The Dunnigan-type
familial partial lipodystrophy (FPLD) is characterized by a variable loss of fat from the extremities and trunk and excess subcutaneous fat in the chin and supraclavicular area. Associated metabolic abnormalities include hypoleptinemia,
insulin resistance, and
dyslipidemia. Our goal was to observe changes in metabolic parameters for patients with FPLD on long-term
leptin replacement and to compare the metabolic characteristics seen in FPLD with those seen in
generalized lipodystrophy (GL) from our previous studies. This was an open-label study of 6 patients with FPLD receiving maximal doses of oral
antidiabetic and
lipid-lowering medications at baseline. Recombinant
leptin was given through twice-daily
subcutaneous injections at a maximal dose of 0.08 mg/kg per day over 12 months to simulate normal to high normal physiologic levels.
Triglycerides were reduced by 65% at 4 months (749+/-331 to 260+/-58 mg/dL) and significantly reduced at 12 months for 5 patients (433+/-125 to 247+/-69 mg/dL; P=.03). Total
cholesterol also decreased (280+/-49 to 231+/-41 mg/dL; P=.01).
Insulin sensitivity and fasting
glucose levels (190+/-26 to 151+/-15 mg/dL; P<.01) improved.
Glucose tolerance and
glycosylated hemoglobin levels (8.4%+/-0.6% to 8.0%+/-0.4%; P=.07) did not change. As shown in patients with GL, patients with FPLD have improvement in
triglycerides, fasting
glucose, and
insulin sensitivity with
leptin replacement. In contrast to the patients with GL, the patients with FPLD are older, have higher
leptin levels, and notably lower insulin secretion for a similar degree of
hyperglycemia. Low-dose
recombinant methionyl human leptin for patients with FPLD has an important role in improving
triglycerides, beyond that of available
lipid-lowering agents. In improving
glycemic control, normalization of
glucose tolerance in hypoinsulinemic patients with FPLD requires
insulin and
leptin therapy. This is the first study to examine the effects of long-term
leptin replacement in patients with FPLD.