Mild Cold Exposure with Shivering Lowers 24-Hour Glucose Levels in Type 2 Diabetes: A Novel Adjunctive Therapy

Highlight

This randomized crossover trial demonstrates that acute mild cold exposure (~15°C) with induced shivering significantly lowers 24-hour glucose levels, fasting glucose, and hyperglycemic time in individuals with type 2 diabetes, but not in those with prediabetes. Moderate cold exposure (~4°C) eliciting greater increases in resting metabolic rate did not confer these glycemic benefits. Baseline fasting glucose, age, and liver enzyme levels predicted response magnitude, highlighting metabolic and hepatic health as important modifiers.

Study Background

Type 2 diabetes (T2D) is a growing global health burden characterized by impaired glucose regulation and insulin resistance. Current management strategies include lifestyle modification, pharmacotherapy, and in some cases, bariatric surgery. However, the search for novel non-pharmacological interventions that can improve glucose homeostasis remains a priority, especially those that may increase energy expenditure and substrate utilization without significant lifestyle disruption.

Cold exposure has recently gained attention as a metabolic stimulus capable of activating thermogenesis and increasing energy expenditure through shivering and nonshivering mechanisms. Animal and human studies suggest it might influence glucose metabolism, potentially improving substrate utilization. However, the acute effects of cold-induced shivering on glycemic control in individuals with impaired glucose regulation have remained unclear.

Study Design

This study was a randomized crossover trial conducted in the South Limburg/Maastricht region of the Netherlands. It included 24 sedentary, non-smoking men and postmenopausal women aged 40–75 years with either prediabetes (n=12) or stable T2D (n=12), and a body mass index between 27 and 35 kg/m². Participants underwent two sessions of whole-body cold exposure using a water-perfused suit designed to elicit increases in resting metabolic rate (RMR) of approximately 1.5-fold (mild cold, 15°C) and 2.5-fold (moderate cold, 4°C). The order of sessions was randomized; participants were blinded to temperature intensity, while investigators were not.

Continuous glucose monitoring was used to assess interstitial glucose levels over 24-hour periods before and after each cold exposure intervention, under standardized diet and activity conditions. Shivering was confirmed using indirect calorimetry and electromyography measurements.

Key Findings

Both mild and moderate cold exposure sessions significantly increased RMR compared to baseline in both groups (p<0.001). In prediabetic participants, mild cold increased RMR by 1.53 times and moderate cold by 1.94 times; in the T2D group, mild cold increased RMR by 1.57 times and moderate cold by 2.09 times during the final hour of exposure.

Despite this metabolic activation, only the T2D group showed significant improvements in glucose homeostasis following mild cold exposure. Key outcomes in the T2D group included:

• A significant reduction in mean 24-hour glucose levels (-0.6 ± 0.5 mmol/L; p=0.003)
• Lower fasting glucose (-0.6 ± 0.8 mmol/L; p=0.019)
• An increase in time spent within normal glucose range (+8.8 ± 10.3%; p=0.013)
• A reduction in time spent in hyperglycemia (-10.9 ± 12.9%; p=0.014)

No significant glucose improvements were observed after moderate cold exposure in T2D participants or after either cold exposure in prediabetic participants.

Predictive analysis identified baseline fasting glucose, age, and alanine aminotransferase (ALT) levels as significant predictors of glucose-lowering response, suggesting younger individuals with higher baseline hyperglycemia and better liver health derive greater benefit.

Expert Commentary

This study provides important mechanistic and clinical insights into cold-induced thermogenesis as a modifiable factor in glucose regulation specifically in established T2D. The dissociation between metabolic rate increases and glycemic improvements—where greater cold intensity (moderate cold) did not translate into better glucose control—suggests that substrate utilization during acute cold exposure may not fully explain the benefits.

Potential biological mechanisms may include improved insulin sensitivity mediated by mild cold-induced shivering thermogenesis enhancing glucose uptake in skeletal muscle or activation of brown adipose tissue, which has been linked to increased glucose clearance. The absence of effect in prediabetes may reflect differences in metabolic adaptability or disease progression stages.

Limitations include the small sample size, short-term follow-up, and lack of mechanistic assays directly measuring insulin sensitivity or brown adipose tissue activity. Additionally, investigator unblinding to cold intensity could introduce bias. Future research should address these gaps and verify whether repeated or chronic mild cold exposure has sustained benefits and favorable safety profiles.

Conclusion

In conclusion, acute mild cold exposure inducing shivering significantly improves 24-hour glucose control and reduces hyperglycemia in individuals with type 2 diabetes but not prediabetes. Baseline metabolic status and liver health appear critical in determining benefit. These findings position mild cold exposure as a promising adjunct non-pharmacological therapy for T2D management.

Further studies with larger cohorts and mechanistic focus are warranted to elucidate underlying pathways and optimize cold exposure protocols for clinical application.

Funding and Registration

This study was funded by the Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062, and is registered at ClinicalTrials.gov under NCT05576025.

References

1. Hashim D, Jörgensen JA, van de Weijer T, Blondin DP, Schrauwen P, Hoeks J. Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes. Diabetologia. 2026 Jul 20. PMID: 42474505.
2. Cedernaes J, Schiöth HB. Cold exposure and metabolic regulation: Potential roles in diabetes and obesity therapies. F1000Research. 2020;9:F1000 Faculty Rev-1140.
3. van Marken Lichtenbelt WD, et al. Cold exposure and brown adipose tissue function in humans. Nat Rev Endocrinol. 2015;11(12):641-650.
4. Blondin DP, et al. Increased Brown Adipose Tissue Activity After Cold Exposure Improves Glucose Homeostasis in Humans. Diabetes. 2014;63(8):2489-2493.