Exercise intensity- and body region-specific differences in sweating in middle-aged to older men with and without type 2 diabetes.

Type 2 diabetes (T2D) is associated with reduced whole body sweating during exercise-heat stress. However, it is unclear if this impairment is related to exercise intensity and whether it occurs uniformly across body regions. We evaluated whole body (direct calorimetry) and local (ventilated-capsule technique; chest, back, forearm, thigh) sweat rates in physically active men with type 2 diabetes [T2D; aged 59 (7) yr; V̇o2peak 32.3 (7.6) mL·kg-1·min-1; n = 26; HbA1c 5.1%-9.1%] and without diabetes [Control; aged 61 (5) yr; V̇o2peak 37.5 (5.4) mL·kg-1·min-1; n = 26] during light- (∼40% V̇o2peak), moderate- (∼50% V̇o2peak), and vigorous- (∼65% V̇o2peak) intensity exercise (elicited by fixing metabolic heat production at ∼150, 200, 250 W·m-2, respectively) in 40°C, ∼17% relative humidity. Whole body sweating was ∼11% (T2D: Control mean difference [95% confidence interval]: -37 [-63, -12] g·m-2·h-1) and ∼13% (-50 [-76, -25] g·m-2·h-1) lower in the T2D compared with the Control group during moderate- and vigorous- (P ≤ 0.001) but not light-intensity exercise (-21 [-47, 4] g·m-2·h-1; P = 0.128). Consequently, the diabetes-related reductions in whole body sweat rate were 2.3 [1.6, 3.1] times greater during vigorous relative to light exercise (P < 0.001). Furthermore, these diabetes-related impairments in local sweating were region-specific during vigorous-intensity exercise (group × region interaction: P = 0.024), such that the diabetes-related reduction in local sweat rate at the trunk (chest, back) was 2.4 [1.2, 3.7] times greater than that at the limbs (thigh, arm). In summary, when assessed under hot, dry conditions, diabetes-related impairments in sweating are exercise intensity-dependent and greater at the trunk compared with the limbs.NEW & NOTEWORTHY This study evaluates the influence of exercise intensity on decrements in whole body sweating associated with type 2 diabetes. Furthermore, it investigates whether diabetes-related sweating impairments were exhibited uniformly or heterogeneously across body regions. We found that whole body sweating was attenuated in the type 2 diabetes group relative to control participants during moderate- and vigorous-intensity exercise but not light-intensity exercise; impairments were largely mediated by reduced sweating at the trunk rather than the limbs.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes.

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

Self-reported sleep quality and exercise in polycystic ovary syndrome: A secondary analysis of a pilot randomized controlled trial.

OBJECTIVE: To examine the proportion of participants with poor sleep quality, evaluate the associations between sleep quality and anthropometric and cardiometabolic health markers, and evaluate the effect of high intensity interval training (HIIT) and continuous aerobic exercise training (CAET) on sleep quality in polycystic ovary syndrome (PCOS). DESIGN: Secondary analysis of a pilot randomized controlled trial. PATIENTS: Women with PCOS aged 18-40 years. MEASUREMENTS: The Pittsburgh Sleep Quality Index (PSQI) was measured at baseline and following a 6-month exercise intervention. A PSQI score >5 indicates poor sleep. Linear regression was used to evaluate the associations between PSQI score and anthropometric and cardiometabolic health markers, and the effect of exercise training on these associations. RESULTS: Thirty-four participants completed the PSQI at baseline, and 29 postintervention: no-exercise control (n = 9), HIIT (n = 12) and CAET (n = 8). At baseline, 79% had poor sleep quality. Baseline PSQI score was positively correlated with body mass index, waist circumference, body weight, haemoglobin A1c and insulin resistance. Mean PSQI score changes were -0.4 (SD 1.1), -0.7 (SD 0.6) and -0.5 (SD 0.9) for control, HIIT and CAET, respectively. For HIIT participants, change in PSQI score was associated with changes in body weight (B = .27, 95% CI 0.10-0.45) and waist circumference (B = .09, 95% CI 0.02-0.17). CONCLUSION: Most participants had poor sleep quality which was associated with poorer anthropometric and cardiometabolic health markers. There were no statistically significant changes in PSQI score with exercise training. With HIIT training, decreases in the sleep efficiency score were associated with reductions in body weight and waist circumference. Further studies are needed to determine the effect of exercise training on sleep quality.

