**6. The mechanisms underlying type 2 diabetes-related impairments in heat dissipation**

To date, few studies have examined the mechanisms underlying type 2 diabetes-related impairments in heat dissipation; however, some information may be gleaned from those studies aimed primarily at assessing the presence of neuropathies. The reduction in nitric oxide bioavailability in individuals with type 2 diabetes is well established [62, 63, 72, 73] and may be further exacerbated by the presence of atherosclerotic plaques which are known to adversely alter endothelial function through interfering with nitric oxide signaling [74]. In fact, one study reported that the relative nitric oxide-dependent vasodilation during whole-body passive heating was similar between healthy controls and type 2 diabetics; however, absolute SkBF was lower in the latter group [72]. Moreover, there is evidence to support an endotheliumindependent component to the impairment in vasodilation as observed during exogenous administration of a nitric oxide donor (e.g., sodium nitroprusside) [63]. Importantly, these diabetes-related changes in SkBF appear to be closely associated with the duration of diabetes and/or the presence of related complications [62, 63]. There is little report on the central versus peripheral mechanisms that form the basis of diabetes-related SkBF responses; one study indicated that onset of vasodilation responses to increased core body temperature was delayed and it was the primary factor, explaining lower SkBF in patients with type 2 diabetes mellitus. This indicates that central mechanisms contribute to the modulation of SkBF [66].

**5. Effects of type 2 diabetes on thermoregulation in warm and hot** 

and hot environments, physical activity, or both) on type 2 diabetics remains limited.

significant, but sustained difference in the rate of non-evaporative heat loss [71].

**6. The mechanisms underlying type 2 diabetes-related impairments** 

To date, few studies have examined the mechanisms underlying type 2 diabetes-related impairments in heat dissipation; however, some information may be gleaned from those studies aimed primarily at assessing the presence of neuropathies. The reduction in nitric oxide bioavailability in individuals with type 2 diabetes is well established [62, 63, 72, 73] and may be further exacerbated by the presence of atherosclerotic plaques which are known to adversely alter endothelial function through interfering with nitric oxide signaling [74]. In fact, one study reported that the relative nitric oxide-dependent vasodilation during whole-body passive

Kenny et al. [71] recently reported that relatively active type 2 diabetics who were otherwise generally healthy (good glycemic control and no diabetes-related complications) have significantly decreased whole-body heat loss during exercise for 60 min (~370 W of metabolic heat production or ~60% of the predetermined VO2max) as assessed by whole-body direct calorimetry. During the exercise bout, due to the lower evaporative heat loss in type 2 diabetes, they stored ~1.5-fold more heat than their healthy counterparts. Regardless of the greater amount of heat accumulation during exercise, the diabetes-related impairment in the capacity to dissipate heat persisted into the 60-minute recovery. Healthy groups lost ~twofold more heat relative to the group with type 2 diabetes, which was associated with slightly and no statistically

Type 2 diabetes typically presents later in life with a mean onset age of 54 years [61]. Type 2 diabetes is associated with multiple comorbidities, including obesity, dyslipidemia, metabolic syndrome, hypertension, and other markers of cardiovascular diseases in addition to the changes associated with aging. Most of the research examining ability of thermoregulation in type 2 diabetic patients has considered not only to estimate itself but also the responses to evaluate the severity of neuropathy along with other diabetes-related complications. Many studies have only measured the local heat dissipative responses of the hands and feet. It is generally reported that type 2 diabetic patients have attenuated SkBF responses evoked by pharmacological stimuli [62, 63], local skin heating [64, 65], and whole-body heating [64, 66]. Importantly, these effects appear to depend on physical fitness level. Type 2 diabetic engaging in physical activity has reduced impairments in skin vasodilation compared with type 2 diabetics who are not physically active [67]. Conversely, studies of local sweating in type 2 diabetics have generally found that these individuals have impaired sweating responses compared to their healthy counterparts [64, 68, 69], despite one study reporting otherwise [70]. The changes in regional sweating with type 2 diabetes are comparable to those observed with type 1 diabetes, such that there is relatively lower body anhidrosis along with euhydrosis or hyperhidrosis compared to the upper body [68]. While these studies have implications for whole-body temperature regulation during heat stress, the evidence regarding the impact of heat stress (as induced by warm

**conditions**

96 Diabetes and Its Complications

**in heat dissipation**

The mechanisms responsible for diabetes-related impairments in sweating during heat stress remain incompletely understood and most of the information is provided from studies which have not examined thermoregulatory control. Petrofsky et al. [64] indicated that, during isometric handgrip exercise to exhaustion, sweating on the arms and legs was significantly lower, but only forehead sweat rate was actually higher in type 2 diabetics than the controls. The primary factors associated with this modulation in sweating include long-term diabetes, poorly controlled glycemia, and the presence of neuropathy. Diabetic neuropathy seems to have an important role in altering the sweat gland innervations [68, 75]. Luo et al. [75, 76] showed that the sweat glands in type 2 diabetics with poor glycemic control exhibit exacerbated reductions in periglandular nerve terminals and in the innervation index. Impairments in sweating during heat stress may also be related to the reduction in nitric oxide bioavailability since the role of nitric oxide-induced sweating during exercise has recently been proven [77, 78].
