Prior undernutrition and insulin production several years later in Tanzanian adults

Abstract

Background: The prevalence, pathology, and existence of malnutrition-associated diabetes remain uncertain, especially with respect to adult-acquired undernutrition.

Objective: The aim was to investigate the association of prior undernutrition (low BMI, in kg/m2), acquired in adulthood and insulin during an oral glucose tolerance test (OGTT).

Methods: We followed up 630 adults recruited 7-14 y previously for other studies. Plasma insulin was measured fasting and at 30 and 120 min during an OGTT. The main exposure was BMI measured 7-14 y prior. The main outcome of interest was plasma insulin, controlling for time during the OGTT using generalized estimating equations, and exploratory outcomes were early insulin response (relative change in insulin and glucose from 0-30 min) and relative insulin and glucose AUCs from 0 to 120 min. Current confounding factors were age, sex, BMI, HIV, socioeconomic status, and physical activity.

Results: In unadjusted analyses, increasing severity of prior malnutrition was associated with lower insulin concentration. In multivariate adjusted analyses, only current BMI was a strong predictor of overall insulin concentration. Associations with prior BMI of insulin responses accounting for glucose were also seen in unadjusted but not adjusted analyses. For insulin concentration but not the outcomes accounting for glucose, there was a sex interaction with prior BMI such that only men had lower insulin if previously malnourished: insulin (pmol/L) at 120 min was 311 (95% CI: 272, 351) for prior BMI ≥18.5, 271 (95% CI: 221, 321) for prior BMI 17.0-18.5, and 237 (95% CI: 194, 297) for prior BMI <17.0; P = 0.03. HIV status showed limited and variable associations with insulin.

Conclusions: Insulin concentration, fasting and during an OGTT, was normalized in women more than in men several years after adult malnutrition. Chronic malnutrition, as indicated by low prior and current BMI, may contribute to diabetes through low insulin secretion.

Keywords: HIV; Tanzania; glucose tolerance; insulin; malnutrition-associated diabetes.

FIGURE 2

Marginal mean insulin concentrations of women and men during an oral glucose tolerance test according to prior BMI (in kg/m²). Values are marginal means from univariable analysis using generalized estimating equations to control for time point during the test. There were 155 female and 137 male participants with prior BMI >18.5, 86 women and 85 men with prior BMI 17.0–18.5, and 100 women and 67 men with prior BMI <17.0. Prior BMI was associated with insulin only in men at 120 min (P = 0.03).

FIGURE 1

Geometric mean values of glucose and insulin during an oral glucose tolerance test according to prior BMI (in kg/m²). There were 292 participants with prior BMI >18.5, 171 with prior BMI 17.0–18.5, and 167 with prior BMI <17.0. Glucose differed among prior malnutrition groups only at time 0; Wald P = 0.005. Insulin differed among groups at all times: times 0 and 120 min, P < 0.001; time 30 min, P = 0.06.