Sharon E Cox, Sana Ahmed, Dixi Paglinawan Modoc, Riddhi Dasgupta, Christina Christoffersen, Molly Chisenga, Julius Patrick Ferrer, Ruth Frikke-Schmidt, Rikke Krogh-Madsen, Belinda Kweka, Nanette Lee, Evangelista Malindisa, Mizinga J Tembo, Patrick Ngoya, Dorothea Nitsch, Daniel Faurholt-Jepsen, George PrayGod, Geeta Trilok-Kumar, Suzanne Filteau, James A M Shaw
PM affects glucose metabolism differently according to current BMI. Remaining underweight is associated with low insulin secretion and weight gain following PM is linked to reduced insulin sensitivity. Our results further inform understanding of the relative roles of reduced insulin secretion and sensitivity in diabetes pathogenesis in LMICs.
AIMS: The role of prior wasting malnutrition (PM) in determining insulin sensitivity and secretion in low- and middle-income countries (LMICs) remains unclear. We investigated associations of insulin indices with PM and whether these were modified by current body mass index (BMI).
METHODS: Participants were enrolled from child and adult cohorts in Zambia, Tanzania, India and the Philippines with previously documented PM or no prior wasting malnutrition (NPM). Plasma glucose, insulin and C-peptide were measured during an oral glucose tolerance test. Static (HOMA2 %S, HOMA2 %B) and dynamic (Matsuda index, insulinogenic index, disposition index) insulin indices were calculated. Adjusted linear regression models compared indices between PM and NPM groups.
RESULTS: In 2172 participants analysed, those with PM had lower current BMI. Children with PM had reduced insulin sensitivity (Matsuda index 20%-24% lower in PM vs. NPM). Adults with PM in early life (36-37 years before) many of whom had high adult BMI, also exhibited lower insulin sensitivity after adjustment for current BMI (Matsuda Index 18% lower in PM vs. NPM). Adults with more recent PM (3-17 years previously), many of whom remained underweight, had low insulin secretion (HOMA2 %B 10%-20% lower in PM vs. NPM) but greater insulin sensitivity associated with their lower BMI (Matsuda index 21%-47% higher in PM vs. NPM). Insulin secretion generally compensated for insulin sensitivity differences, maintaining comparable disposition index and diabetes and prediabetes prevalence between PM and NPM groups.
CONCLUSIONS: PM affects glucose metabolism differently according to current BMI. Remaining underweight is associated with low insulin secretion and weight gain following PM is linked to reduced insulin sensitivity. Our results further inform understanding of the relative roles of reduced insulin secretion and sensitivity in diabetes pathogenesis in LMICs.