This observational study of a large, population-based sample of U.S. youth with diabetes confirmed a general pattern in which the lowest risk of developing type 1 diabetes was experienced by those whose births occurred in the months of November–February. At the same time, most subpopulations in our sample experienced their highest risks of developing type 1 diabetes if their births occurred in months around May.
We found that the observed birth-month patterns applied to those participants whom the providers designated as having type 1 diabetes but that the patterns might not be applicable to type 2 diabetes. This absence of a pattern may stem from different pathophysiological mechanisms or, more simply, from the inadequate statistical power of the study because of the relatively small number of youth with type 2 diabetes. A much larger registry of Ukrainian patients with diabetes, presumably type 2, diagnosed after age 40 years recently reported that the peak risk occurred among adults born in May and the minimum risk occurred among those born in December (13
). The authors of the Ukrainian study commented that the apparent similarity between birth-month patterns for both types of diabetes has implications for exploring hypotheses based on shared etiological pathways.
The approximately sinusoidal pattern with periodicity of 1 year, together with the absence of a birth-month effect in more equatorial latitudes, is consistent with an effect that could be driven by environmental variations in climate or exposure to sunlight. These local variations might operate either through maternal exposures that are temporally related to fetal periods of pancreatic β-cell development or through postnatal exposures related to infancy time windows of pancreatic maturation. Data from 51 regions of the world suggest that residence in areas with low ultraviolet irradiance (estimated on the date of the winter solstice) is associated with high incidence of type 1 diabetes (14
). Ultraviolet radiation contributes substantially to the circulating concentration of vitamin D, and the level of this prohormone may be associated with protection against diabetes through a variety of possible mechanisms (15
). Ultraviolet penetration into deeper skin layers also contributes to the degradation of circulating folic acid, thus suggesting another mechanism by which variation in solar irradiance during time windows of high developmental plasticity might influence metabolism in later life.
As with the other large studies of birth month and diabetes, the SEARCH study lacks information on where the youth resided during infancy, where they were born, and where their mothers resided during the gestational months. For this reason, some of the youth may be misclassified with regard to their geographic residence during early life. Such misclassifications of early residence locations complicate the interpretation of relationships between details of the local environments in which the diabetic children currently reside and their risk of acquiring diabetes. We cannot be certain how the misclassifications might alter the relationship of diabetes risk to birth month.
Another limitation of this analysis is its classification of participants by the racial groups white, black, and other. We used these coarse categories because they were used in the tabulated U.S. birth registers from which we obtained race-specific, expected distributions. These conventional racial categories do not reflect with certainty any genetic differences or biomedical attributes. Nevertheless, if environmental ultraviolet irradiance plays a strong role in the birth-month effect observed, then slight differences in this effect according to racial group might provide hints about the causal mechanisms of diabetes. Individuals classified as black are likely to have darker skin pigmentation than those classified as white or other, and increased superficial skin pigment reduces the cutaneous penetration of ultraviolet sunlight (17
If developmental benefits are derived from increased sunlight in June and July (in the northern hemisphere), then the protection associated with being born in November–February might be related to the maternal concentrations of circulating vitamin D being typically at their maximum in June through August (surveyed at 40° north latitude) (18
). The fortunate fetus would thus be exposed to the highest levels of vitamin D ~3–7 months before birth, a time window that might enhance the prenatal development of pancreatic β-cells or protect them during their primary expansion period that follows the first trimester of human pregnancy (19
). A less fortunate fetus born in May or June would encounter the lowest levels of maternal vitamin D (typically around February-March) (18
) during a time window occurring ~3–4 months before birth. A previous study concerned with dietary sources of vitamin D reported an association of maternal intake of cod liver oil (rich in vitamin D) during pregnancy with a lower risk of type 1 diabetes in offspring, although this protective effect was not observed in the offspring of mothers who took prenatal multivitamin tablets (22
). Maternal intake of dietary vitamin D during late pregnancy has been associated with decreased risk of islet autoimmunity among offspring at high risk of type 1 diabetes (23
Rather than operating during the fetal period, alternative mechanisms of diabetes protection might depend on an infant's postnatal experience with increased concentrations of circulating vitamin D. When a northern-hemisphere baby born in November–February is about 7 months old, the stage at which parents in high-latitude regions would commonly begin to take the infant outside with minimal summertime clothing, the increased solar irradiance of June or July might act to increase the infant's cutaneous production of vitamin D and thus benefit the maturing, postnatal endocrine pancreas. Apart from the possible benefits of increased vitamin D derived from solar irradiance, observational studies have reported that infants' dietary supplementation with vitamin D (24
) or intake of cod liver oil (25
) during the first year of life was associated with reduced risk of type 1 diabetes. This effect was greater for those starting use of cod liver oil at age 7–12 months than for those using cod liver oil at age 0–6 months (25
These data from the SEARCH study suggest that environmental factors associated with birth in early winter in the U.S. may protect children and adolescents against the incidence of type 1 diabetes or that factors related to spring birth, approximately during May in northern latitudes, may be associated with an increased diabetes incidence. If the birth-month effect is linked to reduced ultraviolet irradiance during winter months, this geophysical mechanism might be enhanced by related behavioral changes common to colder periods of the year when mothers and infants exercise less outdoors and wear more clothing that blocks sunlight. Beyond mechanisms that involve cutaneous production of vitamin D, other explanations of the birth-month effect may involve seasonal exposures to microbial agents (including the sterilizing effects of ultraviolet irradiance), toxins, or micronutrients that vary with the season of birth or conception and typical ages at which infants are first introduced to environments beyond the immediate household. Clarification of the mechanisms contributing to this seasonal relationship could lead to testable proposals for interventions to reduce the burden of childhood diabetes.