# 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

## TL;DR

A one-week low-carb diet in people with type 1 diabetes reduced insulin needs and changed hormone levels related to growth and metabolism, but did not affect blood vessel function.

## Contribution

A one-week reduced-carb diet reduced insulin doses by 16% without worsening glycemia.

## Key findings

- The reduced-carb diet lowered insulin requirements and shifted IGF axis hormones and binding proteins.
- Endothelial function, measured by FMD, did not differ between the reduced-carb and standard-carb diets.
- Free IGF-1 levels were more variable and did not significantly differ between the diets.

## Abstract

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.

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).

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.

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.

ClinicalTrials.gov NCT04118374.

The online version contains supplementary material available at 10.1186/s40842-026-00276-6.

What is currently known about this topic? • Peripheral insulin delivery underinsulinizes the liver in type 1 diabetes (T1DM). • Decreased liver insulin alters GH-IGF-1 signaling. • IGF axis abnormalities may contribute to vascular risk in T1DM.

What is the key research question? • Does lowering insulin using a reduced carb diet modify the IGF axis and vascular risk in T1DM?

What is new? • A one-week reduced carb diet reduced insulin doses by 16% without worsening glycemia.• After the reduced carb diet, IGF-1 and IGFBP-3 decreased; IGFBP-1 and IGFBP-2 increased. • Endothelial function was similar between reduced and standard carb diets in this crossover study.

How might this study influence clinical practice? • Diet-driven insulin reduction shifts the IGF axis; clinical impact needs further characterization.

The online version contains supplementary material available at 10.1186/s40842-026-00276-6.