Original Paper
HOR MONE RESEARCH I N PÆDIATRIC S
Horm Res Paediatr 2017;88:265–273 DOI: 10.1159/000479868
Received: January 6, 2017 Accepted: July 24, 2017 Published online: September 12, 2017
Associations between Liver Enzyme Levels and Parameters of the Metabolic Syndrome in Obese Children Christiane S. Hampe a Michele L. Shaffer b, c Christian L. Roth d, e
a Division
of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA; b Seattle Children’s Research Institute, Center for Clinical and Translational Research, Seattle, WA, USA; c Department of Pediatrics, University of Washington, Seattle, WA, USA; d Center for Integrative Brain Research, Seattle Children’s Hospital and Research Institute, Seattle, WA, USA; e Pediatric Endocrinology, Seattle Children’s Hospital and Research Institute, Seattle, WA, USA
Abstract Background: Obesity is strongly associated with insulin resistance, hypertension, dyslipidemia, and therefore risk for metabolic syndrome (MetS), which is an increasing problem in youth. The potential role of elevated liver enzyme levels in this context needs to be further investigated. Methods: This paper provides a post hoc analysis of a cross-sectional study of 77 obese nondiabetic children (51% female; median age 11.7 years; BMI >97th percentile) enrolled at the University of Bonn, Bonn, Germany. Anthropometric parameters, lipid profiles, glycemic control, and liver enzyme levels were evaluated. Glucose and insulin levels were determined during an oral glucose tolerance test (OGTT). Gender- and age-specific cutoff values were used to assess MetS. Results: A high prevalence of hypertension (51%), dyslipidemia (52%), elevated liver enzyme levels (51%), and hyperglycemia (24%) was found. There was considerable overlap between the presence of different MetS risk factors in individuals, and 40% of
© 2017 S. Karger AG, Basel E-Mail [email protected] www.karger.com/hrp
the participants had ≥3 of a maximum of 5 MetS risk factors. Elevated liver enzyme levels were significantly associated with reduced insulin sensitivity, as the OGTT-insulin response was significantly higher in participants with elevated transaminases (p = 0.01). This association was independent of hyperglycemia and dyslipidemia (p = 0.03). Conclusions: We conclude that liver enzyme levels are related to insulin sensitivity in obese children and could therefore be an indirect indicator for MetS. Testing for disturbed glucose metabolism should be considered for obese children with elevated liver enzymes. © 2017 S. Karger AG, Basel
Introduction
Obesity, hyperlipidemia, hypertension, and dysfunctional glycemic control are risk factors for the development of metabolic syndrome (MetS). While these conditions are most common in obese adults, their prevalence among children is increasing at an alarming rate. This increase is tightly correlated with the increase in childhood obesity [1, 2], and 19–35% of obese youth have Christian L. Roth, MD Center for Integrative Brain Research, Seattle Children’s Research Institute 1900 Ninth Ave, P.O. Box 5371 M/S-C9S Seattle, WA 98101 (USA) E-Mail christian.roth @ seattlechildrens.org
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 10:16:27 PM
Keywords Obesity · Metabolic syndrome · Childhood · Liver disease · Insulin resistance
Table 1. Anthropometric and clinical parameters of the study subjects arranged by severity of MetS
Parameter
All subjects (n = 77)
