Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer

Abstract

BackgroundNormotensive non-diabetic relatives of type 1 diabetes (T1D) patients have an abnormal blood pressure response to exercise testing that is associated with indices of metabolic syndrome and increased oxidative stress. The primary aim of this study was to investigate the circadian variability of blood pressure and the ambulatory arterial stiffness index (AASI) in healthy siblings of T1D patients vs healthy control subjects who had no first-degree relative with T1D. Secondary aims of the study were to explore the influence of both cardiovascular autonomic function and erythrocyte electron transfer activity as oxidative marker on the ambulatory blood pressure profile.MethodsTwenty-four hour ambulatory blood pressure monitoring (ABPM) was undertaken in 25 controls, 20 T1D patients and 20 siblings. In addition to laboratory examination (including homeostasis model assessment of insulin sensitivity) and clinical testing of autonomic function, we measured the rate of oxidant-induced erythrocyte electron transfer to extracellular ferricyanide (RBC vfcy).ResultsSystolic blood pressure (SBP) midline-estimating statistic of rhythm and pulse pressure were higher in T1D patients and correlated positively with diabetes duration and RBC vfcy; autonomic dysfunction was associated with diastolic BP ecphasia and increased AASI. Siblings had higher BMI, lower insulin sensitivity, larger SBP amplitude, and higher AASI than controls. Daytime SBP was positively, independently associated with BMI and RBC vfcy. Among non-diabetic people, there was a significant correlation between AASI and fasting plasma glucose.ConclusionsSiblings of T1D patients exhibited a cluster of sub-clinical metabolic abnormalities associated with consensual perturbations in BP variability. Moreover, our findings support, in a clinical setting, the proposed role of transplasma membrane electron transport systems in vascular pathobiology.

Circadian Rhythm of Blood Pressure in Diabetes Mellitus: Evidence, Mechanisms and Implications

“…DNA binding activities of clock-like gene products NAPS2:Bmal1 and CLOCK:Bmal1 are sensitive to the redox state of the cell [66]; equally sirtuin 1 (SIRT1) activity that regulates the amplitude and the duration of circadian gene expression depends on NAD ratio [67]. In a clinical setting, we themselves observed in type 1 diabetes families a relationship between daytime SBP and erythrocyte transplasma membrane electron transport activity that is in turn highly correlated with the intracellular balance of the NADH/NAD redox pair [50]. Delezie and Challet have recently reviewed the literature showing that metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels; they highlighted the role of nutrient sensors NAD(H), NADP(H), SIRT1, and AMPactivated protein kinase in ensuring the fine tuning of metabolic and clock regulations [68].…”

“…Chronobiologically interpreted 7-day ABPM uncovered MESOR-hypertension and circadian hyper-amplitude-tension in subjects with prediabetes [49]. Twenty-four hour ABPM in type 1 diabetes families evidenced: a) SBP MESOR and pulse pressure were higher in patients with type 1 diabetes; b) DBP acrophase was 3 hours earlier in the diabetic than in normal subjects and DBP ecphasia was more pronounced in patients with lower HR variability during deep breathing; c) non-diabetic siblings of patients with type 1 diabetes showed signs of reduced insulin sensitivity, larger circadian amplitude of SBP and higher ambulatory arterial stiffness index [50]. An analogous relationship was previously observed between SBP ecphasia and reduced HR variability in subjects with type 2 diabetes [51].…”

“…If prediabetes is associated with abnormal circadian BP variability [49][50], short-term misalignment between behavioural cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles had adverse cardiometabolic implications in adult humans: systematic increase in postprandial glucose and insulin, increase in mean arterial pressure, decrease in leptin and reduced sleep efficiency [52]. Thus, intricate relationships exist between energy homeostasis and circadian BP rhythm.…”

“…Few researches have evaluated abnormalities in BP or HR circadian patterns in diabetes mellitus using cosinor approach [22,44,[49][50]. Chronobiologically interpreted 7-day ABPM uncovered MESOR-hypertension and circadian hyper-amplitude-tension in subjects with prediabetes [49].…”

Exploring Leukocyte Mitochondrial Membrane Potential in Type 1 Diabetes Families

“…In a recent investigation on the circadian variability of blood pressure in T1D families, we have extensively discussed the metabolic derangement that has been documented in non-diabetic siblings of T1D patients. The combination of higher mean FPG, lower HOMA-IS, and lower HbA1c levels suggested that siblings with isolated IFG (thus impaired basal glucose clearance rate) may also have lower postprandial glycemia values (due to enhanced insulin-stimulated muscle glucose disposal) [19].…”