Long-Term Leptin-Replacement Therapy for Lipoatrophic Diabetes
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Oral et al. reported in 2002 that leptin treatment for a period of four months improved hyperglycemia and hypertriglyceridemia in nine female patients with lipodystrophy.1 We report the efficacy of leptin-replacement therapy given for 12 months with the use of the same protocol in two Japanese patients. Patient 1 was an 11-year-old girl with acquired generalized lipodystrophy. She was normal at birth and in her growth. At nine years of age, cervical lymphangitis and panniculitis developed. After that, she had systematic fat loss, her body weight decreased from 38.5 kg to 26.0 kg, and diabetes emerged within two months. Treatment with pioglitazone (15 mg per day) for 10 months did not improve glycemic control. Just before starting leptin-replacement therapy, she had marked hyperglycemia (glycosylated hemoglobin, 10.0 percent), hypertriglyceridemia (1941 mg per deciliter), and severe fatty liver. Patient 2 was a 29-year-old man with congenital generalized lipodystrophy. A generalized deficiency of body fat was noticed from birth, with the onset of diabetes when he was 11 years old. Glyburide (glibenclamide) (2.5 mg per day) and voglibose (0.6 mg per day) were ineffective. Just before leptin-replacement therapy was initiated, his glycosylated hemoglobin level was 10.3 percent. He had neither hypertriglyceridemia nor fatty liver.
Patients 1 and 2 had extremely low values for body fat (5.2 percent and 4.7 percent, respectively, as measured by dual-energy x-ray absorptiometry) and plasma leptin concentrations (0.92 and 0.82 ng per milliliter, respectively). During leptin-replacement therapy, the serum leptin concentrations increased to 7.9 and 26.7 ng per milliliter at 4 months and 5.9 and 35.4 ng per milliliter at 12 months in Patients 1 and 2, respectively.
Both patients received leptin as inpatients for the first four months of therapy. After the initiation of leptin treatment, fasting plasma glucose levels normalized (208 mg per deciliter in Patient 1 and 142 mg per deciliter in Patient 2). Without the use of oral antidiabetic agents, the glucose levels in both patients were well controlled. The glycosylated hemoglobin levels were reduced to 4.8 percent and 6.5 percent, respectively, at four months and remained below 6.5 percent over a full year (Figure 1). The elevated fasting triglyceride level and severe fatty liver in Patient 1 normalized (Figure 1). During the year of treatment, we observed no adverse effects of leptin-replacement therapy and no skin reactions at the injection sites.
Figure 1. Glycosylated Hemoglobin Levels, Fasting Serum Triglyceride Levels, and Liver Volume in Patients 1 and 2 during 12 Months of Leptin-Replacement Therapy.
Liver volume was calculated with the use of computed tomographic imaging.
Our clinical trials in Japan show that leptin-replacement therapy is highly effective for a full year in patients with generalized lipodystrophy. Leptin-replacement therapy appears to be safe and effective for long-term treatment of lipoatrophic diabetes.
Ken Ebihara, M.D., Ph.D.
Hiroaki Masuzaki, M.D., Ph.D.
Kazuwa Nakao, M.D., Ph.D.
Kyoto University Graduate School of Medicine
Kyoto 606-8507, Japan
kebihara@kuhp.kyoto-u.ac.jp
References
Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002;346:570-578.
Patients 1 and 2 had extremely low values for body fat (5.2 percent and 4.7 percent, respectively, as measured by dual-energy x-ray absorptiometry) and plasma leptin concentrations (0.92 and 0.82 ng per milliliter, respectively). During leptin-replacement therapy, the serum leptin concentrations increased to 7.9 and 26.7 ng per milliliter at 4 months and 5.9 and 35.4 ng per milliliter at 12 months in Patients 1 and 2, respectively.
Both patients received leptin as inpatients for the first four months of therapy. After the initiation of leptin treatment, fasting plasma glucose levels normalized (208 mg per deciliter in Patient 1 and 142 mg per deciliter in Patient 2). Without the use of oral antidiabetic agents, the glucose levels in both patients were well controlled. The glycosylated hemoglobin levels were reduced to 4.8 percent and 6.5 percent, respectively, at four months and remained below 6.5 percent over a full year (Figure 1). The elevated fasting triglyceride level and severe fatty liver in Patient 1 normalized (Figure 1). During the year of treatment, we observed no adverse effects of leptin-replacement therapy and no skin reactions at the injection sites.
Figure 1. Glycosylated Hemoglobin Levels, Fasting Serum Triglyceride Levels, and Liver Volume in Patients 1 and 2 during 12 Months of Leptin-Replacement Therapy.
Liver volume was calculated with the use of computed tomographic imaging.
Our clinical trials in Japan show that leptin-replacement therapy is highly effective for a full year in patients with generalized lipodystrophy. Leptin-replacement therapy appears to be safe and effective for long-term treatment of lipoatrophic diabetes.
Ken Ebihara, M.D., Ph.D.
Hiroaki Masuzaki, M.D., Ph.D.
Kazuwa Nakao, M.D., Ph.D.
Kyoto University Graduate School of Medicine
Kyoto 606-8507, Japan
kebihara@kuhp.kyoto-u.ac.jp
References
Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002;346:570-578.