Researchers have new insight into the complex interchange that can raise blood levels of unhealthy lipids, or fat, in type 1 diabetes, and early evidence that a drug under study to block cancer cell growth can restore healthier levels.
Too much glucose and fat circulating in the blood – and consequently damaging the vascular system and major organs – help make cardiovascular disease the leading cause of death and disability in people with type 1 diabetes, said Dr. Maritza J. Romero, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University.
“When you have patients with diabetes, you immediately think about the lipid levels in their blood and how these patients will do in terms of their vascular and cardiac function,” said Romero, co-corresponding author of the study in the Proceedings of the National Academy of Sciences.
While insulin therapy is the standard for these patients, cardiovascular problems persist, said Dr. Rudolf Lucas, also an MCG vascular biologist and study co-author. The MCG scientists in collaboration with colleagues at the Veterans Affairs Medical Center in Miami and the Miller School of Medicine at the University of Miami, decided to take aim at a different, destructive target.
Levels of growth hormone, produced by the pituitary, are high in diabetes, which increases insulin resistance and lipid levels, and clearly play a role in the dyslipidemia, or high levels of fat, in the blood, Lucas said. In fact, growth hormone therapy to help normalize a child’s growth has been known to increase the child’s risk of type 2 diabetes. Growth hormone-releasing hormone, or GHRH, which regulates growth hormone production, also is elevated in type 1 diabetes.
The scientists found that by targeting the receptor for GHRH, they could normalize lipid production in diabetes without reducing normal blood levels of growth hormones, which could be problematic in growing children, who are typically the ones diagnosed with type 1 diabetes.
“These findings expand the therapeutic potential of antagonists of GHRH to diabetes, which affects a significant percentage of the world’s population,” said Nobel Laureate Dr. Andrew V. Schally. Schally, a professor of medicine at the University of Miami and co-corresponding author of the new study, co-discovered GHRH in the 1970s and provided the MCG scientists a new peptide he made, MIA-602, that blocks GHRH receptor action.
It’s in the intestines that potentially problematic lipids and cholesterol are taken from the food we eat and transformed into lipoproteins that can travel in the blood and linger if levels get too high. MCG scientists had found increased expression of this GHRH receptor in the small intestines of their rat model of type 1 diabetes. They began to suspect GHRH receptors were a worthy target.