1561-P: Insulin Secretion is Markedly Impaired in Young, Lean Rwandan Adults with New-Onset Type 2 Diabetes

Introduction: 80% of cases of type 2 diabetes mellitus (T2D) occur in low- and middle-income countries and primarily afflicts lean people; the reasons for this are unclear but may relate to fat-distribution and/or pancreatic function. We aimed to: 1) compare insulin-secretion rates (ISR) between lean, (BMI <25kg/m2) Rwandan adults with and without new-onset (<1yr) T2D; and 2) to examine the impact of elevated WC (<85cm for women and <90cm for men, >75th %ile of group) on ISR and insulin resistance in people with T2D. Methods: BMI, WC, and a 3-hour frequently-sampled oral-glucose tolerance-test were performed in 23 Rwandans; 15 with T2D (7 Male) and 8 healthy people (5 Male). ISR was determined by mathematical-modeling. Groups were compared with students t-test or ANOVA were appropriate. Results: Healthy and T2D groups were well matched for age (43±3y vs 46±2 y) and BMI (22±1 vs 22±1 kg/m2), respectively. Glucose area under the curve (AUC) was lower (1179±55 vs 2150±196 mg.ml-1.min, P<0.05) and insulinogenic-index was greater (91±18 vs 23±8, P<0.01) in healthy people than people with T2D, respectively. Rwandans with T2D and normal WC had an ISR-AUC ~2 fold lower (54±9 vs 117±20, P=0.07) than T2D and elevated WC. HOMA-IR was greater in Rwandans with T2D and elevated WC than healthy people (2.2±0.4 vs 0.9±0.1, P<0.05). Conclusions: In lean Rwandan people with new-onset T2D but normal WC, alterations in insulin secretion rather than insulin-resistance predominate. In contrast, in Rwandans with T2D and elevated WC, insulin resistance rather than insulin secretion may be a major factor. This suggests that the pathogenesis of T2D differs based on WC in Rwandans with implications for prevention and therapy. Disclosure R. Mugeni: None. G.I. Smith: None. A.E. Sumner: None. W.T. Cade: None. D. Reeds: None. Funding McDonnell FoundationP30DK056341P30DK092950