Association between haemoglobin A1c and whole-body heat loss during exercise-heat stress in physically active men with type 2 diabetes.

NEW FINDINGS: What is the central question of this study? Is the impairment in heat dissipation during exercise observed in men with type 2 diabetes related to glycaemic control (indexed by glycated haemoglobin; haemoglobin A1c )? What is the main finding and its importance? No association was found between haemoglobin A1c (range: 5.1-9.1%) and whole-body heat loss in men with type 2 diabetes during exercise in the heat. However, individuals with elevated haemoglobin A1c exhibited higher body core temperature and heart rate responses. Thus, while haemoglobin A1c is not associated with heat loss per se, it may still have important implications for physiological strain during exercise. ABSTRACT: Type 2 diabetes is associated with a reduced capacity to dissipate heat. It is unknown whether this impairment is related to glycaemic control (indexed by glycated haemoglobin; haemoglobin A1c ) is unknown. We evaluated the association between haemoglobin A1c and whole-body heat loss (via direct calorimetry), body core temperature, and heart rate in 26 physically active men with type 2 diabetes (43-73 years; HbA1c 5.1-9.1%) during exercise at increasing rates of metabolic heat production (∼150, 200, 250 W m-2 ) in the heat (40°C, ∼17% relative humidity). Haemoglobin A1c was not associated with whole-body heat loss (P = 0.617), nor the increase in core temperature from pre-exercise (P = 0.347). However, absolute core temperature and heart rate were elevated ∼0.2°C (P = 0.014) and ∼6 beats min-1 (P = 0.049), respectively, with every percentage point increase in haemoglobin A1c . Thus, while haemoglobin A1c does not appear to modify diabetes-related reductions in capacity for heat dissipation, it may still have important implications for physiological strain during exercise-heat stress.

Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

AIM: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy. METHODS: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time-to-event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. RESULTS: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40-0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14-3.24) and 1.83 (1.03-3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00-3.53) at 48 weeks and 2.05 (0.98-4.29) at 64 weeks. CONCLUSIONS: A 12-week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.

Where to Start? Physical Assessment, Readiness, and Exercise Recommendations for People With Type 1 or Type 2 Diabetes.

Exercise plays an important role in the management of diabetes and is associated with many benefits such as decreased morbidity and mortality. For people exhibiting signs and symptoms of cardiovascular disease, pre-exercise medical clearance is warranted; however, requiring broad screening requirements can lead to unnecessary barriers to initiating an exercise program. Robust evidence supports the promotion of both aerobic and resistance training, with evidence emerging on the importance of reducing sedentary time. For people with type 1 diabetes, there are special considerations, including hypoglycemia risk and prevention, exercise timing (including prandial status), and differences in glycemic responses based on biological sex.

Comparative efficacy and safety of antihyperglycemic drug classes for patients with type 2 diabetes following failure with metformin monotherapy: A systematic review and network meta-analysis of randomized controlled trials.

AIMS: To compare the efficacy and safety of antihyperglycemic agents, taken in combination with metformin, for the treatment of type 2 diabetes mellitus (T2DM). METHODS: A previous 2016 comprehensive search of Ovid MEDLINE, PubMed, and Cochrane CENTRAL was updated to October 2018, and a systematic review and network meta-analysis (NMA) was conducted. Randomized controlled trials (RCTs) of patients with T2DM taking an antihyperglycemic agent in combination with metformin were included. Bayesian NMA was performed to assess the relative efficacy and safety of the antihyperglycemic classes. RESULTS: In total, 204 RCTs were included, which assessed the efficacy and safety of eight antihyperglycemic drug classes (i.e., sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, basal and biphasic insulin, dipeptidyl peptidase 4 inhibitors, glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransport-2 inhibitors). All drug classes significantly reduced haemoglobin A1c (HbA1c) compared to metformin monotherapy (mean reduction from 0.50 to 0.92). The drug classes varied in their relative effects on hypoglycemia, body weight, body mass index, systolic and diastolic blood pressure, total cholesterol, high and low density lipoprotein cholesterol, and the classes had differing safety profiles on total adverse events, urogenital adverse events, heart failure, serious adverse events, and withdraw due to adverse events. CONCLUSIONS: All eight antihyperglycemic drug classes, taken in combination with metformin, reduced HbA1c levels; however, the effects of the agents on other outcomes varied among the classes.

