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© Borgis - Postępy Nauk Medycznych 1/2015, s. 59-63
Magdalena Walicka1, Wojciech Bik2, Ada Sawicka1, Ewa Wolińska-Witort2, Małgorzata Kalisz2, *Ewa Marcinowska-Suchowierska1
Niedobory witaminy D u osób otyłych i ich związek z insulinoopornością oraz leptyną – doniesienie wstępne
Vitamin D deficiency in obesity and its relationship to insulin resistance and plasma leptin levels – preliminary study**
1Department of Family Medicine, Internal Diseases and Metabolic Bone Diseases, Medical Center of Postgraduate Education, Orłowski Hospital, Warsaw
Head of Department: Marek Tałałaj, MD, PhD, Associate Professor
2Department of Clinical Neuroendocrinology, Medical Center of Postgraduate Education, Warsaw
Head of Department: Wojciech Bik, MD, PhD, Associate Professor
Streszczenie
Wstęp. Otyłość jest czynnikiem ryzyka niedoboru witaminy D. Istnieją dowody, że witamina D może odgrywać rolę w patogenezie insulinooporności.
Cel pracy. Celem pracy była ocena, czy u osób otyłych niedobór witaminy D jest związany z insulinoopornością oraz stężeniem leptyny.
Materiał i metody. Do badania włączono 43 otyłych (wskaźnik masy ciała (BMI) ≥ 35 kg/m2) pacjentów przed operacją bariatryczną oraz 16 zdrowych ochotników z prawidłową masą ciała. U wszystkich oszacowano w surowicy stężenie: 25-hydroksywitaminy D (25(OH)D), wapnia, glukozy, insuliny, leptyny, rozpuszczalnego receptora leptyny, dokonano oceny insulinooporności przy pomocy modelu homeostatycznego (HOMA-IR) oraz obliczono indeks wolnej leptyny.
Wyniki. W grupie otyłych 90% osób miało niższe niż zalecane stężenie 25(OH)D, w grupie kontrolnej – 75%. W całej grupie stwierdzono istotną ujemną korelację między 25(OH)D a insuliną, HOMA-IR, leptyną i indeksem wolnej leptyny, natomiast w grupie otyłych powyższe korelacje nie były obserwowane. Stwierdzono istotną ujemną korelację między stężeniem wapnia a BMI, insuliną, HOMA-IR, leptyną oraz indeksem wolnej leptyny, a także istotną dodatnią korelację między stężeniem wapnia a stężeniem wolnego receptora leptyny w całej badanej grupie. W grupie otyłych zaobserwowano korelację między stężeniem wapnia a stężeniem rozpuszczalnego receptora leptyny i indeksem wolnej leptyny.
Wnioski. Niedobór i deficyt witaminy D są częste zarówno u osób otyłych, jak i z prawidłową masą ciała. U osób otyłych nie stwierdza się korelacji między stężeniem 25(OH)D a parametrami insulinooporności oraz leptyną. Witamina D może wpływać na aktywność leptyny poprzez wpływ na stężenie wapnia.
Summary
Introduction. Obesity is a risk factor for vitamin D deficiency and there is some evidence that vitamin D may be involved in the pathogenesis of insulin resistance.
Aim. The aim of the study was to evaluate whether vitamin D deficiency is associated with insulin resistance and leptin level in obese subjects.
Material and methods. 43 obese (body mass index (BMI) ≥ 35 kg/m2) individuals before bariatric surgery and 16 healthy volunteers with normal body weight were enrolled in this study. In all subjects serum level of glucose, 25-hydroxyvitamin D (25(OH)D), calcium, insulin, leptin, leptin soluble receptor were evaluated, insulin resistance was estimated by the homeostasis model assessment (HOMA-IR), free leptin index was calculated.
