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Authors: Revathi S. Rajan, Pratibha Malik, Nupur Garg, Smitha Avula, Kamini A. Rao

Abstract:

This study aimed to analyse the pregnancy outcomes in patients with TPO positivity after appropriate L-Thyroxin supplementation with close surveillance. All pregnant women attending the antenatal clinic at Milann-The Fertility Center, Bangalore, India- from Aug 2013 to Oct 2014 whose booking TSH was more than 2.5 mIU/L were included along with those pregnant women with prior hypothyroidism who were TPO positive. Those with TPO positive status were vigorously managed with appropriate thyroxin supplementation and the doses were readjusted every 3 to 4 weeks until delivery. Women with recurrent pregnancy loss were also tested for TPO positivity and if tested positive, were monitored serially with TSH and fT4 levels every 3 to 4 weeks and appropriately supplemented with thyroxin when the levels fluctuated. The testing was done after an informed consent in all these women. The statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used for the analysis of the data. 460 pregnant women were screened for thyroid dysfunction at booking of which 52% were hypothyroid. Majority of them (31.08%) were subclinically hypothyroid and the remaining were overt. 25% of the total no. of patients screened were TPO positive. The various pregnancy complications that were observed in the TPO positive women were gestational glucose intolerance [60%], threatened abortion [21%], midtrimester abortion [4.3%], premature rupture of membranes [4.3%], cervical funneling [4.3%] and fetal growth restriction [3.5%]. 95.6% of the patients who followed up till the end delivered beyond 30 weeks. 42.6% of these patients had previous history of recurrent abortions or adverse obstetric outcome and 21.7% of the delivered babies required NICU admission. Obstetric outcomes in our study in terms of midtrimester abortions, placental abruption, and preterm delivery improved for the better after close monitoring of the thyroid hormone [TSH and fT4] levels every 3 to 4 weeks with appropriate dose adjustment throughout pregnancy. Euthyroid women with TPO positive status enrolled in the study incidentally were those with recurrent abortions/infertility and required thyroxin supplements due to elevated Thyroid hormone (TSH, fT4) levels during the course of their pregnancy. Significant associations were found with age>30 years and Hyperhomocysteinemia [p=0.017], recurrent pregnancy loss or previous adverse obstetric outcomes [p=0.067] and APLA [p=0.029]. TPO antibody levels >600 I U/ml were significantly associated with development of gestational hypertension [p=0.041] and fetal growth restriction [p=0.082]. Euthyroid women with TPO positivity were also screened periodically to counter fluctuations of the thyroid hormone levels with appropriate thyroxin supplementation. Thus, early identification along with aggressive management of thyroid dysfunction and stratification of these patients based on their TPO status with appropriate thyroxin supplementation beginning in the first trimester will aid risk modulation and also help avert complications.

Keywords: Antinuclear antibody, Subclinical hypothyroidism, Thyroxin, TPO antibody.