Exercise in the heat induces similar elevations in serum irisin in young and older men despite lower resting irisin concentrations in older adults.

Irisin is thought to play a cytoprotective role during acute stressors, such as exercise, by reducing oxidative stress and inflammation. Relative to young adults, older individuals exhibit an impaired capacity to dissipate heat during exercise, which can exacerbate elevations in oxidative stress and the acute inflammatory response especially in the heat. In turn, this could induce a greater increase in circulating irisin. Thus, we evaluated age-related differences in irisin expression during prolonged exercise in a non-heat stress and high-heat stress environment. Specifically, we assessed serum irisin in 12 young (22 ± 3 years) and 12 older (59 ± 4 years) men before and after 3-h moderate-intensity exercise (metabolic rate: 200 W/m2) and 60-min post-exercise recovery in temperate (wet-bulb globe temperature (WBGT) 16 °C) and hot (WBGT 32 °C) environments. Core temperature (Tco) was measured continuously. Post-exercise Tco was similarly higher in the hot compared to the temperate condition for both groups (p < 0.001), although Tco remained elevated at end-recovery in the heat in older but not young adults (p = 0.006). Absolute serum irisin concentrations were significantly higher (p ≤ 0.002) under all conditions in the young relative to older adults. Post-exercise and end-recovery irisin was elevated above baseline in both groups in the hot (+39.3 pg/mL SEM 8 and + 48.9 pg/mL SEM 10, respectively; both p ≤ 0.043) but not the temperate condition. When comparing between conditions, the change in irisin concentrations at post-exercise did not differ, although serum irisin was elevated in the hot (+48.9 pg/mL SEM 10) relative to the temperate (+0.88 pg/mL SEM 0.2) condition in both groups at end-recovery (p = 0.004). Our findings indicate that irisin concentrations were elevated after exercise compared to rest in hot, but not temperate conditions across groups. However, older adults may still have greater cellular vulnerability to heat stress given their blunted circulating irisin levels.

The serum irisin response to prolonged physical activity in temperate and hot environments in older men with hypertension or type 2 diabetes.

Current labor demographics are changing, with the number of older adults increasingly engaged in physically demanding occupations expected to continually rise, which are often performed in the heat. Given an age-related decline in whole-body heat loss, older adults are at an elevated risk of developing heat injuries that may be exacerbated by hypertension (HTN) and type 2 diabetes (T2D). Elevated irisin production may play a role in mitigating the excess oxidative stress and acute inflammation associated with physically demanding work in the heat. However, the effects of HTN and T2D on this response remain unclear. Therefore, we evaluated serum irisin before and after 3-h of moderate intensity exercise (metabolic rate: 200 W/m2) and at the end of 60-min of post-exercise recovery in a temperate (wet-bulb globe temperature (WBGT) 16 °C) and high-heat stress (WBGT 32 °C) environment in 12 healthy older men (mean ± SD; 59 ± 4 years), 10 men with HTN (60 ± 4 years), and 9 men with T2D (60 ± 5 years). Core temperature (Tco) was measured continuously. In the heat, total exercise duration was significantly lower in older men with HTN and T2D (both, p ≤ 0.049). Despite Tco not being different between groups, Tco was higher in the hot compared to the temperate condition for all groups (p < 0.001). Similarly, serum irisin concentrations did not differ between groups under either condition but were elevated relative to the temperate condition during post-exercise and end-recovery in the heat (+93.9 pg/mL SEM 26 and + 70.5 pg/mL SEM 38 respectively; both p ≤ 0.014). Thus, our findings indicate similar irisin responses in HTN and T2D compared to healthy, age-matched controls, despite reduced exercise tolerance during prolonged exercise in the heat. Therefore, older workers with HTN and T2D may exhibit greater cellular stress during prolonged exercise in the heat, underlying greater vulnerability to heat-induced cellular injury.

