Andrzej Milewicz

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe — recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency

INTRODUCTIONnAdequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolism as well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activity appear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest that Vitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conference focused on overcoming Vitamin D deficiency.nnnMETHODSnAfter reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the Vitamin D - minimum, maximum, optimum conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting Vitamin D - minimum, maximum, optimum was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists voting were reviewed and discussed during eight plenary sessions and two workshops.nnnRESULTSnBased on many polemical discussions, including post-conference networking, the key opinion leaders established ranges of serum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed.nnnCONCLUSIONSnImproving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.

Serum lipid peroxides and total antioxidant status in postmenopausal women on hormone replacement therapy

Estradiol (E2) has antioxidant properties. The role of progestins in antioxidant defense is still unknown. We have evaluated the influence of E2 and E2 plus medroxyprogesterone acetate (MPA) on serum lipid peroxide (LPO) levels, a marker of free radical reactions, and serum total antioxidant status (TAS) in postmenopausal women. Subjects consisted of 26 women with surgical menopause, before and after 4 months of estrogen replacement therapy (ERT; E2), and 54 women with natural menopause on hormone replacement therapy (HRT; E2 plus MPA). Forty premenopausal women served as a control group. Serum E2 was estimated by radioimmunoassay, follicle-stimulating hormone by IRMA methods, LPO and TAS by colorimetric methods. Before therapy, LPO levels in the postmenopausal women were significantly higher (pu200a<u200a0.001) than in the control group. After both ERT and HRT, LPO decreased significantly and did not differ between both groups and the control group. TAS was significantly lower in postmenopausal women (pu200a<u200a0.001) than in the control group before therapy. After both ERT and HRT, TAS increased significantly and did not differ between both groups and the control group. We conclude that oxidative stress is increased after menopause. ERT and HRT inhibit the generation of free radicals and raise antioxidant potential to the levels found in premenopausal women. MPA did not influence the antioxidant action of E2.

European silver paper on the future of health promotion and preventive actions, basic research and clinical aspects of age related disease

Background. In September 2008, under the French Presidency of the European Union and with the support of the Polish Minister of Health, a European Summit on Age-Related Disease was organised in Wroclaw (Poland). At this meeting, European politicians, gerontologists and geriatricians gathered to discuss a common approach to future challenges related to age-related disease. Politicians and decision-makers from the European Union and Ministers of Health and their deputies from many European countries raised the problems and difficulties to be tackled in a growing population with a high burden of disease, and asked scientists to write a consensus document with recommendations for future actions and decisions. Scientists and clinicians worked in parallel in three different groups, on health promotion and preventive actions, basic research in age-related disease, and clinical aspects of disease in older people. Beforehand, the format of the paper with recommendations was discussed, and it was finally agreed that, for a better understanding by decision-makers, it would be divided in two different columns: one with facts that were considered settled and agreed by most experts (under the heading We know), and a second with recommendations related to each fact (We recommend). No limit on the number of topics to be discussed was settled. After careful and detailed discussion in each group, which in most cases included the exact wording of each statement, chairpersons presented the results in a plenary session, and new input from all participants was received, until each of the statements and recommendations were accepted by a large majority. Areas with no consensus were excluded from the document. Immediately after the Summit, the chairpersons sent the document both to the main authors and to a list of experts (see footnote) who had made presentations at the summit and agreed to review and critically comment on the final document, which is presented below. As regards the scientific aspects of the planning of the Summit, several organisations, under the leadership of the EUGMS, were asked both to review the program and to suggest names of speakers and participants. After the Summit, the Boards of these organizations (European Union Geriatric Medicine Society (EUGMS), International Association of Gerontology and Geriatrics-European Region (IAGG-ER), European Association of Geriatric Psychiatry (EAGP), International Society of Gerontechnology (ISG) and International Society for the Study of the Aging Male (IS-SAM) agreed to consider the document as an official paper, and help with its dissemination. The name Silver Paper was used, recalling the grey or silvery hair of our older citizens, as an easy reference. It has been sent officially to several bodies of the European Union and to Health Ministers of most European countries; and will be published in other languages in local purnals. Its declared intention is to foster changes in policies which may, in the future, reduce the burden of disease in old age.

Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism

Many animal and human studies show that supraphysiological doses of dehydroepiandrosterone (DHEA) can influence body composition and carbohydrate and lipid metabolism. Most studies have concentrated on women and have not been randomized, thus creating controversial results. With this in mind, we designed a cross-over double-blind placebo-controlled study of 12 men aged 59.0 ± 4.8 years, who received either 50 mg/24 h DHEA or placebo for 3 months to assess the influence of DHEA on the content and distribution of fat tissue and serum insulin, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels, as well as testosterone, estradiol, DHEA-sulfate (S), prostate-specific antigen (PSA) concentrations and indexes of insulin sensitivity and resistance. Patients were recruited from university employees attending for periodic health checks, with normal hepatic and renal function with endogenous DHEA-S level < 1500 ng/dl. Our results did not reveal any significant changes in study parameters, apart from a statistically significant increase in DHEA-S levels after therapy with active substance.

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men. Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (u200a+u200a) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods. Results Men with coronary artery disease had lower total testosterone levels (17.01u200a±u200a6.42 vs. 19.37u200a±u200a6.58u2009nmol/l; pu200a<u200a0.05), testosterone/estradiol ratio (228.5u200a±u200a88.5 vs. 289.8u200a±u200a120.1; pu200a<u200a0.05) and free androgen index (FAI) (59.49u200a±u200a14.79 vs. 83.03u200a±u200a25.81; pu200a<u200a0.0001), and higher levels of estrone (49.5u200a±u200a27.7 vs. 36.6u200a±u200a12.7u2009pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (pu200a<u200a0.05) between testosterone level and serum level of glucose (ru200a=u200a−0.29), triglycerides (ru200a=u200a−0.37), body mass index (ru200a=u200a−0.55), waist (ru200a=u200a−0.43), total body fat mass (ru200a=u200a−0.3) and fasting insulin resistance index. A significant positive association (pu200a<u200a0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (ru200a=u200a0.26). Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.

Silver paper: the future of health promotion and preventive actions, basic research, and clinical aspects of age-related disease--a report of the European Summit on Age-Related Disease.

Background. In September 2008, under the French Presidency of the European Union and with the support of the Polish Minister of Health, a European Summit on Age-Related Disease was organised in Wroclaw (Poland). At this meeting, European politicians, gerontologists and geriatricians gathered to discuss a common approach to future challenges related to age-related disease. Politicians and decision-makers from the European Union and Ministers of Health and their deputies from many European countries raised the problems and difficulties to be tackled in a growing population with a high burden of disease, and asked scientists to write a consensus document with recommendations for future actions and decisions. Scientists and clinicians worked in parallel in three different groups, on health promotion and preventive actions, basic research in age-related disease, and clinical aspects of disease in older people. Beforehand, the format of the paper with recommendations was discussed, and it was finally agreed that, for a better understanding by decision-makers, it would be divided in two different columns: one with facts that were considered settled and agreed by most experts (under the heading We know), and a second with recommendations related to each fact (We recommend). No limit on the number of topics to be discussed was settled. After careful and detailed discussion in each group, which in most cases included the exact wording of each statement, chairpersons presented the results in a plenary session, and new input from all participants was received, until each of the statements and recommendations were accepted by a large majority. Areas with no consensus were excluded from the document. Immediately after the Summit, the chairpersons sent the document both to the main authors and to a list of experts (see footnote) who had made presentations at the summit and agreed to review and critically comment on the final document, which is presented below. As regards the scientific aspects of the planning of the Summit, several organisations, under the leadership of the EUGMS, were asked both to review the program and to suggest names of speakers and participants. After the Summit, the Boards of these organizations (European Union Geriatric Medicine Society (EUGMS), International Association of Gerontology and Geriatrics-European Region (IAGG-ER), European Association of Geriatric Psychiatry (EAGP), International Society of Gerontechnology (ISG) and International Society for the Study of the Aging Male (IS-SAM) agreed to consider the document as an official paper, and help with its dissemination. The name Silver Paper was used, recalling the grey or silvery hair of our older citizens, as an easy reference. It has been sent officially to several bodies of the European Union and to Health Ministers of most European countries; and will be published in other languages in local purnals. Its declared intention is to foster changes in policies which may, in the future, reduce the burden of disease in old age.

Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and cardiovascular risk factors in middle-aged men.

Adiponectin, an adipocyte-derived protein, seems to be a link between obesity, insulin resistance, and atherosclerosis. The present study investigated the association between adiponectin and coronary artery disease in middle-aged men. Material and methods: We examined 48 men (aged 40–60) with angiographically confirmed coronary atherosclerosis and 19 healthy men, matched by age, as a control group. Concentrations of glucose and lipids were estimated with enzymatic methods. Plasma level of adiponectin, total and free testosterone, estradiol, estrone, DHEA-S, and insulin were estimated with RIA commercial kits. Results: Men with coronary atherosclerosis had lower plasma adiponectin level than controls (16.2±9.2 vs 20.5±6.7 µg/mL; p<0.05). However, after including BMI and waist as covariate data in ANCOVA, the difference in adiponectin levels between men with CAD and controls lost statistical significance (respectively for BMI and waist: p=0.4 and p=0.7). Moreover, although not significant, adiponectin levels decreased as a function of the number of significantly narrowed coronary arteries. In a priori comparison the lowest adiponectin plasma concentration was in men with three-vessel coronary artery disease (14.3±9.8 µg/mL) and the highest in controls (20.5±6.8 µg/mL; p=0.09). Adiponectin plasma level correlated negatively (p<0.05) with BMI, waist, percentage of total fat, fasting-insulin-resistance index (FIRI), total cholesterol and triglycerides, and positively with quantitative insulin sensitivity check index (QUICKI), HDL cholesterol, total testosterone, and total testosterone/estradiol ratio. Conclusions: Our data suggest that low plasma adiponectin level is connected with insulin resistance syndrome and atherogenic lipid profile. It seems that adiponectin plays a role in pathogenesis of coronary atherosclerosis, especially in obese and insulin-resistant subjects.

The vitamin D receptor gene BsmI polymorphism is not associated with anthropometric and biochemical parameters describing metabolic syndrome in postmenopausal women

Aim. Vitamin D could have a direct effect on adipocyte differentiation and metabolism and might be involved in glucose regulation of insulin secretion. In recent years several polymorphisms in the gene encoding the vitamin D receptor (VDR), which are potent to alter the activity of VDR protein, have been described. The present study aimed to investigate the prevalence of the VDR BsmI polymorphism and its association with anthropometric and biochemical features of metabolic syndrome in postmenopausal women. Materials and methods. We studied 351 randomly selected healthy postmenopausal women, with mean age of 55.43 ± 2.75 years and mean body mass index (BMI) of 27.5 ± 4.78 kg/m2, to evaluate the frequency of BsmI polymorphism (by restriction fragment length polymorphism–polymerase chain reaction) in the VDR gene and to find out whether there is an association between this polymorphism and BMI, total fat volume and visceral fat (as determined by total body dual-energy X-ray absorptiometry), blood pressure, lipid profile (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides) glucose and fasting insulin in the whole group, as well as subgroups of obese and non-obese women. Results. The prevalence of BsmI genotypes in the study group was 51.0% Bb, 37.3% bb and 11.7% BB. Genotype distribution did not differ from that expected under Hardy–Weinberg equilibrium conditions (χ2 = 2.95, p = 0.22). Apart from LDL-C levels (F = 3.46, p = 0.032), there were no significant differences in anthropometric or metabolic parameters between genotypes. Conclusions. The BsmI polymorphism in the VDR gene does not seem to predispose to obesity and insulin resistance, but the BB genotype is connected with an unfavorable lipid profile.

