Reduced microvascular reactivity in patients with diabetic neuropathy

Author(s):  
K.A. Krasulina ◽  
P.A. Glazkova ◽  
A.A. Glazkov ◽  
D.A. Kulikov ◽  
D.A. Rogatkin ◽  
...  

BACKGROUND: Neurogenic regulation is involved in the development of microcirculation response to local heating. We suggest that microvascular reactivity can be used to estimate the severity of diabetic polyneuropathy (DPN). OBJECTIVE: To evaluate the prospects for using the parameters of skin microvascular reactivity to determine the severity of DPN. METHODS: 26 patients with diabetes mellitus were included in the study (patients with retinopathy (n = 15), and without retinopathy (n = 11)). The severity of DPN was assessed using Michigan Neuropathy Screening Instrument (MNSI) and Norfolk QOL-DN (NQOLDN). Skin microcirculation was measured by laser Doppler flowmetry with local heating test. RESULTS: There were revealed moderate negative correlations between microvascular reactivity and the severity of DPN (for MNSI (Rs = –0.430), for NQOLDN (Rs = –0.396)). In patients with retinopathy, correlations were stronger than in the general group (for MNSI (Rs = –0.770) and NQOLDN (Rs = –0.636)). No such correlations were found in patients without retinopathy. CONCLUSION: Correlation of the microvascular reactivity and DPN was revealed in patients with registered structural disorders in microvessels (retinopathy). The lack of such correlation in patients without retinopathy may be explained by the intact compensatory mechanisms of microvessels without severe disorders.

Author(s):  
P. A. Glazkova ◽  
S. A. Terpigorev ◽  
D. A. Kulikov ◽  
N. A. Ivanova ◽  
A. A. Glazkov

Background.Hypertension (HTN) is associated with impaired skin microcirculation. Laser Doppler flowmetry is an objective, quantitative, instrumental method that allows evaluating skin microcirculation. However, the method was not widely used clinically due to high variability of perfusion and small difference between healthy people and HTN patients and, as a consequence, low diagnostic signifcance.Objective.To provide the grounds for the approaches increasing the informative value of skin microcirculation measurement by laser Doppler flowmetry in HTN patients.Design and methods.The study involved HTN patients (n = 13, the median age was 60 (49; 63) years) and young otherwise healthy volunteers without HTN (n = 12, the median age 26 (25; 27) years). Microcirculation measurement was performed by laser Doppler flowmetry using LAKK-02 device. Registration of microcirculation on the forearm skin was carried out during the occlusionheating test. The Mann-Whitney test was used to compare the parameters in two groups. The diagnostic accuracy of the method for the inverse classifcation of the subjects was evaluated using ROC analysis.Results.In HTN patients, the median baseline perfusion was 3,1 (1,84; 4,31) perfusion units (PU), in healthy volunteers — 4,29 (3,66; 8,14) PU (p = 0,04). The median area under the microcirculation curve for the frst 2 minutes of heating in HTN patients was 1206,7 (813; 1449) PU × s, in healthy volunteers — 1552,3 (1310; 1624) PU × s (p = 0,035). In healthy volunteers, the heating increased the perfusion by 596 % (386%; 878%), and in HTN patients perfusion increased only by 265% (180 %; 318%) (p = 0,01). The relative increase in perfusion during postocclusion hyperemia with continued heating compared with the baseline in healthy volunteers was 651% (493 %; 999%), and in HTN patients — 302 % (182 %; 436%) (p = 0,005). Thus, when comparing the average parameters for each period in the occlusion-heating test, only basic perfusion showed signifcant differences. However, when changed from absolute to relative parameters (the increase in microcirculation in relation to the vasodilating effects), the difference was signifcant. Moreover, sensitivity achieved was 75 % and specifcity — 84,6% (the inverse classifcation of groups).Conclusions.The physiological (the local heating of the forearm skin at a rate of 2 degrees Celsius per second, a combination of vasodilating effects) and mathematical (the transition from absolute to relative values) approaches provided an increase of the informative value of the laser Doppler flowmetry, as well as its sensitivity and specifcity.


