VITAMIN D DEFICIENCY PREDICTS INSULIN RESISTANCE AND HIGH TRIGLYCERIDES LEVELS IN OBESE CHILDREN [P3-415]

Bellone S, Prodam F, Demarchi I, Bonsignori IM, De Rienzo F, Busti A, Bona G; Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, Novara, Italy

In addition to its effects on calcium homeostasis and bone development, abnormal vitamin D metabolism has been implicated in a diverse range of pathologic conditions, including kidney disease, neurodegenerative diseases, and dermatologic diseases.^1-3 A growing body of evidence suggests that vitamin D is also an important modulator of glucose metabolism and insulin resistance. Epidemiologic studies have found that low serum vitamin D levels predict an increased likelihood of type 2 diabetes, and clinical trials have demonstrated improvements in insulin sensitivity with vitamin D supplementation.⁴ Low levels of vitamin D have been linked to several risk factors for diabetes and cardiovascular disease in adults, including pancreatic ß-cell dysfunction, obesity, and the metabolic syndrome.^5,6 However, few studies have specifically examined how vitamin D affects cardiometabolic risk factors in children and adolescents.

In this presentation, the investigators examined the relationship between vitamin D deficiency and the metabolic syndrome in children. They measured 25-hydroxy vitamin D₃ (the metabolically active form of vitamin D) in 64 obese children, as well as fasting glucose, fasting insulin, and insulin 2 hours after an oral glucose tolerance test (OGTT). The investigators used serum vitamin D levels to define 3 groups of children: vitamin D deficiency (vitamin D <20 ng/mL; 30 of the 64 subjects [46.9%]) hypovitaminosis (vitamin D ≥20 mg/mL and <30 mg/dL; 12 of 64 subjects [18.8%]), and the remaining 22 subjects (34.3%) had vitamin D sufficiency (vitamin D ≥30 mg/mL). Fasting glucose values were similar for those in the 3 vitamin D groups. Mean insulin concentrations were significantly higher for the vitamin D deficient group than the vitamin D sufficient group for both fasting and 2 hours post-OGTT. Compared to the vitamin D sufficient group, the deficient group also exhibited significantly increased triglyceride levels and evidence of insulin resistance based on 3 mathematically derived estimates (increased homeostasis model assessment of insulin resistance [HOMA-IR], lower quantitative insulin sensitivity check index [QUICKI], and insulin sensitivity index [ISI]). In a regression analysis, serum vitamin D concentration was positively and significantly associated with triglyceride levels. Thus, vitamin D deficiency was common in this group of overweight children and was significantly associated with insulin resistance and higher serum triglycerides.

These results are consistent with other recent reports suggesting an association between low vitamin D levels and the early development of cardiometabolic risk factors among young people. One recent analysis of data from more than 3700 adolescents from the US National Health and Nutrition Examination Survey found that low serum vitamin D levels were an independent predictor of a range of cardiometabolic risk factors, including hypertension, hyperglycemia, obesity, and the metabolic syndrome.⁷ Recent randomized, placebo-controlled clinical studies in adults have suggested that vitamin D supplementation improves some cardiovascular risk markers in individuals with low vitamin D levels, such as lipid and lipoprotein profiles and insulin resistance.^8,9 The potential beneficial effects of vitamin D supplementation in obese or otherwise high-risk children remain to be described in controlled clinical studies.

References
1. Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006;10:377-385.
2. de Boer IH. Vitamin D and glucose metabolism in chronic kidney disease. Curr Opin Nephrol Hypertens. 2008;17:566-572.
3. Tanghetti EA. The role of topical vitamin D modulators in psoriasis therapy. J Drugs Dermatol. 2009;8(8 suppl):s4-s8.
4. Teegarden D, Donkin SS. Vitamin D: emerging new roles in insulin sensitivity. Nutr Res Rev. 2009;22:82-92.
5. Pérez-López FR. Vitamin D metabolism and cardiovascular risk factors in postmenopausal women. Maturitas. 2009;62:248-262
6. Rammos G, Tseke P, Ziakka S. Vitamin D, the renin-angiotensin system, and insulin resistance. Int Urol Nephrol. 2008;40:419-426.
7. Reis JP, von Mühlen D, Miller ER 3rd, et al. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics. 2009 Aug 3. [Epub ahead of print.]
8. Major GC, Alarie F, Doré J, et al. Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. Am J Clin Nutr. 2007;85:54-59.
9. Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med. 2009;26:19-27.