Trajectories of Body Weight and Fat Mass in Relation to Incident Prediabetes in a Biracial Cohort of Free-Living Adults.

OBJECTIVES: Obesity is a risk factor for type 2 diabetes (T2D), but prospective data relating adiposity measures to incident prediabetes are scant. METHODS: The Pathobiology of Prediabetes in A Biracial Cohort study followed normoglycemic African Americans (AA) and European Americans (EA) with parental history of T2D for the primary outcome of incident prediabetes (impaired fasting glucose and/or impaired glucose tolerance) for 5.5 years. Serial assessments included anthropometry and body fat composition. We analyzed weight, body mass index (BMI), waist, total, and abdominal fat mass in relation to incident prediabetes risk. RESULTS: Of the 376 subjects enrolled (217 AA, 159 EA; mean age 44.2 years, BMI 31.4 kg/m2), 343 (192 AA, 151 EA) had evaluable follow-up data. A total of 101 (52 AA, 49 EA) developed prediabetes during follow-up. Progressors to prediabetes had a mean baseline weight of 90.0 ± 20.4 kg versus 82.9 ± 21.7 kg among nonprogressors (P = 0.0036). During 5.5 (mean 2.62) years of follow-up, the weight change among nonprogressors was 0.63 ± 6.11 kg compared with 2.54 ± 6.91 kg among progressors (ANOVA P = 0.0072). Progressors also showed greater increases in total fat (P = 0.0015) and trunk fat (P = 0.0005) mass than nonprogressors. Adjusted for age and sex, the significant predictors of incident prediabetes were BMI (P = 0.0013), waist (P < 0.0001), total fat (P = 0.0025), and trunk fat (P < 0.0001) mass. CONCLUSIONS: Among obese free-living offspring of parents with T2D, long-term normoglycemic status was associated with a weight gain of ~0.2 kg/y, whereas progression to prediabetes was associated with a weight gain of ~1 kg/y.

Five-Year Glycemic Trajectories Among Healthy African-American and European-American Offspring of Parents With Type 2 Diabetes.

BACKGROUND: Cross-sectional surveys report a higher prevalence of diagnosed type 2 diabetes mellitus (T2DM) in African Americans (AA) than European Americans (EA). We studied 5-year glycemic excursions among AA and EA in the Pathobiology of Prediabetes in A Biracial Cohort study, to assess ethnic disparities. MATERIALS AND METHODS: Pathobiology of Prediabetes in A Biracial Cohort followed normoglycemic offspring of parents with T2DM for 5 years, with serial assessments of oral glucose tolerance test , anthropometry, body fat, insulin sensitivity and beta-cell function. The primary outcome was progression to prediabetes (impaired fasting glucose and/or impaired glucose tolerance). We further analyzed 5-year changes in fasting (FPG) and 2-hour plasma glucose (2hrPG). RESULTS: One hundred and one (52 AA, 49 EA) out of 343 subjects developed prediabetes during follow-up. The change in FPG ranged from -24 mg/dl to +38 mg/dl. The FPG remained stable (± 5 mg/dl from baseline) in 50% of EA and 46.8% of AA and the 2hrPG remained stable (± 25 mg/dl from baseline) in 73.7% of EA and 71.0 % of AA during follow-up. The proportions with change in FPG of 5mg/dl to >25 mg/dl and 2hrPG of 25 mg/dl to >50 mg/dl were similar in EA and AA offspring, as were the 10th - 90th percentiles of the distribution of 5-year changes in FPG and 2hrPG. CONCLUSIONS: During 5 years of follow-up, black and white offspring of parents with T2DM exhibited remarkable phenotypic concordance of glycemic trajectories. Thus, parental history of T2DM may be a stronger factor than race/ethnicity in the prediction of longitudinal glycemic trends.

Multi-year reproducibility of hyperinsulinemic euglycemic clamp-derived insulin sensitivity in free-living adults: Association with incident prediabetes in the POP-ABC study.