Author(s):  
П.А. Глазкова ◽  
К.А. Красулина ◽  
А.А. Глазков ◽  
Д.А. Куликов ◽  
В.Е. Логина ◽  
...  

Известно, что с возрастом и при ряде хронических заболеваний происходит снижение реактивности микроциркуляторного звена кровообращения. Целью данного исследования стала оценка взаимосвязи параметров кожной микроциркуляции с биологическим и хронологическим возрастом у пациентов с сахарным диабетом. В исследование были включены 11 человек с сахарным диабетом [медиана возраста 57 (51; 64) лет]; биологический возраст определяли с помощью калькулятора Aging.AI. Показатели кожной микроциркуляции оценивали с помощью метода лазерной допплеровской флоуметрии в ходе окклюзионно-теплового теста. Для анализа взаимосвязи количественных параметров рассчитывали коэффициенты ранговой корреляции Спирмена. Были выявлены значимые множественные отрицательные корреляции биологического возраста с показателями реактивности микрососудов как при тепловом, так и при окклюзионном воздействии (сила корреляций от -0,618 до -0,97, p<0,05). У лиц с сахарным диабетом снижение реактивности микрососудов в большей мере ассоциировано с биологическим возрастом, чем с хронологическим. It has been established that the age together with the number of chronic diseases cause the decrease of the reactivity of the microcirculatory bed. This study aims to evaluate the relationship between cutaneous microcirculation parameters and biological and chronological age of patients with diabetes mellitus. 11 diabetic patients (median age 57 (51; 64) years) were examined in course of this study; biological age was figured by Aging.AI calculator. Cutaneous microcirculation parameters were measured by laser Doppler flowmetry with an occlusion-heating test. Spearman’s rank correlation coefficients were calculated to analyze the relationships between quantitative parameters. Significant multiple negative correlations of biological age and microvascular reactivity indices on exposure to both heat and occlusion (correlation strength from -0,618, to -0,97, p<0,05) were found. Diabetic patients have decreased microvascular reactivity that is more associated with biological age than with chronological age.


2021 ◽  
pp. 5-5
Author(s):  
Vesna Grbovic ◽  
Svetlana Djukic ◽  
Srdjan Stefanovic ◽  
Natasa Zdravkovic-Petrovic ◽  
Stefan Simovic ◽  
...  

Introduction: Diabetic polyneuropathy is a common chronic complication in patients with diabetes mellitus. This study aimed to determine the importance of applied physical procedures on the functional status in diabetic polyneuropathy patients in comparison to the group of respondents with the applied alpha-lipoic acid. Materials and Methods: 60 subjects were divided into two groups: group A - diabetic polyneuropathy patient?s treatment with physical procedures; and group B - diabetic polyneuropathy patient?s treatment with alpha-lipoic acid. The study protocol implied that the study has lasted for three diagnostic and therapeutic cycles, each lasting for 16 days with the time between cycles of 6 weeks. Results: Manual muscle test, range of motion, Michigan Neuropathy Screening Instrument and Berg balance scale values showed statistically significant improvement at the end of testing the group A respondents, while in the group B respondents there was not any improvement shown. Conclusions: The application of the combined physical procedures shows clear benefit for improvement of muscle strength and mobility of the ankle joint in respondents with diabetic polyneuropathy.


