Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus

Wick, Diane E.; Roberts, Shelly K.; Basu, Ananda; Sandroni, Paola; Fealey, Robert D.; Sletten, David M.; Charkoudian, Nisha

doi:10.1152/japplphysiol.00943.2005

Cited by 70 publications

(54 citation statements)

References 24 publications

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“…51 Another study showed that the internal temperature at which vasodilation took place during passive whole-body heat exposure was higher for people with type 2 diabetes than for healthy individuals. 53 The delayed onset of skin vasodilation was due to a delay in the active vasodilatory response, not to an increase in vasoconstrictor activity.…”

Section: Diabetes Mellitusmentioning

confidence: 98%

Heat stress in older individuals and patients with common chronic diseases

Kenny

Yardley²,

Brown³

et al. 2009

Canadian Medical Association Journal

485

313

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Key points• People with age over 60 years, obesity, cardiovascular disease, pulmonary disease or long-standing diabetes are at increased risk of heat-related illness during heat waves because of physiological impairments in the regulation of body core temperature in hot conditions.• A homebound lifestyle, lack of contact with other people and decreased mobility can also contribute to an increased risk of heat-related illness.• Working home air conditioners, fans, access to transportation and access to cool environments during prolonged heat events have a protective effect against heat-related illness and deaths.• Physicians should be aware of these risk factors and protective factors against heat illness, and should counsel at-risk patients accordingly.CMAJ 2009. DOI:10.1503/cmaj.081050Previously published at www.cmaj.caReview rise in body core temperature may lead to heat illness and eventually death. Exposure to the combination of external heat stress and metabolically generated heat can lead to heat-related disorders. The prevalence of heat stress symptoms increases in direct proportion to the elevation of body core temperature. The major heat-related disorders -heat cramps, heat exhaustion and heatstroke -involve various degrees of thermoregulatory failure, which occurs when a person is exposed to excessive heat or elevations in body core temperature over a prolonged period. Risk factors for heat stress AgeObservational studies have shown that people aged 60 years and older are among the worst affected by extreme heat, 3−5 with those living in institutions, confined to bed or living alone having the highest rates of illness, injury and death. 5,8,15−17 In their ecological time-series study, Fouillet and associates 2 showed that during the 2003 heat wave in Europe, mortality ratios (ratios of observed deaths to expected deaths) in France increased continuously with age, from 1.3 for people 35-74 years of age to more than 1.7 for those over the age of 75 (Figure 1). Although the greater prevalence of comorbidities and medication use in this population may be responsible for some of the heat-related deaths, laboratory-based physiological studies have indicated that the ability to sense heat 20 and to manifest appropriate behavioural (especially fluid intake) 21−26 and physiological (e.g., blood distribution, sweating) responses 27−33 during exposure to heat may be compromised in otherwise healthy older individuals.The ability to physiologically maintain body core temperature during heat stress becomes compromised with age. 27 This decrease in thermoregulatory ability can be attributed to a combination of factors, including changes in sweating, [28][29][30]34 blood flow to the skin 30,31,34,35 and cardiovascular function. 32The problem can be exacerbated by the decreases in overall physical fitness and increases in body adiposity that may accompany aging. 36 Experts have suggested that, in combination, these age-related changes in thermoregulatory and cardiovascular function can decrease the body's abilit...

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Section: Diabetes Mellitusmentioning

confidence: 98%

Heat stress in older individuals and patients with common chronic diseases

Kenny

Yardley²,

Brown³

et al. 2009

Canadian Medical Association Journal

485

313

View full text Add to dashboard Cite

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“…As the incidence and prevalence of T2DM are increasing, also increasing are the number of individuals who are otherwise relatively healthy and live with T2DM but manage it well so that the number of comorbid conditions is minimal. We have therefore focused our efforts on this growing population in our attempts to understand mechanisms of cutaneous microvascular dysfunction in T2DM (12)(13)(14). Recent studies in our laboratory have shown that relatively healthy individuals with T2DM exhibit less nitric oxide-dependent vasodilation during local and whole body thermal stimuli compared with age-matched controls (12,13).…”

mentioning

confidence: 99%

Local sensory nerve control of skin blood flow during local warming in type 2 diabetes mellitus