OBJECTIVE: The hyperinsulinemic euglycemic clamp (HEC) is the "gold standard" for measuring insulin sensitivity (Si-clamp). Here, we determined the reproducibility of serial HEC data in healthy subjects. RESEARCH DESIGN AND METHODS: The Pathobiology of Prediabetes in A Biracial Cohort study assessed incident prediabetes in healthy African Americans (AA) and European Americans (EA) with parental type 2 diabetes mellitus during 5.5 years of follow-up. Assessments included anthropometry, OGTT, and HEC. Ninety subjects (44 AA, 46 EA) who underwent Year-1HEC consented to Year-3 HEC. We calculated coefficients of variation (CVs), 95% limits of agreement, and repeatability coefficients for Year-1 and Year-3 data, and assessed the association of change in Si-clamp with incident prediabetes. RESULTS: The mean (SD) baseline age was 47.5 ±â€¯8.13y, body mass index was 30.4 ±â€¯9.16 kg/m2, fasting plasma glucose was 93.7 ±â€¯7.82 mg/dL and 2-hrPG was 126 ±â€¯26.8 mg/dL. Si-clamp (umol/kg/min·pmol/L-1) was 0.071 ±â€¯0.04 in Year 1 and 0.067 ±â€¯0.04 in Year 3 (P = 0.22). Year 1 and Year 3 values were strongly correlated (r = 0.81, P < 0.0001); the CV was 13.6% and repeatability coefficient was ±0.025. Intrasubject differences in serial Si-clamp were less than the repeatability coefficients and within the 95% limits of agreement. After 5.5 years of follow-up, 40 subjects progressed to prediabetes and 50 were nonprogressors. The change in Si-clamp was greater in progressors than nonprogressors (-10% vs. -2.5%, P = 0.02). CONCLUSIONS: The HEC is reproducible over ~2 years in free-living individuals, with a temporal decline in Si-clamp that predicts prediabetes risk.

Basal and Dynamic Leptin Secretion: Association with Cardiometabolic Risk and Body Weight Trajectories in African-Americans and European-Americans.

BACKGROUND: Fasting plasma leptin levels reflect fat mass, but dynamic leptin responses to secretagogues, and the influence of race/ethnicity, have not been well studied. Here, we compared basal and stimulated leptin levels in relation to cardiometabolic risk and weight trajectories in black and white subjects. SUBJECTS AND METHODS: We studied 254 (127 black and 127 white) normoglycemic adults enrolled in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. At baseline and annually, POP-ABC participants underwent physical examination, oral glucose tolerance test, and measurements of body fat (dual energy X-ray absorptiometry), fasting plasma leptin, insulin, cortisol, lipids, and leptin secretory response to single-dose (2 mg) dexamethasone (dex). The interactions among basal and stimulated leptin and changes in adiposity/cardiometabolic measures during the ensuing year were then analyzed. RESULTS: The mean (±SD) fasting leptin level (50.6 ± 47.7 vs. 39.5 ± 37.6 ng/mL, P = 0.004) and body mass index (BMI) (31.9 ± 7.14 vs. 29.0 ± 7.66 kg/m2, P = 0.0043) were higher in black women vs. white women, but similar in black men vs. white men (leptin: 12.4 ± 2.07 vs. 11.1 ± 1.40 ng/mL; BMI: 29.4 ± 7.68 vs. 28.1 ± 4.23 kg/m2). The peak leptin response to dex (~200% baseline) did not differ significantly by gender or race. Total body fat correlated positively with fasting leptin (r = 0.81, P < 0.0001) and inversely stimulated leptin levels (r = -0.26, P < 0.0001). Fasting leptin was unrelated to 1-year change in weight or fat mass, whereas stimulated leptin levels were significantly associated with 1-year trajectories in weight (P = 0.0016) and total fat mass (P = 0.0035). Stimulated leptin levels also had significant interactions with insulin sensitivity (homeostasis model of insulin resistance, P = 0.01), triglycerides (P = 0.0078), fasting glucose (P = 0.027), systolic blood pressure (P = 0.037), and high-sensitivity C-reactive protein (P = 0.027). CONCLUSION: We found no significant ethnic disparities in basal or dynamic leptin secretion in relation to adiposity. Fasting leptin levels were not associated with 1-year weight change, while stimulated levels showed weak though significant association with 1-year weight change.

Relationships between blood pressure and blood glucose among offspring of parents with type 2 diabetes: Prediction of incident dysglycemia in a biracial cohort.

