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The pathogenesis of metabolic diseases such as obesity and type 2 diabetes are characterized by a progressive dysregulation in energy partitioning, often leading to end-organ complications. One emerging approach proposed to target this metabolic dysregulation is the application of mild cold exposure. In healthy individuals, cold exposure can increase energy expenditure and whole body glucose and fatty acid utilization. Repeated exposures can lower fasting glucose and insulin levels and improve dietary fatty acid handling, even in healthy individuals. Despite its apparent therapeutic potential, little is known regarding the effects of cold exposure in populations for which this stimulation could benefit the most. The few studies available have shown that both acute and repeated exposures to the cold can improve insulin sensitivity and reduce fasting glycemia in individuals with type 2 diabetes. However, critical gaps remain in understanding the prolonged effects of repeated cold exposures on glucose regulation and whole body insulin sensitivity in individuals with metabolic syndrome. Much of the metabolic benefits appear to be attributable to the recruitment of shivering skeletal muscles. However, further work is required to determine whether the broader recruitment of skeletal muscles observed during cold exposure can confer metabolic benefits that surpass what has been historically observed from endurance exercise. In addition, although cold exposure offers unique cardiovascular responses for a physiological stimulus that increases energy expenditure, further work is required to determine how acute and repeated cold exposure can impact cardiovascular responses and myocardial function across a broader scope of individuals.

Because the majority of cold exposure studies are constrained to short-term durations of several hours, the long-term metabolic demands of cold exposure, such as during survival situations, remain largely unknown. The present study provides the first estimates of thermogenic rate, oxidative fuel selection, and muscle recruitment during a 24-h cold-survival simulation. Using combined indirect calorimetry and electrophysiological and isotopic methods, changes in muscle glycogen, total carbohydrate, lipid, protein oxidation, muscle recruitment, and whole body thermogenic rate were determined in underfed and noncold-acclimatized men during a simulated accidental exposure to 7.5°C for 12 to 24 h. In noncold-acclimatized healthy men, cold exposure induced a decrease of ∼0.8°C in core temperature and a decrease of ∼6.1°C in mean skin temperature (range, 5.4-6.9°C). Results showed that total heat production increased by approximately 1.3- to 1.5-fold in the cold and remained constant throughout cold exposure. Interestingly, this constant rise in Ḣprod and shivering intensity was accompanied by a large modification in fuel selection that occurred between 6 and 12 h; total carbohydrate oxidation decreased by 2.4-fold, and lipid oxidation doubled progressively from baseline to 24 h. Clearly, such changes in fuel selection dramatically reduces the utilization of limited muscle glycogen reserves, thus extending the predicted time to muscle glycogen depletion to as much as 15 days rather than the previous estimates of approximately 30–40 h. Further research is needed to determine whether this would also be the case under different nutritional and/or colder conditions.

One of the factors limiting the oxidation of exogenous glucose during cold exposure may be the delay in establishing a shivering steady state (approximately 60 min), reducing glucose uptake into skeletal muscle. Therefore, using indirect calorimetry and isotopic methodologies in non-cold-acclimatized men, the main purpose of this study was to determine whether ingesting glucose at a moment coinciding with the maximal shivering intensity could increase the utilization rate of the ingested glucose. (13)C-enriched glucose was ingested (800 mg/min) from the onset (G0) or after 60 min (G60) of cold exposure when the thermogenic rate was stabilized to low-intensity shivering (approximately 2.5 times resting metabolic rate). For the same quantity of glucose ingested, the oxidation rate of exogenous glucose was 35% higher in G60 (159+/-17 vs. 118+/-17 mg/min in G0) between minutes 60 and 90. By the end of cold exposure, exogenous glucose oxidation was significantly greater in G0, reaching 231+/-14 mg/min, approximately 15% higher than the only rates previously reported. This considerably reduced the utilization of endogenous reserves over time and compared with the G60 condition. This study also demonstrates a fall in muscle glycogen utilization, when glucose was ingested from the onset of cold exposure (from approximately 150 to approximately 75 mg/min). Together, these findings indicate the importance of ingesting glucose immediately on exposure to a cold condition, relying on shivering thermogenesis and sustaining that consumption for as long as possible. This substrate not only provides an auxiliary fuel source for shivering thermogenesis, but, more importantly, preserves the limited endogenous glucose reserves.