Rita Basu, M.D.A new study by Rita Basu, M.D., and collaborators, finds that restoring hepatic glycogen improves nocturnal glucose regulation in humans with Type 2 diabetes.
Rita Basu holds the Endowed Professorship in Diabetes Science in the UAB Department of Medicine Division of Endocrinology, Diabetes, and Metabolism and is a senior scientist in the UAB Comprehensive Diabetes Center.
Her research focuses on diurnal and nocturnal regulation of glucose production in humans with Type 2 diabetes (T2D).
The new study, “Role of Hepatic Glycogen on Nocturnal Gluconeogenesis in Type 2 Diabetes Mellitus,” was published in The Journal of Clinical Endocrinology and Metabolism (JCEM).
Gluconeogenesis (GNG) is a metabolic process in the liver that maintains blood sugar levels by producing glucose from non-carbohydrate sources such as lactate, glycerol, and amino acids.
The liver releases stored glucose called hepatic glycogen into the bloodstream overnight to maintain blood sugar levels through a process called nocturnal endogenous glucose production (EGP). Studies have shown higher GNG contributes to higher nocturnal EGP in T2D, leading to early morning hyperglycemia in T2D.
Previous studies using 13C magnetic resonance spectroscopy (MRS) have confirmed lower hepatic glycogen content in subjects with T2D than in subjects without diabetes.
Therefore, researchers hypothesized that increasing post-dinner hepatic glycogen content would restore regulation of GNG in T2D. To test this, they set out to determine the role of glycogen loading (GL) versus non-glycogen loading (NGL) on the contribution of GNG to nocturnal EGP in T2D.
Fourteen subjects with T2D and 15 subjects without diabetes (ND) were studied on two occasions, with GL (60% carbohydrate) versus NGL (40% carbohydrate) isocaloric meals for three days overnight. 13C MRS scans were performed in fed and fasted states to measure hepatic glycogen content.
Rita Basu’s team found that hepatic glycogen content and nocturnal EGP were higher in the GL versus NGL meals in both cohorts. The percent of GNG to EGP averaged ∼50% in subjects without diabetes throughout the night after both meals. In contrast, the percent of GNG to nocturnal EGP in T2D was lower with GL versus NGL and matched the pattern observed in subjects without diabetes with GL lowering overnight rates of GNG in subjects with T2D.
“Our study shows that by restoring liver glycogen stores in people with T2D with a higher carbohydrate meal at dinner, we are able to near normalize the relative contributions of GNG in the overnight state in people with T2D to that observed in healthy people without diabetes,” Rita Basu said. “This is an important finding and advancement as we previously have reported that patients with T2D experience a dysregulation of both nocturnal GNG and glycogenolysis (GGL), with progressive increase in GNG and a proportional decrease in GGL through the night.”
Researchers concluded that selective targeting of GNG at night with appropriate medications could reduce nocturnal and early morning hyperglycemia and hepatic insulin resistance in people with T2D.
Rita Basu commented that approaches looking at different strategies to achieve this (e.g., different carbohydrate compositions or different timing of the meals), as well as therapeutic strategies specifically targeting GNG (e.g., medications such as metformin) may hold the key for the normalization of nocturnal EGP in people with T2D.
Other study authors from the UAB Heersink School of Medicine Department of Medicine Division of Endocrinology, Diabetes and Metabolism are Uma S. Unni, Ph.D., Fernando Bril, M.D., and Ananda Basu, M.D. Other authors are John P. Mugler, III, Ph.D., from the University of Virginia School of Medicine and Rickey E. Carter, Ph.D., from Mayo Clinic. The study was funded by a long-standing NIH grant held by Rita Basu R01 DK 029953-42.