Lakmini Pinnaduwage1, Chang Ye1, Anthony J Hanley1,2,3, Philip W Connelly2,4, Mathew Sermer5, Bernard Zinman1,2,6, Ravi Retnakaran1,2,6. 1. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada. 2. Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada. 3. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. 4. Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada. 5. Division of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada. 6. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Abstract
Context: Serum concentrations of liver enzymes and the hepatokine fetuin-A have been linked to the risk of type 2 diabetes, but their longitudinal impact on insulin resistance and β-cell dysfunction is unclear. Objective: To evaluate the impact of changes over 2 years in fetuin-A and the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) on changes in insulin sensitivity, β-cell function, and glycemia in women with varying degrees of previous gestational dysglycemia, reflecting a range of future diabetic risk. Design/Setting/Participants: In total, 336 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT and measurement of ALT/AST/GGT/fetuin-A at both 1 year and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: gestational diabetes (n = 104), gestational impaired glucose tolerance (n = 59), abnormal GCT with normal OGTT (n = 98), and normal GCT/OGTT (n = 75). Results: At 1 and 3 years postpartum, ALT, AST, GGT, and fetuin-A did not differ across the four groups, but the intervening change in ALT/AST ratio was greater in the gestational dysglycemia groups (P = 0.05). Higher baseline ALT/AST (t = -1.99, P = 0.05) and fetuin-A (t = -3.17, P = 0.002) predicted lower insulin sensitivity (Matsuda) at 3 years, as did their respective changes from 1 to 3 years (ALT/AST: t = -5.47, P < 0.0001; fetuin-A: t = -3.56, P = 0.0004). Change in ALT/AST predicted lower β-cell function (t = -2.33, P = 0.02) and higher fasting glucose at 3 years (t = 2.55, P = 0.01). Moreover, baseline fetuin-A predicted prediabetes/diabetes at 3 years (OR, 1.38; 95% CI, 1.01 to 1.88). Conclusion: Circulating hepatic markers, particularly ALT/AST ratio and fetuin-A, track with changes in insulin sensitivity and β-cell function, supporting a pathophysiologic basis in their prediction of diabetic risk.
Context: Serum concentrations of liver enzymes and the hepatokine fetuin-A have been linked to the risk of type 2 diabetes, but their longitudinal impact on insulin resistance and β-cell dysfunction is unclear. Objective: To evaluate the impact of changes over 2 years in fetuin-A and the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) on changes in insulin sensitivity, β-cell function, and glycemia in women with varying degrees of previous gestational dysglycemia, reflecting a range of future diabetic risk. Design/Setting/Participants: In total, 336 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT and measurement of ALT/AST/GGT/fetuin-A at both 1 year and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: gestational diabetes (n = 104), gestational impaired glucose tolerance (n = 59), abnormal GCT with normal OGTT (n = 98), and normal GCT/OGTT (n = 75). Results: At 1 and 3 years postpartum, ALT, AST, GGT, and fetuin-A did not differ across the four groups, but the intervening change in ALT/AST ratio was greater in the gestational dysglycemia groups (P = 0.05). Higher baseline ALT/AST (t = -1.99, P = 0.05) and fetuin-A (t = -3.17, P = 0.002) predicted lower insulin sensitivity (Matsuda) at 3 years, as did their respective changes from 1 to 3 years (ALT/AST: t = -5.47, P < 0.0001; fetuin-A: t = -3.56, P = 0.0004). Change in ALT/AST predicted lower β-cell function (t = -2.33, P = 0.02) and higher fasting glucose at 3 years (t = 2.55, P = 0.01). Moreover, baseline fetuin-A predicted prediabetes/diabetes at 3 years (OR, 1.38; 95% CI, 1.01 to 1.88). Conclusion: Circulating hepatic markers, particularly ALT/AST ratio and fetuin-A, track with changes in insulin sensitivity and β-cell function, supporting a pathophysiologic basis in their prediction of diabetic risk.
Authors: Alessandro Volpe; Chang Ye; Anthony J Hanley; Philip W Connelly; Bernard Zinman; Ravi Retnakaran Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958
Authors: Thiago Gagliano-Jucá; M Furkan Burak; Karol M Pencina; Zhuoying Li; Robert R Edwards; Thomas G Travison; Shehzad Basaria Journal: J Clin Endocrinol Metab Date: 2018-10-01 Impact factor: 5.958
Authors: Mugdha V Joglekar; Wilson K M Wong; Fahmida K Ema; Harry M Georgiou; Alexis Shub; Anandwardhan A Hardikar; Martha Lappas Journal: Diabetologia Date: 2021-03-23 Impact factor: 10.122