Ramy H Bishay1,2,3, Katherine T Tonks1,4,5, Jacob George6, Dorit Samocha-Bonet4,5, Gideon Meyerowitz-Katz7, Donald J Chisholm1,4,5, David E James8, Jerry R Greenfield1,4,5. 1. Department of Endocrinology & Diabetes, St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia. 2. Metabolic & Weight Loss Program, Department of Endocrinology & Diabetes, Blacktown-Mt Druitt Hospital, Blacktown, Sydney, New South Wales, Australia. 3. Blacktown Clinical School, Western Sydney University, New South Wales, Australia. 4. Healthy Ageing, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia. 5. St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales, Australia. 6. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, New South Wales, Australia. 7. Western Sydney Diabetes, Blacktown Hospital, Blacktown, Sydney, New South Wales, Australia. 8. The Charles Perkins Centre, School of Life & Environmental Sciences and Sydney Medical School, University of Sydney, New South Wales, Australia.
Abstract
CONTEXT: The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown. OBJECTIVE: This work aimed to determine whether plasma BAs are elevated in human obesity and/or insulin resistance. METHODS: This observational study was conducted at an academic research center. Seventy-one adult volunteers formed 4 groups: lean insulin-sensitive (body mass index [BMI] ≤ 25 kg/m2, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] < 2.0, n = 19), overweight/obese nondiabetic who were either insulin sensitive (Obsensitive, BMI > 25 kg/m2, HOMA-IR < 1.5, n = 11) or insulin resistant (Obresistant, BMI > 25 kg/m2, HOMA-IR > 3.0, n = 20), and type 2 diabetes (T2D, n = 21). Main outcome measures included insulin sensitivity by hyperinsulinemic-euglycemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution, and liver density by computed tomography and plasma BA. RESULTS: In the Obresistant group, glucose infusion rate/fat-free mass (GIR/FFM, an inverse measure of insulin resistance) was significantly lower, and visceral and liver fat higher, compared to lean and Obsensitive individuals, despite similar total adiposity in Obresistant and Obsensitive. Total BA concentrations were higher in Obresistant (2.62 ± 0.333 mmol/L, P = .03) and T2D (3.36 ± 0.582 mmol/L, P < .001) vs Obsensitive (1.16 ± 0.143 mmol/L), but were similar between Obsensitive and lean (2.31 ± 0.329 mmol/L) individuals. Total BAs were positively associated with waist circumference (R = 0.245, P = .041), visceral fat (R = 0.360, P = .002), and fibroblast growth factor 21 (R = 0.341, P = .004) and negatively associated with insulin sensitivity (R = -0.395, P = .001), abdominal subcutaneous fat (R = -0.352, P = .003), adiponectin (R = -0.375, P = .001), and liver fat (Hounsfield units, an inverse marker of liver fat, R = -0.245, P = .04). Conjugated BAs were additionally elevated in T2D individuals (P < .001). CONCLUSIONS: BA concentrations correlated with abdominal, visceral, and liver fat in humans, though an etiological role in insulin resistance remains to be verified.
CONTEXT: The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown. OBJECTIVE: This work aimed to determine whether plasma BAs are elevated in humanobesity and/or insulin resistance. METHODS: This observational study was conducted at an academic research center. Seventy-one adult volunteers formed 4 groups: lean insulin-sensitive (body mass index [BMI] ≤ 25 kg/m2, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] < 2.0, n = 19), overweight/obese nondiabetic who were either insulin sensitive (Obsensitive, BMI > 25 kg/m2, HOMA-IR < 1.5, n = 11) or insulin resistant (Obresistant, BMI > 25 kg/m2, HOMA-IR > 3.0, n = 20), and type 2 diabetes (T2D, n = 21). Main outcome measures included insulin sensitivity by hyperinsulinemic-euglycemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution, and liver density by computed tomography and plasma BA. RESULTS: In the Obresistant group, glucose infusion rate/fat-free mass (GIR/FFM, an inverse measure of insulin resistance) was significantly lower, and visceral and liver fat higher, compared to lean and Obsensitive individuals, despite similar total adiposity in Obresistant and Obsensitive. Total BA concentrations were higher in Obresistant (2.62 ± 0.333 mmol/L, P = .03) and T2D (3.36 ± 0.582 mmol/L, P < .001) vs Obsensitive (1.16 ± 0.143 mmol/L), but were similar between Obsensitive and lean (2.31 ± 0.329 mmol/L) individuals. Total BAs were positively associated with waist circumference (R = 0.245, P = .041), visceral fat (R = 0.360, P = .002), and fibroblast growth factor 21 (R = 0.341, P = .004) and negatively associated with insulin sensitivity (R = -0.395, P = .001), abdominal subcutaneous fat (R = -0.352, P = .003), adiponectin (R = -0.375, P = .001), and liver fat (Hounsfield units, an inverse marker of liver fat, R = -0.245, P = .04). Conjugated BAs were additionally elevated in T2D individuals (P < .001). CONCLUSIONS:BA concentrations correlated with abdominal, visceral, and liver fat in humans, though an etiological role in insulin resistance remains to be verified.
Authors: Jennifer Jao; Lauren C Balmert; Shan Sun; Grace A McComsey; Todd T Brown; Phyllis C Tien; Judith S Currier; James H Stein; Yunping Qiu; Derek LeRoith; Irwin J Kurland Journal: J Clin Endocrinol Metab Date: 2022-01-01 Impact factor: 6.134