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Leptin Reverses The Symptoms Of A Rare Form Of Diabetes

Date:
February 21, 2002
Source:
National Institute Of Diabetes And Digestive And Kidney Diseases
Summary:
Researchers have successfully used the hormone leptin to treat patients suffering from lipodystrophy, a rare and difficult-to-treat disorder that shares some of the characteristics of typical type 2 diabetes.

Researchers have successfully used the hormone leptin to treat patients suffering from lipodystrophy, a rare and difficult-to-treat disorder that shares some of the characteristics of typical type 2 diabetes. The findings by scientists at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the University of Texas Southwestern Medical Center appear in the February 21, 2002, issue of the New England Journal of Medicine. "This is the first example of leptin's use in a therapeutic role in a rare form of diabetes," says NIDDK's Phillip Gorden, M.D., the study's senior investigator.

People with lipodystrophy have few or no fat cells and thus lack leptin, a hormone produced by and stored in fat cells. Because they have no fat cells, people with the condition usually store huge amounts of lipids (fat) in inappropriate places like muscle or liver, and they have extremely high levels of lipids in their blood. These patients are likely to be insulin resistant, meaning their bodies don't readily respond to insulin, the hormone that allows muscle and fat cells to properly use glucose. The condition can be congenital or acquired.

Eight of the nine female patients who participated in the study had diabetes and were taking either insulin or a diabetes drug, or a combination of the two. During the four-month study, most patients experienced significant improvements in levels of fasting glucose, hemoglobin A1c (A1c), which measures a person's average blood glucose over the three previous months, and triglycerides (a kind of lipid). Patients were able to reduce or stop using insulin and drugs to control their diabetes, and they reported eating less following treatment. The findings suggest that leptin reduces insulin resistance and prevents the body from accumulating fat in the wrong places.

"It is too soon to make the assumption that leptin will be useful in typical type 2 diabetes," says Gorden. Although people with lipodystrophy and type 2 diabetes can develop some of the same complications when blood glucose is uncontrolled, the two conditions differ in fundamental ways. Most people with typical type 2 diabetes are overweight and not deficient in leptin. In fact, their leptin levels are usually high, and they may be resistant to leptin's effects, says Gorden.

The rationale for treating lipodystrophy with leptin comes from classical endocrinology. "The idea is that if people have a hormone deficiency and they are given replacement hormone, they should respond," says Gorden.

"What we have shown is that in a leptin-deficient state, we can correct many of the abnormalities that come with it," adds Elif Arioglu Oral, M.D., the paper's lead author and a former research fellow at NIDDK. The results also suggest that leptin deficiency may explain the insulin resistance seen in people with lipodystrophy. "For the first time, we're seeing leptin working as an insulin-sensitizing agent," adds Oral, now an assistant professor at the University of Michigan in Ann Arbor. Earlier leptin studies showed that lack of the hormone caused obesity in mice; resistance to leptin likewise contributed to obesity in mice and humans.

In the eight diabetic patients in the study, the decrease in hemoglobin A1c was 1.9 percentage points. Healthy people with no diabetes have an A1c lower than 6; the goal for people with diabetes is lower than 7. At the beginning of the study, only two patients had an A1c lower than 8; by the end of the study eight patients had A1c levels lower than 8.

For all patients, average fasting triglyceride levels dropped by approximately 60% and liver volume dropped by 28%. The normal range for plasma triglycerides is 35 to 155 mg/dL. The level for patients at the start of the study ranged from 445 to 9,560. At the study's conclusion, the range was 123 to 1,214.

The change in the patient with the highest triglyceride level was dramatic, says Oral. No medications had worked for this patient. The extra lipid had deposited in the skin, causing a lot of pain, and her liver was very enlarged. To remove the triglycerides, every week she had to go through pheresis, a process where blood is removed, components are separated out, and the blood is returned to the body. "Within three months of leptin therapy her liver had shrunk, and she was off pheresis," says Oral. "Treatment made a difference in her quality of life."

To better understand how much leptin people really need, NIDDK has begun studying people with less severe lipodystrophy. "There is probably a critical level for normal insulin sensitivity," says Oral.

Other researchers who participated in this study are Vinaya Simha, M.D., Elaine Ruiz, N.P, Alexa Andewelt, B.S., Ahalya Premkumar, M.D., Peter Snell, Ph.D., Anthony J. Wagner, Ph.D., Alex M. DePaoli, M.D., Marc L. Reitman, M.D., Ph.D., Simeon I. Taylor, M.D., Ph.D., and Abhimanyu Garg, M.D.

Wagner and DePaoli are from Amgen Inc. in Thousand Oaks, California. Amgen supplied the recombinant leptin used in the study. Simha, Snell, and Garg are from the University of Texas Southwestern Medical Center in Dallas. Two patients were studied at the University of Texas. Taylor, formerly of NIDDK, is now at Eli Lilly in Indianapolis, Indiana.


Story Source:

The above story is based on materials provided by National Institute Of Diabetes And Digestive And Kidney Diseases. Note: Materials may be edited for content and length.


Cite This Page:

National Institute Of Diabetes And Digestive And Kidney Diseases. "Leptin Reverses The Symptoms Of A Rare Form Of Diabetes." ScienceDaily. ScienceDaily, 21 February 2002. <www.sciencedaily.com/releases/2002/02/020221074013.htm>.
National Institute Of Diabetes And Digestive And Kidney Diseases. (2002, February 21). Leptin Reverses The Symptoms Of A Rare Form Of Diabetes. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2002/02/020221074013.htm
National Institute Of Diabetes And Digestive And Kidney Diseases. "Leptin Reverses The Symptoms Of A Rare Form Of Diabetes." ScienceDaily. www.sciencedaily.com/releases/2002/02/020221074013.htm (accessed July 30, 2014).

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