Ryan McGinn

Body temperature regulation in diabetes

ABSTRACT The effects of type 1 and type 2 diabetes on the bodys physiological response to thermal stress is a relatively new topic in research. Diabetes tends to place individuals at greater risk for heat-related illness during heat waves and physical activity due to an impaired capacity to dissipate heat. Specifically, individuals with diabetes have been reported to have lower skin blood flow and sweating responses during heat exposure and this can have important consequences on cardiovascular regulation and glycemic control. Those who are particularly vulnerable include individuals with poor glycemic control and who are affected by diabetes-related complications. On the other hand, good glycemic control and maintenance of aerobic fitness can often delay the diabetes-related complications and possibly the impairments in heat loss. Despite this, it is alarming to note the lack of information regarding diabetes and heat stress given the vulnerability of this population. In contrast, few studies have examined the effects of cold exposure on individuals with diabetes with the exception of its therapeutic potential, particularly for type 2 diabetes. This review summarizes the current state of knowledge regarding the impact of diabetes on heat and cold exposure with respect to the core temperature regulation, cardiovascular adjustments and glycemic control while also considering the beneficial effects of maintaining aerobic fitness.

Evidence for cyclooxygenase‐dependent sweating in young males during intermittent exercise in the heat

Previous studies implicate nitric oxide (NO) in the control of sweating during exercise in the heat; however, it is unclear whether cyclooxygenase (COX) is also involved. We demonstrated that exercise‐induced sweating at a moderate heat production (400 W, ∼40% V̇O2 max ) was similarly reduced when COX and NO synthase were inhibited separately and in combination. Alternatively, inhibiting COX and/or NO synthase did not influence exercise‐induced sweating at a high heat production (700 W, ∼70% V̇O2 max ). We show that both COX and NO are involved in sweating during exercise at moderate heat production and that the effects may not be independent. However, roles for COX and NO are less evident when heat production is elevated. The results lead to better understanding of the mechanisms of sweating and indicate that COX inhibitors (e.g. aspirin) may impair core body temperature regulation and thereby increase the risk of heat‐related illness.

Cyclooxygenase inhibition does not alter methacholine-induced sweating

Cholinergic agents (e.g., methacholine) induce cutaneous vasodilation and sweating. Reports indicate that either nitric oxide (NO), cyclooxygenase (COX), or both can contribute to cholinergic cutaneous vasodilation. Also, NO is reportedly involved in cholinergic sweating; however, whether COX contributes to cholinergic sweating is unclear. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) were evaluated in 10 healthy young (24 ± 4 yr) adults (7 men, 3 women) at four skin sites that were continuously perfused via intradermal microdialysis with 1) lactated Ringer (control), 2) 10 mM ketorolac (a nonselective COX inhibitor), 3) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME, a nonselective NO synthase inhibitor), or 4) a combination of 10 mM ketorolac + 10 mM l-NAME. At the four skin sites, methacholine was simultaneously infused in a dose-dependent manner (1, 10, 100, 1,000, 2,000 mM). Relative to the control site, forearm CVC was not influenced by ketorolac throughout the protocol (all P > 0.05), whereas l-NAME and ketorolac + l-NAME reduced forearm CVC at and above 10 mM methacholine (all P < 0.05). Conversely, there was no main effect of treatment site (P = 0.488) and no interaction of methacholine dose and treatment site (P = 0.711) on forearm sweating. Thus forearm sweating (in mg·min(-1)·cm(-2)) from baseline up to the maximal dose of methacholine was not different between the four sites (at 2,000 mM, control 0.50 ± 0.23, ketorolac 0.44 ± 0.23, l-NAME 0.51 ± 0.22, and ketorolac + l-NAME 0.51 ± 0.23). We show that both NO synthase and COX inhibition do not influence cholinergic sweating induced by 1-2,000 mM methacholine.

Age-related differences in postsynaptic increases in sweating and skin blood flow postexercise

The influence of peripheral factors on the control of heat loss responses (i.e., sweating and skin blood flow) in the postexercise period remains unknown in young and older adults. Therefore, in eight young (22 ± 3 years) and eight older (65 ± 3 years) males, we examined dose‐dependent responses to the administration of acetylcholine (ACh) and methacholine (MCh) for sweating (ventilated capsule), as well as to ACh and sodium nitroprusside (SNP) for cutaneous vascular conductance (CVC, laser‐Doppler flowmetry, % of max). In order to assess if peripheral factors are involved in the modulation of thermoeffector activity postexercise, pharmacological agonists were perfused via intradermal microdialysis on two separate days: (1) at rest (DOSE) and (2) following a 30‐min bout of exercise (Ex+DOSE). No differences in sweat rate between the DOSE and Ex+DOSE conditions at either ACh or MCh were observed for the young (ACh: P = 0.992 and MCh: P = 0.710) or older (ACh: P = 0.775 and MCh: P = 0.738) adults. Similarly, CVC was not different between the DOSE and Ex+DOSE conditions for the young (ACh: P = 0.123 and SNP: P = 0.893) or older (ACh: P = 0.113 and SNP: P = 0.068) adults. Older adults had a lower sweating response for both the DOSE (ACh: P = 0.049 and MCh: P = 0.006) and Ex+DOSE (ACh: P = 0.050 and MCh: P = 0.029) conditions compared to their younger counterparts. These findings suggest that peripheral factors do not modulate postexercise sweating and skin blood flow in both young and older adults. Additionally, sweat gland function is impaired in older adults, albeit the impairments were not exacerbated during postexercise recovery.

