A one-week reduced-carbohydrate diet lowers insulin requirements and shifts the IGF axis with no detectable short-term change in endothelial function in a randomized, crossover trial of adults with type 1 diabetes

Background Individuals with type 1 diabetes mellitus (T1DM) must deliver insulin into the peripheral circulation rather than more physiologically into the hepatic portal circulation, leading to a chronic state of underinsulinization in the liver. Previous research suggests that decreased hepatic insulin perturbs the growth hormone-IGF-1 system in these patients. We tested whether short-term carbohydrate restriction, by lowering exogenous insulin requirements and exacerbating hepatic underinsulinization, modifies IGF axis hormones, binding proteins, and vascular function. Methods We performed a secondary analysis of plasma samples collected during a single-blind crossover study of twelve adults with T1DM using automated insulin delivery. In random order, the participants consumed a one-week reduced carbohydrate diet (RCD) and an isocaloric standard carbohydrate diet (SCD), each followed by a study visit. We measured total and free IGF-1 and IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3) after overnight fasting and during the final 30 min of a hyperinsulinemic-euglycemic clamp. We also measured endothelial function using brachial artery flow-mediated dilation (FMD). Results The RCD lowered the total daily insulin dose versus SCD (16% during the week and 24% in the 24 h before testing), with similar glucose levels across diets. Compared with SCD, RCD reduced total IGF-1 and IGFBP-3 and increased IGFBP-1 and IGFBP-2 at baseline. These patterns also persisted during insulin-stimulated conditions. Free IGF-1 was more variable and did not differ significantly between diets. Despite clear shifts in the IGF axis, FMD did not differ between diets and did not correlate with IGF axis markers after either intervention. Conclusions In adults with T1DM studied under nearly matched glycemia, one week of carbohydrate reduction lowered insulin requirements and shifted the IGF axis in a pattern akin to reduced portal insulin exposure, without detectable changes in conduit artery endothelial function. These findings identify the IGF axis as a sensitive physiologic readout of insulin exposure. Longer-term studies are needed to determine whether sustained changes in the IGF axis impact vascular biology or cardiometabolic risk. Trial registration ClinicalTrials.gov NCT04118374.