AIMS: We assessed blood pressure (BP) and blood glucose (BG) values in healthy subjects, and examined baseline BP as a predictor of incident prediabetes during follow-up. METHODS: Participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study underwent screening assessments (anthropometry, BP, OGTT) and were stratified into normal BP (NBP), prehypertension, or hypertension, and normal glucose regulation (NGR), prediabetes (IFG/IGT), or type 2 diabetes (T2D) status. NGR subjects who met all inclusion criteria were enrolled in a 5-yr prospective study, with the primary outcome of incident prediabetes. RESULTS: We screened 602 adults (341 black, 261 white) and enrolled 343 (193 black, 150 white) for prospective follow-up. Systolic and diastolic BP correlated significantly with fasting and nonfasting BG (P=0.003-<0.0001). Compared to NGR group, more prediabetic subjects had prehypertension (42.5% vs. 36.2%) and fewer had NBP (35.9% vs. 48.6%) (P=0.009). During ~5years of follow-up, 26.3% of NBP and 35.7% of prehypertensive subjects developed prediabetes (P=0.02). Kaplan-Meier analysis showed higher probability of incident prediabetes among participants with prehypertension compared to NBP during ~5years of follow-up (P=0.0012). CONCLUSIONS: In our biracial cohort, BP and BG values were significantly correlated, and BP status predicted incident prediabetes among initially normoglycemic individuals. These findings suggest co-evolution of factors involved in the dysregulation of BP and BG.

Dietary habits and leisure-time physical activity in relation to adiposity, dyslipidemia, and incident dysglycemia in the pathobiology of prediabetes in a biracial cohort study.

BACKGROUND: Dietary and exercise data are frequently recorded in clinical research, but their correlation with metabolic measures needs further evaluation. OBJECTIVE: We examined the association of food and exercise habits with body size, lipid profile, and glycemia in a prospective biracial cohort. METHODS: The Pathobiology of Prediabetes in A Biracial Cohort study followed initially normoglycemic offspring of parents with type 2 diabetes (T2DM) for the occurrence of incident prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). At enrollment, participants underwent a 75-gram OGTT, anthropometry, measurement of fasting lipids, insulin, and body fat (DEXA), and completed the Food Habits Questionnaire (FHQ), and Modifiable Activity Questionnaire (MAQ). We assessed the relationship between FHQ and MAQ scores and adiposity, cardiometabolic measures, and incident dysglycemia. RESULTS: Among our cohort of 338 subjects (188 black, 150 white; mean age {±SD} 45.2±10.2 years, BMI 30.3±7.2 kg/m(2)), FHQ and MAQ scores were individually correlated with BMI (r=0.14, -0.12; P=0.01, 0.03) and waist circumference (r=0.19, -0.11; P=0.004, 0.05). Diet-adjusted leisure activity (MAQ/FHQ) was significantly correlated with total body fat (r=-0.20, P=0.0007), trunk fat (r=-0.20, P=0.0006), and serum triglycerides (r=-0.17, P=0.003) and HDL cholesterol (r=0.11, P=0.04) levels. During 5.5 years of follow-up, 111 subjects (Progressors) developed prediabetes (n=101) or diabetes (n=10) and 227 remained normoglycemic (Non-progressors). Age, BMI, MAQ and MAQ/FHQ values were significant predictors of incident prediabetes/diabetes. Progressors reported similar dietary habits (FHQ score 2.57±0.49 vs. 2.57±0.53) but 30% lower physical activity (MAQ score 15.2±20.5 vs. 22.3±30.5 MET-hr/wk, P=0.015) compared with non-progressors. CONCLUSIONS: Among African-American and Caucasian offspring of parents with T2DM, self-reported dietary and exercise habits correlated with measures of adiposity and dyslipidemia; however, physical activity, but not dietary recall, significantly predicted incident dysglycemia during 5.5 years of follow-up.

Lack of racial disparity in incident prediabetes and glycemic progression among black and white offspring of parents with type 2 diabetes: the pathobiology of prediabetes in a biracial cohort (POP-ABC) study.

