MAL-ED Metabolic: A Follow-Up of Chronic Disease at Puberty

The relationship between prenatal challenges and later risk for chronic disease has been well established. Our group previously assessed the hypothesis that post-natal challenges (similar to prenatal ones) would exhibit links to later cardiometabolic disease. This was performed using retrospective data from a long-term cohort of children in Guatemala, demonstrating novel findings that higher degrees of diarrhea burden in the first 6 months of life (as a marker of nutritional and/or inflammatory stressors) were associated with a greater risk of metabolic syndrome as adults The causes of these findings are not known, though postulated mechanisms include epigenetic reprograming of metabolic rate, hormonal regulation and vascular tone. Unfortunately, long-term cohort studies are few, limiting opportunities to evaluate these links prospectively.

The Haydom Global Health Research Center in north central Tanzania represents an important rural setting for performing high-quality medical research in sub-Saharan Africa (5). The region around Haydom has a high degree of stunting and enteric pathogen carriage among a cohort of children followed in the area from 2009-2013 as part of the multi-country study "The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED)."

These children followed in Haydom during MAL-ED had monthly anthropometry and stool pathogen analysis, as well as extensive demographic data. This provides an opportunity to follow up on these children to assess for potential links between early life challenges (both enteric disease, infections and nutritional deficiencies) and later chronic disease risk, including lipid abnormalities, glucose intolerance and blood pressure elevations. The current proposal is to follow up on these children at the age of typical entry into puberty, as this is a common shift in metabolism when many children begin to exhibit metabolic abnormalities. We will assess these children for multiple measures:

• Anthropometry (height, weight, BMI, waist circumference)
• Assessment of pubertal stage by exam or questionnaire
• Blood pressure
• Lipids (LDL, HDL, triglycerides)
• CRP
• Oral glucose tolerance test (OGTT)
• Fasting insulin
• Metabolic syndrome (MetS) severity score
• Blood saved for future epigenetic testing

We will use linear and and logistic regression to determine associations between 1) mean number of monthly pathogens (individual pathogens and in aggregate) and 2) reported symptoms (fever, cough, diarrhea), with multiple MetS-related outcomes: BMI percentile, WC, fasting insulin, 2-hour glucose following OGTT, triglycerides, HDL cholesterol, normalized BP and a MetS diagnosis.

The underlying hypothesis is that there will be consistent links between features of MetS (in particular blood pressure, waist circumference and insulin resistance) with 1) enteric pathogen burden (overall and for particularly virulent pathogens such as Enterotoxigenic E.coli) and 2) poor early life growth.

Inclusion criteria

• Participated in original MAL-ED cohort

Exclusion criteria

• Did not participate in original MAL-ED cohort