Higher blood 25 (OH) D is associated with lower risk of type 2 diabetes (T2D) in people with prediabetes. Blood 25 (OH) D can vary due to skin color and weight. It is not known if blood 25 (OH) D levels have similar impact on T2D risk for people of color or higher weight. The vitamin D and type 2 diabetes (D2d) study is a randomized clinical trial of participants with high-risk prediabetes and overweight/obesity who were randomized to vitamin D3 4000 IU daily vs. placebo and followed for 2.5 years for the primary outcome of T2D. We compared baseline and intra-trial (mean achieved) serum 25 (OH) D among race-weight groups. We used Cox models to determine the associations between intra-trial serum 25 (OH) D and T2D risk by race-weight groups; we additionally tested for interactions between intra-trial serum 25 (OH) D and race or weight. Of 2362 D2d participants with self-reported race, Black (n = 616) and White (n = 1616) participants were included in analyses. Baseline serum 25 (OH) D was lower in Black (24.2 ng/mL ± 10.9) compared to White (29.6 ng/mL ± 9.5) participants (P<0.001) ; and were lower in those with higher vs. lower BMI in both races. Intra-trial serum 25 (OH) D was lower in Black participants (P<0.001) overall and those with higher baseline BMI. Both Black and White participants with intra-trial serum 25 (OH) D ≥ 40 ng/mL had significantly reduced risk of T2D [HR (95% CI) ]; Black: 0.51 (0.29, 0.92) ; White 0.42 (0.30, 0.60) ] with no significant race*BMI interaction. Participants with baseline BMI ≤ 40 kg/m2 who achieved intra-trial serum 25 (OH) D levels ≥ 40 ng/mL had significantly reduced risks of T2D but not those with a BMI > 40 kg/m2 with no significant BMI*race interaction. Conclusions: An intra-trial mean serum 25 (OH) D level ≥ 40 ng/mL was associated with significantly reduced risk of T2D in Black and White D2d participants, but only among those with BMI < 40 kg/m2. Targeting a serum 25 (OH) D level ≥ 40 ng/mL would optimize T2D prevention efforts among people with high-risk prediabetes. Disclosure R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. B.Dawson-hughes: None. D2d research group: n/a. C.A.Davenport: None. K.C.Johnson: None. S.Kashyap: Advisory Panel; Fractyl Health, Inc., GI Dynamics, Research Support; Janssen Pharmaceuticals, Inc. E.S.Leblanc: n/a. J.P.Nelson: None. E.Vickery: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. A.G.Pittas: None. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)
Rate of progression from prediabetes to diabetes varies greatly, and better risk stratification would help guide prevention efforts. We evaluated predictors of incident diabetes in the placebo arm (n=1212) of the vitamin D and type 2 diabetes (D2d) study. At baseline, participants met 2 or 3 ADA glycemic criteria for prediabetes (fasting glucose, FPG, 100-125mg/dL; 2-hour glucose during a 75-g OGTT, 2hPG, 140-199 mg/dL; HbA1c, 5.7-6.4%). Diabetes was diagnosed based on semiannual testing. After a median follow up of 2.5 years, 27% met criteria for diabetes. Among those who did and did not develop diabetes, mean BMI (±SD) was similar (32.1 kg/m2 ± 4.4), as well as other demographic factors including age, race, and ethnicity. More men than women developed diabetes (29% vs 23%, p=0.02). Incident diabetes rates differed by prediabetes subgroups (Figure); and those meeting all three prediabetes criteria at baseline (35.4%) were most likely to develop diabetes (log-rank p <0.001). There were no differences in the incident diabetes rate among those people meeting only 2 of the prediabetes criteria (Figure). Also, area under the receiver operator characteristic curves for incident diabetes at 36 months increased when all 3 criteria were used in the diagnosis (0.736) vs only FPG and HbA1c (0.686). We conclude that ‘prediabetes’ is heterogeneous, and the 2hPG may refine diabetes risk and guide intervention strategies in adults with high-risk prediabetes. Disclosure S. H. Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. D. S. Hsia: None. E. S. Leblanc: Other Relationship; Dexcom, Inc. M. Staten: None. R. Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. N. Rasouli: Research Support; Novo Nordisk, Eli Lilly and Company, Somalogic. V. R. Aroda: Consultant; Applied Therapeutics Inc., Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Applied Therapeutics Inc., Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Sanofi. A. G. Pittas: None. Funding National Institutes of Health (U01DK098245)
