTrials.gov ID NCT05722873. [ABSTRACT FROM AUTHOR]

Although the risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD) are well known, identification and reduction of individual risk remains less than optimal. This may be due in part to a general lack of structured prevention screening approaches. Therefore the effectiveness of a systematic birthday-based prevention screening program for identification and reduction of T2D and CVD risk was assessed in a primary care practice (PCP) setting. The screening program incorporated national guidelines for T2D and CVD risk identification and management. Patients in 4 PCPs were grouped according to the quarter of their birthdate; those with birthdates within 1 quarter were invited to attend a screening visit. Prevention screening was completed over a 3 month period by a practice preventionist (attained health professional e.g., nurse, nutritionist or CDE); 18 percent of those invited agreed to be screened. Chart review was conducted by trained third-party reviewers for two 13-month periods preceding and following the screening invitation for those invited for screening (n=1,599). A comparison group consisting of those with birthdates in another quarter of the year and not invited for screening (n=1,651) was similarly examined. Measures assessed included the prevalence of elevated LDL cholesterol, fasting blood glucose and blood pressure. The screened/target cohort showed an increased prevalence of clinically diagnosed hypereholesterolemia (p=0.05) as well as a marginal increase in the prevalence of diagnosed prediabetes (p=0.09). No such differences were seen in the comparison group. The prevalence of hypertension and diabetes did not change materially in either cohort. Though 92 cases of new (based on patient history) hypercholesterolemia, hypertension, diabetes or pre-diabetes were potentially identified at screening, 23% of those were already noted in the chart. As the screening was not contingent upon lack of previous diagnosis, it is unlikely that denial of a previous diagnosis was made in order to attend screening. While these results suggest that systematic screening is somewhat effective in new identification of cardiometabolic risk, it also appears that a high proportion of patients are neither aware of their diagnosis or being treated. Better utilization of existing data for treatment and patient education is needed. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD), a leading cause of death in type 1 diabetes (T1D), often occurs two or more decades earlier in this population. Although CAD generally increases with adiposity, this association is unclear in T1D. We thus examined the associations of adiposity with Coronary Artery Calcium (CAC-previously shown to correlate strongly with CAD in this T1D population) in 225 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study, a 16-yr prospective study of childhood onset T1D. Mean age and diabetes duration were 42 and 34 yrs, respectively at the time of assessment, which included CAC, visceral adiposity (VAT) and subcutaneous adiposity (SAT) by electron beam tomography, BMI and waist circumference (WC). Chi-square frequencies and generalized linear models were used to compare the presence of any CAC and age-adjusted mean (log-transformed) CAC total volume score, respectively, by quartiles of adiposity. There was a positive relationship between the presence of CAC and VAT (p trend<0.0001 both genders), SAT (p for trend <0.001 both genders), and with BMI and WC in males (p trend=0.0005 and 0.001, respectively) but not females. However, given the presence of CAC, the relationship of VAT, SAT, and BM1 with the severity of CAC was inverse in women and (with the exception of BMI -also inverse) absent in men. Women in the lowest quartile of SAT and BMI had more CAC than those in the second and third quartiles (p<0.008). Men in the lowest BMI quartile had more CAC than those in the fourth (p<0.0008). There was no association between WC and degree of CAC in either gender. These associations were observed even though standard CAD risk factors such as LDLc, triglycerides and SBP, increased while HDL decreased with adiposity (p trend <0.05). No association was observed with HbA1c, albumin excretion rate, estimated glomerular filtration rate, or smoking. Adiposity is positively associated with the presence of CAC, but inversely associated with its severity in T1D. This double-edged association, which appears to be more pronounced in women, emphasizes the complex relationship between adiposity and cardiovascular risk in diabetes. [ABSTRACT FROM AUTHOR]

