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• The hot environment hypothesis in diabetes pathophysiology
  Sophie Antoine-Jonville, Olivier Hue
  Published on: 8 June 2017

• Published on: 8 June 2017

  The hot environment hypothesis in diabetes pathophysiology

  • Sophie Antoine-Jonville, Assistant Professor in exercise physiology ACTES laboratory (EA3596), University of the French West Indies, BP 250. 97157 Pointe-à-Pitre, Guadeloupe, France
  • Other Contributors:
    • Olivier Hue, Professor in exercise physiology

  Dear editor,

  The study published in a recent volume of the journal by Blauw et al. is an excellent opportunity to highlight an under-examined environmental hypothesis in the pathophysiology of type 2 diabetes.1 In their epidemiological study, the authors used meta-regression models and demonstrated that diabetes incidence rate in the USA has increased with higher outdoor temperatures from 1996 and 2009, after adjustment for most common confounders. They also evidenced an independent association between the prevalence of glucose intolerance worldwide and mean annual temperature on a global scale. The theoretical background for the work mainly stands on the reduction in brown adipose tissue activity due to high ambient temperature that is expected to negatively impact glucose metabolism. This view is plausible, particularly since recent data uncovered potential crosstalk between brown adipose tissue and glucose regulatory pathways,2 but it is important for us to discuss the context of the study.

  We are definitely concerned about the burden of consequences of climate change including biodiversity assault, threats to the human species’ safety, health and well-being because of increased risks related to extreme weather events, wildfire, air quality, and other environmental disease carriers. However, isn’t it cynical that the glucose metabolism disturbance observed in warm environmental temperature might become a serious working hypothesis concomitantly with (b...

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  Dear editor,

  The study published in a recent volume of the journal by Blauw et al. is an excellent opportunity to highlight an under-examined environmental hypothesis in the pathophysiology of type 2 diabetes.1 In their epidemiological study, the authors used meta-regression models and demonstrated that diabetes incidence rate in the USA has increased with higher outdoor temperatures from 1996 and 2009, after adjustment for most common confounders. They also evidenced an independent association between the prevalence of glucose intolerance worldwide and mean annual temperature on a global scale. The theoretical background for the work mainly stands on the reduction in brown adipose tissue activity due to high ambient temperature that is expected to negatively impact glucose metabolism. This view is plausible, particularly since recent data uncovered potential crosstalk between brown adipose tissue and glucose regulatory pathways,2 but it is important for us to discuss the context of the study.

  We are definitely concerned about the burden of consequences of climate change including biodiversity assault, threats to the human species’ safety, health and well-being because of increased risks related to extreme weather events, wildfire, air quality, and other environmental disease carriers. However, isn’t it cynical that the glucose metabolism disturbance observed in warm environmental temperature might become a serious working hypothesis concomitantly with (because of?) rising climate change concerns? The question particularly arises when other questions are considered, such as: Are there earlier pieces of evidence feeding this idea? How discordant were the rare previous studies on the question? How confident and compelling were the authors?

  Yes, there have been earlier experimental studies. The potential role of environmental factors in diabetes pathophysiology certainly has emerged from observations of diabetes overprevalence in native American Pima Indians, but also in urbanized Melanesians,3 leading to a cascade of studies with genetic and evolutionary considerations. However, the first landmark observation on the question seems to be the communication by Akanji et al. in 1987.4 They investigated the metabolic effect of the ingestion of a meal or a glucose load in non-diabetic obese and non-obese subjects. The plasma glucose concentration excursion was significantly increased when the ambient temperature was 33°C as compared with 23°C. This result was confirmed and completed by other experimental studies.5-10 The a priori discordant results come from animal model studies. In rodents, heat treatment, typically administered through warm baths, improve glucose tolerance.11 However, the apparent disagreement with results of human studies may fade with the consideration that the cutaneous blood flow of humans and furred animals is incomparable. Our understanding of the human model is that the more or less recent studies displayed very strong agreement in their results, systematically corroborating glucose metabolism impairment in warm environment. Also, another recurrent feature in these studies was the high level of prudence by the authors, respecting the caution required by the scientific method, since the observations were isolated and the number of subjects remained limited. They got cold feet because they had to reduce the (alpha) risk of falsely rejecting the null hypothesis (or type I error) and avoid claiming by error to the world that exposure to warm temperature causes diabetes. Interestingly, some authors even proposed that the phenomenon was only apparent.5,7 If that were the case, which has not been confirmed or denied yet, this is still calling for correction factors for the interpretation of glucose tolerance testing, which remain inexistent so far.

