Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season

Abstract

Low 25-hydroxyvitamin D (25[OH] D) results in hyperparathyroidism and is among the endocrine derangements of adult obesity. There are differing recommendations on defining low 25(OH) D: hypovitaminosis D (serum 25[OH] D concentration <75 nmol/L) and vitamin D deficiency (serum 25[OH] D concentration <50 nmol/L). We sought to evaluate the prevalence of low levels of 25(OH) D by examining hypovitaminosis D (<75 nmol/L), vitamin D sufficiency (≥75 nmol/L), vitamin D insufficiency (50-74.9 nmol/L), and vitamin D deficiency (<50 nmol/L) in pediatric obesity and the relationship to other calciotropic hormones and adiposity. Serum 25(OH) D, intact parathyroid hormone (iPTH), ionized calcium, glucose, and insulin levels along with hemoglobin A_1c (HbA_1c) and quantitative insulin sensitivity check index (QUICKI) were determined in 127 subjects aged 13.0 ± 3.0 years (49 Caucasian [C], 39 Hispanic [H], and 39 African American [AA]; 61.2% female; body mass index 36.4 ± 8.1 kg/m²) during fall/winter (F/W) and spring/summer (S/S). Body composition was determined by bioelectrical impedance. Hypovitaminosis D was present in 74% of the cohort, but was more prevalent in the H (76.9%, P < .05) and AA (87.2%, P < .05) groups than in the C group (59.1%). Hypovitaminosis D corresponded to decreased vitamin D intake (P < .005) and was more prevalent in F/W than S/S (98.4% vs 49.2, P < .01). Vitamin D deficiency was identified in 32.3% of the entire cohort and was more prevalent in the H (43.6%, P < .0001) and AA (48.7%, P < .0001) groups than in the C group (10.2%) associated with decreased vitamin D intake (P < .0001). Vitamin D insufficiency was present in 41.7% of the cohort, with similar prevalence among C (48.9%), H (33.3%), and AA (38.5%). Vitamin D insufficiency corresponded to decreased vitamin D intake (P < .005), with similar prevalence in F/W and S/S (45.3% vs 38.1%), whereas vitamin D deficiency was not only accompanied by decreased vitamin D intake (P < .0001) but was more prevalent in F/W than S/S (53.1% vs 11.1%, P < .0001). Serum 25(OH) D and iPTH (r = −0.41, P < .0001) levels were negatively correlated without seasonal and ethnic/racial influences. Hypovitaminosis D and vitamin D–deficient groups had higher body mass index, fat mass (FM), and iPTH, but had lower QUICKI than vitamin D–sufficient group (P < .01). Whereas FM was negatively correlated with 25(OH) D (r = −0.40, P < .0001), it was positively correlated with iPTH (r = 0.46, P < .0001) without seasonal and racial/ethnic influences. Serum 25(OH) D was also positively correlated with QUICKI (r = 0.24, P < .01), but was inversely correlated with HbA_1c (r = −0.23, P < .01). Hypovitaminosis D was identified in 74% of obese subjects, whereas vitamin D deficiency was observed in 32.3% of our cohort. Vitamin D status was influenced by vitamin D intake, season, ethnicity/race, and adiposity. Interrelationships between 25(OH) D, iPTH, and FM were not influenced by season and race/ethnicity. Furthermore, serum 25(OH) D was positively correlated with insulin sensitivity, which was FM mediated, but negatively correlated with HbA_1c, implying that obese children and adolescents with low vitamin D status may be at increased risk of developing impaired glucose metabolism independent of body adiposity. Additional studies are needed to evaluate the underlying mechanisms.

Introduction

It has been shown that vitamin D regulates calcium metabolism through its endocrine function and its noncalciotropic effects such as cellular differentiation and replication in many organs via its paracrine and autocrine role [1], [2]. These noncalciotropic functions comprise the immune system, endocrine pancreas, liver, skeletal muscles, and adipocytes [2]. The vitamin D endocrine system plays a role in glucose homeostasis, especially in the mechanism of insulin secretion [3], [4], [5], [6]. Therefore, vitamin D deficiency and insufficiency (hypovitaminosis D) can adversely affect tissues that are not involved in calcium homeostasis and bone metabolism [7].

Serum 25-hydroxyvitamin D (25[OH] D) concentrations are largely determined by environmental factors, mainly through vitamin D intake (cholecalciferol and ergocalciferol) and ultraviolet radiation of 7-dehydrocholesterol in the skin (cholecalciferol) [8], [9]. The serum concentration of 25(OH) D is the best marker of total body vitamin D status [10], [11]; however, the definition of acceptable serum concentration of 25(OH) D is equivocal. Recently, a consensus statement for vitamin D nutritional guidelines issued by scientists and nutritional experts suggested that serum 25(OH) D ≥75 nmol/L concentration is the minimum acceptable level for maintenance of bone health and health in general [12]. There was also a general recommendation that blood concentration of 25(OH) D should at the very least meet, or exceed, a minimum desirable level of 50 nmol/L in all age groups [13]. Indeed, vitamin D deficiency, defined as serum 25(OH) D <50 nmol/L [13], has been shown to be common in healthy adolescent population, with a higher prevalence in African American youth and during winter months [14], [15], [16]. Indeed, low serum 25(OH) D and the resultant hyperparathyroidism are among the endocrine derangements of obesity [17]. Despite this discrepancy in proposed minimum level of acceptable serum concentration of 25(OH) D, obese adults and children have been shown to have low serum 25(OH) D and elevated intact parathyroid hormone (iPTH) levels [18], [19], [20]. Adult subjects with hypovitaminosis D are also believed to be at higher risk of insulin resistance and metabolic syndrome [6], [7]. Hypovitaminosis D has been implicated in the pathogenesis of insulin resistance, β-cell dysfunction, and type 1 and type 2 diabetes mellitus [21], [22].

In young children and adolescents living in the northern parts of the United States, a rise in parathyroid hormone level occurs at low-normal concentrations of vitamin D [15], [23], [24]. One hypothesis is that this physiologic increase in parathyroid hormone levels in response to hypovitaminosis D state is believed to increase intracellular calcium in adipocytes, which leads to increased lipogenesis and weight gain [25]. To date, the prevalence of vitamin D deficiency and hypovitaminosis D, the identification of the resultant hyperparathyroidism, and the impact on insulin sensitivity and glucose homeostasis among obese children have not been evaluated. Therefore, we evaluated the levels of fasting serum calciotropic hormones, ionized calcium (iCa⁺²), phosphate, insulin, glucose hemoglobin A_1c (HbA_1c), and an index of insulin sensitivity and dietary intake of vitamin D and calcium in relationship to adiposity, season, and ethnicity/race in a group of obese children and adolescents residing in a northern climate (43° N).