The autosomal dominant trait of obesity, acanthosis nigricans, hypertension, ischemic heart disease and diabetes type 2

N Kerem, H Guttmann, Z Hochberg
Hormone Research 2001, 55 (6): 298-304

OBJECTIVE: Among obese subjects, acanthosis nigricans in both males and females is not as uncommon as previously thought. Whereas this finding was extensively evaluated in females, mostly in the context of polycystic ovaries syndrome, little attention has been paid to obese males with acanthosis nigricans. As acanthosis seems to be a marker for insulin resistance, the present study was designed to evaluate the hypothesis that the clinical syndrome of obesity and acanthosis would take a different clinical course than that of simple obesity.

METHODS: To characterize the course of acanthosis nigricans and obesity in males, we examined 22 children and adolescents with this complex, together with their parents and grandparents and found them to follow a detrimental sequence of the metabolic syndrome. We compared the findings to 13 age-matched males with obesity but no clinical apparent acanthosis nigricans. We analyzed the clinical course, fat distribution, glucose, insulin and C-peptide and lipoproteins.

RESULTS: Onset of obesity in the metabolic syndrome group was at a mean age of 6.4 years, as compared to 2.3 years in the controls. The metabolic syndrome patients had a truncal (android) distribution of fat and their fasting blood glucose was significantly higher. HDL/total cholesterol was lower. Examination of the pedigrees suggested autosomal dominant inheritance of the obesity and acanthosis nigricans complex, extending to hypertension and ischemic heart disease in the parents' generation, and further extending to include diabetes type 2 in the grandparents' generation.

CONCLUSIONS: This metabolic syndrome is inherited as an autosomal dominant trait, with onset of truncal obesity at age 6-7 years, acanthosis nigricans during childhood or adolescence, extending to hypertension and ischemic heart disease during young adulthood, and further extending to include diabetes type 2 in late adulthood. It is recommended that such children should be followed up as an 'at-risk' group, and would probably benefit from intensive weight reduction, which may prevent the later manifestations of the syndrome.

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