Exercise training and reproductive outcomes in women with polycystic ovary syndrome: A pilot randomized controlled trial.

OBJECTIVE: Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no-exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS. DESIGN: Pilot randomized controlled trial. PARTICIPANTS: Previously inactive women aged 18-40 years with PCOS. MEASUREMENTS: Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers. RESULTS: Forty-seven women were randomized to no-exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK-testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (-1.0 kg/m2 , p = .01) and HIIT (-0.9 kg/m2 , p = .04). Mean waist circumference decreased in all groups (-7.3 cm, -6.9 cm, -4.5 cm in HIIT, CAET and control) with no significant between-group differences. Mean LDL-C was significantly reduced for HIIT compared to CAET (-0.33 mmol/L, p = .03). HDL-C increased in HIIT compared with control (0.18 mmol/L, p = .04). CONCLUSIONS: There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.

Type 2 diabetes impairs vascular responsiveness to nitric oxide, but not the venoarteriolar reflex or post-occlusive reactive hyperaemia in forearm skin.

The venoarteriolar reflex (VAR) is a local mechanism by which vasoconstriction is mediated in response to venous congestion. This response may minimize tissue overperfusion, preventing capillary damage and oedema. Post-occlusive reactive hyperaemia (PORH) is used to assess microvascular function by performing a brief local arterial occlusion resulting in a subsequent rapid transient vasodilation. In the current study, we hypothesized that type 2 diabetes (T2D) attenuates VAR and PORH responses in forearm skin in vivo. In 11 healthy older adults (Control, 58 ± 8 years) and 13 older adults with controlled T2D (62 ± 10 years), cutaneous blood flow measured by laser-Doppler flowmetry was monitored following a 3-min venous occlusion of 45 mm Hg that elicited the VAR, followed by a 3-min recovery period and then a 5-min arterial occlusion of 240 mm Hg that induced PORH. Finally, sodium nitroprusside, a nitric oxide donor, was administered to induce maximum vasodilation. VAR and PORH variables were similar between groups. By contrast, maximal cutaneous blood flow induced by sodium nitroprusside was lower in the T2D group. Taken together, our observations indicate that T2D impairs vascular smooth muscle responsiveness to nitric oxide, but not VAR and PORH in forearm skin.

Effects of short-term heat acclimation on whole-body heat exchange and local nitric oxide synthase- and cyclooxygenase-dependent heat loss responses in exercising older men.