Serum adiponectin concentration and cardiovascular risk factors in climacteric women

Objective Adiponectin plays a significant role in the modulation of glucose tolerance and insulin sensitivity. We attempted to evaluate the relationship between adiponectin level and parameters of the menopausal metabolic syndrome: body mass index, waist-to-hip ratio, lipid profile and insulin resistance indices. Subjects and methods Thirty-two women and ten men aged 40–63 years were included. The percentage of body fat and of abdominal fat deposits were measured with dual-energy X-ray absorptiometry. Serum adiponectin, tumour necrosis factor-α (TNFα) and leptin were measured with commercially available radioimmunoassay kits. To exclude the influence of nutritional factors on adiponectin secretion, diet content was analysed in the preceding three days. Results Postmenopausal non-obese women had a non-significantly lower level of adiponectin compared with premenopausal women of corresponding body mass. Serum adiponectin level was significantly lower in postmenopausal obese women than in non-obese women (pu200a=u200a0.0023). Men with similar age and body mass to the women had the lowest level of adiponectin (pu200a=u200a0.06). Three months of estrogen replacement therapy in women with surgical menopause did not significantly change the serum level of adiponectin. We found a negative correlation of adiponectin with leptin, insulin resistance index and total cholesterol, and a positive correlation with high-density lipoprotein cholesterol. Adiponectin level was negatively correlated with free testosterone, but we did not find such a relationship with estradiol. There was no correlation of adiponectin level with TNFα; however, serum TNFα correlated positively with leptin. The dietary analysis showed no differences between the diets of obese and non-obese women over the preceding three days. Moreover, mean diastolic and systolic blood pressures were noted to be significantly lower in premenopausal women than in postmenopausal non-obese women (pu200a=u200a0.05). Conclusions Our results suggest that adiponectin could be a marker of risk for developing menopausal metabolic syndrome. Moreover, it is possible that sex steroids have an influence on adiponectin secretion.

Waist circumference and serum adiponectin levels in obese and non-obese postmenopausal women.

OBJECTIVESnA proposed missing link between obesity and metabolic disturbances is adiponectin, an adipocyte-derived peptide. Adiponectin is a potent antidiabetic hormone and seems to have a beneficial influence on lipid profile as well. The need to explain the complex physiological roles of this hormone prompted the authors to study the relationship between adiponectin level and obesity - related abnormalities in a homogenous population of postmenopausal women.nnnSTUDY DESIGNnThe study involved 272 postmenopausal women aged 50-60 years. Invitations to participate in the study were sent to 4000 randomly chosen women from the Wroclaw city population fulfilling the age criterion. A telephone questionnaire was administered to the group of 1731 women who responded to the invitation and then subjects for the study were selected. Main outcome measures anthropometrical measurements of body fat tissue content and fat tissue distribution assessment were carried out in all the women. Moreover, serum concentrations of adiponectin, glucose, total cholesterol, HDL cholesterol, triglycerides and insulin were measured.nnnRESULTSnThe most frequent (76%) phenotype among the investigated women was obesity (BMI >25) with abnormal (=80cm) waist circumference (OAW), Obesity with normal (<80cm) waist (ONW) and normal weight with abnormal waist (NOAW) were observed in only 5% and 14% of the women, respectively. Non-obese women with normal waist (NONW) were noted in only 5% of the subjects. Serum adiponectin levels in both groups of non-obese women (NOAW and NONW) were significantly higher (p<0.05) than in the women with obesity or overweight and abnormal waist circumference (OAW group). Adiponectin levels in the women with obesity or overweight and normal waist (ONW) were also higher than in the OAW group; however, this difference was not statistically significant (p=0.05). In all the women, serum adiponectin level correlated negatively with BMI (r=-0.34, p=0.0001), total fat (r=-0.28, p=0.0001), android fat deposit (r=-0.23, p=0.0001), waist circumference (r=-0.33, p=0.0001), glucose (r=-0.27, p=0.0001), triglycerides (r=-0.34, p=0.0001), and FIRI (r=-0.34, p=0.0001) and positively with the gynoid/android fat deposit ratio (r=0.28, p=0.0001) and HDL cholesterol (r=0.36, p=0.0001).nnnCONCLUSIONSnThese results confirm that adiponectin could be a marker of the development of menopausal insulin resistance syndrome.