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OBJECTIVE: The potential for choline metabolism to influence the development of diabetes has received increased attention. Previous studies on circulating choline metabolites and incident diabetes have been conducted in samples of older adults, often with a high prevalence of risk factors. RESEARCH DESIGN AND METHODS: Participants were from year 15 of follow-up (2000-2001) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (n = 3,133, aged 33–45 years) with plasma choline metabolite (choline, betaine, and trimethylamine N-oxide [TMAO]) data. We quantified associations between choline metabolites and 15-year risk of incident diabetes (n = 387) among participants free of diabetes at baseline using Cox proportional hazards regression models adjusted for sociodemographics, health behaviors, and clinical variables. RESULTS: Betaine was inversely associated with 15-year risk of incident diabetes (hazard ratio 0.76 [95% CI 0.67, 0.88] per 1-SD unit betaine), and TMAO was positively associated with 15-year risk of incident diabetes (1.11 [1.01, 1.22] per 1-SD unit). Choline was not significantly associated with 15-year risk of incident diabetes (1.05 [0.94, 1.16] per 1-SD). CONCLUSIONS: Our findings are consistent with other published literature supporting a role for choline metabolism in diabetes. Our study extends the current literature by analyzing a racially diverse population-based cohort of early middle-aged individuals in whom preventive activities may be most relevant. [ABSTRACT FROM AUTHOR]

Objective: To examine childhood BMI, fasting glucose, and insulin in relation to incident adult type 2 diabetes mellitus (T2DM).Research Design and Methods: We used data from the International Childhood Cardiovascular Cohort (i3C) Consortium. Data included childhood (age 3-19 years) measurements obtained during the 1970s-1990s; a health questionnaire, including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years; and a medical diagnosis registry (Finland).Results: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20 and 59 (mean 40.8) years, and 86% of them reported use of a confirmed antidiabetic medication. BMI and glucose (age and sex standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age, and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to an incrementally increased risk of T2DM beginning at age 30 years, beginning at cut points <95th percentile for BMI and <100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination.Conclusions: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy-to-apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations between change in plant-centered diet quality and type 2 diabetes risk and change in body size.Research Design and Methods: A prospective study conducted in the U.S. enrolled adults ages 18-30 years in 1985-1986 (examination year [Y0]) and followed them through 2015-2016. We analyzed the associations between change in plant-centered diet quality over 20 years (Y0-Y20) and diabetes (Y20-30; n = 2,534) and change (Y0-Y20 and Y20-30) in BMI, waist circumference (WC), and weight (n > 2,434). Plant-centered diet quality was measured using the A Priori Diet Quality Score (APDQS); a higher score favors nutritionally rich plant foods. Cox regression models were used to assess diabetes risk, and linear regression models were used to examine change in body size.Results: During a mean follow-up of 9.3 (± 1.7) years, 206 case subjects with incident diabetes were observed. In multivariable analysis, participants with the largest increase in APDQS over 20 years had a 48% (95% CI 0.31-0.85; Ptrend < 0.001) lower risk of diabetes over the subsequent 10 years compared with participants whose score remained stable. Each 1-SD increment in APDQS over 20 years was associated with lower gains in BMI (-0.39 kg/m2; SE 0.14; P = 0.004), WC (-0.90 cm; SE 0.27; P < 0.001) and weight (-1.14 kg; SE 0.33; P < 0.001) during the same period, but not with subsequent changes.Conclusions: Young adults who increased plant-centered diet quality had a lower diabetes risk and gained less weight by middle adulthood. [ABSTRACT FROM AUTHOR]