NEW FINDINGS: What is the central question of this study? Does short-term heat acclimation enhance whole-body evaporative heat loss and augment nitric oxide synthase (NOS)-dependent cutaneous vasodilatation and NOS- and cyclooxygenase (COX)-dependent sweating, in exercising older men? What is the main finding and its importance? Our preliminary data (n = 8) demonstrated that short-term heat acclimation improved whole-body evaporative heat loss, but it did not influence the effects of NOS and/or COX inhibition on cutaneous vasodilatation or sweating in older men during an exercise-heat stress. These outcomes might imply that although short-term heat acclimation enhances heat dissipation in older men, it does not modulate NOS- and COX-dependent control of cutaneous vasodilatation or sweating on the forearm. ABSTRACT: Ageing is associated with decrements in whole-body heat loss (evaporative + dry heat exchange), which might stem from alterations in nitric oxide synthase (NOS)- and cyclooxygenase (COX)-dependent cutaneous vasodilatation and sweating. We evaluated whether short-term heat acclimation would (i) enhance whole-body heat loss primarily by increasing evaporative heat loss, and (ii) augment NOS-dependent cutaneous vasodilatation and NOS- and COX-dependent sweating, in exercising older men. Eight older men [mean (SD) age, 59 (8) years] completed a calorimetry and microdialysis trial before and after 7 days of exercise-heat acclimation. For the calorimetry trials, whole-body evaporative and dry heat exchange were assessed using direct calorimetry during 30 min bouts of cycling at light, moderate and vigorous metabolic heat productions (150, 200 and 250 W/m2 , respectively) in dry heat (40°C, 20% relative humidity). For the microdialysis trials, local cutaneous vascular conductance and sweat rate were assessed during 60 min exercise in the heat (35°C, 20% relative humidity) at four dorsal forearm skin sites treated with lactated Ringer solution (control), NOS inhibitor, COX inhibitor or combined NOS and COX inhibitors, via microdialysis. Evaporative heat loss during moderate (P = 0.036) and vigorous (P = 0.021) exercise increased after acclimation. Inhibition of NOS alone reduced cutaneous vascular conductance to a similar extent before and after acclimation (P < 0.040), whereas separate and combined NOS and COX inhibition had no significant effects on sweating relative to the control site (P = 0.745). Our preliminary results might suggest that short-term heat acclimation improves evaporative heat loss, but does not significantly modulate the contributions of NOS or COX to cutaneous vasodilatation or sweating on the forearm in older men during an exercise-heat stress.

Comparative Success of Recruitment Strategies for an Exercise Intervention Trial Among Women With Polycystic Ovary Syndrome: Observational Study.

BACKGROUND: Effective and efficient participant recruitment is a key determinant of the success of a research program. Previously reported recruitment strategies have displayed variable success rates in studies on women with polycystic ovary syndrome (PCOS). OBJECTIVE: This study aimed to evaluate the effectiveness and cost per participant of the recruitment strategies that we used in a prospective randomized controlled trial to examine the effects of exercise training among inactive women with PCOS, who are aged 18-40 years. METHODS: The 4 recruitment methods we used were as follows: (1) referral by health care providers or by word of mouth, (2) media (eg, local newspaper stories and radio interviews), (3) Facebook advertisements, and (4) unpaid advertisements including posters and websites. The proportions of potential, eligible, and enrolled participants recruited with each method were determined and compared using tests of proportion. The time investment and cost per participant enrolled were calculated for each recruitment strategy. RESULTS: Of 200 potential participants screened, 98 (49%) were recruited from unpaid advertisements (posters and websites), 70 (35%) from Facebook advertisements, 16 (8%) by referral, and 16 (8%) from traditional media (newspaper and radio). Every potential participant was recruited from separate means (ie, no participant was approached through more than one recruitment method). A total of 109 (54.5%) women were deemed eligible for participation in the trial, and 60 (30.0%) were enrolled. The proportion of potential participants who completed the trial was higher for those recruited from traditional media than from Facebook advertisements (n=7/16, 44% vs n=13/70, 19%, respectively; P=.03) or unpaid advertisements (n=7/16, 44% vs n=13/98, 13%, respectively; P=.002). The cost per participant was Can $18.21 (US $14.46) for Facebook advertisements and Can $43.88 (US $34.85) for unpaid advertisements. There were no direct trial costs for referrals or traditional media. CONCLUSIONS: For this trial, each method was important for recruiting inactive women with PCOS because no participant reported learning about the trial through more than one method. Unpaid advertisements and Facebook advertisements helped recruit the largest number of participants in the trial, the former resulting in a higher cost per participant than the latter. TRIAL REGISTRATION: ClinicalTrials.gov NCT03362918; https://clinicaltrials.gov/ct2/show/NCT03362918.

Ageing augments ß-adrenergic cutaneous vasodilatation differently in men and women, with no effect on ß-adrenergic sweating.