Strom

Sawyer

Roberts

et al. 2010

Journal of Applied Physiology

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SM, Charkoudian N. Local sensory nerve control of skin blood flow during local warming in type 2 diabetes mellitus. J Appl Physiol 108: 293-297, 2010. First published December 3, 2009 doi:10.1152/japplphysiol.01077.2009.-Cutaneous sensory nerve-mediated vasodilation is an important component of normal microvascular responsiveness to thermal and nonthermal stimuli. Since both neural and microvascular function can be impaired in type 2 diabetes mellitus (T2DM), we tested the hypothesis that local sensory nerve-mediated vasodilation during nonpainful local warming of the skin is less in T2DM compared with healthy controls (C) matched for age and body size. The rapid vasodilation during the first ϳ5 min of this local warming ("initial peak") was previously shown to rely primarily on local sensory nerves. We measured skin blood flow in T2DM and C subjects (n ϭ 7 in each group) at baseline and during 35 min of local warming of the skin to 42°C at two sites on the ventral forearm. One site was pretreated with 4% lidocaine (LIDO) to block local sensory innervation. During local warming, cutaneous vascular conductance (CVC) during the initial peak was not different between groups, either at the untreated site [T2DM 75 Ϯ 2 vs. C 81 Ϯ 6% of maximum CVC (%maxCVC); P Ͼ 0.05] or at the LIDO site (T2DM 63 Ϯ 7 vs. C 64 Ϯ 6%maxCVC; P Ͼ 0.05). The difference between untreated and LIDO sites (sensory nerve contribution) was also similar between groups (T2DM 13 Ϯ 5 vs. C 18 Ϯ 5%maxCVC; P Ͼ 0.05) and was smaller with LIDO than was previously shown with other local anesthetics. Our results suggest that relatively healthy individuals with T2DM do not exhibit impairments in local sensory nerve vasodilation during thermal stimulation compared with controls of similar age and body size. cutaneous circulation; vasodilation; temperature; metabolic syndrome IN HUMANS, nonpainful local warming of the skin elicits a biphasic vasodilation involving local sensory nerve mechanisms and nitric oxide (6, 8). Initial, rapid blood flow increases during the first 3-5 min (called the "initial peak" of the vasodilator response) are thought to be caused primarily by direct action of local sensory nerves, potentially through release of local vasodilators such as calcitonin gene-related peptide (CGRP) and substance P (5, 8). The second phase of the vasodilation is nitric oxide dependent and occurs over a longer period, typically 25-30 min, after which a plateau in blood flow is reached (6,8).Type 2 diabetes mellitus (T2DM) is strongly associated with neural and microvascular dysfunction. As the incidence and prevalence of T2DM are increasing, also increasing are the number of individuals who are otherwise relatively healthy and live with T2DM but manage it well so that the number of comorbid conditions is minimal. We have therefore focused our efforts on this growing population in our attempts to understand mechanisms of cutaneous microvascular dysfunction in T2DM (12)(13)(14). Recent studies in our laboratory have shown that relatively healthy individual...

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“…SkBF was measured as cutaneous red blood cell flux using Periflux laser-Doppler flowmetry (LDF) as previously described (11,13). One LDF probe (Periflux System 5000; Perimed, Stockholm, Sweden) was attached adhesively to the ventral side of the left forearm in a specialized holder that measures and controls temperature over an area of 12 cm 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Prior to local warming, baseline data were recorded for 7-10 min while local temperature was held constant at 32°C. Local temperature was then increased to 42°C at a rate of 1°C/s, and held at 42°C for 35 min, as previously described (11,13). Subjects were asked whether they felt any pain or discomfort during the local warming; no subject reported feeling any pain or discomfort.…”

Section: Methodsmentioning

confidence: 99%

Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men

Sokolnicki

Khosla

Charkoudian

2007

American Journal of Physiology-Endocrinology and Metabolism

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Sokolnicki LA, Khosla S, Charkoudian N. Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men. Am J Physiol Endocrinol Metab 293: E1426-E1429, 2007. First published September 25, 2007; doi:10.1152/ajpendo.00535.2007.-Microvascular vasodilation in humans can become impaired with age, leading to cardiovascular diseases ranging from mild to life-threatening. Reproductive hormones may confer some protection on the vascular system in women; however, it is unclear whether the same is true in men. Our goal was to evaluate the impact of four hormonal conditions (testosterone only, estradiol only, testosterone and estradiol, no testosterone and no estradiol) on microvascular vasodilator responsiveness in the skin of older men. We hypothesized that in older healthy men estradiol promotes cutaneous microvascular dilation during local warming of the skin and that testosterone inhibits this dilation. We measured skin blood flow using laser Doppler flowmetry during 35 min of cutaneous local warming to 42°C in 52 healthy men (average age 67 Ϯ 1 yr). Subjects were randomized to one of the four hormonal conditions and were studied before and after hormone treatments. The endothelium-dependent vasodilator response to local warming was not different among groups either before or after hormone treatment. For example, with testosterone-only treatment this vasodilator response was 220 Ϯ 13 AU, and with estrogen only the response averaged 246 Ϯ 12 AU (P Ͼ 0.05). We conclude that, within the doses employed in the present study, testosterone and estradiol did not consistently alter cutaneous vasodilator responsiveness in healthy older men. reproductive hormones; skin blood flow; aging; microvasculature A MAJOR HEALTH CONCERN associated with the growing elderly population in the United States is the increased risk for cardiovascular diseases with advancing age. The ability of the microvasculature to dilate has significant implications for protection against these diseases, including hypertension, stroke, and myocardial infarction. Microvascular endothelial function in health and disease has been evaluated by measurement of the cutaneous vasodilator response to local warming (6, 9, 11, 12). During local warming, cutaneous vasodilation occurs via two independent pathways: an initial rapid peak caused by local sensory nerves, followed by a slow rise in skin blood flow (SkBF) that plateaus after ϳ30 min of heating. The plateau phase of vasodilation is mediated in large part by local nitric oxide (NO) release (6, 9).Previously, Charkoudian et al. (3) demonstrated that cutaneous vasodilation to local warming was augmented by exogenous reproductive hormones (oral contraceptives) in young women. The authors hypothesized that this was primarily an effect of estrogen to augment the NO-dependent vasodilator response. In men, testosterone may inhibit NO-dependent vasodilation (5). The effects of estrogen on vascular control in women have been well documented; however, vascular influences of reproductive h...

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Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus

Cited by 70 publications

References 24 publications

Heat stress in older individuals and patients with common chronic diseases

Heat stress in older individuals and patients with common chronic diseases

Local sensory nerve control of skin blood flow during local warming in type 2 diabetes mellitus

Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men

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