Background: To determine the role of ethnicity vs. heredity in glucoregulation, we assessed insulin secretion in healthy Black and White offspring of parents with T2DM. Methods: Participants were screened with 75-g OGTT, and normoglycemic enrollees underwent assessments, including anthropometry, insulin sensitivity and secretion. Basal insulin secretion (fasting insulin {FI} and HOMA-B) and dynamic secretion (insulinogenic index; corrected insulin response {CIR} from OGTT data; acute insulin response to i.v. glucose {AIR}, insulin-AUC during FSIGT, and disposition index {DI} were quantified. Insulin sensitivity (ISI) was measured with euglycemic clamp. Basal insulin clearance (molar ratio of fasting C-peptide to insulin) and dynamic clearance (molar ratio of plasma C-peptide to insulin levels during FSIGT) were determined. Results: We studied 145 Black and 123 White adults (N=268); 72% women; mean age 44.6±10.1 y. At baseline, fasting glucose (91.0 ± 7.26 vs.93.1 ± 6.31 mg/dl, P=0.012) and ISI (0.062 ± 0.048 vs. 0.077 ± 0.04, P=.014) were lower, and BMI (31.6 ± 7.64 vs. 28.9 ± 6.79, P=.0032) higher, in Black vs. White subjects. Basal insulin secretion was similar, but all measures of dynamic secretion were higher in Black vs. White offspring (Table 1). Conclusions: Insulin clearance is lower but dynamic insulin secretion is greater in Black versus White individuals with parental diabetes. Disclosure P. Asuzu: None. A. Patel: None. J. Y. Wan: None. S. Dagogo-jack: None.

Background: Body mass index (BMI) and waist circumference (WC) are routine clinical estimates of obesity. We tested the fidelity of BMI and WC against direct body fat measures in Black (B) vs. White (W) Americans. Subjects and Methods: We analyzed the relationship between BMI vs. total fat, WC vs. trunk fat, and weight vs. lean fat free mass (FFM) in healthy B and W adults. Assessments included clinical exam, biochemistries and a 75-g OGTT. All subjects had normal fasting and 2-hr OGTT glucose levels. Total fat mass, trunk fat mass and FFM were measured using DXA. Results: The participants (n=376; 217 B, 159 W) had an age range of 18-65 years and BMI range of 16.8-66.3 kg/m2 (mean 30.1) . The W vs. B values were: age 46.5 ± 10.5 vs. 42.5 ± 10.3 y, P=0.0003; BMI 28.8 ± 6.78 vs. 31.2 ± 7.40, P=0.0015; total fat mass 29.4 ± 13.21 vs. 31.8 ± 13.76 kg, P=0.11; trunk fat mass 14.77 ± 6.96 vs. 15.34 ± 7.50 kg, P=0.48; FFM 50.12 ± 11.9 vs. 53.± 11.74 kg, P= 0.03. There were tight correlations between adiposity measures: total fat and BMI (r=0.90 in W, 0.92 in B) ; trunk fat and WC (r=0.85 in W, 0.82 in B) ; FFM and weight (r=0.83 in W, 0.87 in B) , with heterogeneity by sex and race. White men and women (vs B) tended to have more body fat per unit BMI or WC and less FFM per unit weight. We assessed 3 integrated ratios (total Fat/BMI, trunk Fat/Waist, FFM/Weight) by sex and race. Total fat/BMI was higher (P<0.0001) in W vs. B (men: 0.946 ± 0.159 vs. 0.833 ± 0.210; women: 1.36 ± 0.189 vs. 1.25 ± 0.164) . Trunk fat/waist was higher in W vs. B men (0.294 + 0.043 in W vs. 0.257 + 0.072, P=0.0046) but similar in women. In contrast, FFM/weight ratio showed no race disparities (men: 0.696 ± 0.055 vs. 0.678 ± 0.200; women: 0.586 ± 0.1vs 0.579 ± 0.076) . The proportion with >3 metabolic syndrome markers was 24.5% in W and 15.7% in B. Conclusion: Among otherwise healthy subjects with a wide BMI range, African Americans had lower body fat than Whites. This finding that argues for ethnic-specific BMI cut-offs for obesity classification. Disclosure Z.Liu: None. A.A.Patel: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. Funding American Diabetes Association (7-07-MN-13) ; NIH, R01 DK067269

