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GH receptor deficiency may enhance insulin sensitivity, protect against diabetes
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In Ecuadorian adults, growth hormone receptor deficiency without growth hormone counterregulation appears to result in enhanced insulin sensitivity and avoidance of diabetes, according to recent study findings published in The Journal of Clinical Endocrinology & Metabolism.
In the study, Jaime Guevara-Aguirre, MD, of the Universidad San Francisco de Quito in Ecuador, and colleagues evaluated 27 adults with GH receptor deficiency (GHRD) and 35 age-, gender- and BMI-matched control relatives. The study consisted of four analyses: carbohydrate, lipid and adipocytokine concentrations; metabolomics evaluation; metabolic responses to a high-calorie meal; and oral glucose tolerance testing.
The researchers found that despite a higher mean percent of body fat vs. the control participants, GHRD participants had lower fasting insulin, 2-hour blood glucose and triglyceride levels. They also had a higher indicator of insulin sensitivity (P < .0001) and a lower measure of insulin resistance (P = .0025).
The disparities in metabolomics between the GHRD participants and controls corresponded to their differences in insulin sensitivity. In particular, GHRD participants had acute post-meal reductions of branched chain acids, which were significantly greater in controls. Compared with controls, GHRD participants had higher molecular weight (P = .0004), higher total adiponectin concentrations (P = .0128) and lower concentrations of leptin (P = .02).
Although the GHRD participants had a mean weight that was only approximately 65% that of the controls, these participants ate the same high-calorie meals as controls. However, their mean glucose levels were lower than the controls, and their mean insulin levels were one-third those of the controls. The groups had similar results in the 2-hour OGTT.
According to the researchers, the role of GH in insulin resistance and sensitivity must be further explored.
“In summary, subjects with GHRD do not develop diabetes because they lack the counterregulatory effect of GH, thereby inducing a state of enhanced insulin sensitivity compared to control relatives without diabetes, and despite less insulin secretion,” the researchers wrote. “This critical role for GH action in the induction of insulin resistance is an important consideration in the frequent administration of pharmacologic doses of recombinant human GH for growth promotion in children who do not have GH deficiency.” – by Jennifer Byrne
Disclosure: Guevara-Aguirre reports filing provisional patents related to the development of GH receptor blockers. Please see the full study for a list of all other authors’ relevant financial disclosures.
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