NEW FINDINGS: What is the central question of this study? ß-Adrenergic receptor activation modulates cutaneous vasodilatation and sweating in young adults. In this study, we assessed whether age-related differences in ß-adrenergic regulation of these responses exist and whether they differ between men and women. What is the main finding and its importance? We showed that ageing augmented ß-adrenergic cutaneous vasodilatation, although the pattern of response differed between men and women. Ageing had no effect on ß-adrenergic sweating in men or women. Our findings advance our understanding of age-related changes in the regulation of cutaneous vasodilatation and sweating and provide new directions for research on the significance of enhanced ß-adrenergic cutaneous vasodilatation in older adults. ABSTRACT: ß-Adrenergic receptor agonists, such as isoprenaline, can induce cutaneous vasodilatation and sweating in young adults. Given that cutaneous vasodilatation and sweating responses to whole-body heating and to pharmacological agonists, such as acetylcholine, ATP and nicotine, can differ in older adults, we assessed whether ageing also modulates ß-adrenergic cutaneous vasodilatation and sweating and whether responses differ between men and women. In the context of the latter, prior reports showed that the effects of ageing on cutaneous vasodilatation (evoked with ATP and nicotine) and sweating (stimulated by acetylcholine) were sex dependent. Thus, in the present study, we assessed the role of ß-adrenergic receptor activation on forearm cutaneous vasodilatation and sweating in 11 young men (24 ± 4 years of age), 11 young women (23 ± 5 years of age), 11 older men (61 ± 8 years of age) and 11 older women (60 ± 8 years of age). Initially, a high dose (100 µm) of isoprenaline was administered via intradermal microdialysis for 5 min to induce maximal ß-adrenergic sweating. Approximately 60 min after the washout period, three incremental doses of isoprenaline were administered (1, 10 and 100 µm, each for 25 min) to assess dose-dependent cutaneous vasodilatation. Isoprenaline-mediated cutaneous vasodilatation was greater in both older men and older women relative to their young counterparts. Augmented cutaneous vasodilatory responses were observed at 1 and 10 µm in women and at 100 µm in men. Isoprenaline-mediated sweating was unaffected by ageing, regardless of sex. We show that ageing augments ß-adrenergic cutaneous vasodilatation differently in men and women, without influencing ß-adrenergic sweating.

Evidence for age-related differences in heat acclimatisation responsiveness.

NEW FINDINGS: What is the central question of this study? Repeated heat exposure during the summer months can enhance heat loss in humans (seasonal heat acclimatisation), but does the magnitude of that enhancement differ between young and older adults when assessed during passive heat exposure? What is the main finding and its importance? While seasonal heat acclimatisation enhanced evaporative heat loss (i.e. sweating) in both young and older adults, those improvements led to a greater reduction in body heat storage in older adults. These outcomes indicate that heat acclimatisation may confer greater thermoregulatory benefits with increasing age. ABSTRACT: Repeated heat exposure throughout summer can enhance heat loss in humans (seasonal heat acclimatisation), although the effect of ageing on those improvements remains unclear. We therefore sought to assess thermoregulatory function in young and older adults during environmental heat exposure prior to and following seasonal heat acclimatisation, hypothesizing that the magnitude of adaptation would be greater in older relative to young adults. To achieve this, 14 young (19-27 years) and 10 older adults (55-72 years), who resided in a temperate humid-continental climate, completed a 3 h resting heat exposure (44°C, ∼30% relative humidity) in the winter-spring months as part of a larger investigation (pre-acclimatisation), before being re-evaluated using the same heat stress test following the summer months (post-acclimatisation). Whole-body dry and evaporative heat exchange, and metabolic rate were measured throughout using direct and indirect calorimetry (respectively), and used to quantify body heat storage (metabolic rate + dry heat gain - evaporative heat loss). Evaporative heat loss increased in both groups following acclimatisation, but those improvements led to a decrease in body heat storage in older (mean difference (95% CI); 213 (295, 131) kJ; P < 0.001), but not young adults (-25 (-94, 44) kJ; P = 0.458). Thus, body heat storage was greater in older compared to young adults before (222 (123, 314) kJ; P < 0.001), but not following acclimatisation (34 (-55, 123) kJ; P = 0.433). Although there is a need for larger and more controlled confirmatory studies, our findings indicate that seasonal heat acclimatisation may induce greater thermoregulatory adaptation in older compared to young adults.