Aims Because blood-based screening to identify those with prediabetes to take part in Diabetes Prevention Program (DPP) translation efforts can be costly and time-consuming, non-invasive methods are needed. The aims of this paper are to evaluate the ability of the American Diabetes Association (ADA) risk test in identifying individuals with prediabetes, as well as the use of body composition measures for this purpose. In addition the utility of these alternate methods to ascertain the presence of the metabolic syndrome was assessed. Methods Potential participants were recruited from a worksite and three community centers to take part in a DPP translation study. Participants completed onsite screening where anthropometric measures, fasting lipids and glucose, and hemoglobin A1c were assessed. Those with a BMI ≥24 kg/m 2 and prediabetes and/or the metabolic syndrome were eligible to participate. Non-invasive screening methods were evaluated for their ability to identify those with prediabetes and the metabolic syndrome based on clinically measured values. Results All non-invasive methods were highly sensitive (68.9% to 98.5%) in the detection of prediabetes, but specificity was low (6.7% to 44.5%). None of the alternatives evaluated achieved acceptable discrimination levels in ROC analysis. Similar results were noted in identifying the metabolic syndrome. Conclusions The non-invasive methods evaluated in this study effectively identify participants with prediabetes, but would also allow for enrollment of a large number of individuals who do not have prediabetes. Deciding whether to use these alternatives, blood-based measures, or a combination of both will ultimately depend on the purpose of the program and the level of flexibility regarding participant eligibility. [ABSTRACT FROM AUTHOR]

Introduction: Lifestyle interventions promoting weight loss and physical activity are important elements of prevention efforts with the evaluation of program impact typically limited to weight loss. Unfortunately, diabetes/cardiovascular disease risk factors and activity are infrequently reported and inconsistent in findings when examined. This inconsistency may partially be due to a lack of consideration for ceiling effects because of broad risk profile inclusion criteria in community translation efforts. To demonstrate this, change in each individual cardiometabolic risk factor limited to those who, at baseline, had a clinically defined abnormal value for that risk factor was examined in 2 cohorts using identical community translations of the Diabetes Prevention Program lifestyle intervention.Methods: For both studies (2010-2014, 2014-2019), adults with prediabetes and/or metabolic syndrome were recruited through community centers. Outcome measures collected at baseline and 6 months included BMI, activity, blood pressure, lipids, and fasting glucose. Data analyses examined pre-post change in each variable after 6 months of intervention and change within randomized groups at 6 months.Results: Change results were examined for the entire cohort and separately for participants with baseline values outside the recommended range for that risk factor. Whether assessing the pre-post intervention change or change within the randomized groups at 6 months, often the risk factor-specific approach demonstrated a greater effect size for that variable and sometimes newly reached statistical significance.Conclusions: When examining the effectiveness of community translation efforts, consideration of the individual's baseline profile with risk factor-specific analysis is suggested to understand the full extent of the impact of the intervention. [ABSTRACT FROM AUTHOR]

Objectives: Patients with type 1 diabetes (T1D) exhibit modest lipid abnormalities as measured by traditional metrics. This study aimed to identify lipidomic predictors of rapid decline of kidney function in T1D.Research Design and Methods: In a case-control study, 817 patients with T1D from three large cohorts were randomly split into training and validation subsets. Case was defined as >3 mL/min/1.73 m2 per year decline in estimated glomerular filtration rate (eGFR), while control was defined as <1 mL/min/1.73 m2 per year decline over a minimum 4-year follow-up. Lipids were quantified in baseline serum samples using a targeted mass spectrometry lipidomic platform.Results: At individual lipids, free fatty acid (FFA)20:2 was directly and phosphatidylcholine (PC)16:0/22:6 was inversely and independently associated with rapid eGFR decline. When examined by lipid class, rapid eGFR decline was characterized by higher abundance of unsaturated FFAs, phosphatidylethanolamine (PE)-Ps, and PCs with an unsaturated acyl chain at the sn1 carbon, and by lower abundance of saturated FFAs, longer triacylglycerols, and PCs, PEs, PE-Ps, and PE-Os with an unsaturated acyl chain at the sn1 carbon at eGFR ≥90 mL/min/1.73 m2. A multilipid panel consisting of unsaturated FFAs and saturated PE-Ps predicted rapid eGFR decline better than individual lipids (C-statistic, 0.71) and improved the C-statistic of the clinical model from 0.816 to 0.841 (P = 0.039). Observations were confirmed in the validation subset.Conclusions: Distinct from previously reported predictors of GFR decline in type 2 diabetes, these findings suggest differential incorporation of FFAs at the sn1 carbon of the phospholipids' glycerol backbone as an independent predictor of rapid GFR decline in T1D. [ABSTRACT FROM AUTHOR]