Age, years 11.7 (8.2–14) Systolic BP, mm Hg 124 (112–137) Systolic BP >95th perc., % of subjects 49 Diastolic BP, mm Hg 71 (64–80) Diastolic BP >95th perc., % of subjects 19 BMI 32 (27–35) SDS BMI 2.9 (2.6–3.3) gGT, U/L 22 (18–28) AST, U/L 28 (23–34) ALT, U/L 29 (24–38) TG, mg/dL 98 (73–137) Cholesterol, mg/dL 161 (147–178) HDL, mg/dL 43 (36–49) LDL, mg/dL 100 (85–120) HbA1c, % 5.3 (5.1–5.5) Glc0, mmol/L 4.7 (4.4–5) Glc120, mmol/L 6.4 (5.8–7.5) Ins0, mU/L 10.2 (6–17) Ins120, mU/L 91 (43–149)
MetS score 1–2 (n = 46)
MetS score ≥3 (n = 31)
p value MetS scores 1–2 vs. ≥3
11.2 (6.5–13.4) 120 (110–130.3) 37 71 (65.5–80) 17 30 (27–33) 2.9 (2.6–3.3) 21 (18–28) 27 (22–32) 28 (22–35) 76 (59–98.5) 162 (144–177) 48 (41–51) 99 (84–115) 5.3 (5.1–5.5) 4.6 (4.4–4.8) 6.2 (5.3–7.2) 9.5 (5.5–15.3) 72 (39–121)
12.1 (9.2–14.5) 131 (115–140) 68 70 (64–77) 23 34 (28–36) 2.9 (2.7–3.2) 23 (17–29) 29 (24–36) 32 (26–53) 145 (120–180) 160 (151–196) 37 (34–45) 100 (86–125) 5.3 (5.1–5.5) 5 (4.2–5.2) 6.8 (6–7.9) 11.3 (6.9–19.4) 136 (89–195)
ns 0.02 0.01a ns nsa ns ns ns ns 0.04 97th percentile for age and sex) who underwent metabolic testing including an oral glucose tolerance test (OGTT) with venous blood sampling for the analysis (Table 1). Of these, 63 (81%) were >99.5th percentile for the BMI. All participants were recruited in the area of Bonn, Germany. The study protocols were approved by the local standing committee for clinical studies and the Committee on Ethical Practice at the University of Bonn, Bonn, Germany, as well as by the Institutional Review Board at Seattle Children’s Research Institute (#12858). Written parental consent and/or patient assent was obtained, and the investigations were conducted according to the principles expressed in the Declaration of Helsinki.
Hampe/Shaffer/Roth
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 10:16:27 PM
overt MetS compared with
HOR MONE RESEARCH I N PÆDIATRIC S
Horm Res Paediatr 2017;88:265–273 DOI: 10.1159/000479868
Received: January 6, 2017 Accepted: July 24, 2017 Published online: September 12, 2017
Associations between Liver Enzyme Levels and Parameters of the Metabolic Syndrome in Obese Children Christiane S. Hampe a Michele L. Shaffer b, c Christian L. Roth d, e
a Division
of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA; b Seattle Children’s Research Institute, Center for Clinical and Translational Research, Seattle, WA, USA; c Department of Pediatrics, University of Washington, Seattle, WA, USA; d Center for Integrative Brain Research, Seattle Children’s Hospital and Research Institute, Seattle, WA, USA; e Pediatric Endocrinology, Seattle Children’s Hospital and Research Institute, Seattle, WA, USA
Abstract Background: Obesity is strongly associated with insulin resistance, hypertension, dyslipidemia, and therefore risk for metabolic syndrome (MetS), which is an increasing problem in youth. The potential role of elevated liver enzyme levels in this context needs to be further investigated. Methods: This paper provides a post hoc analysis of a cross-sectional study of 77 obese nondiabetic children (51% female; median age 11.7 years; BMI >97th percentile) enrolled at the University of Bonn, Bonn, Germany. Anthropometric parameters, lipid profiles, glycemic control, and liver enzyme levels were evaluated. Glucose and insulin levels were determined during an oral glucose tolerance test (OGTT). Gender- and age-specific cutoff values were used to assess MetS. Results: A high prevalence of hypertension (51%), dyslipidemia (52%), elevated liver enzyme levels (51%), and hyperglycemia (24%) was found. There was considerable overlap between the presence of different MetS risk factors in individuals, and 40% of