Superoxide and NADPH oxidase do not modulate skin blood flow in older exercising adults with and without type 2 diabetes.

OBJECTIVE: High aerobic fitness may prevent age-related decrements in cutaneous vasodilation while type 2 diabetes may exacerbate this decline. The mechanisms underlying these responses remain unclear, but may be due to an excess of reactive oxygen species. We hypothesized that superoxide scavenging or NADPH oxidase inhibition would improve cutaneous vasodilation in older adults exercising in the heat, particularly in healthy low-fit individuals and those with type 2 diabetes. METHODS: Twenty seven older adults were evenly separated into three groups (healthy low-fit: VO2peak = 24.4 ±â€¯2.4 ml·kg-1·min-1, 61 ±â€¯8 years; healthy high-fit: 42.5 ±â€¯9.7 ml·kg-1·min-1, 56 ±â€¯6 years; type 2 diabetes: 30.0 ±â€¯7.6, ml·kg-1·min-1, 58 ±â€¯7 years). The healthy low-fit and type 2 diabetes groups performed two successive 30-min cycling bouts at 65%VO2peak in the heat (35°C), separated by 30-min rest. The high-fit group cycled at the same absolute heat load (and therefore requirement for heat loss) as their healthy low-fit counterparts during the first exercise bout (Ex1) and at the same relative intensity (65%VO2peak) during the second (Ex2). Forearm cutaneous vascular conductance (CVC%max) was measured at microdialysis sites perfused with: 1) lactated Ringer's solution (control); 2) 10 mM NG-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor); 3) 100 µM apocynin (NADPH oxidase inhibitor); 4) 10 µM tempol (superoxide dismutase mimetic), with responses compared at baseline, end-Ex1, and end-Ex2. RESULTS: In all groups, L-NAME consistently reduced CVC%max relative to the other treatment sites by ~16-21% during Ex1 and by ~22-27% during Ex2 (all P < 0.05). Conversely, superoxide scavenging and NADPH oxidase inhibition did not influence CVC%max (all P > 0.05). CONCLUSION: Superoxide and NADPH oxidase do not modulate cutaneous vasodilation in healthy low- or high-fit older adults exercising in the heat, regardless of aerobic fitness level or relative exercise intensity employed, nor do they influence cutaneous vasodilation during an exercise-heat stress in those with type 2 diabetes. However, NOS remains an important modulator of cutaneous vasodilation during exercise in all groups.

Ageing attenuates muscarinic-mediated sweating differently in men and women with no effect on nicotinic-mediated sweating.

Ageing attenuates muscarinic-mediated sweating. However, whether ageing also impairs nicotinic-mediated sweating remains unclear. Further, despite the known sex-related differences in peripheral sweat gland function, it remains unclear whether age-related modifications of muscarinic and nicotinic-mediated sweating, if any, are similar between men and women. We assessed local sweating in young and older healthy men and women (n = 11, each group) at two dorsal forearm skin sites receiving either: (a) methacholine (muscarinic receptor agonist, 5 doses: 0.0125, 0.25, 5, 100, 2000 mmol/L) or (b) nicotine (nicotinic receptor agonist, 5 doses: 1.2, 3.6, 11, 33, 100 mmol/L) via intradermal microdialysis. Age-related reductions in methacholine-induced sweating were observed at low-to-moderate doses (0.0125-5 mmol/L; all P ≤ 0.05) in men, whereas a reduction was only evident at the highest methacholine dose (2000 mmol/L; P ≤ 0.05) in women. No effect of ageing was observed for nicotine-induced sweating (all P > 0.26 for main effects of age, dose and all interactions). We showed that while healthy ageing attenuates low-to-moderate levels of muscarinic-mediated sweating in men, reductions are only observed at high levels of muscarinic-mediated sweating in women. However, healthy ageing does not modulate nicotinic-mediated sweating in either men or women.