We aimed to quantify the association between existing microvascular diseases and risk of subsequent HF in adults with T1D. Participants from Pittsburgh Epidemiology of Diabetes Complication (EDC) Study without known baseline HF (n=655) were classified into 4 groups based on the number (n=0-3) of existing microvascular diseases, i.e., overt nephropathy, proliferative retinopathy, and confirmed distal symmetric polyneuropathy (CDSP). Overt nephropathy was defined as an AER >300mg/24h in ≥ 2 of three validated timed biennial urine collections. Proliferative retinopathy was based on stereoscopic fundus photographs or a history of receiving laser therapy for proliferative diabetes retinopathy. CDSP was identified by following the Michigan Neuropathy Screening Instrument and the Michigan Diabetes Neuropathy Score. HF was determined by hospitalization, cause-of-death records, clinic exams, and/or self-reports of physician diagnosis. We applied Cox PH models to quantify the association between the number of existing microvascular diseases and risk of subsequent HF over 25 years follow-up controlling for diabetes duration (or age), sex, HbA1c, and CAD comorbidity. Mean baseline age and T1D duration were 27 years and 19 years. The 25-year cumulative incidence of HF was 6.6% (43/655). Over half didn't have any microvascular disease at baseline; 19.7%, 16.7% and 10.8% had 1, 2 and 3 microvascular diseases, respectively. In participants with 1, 2, and 3 microvascular diseases, the adjusted HR (95%CI) of any clinically defined HF was 3.1 (1.3, 7.6), 2.5 (0.9, 6.9), and 4.0 (1.3, 11.9), compared with those without any microvascular disease. The HR (95%CI) of hospitalization or death for HF was 2.0 (0.6, 7.3), 2.2 (0.6, 8.7), and 4.1 (1.0, 16.4). As microvascular disease burden increases so does the risk of HF, independently of diabetes duration, sex, HbA1c, and CAD among adults with long-duration childhood-onset T1D. Disclosure: J. Guo: None. T. Costacou: None. R. G. Miller: None. T. J. Orchard: None. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034818) [ABSTRACT FROM AUTHOR]

In the general population, chronic obstructive pulmonary disease (COPD) and Preserved Ratio Impaired Spirometry (PRISm) have been shown to increase mortality risk. While increased respiratory disease risk has been observed in type 1 diabetes (T1D), data on PRISm and COPD, especially in middle-age, are scarce in T1D. We thus assessed correlates of COPD and PRISm among individuals with childhood-onset T1D. Data were from the 30-year visit of the EDC study (n=162, median age/T1D duration, 56/47 years). Pulmonary function was assessed with the NDD EasyOne™ Spirometer using NHANES reference values for the predicted values. COPD was defined as Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC)<0.7. PRISm was defined as FEV1% predicted<80% and FEV1/FVC≥0.7. The majority of participants were classified as having COPD (43.2%) or PRISm (25.9%), with only 30.9% having normal pulmonary function. Univariate differences by pulmonary disease status are shown in the Table. Multinomial logistic regression models were constructed to assess independent correlates of COPD and PRISm. High ABI (>1.3) was associated with greater odds of COPD (OR=4.64, 95% CI: 1.42-15.13, p=0.01) and BMI with PRISm (OR=1.10, 95% CI: 1.01-1.21, p=0.03). No other risk factor was associated with COPD or PRISm. In conclusion, high ABI and BMI appear to be independently associated with greater odds of COPD and PRISm, respectively, in T1D. Disclosure: J. Ju: None. G. L. Kinney: None. R. G. Miller: None. T. J. Orchard: None. T. Costacou: None. Funding: National Institutes of Health (DK34818) [ABSTRACT FROM AUTHOR]

