SUMMARY
Adrian Vella, M.D., researches the mechanisms underlying the progression of prediabetes to type 2 diabetes. Individuals with prediabetes are at high risk of progression to diabetes. People with a fasting glucose greater than 110 milligrams per deciliter (mg/dL), which is 6.1 millimoles per liter (mmol/L), to10 mg/dL (0.6 mmol/L) above typical fasting glucose levels have a 40% greater risk of developing diabetes. While this percentage is high, the converse argument is that 60% of these individuals never develop diabetes.
Dr. Vella investigates this difference. Greater understanding will likely provide clues to the pathogenesis of diabetes.
Dr. Vella studies genetic variation associated with type 2 diabetes as a probe to find mechanisms that drive these changes. One mechanism he studies is changes in alpha-cell function, which contribute to hyperglycemia and problems with beta cell function.
Focus areas
Links between TCF7L2 and type 2 diabetes. TCF7L2 is a transcription factor that may modulate signaling pathways necessary to keep blood glucose stable, called blood glucose homeostasis. Research has shown that individuals with the diabetes-associated variants of this gene secrete less insulin during oral glucose tolerance tests.
Dr. Vella works to understand how variation in the TCF7L2 locus affects blood glucose homeostasis in humans with and without problems related to fasting glucose, problems with glucose tolerance or both. He strives to learn how this gene contributes to the development of diabetes.
- Effects of GLP-1 on glucose metabolism. Glucagon-like peptide 1 (GLP-1) is an incretin hormone that powerfully stimulates insulin secretion. Various therapeutic interventions use the hormonal pathway that regulates GLP-1 production to improve blood glucose homeostasis in people with type 2 diabetes. Dr. Vella's research team has recently shown that GLP-1 also is produced in the islet and modulates islet function to improve blood glucose homeostasis.
- Effects of glucagon on glucose metabolism. Dr. Vella and his team have recently shown that alpha cell dysfunction likely explains fasting hyperglycemia. He developed a novel index of alpha cell suppression with glucose to quantitate this dysfunction.
Significance to patient care
A better understanding of the processes that interact to cause the changes present in type 2 diabetes have important implications in terms of preventing and treating the disease. Finding out how genes and the environment interact to affect insulin secretion, insulin action, weight and appetite will help in developing more-rational interventions to prevent and treat type 2 diabetes.
Professional highlights
- Associate editor, Diabetes Care, Obesity, 2021-present.
- Editor, Metabolic Syndrome and Related Disorders, 2017-present.
- Elected, American Society for Clinical Investigation, 2018.
- Associate editor, Diabetes, 2011-2016.
- Earl and Annette R. McDonough Professor of Medicine, Mayo Clinic, 2015.
- Member, Self-Assessment Committee, Endocrine Society, 2009-2014.
- Fellow, Royal College of Physicians of the United Kingdom, 1996-2007.
- Randall Sprague Award for Outstanding Achievement as an Endocrine Fellow, Mayo Clinic, 2001.