# Parameters of Micro- and Macrocirculation in Young Uncomplicated Type 1 Diabetic Patients—The Role of Metabolic Memory

## TL;DR

This study examines how early poor blood sugar control affects blood vessel health in young type 1 diabetes patients, finding that disease duration, not early control, mainly influences early microvascular changes.

## Contribution

The study reveals that disease duration, not metabolic memory, is the key factor in early microvascular changes in young type 1 diabetes patients.

## Key findings

- Micro- and macrovascular parameters were similar between groups with different metabolic memory levels.
- Shorter disease duration was linked to higher capillary density and lower AGE levels.
- Shorter duration groups showed better inflammatory profiles, including lower TNF-α/IL-35 ratios and higher IL-35, IL-4, and IL-12 levels.

## Abstract

In the current study, we focus on analyzing the relationship between changes in micro- and macrocirculation and different stages of metabolic memory. We hypothesized that early poor glycemic control induces lasting endothelial changes detectable in pediatric type 1 diabetes (T1D) microcirculation. We assessed microcirculation structure and function using capillaroscopy, transcutaneous oxygen pressure (TcPO2), and optical coherence tomography (OCT). We evaluated macrovascular circulation using pulsatility index (PI), ankle-brachial index (ABI) and pulse pressure (PP). We also examined the relationship between circulation parameters, the age at onset, and diabetes duration. The study included 67 patients with uncomplicated type 1. We divided all patients into four groups based on their HbA1c levels at T1D onset and their average HbA1c after one and two years. We assessed the concentrations of TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, serum angiogenin, VEGF, sVCAM-1, ICAM-1, sP-Selectin, AGEs, and sRAGE. We compared subgroups with different levels of metabolic memory but comparable T1D duration and age at diagnosis. Micro- and macrovascular parameters were similar between the groups. Our comparison of subgroups with identical metabolic memory but different durations and ages at diagnosis revealed clear differences. The subgroup with a shorter T1D duration showed higher capillary density and a smaller inter-capillary distance compared to those with a longer diabetes duration. This subgroup with shorter duration had significantly lower AGE levels and a reduced TNF-α/IL-35 ratio, along with higher levels of IL-35, IL-4, and IL-12, compared to the longer-duration group. Our findings indicate that in youths with uncomplicated T1D, disease duration—not metabolic memory—plays a dominant role in early microvascular alterations.