Evidence suggests that insulin deficiency and hyperglycemia may disrupt the normal function of the female reproductive system, leading to delayed menarche and premature ovarian aging. We compared the length of the reproductive period of women with T1D and women without diabetes. We assessed age at menarche and natural menopause in women with childhood-onset T1D (diagnosed in 1950-80) who participated in the Pittsburgh EDC study's 2010-16 follow-up (where reproductive history was assessed) and nondiabetic participants from the Pittsburgh site of the SWAN study. Women who had not yet reached natural menopause, had a hysterectomy/oophorectomy before menopause or received sex hormone therapy during the menopausal transition were excluded from analyses. In EDC, covariate data were selected from the follow-up visit where chronological age was closest to the baseline age in SWAN. Reproductive history was self-reported. The Women's Ischemia Syndrome Evaluation historical and hormonal algorithms were also used to assess menopause status. Women with T1D (n=105) were younger (42.8 vs. 46.0 yrs, p=.0003), more likely to be white (96.2% vs. 68.3%, p<.0001), never smokers (67.3% vs. 48.1%, p=.002), with lower BMI (25.2 vs. 26.5 kg/m2, p=.002) and higher HDL-C (61.0 vs. 53.0 mg/dl, p<.0001) compared with women without diabetes (n=341). Women with T1D were also older at menarche (13.3 vs. 12.6 yrs, p<.0001) but younger at natural menopause (50.1 vs. 51.9 yrs, p<.0001). Adjusting for age, race, smoking status, BMI, HDL, and number of pregnancies, T1D was associated with 3.3 (95% CI: 2.5-4.0) fewer reproductive years. The length of the reproductive period of women with T1D is shorter, having delayed menarche and earlier natural menopause, compared with women without diabetes. Factors that could be related to a shorter reproductive period in T1D should be investigated. Disclosure: Y. Yi: None. S.R. El Khoudary: None. R.G. Miller: None. D. Rubinstein: None. K.A. Matthews: None. T.J. Orchard: None. T. Costacou: None. Funding: National Institutes of Health (DK34818); Rossi Memorial Fund; National Institute on Aging; National Institute of Nursing Research; Office of Research on Women's Health [ABSTRACT FROM AUTHOR]

Abstract Background and aims We assessed the predictive role of coronary artery calcification (CAC) in clinically relevant cognitive impairment in 148 middle-aged individuals with childhood-onset type 1 diabetes (T1D) from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. Methods Baseline CAC was measured in 1996–98 and repeated 4–8 years later. Per extensive neuropsychological testing in 2010–15, 28% (41/148) of participants met the study definition of clinically relevant cognitive impairment (two or more of 7 select test scores ≥1.5SD worse than demographically appropriate published norms). Logistic regression models with backward selection were constructed for statistical analysis. Results Mean age and T1D duration at first CAC measure were 37 and 29 years, respectively. A greater burden of initial CAC was associated with cognitive impairment determined 14 years later. Compared to Agatston score = 0, odds ratio (OR) and 95% confidence intervals (CI) of 0<−100, 100<−300 and >300 were 1.4 (0.6, 3.6), 2.3 (0.6, 9.7), and 7.9 (1.6, 38.5), respectively. With both initial and progression of CAC in the multivariable model, backward selection retained only CAC progression, showing it was significantly associated with cognitive impairment (OR [95% CI]: 1.7 [1.1, 2.9]). In those with an initial CAC>0, CAC density was marginally, inversely, associated with cognitive impairment when controlling for CAC volume (OR [95%CI]: 0.3 (0.1, 1.2), p value = 0.078). Conclusions Greater CAC burden was associated with clinically relevant cognitive impairment in middle-aged adults with childhood-onset T1D. CAC progression appears to be a more powerful predictor than initial calcification. Graphical abstract Image 1 Highlights • Coronary artery calcification (CAC) is associated with cognitive impairment in middle-aged type 1 diabetes individuals. • CAC progression is more informative than initial CAC in predicting impaired cognition in type 1 diabetes. • CAC and high ankle-brachial index are independently associated with cognitive impairment in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: The presence of risk factors for type 2 diabetes and cardiovascular disease, or the conditions themselves, contributes to lower health-related quality of life (HRQoL) among adults. Although community-based lifestyle intervention programs have been shown to be effective for improving risk factors for these diseases, the impact of these interventions on HRQoL has rarely been described.Purpose: To examine changes in HRQoL following participation in the Group Lifestyle Balance program, a community translation of the Diabetes Prevention Program lifestyle intervention for adults with prediabetes and/or the metabolic syndrome.Methods: Participants enrolled in the 12-month, 22-session intervention program (N = 223) completed the EuroQol Health Questionnaire (EQ-5D-3L) at baseline, 6, and 12 months. Linear mixed-effects regression models determined change in EQ-5D-visual analog scale (VAS) and Index scores post-intervention.Results: Mean EQ-5D-VAS was improved by +7.38 (SE = 1.03) at 6 months and by +6.73 (SE = 1.06) at 12 months post-intervention (both; p < 0.0001). Mean changes in EQ-5D index values were +0.00 (SE = 0.01; NS) and +0.01 (SE = 0.01; p < 0.05), respectively. Adjusted for age, baseline score, and achieving intervention goals, mean change in EQ-5D-VAS was +11.83 (SE = 1.61) at 6 months and +11.23 (SE = 1.54) at 12 months (both; p < 0.0001). Adjusted mean change in EQ-5D index value was +0.04 (SE = 0.01) at 6 months and +0.05 (SE = 0.01) at 12 months (both; p < 0.01).Conclusion: Participation in a community lifestyle intervention program resulted in improved HRQoL among adults with prediabetes and/or the metabolic syndrome. These benefits to HRQoL, together with improved clinical and behavioral outcomes, should increase the appeal of such programs for improving health. [ABSTRACT FROM AUTHOR]

