Vitamin D Levels and Insulin Resistance in Children Born with Severe Growth Restriction

Abstract

This study was designed to examine differences in serum 25(OH)D levels between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) prepubertal children in correlation with birth weight and indices of insulin resistance and β-cell function. Sixty-five nonobese children were examined at age 5–7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and waist circumference were recorded and fasting serum levels of glucose, insulin, 25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) and the β-cell function index (HOMA-β%) were estimated. The mean level of 25(OH)D was higher in the SGA group (26.2±10 vs. 17.2±7 ng/ml, p<0.01) but that of PTH was no different. The insulin resistance and β-cell function indices were higher in the SGA group: HOMA-IR 1.34±0.67 vs. 0.99±0.53, and HOMA-β% 135±56 vs. 97±60 in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated with HOMA-β% but not with HOMA-IR or insulin. In multiple regression, in the total cohort 25(OH)D and HOMA-IR were independently negatively correlated with birth weight (β= − 0.31, β= − 0.36, p<0.05) respectively. In conclusion, at prepuberty severely in utero growth restricted children have increased birth weight dependent levels of 25(OH)D, which might exert a regulatory role on β-cell function.

Key words

vitamin D - small-for-gestational-age - insulin resistance - β-cell function - in utero growth restriction

• References

• 1 Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004; 79: 362-371
• 2 Teegarden D, Donkin SS. Vitamin D: emerging new roles in insulin sensitivity. Nutr Res Rev 2009; 22: 82-92
• 3 Boucher BJ, Mannan N, Noonan K, Hales CN, Evans SJ. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia 1995; 38: 1239-1245
• 4 Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004; 79: 820-825
• 5 Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 2009; 139: 329-334
• 6 Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36: 62-67
• 7 Mericq V, Ong KK, Bazaes R, Peña V, Avila A, Salazar T, Soto N, Iñiguez G, Dunger DB. Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children. Diabetologia 2005; 48: 2609-2614
• 8 Ong KK, Petry CJ, Emmett PM, Sandhu MS, Kiess W, Hales CN, Ness AR, Dunger DB. ALSPAC study team . Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia 2004; 47: 1064-1070
• 9 Giapros V, Andronikou S. Serum Adiponectin Levels, Insulin Resistance, and Lipids in Catch-Up and No Catch-Up Growth. In Preedy VR. (ed.). Handbook of Growth and Growth Monitoring in Health and Disease. New York: Springer; 2012: 987-1005
• 10 Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-1495
• 11 Altman D. Practical Statistics for Medical Research. London: Chapman and Hall; 1991: 456-460
• 12 Kayaniyil S, Vieth R, Harris SB, Retnakaran R, Knight JA, Gerstein HC, Perkins BA, Zinman B, Hanley AJ. Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components. J Clin Endocrinol Metab 2011; 96: 168-175
• 13 Olson ML, Maalouf NM, Oden JD, White PC, Hutchison MR. Vitamin d deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab 2012; 97: 279-285
• 14 Devaraj S, Jialal G, Cook T, Siegel D, Jialal I. Low vitamin D levels in Northern American adults with the metabolic syndrome. Horm Metab Res 2011; 43: 72-74
• 15 Del Gobbo LC, Song Y, Dannenbaum DA, Dewailly E, Egeland GM. Serum 25-hydroxyvitamin D is not associated with insulin resistance or beta cell function in Canadian Cree. J Nutr 2011; 141: 290-295
• 16 Reinehr T, de Sousa G, Alexy U, Kersting M, Andler W. Vitamin D status and parathyroid hormone in obese children before and after weight loss. Eur J Endocrinol 2007; 157: 225-232
• 17 Erdönmez D, Hatun S, Çizmecioğlu FM, Keser A. No relationship between vitamin D status and insulin resistance in a group of high school students. J Clin Res Pediatr Endocrinol 2011; 3: 198-201
• 18 Delvin EE, Lambert M, Levy E, O’Loughlin J, Mark S, Gray-Donald K, Paradis G. Vitamin D status is modestly associated with glycemia and indicators of lipid metabolism in French-Canadian children and adolescents. J Nutr 2010; 140: 987-991
• 19 Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF. Elizabeth Glaser Pediatric Research Network Obesity Study Group . Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr 2009; 90: 459-467
• 20 Rajakumar K, de las Heras J, Lee S, Holick MF, Arslanian SA. 25-hydroxyvitamin D concentrations and in vivo insulin sensitivity and β-cell function relative to insulin sensitivity in black and white youth. Diabetes Care 2012; 35: 627-633
• 21 Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati G, Anhalt H, Ten S. Prevalence of vitamin D insufficiency in obese children and adolescents. J Pediatr Endocrinol Metab 2007; 20: 817-823
• 22 Gannagé-Yared MH, Chedid R, Khalife S, Azzi E, Zoghbi F, Halaby G. Vitamin D in relation to metabolic risk factors, insulin sensitivity and adiponectin in a young Middle-Eastern population. Eur J Endocrinol 2009; 160: 965-971
• 23 Pacifico L, Anania C, Osborn JF, Ferraro F, Bonci E, Olivero E, Chiesa C. Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents. Eur J Endocrinol 2011; 165: 603-611
• 24 Zitterman A. Vitamin D in preventive medicine: are we ignoring the evidence?. Br J Nutr 2003; 89: 552-572
• 25 Vieth R. Vitamin D supplementation, 25- hyrdoxyvitamin D concentrations and safety. Am J Clin Nutr 1999; 69: 842-856
• 26 Soares MJ, Ping-Delfos WC, Sherriff JL, Nezhad DH, Cummings NK, Zhao Y. Vitamin D and parathyroid hormone in insulin resistance of abdominal obesity: cause or effect?. Eur J Clin Nutr 2011; 65: 1348-1352
• 27 Ashraf A, Alvarez J, Saenz K, Gower B, McCormick K, Franklin F. Threshold for effects of vitamin D deficiency on glucose metabolism in obese female African-American adolescents. J Clin Endocrinol Metab 2009; 94: 3200-3206
• 28 Kayaniyil S, Retnakaran R, Harris SB, Vieth R, Knight JA, Gerstein HC, Perkins BA, Zinman B, Hanley AJ. Prospective associations of vitamin D with β-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study. Diabetes 2011; 60: 2947-2953
• 29 Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Nathan L, Rifai N, Liu S. Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: the Women’s Health Initiative Observational Study. Diabetes Care 2007; 30: 1747-1752
• 30 Ibáñez L, Lopez-Bermejo A, Díaz M, Suárez L, de Zegher F. Low-Birth Weight Children Develop Lower Sex Hormone Binding Globulin and Higher Dehydroepiandrosterone Sulfate Levels and Aggravate their Visceral Adiposity and Hypoadiponectinemia between Six and Eight Years of Age. J Clin Endocrinol Metab 2009; 94: 3696-3699
• 31 Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23: 57-63