Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study

Area of Science:

• Vascular biology and metabolic disease research.

Background:

• Type 2 diabetes (T2DM) significantly increases cardiovascular disease (CVD) risk, partly due to large-artery dysfunction present even in prediabetes.
• The presence and severity of microvascular dysfunction in prediabetes and T2DM remain unclear.

Purpose of the Study:

• To investigate microvascular function in individuals with normal glucose metabolism, prediabetes, and T2DM.
• To determine if microvascular dysfunction is present in prediabetes and worsens in T2DM, supporting the 'ticking clock hypothesis' for microvasculature.

Main Methods:

• The Maastricht Study, a cohort of 2213 participants (51% men, aged ~60 years) with enriched T2DM prevalence, assessed microvascular function.
• Measurements included flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia, alongside glucose metabolism status via oral glucose tolerance test.
• Multivariable regression analyses adjusted for numerous clinical and demographic factors were employed.

Main Results:

• Retinal arteriolar dilation was reduced in prediabetes (3.0±2.7%) and further impaired in T2DM (2.3±2.6%) compared to normal glucose metabolism (3.4±2.8%), with a significant trend (P=0.001).
• Skin hyperemia also showed a progressive decline: normal (1235±810), prediabetes (1109±748), and T2DM (937±683), with a significant trend (P=0.001).
• Higher HbA1c and fasting plasma glucose levels were independently associated with reduced retinal arteriolar dilation and skin hyperemia.

Conclusions:

• Prediabetes and T2DM are independently linked to impaired microvascular function in both the retina and skin.
• These findings suggest microvascular dysfunction precedes T2DM-related CVD and other complications, potentially originating from microvascular issues.