Exploring the mechanisms underpinning sweating: the development of a specialized ventilated capsule for use with intradermal microdialysis

Many studies have aimed to identify the controllers of sweating using ventilated capsules with intradermal microdialysis. It is unclear, however, if the surface area covered by the capsule influences the observed response as a result of differences in the number of sweat glands affected by the infused pharmacological agent relative to the total glands captured by the capsule. We evaluated the area of skin perfused with agents delivered via microdialysis. Thereafter, we developed a specialized sweat capsule (1.1 cm2) and compared the sweating response with a classic capsule (2.8 cm2). In Protocol 1 (n = 6), methacholine was delivered to forearm skin in a dose‐dependent manner (1–2000 mmol L−1). The area of activated sweat glands was assessed via the modified iodine‐paper technique. In Protocol 2 (n = 6), the area of inhibited sweat glands induced by ouabain and atropine was assessed during moderate‐intensity cycling. Marked variability in the affected skin area was observed (0.9 ± 0.4 to 5.2 ± 1.1 cm2). In Protocol 3 (n = 6), we compared the attenuation in local sweat rate (LSR) induced by atropine between the new and classic capsule during moderate‐intensity cycling. Atropine attenuated sweating as assessed using the new (control: 0.87 ± 0.23 mg min−1 cm−2 vs. atropine: 0.54 ± 0.22 mg min−1 cm−2; P < 0.01) and classic (control: 0.85 ± 0.33 mg min−1 cm−2 vs. atropine: 0.60 ± 0.26 mg min−1 cm−2; P = 0.05) capsule designs. Importantly, responses did not differ between capsule designs (P = 0.23). These findings provide critical information regarding the skin surface area perfused by microdialysis and suggest that use of a larger capsule does not alter the mechanistic insight into the sweating response gained when using microdialysis.

Mechanisms underlying the postexercise baroreceptor‐mediated suppression of heat loss

Reports indicate that postexercise heat loss is modulated by baroreceptor input; however, the mechanisms remain unknown. We examined the time‐dependent involvement of adenosine receptors, noradrenergic transmitters, and nitric oxide (NO) in modulating baroreceptor‐mediated changes in postexercise heat loss. Eight males performed two 15‐min cycling bouts (85% VO2max) each followed by a 45‐min recovery in the heat (35°C). Lower body positive (LBPP), negative (LBNP), or no (Control) pressure were applied in three separate sessions during the final 30‐min of each recovery. Four microdialysis fibres in the forearm skin were perfused with: (1) lactated Ringers (Ringers); (2) 4 mmol·L−1 Theophylline (inhibits adenosine receptors); (3) 10 mmol·L−1 Bretylium (inhibits noradrenergic transmitter release); or (4) 10 mmol·L−1 l‐NAME (inhibits NO synthase). We measured cutaneous vascular conductance (CVC; percentage of maximum) calculated as perfusion units divided by mean arterial pressure, and local sweat rate. Compared to Control, LBPP did not influence CVC at l‐NAME, Theophylline or Bretylium during either recovery (P > 0.07); however, CVC at Ringers was increased by ~5‐8% throughout 30 min of LBPP during Recovery 1 (all P < 0.02). In fact, CVC at Ringers was similar to Theophylline and Bretylium during LBPP. Conversely, LBNP reduced CVC at all microdialysis sites by ~7–10% in the last 15 min of Recovery 2 (all P < 0.05). Local sweat rate was similar at all treatment sites as a function of pressure condition (P > 0.10). We show that baroreceptor input modulates postexercise CVC to some extent via adenosine receptors, noradrenergic vasoconstriction, and NO whereas no influence was observed for postexercise sweating.

Impairments in local heat loss in type 1 diabetes during exercise in the heat.