Objective: Ceramides (CER) and sphingolipids (SPL) have been linked to type 2 Diabetes (T2D) . Here we compared plasma SPL profiles in Black and White adults without a family history of T2D (FH−) vs. those with parental T2D (FH+) . Methods: We studied 240 healthy subjects: 140 FH+ (70 B, 70 W) and 100 FH− (50 B, 50 W) . Assessments included OGTT, insulin sensitivity (Si-clamp) and insulin secretion (AIRg) . Liquid chromatography/mass spectrometry was used to assay fasting plasma levels of 54 SPL species (18 each from 3 major classes: CER, monohexosyl ceramide {MHC}, and sphingomyelins {SM}) . We compared mole percent composition of SPL species within each class in FH+ and FH− groups. Results: The subjects’ mean (SD) age was 43.1 + 12.0 y, BMI 29.4 + 6.21, fasting glucose 91.4 + 6.90 mg/dl and 2-hr plasma glucose (2hPG) 123 + 26.3 mg/dl. Total levels of SPL, CER, MHC and SM did not differ by race or sex, and correlated with 2hPG and AIRg but not age, BMI, FPG or Si-clamp. FH+ and FH− adults were concordant for 37 of 54 SPL and discordant for 17 species. Compared with FH−, the FH+ subjects had higher molar abundance of 8 CER, 4 MHC and 2 SM, but lower values for C24:0 Cer, C24:0 MHC, and C26:0 MHC (Table 1) . Conclusion: Plasma SPL species correlate with glucose tolerance, are altered by parental T2D history, and may reflect heritable elements linking SPL and glucose metabolism. Disclosure N. Mandal: None. J. Y. Wan: None. F. B. Stentz: None. E. Nyenwe: None. A. A. Patel: None. S. Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. Funding National Institutes of Health (5R01DK128129)

Background: Type 2 Diabetes (T2D) is associated with alterations in BMD, but association between prediabetes and BMD is less clear. Subjects and Methods: We analyzed BMD in relation to demographic and metabolic parameters among the initially normoglycemic offspring of T2D parents in the POP-ABC (Pathobiology of Prediabetes in a Biracial Cohort) study. We further assessed the relationship between BMD and the risk of progression to prediabetes during 5 years of follow-up. Results: A total of 376 participants underwent DEXA (Dual-energy X-ray absorptiometry) during Year 1 of POP-ABC and were followed quarterly for 5 years, the primary outcome being progression from normoglycemia to prediabetes. The mean age was 44.2 ± 10.6 years; BMI was 30.2 ± 7.23 kg/m2; 217 Black, 159 White, with 71% female. At baseline, the mean BMD was 1.176 ± 0.135 g/cm2 for the entire cohort; 1.230 ± 0.124 g/cm2 in men vs. 1.154 ± 0.134 g/cm2 in women (P<0.0001) ; 1.203 ± 0.114 g/cm2 in Black vs. 1.146 ± 0.150 g/cm2 in White participants (P=0.0003) . There was an inverse relationship between BMD and age (r= −0.254, P<0.0001) and a direct association with BMI (r=0.173, P=0.0028) and weight (r=0.315, P<0.0001) . The BMD showed no significant correlation with insulin secretion or insulin sensitivity. However, the BMD z score, which compares BMD to the average values for a person of same age and gender, was significantly correlated with risk of progression to prediabetes (r = 0.173, P=0.0029) and showed positive association with total body fat mass (r=0.208, p=0.0003) and trunk fat mass (r= 0.178, P= 0.0021) . BMD z score was not significantly correlated with either CRP or adiponectin level. Conclusion: Among POP-ABC participants, BMD had the expected relationships with age, sex, and race. Higher BMD z score was predictive of progression to prediabetes among initially normoglycemic offspring of T2D parents during 5-year follow-up, an association that requires further mechanistic insights. Disclosure Z.Liu: None. A.A.Patel: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. Funding American Diabetes Association (7-07-MN-13) ; National Institutes of Health (RDK067269)