Insulin Resistance is Associated With Total Bile Acid Level in Type 2 Diabetic and Nondiabetic Population

Abstract

Bile acid metabolism was reported to be involved in glucose metabolism homeostasis. However, the exact relationship between bile acid and glucose metabolism as well as insulin sensitivity is not clarified. Therefore, we sought to investigate the association between insulin sensitivity and hyperbileacidemia in type 2 diabetic and nondiabetic population.This community-based cross-sectional study included 9603 residents from Jiading, Shanghai, China, who were 40 years and older. Standardized questionnaire, anthropometric measurements and laboratory tests were conducted. Homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.7 was defined as insulin resistance and fasting TBA ≥ 10 mmol/L was defined as hyperbileacidemia.Multivariate stepwise regression analysis revealed that HOMA-IR, age, and male sex were positively associated with hyperbileacidemia in both nondiabetic and diabetic participants. In multivariate logistic models, participants with insulin resistance had significantly higher risk of hyperbileacidemia compared to those who have no insulin resistance, in both nondiabetic and diabetic population (nondiabetic: OR = 1.76; 95% CI 1.42–2.19; P < 0.001; diabetic: OR = 1.56; 95% CI 1.06 – 2.31; P = 0.025, respectively). Further adjustment for the HbA1c level in diabetic population did not change the significant association (OR = 1.59; 95% CI 1.06 − 2.40; P = 0.024). In nondiabetic participants, each 1-unit increment of HOMA-IR conferred an 18% higher risk of hyperbileacidemia (95% CI 1.04–1.35; P = 0.013), whereas in diabetic participants, this association was similar but not significant (95% CI 0.95–1.59; P = 0.117).Insulin resistance was positively associated with hyperbileacidemia in both nondiabetic and diabetic population. The increase in the bile acid level in insulin-resistant population regardless of status of diabetes and glucose level indicated the important role of insulin resistance in the regulation of bile acid metabolism in human.

Bile acid alterations in nonalcoholic fatty liver disease, obesity, insulin resistance and type 2 diabetes: what do the human studies tell?

“…Mechanistic studies in insulin-resistant mice suggest that impaired insulin-mediated repression of FoxO1 results in higher 12α-hydroxylase CYP8B1 expression [17]. Moreover, insulin resistance was associated with increased total BA concentrations [18,19], fasting tauro-conjugated BAs [20], CDCA, CA, DCA [13] and GCDCA [21].…”

Bile acids and bariatric surgery

“…It is clear from the literature that there are fundamental differences in bile acid metabolism regulated by total body adiposity between lean and obese individuals independent of insulin resistance. Several groups have shown decreased circulating concentrations of bile acids in obesity relative to leans (Albaugh et al, 2015; Cariou et al, 2011), though others suggest that insulin resistance drives increased bile acid synthesis and circulating bile acids (Haeusler et al, 2015; Sun et al, 2016). In addition to increasing synthesis and pool size, insulin resistance is associated with altered bile acid composition, specifically increased abundance of 12α-hydroxylated bile acid species which may be important negative regulators of insulin action (Haeusler et al, 2013).…”

Ultra-Early and Early Changes in Bile Acids and Insulin after Sleeve Gastrectomy among Obese Patients

“…Alterations in total BA have been shown in subjects with prediabetes, T2DM, and IR [41]. In a cross-sectional study that included 9603 subjects, Sun et al [42] showed an increase of BA in IR individuals regardless of the presence/absence of T2DM, and they pointed out the important role of IR in BA metabolism regulation. However, noteworthily, the study enrolled subjects that were not severely obese.…”