The impact of prediabetes and diabetes on endothelial function in a large population-based cohort

Abstract

Background

Diabetes and prediabetes are well-recognized risk factors for cardiovascular disease (CVD) and are marked by vascular endothelial dysfunction (ED). However, there is a scarcity of thorough population-based studies examining ED in individuals with diabetes/prediabetes free from manifest CVD. Here, we examined the association between ED assessed by reactive hyperaemia index (RHI) in the finger and diabetes/prediabetes in a large middle-aged population cohort.

Methods

Within the Malmö Offspring Study, following the exclusion of participants <30 years and participants with prevalent CVD, 1384 participants had complete data on all covariates. The RHI was calculated using pulse amplitude tonometry. ED was defined as RHI < 1.67. Multivariable logistic and linear regression models were conducted to investigate associations between ED and RHI with diabetes and prediabetes.

Results

The study population had a mean age of 53.6 ± 7.6 years (53% women). In study participants with manifest diabetes (n = 121) and prediabetes (n = 514), ED was present in 42% and 25% respectively, compared to 23% in those with normal glucometabolic status. In multivariable logistic regression analyses, prevalent diabetes was significantly associated with ED (OR 1.95; 95%CI 1.57-3.39; p = 0.002), as well as with lower RHI (β-coeff. -0.087; p = 0.002). However, prediabetes showed no association with neither ED nor RHI.

Conclusion

In a population free from CVD, vascular endothelial dysfunction was primarily associated with manifest diabetes, but not with prediabetes, implying that finger ED may develop when diabetes is established, rather than being an early sign of glucose intolerance. Further research is needed to explore whether addressing glucose intolerance could potentially delay or prevent vascular ED onset.

Plain language summary

What is the context?

Diabetes and prediabetes are known to increase the risk of cardiovascular disease (CVD) through a condition called vascular endothelial dysfunction (ED). However, there is a lack of comprehensive studies on ED in individuals with diabetes/prediabetes who do not already have CVD. In this study, we investigated the association between ED, assessed using the reactive hyperaemia index (RHI) in a finger, and diabetes/prediabetes in a large group of middle-aged individuals.

What is new?

We conducted this study within the Malmö Offspring Study, involving 1384 participants who were over 30 years old and did not have pre-existing CVD. The average age of the participants was 53 years, with 53% being women. Among those with diagnosed diabetes (121 individuals) and prediabetes (5141 individuals), 42% and 25% respectively showed signs of ED, compared to 23% in those with normal glucose metabolism. In our analyses, we found that established diabetes was significantly associated with ED, as well as with lower finger RHI values. However, prediabetes did not show any significant association with either ED or RHI.

What is the impact? In a healthy population without pre-existing CVD, vascular endothelial dysfunction was predominantly linked to diagnosed diabetes, rather than prediabetes. This suggests that ED may develop once diabetes is established, rather than being an early indicator of glucose intolerance. Further research is necessary to investigate whether addressing glucose intolerance could potentially delay or prevent the onset of vascular ED.

Keywords:

• Cardiovascular disease
• Diabetes
• Endothelial dysfunction
• Prediabetes
• Reactive hyperaemia index

Declaration of Interests Statement

The authors have no conflicting interests to report.

Data availability statement

The dataset for this manuscript cannot be made publicly available because of ethical and legal restrictions. Requests to access the dataset should be directed to the Chair of the Steering Committee for the Malmö cohorts, see instructions at https://www.malmo-kohorter.lu.se/english.

Additional information

Funding

Hjärt-Lungfonden; Hulda och E Conrad Mossfelts Stiftelse för Vetenskaplig Forskning Inom Hjärt- och Kärlsjukdomarnas Område; Region Skåne; Vetenskapsrådet; The Malmö Offspring Study (MOS) has been funded by the Research Council of Sweden (Grant 521-2013-2756), the Heart and Lung Foundation (Grant 20150427), and by funds obtained from the local Region Skane County Council (ALF) to PM Nilsson. In addition, funding has been obtained from Ernhold Lundströms Stiftelse, donations to the Skane University Hospital, a research grant from Oral Health Related Research by Region Skane to Malmo University, Faculty of Odontology, Periodontal Department, and the European Research Council. Amra Jujic received funding from Hulda and E Conrad Mossfelt foundation.