The results, presented at The Endocrine Society's 94th Annual Meeting here, suggest an adverse role for a previously described genetic variant, the BclI polymorphism.
"Our findings support the idea that even small variations in hormone receptor sensitivity can have metabolic implications, such as obesity or diabetes," said co-author Bastiaan Havekes, of Maastricht University Medical Center in the Netherlands.
"Endocrinologists should not just focus on hormone levels themselves. Taking into account hormone receptor sensitivity could help in better understanding hormone-mediated effects on metabolism," he said.
The inherited BclI polymorphism occurs in the gene encoding for the glucocorticoid receptor, which controls the actions of glucocorticoids or steroid hormones that affect every system in the body.
According to the researchers, this small variant makes the receptor more sensitive to glucocorticoids, resulting in greater effects with similar hormone levels. The effects of this change seem to be similar to the excessive glucocorticoid exposure that occurs from certain drugs or diseases.
Such excess exposure, which often occurs from long-term use of prednisone or other glucocorticoid medications widely used to treat inflammatory diseases or to suppress the immune system, can cause weight gain, especially in the abdomen, and disturbed blood sugar metabolism.
In the study, the researchers looked at 1,228 adults who participated in one of two Dutch studies focusing on diabetes in the general population. Over half of the participants had either prediabetes or Type 2 diabetes. All subjects underwent genetic testing for the BclI polymorphism.
Those who had the BclI polymorphism on each chromosome had a significantly higher body mass index and larger waist and hip circumferences than did noncarriers or heterozygous carriers, the researchers found. This was reflected by greater insulin resistance, meaning that insulin is less effective at lowering blood glucose, they said.
"Determining one's genetic risk profile for metabolic disease is of great importance to prevent development of cardiovascular diseases," Havekes added.