Objective: To determine whether intraindividual variability in fasting glucose (FG) below the threshold of diabetes is associated with cognitive function in middle adulthood beyond increasing FG.Research Design and Methods: We studied 3,307 CARDIA (Coronary Artery Risk Development in Young Adults) Study participants (age range 18-30 years and enrolled in 1985-1986) at baseline and calculated two measures of long-term glucose variability: the coefficient of variation about the mean FG (CV-FG) and the absolute difference between successive FG measurements (average real variability [ARV-FG]) before the onset of diabetes over 25 and 30 years of follow-up. Cognitive function was assessed at years 25 (2010-2011) and 30 (2015-2016) with the Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment, and category and letter fluency tests. We estimated the association between glucose variability and cognitive function test score with adjustment for clinical and behavioral risk factors, mean FG level, change in FG level, and diabetes development, medication use, and duration.Results: After multivariable adjustment, 1-SD increment of CV-FG was associated with worse cognitive scores at year 25: DSST, standardized regression coefficient -0.95 (95% CI -1.54, -0.36); RAVLT, -0.14 (95% CI -0.27, -0.02); and Stroop Test, 0.49 (95% CI 0.04, 0.94). Findings were similar between CV-FG with each cognitive test score at year 30 and when we used an alternative measure of variability (ARV-FG) that captures variability in successive FG values.Conclusions: Higher intraindividual FG variability during young adulthood below the threshold of diabetes was associated with worse processing speed, memory, and language fluency in midlife independent of FG levels. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes mellitus (GDM) predicts incident cardiovascular disease (CVD). However, mechanisms linking GDM to CVD beyond intervening incident diabetes are not well understood. We examined the relation of GDM with echocardiographic parameters of left ventricular (LV) structure and function, which are important predictors of future CVD risk.Research Design and Methods: We studied 609 women (43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who delivered one or more births during follow-up and had echocardiograms in 1990-1991 (mean age 28.8 years) and 2010-2011.Results: During the 20-year follow-up, 965 births were reported, with GDM developing in 64 women (10.5%). In linear regression models adjusted for sociodemographic factors, BMI, physical activity, parity, smoking, use of oral contraceptives, alcohol intake, family history of coronary heart disease, systolic blood pressure, and lipid levels, women with GDM had impaired longitudinal peak strain (-15.0 vs. -15.7%, P = 0.025), circumferential peak strain (-14.8 vs. -15.6%, P = 0.028), lateral e' wave velocity (11.0 vs. 11.8 cm/s, P = 0.012), and septal e' wave velocity (8.6 vs. 9.3 cm/s, P = 0.015) in 2010-2011 and a greater 20-year increase in LV mass indexed to body surface area (14.3 vs. 6.0 g/m(2), P = 0.006) compared with women with non-GDM pregnancies. Further adjustment for incident type 2 diabetes after pregnancy did not attenuate these associations.Conclusions: Pregnancy complicated by GDM is independently associated with increased LV mass and impaired LV relaxation and systolic function. Implementation of postpartum cardiovascular health interventions in women with a history of GDM may offer an additional opportunity to reduce future CVD risk. [ABSTRACT FROM AUTHOR]

Objective: To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults.Research Design and Methods: We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: ≥30 and <45 years; middle-aged: ≥45 and <60 years) and examined for incident diabetes (median follow-up 9 years). Duration and degree of gain in BMI were calculated as "BMI-years" above one's baseline BMI.Results: Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BMI and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 (P = 0.02) and 1.02 (P = 0.39), respectively (P for interaction by age-group = 0.047), and in whites were 1.35 (P < 0.001) and 1.11 (P < 0.001), respectively (P for interaction by age-group = 0.008).Conclusions: Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain. [ABSTRACT FROM AUTHOR]

