Cesarean Delivery and Insulin Sensitivity in the Older Adult

The Microbiome and Insulin Longitudinal Evaluation Study

Elizabeth T. Jensen; Alain G. Bertoni; Osa L. Crago; Jerome I. Rotter; Yii-Der I. Chen; Alexis Wood; Stephen S. Rich; Mark O. Goodarzi


J Endo Soc. 2022;6(7) 

In This Article

Abstract and Introduction


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 nondiabetic, 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/m2), 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 [aβ] 3.53 kg/m2; 95% CI 0.15, 6.91) and fasting glucose (aβ 5.12; 95% CI 0.01, 10.23), a 14% decrease in insulin sensitivity (aβ –0.14; 95% CI –0.28, −0.01), and a 58% increased risk (adjusted relative risk [aRR] 1.58; 95% CI 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 = .03), fasting insulin (proportion mediated 58.0%; P = .05), and insulin sensitivity index (proportion mediated 45.9%; P = .05). Independent of mediation, a significant direct effect of cesarean delivery on glycemic status was observed (aRR 1.88; 95% CI 1.16, 2.60). Cesarean delivery may lead to reduced insulin sensitivity and, ultimately, increased risk for developing prediabetes and diabetes.


While the evidence is mixed, a few studies have reported an association between cesarean delivery and increased risk of obesity in children, and a recent report from the Nurses' Health Study indicated an increased risk of obesity and type 2 diabetes for women who were born via cesarean delivery.[1,2] The pathophysiology underlying any association between cesarean delivery and metabolic derangements is unknown; however, it is hypothesized to be a result of alterations in the gut microbiome in early life that may lead to obesity, metabolic derangement, and, ultimately, impaired glucose homeostasis.[3] One challenge in assessing the association between cesarean delivery and development of diabetes is the potential for confounding from maternal factors. For example, shared familial dietary and physical activity patterns could contribute to both maternal obesity, increased risk of cesarean delivery, and increased risk of obesity and development of diabetes in later life in her offspring. Additionally, maternal history of diabetes could be associated with both an increased risk for cesarean delivery and risk of diabetes in her offspring (through genetic factors).[4] In the present study we evaluated risk for obesity and diabetes, in relation to having been born through cesarean delivery, accounting for maternal history of diabetes.