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Vitamin D deficits more closely related to diabetes than to obesity
Diminished levels of vitamin D in adults with prediabetes and diabetes, occurring regardless of BMI, suggest the deficiency is more related to carbohydrate metabolism than to obesity, according to research published in The Journal of Clinical Endocrinology & Metabolism.
In a cross-sectional cohort study of adults at a wide range of weights and varied glycemic status, researchers in Spain found that adipose tissue appears to respond differently to 1,25-dihydroxyvitamin D3, depending on the degree of obesity.
“The study suggests that vitamin D deficiency and obesity interact synergistically to heighten the risk of diabetes and other metabolic disorders,” Manuel Macias-Gonzalez, MD, of Instituto de Investigación Biomédica de Málaga, told Endocrine Today. “The average person may be able to reduce their risk by maintaining a healthy diet and getting enough outdoor activity.”
Macias-Gonzalez, with Mercedes Clemente-Postigo, MSc, also of IBIMA, and colleagues from other institutions studied 118 adults categorized by BMI (lean, overweight, obese or morbidly obese) and glycemic status (normoglycemia or prediabetes and diabetes), along with 30 patients with obesity (BMI > 30 kg/m2) from a second site also classified by glycemic status.
The investigators analyzed vitamin D receptor gene expression during preadipocyte differentiation and in vitro stimulation using 1,25-dihydroxyvitamin D3 of adipose tissue from participants with varying BMI.
The main outcome measures sought were serum 25-hydroxyvitamin D, parathyroid hormone and adipose tissue vitamin D receptor gene expression.
Serum 25-hydroxyvitamin D levels were lower in patients with prediabetes and diabetes compared to those with normoglycemia, especially in the lean and morbidly obese groups (P < .05); the levels negatively correlated with a homeostasis model of assessment for insulin resistance (r = –0.20; P = .032) and glucose (r = – 0.295; P = .001) but not BMI.
Higher vitamin D receptor gene expression was observed in adults with morbid obesity compared with other BMI levels (P = .05). In adipose tissue from patients with obesity, 1,25-dihydroxyvitamin D3 increased vitamin D receptor gene expression (P < .05).
“The deficit of vitamin D is associated more with diabetes and less with obesity, and there is a significant deficit in lean subjects with diabetes,” Macias-Gonzalez said. “Further studies will be necessary to understand the physiological consequences of the different adipose tissue responses to 1,25-dihydroxyvitamin D3 depending on the degree of obesity and its relevance in clinical practice, as well as to confirm the role of vitamin D receptor in diabetes,” Macias-Gonzalez said. – by Allegra Tiver
For more information:
Manuel Macias Gonzalez, MD, can be reached at Instituto de Investigación Biomédica de Málaga, Laboratorio Investigacion Biomedica, 1ª Planta, Hospital Universitario Virgen de la Victoria, Campus de Teatinos s/n, 29010 Malaga, Spain; e-mail: mmacias.manuel@gmail.com.
Disclosure: The researchers report no relevant financial disclosures.
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Vitamin D is different from other vitamins. It appears in the body from what we consume, but it is also produced in the skin in response to sunlight. Although vitamin D is historically known for its association with calcium metabolism, observations made in the last couple decades suggest additional functions. It is a vitamin that also appears to act like a hormone.
In more recent times, the observation has been made that lower vitamin D levels are associated with type 2 diabetes. A paper in Lancet last October suggested no connection. The current paper by Clemente-Postigo and colleagues suggests two things — lower vitamin D levels are associated with type 2 diabetes and the association is independent of weight.
Researchers in the United States and elsewhere are currently conducting studies that aim to firm up such associations. To date there is no recognized functional relation between vitamin D and type 2 diabetes. However, there are many questions to be answered. Is low vitamin D a marker for type 2 diabetes? Is low vitamin D a parallel genetic issue?
The findings do suggest that people at risk for type 2 diabetes should have their vitamin D levels checked during annual screening and treat it accordingly until we know what it means.
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Clemente-Postigo and colleagues add to the growing literature regarding the relationship between vitamin D deficiency and glucose intolerance. Using a cross-sectional design, they show a modest (r = –0.295), but significant, inverse association between serum 25-hydroxyvitamin D levels and fasting glucose but not BMI. When the study population is stratified by BMI and glucose status, serum 25-(OH)D levels are significantly lower in the prediabetes/diabetes group compared with the normal-glucose group regardless of BMI. The authors conclude that vitamin D deficiency is associated more with carbohydrate metabolism than with obesity.
While this study demonstrates that vitamin D deficiency is not related to BMI, the causal relationship between vitamin D and glucose homeostasis remains unclear. The authors suggest that vitamin D deficiency may lead to pancreatic beta-cell dysfunction. However, vitamin D deficiency may also increase insulin resistance and mediate the association between serum serum 25-(OH)D and fasting glucose in this study. The authors did report a negative association between serum 25(OH)D and a surrogate estimate of insulin resistance (HOMA-IR, r = –0.2); however, the relationship was no longer significant when adjusted for glucose and insulin; insulin and HOMA-IR are highly correlated and perhaps should not have been included in the model.
Finally, the authors report on differential vitamin D receptor (VDR) expression in visceral adipose tissue between a small group of morbidly obese and lean individuals (3 each). Although homologous up-regulation of VDR expression by vitamin D 1,25 has been previously established, higher VDR expression was only seen in the obese group in the current study. While interesting, these results need validation.
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Considerable interest continues in the potential for vitamin D replacement to treat chronic diseases inclusive of diabetes. However, the evidence base remains weak. While the study by Clemente-Postigo and colleagues adds another dimension by adding adipose tissue vitamin D receptor (VDR) gene expression in individuals across a range of adiposity and carbohydrate intolerance, it does not advance causal inferences. This small study shows greater VDR gene expression in the obese, not surprising since obesity drives down circulating 25OHD levels, perhaps due to greater adipose tissue sequestration. However, there is no convincing evidence for improvements in glycemia levels with vitamin D replacement, and genetic studies also do not support a causal role for vitamin D in type 2 diabetes. Thus, as we reiterated recently, the results of major ongoing trials are needed to form robust conclusions. Currently, vitamin D replacement cannot be recommended to treat chronic diseases outside of the bone area.
References:
Vimaleswaran KS, et al. PLoS Med. 2013;doi:10.1371/journal.pmed.1001383.
Welsh P, et al. BMJ. 2014;doi:10.1136/bmj.g2280.
Ye Z, et al. Lancet Diabetes Endocrinol. 2015;doi:10.1016/S2213-8587(14)70184-6.