Ageing augments nicotinic and adenosine triphosphate-induced, but not muscarinic, cutaneous vasodilatation in women.

NEW FINDINGS: What is the central question of this study? Does ageing augment muscarinic, nicotinic and/or ATP-mediated cutaneous vasodilatation in women? What is the main finding and its importance? Ageing augments nicotinic and ATP-induced, but not muscarinic, cutaneous vasodilatation in women. This will stimulate future studies assessing the pathophysiological significance of the augmented microvascular responsiveness in older women compared to their young counterparts. ABSTRACT: We previously reported that ageing attenuates adenosine triphosphate (ATP)-induced, but not muscarinic and nicotinic, cutaneous vasodilatation in men, and that ageing may augment cutaneous vascular responses in women. In the present study, we evaluated the hypothesis that ageing augments muscarinic, nicotinic and/or ATP-mediated cutaneous vasodilatation in healthy women. In 11 young (23 ± 5 years) and 11 older (60 ± 8 years) women, cutaneous vascular conductance was evaluated at three forearm skin sites that were perfused with (1) methacholine (muscarinic receptor agonist, 5 doses: 0.0125, 0.25, 5, 100, 2000 mm), (2) nicotine (nicotinic receptor agonist, 5 doses: 1.2, 3.6, 11, 33, 100 mm), or (3) ATP (purinergic receptor agonist, 5 doses: 0.03, 0.3, 3, 30, 300 mm). Each agonist was administered for 25 min per dose. Methacholine-induced increases in cutaneous vascular conductance were not different between groups at all doses (all P > 0.05). However, a nicotine-induced elevation in cutaneous vascular conductance at the lowest concentration (1.2 mm) was greater in older vs. young women (43 ± 15 vs. 26 ± 10%max, P = 0.04). ATP-induced increases in cutaneous vascular conductance at moderate and high doses (3 and 30 mm) were also greater in older relative to young women (3 mm, 44 ± 11 vs. 28 ± 10%max, P = 0.02; 30 mm, 83 ± 14 vs. 64 ± 17%max, P = 0.05). Therefore, ageing augments nicotinic and ATP-induced, but not muscarinic, cutaneous vasodilatation in women.

Body Core Temperature After Foot Immersion and Neck Cooling in Older Adults Exposed to Extreme Heat.

This randomized study evaluates the hypothesis that foot immersion in cool water alone or with supplemental neck cooling mitigates increases in core temperature in older adults exposed to environmental conditions simulating deadly heat waves in North America.

Aging attenuates adenosine triphosphate-induced, but not muscarinic and nicotinic, cutaneous vasodilation in men.

OBJECTIVE: We evaluated the hypothesis that aging attenuates muscarinic, nicotinic, and ATP-related cutaneous vasodilation. METHODS: In 11 young (24 ± 4 years) and 11 older males (61 ± 8 years), CVC was assessed at 3 forearm skin sites that were infused with either: (i) methacholine (muscarinic receptor agonist, 5 doses: 0.0125, 0.25, 5, 100, 2000 mmol/L), (ii) nicotine (nicotinic receptor agonist, 5 doses: 1.2, 3.6, 11, 33, 100 mmol/L), or (iii) ATP (purinergic receptor agonist, 5 doses: 0.03, 0.3, 3, 30, 300 mmol/L). Each agonist was administered for 25 minutes per dose. RESULTS: We showed that CVC at all doses of methacholine did not differ between groups. Similarly, no between-group differences in CVC were observed during nicotine administration at all doses administered. By contrast, while no differences in CVC were measured during the administration of ATP at low (0.03 and 0.3 mmol/L) or high (300 mmol/L) concentrations, CVC was reduced in the older relative to the young males at moderate concentrations of ATP (3 mmol/L: 23 ± 6 vs 40 ± 13%max, 30 mmol/L: 62 ± 11 vs 83 ± 8%max, both P ≤ .05). CONCLUSIONS: We show that aging attenuates ATP-induced, but not muscarinic or nicotinic, cutaneous vasodilation in men.