2015 ◽  
Vol 14 (3) ◽  
pp. 27-33 ◽  
Author(s):  
N. A. Zubareva ◽  
S. Y. Podtaev ◽  
A. A. Parshakov

Introduction and purpose. The aim of investigation was to evaluate the possibility of using the method of wavelet analysis of skin temperature during the local heating test for the study of the microvascular tone regulation in patients with diabetic foot syndrome (DFS). Materials and methods. The study was performed in 15 healthy subjects and 10 patients with neuro-ischemic form of DFS complicated by trophic ulcers. The temperature of the plantar surface of the hallux was recorded by «Microtest» (Perm, Russia) with temperature resolution 0,002°C. Time-frequency analysis of temperature fluctuations was performed using wavelet analysis. For the reconstruction of the oscillations in endothelial (0.02-0.0095 Hz), neurogenic (0.05-0.02 Hz) and myogenic (0.05-0.14 Hz) frequency ranges we used inverse wavelet transform. Results. In healthy people, indexes of vasodilation (relative changes in the oscillation amplitudes) in the myogenic, neurogenic, and endothelial frequency ranges were 3.04, 4.01 and 2.25 respectively. In patients with DFS the values were significantly lower than in healthy subjects (0.60, 0.67 and 0.51, respectively). Conclusion. In contrast to healthy subjects, the combination of diabetic polyneuropathy with endothelial dysfunction and macroangiopathy in patients with neuro-ischemic form of DFS leads to the progression of mutually aggravating pathological processes and lower limb ischemia. Further implementation of the local heating test at the early stages of diabetic foot is of interest for the prognosis of the disease, evaluating the effectiveness of conservative treatment and endovascular interventions.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Katherine Haigh ◽  
Ronald F Feinberg ◽  
Hugh S Taylor ◽  
Megan M Wenner

Our laboratory has recently demonstrated that a loss of endothelin-B (ETB) receptor mediated dilation contributes to impaired vasodilatory function in postmenopausal women. It is unclear if these changes are due to aging, or alterations in ovarian hormones that occur after menopause. The purpose of this study was to test the hypothesis that in a low estradiol state, there is a loss of ETB mediated dilation, and that estradiol administration reverses these responses and mediates dilation. Methods: We tested 8 young women (YW: 24±2 years, 23±1 kg/m 2 , mean arterial BP 84±2mHg) and 6 postmenopausal women (PMW: 56±1 years, 24±1 kg/m 2 , mean arterial BP 94±2mHg). In YW, we suppressed endogenous ovarian hormone production with daily gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) administration for 10 days, adding estradiol (E2, 0.1 mg/day, Vivelle dot patch) on days 4-10. PMW were tested at baseline and after 1-week E2 administration (0.1 mg/day, Vivelle dot patch). We measured nitric-oxide mediated vasodilation in the cutaneous circulation during local heating (42°C) via laser Doppler flowmetry, followed by microdialysis perfusions of sodium nitroprusside (28mM) with local heating to 43°C to elicit maximal dilation. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial blood pressure, and expressed as a percent of maximal dilation. Results: ETB receptor blockade increased vasodilation in YW during hormone suppression with GnRHant (control: 88±3 vs. BQ-788: 94±2 CVC %max, P <0.05). However, ETB receptor blockaded tended to reduce vaodilation during E2 administration (control: 88±3 vs. BQ-788: 82±2 CVC %max, P =0.12). In PMW, ETB receptor blockade had no significant effect on vasodilatory responses (control: 90±4 vs. BQ-788: 95±2 CVC %max, P =0.20). Similarly, ETB receptor blockade did not alter vasodilation after E2 administration (control: 88±7 vs. BQ-788: 88±4 CVC %max). Conclusions: These preliminary data suggest that suppression of endogenous ovarian hormone production alters ETB receptor responses in young women, which is partially mediated by E2. Additional data are needed to determine ETB receptor sensitivity to E2 after menopause.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Jordan C Patik ◽  
Joseph M Stock ◽  
Nathan T Romberger ◽  
Shannon L Lennon ◽  
William B Farquhar ◽  
...  