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Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Obesity is known to be associated with many clinically important diseases including metabolic syndrome (MetS). Vitamin B₁₂ plays essential roles in fat and protein metabolisms and its cooperation with vitamin B₉ is well-known. The aim of this study is to investigate the possible contributions as well as associations of these micronutrients upon obesity and MetS during childhood. A total of 128 children admitted to Namik Kemal University, Medical Faculty, Department of Pediatrics Outpatient Clinics were included into the scope of this study. The mean age±SEM of 92 morbid obese (MO) children and 36 with MetS were 118.3±3.8 months and 129.5±6.4 months, respectively (p > 0.05). The study was approved by Namık Kemal University, Medical Faculty Ethics Committee. Written informed consent forms were obtained from the parents. Demographic features and anthropometric measurements were recorded. WHO BMI-for age percentiles were used. The values above 99 percentile were defined as MO. Components of MetS [waist circumference (WC), fasting blood glucose (FBG), triacylglycerol (TRG), high density lipoprotein cholesterol (HDL-Chol), systolic pressure (SP), diastolic pressure (DP)] were determined. Routine laboratory tests were performed. Serum vitamin B₁₂ concentrations were measured using electrochemiluminescence immunoassay. Vitamin B₉ was analyzed by an immunoassay analyzer. Values for vitamin B₁₂ < 148 pmol/L, 148-221 pmol/L, > 221 pmol/L were accepted as low, borderline and normal, respectively. Vitamin B₉ levels ≤ 4 mcg/L defined deficiency state. Statistical evaluations were performed by SPSSx Version 16.0. p≤0.05 was accepted as statistical significance level. Statistically higher body mass index (BMI), WC, hip circumference (C) and neck C were calculated in MetS group compared to children with MO. No difference was noted for head C. All MetS components differed between the groups (SP, DP p < 0.001; WC, FBG, TRG p < 0.01; HDL-Chol p < 0.05). Significantly decreased vitamin B₉ and vitamin B₁₂ levels were detected (p < 0.05) in children with MetS. In both groups percentage of folate deficiency was 5.5%. No cases were below < 148 pmol/L. However, in MO group 14.3% and in MetS group 22.2% of the cases were of borderline status. In MO group B₁₂ levels were negatively correlated with BMI, WC, hip C and head C, but not with neck C. WC, hip C, head C and neck C were all negatively correlated with HDL-Chol. None of these correlations were observed in the group of children with MetS. Strong positive correlation between FBG and insulin as well as strong negative correlation between TRG and HDL-Chol detected in MO children were lost in MetS group. Deficiency state end-products of both B₉ and B₁₂ may interfere with the expected profiles of MetS components. In this study, the alterations in MetS components affected vitamin B₁₂ metabolism and also its associations with anthropometric body measurements. Further increases in vitamin B₁₂ and vitamin B₉ deficiency in MetS associated with the increased vitamin B₁₂ as well as vitamin B₉ deficiency metabolites may add to MetS parameters.

Keywords: Children, cobalamin, folate, metabolic syndrome, obesity.

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Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Cardiovascular (CV) pathology is one of the expected consequences of excessive fat gain. The role of zinc (Zn) in thyroid hormone metabolism (THM) is a matter of debate. Both thyroid stimulating hormone (TSH) and Zn levels are subject to variation in obese individuals. Zn participates in THM. It is closely related to TSH. Since thyroid hormones are required for Zn absorption, hypothyroidism can lead to Zn deficiency and vice versa. Zn exhibits protective effects on CV health and it is inversely correlated with CV markers in childhood obesity. The association between subclinical hypothyroidism (SCHT) and metabolic disorders is under investigation due to its clinical importance. SCHT is defined as the elevated serum TSH levels in the presence of normal free thyroxin (T4) concentrations. The aim of this study is to evaluate the associations between TSH levels and Zn concentrations in SCHT cases detected in morbid obese (MO) children with and without metabolic syndrome (MetS) [(MOMetS+ and MOMetS-)], respectively. 42 children were present in each study group. Informed consent forms were obtained. Tekrdag Namik Kemal University Faculty of Medicine Non-Interventional Clinical Investigations Ethical Committee approved the study protocol. World Health Organization criteria were used for obesity classification. Children with age and sex-dependent body mass index percentile values above 99 were defined as MO. Children exhibiting at least two of MetS criteria were included in MOMetS+ group. Elevated fasting blood glucose, elevated triglycerides (TRG)/decreased high density lipoprotein-cholesterol (HDL-C) concentrations, elevated blood pressure values in addition to central obesity were listed as MetS criteria. Anthropometric measures were recorded. Routine biochemical analyses were performed. In MOMetS- group 13, in MOMetS+ group 15 children were with SCHT. Statistical analyses were performed. p < 0.05 was accepted as statistically significant. In MOMetS- and MOMetS+ groups, TSH levels were 4.1 ± 2.9 mU/L and 4.6 ± 3.1 mU/L, respectively. Corresponding values for SCHT cases were 7.3 ± 3.1 mU/L and 8.0 ± 2.7 mU/L. Free T4 levels were within normal limits. Zn concentrations were negatively correlated with TSH levels in both groups. Significant negative correlation calculated in MOMetS+ group (r = -0.909; p < 0.001) was much stronger than that found in MOMetS- group (r = -0.706; p < 0.05). This strong correlation (r = -0.909; p < 0.001) calculated for cases with SCHT in MOMetS+ group was much lower in the same group (r = -0.793; p < 0.001) when all cases were considered. In conclusion, the presence of strong correlations between TSH and Zn in SCHT in both MOMetS- and MOMetS+ groups have pointed out that MO children were under the threat of CV pathologies. The detection of the much stronger correlation in MOMetS+ group in comparison with the correlation found in MOMetS- group was the indicator of greater CV risk due to the presence of MetS. In MOMetS+ group, correlation in SCHT cases found higher than correlation calculated for all cases confirmed much higher CV risk due to the contribution of SCHT.

