Cesarean delivery and insulin sensitivity in the older adult: The Microbiome and Insulin Longitudinal Evaluation Study

Authors: JENSEN, ELIZABETH - Wake Forest School Of Medicine; BERTONI, ALAIN - Wake Forest School Of Medicine; CRAGO, OSA - Wake Forest School Of Medicine; ROTTER, JEROME - Harbor-Ucla Medical Center; CHEN, YII - Harbor-Ucla Medical Center; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); RICH, STEPHEN - University Of Virginia School Of Medicine; GOODARZI, MARK - Cedars-Sinai Medical Center

Submitted to: Journal of the Endocrine Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/27/2022
Publication Date: 5/4/2022
Citation: Jensen, E.T., Bertoni, A.G., Crago, O.L., Rotter, J.I., Chen, Y.D., Wood, A., Rich, S.S., Goodarzi, M.O. 2022. Cesarean delivery and insulin sensitivity in the older adult: The Microbiome and Insulin Longitudinal Evaluation Study. Journal of the Endocrine Society. https://doi.org/10.1210/jendso/bvac072.
DOI: https://doi.org/10.1210/jendso/bvac072

Interpretive Summary: While the evidence is mixed, a few studies have reported an association between cesarean delivery and increased risk of obesity in children. It is not known whether these associations persist past childhood, however. To address this gap in our understanding of the long-term effects of being born by caesarian on adiposity, we conducted a secondary analysis of an existing racially-diverse, prospective cohort study of non-diabetic, older adults (>=40 years). In these analyses, we found an association between cesarian delivery (vs. vaginal delivery) with a significantly higher body mass index (BMI) as well as with higher fasting glucose and lower insulin sensitivity. Unsurprisingly, there was also a 58% increased risk for prediabetes and/or type 2 diabetes associated with cesarean delivery. When analyzing the health factors as a whole, higher BMI appeared to mediate the associations between cesarean delivery and risk factors related to type 2 diabetes (i.e., fasting glucose and insulin sensitivity). Our results imply that cesarean delivery may increase risk of type 2 diabetes later in life, likely operating via increases in adiposity.

Technical Abstract: The present study was designed to evaluate if mode of delivery at birth is associated with body mass index (BMI) and glucose homeostasis traits in later life, controlling for possible confounders, including maternal history of diabetes. Data were obtained through a racially-diverse, prospective cohort study of non-diabetic, older adults, the Microbiome and Insulin Longitudinal Evaluation Study (MILES). We used generalized linear models to estimate the association between mode of delivery and glycemic status, BMI (kg/m**2), waist circumference (cm), fasting glucose, fasting insulin, insulin secretion, insulin sensitivity and insulin clearance. Further, we estimated the direct and indirect effects of cesarean delivery on glucose and insulin-related traits, as mediated by BMI status. Relative to vaginal delivery, cesarean delivery was associated with a significantly higher BMI (adjusted Beta: 3.53 kg/m**2; 95% confidence interval: 0.15, 6.91) and fasting glucose (adjusted Beta: 5.12; 95% confidence interval: 0.01, 10.23), a 14% decrease in insulin sensitivity (adjusted Beta: -0.14; 95% confidence interval: -0.28, -0.01), and a 58% increased risk (adjusted relative risk: 1.58; 95% confidence interval: 1.08, 2.31) for prediabetes/diabetes. Associations were mediated in part by BMI, with the strongest evidence observed for glycemic status (proportion mediated 22.6%; p=0.03), fasting insulin (proportion mediated 58.0%; p=0.05) and insulin sensitivity index (proportion mediated 45.9%; p=0.05). Independent of mediation, a significant direct effect of cesarean delivery on glycemic status was observed (adjusted relative risk: 1.88; 95% confidence interval: 1.16, 2.60). Cesarean delivery may lead to reduced insulin sensitivity and, ultimately, increased risk for developing pre-diabetes and diabetes.