Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329
The article on seasonal variation of hemoglobin A1c by Tseng et al. (1) leaves no doubt that there is a distinctive variation in this physiologic parameter and comprehensively reviews published evidence of similar variations in blood pressure, serum cortisol, and a range of other physiologic parameters observed by other medical researchers. It is interesting to speculate that such seasonal variations in physiologic parameters might underlie the distinct seasonal variation in a range of infectious diseases by altering the susceptibility of host cells to infection (2
). Importantly, an enhanced understanding of the forces driving seasonal physiologic changes may uncover unimagined opportunities for disease prevention.
The authors take their analysis a step further and attribute the variation to cold air in winter, after briefly examining several readily available weather parameters from various locations across the United States. However, they appear to have overlooked the most likely explanation, which is to be found in the substantial nonmedical literature on biologic rhythms. Seasonal changes in physiologic parameters are nearly ubiquitous in mammals, as well as birds, reptiles, and even plants (35
). Although cold air and other weather parameters have been extensively explored as potential drivers of seasonal physiologic variation, by far the most common and important guide for seasonal changes in mammalian physiology is the change in photoperiod, or the light-dark cycle. This in turn drives changes in the length of the daily melatonin pulse, signaling the change in seasons to cells throughout the organism (6
). Humans retain the ability to respond to photoperiod and the effects of melatonin (7
).
Therefore, the authors should also consider evaluating the effects of changing photoperiod on the seasonal changes in hemoglobin A1c. Because photoperiod is determined only by latitude and calendar time, there is a close, but not invariant, correlation between photoperiod and air temperature. Could the puzzling observation that hemoglobin A1c levels dropped with colder air but rose again at the extremes of cold be explained by differences between cold and latitude, for example, if the more northern areas were in temperate coastal cities such as Seattle?
Correlations between seasonal variations in physiology and a range of climate changes and other seasonal parameters are easy to find. The fact that seasonal variations in pneumococcal disease incidence correlated with seasonal patterns of public construction expenditures did not mean that one caused the other but rather emphasized that many things vary seasonally (8). If cold air caused the elevations in hemoglobin A1c, were elevated levels seen in areas with temperature anomalies, such as unusually cool summers? Were the A1c levels highest in the coldest cities? Interactions among air temperature, other weather parameters, latitude, and photoperiod are complex and challenging to sort out. Because endogenous biologic rhythms guided by photoperiod and melatonin underlie the seasonal physiologic variations in such an enormous range of other animals, such endogenous rhythms should be consistently evaluated as potential causes of seasonal physiologic variations in humans before cold air or other unusual explanations are accepted.
ACKNOWLEDGMENTS
Conflict of interest: none declared.
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