Keywords: Cardiovascular risk, child morbid obesity, subclinical hypothyroidism, zinc.

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Authors: Mike Climstein, Joe Walsh, John Best, Ian Timothy Heazlewood, Stephen Burke, Jyrki Kettunen, Kent Adams, Mark DeBeliso

Abstract:

Recently, the health of retired National Football League players, particularly lineman has been investigated. A number of studies have reported increased cardiometabolic risk, premature cardiovascular disease and incidence of type 2 diabetes. Rugby union players have somatotypes very similar to National Football League players which suggests that rugby players may have similar health risks. The International Golden Oldies World Rugby Festival (GORF) provided a unique opportunity to investigate the demographics of veteran rugby players. METHODOLOGIES: A cross-sectional, observational study was completed using an online web-based questionnaire that consisted of medical history and physiological measures. Data analysis was completed using a one sample t-test (<50yrs versus >50yrs) and Chi-square test. RESULTS: A total of 216 veteran rugby competitors (response rate = 6.8%) representing 10 countries, aged 35-72 yrs (mean 51.2, S.D. ±8.0), participated in the online survey. As a group, the incidence of current smokers was low at 8.8% (avg 72.4 cigs/wk) whilst the percentage consuming alcohol was high (93.1% (avg 11.2 drinks/wk). Competitors reported the following top six chronic diseases/disorders; hypertension (18.6%), arthritis (OA/RA, 11.5%), asthma (9.3%), hyperlipidemia (8.2%), diabetes (all types, 7.5%) and gout (6%), there were significant differences between groups with regard to cancer (all types) and migraines. When compared to the Australian general population (Australian Bureau of Statistics data, n=18,000), GORF competitors had a significantly lower incidence of anxiety (p<0.01), arthritis (p<0.06), depression (p<.01) however, a significantly higher incidence of diabetes (p<0.03) and hypertension (p<0.01). The GORF competitors also reported taking the following prescribed medications; antihypertensive (13%), hypolipidemics (8%), non-steroidal anti-inflammatory (6%), and anticoagulants (4%). Significant differences between groups were observed in antihypertensives, anticoagulants and hypolipidemics. There were significant (p<0.05) differences between groups (<50yrs versus >50yrs) with regard to height (180 vs 177cm), weight (97.6 vs 93.1Kg-s), BMI (30 vs 29.7kg/m2) and waist circumference (85.7 vs 93.1cm) however, there were no differences in subsequent parameters of systolic blood pressure, diastolic blood pressure, total cholesterol, HDL-C, LDL-C, triglycerides-C or fasting plasma glucose. CONCLUSIONS: This represents the first collection of demographics on this cohort. GORF participants demonstrated increased cardiometabolic risk with regard to the incidence of hypercholesterolemia, hypertension and type 2 diabetes. Preventative strategies should be developed to reduce this risk with education of these risks for future participants.