Impaired vascular function likely contributes to the association between dietary sodium intake and the development of cardiovascular disease. Using the cutaneous microvasculature as a model, we have previously shown that a high sodium (HS) diet blunts local heating-induced vasodilation in normotensive individuals with salt resistant (SR) blood pressure (BP). However, the effect of a HS diet on the cutaneous microvasculature in normotensive salt sensitive (SS) individuals remains unclear. Therefore, we tested the hypothesis that cutaneous microvascular function is reduced by a HS diet to a greater degree in SS compared to SR individuals. After each 7-day controlled feeding diet (low sodium (LS) = 20 mmol/day; HS = 300 mmol/day), an intradermal microdialysis fiber was inserted in the ventral forearm and perfused with Ringer’s solution. Skin blood flow (SkBF) was continuously monitored via laser Doppler flowmetry and a local heating unit was placed over the fiber and heated to 42°C until SkBF reached a stable plateau. Site-specific maximal SkBF was determined by perfusing 28mM sodium nitroprusside and heating to 43°C. Mean arterial pressure (MAP) was assessed at regular intervals on the contralateral arm and was used to calculate cutaneous vascular conductance (CVC = SkBF / MAP). Subjects wore a 24-hr ambulatory BP monitor and collected their urine on the final day of each diet. Fourteen subjects (9W / 5M, 42 ± 14 yr) whose MAP increased >5 mmHg (Δ8 ± 1 mmHg) on the HS diet were defined as SS and were compared to 14 age- (43± 14 yr) and sex-matched SR subjects (Δ1 ± 3 mmHg). SS and SR had similar MAP at baseline (88 ± 9 vs. 90 ± 8 mmHg, P = 0.88) and urinary sodium excretion was increased similarly across groups by the HS diet (Δ239 ± 104 vs. Δ220 ± 66 mmol / 24 hr, P = 0.20). Cutaneous vasodilation in response to local heating was decreased on the HS diet relative to the LS diet in both SS (Δ-9 ± 9 %CVCmax, P = 0.005) and SR (Δ-9 ± 9 %CVCmax, P=0.005); however, there was not a group x diet interaction (P = 0.99). In contrast to our hypothesis, these results suggest that the deleterious effects of high sodium diets on cutaneous microvascular function are similar in normotensive salt sensitive and salt resistant individuals.


2006 ◽  
Vol 100 (2) ◽  
pp. 535-540 ◽  
Author(s):  
Brett J. Wong ◽  
Sarah J. Williams ◽  
Christopher T. Minson

The precise mechanism(s) underlying the thermal hyperemic response to local heating of human skin are not fully understood. The purpose of this study was to investigate a potential role for H1 and H2 histamine-receptor activation in this response. Two groups of six subjects participated in two separate protocols and were instrumented with three microdialysis fibers on the ventral forearm. In both protocols, sites were randomly assigned to receive one of three treatments. In protocol 1, sites received 1) 500 μM pyrilamine maleate (H1-receptor antagonist), 2) 10 mM l-NAME to inhibit nitric oxide synthase, and 3) 500 μM pyrilamine with 10 mM NG-nitro-l-arginine methyl ester (l-NAME). In protocol 2, sites received 1) 2 mM cimetidine (H2 antagonist), 2) 10 mM l-NAME, and 3) 2 mM cimetidine with 10 mM l-NAME. A fourth site served as a control site (no microdialysis fiber). Skin sites were locally heated from a baseline of 33 to 42°C at a rate of 0.5°C/5 s, and skin blood flow was monitored using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated as LDF/mean arterial pressure. To normalize skin blood flow to maximal vasodilation, microdialysis sites were perfused with 28 mM sodium nitroprusside, and control sites were heated to 43°C. In both H1 and H2 antagonist studies, no differences in initial peak or secondary plateau phase were observed between control and histamine-receptor antagonist only sites or between l-NAME and l-NAME with histamine receptor antagonist. There were no differences in nadir response between l-NAME and l-NAME with histamine-receptor antagonist. However, the nadir response in H1 antagonist sites was significantly reduced compared with control sites, but there was no effect of H2 antagonist on the nadir response. These data suggest only a modest role for H1-receptor activation in the cutaneous response to local heating as evidenced by a diminished nadir response and no role for H2-receptor activation.


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