© 2017 S. Karger AG, Basel E-Mail [email protected] www.karger.com/hrp
the participants had ≥3 of a maximum of 5 MetS risk factors. Elevated liver enzyme levels were significantly associated with reduced insulin sensitivity, as the OGTT-insulin response was significantly higher in participants with elevated transaminases (p = 0.01). This association was independent of hyperglycemia and dyslipidemia (p = 0.03). Conclusions: We conclude that liver enzyme levels are related to insulin sensitivity in obese children and could therefore be an indirect indicator for MetS. Testing for disturbed glucose metabolism should be considered for obese children with elevated liver enzymes. © 2017 S. Karger AG, Basel
Introduction
Obesity, hyperlipidemia, hypertension, and dysfunctional glycemic control are risk factors for the development of metabolic syndrome (MetS). While these conditions are most common in obese adults, their prevalence among children is increasing at an alarming rate. This increase is tightly correlated with the increase in childhood obesity [1, 2], and 19–35% of obese youth have Christian L. Roth, MD Center for Integrative Brain Research, Seattle Children’s Research Institute 1900 Ninth Ave, P.O. Box 5371 M/S-C9S Seattle, WA 98101 (USA) E-Mail christian.roth @ seattlechildrens.org
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 10:16:27 PM
Keywords Obesity · Metabolic syndrome · Childhood · Liver disease · Insulin resistance
Table 1. Anthropometric and clinical parameters of the study subjects arranged by severity of MetS
Parameter
All subjects (n = 77)
Age, years 11.7 (8.2–14) Systolic BP, mm Hg 124 (112–137) Systolic BP >95th perc., % of subjects 49 Diastolic BP, mm Hg 71 (64–80) Diastolic BP >95th perc., % of subjects 19 BMI 32 (27–35) SDS BMI 2.9 (2.6–3.3) gGT, U/L 22 (18–28) AST, U/L 28 (23–34) ALT, U/L 29 (24–38) TG, mg/dL 98 (73–137) Cholesterol, mg/dL 161 (147–178) HDL, mg/dL 43 (36–49) LDL, mg/dL 100 (85–120) HbA1c, % 5.3 (5.1–5.5) Glc0, mmol/L 4.7 (4.4–5) Glc120, mmol/L 6.4 (5.8–7.5) Ins0, mU/L 10.2 (6–17) Ins120, mU/L 91 (43–149)
MetS score 1–2 (n = 46)
MetS score ≥3 (n = 31)
p value MetS scores 1–2 vs. ≥3
11.2 (6.5–13.4) 120 (110–130.3) 37 71 (65.5–80) 17 30 (27–33) 2.9 (2.6–3.3) 21 (18–28) 27 (22–32) 28 (22–35) 76 (59–98.5) 162 (144–177) 48 (41–51) 99 (84–115) 5.3 (5.1–5.5) 4.6 (4.4–4.8) 6.2 (5.3–7.2) 9.5 (5.5–15.3) 72 (39–121)
12.1 (9.2–14.5) 131 (115–140) 68 70 (64–77) 23 34 (28–36) 2.9 (2.7–3.2) 23 (17–29) 29 (24–36) 32 (26–53) 145 (120–180) 160 (151–196) 37 (34–45) 100 (86–125) 5.3 (5.1–5.5) 5 (4.2–5.2) 6.8 (6–7.9) 11.3 (6.9–19.4) 136 (89–195)
ns 0.02 0.01a ns nsa ns ns ns ns 0.04 97th percentile for age and sex) who underwent metabolic testing including an oral glucose tolerance test (OGTT) with venous blood sampling for the analysis (Table 1). Of these, 63 (81%) were >99.5th percentile for the BMI. All participants were recruited in the area of Bonn, Germany. The study protocols were approved by the local standing committee for clinical studies and the Committee on Ethical Practice at the University of Bonn, Bonn, Germany, as well as by the Institutional Review Board at Seattle Children’s Research Institute (#12858). Written parental consent and/or patient assent was obtained, and the investigations were conducted according to the principles expressed in the Declaration of Helsinki.
Hampe/Shaffer/Roth
Downloaded by: Göteborgs Universitet 130.241.16.16 - 10/1/2017 10:16:27 PM
overt MetS compared with
