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      Elevated Serum Gamma-Glutamyltransferase Is a Strong Marker of Insulin Resistance in Obese Children

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          Abstract

          Elevated levels of serum gamma-glutamyltransferase (GGT) levels have been found to predict the development of type 2 diabetes in adults. The role of GGT in insulin resistance (IR) among children is largely unknown. We investigated whether GGT among hepatic enzymes is independently associated with IR in obese Korean children. A total of 1308 overweight (above the 85th BMI percentile of Korean reference) boys ( n = 822) and girls ( n = 486), aged 9–15 years, were studied. Measures acquired included weight, height, percent body fat (BF%), waist circumference, blood pressure, blood glucose and insulin, C-reactive protein, total cholesterol, triglycerides, HDL-Cholesterol, GGT, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IR was calculated using the homeostasis model assessment (HOMA-IR). Serum GGT and ALT, but not AST, were positively correlated with HOMA-IR in boys ( r = 0.222 for GGT; P < 0.05, r = 0.188 for ALT; P < 0.05) and girls ( r = 0.292 for GGT; P < 0.05, r = 0.258 for ALT; P < 0.05). In multiple regression analysis for HOMA-IR as dependent variable, GGT ( β = 0.068; P = 0.053 in boys, β = 0.145; P = 0.002 in girls) and ALT ( β = 0.074; P = 0.034 in boys, β = 0.130; P = 0.005 in girls) emerged as determinants of HOMA-IR after adjusting age, BMI, tanner stage, and triglycerides. Serum GGT level is a strong marker of IR in obese Korean children.

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          Gamma glutamyl transferase.

          Serum gamma-glutamyl transferase (GGT) has been widely used as an index of liver dysfunction and marker of alcohol intake. The last few years have seen improvements in these areas and advances in understanding of its physiological role in counteracting oxidative stress by breaking down extracellular glutathione and making its component amino acids available to the cells. Conditions that increase serum GGT, such as obstructive liver disease, high alcohol consumption, and use of enzyme-inducing drugs, lead to increased free radical production and the threat of glutathione depletion. However, the products of the GGT reaction may themselves lead to increased free radical production, particularly in the presence of iron. There have also been important advances in the definition of the associations between serum GGT and risk of coronary heart disease, Type 2 diabetes, and stroke. People with high serum GGT have higher mortality, partly because of the association between GGT and other risk factors and partly because GGT is an independent predictor of risk. This review aims to summarize the knowledge about GGT's clinical applications, to present information on its physiological roles, consider the results of epidemiological studies, and assess how far these separate areas can be combined into an integrated view.
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            Insulin resistance in children: consensus, perspective, and future directions.

            Emerging data indicate that insulin resistance is common among children and adolescents and is related to cardiometabolic risk, therefore requiring consideration early in life. However, there is still confusion on how to define insulin resistance, how to measure it, what its risk factors are, and whether there are effective strategies to prevent and treat it. A consensus conference was organized in order to clarify these points. The consensus was internationally supported by all the major scientific societies in pediatric endocrinology and 37 participants. An independent and systematic search of the literature was conducted to identify key articles relating to insulin resistance in children. The conference was divided into five themes and working groups: background and definition; methods of measurement and screening; risk factors and consequences; prevention; and treatment. Each group selected key issues, searched the literature, and developed a draft document. During a 3-d meeting, these papers were debated and finalized by each group before presenting them to the full forum for further discussion and agreement. Given the current childhood obesity epidemic, insulin resistance in children is an important issue confronting health care professionals. There are no clear criteria to define insulin resistance in children, and surrogate markers such as fasting insulin are poor measures of insulin sensitivity. Based on current screening criteria and methodology, there is no justification for screening children for insulin resistance. Lifestyle interventions including diet and exercise can improve insulin sensitivity, whereas drugs should be implemented only in selected cases.
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              Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study.

              A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [S(i)]), which is important given associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S(i), and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies.
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                Author and article information

                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi Publishing Corporation
                1687-8337
                1687-8345
                2013
                12 March 2013
                : 2013
                : 578693
                Affiliations
                1Department of Family Medicine, Inje University, College of Medicine, Sanggyepaik Hospital, Nowon-Gu, Seoul 139-707, Republic of Korea
                2Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 108 Pyongdong, Jongro-Gu, Seoul 110-746, Republic of Korea
                3Department of Occupational Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 108 Pyongdong, Jongro-Gu, Seoul 110-746, Republic of Korea
                4Health Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul 110-746, Republic of Korea
                Author notes

                Academic Editor: Barry Posner

                Article
                10.1155/2013/578693
                3610353
                23573088
                1a6c6771-521b-40a3-83d0-ca31ec226223
                Copyright © 2013 Seon Yeong Lee et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 October 2012
                : 29 January 2013
                : 15 February 2013
                Categories
                Research Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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