BACKGROUND: Although the incidence of type 2 diabetes (T2D) among persons with prediabetes is well known (∼10%/y), the incidence of prediabetes among normoglycemic persons is unclear. Also, in the Diabetes Prevention Program, no racial/ethnic differences were seen in diabetes incidence, whereas marked racial/ethnic disparities are reported in the prevalence of T2D. We aimed to obtain estimates of incident prediabetes and determine whether racial disparities manifest during transition to prediabetes. DESIGN AND METHODS: We enrolled 376 (217 black, 159 white) nondiabetic offspring of parents with T2D (mean age 44.2 y) and followed them up quarterly for 5.5 years. Assessments included anthropometry, body composition, oral glucose tolerance test, biochemistries, energy expenditure, insulin sensitivity, and insulin secretion. The primary outcome was progression to impaired fasting glucose and/or impaired glucose tolerance (or diabetes). RESULTS: Of 343 participants with evaluable data, 101 subjects (49 white, 52 black) developed prediabetes, and 10 (4 white, 6 black) developed diabetes during a mean follow-up of 2.62 years. There was no significant racial difference in the cumulative incidence of prediabetes (32.7% white, 30% black) or combined prediabetes/diabetes (35% white, 30% black). Significant predictors of prediabetes included age, gender, trunk fat, 2-hour postload glucose (2hrPG), insulin sensitivity, and insulin secretion. In a Cox proportional-hazards model, with adjustment for age and sex, the 2hrPG and abdominal obesity were independent predictors of incident prediabetes/diabetes [relative hazards (95% confidence interval [CI]) for the 90th vs 10th percentile: trunk fat mass 2.90 (95% CI 1.74-4.82), P < .0001; 2hrPG 2.54 (95% CI 1.46-4.40), P = .0009]. Having the trunk fat mass and the 2hrPG at the 90th percentile conferred a 7-fold hazard of prediabetes compared with persons at the 10th percentile for both measures. CONCLUSION: Black and white offspring of parents with type 2 diabetes develop prediabetes at a similar high rate of approximately 11% per year. Therefore, close surveillance, with prompt intervention to prevent dysglycemia, is warranted in persons with parental diabetes.

Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels.

OBJECTIVE: A hemoglobin (Hb) A1c range of 5.7%-6.4% has been recommended for the diagnosis of prediabetes. To determine the significance of such "prediabetic" HbA1c levels, we compared glucoregulatory function in persons with HbA1c levels of 5.7%-6.4% and those with HbA1c<5.7%. METHODS: We studied 280 nondiabetic adults (142 black, 138 white; mean (±SD) age 44.2±10.6 years). Each subject underwent clinical assessment, blood sampling for HbA1c measurement, and a 75-g oral glucose tolerance test at baseline. Additional assessments during subsequent outpatient visits included insulin sensitivity, using homeostasis model assessment (HOMA)-IR and the hyperinsulinemic euglycemic clamp; insulin secretion, using HOMA-B and frequently samples intravenous glucose tolerance test (FSIVGTT) and disposition index (DI); and measurement of fat mass, using DXA. RESULTS: Compared to subjects with HbA1c<5.7%, persons with HbA1c levels of 5.7%-6.4% were older, and had higher body mass index (BMI) and insulin secretion but similar insulin sensitivity. When the two groups were matched in age and BMI, persons with HbA1c 5.7%-6.4% were indistinguishable from those with HbA1c <5.7% with regard to all measures of glycemia and glucoregulatory function. CONCLUSIONS: Unlike glucose-defined prediabetes status, an HbA1c range of 5.7%-6.4% does not reliably identify individuals with impaired insulin action or secretion, the classical defects underlying the pathophysiology of prediabetes. Thus, HbA1c cannot validly replace blood glucose measurement in the diagnosis of prediabetes. If utilized as a screening test due to convenience, aberrant HbA1c values should be corroborated with blood glucose measurement before therapeutic intervention.

Recruitment strategies and yields for the Pathobiology of Prediabetes in a Biracial Cohort: a prospective natural history study of incident dysglycemia.

BACKGROUND: The Pathobiology of Prediabetes in A Biracial Cohort study is a prospective evaluation of the transition from normal to impaired glucose regulation among African American and Caucasian adults with parental type 2 diabetes. This report describes recruitment strategies and relative yields for the 376 enrolled subjects. METHODS: Recruitment occurred over 3.4 years, with clinical and metabolic assessments during 2.1-5.5 years of quarterly follow-up. The major recruitment sources were advertisements, community outreach, and clinical facilities. Advertisements included newspaper, television, radio, Internet, distributed brochures, utility bill inserts, and direct mailing. Community outreach included screening events during religious gatherings and health fairs, and referral by friends and families. The category of clinical facilities covered all subjects referred by health workers or recruited through area clinics and hospitals. RESULTS: 57.7% of participants were African American and 42.3% were Caucasian; the mean age (± SD) was 44.2 ± 10.6 years, and ~70% were female. Advertisements yielded 52.4% of all participants, compared to 34.8% from community outreach and 12.8% from clinical facilities (P for trend < 0.0001). More Caucasians than African Americans cited advertising as the source of study information, whereas more African Americans than Caucasians cited community outreach. The accrual from clinical facilities was similar in both groups. CONCLUSIONS: Advertisements and community outreach were robust recruitment sources for assembling a diverse longitudinal diabetes offspring cohort, but each had differential yields in African Americans and Caucasians. Thus, a multifaceted approach comprising passive and active components is needed to recruit a multiracial clinical research population.

Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study: baseline characteristics of enrolled subjects.

BACKGROUND: The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study is a prospective evaluation of the natural history impaired glucose regulation. DESIGN AND METHODS: The eligibility requirements include age 18-65 yr, history of type 2 diabetes in one or both parents, normal fasting plasma glucose (FPG) or normal glucose tolerance, and African-American or Caucasian status. Participants underwent assessments (including dietary and exercise behavior, clinical examination, glucose tolerance, insulin sensitivity, ß-cell function, body composition, energy expenditure) during 2.25-5.5 yr of quarterly follow-up. The primary outcome is the occurrence of prediabetes. Baseline data are presented for the 376 enrolled participants. The cohort was also compared with National Health and Nutrition Examination Survey 2007/2008 participants meeting the age and glycemic criteria for the POP-ABC study. RESULTS: The POP-ABC cohort [mean (±SD) age was 44.2 ± 10.6 yr] was 57.7% African-Americans, 42.3% Caucasians, and 70.7% females; 86% had one parent with diabetes and 14% had both parents affected. Although greater than 70% of the cohort were employed and 75% had more than 13 yr of education, more African-Americans reported incomes less than $20,000 and fewer reported incomes more than $75,000 compared with Caucasians. Compared with Caucasians, African-Americans had a higher body mass index (31.3 ± 7.8 vs. 28.8 ± 7.8 kg/m(2), P = 0.001), a lower FPG (90.0 ± 7.72 vs. 92.2 ± 7.60 mg/dl, P = 0.008), higher glycosylated hemoglobin, lower triglycerides, and similar blood pressure, and homeostasis model assessment of insulin resistance, homeostasis model assessment of ß-cell function, high-density lipoprotein, and low-density lipoprotein cholesterol levels. Compared with a cross-section of U.S. subjects (National Health and Nutrition Examination Survey 2007/2008) with normal FPG and normal glucose tolerance, participants in the POP-ABC study had similar lipid profile but were more educated and had higher body mass index, glycosylated hemoglobin, and blood pressure. CONCLUSIONS: The POP-ABC study has successfully enrolled healthy African-American and Caucasian adults with parental type 2 diabetes mellitus. The study will generate novel data on incidence rates and predictors of prediabetes, and clarify the role of race/ethnicity on early dysglycemia.

Leukocyte count and cardiometabolic risk among healthy participants with parental type 2 diabetes: the Pathobiology of Prediabetes in a Biracial Cohort study.

OBJECTIVE: White blood cell (WBC) count has been associated with cardiometabolic risk, but the data for African Americans are conflicting. We determined whether WBC count predicts subclinical inflammation and cardiometabolic risk in African Americans, despite their known lower WBC count, compared to Caucasians. RESEARCH DESIGN AND METHODS: The study cohort consisted of 334 normoglycemic subjects (153 Caucasian, 181 African American) with parental type 2 diabetes (T2DM), mean (+/- SD) age 43.90 +/- 10.25 y and BMI 30.1 +/- 6.84 kg/m2. Each subject underwent clinical examination and a standard oral glucose tolerance test (OGTT) to document glycemic status. Blood specimens were obtained for determination of WBC counts, lipid profile and C-reactive protein (CRP) levels. Metabolic syndrome components were identified, using the NCEP cut-offs for waist circumference, blood pressure, HDL cholesterol and triglyceride levels. RESULTS: Leukocyte counts were lower by approximately 400/cm3 (P=.04) in African Americans than Caucasians, and were significantly correlated with waist circumference, HDL cholesterol, triglycerides and 2-h OGTT plasma glucose (P=.024-.0009), but not blood pressure in both races. Leukocyte counts significantly predicted the presence of three or more components of the metabolic syndrome similarly in African Americans (P=.0076) and Caucasians (P=.0078), as did CRP levels. Leukocyte counts correlated significantly with CRP levels in African Americans (r=.30, P<.0001) and Caucasians (r=.29, P=.0003). CONCLUSIONS: Our data indicate that WBC count, despite being lower in African Americans than Caucasians, predicts low-grade inflammation and cardiometabolic risk with similar magnitude in normoglycemic African Americans and Caucasians with parental T2DM.

Ethnic disparity in hemoglobin A1c levels among normoglycemic offspring of parents with type 2 diabetes mellitus.