Objective: Higher levels of hemoglobin A1c (HbA1c) are associated with increased cardiovascular disease risk among individuals without diabetes and may also be positively associated with coronary artery calcification (CAC). This study investigated the association of HbA1c with CAC progression in the Coronary Artery Risk Development in Young Adults study.Research Design and Methods: We included 2,076 participants with HbA1c and noncontrast computed tomography (CT) assessed at baseline (2005-2006), and CT repeated 5 years later (2010-2011). CAC progression was defined as 1) incident CAC (increase >0 Agatston units among those with no CAC at baseline), 2) any CAC progression (increase >10 Agatston units between examinations), and 3) advanced CAC progression (increase >100 Agatston units between examinations).Results: During the 5-year follow-up period, 12.9% of participants without baseline CAC developed incident CAC; among all participants, 18.2% had any CAC progression and 5.4% had advanced CAC progression. Higher HbA1c was associated with incident CAC (risk ratio [RR] = 1.45; 95% CI 1.02, 2.06), any CAC progression (RR = 1.51; 95% CI 1.16, 1.96), and advanced CAC progression (RR = 2.42; 95% CI 1.47, 3.99) after adjustment for sociodemographic factors. Additional adjustment for cardiovascular risk factors attenuated the associations of HbA1c with incident CAC (RR = 1.05; 95% CI 0.74, 1.49) and any CAC progression (RR = 1.13; 95% CI 0.87, 1.47). In contrast, the association of HbA1c with advanced CAC progression persisted in multivariable adjusted models (RR = 1.78; 95% CI 1.08, 2.95).Conclusions: Higher HbA1c was independently associated with advanced CAC progression among individuals without diabetes, while the associations with incident CAC and any CAC progression were accounted for by other established cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

OBJECTIVE Higher levels of hemoglobin A1c (HbA1c) are associated with increased cardiovascular disease risk among individuals without diabetes and may also be positively associated with coronary artery calcification (CAC). This study investigated the association of HbA1c with CAC progression in the Coronary Artery Risk Development in Young Adults study. RESEARCH DESIGN AND METHODS We included 2,076 participants with HbA1c and noncontrast computed tomography (CT) assessed at baseline (2005-2006), and CT repeated 5 years later (2010-2011). CAC progression was defined as 1) incident CAC (increase >0 Agatston units among those with no CAC at baseline), 2) any CAC progression (increase >10 Agatston units between examinations), and 3) advanced CAC progression (increase >100 Agatston units between examinations). RESULTS During the 5-year follow-up period, 12.9% of participants without baseline CAC developed incident CAC; among all participants, 18.2% had any CAC progression and 5.4% had advanced CAC progression. Higher HbA1c was associated with incident CAC (risk ratio [RR] = 1.45; 95% CI 1.02, 2.06), any CAC progression (RR = 1.51; 95% CI 1.16, 1.96), and advanced CAC progression (RR = 2.42; 95% CI 1.47, 3.99) after adjustment for sociodemographic factors. Additional adjustment for cardiovascular risk factors attenuated the associations of HbA1c with incident CAC (RR = 1.05; 95% CI 0.74, 1.49) and any CAC progression (RR = 1.13; 95% CI 0.87, 1.47). In contrast, the association of HbA1c with advanced CAC progression persisted in multivariable adjusted models (RR = 1.78; 95% CI 1.08, 2.95). CONCLUSIONS Higher HbA1c was independently associated with advanced CAC progression among individuals without diabetes, while the associations with incident CAC and any CAC progression were accounted for by other established cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The relation of breakfast intake frequency to metabolic health is not well studied. The aim of this study was to examine breakfast intake frequency with incidence of metabolic conditions. RESEARCH DESIGN AND METHODS--We performed an analysis of 3,598 participants from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study who were free of diabetes in the year 7 examination when breakfast and dietary habits were assessed (1992-1993) and participated in at least one of the five subsequent follow-up examinations over 18 years. RESULTS--Relative to those with infrequent breakfast consumption (0-3 days/week), participants who reported eating breakfast daily gained 1.9 kg less weight over 18 years (P = 0.001). In a Cox regression analysis, there was a stepwise decrease in risk across conditions in frequent breakfast consumers (4-6 days/week) and daily consumers. The results for incidence of abdominal obesity, obesity, metabolic syndrome, and hypertension remained significant after adjustment for baseline measures of adiposity (waist circumference or BMI) in daily breakfast consumers. Hazard ratios (HRs) and 95% CIs for daily breakfast consumption were as follows: abdominal obesity HR 0.78 (95% CI 0.66-0.91), obesity 0.80 (0.67-0.96), metabolic syndrome 0.82 (0.69-0.98), and hypertension 0.84 (0.72-0.99). For type 2 diabetes, the corresponding estimate was 0.81 (0.63-1.05), with a significant stepwise inverse association in black men and white men and women but no association in black women. There was no evidence of differential results for high versus low overall dietary quality. CONCLUSIONS--Daily breakfast intake is strongly associated with reduced risk of a spectrum of metabolic conditions. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Persistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly. RESEARCH DESIGN AND METHODS--Nineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). RESULTS--After adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8- 42.7), and 7.5 (1.4-38.8) (Ptrend <0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that Ptrend = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0-11.7) (Ptrend = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes. CONCLUSIONS--Despite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- To investigate the long-term associations of magnesium intake with incidence of diabetes, systemic inflammation, and insulin resistance among young American adults. RESEARCH DESIGN AND METHODS-- A total of 4,497 Americans, aged 18-30 years, who had no diabetes at baseline, were prospectively examined for incident diabetes based on quintiles of magnesium intake. We also investigated the associations between magnesium intake and inflammatory markers, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin6 (IL-6), and fibrinogen, and the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS-- During the 20-year follow-up, 330 incident cases of diabetes were identified. Magnesium intake was inversely associated with incidence of diabetes after adjustment for potential confounders. The multivariable-adjusted hazard ratio of diabetes for participants in the highest quintile of magnesium intake was 0.53 (95% CI, 0.32- 0.86; P[sub trend] < 0.01) compared with those in the lowest quintile. Consistently, magnesium intake was significantly inversely associated with hs-CRP, IL-6, fibrinogen, and HOMA-IR, and serum magnesium levels were inversely correlated with hs-CRP and HOMA-IR. CONCLUSIONS-- Magnesium intake was inversely longitudinally associated with incidence of diabetes in young American adults. This inverse association may be explained, at least in part, by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To test the hypothesis that A1C is associated with subclinical cardiovascular disease (CVD) in a population without evident diabetes, after adjusting for traditional CVD risk factors and BMI. RESEARCH DESIGN AND METHODS -- This was a cross-sectional study of 5,121 participants without clinically evident CVD or diabetes (fasting glucose ≥7.0 mmol/l or use of diabetes medication), aged 47-86 years, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Measurements included carotid intimal-medial wall thickness (CIMT) and coronary artery calcification (CAC). Results were adjusted for age, sex, ethnicity, smoking, systolic blood pressure, LDL cholesterol, HDL cholesterol, antihypertensive medication use, lipid-lowering medication use, and BMI. RESULTS -- Compared with those in the lowest quartile for A1C ([mean ± SD] 5.0 ± 0.2%), participants in the highest quartile (6.0 ± 0.3%) had higher adjusted mean values for common CIMT (0.85 vs. 0.87 mm, P = 0.003) and internal CIMT (1.01 vs. 1.08 mm, P = 0.003). A1C quartile was not associated with prevalence of CAC in the entire cohort (P = 0.27); however, the association was statistically significant in women (adjusted prevalence of CAC in lowest and highest A1C quartiles 37.5 vs. 43.0%, P = 0.01). Among those with some CAC, higher A1C quartile tended to be associated with higher CAC score, but the results were not statistically significant (adjusted P = 0.11). CONCLUSIONS -- In this multiethnic cohort, there were small, positive associations between A1C, common CIMT, and internal CIMT in the absence of clinically evident diabetes. An association between higher A1C and CAC prevalence was evident only in women. