Familial partial lipodystrophy: Complications of obesity in the non-obese?

The increased frequency of metabolic perturbations in overweight individuals whose fat is predominantly central, as compared with those whose fat is more generalized in distribution suggests that characteristics of fat other than an excess promote the morbidity of the obese. In this report we describe the location and quantity of body fat together with the status of carbohydrate and lipid metabolism in 8 females affected with familial partial lipodystrophy, a rare condition in which peripheral subcutaneous fat is mostly absent while there is retention or an increase in central adiposity. The 8 subjects had normal or reduced amounts of body fat as determined by body density measurements. Computerized axial tomograms in two subjects showed that there was normal to increased amounts of intra-abdominal fat and irregular pockets of subcutaneous fat overlying the abdomen. Plasma triglycerides varied but were elevated in all subjects ranging from 171 to 3720 mg/dl (normal = 103 ± 36). Mild sustained elevations in mean systolic blood pressure (> 135 mm Hg) occurred in 4. Two of the 8 had fasting hyperglycemia (>140 mg/dL) and a third was intolerant to oral, but not to intravenous glucose. Fasting serum insulin concentrations were uniformly elevated (22 to 51 uU/ml) and, in most instances, responded to both glucose and arginine with exaggerated increments, but there was no delay in insulin release. Mild insulin resistance was documented by the failure to respond to standard insulin injections, and there were decreased insulin receptors on erythrocytes. Basal plasma glucagon concentrations were generally elevated, did not suppress during oral glucose administrations and rose 2 to 5 times basal levels during intravenous infusion of arginine.These studies emphasize that the various complications of the obese, especially those with centralized obesity, are seen in a non-obese condition characterized by an increase in the ratio of central to peripheral fat.