Yale Bulletin and Calendar

September 23, 2005|Volume 34, Number 4

Early signs of diabetes exist before
symptoms appear, study shows

The rate of insulin-stimulated energy production is significantly reduced in the muscles of lean, healthy young adults who have already developed insulin resistance and are at increased risk of developing diabetes later in life, according to a School of Medicine study.

The new research by Dr. Gerald Shulman, professor of internal medicine (endocrinology) and senior author of the study, indicates that a decreased ability to burn sugars and fats efficiently is an early and central part of the diabetes problem. The new data also suggest that the basic defect lies within the mitochondria, which are the energy factories inside cells that produce most of the chemical power needed to sustain life.

The young adults studied by the research team are the offspring of parents who have type 2 diabetes, adding support to the idea that the risk can be inherited and that the problem begins well before diabetes symptoms become evident, Shulman notes.

The researchers observed that the mitochondria in the subjects' muscle cells responded poorly to insulin stimulation. Normal mitochondria react to insulin by boosting production of an energy-carrying molecule, ATP, by 90%. But the mitochondria from the insulin-resistant people they tested only boosted ATP production by 5%.

Among their findings is also evidence of a severe reduction in the amount of insulin-stimulated phosphorus transport into the muscle cells of the insulin-resistant participants. (Phosphorus is a key element in the mithochondrion's complex energy-production process.) This also points to a dramatic defect in insulin signaling and may explain the observed abnormalities in insulin-stimulated power production in the insulin-resistant study subjects.

The co-authors are Kitt Petersen and Sylvie Dufour.

-- By Jacqueline Weaver

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