  Of course, there have also been previous epidemiological studies. A key observation was the doubling of glucose intolerance rates in pregnant women tested on warmer days as compared with those tested in the coldest period of the year.12 Together with the experimental studies of the same period, these early results were interpreted with extreme caution, calling for confirmation, and have gained little attention, or at least were poorly cited. However, it should be noted that later results of epidemiological studies focusing on seasonality and temperature effects on glucose metabolism are strikingly convergent. Both warm13 and cold14 environments were associated, after adjustments, with higher fasting plasma glucose than moderate temperature (18.1°C) in a large population of individuals tested several times.

  So, there are regrets concerning the time it has taken to seriously consider the putative contribution of exposure to warmth in the development of glucose metabolism impairment, in particular for residents in India, the Middle-East, Central America, the Caribbean and Mexico for example. These regions are chronically exposed to heat; they have a very high prevalence of type 2 diabetes, yet this coincidence has long been ignored. It may be that climate change concerns acted as a trigger to improve the community readiness to be convinced by the evidence of glucose metabolism impairment in warm environments.

  We wish that the paper by Blauw et al. and all their/our precursors will inspire other teams so as to really improve the understanding of the phenomenon, for a global shared benefit.

  References:

  1. Blauw LL, Aziz NA, Tannemaat MR, et al. Diabetes incidence and glucose intolerance prevalence increase with higher outdoor temperature. BMJ Open Diabetes Res Care 2017;5:e000317.
  2. Lee P, Bova R, Schofield L, et al. Brown adipose tissue exhibits a glucose-responsive thermogenic biorhythm in humans. Cell Metab 2016;23:602-9.
  3. Zimmet P, Taylor R, Ram P, et al. Prevalence of diabetes and impaired glucose tolerance in the biracial (Melanesian and Indian) population of Fiji: a rural- urban comparison. Am J Epidemiol 1983;118:673-88.
  4. Akanji AO, Bruce M, Frayn K, et al. Oral glucose tolérance and ambient temperature in non-diabetic subjects. Diabetologia 1987;30:431–3.
  5. Frayn KN, Whyte PL, Benson HA, Earl DJ, Smith HA. Changes in forearm blood flow at elevated ambient temperature and their role in the apparent impairment of glucose tolerance. Clin. Sci. (Lond). 1989;76:323–8.
  6. Akanji AO, Oputa RN. The effect of ambient temperature on glucose tolerance. Diabet Med 1991;8:946–8.
  7. Moses RG, Patterson MJ, Regan JM, et al. A non-linear effect of ambient temperature on apparent glucose tolerance. Diabetes Res Clin Pract 1997;36:35–40.
  8. Dumke CL, Slivka DR, Cuddy JS, et al. The effect of environmental temperature on glucose and insulin after an oral glucose tolerance test in healthy young men. Wilderness Environ Med 2015;26:335-42.
  9. Faure C, Charlot K, Henri S, et al. Impaired glucose tolerance after brief heat exposure: a randomized crossover study in healthy young men. Clin Sci (Lond) 2016;130:1017-25.
  10. Antoine-Jonville S, Faure C, Hue O, et al. Ambient temperature-related exaggerated post-prandial insulin response in a young athlete: a case report and implications for climate change. Accepted for publication in the Asia Pacific Journal of Clinical Nutrition.
  11. Gupte AA, Bomhoff GL, Touchberry CD, et al. Acute heat treatment improves insulin-stimulated glucose uptake in aged skeletal muscle. J Appl Physiol 1985;110:451–7.
  12. Schmidt MI, Matos MC, Branchtein L, et al. Variation in glucose tolerance with ambient temperature. Lancet (London, England) 1994;344:1054–5.
  13. Li S, Zhou Y, Williams G, et al. Seasonality and temperature effects on fasting plasma glucose: A population-based longitudinal study in China. Diabetes Metab 2016;42:267-75
  14. Suarez L, Barrett-Connor E. Seasonal variation in fasting plasma glucose levels in man. Diabetologia 1982;22:250-3.

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  Conflict of Interest:
  None declared.

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