1951-P: Glucose Effectiveness Fails to Compensate for Insulin Resistance after Fat Feeding in Dogs

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: ADER, MARILYN, KOLKA, CATHRYN M., BERGMAN, RICHARD N.
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2020
• Subjects: Body weight gain; Diabetes; Feeding; Glucose; Glucose tolerance; High fat diet; Homeostasis; Hyperglycemia; Hyperinsulinemia; Insulin; Insulin resistance; Intravenous administration; Obesity; Somatostatin
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-1951-P

Glucose homeostasis involves actions of both insulin and glucose per se (“glucose effectiveness, SG”). While consumption of a high fat diet typically induces insulin resistance, it is unclear whether SG is altered by fat feeding. We quantified SG from the intravenous glucose tolerance test (IVGTT; n=36) or hyperglycemic clamp at basal insulin (HGC; n=5) in dogs, tested before and after 6 weeks fat feeding (+ 6 g/kg per day). SG from IVGTTs were quantified by minimal model (SG-MINMOD). In HGCs, glucose was sequentially raised to 125, 180, and 250 mg/dl during somatostatin (SRIF) and basal insulin replacement; SG-HGC was calculated as the slope of steady state glucose infusion rate and plasma glucose. Insulin sensitivity (SI) was calculated from IVGTTs and from euglycemic clamps. Fat feeding induced weight gain (28.8±0.4 to 31.2±2.5 kg; p<0.0001) and insulin resistance at both liver (p<0.0001) and periphery (p<0.0001). SG-MINMOD was reduced after fat feeding (0.036±0.002 vs. 0.041±0.002 min-1; p<0.001). The direct measure of SG from HGCs at basal insulin (SG-HGC) suggest similar diet-induced reduction (21%), although sample size was diminished due to SRIF breakthrough and resulting hyperinsulinemia in 2 animals. After fat feeding, there was no increase in glucose effectiveness that may be expected as compensation for diet-induced insulin resistance. Rather, glucose effectiveness decreased. These data indicate that obesity results in diminished actions of both insulin and glucose per se on glucose homeostasis. Disclosure M. Ader: None. C.M. Kolka: Research Support; Self; AstraZeneca. R.N. Bergman: None. Funding National Institutes of Health (DK29867, DK27619)