Results. In the obese group 90% of patients had lower than recommended level of 25(OH)D, in the control group – 75%. In all investigated groups significant negative correlations between 25(OH)D and insulin, HOMA-IR, leptin, and free leptin index were found but in obese subjects this correlations were not observed. There were significant negative correlations between serum calcium and BMI, insulin, HOMA-IR, leptin, and free leptin index and a significant positive correlation between serum calcium and leptin receptor in all investigated groups. In obese subjects there were correlations between calcium levels and soluble leptin receptor as well as free leptin index.
Conclusions. Vitamin D deficiency and insufficiency are common in obese and normal weight subjects. There is a lack of correlation between 25(OH)D concentration and insulin resistance parameters and leptin in obese subjects. Vitamin D may impact leptin activity through calcium concentration.
INTRODUCTION
Health care of obese people is one of the biggest challenges of medicine nowadays. The new IASO/IOTF (International Association for the Study of Obesity/International Obesity Task Force) analysis (2010) estimates that approximately 1.0 billion adults worldwide are currently overweight (with body mass index (BMI) 25-29.9 kg/m2), and another 475 million are obese (1) which means that around 1.5 billion adults have inappropriate, elevated body mass. The survey performed in Poland in the years 2003-2007 found that among men 40.3 percent (aged 20+) were overweight and 20.8 percent (aged 20+) were obese. Among females 28.4 percent (aged 20+) were overweight and 23.8 percent (aged 20+) were obese (2).
Obesity is the major determinant of metabolic syndrome, presumably through its effect on insulin resistance. Insulin resistance is the condition in which normal amounts of insulin are inadequate to cause a proper insulin response from fat, muscle and liver cells. Each standard deviation (SD) increase in visceral adipose tissue mass increases the odds of insulin resistance by 80% (3).
The mechanisms of insulin resistance are not elucidated yet in details. In the first hypothesis, lipid accumulation in skeletal muscle and liver cells plays the central role, however in the second theory, the most important mechanism is lipid accumulation in adipocytes and local inflammation. There is also some evidence that vitamin D may be involved in the pathogenesis of insulin resistance (4). This observation is especially important in obesity because in obese subjects aberrations in the correlation between the vitamin D and endocrine system were identified (5). Many studies reported an association between obesity and low serum 25-hydroksyvitamin D (25(OH)D) concentrations, as well as with high concentrations of parathyroid hormone (PTH) (6, 7).
Vitamin D is a regulator of bone and mineral metabolism homeostasis. In addition to its classical actions, vitamin D plays multiple biological roles. In details, more than 200 genes are controlled directly or indirectly by the active form of this vitamin – 1,25 dihydroxyvitamin D (1,25(OH)2D), regulating cellular proliferation, differentiation, apoptosis and angiogenesis (8). Moreover, vitamin D receptor (VDR) is distributed in more than 38 types of tissue (9) including insulin-responsive tissues and pancreatic beta cells.
Epidemiological studies showed correlations between low serum 25(OH)D concentration, an indicator of organism supply with vitamin D, and increased insulin resistance (10, 11). Vitamin D may have effect on insulin resistance through direct action via VDR or indirectly via calcium and PTH levels. 1,25(OH)2D can bind to VDR in beta cells and therefore may stimulate the expression of insulin receptor and promote insulin-mediated glucose transport (12). Additionally, vitamin D may reduce the low-grade chronic inflammation that is present in obesity by decreasing the production of inflammatory factors (i.e. cytokines) by activated macrophages (13).
It is widely known that vitamin D regulates serum calcium levels. Calcium is a crucial ion in insulin action (14), thus vitamin D deficiency may induce hypocalcaemia and insulin resistance at the target tissues level. On the other hand, hypovitaminosis D induces the elevation of PTH concentration. Some studies demonstrated that PTH decreased insulin-induced glucose transport in adipocytes (15). It has been also reported that PTH in obese adolescents was associated with biomarkers of insulin resistance and inflammation, independently of vitamin D levels (16).
Interestingly, vitamin D may impact on adipocytokines homeostasis. 25(OH)D levels were positively correlated with adiponectin (17), which increases insulin sensitivity and reveals anti-inflammatory action. However, data concerning the correlation between leptin, an adipokine that plays a key role in regulating energy intake and energy expenditure in human, and vitamin D are controversial. Some studies reported that 1,25(OH)2D suppressed leptin (18) while other authors demonstrated that 1,25(OH)2D stimulated leptin production in mouse adipose tissue (19).
