Type 2 Diabetes in Children is Frequently Associated with Elevated Alanine Aminotransferase

Nadeau, Kristen J.; Klingensmith, Georgeanna J.; Zeitler, Philip

doi:10.1097/01.mpg.0000164698.03164.e5

Cited by 134 publications

(89 citation statements)

References 39 publications

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“…5,40 In contrast, by the time type 2 diabetes mellitus is diagnosed in children, approximately one half have suspected fatty liver because of elevated alanine aminotransferase. 41 Hepatocyte triglyceride storage causes acquired insulin signaling defects, leading to insulin resistance, glucose intolerance, and type 2 diabetes mellitus. 42 The high rates of overweight, insulin-resistant children with NAFLD meeting the criteria for metabolic syndrome suggest that a large number of these children will go on to develop diabetes.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease

et al. 2008

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Background-Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in children, is associated with obesity and insulin resistance. However, the relationship between NAFLD and cardiovascular risk factors in children is not fully understood. The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children. Methods and Results-This case-control study of 150 overweight children with biopsy-proven NAFLD and 150 overweight children without NAFLD compared rates of metabolic syndrome using Adult Treatment Panel III criteria. Cases and controls were well matched in age, sex, and severity of obesity. Children with NAFLD had significantly higher fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure than overweight and obese children without NAFLD. Subjects with NAFLD also had significantly lower high-density lipoprotein cholesterol than controls. After adjustment for age, sex, race, ethnicity, body mass index, and hyperinsulinemia, children with metabolic syndrome had 5.0 (95% confidence interval, 2.6 to 9.7) times the odds of having NAFLD as overweight and obese children without metabolic syndrome. Conclusions-NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors.The identification of NAFLD in a child should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes. (Circulation. 2008; 118:277-283.)

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease

et al. 2008

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“…As high a proportion as 50% of such patients are suspected to have a fatty liver at the time of diagnosis. 33 The prevalence of fatty liver in children is not precisely known. This is difficult to determine, in part, because liver biopsy presents the most definitive diagnosis.…”

Section: Gastrointestinalmentioning

confidence: 99%

Complications of obesity in children and adolescents

2009

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The increasing prevalence and severity of obesity in children and adolescents has provided greater emphasis on the wide variety of comorbid conditions and complications that can be experienced as a consequence of obesity. These complications can occur both in the short term and in the long term. Some complications, earlier thought to be long-term issues, which would only occur in adulthood, have now been shown to occur in children and adolescents. These findings have raised concerns about the overall health experience of those who develop obesity early in life and have even raised questions about whether the obesity epidemic might shorten the life span of the current generation of children. In this paper, I will examine current knowledge regarding the different organ systems that may be impacted by childhood obesity.

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“…It is becoming increasingly clear that fat accumulation in the liver, per se, is not a benign condition (3). Indeed, it is frequently associated with type 2 diabetes in both adults and children (4,5) and has been labeled as the hepatic component of the metabolic syndrome (2,3).…”

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confidence: 99%

Intrahepatic Fat Accumulation and Alterations in Lipoprotein Composition in Obese Adolescents

et al. 2007

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OBJECTIVE -Among other metabolic consequences, a dyslipidemic profile often accompanies childhood obesity. In adults, type 2 diabetes and hepatic steatosis have been shown to alter lipoprotein subclass distribution and size; however, these alterations have not yet been shown in children or adolescents. Therefore, our objective was to determine the effect of hepatic steatosis on lipoprotein concentration and size in obese adolescents.RESEARCH DESIGN AND METHODS -Using fast magnetic resonance imaging, we measured intrahepatic fat content in 49 obese adolescents with normal glucose tolerance. The presence or absence of hepatic steatosis was determined by a threshold value for hepatic fat fraction (HFF) of 5.5%; therefore, the cohort was divided into two groups (HFF Ͼ or Ͻ5.5%). Fasting lipoprotein subclasses were determined using nuclear magnetic resonance spectroscopy.RESULTS -Overall, the high-HFF group had 88% higher concentrations of large VLDL compared with the low-HFF group (P Ͻ 0.001). Likewise, the high-HFF group had significantly higher concentrations of small dense LDL (P Ͻ 0.007); however, the low-HFF group had significantly higher concentrations of large HDL (P Ͻ 0.001). Stepwise multiple regression analysis revealed that high HFF was the strongest single correlate, accounting for 32.6% of the variance in large VLDL concentrations (P Ͻ 0.002).CONCLUSIONS -The presence of fatty liver was associated with a pronounced dyslipidemic profile characterized by large VLDL, small dense LDL, and decreased large HDL concentrations. This proatherogenic phenotype was strongly related to the intrahepatic lipid content. Diabetes Care 30:3093-3098, 2007S tudies from autopsies on 742 children (aged 2-19 years) reported fatty liver prevalence at 9.6%, and in obese children this rate increased to an alarming 38% (1). An imbalance between fatty acid flux and utilization and VLDL secretion leads to an accumulation of triglycerides within the hepatocytes and ultimately to hepatic steatosis (2). It is becoming increasingly clear that fat accumulation in the liver, per se, is not a benign condition (3). Indeed, it is frequently associated with type 2 diabetes in both adults and children (4,5) and has been labeled as the hepatic component of the metabolic syndrome (2,3).Worsening of the dyslipidemic profile has been described in adults in association with insulin resistance and type 2 diabetes (6 -8). Garvey et al. (7) have shown that subjects with type 2 diabetes have larger VLDL and smaller LDL and HDL particles compared with insulinsensitive subjects. The insulin-resistant and type 2 diabetic groups also had greater concentrations of these atherogenic particles. Further studies by Toledo et al. (8) reported that the presence of hepatic steatosis in obese subjects with type 2 diabetes further altered lipoprotein composition compared with type 2 diabetic subjects without fatty liver. Type 2 diabetic subjects with fatty liver had larger triglyceride-rich VLDL particles, smaller LDL and HDL particles, and reduced concentrations o...

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Type 2 Diabetes in Children is Frequently Associated with Elevated Alanine Aminotransferase

Cited by 134 publications

References 39 publications

Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease

Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease

Complications of obesity in children and adolescents

Intrahepatic Fat Accumulation and Alterations in Lipoprotein Composition in Obese Adolescents

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