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We reported strong relations between serum concentrations of persistent organic pollutants (POPs), especially organochlorine (OC) pesticides or nondioxin-like polychlorinated biphenyls (PCBs), and prevalence of diabetes in a U.S population with background exposure to POPs. Here, we investigated POPs and insulin resistance, a frequent pathogenic precursor of type 2 diabetes. RESEARCH DESIGN AND METHODS -- Serum POPs and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated cross-sectionally in 749 nondiabetic participants aged ≥20 years. Nineteen POPs in five subclasses were selected, detectable in ≥60% of participants. RESULTS -- Among subclasses, OC pesticides were most strongly associated with HOMA-IR. Adjusted geometric means of HOMA were 3.27, 3.36, 3.48, and 3.85 (P for trend <0.01) across quartiles of OC pesticides. The relationship strengthened with increasing HOMA-IR percentile: adjusted odds ratios comparing the highest versus lowest POPs quartile were 1.8 for being ≥50th percentile of HOMA-IR, 4.4 for being ≥75th percentile, and 7.5 for being ≥90th percentile. Associations with elevated HOMA-IR appeared to be specific to oxychlordane and trans-nonachlor but also were found for two nondioxin-like PCBs. No HOMA-IR associations were seen in the other three POP subclasses. The association between OC pesticides and HOMA-IR tended to strengthen as waist circumference increased, with no apparent association in the lowest quartile of OC pesticide concentrations. CONCLUSIONS -- These findings, coupled with those concerning diabetes prevalence, suggest that OC pesticides and nondioxin-like PCBs may be associated with type 2 diabetes risk by increasing insulin resistance, and POPs may interact with obesity to increase the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE A relationship between birth weight and the insulin resistance syndrome has been reported in adults but has not been defined in adolescents. RESEARCH DESIGN AND METHODS — Data were analyzed in 296 children (132 girls and 164 boys) mean age 15.0 ± 1.2 years who had euglycemic insulin clamp studies (intravenous administration of 1 mU · kg[sup -1] · min[sup -1] of insulin balanced by a variable infusion of 20% glucose to maintain blood glucose at 100 mg/dl). Insulin sensitivity (M[sub LBM]) was determined by glucose uptake per kg lean body mass (LBM), and parents reported birth weight. RESULTS — Birth weight ranged from 1,021 to 4,848 g (mean ± SD 3,433 ± 551), with 4.0% <2,500 g. Fat mass and BMI had U-shaped relations with birth weight after adjustment for race, age, sex, and blood pressure. Lean mass index (lean mass/height squared) was stable across birth weight quartiles. Fasting insulin decreased nonsignificantly across birth weight quartiles but became significant after adjustment for adolescent weight (P = 0.008). Although M[sub LBM] was highest in the highest birth weight quartile, the pattern was not significant. Triglycerides tended to increase with birth weight, whereas LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) tended to decrease. Blood pressure was unrelated to birth weight. CONCLUSIONS — In this cohort, fat mass was greater in adolescents with low and high birth weight; fasting insulin was lower with higher birth weight after adjustment for adolescent weight. Insulin sensitivity increased nonsignificantly with birth weight. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations between reported intakes of dietary fat and incident type 2 diabetes.Research Design and Methods: We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up.Results: After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with omega-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score.Conclusions: These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the prospective association between accordance with the 2005 Dietary Guidelines for Americans (DGA) and subsequent diabetes incidence and changes in cardiometabolic risk factors. RESEARCH DESIGN AND METHODS--The sample consisted of 4,381 black and white young adults examined repeatedly from 1985 to 2005. We used the 2005 Diet Quality Index (DQI) to rate participants' diets based on meeting key dietary recommendations conveyed by the 2005 DGA. RESULTS--Overall, we found no association between DQI score and diabetes risk using Cox models adjusted for potential confounders. Higher DQI scores were associated with favorable changes in HDL cholesterol and blood pressure overall (P for trend <0.05), but with increased insulin resistance among blacks (P for trend <0.01). CONCLUSIONS--Our findings highlight the need for evaluation of the DGA's effectiveness, particularly among ethnic minority populations. Clinicians should be aware that following the DGA might not lower diabetes risk. [ABSTRACT FROM AUTHOR]