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.

Apparent Insulin Deficiency in an Adult African Population With New-Onset Type 2 Diabetes

“…The developmental origins of health and disease (DOHaD) concept emphasises the direct influence of chronic infections and undernutrition on structural development and physiologic function of most critical body organs during the early stages of life and development, hence increasing the future risk of metabolic conditions like type 2 diabetes (31). Undernutrition and chronic infections remain common in SSA and could explain the high rates of pancreatic beta-cell dysfunction and insulin deficiency noted in adult African patients with type 2 diabetes (32)(33)(34)(35)(36).…”

Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol

“…6 There are heterogeneous reports of atypical diabetes in LMICs, describing an entity of malnutrition-related, insulin-deficient diabetes related to pancreatic damage, for example, a phenotype termed fibrocalculous pancreatic diabetes, 7 but these studies often report highly selected patients, which can provide mechanistic but not epidemiologic information, 8 or precede the availability of modern assessment methods. 9 Our own work has shown that prior malnutrition in Tanzanian adults is associated with lower insulin production in men 10 and that insulin deficiency is a more common cause of diabetes than insulin resistance. 11 If malnutrition is associated with an atypical form of diabetes, driven by insulin deficiency and not resistance, then this has major implications for health policy, planning, investigation and treatment of diabetes in LMICs, because current first-line treatments of diabetes in these settings usually use treatments such as metformin which would be inappropriate for insulin-deficient diabetes.…”

The association of physical activity and cardiorespiratory fitness with β-cell dysfunction, insulin resistance, and diabetes among adults in north-western Tanzania: A cross-sectional study

“…In SSA, the increasing diabetes burden is partly driven by insulin resistance from overweight particularly seen in urban settings, associated with intake of high-calorie low-fibre diets, low levels of physical activity ( 3 , 4 ), and from infections like HIV ( 5 , 6 ). However, reduced insulin secretion due to under nutrition could also contribute to diabetes ( 7 , 8 ).…”