Keywords: Masters athlete, rugby union, risk factors, chronic disease

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Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Metabolisms of macrominerals, those of calcium, phosphorus and magnesium, are closely associated with the metabolism of vitamin D. Particularly magnesium, the second most abundant intracellular cation, is related to biochemical and metabolic processes in the body, such as those of carbohydrates, proteins and lipids. The status of each mineral was investigated in obesity to some extent. Their products and ratios may possibly give much more detailed information about the matter. The aim of this study is to investigate possible relations between each macromineral and some obesity-related parameters. This study was performed on 235 children, whose ages were between 06-18 years. Aside from anthropometric measurements, hematological analyses were performed. TANITA body composition monitor using bioelectrical impedance analysis technology was used to establish some obesity-related parameters including basal metabolic rate (BMR), total fat, mineral and muscle masses. World Health Organization body mass index (BMI) percentiles for age and sex were used to constitute the groups. The values above 99^th percentile were defined as morbid obesity. Those between 95^th and 99^th percentiles were included into the obese group. The overweight group comprised of children whose percentiles were between 95 and 85. Children between the 85^th and 15^th percentiles were defined as normal. Metabolic syndrome (MetS) components (waist circumference, fasting blood glucose, triacylglycerol, high density lipoprotein cholesterol, systolic pressure, diastolic pressure) were determined. High performance liquid chromatography was used to determine Vitamin D status by measuring 25-hydroxy cholecalciferol (25-hydroxy vitamin D₃, 25(OH)D). Vitamin D values above 30.0 ng/ml were accepted as sufficient. SPSS statistical package program was used for the evaluation of data. The statistical significance degree was accepted as p < 0.05. The important points were the correlations found between vitamin D and magnesium as well as phosphorus (p < 0.05) that existed in the group with normal BMI values. These correlations were lost in the other groups. The ratio of phosphorus to magnesium was even much more highly correlated with vitamin D (p < 0.001). The negative correlation between magnesium and total fat mass (p < 0.01) was confined to the MetS group showing the inverse relationship between magnesium levels and obesity degree. In this group, calcium*magnesium product exhibited the highest correlation with total fat mass (p < 0.001) among all groups. Only in the MetS group was a negative correlation found between BMR and calcium*magnesium product (p < 0.05). In conclusion, magnesium is located at the center of attraction concerning its relationships with vitamin D, fat mass and MetS. The ratios and products derived from macrominerals including magnesium have pointed out stronger associations other than each element alone. Final considerations have shown that unique correlations of magnesium as well as calcium*magnesium product with total fat mass have drawn attention particularly in the MetS group, possibly due to the derangements in some basic elements of carbohydrate as well as lipid metabolism.

Keywords: Macrominerals, metabolic syndrome, pediatric obesity, vitamin D.

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Authors: Orkide Donma, Mustafa M. Donma, Muhammet Demirkol, Murat Aydin, Tuba Gokkus, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

Abstract:

