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How to consider low serum vitamin D as a risk factor for insulin resistance?

Institute of Internal Medicine
Catholic University
Largo A. Gemelli, 8
00168 Rome
Italy
E-mail: melania.manco{at}rm.unicatt.it

Dear Sir:

Chiu et al (1) provide elegant evidence that the 25-hydroxyvitamin D [25(OH)D] concentration has a positive relation to insulin sensitivity in healthy, nearly normal-weight, glucose-tolerant subjects. They conclude that a low concentration of 25(OH)D can be an independent risk factor for metabolic syndrome in large populations.

We have some concerns. First, the authors recognize the significant relation between serum concentrations of 25(OH)D and latitude in the European population (2). Thus, we should infer a correlation between latitude and insulin sensitivity. The European Group of Insulin Resistance failed to find any correlation between latitude and insulin sensitivity in a cohort of 1146 European subjects (3). Moreover, because concentrations of 25(OH)D depend on sunlight exposure (4, 5), for each patient we could find seasonal differences in insulin sensitivity. The authors report a marginal effect (P = 0.0729) of season on 25(OH)D, which could be biased by the prevalence of subjects studied or by the time definition for each season.

Second, the incidence of metabolic syndrome was 30% in 47 subjects with hypovitaminosis D (<20 ng/mL) compared with 11% in 79 subjects with normal concentrations of 25(OH)D. Because the 25(OH)D concentration was an independent predictor for BMI, was BMI equally distributed between the 2 groups? Moreover, the authors did not provide data on body composition. The percentage of fat is inversely related to the serum 25(OH)D concentration (5). A high percentage of body fat could play a key role in explaining the relation between low serum vitamin D concentrations and insulin resistance.

The last, but main, concern comes from evidence of hypovitaminosis D coupled with normal insulin sensitivity in obese subjects undergoing biliopancreatic diversion (BPD), a type of bariatric surgery (6). BPD basically causes weight loss through severe lipid malabsorption (6) and leads to mild-to-severe hypocalcemia, low concentrations of vitamin D, and hyperparathyroidism in large cohorts of subjects (7, 8). BPD patients do not have serum 25(OH)D concentrations that are higher than those of obese subjects (9). However, BPD increases insulin sensitivity up to 3-fold with respect to baseline (10) and significantly reduces fat mass and cardiovascular disease risk (11).

REFERENCES

1. Chiu KC, Chu A, Go VLW, Saad MF. Hypovitaminosis D is associated with insulin resistance and ß cell dysfunction. Am J Clin Nutr 2004;79:820-5.[Abstract/Free Full Text]
2. Lips P, Duong T, Oleksik A, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 2001;86:1212-21.[Abstract/Free Full Text]
3. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997;100:1166-73.[Medline]
4. Fuleihan GE, Debb M. Hypovitaminosis D in a sunny country. N Engl J Med 1999;340:1840-1.[Free Full Text]
5. Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab 2003;88:157-61.[Abstract/Free Full Text]
6. Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Bilio-pancreatic bypass for obesity: II. Initial experience in man. Br J Surg 1979;66:618-20.[Medline]
7. Slater GH, Ren CJ, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg 2004;8:48-55.[Medline]
8. Newbury L, Dolan K, Hatzifotis M, Low N, Fielding G. Calcium and vitamin D depletion and elevated parathyroid hormone following biliopancreatic diversion. Obes Surg 2003;13:893-5.[Medline]
9. Parikh SJ, Edelman M, Uwaifo GI, et al. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab 2004;89:1196-9.[Abstract/Free Full Text]
10. Greco AV, Mingrone G, Giancaterini A, et al. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes 2002;51:144-51.[Abstract/Free Full Text]
11. Mingrone G, Rosa G, Greco AV, et al. Intramyocitic lipid accumulation and SREBP-1c expression are related to insulin resistance and cardiovascular risk in morbid obesity. Atherosclerosis. 2003;170:155-61.[Medline]

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