UNLABELLED Studies show that vasomotor and sudomotor activities are compromised in individuals with Type 1 diabetes mellitus (T1DM), which could lead to impaired skin blood flow (SkBF) and sweating during heat stress. However, recent work suggests the impairments may only be evidenced beyond a certain level of heat stress. PURPOSE We examined T1DM-related differences in heat loss responses of SkBF and sweating during exercise performed at progressive increases in the requirement for heat loss. METHODS Sixteen adults (10 males and six females) with (T1DM, n = 8) and without T1DM (control, n = 8) matched for age, sex, body surface area, and fitness cycled at fixed rates of metabolic heat production of 200, 250, and 300 W·m in the heat (35°C and 20% relative humidity). Each rate was performed sequentially for 30 min. Local sweat rate (LSR, ventilated capsule), sweat gland activation (modified iodine paper technique), and sweat gland output were measured on the forearm, upper back, and chest, whereas SkBF (laser Doppler) was measured on the forearm and upper back. RESULTS Despite a similar requirement for heat loss, LSR was lower in T1DM on the forearm and chest relative to that in the control. Reductions were measured in the second (forearm: 0.68 ± 0.14 vs 0.85 ± 0.11 mg·min·cm, P = 0.004; chest: 0.58 ± 0.08 vs 0.82 ± 0.12 mg·min·cm, P = 0.046) and third exercise bouts (forearm: 0.75 ± 0.11 vs 0.98 ± 0.12 mg·min·cm, P = 0.005; chest: 0.66 ± 0.1 vs 1.02 ± 0.16 mg·min·cm, P = 0.032). Differences in forearm LSR were the result of a reduction in sweat gland output, whereas the decrease in chest LSR was due to lower sweat gland activation. SkBF did not differ between groups. CONCLUSIONS We show that T1DM is associated with impairments in heat dissipation during exercise in the heat, as evidenced by attenuated LSR. However, these differences are only shown beyond a certain requirement for heat loss.

Cutaneous vascular and sweating responses to intradermal administration of ATP: a role for nitric oxide synthase and cyclooxygenase?

In humans in vivo, the mechanisms behind ATP‐mediated cutaneous vasodilatation along with whether and how ATP increases sweating remains uncertain. Recent work has implicated nitric oxide synthase (NOS), cyclooxygenase (COX) and/or adenosine in the modulation of cutaneous vasodilatation and sweat production during both local (i.e. localized heating) and whole‐body heat stress (i.e. exercise‐induced heat stress). We evaluated whether ATP‐mediated cutaneous vasodilatation and sweating is mediated via NOS, COX and/or adenosine. We show that in humans in vivo, intradermal administration of ATP induces pronounced vasodilatation which is partially mediated by NOS, but neither COX nor adenosine influences ATP‐mediated vasodilatation, and ATP alone does not induce an increase in sweating. These findings advance our basic physiological knowledge regarding control of skin blood flow and sweating, and provide insight into the mechanisms governing thermoeffector activity, which has major implications for whole‐body heat exchange and therefore core temperature regulation in humans during heat stress.

Age, human performance, and physical employment standards

The proportion of older workers has increased substantially in recent years, with over 25% of the Canadian labour force aged ≥55 years. Along with chronological age comes age-related declines in functional capacity associated with impairments to the cardiorespiratory and muscular systems. As a result, older workers are reported to exhibit reductions in work output and in the ability to perform and/or sustain the required effort when performing work tasks. However, research has presented some conflicting views on the consequences of aging in the workforce, as physically demanding occupations can be associated with improved or maintained physical function. Furthermore, the current methods for evaluating physical function in older workers often lack specificity and relevance to the actual work tasks, leading to an underestimation of physical capacity in the older worker. Nevertheless, industry often lacks the appropriate information and/or tools to accommodate the aging workforce, particularly in the context of physical employment standards. Ultimately, if appropriate workplace strategies and work performance standards are adopted to optimize the strengths and protect against the vulnerability of the aging workers, they can perform as effectively as their younger counterparts. Our aim in this review is to evaluate the impact of different individual (including physiological decline, chronic disease, lifestyle, and physical activity) and occupational (including shift work, sleep deprivation, and cold/heat exposure) factors on the physical decline of older workers, and therefore the risk of work-related injuries or illness.

Adenosine receptor inhibition attenuates the suppression of postexercise cutaneous blood flow

Skin blood flow (SkBF) is an important avenue for heat loss; however, it is rapidly suppressed after exercise despite persistently high core and muscle temperatures. This has been ascribed to altered active vasodilation; however, recent work has identified a role for adenosine receptors in the decrease in SkBF following passive heating. In this study, we examined whether adenosine receptors are involved in the postexercise regulation of SkBF by infusion of 4 mm theophylline (a non‐selective adenosine receptor antagonist) via microdialysis. We show that adenosine receptors have a major role in modulating postexercise SkBF, as evidenced by a marked elevation during theophylline infusion compared to a control site. These results help us to better understand the mechanisms underlying the postexercise reduction in SkBF and subsequently heat loss which is associated with heat‐related illness and/or injury.