Skeletal muscle morphology and exercise response in congenital generalizedlipodystrophy

OBJECTIVE - Congenital generalized lipodystrophy (CGL) is an autosomal rece ssive genetic disorder characterized by almost complete absence of adipose tissue, muscular appearance, and severe insulin resistance since birth. We investigated whether insulin resistance in CGL patients is associated with abnormal muscle morphology and whether increased muscularity imparts increa sed muscle strength and exercise capacity. RESEARCH DESIGN AND METHODS - We obtained quadriceps muscle biopsies to stu dy muscle fiber types and capillary density in three African-American women (aged 17-20 years) with CGL. We also assessed quadriceps muscle strength, muscle metabolism, and maximal O-2 consumption in the patients. RESULTS - Quadriceps muscle biopsies revealed a markedly higher percentage of type II (fast-twitch glycolytic) muscle fibers in patients with CGL vers us sedentary young women (75-78 vs. 47-57%, respectively). The capillary-to -fiber ratio (2.7-3.0), however, was normal. Cross-sectional areas of type I (slow-twitch oxidative) (1,262-2,685 mu m(2)) and type II (2,304-3,594 mu m(2)) fibers were far below the normal values (3,811-4,310 and 3,115-4,193 mu m(2), respectively), suggesting muscle hyperplasia but not hypertrophy. The quadriceps muscle strength, as measured by Cybex, was below average; t he maximal O-2 consumption (23-32 ml . kg(-1) . min(-1)) was also below ave rage. P-31 nuclear magnetic resonance spectroscopy of the forearm muscles r evealed normal pH and metabolic responses to static and dynamic exercises. CONCLUSIONS - We conclude that insulin resistance in patients with CGL is a ssociated with an increased proportion of type II muscle fibers but not red uced capillary density. Increased muscularity in CGL is due to muscle hyper plasia and is not associated with increased muscle strength.