OBJECTIVE: To investigate the racial/ethnic disparities in hemoglobin A1c levels among nondiabetic persons with similar parental history of type 2 diabetes mellitus. METHODS: We studied a community-based sample of adult offspring of parents with type 2 diabetes mellitus. Measurements included anthropometry, hematology assessments, serial fasting plasma glucose, oral glucose tolerance testing, plasma insulin, hemoglobin A1c, insulin sensitivity, and ß-cell function, using a homeostasis model assessment. RESULTS: The study included 302 participants (135 white, 167 black). Compared with white participants, black participants had lower fasting plasma glucose levels (91.9 ± 0.51 mg/dL vs 93.6 ± 0.50 mg/dL, P = .015), lower area under the curve of plasma glucose during oral glucose tolerance testing (P = <.001), higher body mass index (31.1 ± 0.61 kg/m² vs 28.5 ± 0.57 kg/m², P = <.001), and similar insulin sensitivity and ß-cell function. Hemoglobin A1c was higher in black participants than in white participants (5.68 ± 0.033% vs 5.45 ± 0.028%, P<.001). The absolute black-white difference in hemoglobin A1c level of approximately 0.22% persisted after adjusting for age, hemoglobin, hematocrit, body mass index, waist circumference, fasting plasma glucose, glucose area under the curve, and other covariates. CONCLUSIONS: Among healthy offspring of parents with type 2 diabetes mellitus in this study, African American participants had higher hemoglobin A1c levels than white participants after adjusting for age, adiposity, blood glucose, and known variables. Thus, plasma glucose level is more valid than hemoglobin A1c for diagnosing prediabetes or diabetes in black persons.

Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC): design and methods.

In contrast to the widely reported ethnic differences in prevalence, the incidence of type 2 diabetes was surprisingly similar (approximately 11%) among individuals from the different US ethnic groups in the Diabetes Prevention Program (DPP). Because DPP participants had impaired glucose tolerance (IGT) at baseline, we hypothesized that ethnic disparities are initiated at the pre-IGT stage during evolution of type 2 diabetes. The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) is designed to test that hypothesis by tracking the natural history of early dysglycemia in a biracial cohort comprising offspring of parents with type 2 diabetes. The POP-ABC study has an enrollment target of 400 participants (200 African American, 200 Caucasian), aged 18-65 years, with at least 1 parent with type 2 diabetes. All subjects must have normal fasting glucose and/ or normal glucose tolerance, as determined by a 75-gram oral glucose tolerance test (OGTT). Subjects are recruited over approximately 3 years and followed for another 2 years, with repeated metabolic assessments. The latter include OCTT, body composition, indirect calorimetry, euglycemic clamp, beta cell function, and biochemistries. Repository specimens (DNA, RNA and proteome) are obtained for future studies. The primary outcome is the occurrence of prediabetes (ICT and/or impaired fasting glucose). The sample size provides 85% power to detect a hazard ratio of 1.75 between Black and White offspring in the primary outcome (alpha = .05). Secondary endpoints include behavioral, biochemical and socioeconomic predictors of dysglycemia. The POP-ABC study will elucidate the nosogeny of ethnic disparities in glucose dysregulation.

Principles and practice of nonpharmacological interventions to reduce cardiometabolic risk.

The components of the metabolic syndrome, including prediabetes, prehypertension and dyslipidemia, represent prodromal stages of major cardiometabolic disorders. Lifestyle interventions have been shown to ameliorate or prevent the progression of individual components of the metabolic syndrome. The specific interventions utilized in randomized controlled studies often include dietary modification and physical activity. The effects of smoking cessation and the reduction of psychosocial stress on cardiometabolic risk factors need to be studied more. Because of the close concordance between the metabolic syndrome and multiple cardiometabolic diseases, the adoption of an effective lifestyle change upon initial recognition of the metabolic syndrome can be expected to delay or prevent the future development of sequelae such as diabetes, hypertension, and atherosclerotic cardiovascular and cerebrovascular diseases. Such a nonpharmacological approach to primary prevention and disease interruption carries enormous public health significance. Meeting the challenge of an implementation of effective lifestyle change at the community level requires (a) a system for the identification of at-risk populations, (b) an optimization of the knowledge base and practices of health care providers, and (c) a piloting of targeted biobehavioral intervention programs. Once identified, persons and communities at risk for cardiometabolic disorders can be empowered through increased health and nutritional literacy, the promotion of lifestyle interventions, provision of community resources, and pertinent legislative action that rewards preventive behavior. This paper reviews landmark studies that demonstrate the principles of nonpharmacological approaches to the reduction of cardiometabolic risk. We also discuss the physiological and emerging molecular genetic mechanisms that underlie the efficacy of lifestyle interventions.