Metabolic Factors Predict Changes in Endothelial Function During the Early Course of Type 1 and Type 2 Diabetes

Oana Patricia Zaharia, Martin Schön, Luca Löffler, Klaus Strassburger, Clara Möser, Iryna Yurchenko, Kálmán Bódis, Sofia Antoniou, Yanislava Karusheva, Julia Szendroedi, Volker Burkart, Michael Roden, Oana Patricia Zaharia, Martin Schön, Luca Löffler, Klaus Strassburger, Clara Möser, Iryna Yurchenko, Kálmán Bódis, Sofia Antoniou, Yanislava Karusheva, Julia Szendroedi, Volker Burkart, Michael Roden

Abstract

Context: Endothelial dysfunction may occur early in the development of cardiovascular and metabolic diseases; however, it remains often underestimated and studies rarely discriminate between diabetes types. We have examined endothelial function and its determinants during the early course of type 1 and type 2 diabetes.

Methods: Caucasian participants of the prospective German Diabetes Study (GDS) with known diabetes duration <1 year (n = 398) or without diabetes, but of similar age, body mass index (BMI) and sex distribution (n = 109), underwent measurements of flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD). Whole-body insulin sensitivity (M-value) was assessed by hyperinsulinemic-euglycemic clamps and physical fitness (VO2max) by spiroergometry. A subset of individuals with type 1 or type 2 diabetes (n = 108) was re-evaluated after 5 years.

Results: At baseline, neither FMD nor NMD differed between people with diabetes and the matched glucose-tolerant groups. At the 5-year follow-up, decline in FMD (-13.9%, P = .013) of persons with type 2 diabetes was independent of age, sex, and BMI, but associated with baseline adipose tissue insulin resistance and indices of liver fibrosis. The M-value decreased in both type 1 and type 2 diabetes groups by 24% and 15% (both P < .001, respectively) over 5 years. Higher HbA1c, lower M-value, and lower VO2max at baseline was associated with lower FMD in both type 1 and type 2 diabetes.

Conclusion: Endothelial function decreases during the early course of type 2 diabetes. In addition to age and BMI, insulin sensitivity at diagnosis was the best predictor of progressive impairment in endothelial function in type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01055093.

Keywords: endothelial function; flow-mediated dilatation; insulin resistance; nitroglycerin-mediated dilatation.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Endothelial function of the study population, parameters of endothelial function in patients with newly diagnosed type 1 diabetes (T1D), type 2 diabetes (T2D), and matched glucose-tolerant controls (CON1 and CON2) showing flow-mediated dilation (FMD) (A, C) and nitroglycerin-mediated dilation (NMD) (B, D) at baseline (BL), and at the 5-year follow-up (FU) in a subgroup of patients with type 1 and type 2 diabetes. Scatter plot with mean. *P < .05. #P < .05 adjusted for age, sex, BMI, and baseline value.
Figure 2.
Figure 2.
Baseline characteristics of the study population, physical fitness (A), resting heart rate (B), systolic blood pressure (C), and ankle–brachial index (D), insulin sensitivity (E), beta-cell function (F), indices of liver steatosis (G) and liver fibrosis (H) in patients with newly diagnosed type 1 diabetes (T1D), type 2 diabetes (T2D) and matched glucose-tolerant controls (CON1 and CON2, respectively) at baseline. Scatter plot with mean. *P < .05.
Figure 3.
Figure 3.
Follow-up characteristics of the study population, Physical fitness (A), resting heart rate (B), systolic blood pressure (C), and ankle–brachial index (D), insulin sensitivity (E), beta-cell function (F), indices of liver steatosis (G), and liver fibrosis (H) in patients with type 1 diabetes (T1D), type 2 diabetes (T2D) at baseline (BL) as well as at the 5-year follow-up (FU). Scatter plot with mean. *P < .05. #P < .05 adjusted for age, sex, BMI, and baseline value.

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