Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 2018 Jul 1;103(7):2651-2659. doi: 10.1210/jc.2018-00306.
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.
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).
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).
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.
血清肝酶浓度和肝分泌因子胎球蛋白 A 与 2 型糖尿病风险相关，但它们对胰岛素抵抗和β细胞功能的纵向影响尚不清楚。
评估 2 年内胎球蛋白 A 和肝酶丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和γ-谷氨酰转移酶（GGT）变化对不同程度既往妊娠期糖代谢异常女性的胰岛素敏感性、β细胞功能和血糖变化的影响，反映出不同的未来糖尿病风险。
设计/设置/参与者：共有 336 名女性在妊娠期间接受了葡萄糖负荷试验（GCT）和口服葡萄糖耐量试验（OGTT），随后在产后 1 年和 3 年重复进行 OGTT 并测量 ALT/AST/GGT/胎球蛋白 A。产前 GCT/OGTT 将妊娠期血糖耐量分为四组：妊娠期糖尿病（n = 104）、妊娠期糖耐量受损（n = 59）、异常 GCT 伴正常 OGTT（n = 98）和正常 GCT/OGTT（n = 75）。
产后 1 年和 3 年，四组间 ALT、AST、GGT 和胎球蛋白 A 无差异，但妊娠期糖代谢异常组的 ALT/AST 比值变化更大（P = 0.05）。较高的基线 ALT/AST（t = -1.99，P = 0.05）和胎球蛋白 A（t = -3.17，P = 0.002）预测产后 3 年胰岛素敏感性（Matsuda）降低，其各自从 1 年到 3 年的变化也是如此（ALT/AST：t = -5.47，P < 0.0001；胎球蛋白 A：t = -3.56，P = 0.0004）。ALT/AST 的变化预测 3 年时β细胞功能降低（t = -2.33，P = 0.02）和空腹血糖升高（t = 2.55，P = 0.01）。此外，基线胎球蛋白 A 预测产后 3 年时出现糖尿病前期/糖尿病（OR，1.38；95%CI，1.01 至 1.88）。
循环肝标志物，尤其是 ALT/AST 比值和胎球蛋白 A，与胰岛素敏感性和β细胞功能的变化相关，为其预测糖尿病风险提供了病理生理学基础。