Understanding the association between glycemia and A1c by race can improve screening for prediabetes and type 2 diabetes (T2D) . This association was examined cross-sectionally in 1016 Black and 2658 White persons screened for D2d (mean age 60; fasting glucose [FG] 1mg/dL; A1c 5.9%) . Of these, 22with at least 2-of-3 ADA glycemic criteria for prediabetes (mean age 60, FG 1mg/dL, A1c 5.9%, 28% Black) were followed longitudinally for median 2.5 years with annual OGTT and semi-annual FG and A1c. Numerical integration methods were used for the estimation of area under the OGTT-derived glucose curve (AUC) . Mean A1c was estimated for a given AUC quintile using linear regression for Whites, Blacks, and Asians. Adjusting for covariates, the A1c was higher by 0.2-0.25% among Black vs. White participants with similar glycemia in all AUC quintiles. During follow-up, Black participants were more likely to be diagnosed with T2D based on A1c; White participants were more likely to be diagnosed by FG. The absolute increase in A1c over time according to baseline AUC-glucose quintiles differed by race. Compared to White participants, Black participants in lower baseline AUC quintiles had greater increases in A1c over time, while A1c increased similarly in White and Black persons in the two highest baseline AUC quintiles. In summary, Black participants had higher A1c than White participants for similar degree of glycemia defined by AUC; the glycemic criteria contributing to the diagnosis of T2D differed by race; and there were AUC by racial interactions in A1c increase over time. Disclosure E.S.Leblanc: n/a. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. J.P.Nelson: None. D.S.Hsia: None. D2d research group: n/a. A.G.Pittas: None. R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. M.K.Rhee: Research Support; Kowa Company, Ltd. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. C.Desouza: Advisory Panel; AstraZeneca, Bayer AG, Novo Nordisk A/S, Consultant; Asahi Kasei Corporation. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Amryt Pharma Plc, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company. A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)
Prediabetes is a recognized entity but has been incompletely characterized in a contemporary context. We sought to characterize participants with prediabetes with extensive multi-dimensional clinical and laboratory data and to identify predictors of progression to diabetes. The Project Baseline Health Study (PBHS) is a multi-site prospective U.S. cohort study of 2502 adults with deep clinical phenotyping at enrollment. At enrollment and follow-up, participants were classified by diabetes status (diabetes [DM], prediabetes [preDM], or no diabetes [noDM]) based on glucose, A1c, medications, and self-reported medical history. Principal component analysis (PCA) was performed on 1clinical, survey, and lab variables to create orthogonal factors composed of correlated variables, which were compared between groups using linear models. Logistic regression was used to identify factors associated with progression from preDM to DM. At enrollment, 16participants had noDM; 544 had preDM; and 352 had DM. Over up to 4 years of follow-up, 52 participants with preDM developed DM. PCA identified 33 factors composed of clusters of clinical variables; 24 factors differed significantly by diabetes status: 6 factors significantly differed between noDM and both preDM and DM after adjustment for multiple comparisons, including factors with variables of glucose measures, anthropometry and physical function (q= 1.3 × 10−21) , red blood cell indices (q= 8.3 × 10−10) , lung function (q= 2.0 × 10−6) , cardiac function (q= 0.001) , and risk of chronic disease. Five factors were significantly associated with progression to DM, including factors of anthropometry and physical function [OR (95% CI) 0.6 (0.5,0.9) ], hematologic measures, and cardiac function. Conclusions: PBHS participants with preDM demonstrated pathophysiologic changes in cardiac, pulmonary, and hematology measures and declines in physical function that precede DM and could be markers of higher risk of progression to DM and complications. Disclosure R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. L.C.Kwee: None. N.Pagidipati: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, ESPERION Therapeutics, Inc., Consultant; Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eggland's Best, Eli Lilly and Company, Novartis AG, Novo Nordisk, Sanofi, Verily Life Sciences. A.F.Hernandez: Consultant; Merck & Co., Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH. F.Rodriguez: Advisory Panel; Amgen Inc., Consultant; HealthPals, Novartis Pharmaceuticals Corporation, Novo Nordisk, Stock/Shareholder; Carta Healthcare, Inc. K.W.Mahaffey: Consultant; Novo Nordisk. L.Palaniappan: Consultant; Amgen Inc. S.H.Shah: Research Support; Verily Life Sciences. Funding The Baseline Health Study and this analysis were funded by Verily Life Sciences, San Francisco, California.
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