The role of Vitamin D in the development of insulin resistance is well supported by experimental data, however results from interventional studies provided contradictory results. Some studies (20) failed to confirm effects on insulin sensitivity after supplementation with vitamin D, while in others, this kind of improvement was observed (21). Recently published misanalysis demonstrated, that currently there is an insufficient evidence of beneficial effect to recommend vitamin D supplementation as a means of improving glycaemia or lowering insulin resistance in patients with diabetes, normal fasting glucose or impaired glucose tolerance (22).
AIM
Because of these ambiguous data, we aimed to evaluate whether vitamin D deficiency is associated with insulin resistance and leptin level in obese subjects.
MATERIAL AND METHODS
Subjects
Forty three obese individuals with body mass index (BMI) ≥ 35 kg/m2, including 12 male and 31 females, were enrolled in the study. All individuals were Caucasians and were recruited among the patients of Department of Family, Internal Medicine and Metabolic Bone Diseases, Orlowski Hospital, Centre of Postgraduate Medical Education in Warsaw, Poland. All subjects were admitted to the hospital for internal examination prior to the bariatric surgery. Exclusion criteria from the study were as follows: selected endocrine dysfunctions (hyper- or hypothyreosis, Cushing disease) chronic kidney and liver disease. None of examined subjects had a history of excessive alcohol consumption. None of subjects took vitamin D supplements. The control group consisted of 16 healthy volunteers (6 male and 10 female) with normal body weight (BMI 19-24 kg/m2).
The study protocol was accepted by the Bioethical Committee of the Centre of Postgraduate Medical Education.
Blood analyses
Blood samples were obtained at 8.00 am after overnight fasting and were immediately centrifuged at 4°C. Plasma was stored at -30°C for further analyses of insulin, leptin and leptin soluble receptor concentration. Additionally serum was immediately used for other analytical analyses.
Insulin concentration was measured using IRMA methods (Immunotech, Czech Republic). Leptin level was estimated with RIA method (Linco Research). Leptin soluble receptor concentration was assessed with ELISA (Bio Vendor Laboratory Medicine).
Intra- and inter-assay coefficient was below 10% for all investigated parameters. Leptin, leptin soluble receptor and insulin levels were investigated in the Department of Neuroendocrinology, Centre of Postgraduate Medical Education in Warsaw.
Blood glucose and calcium concentrations were measured by certified hospital laboratory applying standard clinical biochemistry methods. 25(OH)D concentration was measured by the same laboratory using ARCHITECT 25-OH Vitamin D assay (fully automated immunoassay).
In all subjects insulin resistance was estimated by homeostasis model assessment (HOMA-IR), according to the formula:
HOMA-IR = fasting glucose (mmol/l) x fasting plasma insulin (μIU/ml) / 22.5.
Free leptin index (FLI) was calculated as a quotient leptin / leptin receptor X 100.
Statistical analysis
Statistica 6.1 was used for statistical analysis. Data are shown as means ± standard deviation. The normality of distribution was investigated using the Shapiro-Wilk test. The differences between groups were calculated using Mann-Whitney U-test. The Spearman test was used to estimate correlations between 25(OH)D and biochemical parameters as well as serum calcium concentrations and BMI and adipokines. Significance level was defined as p-value < 0.05.
RESULTS

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Piśmiennictwo
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otrzymano: 2014-12-16
zaakceptowano do druku: 2015-01-05

Adres do korespondencji:
*Ewa Marcinowska-Suchowierska
Department of Family Medicine, Internal Diseases and Metabolic Bone Diseases Medical Center of Postgraduate Education, Orłowski Hospital
ul. Czerniakowska 231, 00-416 Warszawa
tel. +48 (22) 584-11-01
ewa.marcinowska@w.pl

Postępy Nauk Medycznych 1/2015
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