Impaired insulin clearance, initial regulator of obesity-associated hyperinsulinemia, study finds
China: Hyperinsulinemia in obese patients may be due to decreased insulin clearance rather than increased insulin secretion, reveals a recent study in the journal Diabetes Care. Further, it was found that changes in circulating conjugated bile acids (BAs) may be an important player in regulating insulin clearance.
In the study, Hongwen Zhou, Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China, and colleagues aimed to examine the roles of insulin clearance and insulin secretion in the development of hyperinsulinemia in obese patients and to reveal the association between insulin clearance and bile acids.
In cohort 1, the researchers evaluated insulin secretion, sensitivity, and endogenous insulin clearance using a glucose tolerance test in 460 recruited participants. In cohort 2, they assessed insulin secretion, endogenous and exogenous insulin clearance, and insulin sensitivity in 2, 81 participants who underwent an intravenous glucose tolerance test and a hyperinsulinemic-euglycemic clamp. Obese participants without diabetes were further divided into 10 quantiles in cohort 1 and into tertiles in cohort 2 based on insulin resistance levels ranging from mild to severe. In order to examine the association between BAs and insulin clearance, forty serum BAs were measured in cohort 2.
Based on the study, the researchers found the following:
- All obese participants had impaired insulin clearance, and it worsened with additional insulin resistance in obese subjects without diabetes.
- Insulin secretion was unchanged from quantile 1 to 3 in cohort 1, and no difference was found in cohort 2.
- After adjustments for all confounding factors, serum-conjugated BAs, especially glycodeoxycholic acid (GDCA; β = −0.335) and taurodeoxycholic acid (TDCA; β = −0.333), were negatively correlated with insulin clearance.
- The ratio of unconjugated to conjugated BAs (β = 0.335) was positively correlated with insulin clearance.
"Hyperinsulinemia in obese patients might primarily be induced by decreased insulin clearance rather than increased insulin secretion," wrote the authors. "Changes in circulating conjugated BAs, especially GDCA and TDCA, might play an important role in regulating insulin clearance."
Reference:
Zhenzhen Fu, Qinyi Wu, Wen Guo, Jingyu Gu, Xuqin Zheng, Yingyun Gong, Chenyan Lu, Jingya Ye, Xuan Ye, Wanzi Jiang, Moran Hu, Baowen Yu, Qi Fu, Xiang Liu, Jianling Bai, John Zhong Li, Tao Yang, Hongwen Zhou; Impaired Insulin Clearance as the Initial Regulator of Obesity-Associated Hyperinsulinemia: Novel Insight Into the Underlying Mechanism Based on Serum Bile Acid Profiles. Diabetes Care 1 February 2022; 45 (2): 425–435. https://doi.org/10.2337/dc21-1023
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