title: New evidence for an association between liver enzymes and pancreatic islet β-cell dysfunction in young obese patients.
abstract: To explore the relationship between serum liver enzymes and both the glucose tolerance status and insulin secretion in young obese patients. A total of 734 young obese patients (BMI ≥ 25 kg m(-2)) and 231 lean healthy volunteers matched in age (BMI < 23 kg m(-2)) were enrolled in this cross-sectional observational study. The 734 obese patients were subdivided to three groups (OB-NGR, OB-IGR, and OB-DM) according to their glucose tolerance status. FSIVGTT was performed to assess the degree of insulin sensitivity (SI) and islet secretion function (AIRg). The disposition index (DI; product of SI and AIRg) was calculated as an integrated measurement of insulin secretion and insulin action after compensating for insulin resistance. The extent and distribution of hepatic fat infiltration was assessed using the liver/spleen ratio (L/S ratio) with CT scan. ALT and GGT levels in OB-NGR, OB-IGR, and OB-DM groups were significantly increased compared to the normal controls, and were incrementally increased in turn in the three groups, whereas DI decreased at the same time. One standard deviation increment in ALT and GGT increased the risk of β-cell dysfunction after controlling for potential confounders such as sex, age, BMI, waist-hip ratio, and blood pressure. Even after the adjustment of the serum lipid profile and L/S ratio, the odds ratio of ALT remained statistically significant (OR, 1.603; 95 % CI, 1.225-2.096). Serum levels of liver enzymes showed an independent close relationship with insulin secretion capacity. Excluding the impact of a fatty liver, increased ALT and GGT levels indicated a significant association with the attenuation of pancreatic β-cell function. This study provides the possibility that elevated liver enzymes might be treated as simple biomarkers of early insulin secretion deficit in type 2 diabetes, especially in young obese patients.
authors.affiliation: Department of Endocrinology and Metabolism, Rui-jin Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, 197 Ruijin Er Road, Shanghai, 200025, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Bokai
authors.initials: B
authors.lastname: Wang
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Weiqiong
authors.initials: W
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D008099:Liver / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009765:Obesity / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase
references.citation: J Intern Med. 2005 Dec;258(6):527-35
references.pmid: 16313476
references.citation: N Engl J Med. 1996 Mar 21;334(12):777-83
references.pmid: 8592553
references.citation: Am J Epidemiol. 1990 Aug;132(2):318-26
references.pmid: 1973595
references.citation: Mutagenesis. 1991 Jul;6(4):241-5
references.pmid: 1682786
references.citation: Diabetologia. 2006 Nov;49(11):2599-603
references.pmid: 16969645
references.citation: Carcinogenesis. 1994 Feb;15(2):343-8
references.pmid: 7906207
references.citation: Eur J Endocrinol. 2008 Sep;159(3):251-7
references.pmid: 18583389
references.citation: Free Radic Biol Med. 1997;22(5):853-60
references.pmid: 9119254
references.citation: Diabetes Res Clin Pract. 2007 Aug;77(2):306-13
references.pmid: 17353063
references.citation: Endocrine. 2010 Oct;38(2):181-7
references.pmid: 20972737
references.citation: Science. 2008 Nov 21;322(5905):1250-4
references.pmid: 19023081
references.citation: Lancet. 2004 Jan 10;363(9403):157-63
references.pmid: 14726171
references.citation: Acad Radiol. 2012 Jul;19(7):811-8
references.pmid: 22521729
references.citation: Diabetes. 2002 Jun;51(6):1889-95
references.pmid: 12031978
references.citation: Endocrine. 2011 Oct;40(2):265-72
references.pmid: 21523521
references.citation: Am J Physiol. 1998 Apr;274(4):E592-9
references.pmid: 9575818
references.citation: Diabetes. 1993 Feb;42(2):250-6
references.pmid: 8425661
references.citation: Diabetologia. 2003 Mar;46(3):359-64
references.pmid: 12687334
references.citation: Endocrine. 2007 Apr;31(2):93-9
references.pmid: 17873317
references.citation: Diabetes Care. 2005 Dec;28(12):2913-8
references.pmid: 16306554
references.citation: J Clin Endocrinol Metab. 2004 Nov;89(11):5410-4
references.pmid: 15531490
references.citation: Diabetes Care. 2007 Nov;30(11):2916-21
references.pmid: 17666465
references.citation: Diabetes Res Clin Pract. 2009 May;84(2):152-7
references.pmid: 19264371
references.citation: Am J Respir Cell Mol Biol. 1994 Nov;11(5):586-92
references.pmid: 7946387
references.citation: N Engl J Med. 2010 Mar 25;362(12):1090-101
references.pmid: 20335585
references.citation: J Clin Invest. 1981 Dec;68(6):1456-67
references.pmid: 7033284
references.citation: Free Radic Biol Med. 1998 Nov 1;25(7):786-92
references.pmid: 9823544
references.citation: Diabetes. 2011 Jun;60(6):1660-7
references.pmid: 21521874
references.citation: Endocrine. 2012 Feb;41(1):70-5
references.pmid: 21796479
references.citation: Gastroenterology. 2002 Sep;123(3):745-50
references.pmid: 12198701
references.citation: J Biol Chem. 2001 Feb 9;276(6):3798-804
references.pmid: 11080500
references.citation: Mol Cell. 2000 Jul;6(1):87-97
references.pmid: 10949030
references.citation: Endocrine. 2013 Jun;43(3):504-13
references.pmid: 23132321
references.citation: Toxicol Appl Pharmacol. 1997 Apr;143(2):388-96
references.pmid: 9144455
references.citation: Endocrine. 2011 Dec;40(3):332-43
references.pmid: 21894514