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Insulin-Resistant Diabetes Mellitus and Hypermetabolism in Mandibuloacral Dysplasia: A Newly Recognized Form of Partial Lipodystrophy^*

D. L. CUTLER, S. KAUFMANN and G. R. FREIDENBERG

Department of Medicine, University of California-San Diego La Jolla, California 92093
Department of Pediatrics, University of California-San Diego La Jolla, California 92093

Address all correspondence and requests for reprints to: David L. Cutler, M.D., UCSD Medical Center, H-203, 225 Dickinson Street, San Diego, California 92103.

Mandibuloacral dysplasia (MAD) is a syndrome characterized by partial lipodystrophy and a distinct phenotype, which includes progressive osteolysis of the mandible and clavicles, cutaneous atrophy, joint contractures, and diabetes mellitus. We now describe the results of hyperinsulinemic glucose clamps performed in conjunction with indirect calorimetry in two subjects with MAD. At a glucose level of 5 mmol/L and insulin concentration of over 6.5 x 10⁴ pmol/L, glucose disposal rates were less than 20% of maximum insulin-stimulated glucose disposal in five nondiabetic controls. Basal hepatic glucose output was elevated in the two patients and was incompletely suppressed by a 1200 mU/m²-min infusion of insulin. Glucose and lipid oxidation rates were inappropriately elevated, reflecting marked hypermetabolism. Pharmacological concentrations of insulin failed to normally suppress lipid oxidation, diminish FFA levels, or adequately suppress glucagon levels. In summary, MAD is a unique form of lipodystrophic diabetes characterized by typical somatic features, extreme insulin resistance, and marked hypermetabolism.

^* This work was supported by General Clinical Research Center Grant M01-RR-00827.

Supported in part by the Juvenile Diabetes Foundation (Grant 388348).

Received January 24, 1991.

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