Findings from a study suggest that primary beta-cell dysfunction plays a key role in the pathogenesis of low birth weight (LBW)-associated type 2 diabetes.
It seems that the condition involves hyperinsulinism, without peripheral insulin resistance.
Although LBW status is a known risk factor for diabetes, the mechanisms involved in the association were unclear.
Dr. Mary-Elizabeth Patti, from Harvard Medical School in Boston, and colleagues created a murine model of LBW resulting from restricted maternal food intake. Although weight normalization occurred after birth, these animals still developed severe glucose intolerance by 6 months, the investigators note.
To determine the origin of this disturbance, the authors assessed glucose metabolism in these mice at age 2 months before the intolerance had set in. These results were then compared with those seen in control animals.
The authors found that insulin levels in fed animals were 1.7-times higher in the prediabetic mice than in controls. By contrast, insulin sensitivity, insulin tolerance, insulin-stimulated glucose disposal, and muscle/adipose glucose uptake seemed to be normal in these mice.
There was a mild impairment of insulin clearance in prediabetic mice, but the main problem was dysregulated insulin secretion, the investigators point out. Although the beta-cell mass was normal, the islet cells displayed basal hypersecretion of insulin, no responsiveness to glucose, and elevated hexokinase activity.
"Insulin secretory abnormalities in LBW mice may result from appropriate fetal adaptation (‘programming’) to a suboptimal nutritional state during intrauterine life, but ultimately are maladaptive when presented with a high carbohydrate diet following weaning," the authors conclude.
Diabetes March, 2005.
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Exubera, The Inhaled Insulin Passes FDA
The US Food and Drug Administration has accepted a new drug application by Sanofi-Aventis and Pfizer of the United States for Exubera, a dry powder form of insulin that is inhaled into the lungs prior to eating.
The treatment has been tested on more than 3,400 patients, some for more than seven years, the statement said.