It is well known that those with metabolic syndrome (MS) are at risk for development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Prospective data evaluating the relationship between perception of disease risk and achievement of lifestyle changes for risk reduction are lacking. Fifty-one patients (42 female) with MS who participated in the Group Lifestyle Balance (GLB) were asked to complete a modified Risk Perception Survey for Developing Diabetes (RPS-DD). The GLB, a 12-week lifestyle change program adapted from the Diabetes Prevention Program (DPP) included the same intervention goals (7% weight loss, 150 minutes of physical activity) with minor modifications. Participants had no prior history of diabetes, a BMI ≥25 and MS (NCEPATPIII definition) with glucose criterion ≥100mg/dl (ADA pre-diabetes definition). The survey which included questions concerning attitude about lifestyle behaviors, health, environmental and individual risk was completed pre and post intervention. For those completing both surveys, belief in personal control over health risk and feelings that personal effort may control diabetes risk showed marginally significant increases (p=0.06, p=0.07 respectively); a significant increase in the perceived personal control subscale score was also noted (p=0.02). The anticipated weight loss at 3 months was 3%; a greater number of patients who experienced a 3% weight loss believed, prior to starting, that they had high risk of developing diabetes within the next year if they did not change their current lifestyle behaviors than those who did not achieve 3% (63.2% v 28.1%, p=0.06). No notable differences were seen in this group regarding lifestyle change and diabetes development within the next 10 years. Post intervention survey responses showed a positive correlation between belief that regular exercise and diet will prevent diabetes development and weight loss (r=0.35, p<0.05) however no relationship was noted in pre-survey responses. For people at risk for T2D and CVD, results of this survey suggest that participation in a lifestyle change program may increase feelings of personal control and responsibility for health risk as well as positively influence attitude toward making healthy changes. Furthermore, concern regarding imminent development of diabetes may be a contributing factor to success in making lifestyle changes; health education regarding disease risk is essential. [ABSTRACT FROM AUTHOR]

Objective: To determine whether an evidence-based, behavioral lifestyle intervention program delivered at a worksite setting is effective in improving type 2 diabetes and cardiovascular disease risk factors. Methods: A ran domized 6-month delayed control design was utilized, with two thirds of the participants assigned to begin intervention immediately, and one third beginning 6 months later. The year-long program (weekly for 3 months transitioning to monthly) focused on weight loss and increasing physical activity. Results: The immediate intervention group had greater mean weight loss (-10.4 lb, 5.1%, vs —2.3 lb, 1%; P = 0.0001) than the delayed control group at 6 months and relatively greater improvements in activity, HbAlc, and other risk factors. The delayed group experienced similar improvements after completing the intervention program. Conclusions: A worksite behavioral lifestyle intervention is feasible and effective in significantly improving risk factors for type 2 diabetes and cardiovascular disease. [ABSTRACT FROM AUTHOR]