Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol [version 2; peer review: 2 approved]

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.