Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction

Sörensen, Ben M; Houben, Alfons J.H.M.; Berendschot, Tos T. J. M.; Schouten, Jan S.A.G.; Kroon, Abraham A.; Kallen, Carla; Henry, Ronald M.A.; Koster, Annemarie; Sep, Simone J. S.; Dagnelie, Pieter C.; Schaper, Nicolaas C.; Schram, Miranda T.; Stehouwer, Coen D. A.

doi:10.1161/circulationaha.116.023446

Cited by 202 publications

(187 citation statements)

References 44 publications

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“…Consistently, in this study with relative large sample size, we did not observe significant difference in baseline ACh or NaNP between patients with normoalbuminuria and microalbuminuria in cross‐sectional analysis, supporting that endothelial function maybe already impaired in patients with T2DM even at early stage of nephropathy (ie, normoalbuminuria) . In Maastricht study, compared with healthy subjects, there is significantly impaired microvascular function in prediabetes and T2DM, further supporting the concept that microvascular dysfunction may occur in T2DM or even prediabetes and thus may contribute to its complications . The stratified analysis by albuminuria revealed that the longitudinal association exists only in patients with baseline normoalbuminuria.…”

Section: Discussionsupporting

confidence: 84%

Microvascular endothelial function is an independent predictor for albuminuria progression among Asians with type 2 diabetes—A prospective cohort study

et al. 2018

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Section: Discussionsupporting

confidence: 84%

Microvascular endothelial function is an independent predictor for albuminuria progression among Asians with type 2 diabetes—A prospective cohort study

et al. 2018

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“…It is reasonable to hypothesize that the metabolic process causing microvascular dysfunction would not be limited to the renal vasculature but affect other sensitive vascular beds including the heart. This concept has been recently demonstrated in other organs with microvascular disease such as retina and skin [41]. …”

Section: Discussionmentioning

confidence: 99%

Sex difference in the risk for exercise-induced albuminuria correlates with hemoglobin A1C and abnormal exercise ECG test findings

Brzezinski

Etz-Hadar

Grupper

et al. 2017

Cardiovasc Diabetol

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BackgroundAlbuminuria is an established marker for endothelial dysfunction and cardiovascular risk in diabetes and prediabetes. Exercise induced albuminuria (EiA) appears earlier and may be a more sensitive biomarker for renal endothelial damage. We sought to examine the association between EiA, parameters of the metabolic syndrome, A1C levels, exercise ECG test results and sex related differences in a large cohort of healthy, pre-diabetic and diabetic subjects.MethodsA total of 3029 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 46 years, 73% men) were analyzed. Multiple physiologic and metabolic parameters including A1C were collected and albuminuria was measured in all subjects before and immediately after completing an exercise ECG test.ResultsExercise increased urinary albumin to creatinine ratio (ΔEiA) by 2.8 (0–13.6) mg/g for median (IQR) compared to rest albuminuria (p < 0.001). An increase in ΔEiA was observed with accumulating parameters of the metabolic syndrome. ΔEiA showed significant interaction with sex and A1C levels; i.e. women with A1C > 6.5% had an increased risk of higher ΔEiA (p < 0.001). Using a cutoff of ΔEiA > 13 mg/g (top quartile) we found that women with ΔEiA > 13 mg/g were at greater risk for abnormal exercise ECG findings, (OR = 2.7, p = 0.001).ConclusionExercise promotes excessive urinary albumin excretion in dysmetabolic patients. In women, a significant correlation exists between ΔEiA and A1C levels. A cutoff of ΔEiA > 13 mg/g in women may be used to identify populations at risk for abnormal exercise ECG test findings and perhaps increased cardiovascular risk. Future studies will be needed to further validate the usefulness of ΔEiA as a biomarker for cardiovascular risk in women with and without diabetes.

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“…The human cutaneous circulation is a validated model to assess mechanisms underlying microvascular dysfunction 17, 18 , as the pathogenesis of hypertension-associated microvascular dysfunction occurs simultaneously in multiple vascular beds 17, 19, 20 . We hypothesized that CSE and 3-MPST expression, as well as endogenous production of H 2 S, would be reduced in HTN compared to normotensive (NTN) adults.…”

Section: Introductionmentioning

confidence: 99%

Impaired Hydrogen Sulfide–Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults

et al. 2017

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Reductions in hydrogen sulfide (H2S) production have been implicated in the pathogenesis of vascular dysfunction in animal models of hypertension; however, no studies have examined a functional role for H2S contributing to microvascular dysfunction in hypertensive (HTN) adults. We hypothesized that endogenous production of H2S would be reduced, impaired endothelium-dependent vasodilation would be mediated by reductions in H2S-dependent vasodilation, and vascular responsiveness to exogenous H2S (Na2S) would be attenuated in HTN compared to normotensive (NTN) adults. Fifteen NTN [51±2 yrs; blood pressure (BP) 116±3/76±3 mmHg] and 14 HTN adults (57±2 yrs; BP 140±3/89±2 mmHg) participated. H2S biosynthetic enzyme expression (Western blot) and substrate-dependent H2S production (amperometric probe) were measured in cutaneous tissue homogenates. Red cell flux (laser Doppler flowmetry) was measured during graded perfusions of acetylcholine (ACh; 10−6 –10−1 mol∙L−1) and Na2S (10−5–101 mol∙L−1) using intradermal microdialysis; the functional role of H2S was determined using pharmacological inhibition with aminooxyacetic acid (AOAA; 0.5 mmol∙L−1). H2S biosynthetic enzyme expression and substrate-dependent H2S production were reduced in HTN adults (all p<0.05). ACh-induced endothelium-dependent vasodilation was blunted in HTN compared to NTN adults (p=0.012). AOAA attenuated ACh-induced vasodilation in NTN adults (ACh: 1.31±0.13 vs. ACh+AOAA: 1.07±0.09 flux∙mmHg−1; P=0.025) but had no effect on vasodilation in HTN adults (ACh: 1.16±0.10 v. ACh+AOAA: 1.37±0.11 flux∙mmHg−1; p=0.47). Na2S-induced vasodilation was not different between groups. Collectively, these findings indicate that while the microvasculature maintains the ability to vasodilate in response to exogenous H2S, reductions in endogenous synthesis and H2S-dependent vasodilation contribute to endothelial dysfunction in human hypertension.

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Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction

Cited by 202 publications

References 44 publications

Microvascular endothelial function is an independent predictor for albuminuria progression among Asians with type 2 diabetes—A prospective cohort study

Microvascular endothelial function is an independent predictor for albuminuria progression among Asians with type 2 diabetes—A prospective cohort study

Sex difference in the risk for exercise-induced albuminuria correlates with hemoglobin A1C and abnormal exercise ECG test findings

Impaired Hydrogen Sulfide–Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults

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