Obesity in childhood establishes a ground for adulthood obesity. Especially morbid obesity is an important problem for the children because of the associated diseases such as diabetes mellitus, cancer and cardiovascular diseases. In this study, body mass index (BMI), body fat ratios, anthropometric measurements and ratios were evaluated together with different laboratory indices upon evaluation of obesity in morbidly obese (MO) children. Children with nutritional problems participated in the study. Written informed consent was obtained from the parents. Study protocol was approved by the Ethics Committee. Sixty-two MO girls aged 129.5±35.8 months and 75 MO boys aged 120.1±26.6 months were included into the scope of the study. WHO-BMI percentiles for age-and-sex were used to assess the children with those higher than 99^th as morbid obesity. Anthropometric measurements of the children were recorded after their physical examination. Bio-electrical impedance analysis was performed to measure fat distribution. Anthropometric ratios, body fat ratios, Index-I and Index-II as well as insulin sensitivity indices (ISIs) were calculated. Girls as well as boys were binary grouped according to homeostasis model assessment-insulin resistance (HOMA-IR) index of <2.5 and >2.5, fasting glucose to insulin ratio (FGIR) of <6 and >6 and quantitative insulin sensitivity check index (QUICKI) of <0.33 and >0.33 as the frequently used cut-off points. They were evaluated based upon their BMIs, arms, legs, trunk, whole body fat percentages, body fat ratios such as fat mass index (FMI), trunk-to-appendicular fat ratio (TAFR), whole body fat ratio (WBFR), anthropometric measures and ratios [waist-to-hip, head-to-neck, thigh-to-arm, thigh-to-ankle, height/2-to-waist, height/2-to-hip circumference (C)]. SPSS/PASW 18 program was used for statistical analyses. p≤0.05 was accepted as statistically significance level. All of the fat percentages showed differences between below and above the specified cut-off points in girls when evaluated with HOMA-IR and QUICKI. Differences were observed only in arms fat percent for HOMA-IR and legs fat percent for QUICKI in boys (p≤ 0.05). FGIR was unable to detect any differences for the fat percentages of boys. Head-to-neck C was the only anthropometric ratio recommended to be used for all ISIs (p≤0.001 for both girls and boys in HOMA-IR, p≤0.001 for girls and p≤0.05 for boys in FGIR and QUICKI). Indices which are recommended for use in both genders were Index-I, Index-II, HOMA/BMI and log HOMA (p≤0.001). FMI was also a valuable index when evaluated with HOMA-IR and QUICKI (p≤0.001). The important point was the detection of the severe significance for HOMA/BMI and log HOMA while they were evaluated also with the other indices, FGIR and QUICKI (p≤0.001). These parameters along with Index-I were unique at this level of significance for all children. In conclusion, well-accepted ratios or indices may not be valid for the evaluation of both genders. This study has emphasized the limiting properties for boys. This is particularly important for the selection process of some ratios and/or indices during the clinical studies. Gender difference should be taken into consideration for the evaluation of the ratios or indices, which will be recommended to be used particularly within the scope of obesity studies.

Keywords: Anthropometry, childhood obesity, gender, insulin sensitivity index.

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Authors: Orkide Donma, Mustafa M. Donma

Abstract:

Childhood obesity, which may lead to increased risk for heart diseases in children as well as adults, is one of the most important health problems throughout the world. Prevalences of morbid obesity and metabolic syndrome (MetS) are being increased during childhood age group. MetS is a cluster of metabolic and vascular abnormalities including hypercoagulability and an increased risk of cardiovascular diseases (CVDs). There are also some relations between some components of MetS and leukocytes. The aim of this study is to investigate complete blood cell count parameters that differ between morbidly obese boys and girls with MetS diagnosis. A total of 117 morbid obese children with MetS consulted to Department of Pediatrics in Faculty of Medicine Hospital at Namik Kemal University were included into the scope of the study. The study population was classified based upon their genders (60 girls and 57 boys). Their heights and weights were measured and body mass index (BMI) values were calculated. WHO BMI-for age and sex percentiles were used. The values above 99 percentile were defined as morbid obesity. Anthropometric measurements were performed. Waist-to-hip and head-to-neck ratios as well as homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Hematological variables were measured. Statistical analyses were performed using SPSS. The degree for statistical significance was p ≤ 0.05. There was no statistically significant difference between the ages (11.2±2.6 years vs 11.2±3.0 years) and BMIs (28.6±5.2 kg/m² vs 29.3±5.2 kg/m²) of boys and girls (p ≥ 0.05), respectively. Significantly increased waist-to-hip ratios were obtained for boys (0.94±0.08 vs 0.91±0.06; p=0.023). Significantly elevated values of hemoglobin (13.55±0.98 vs 13.06±0.82; p=0.004), mean corpuscular hemoglobin concentration (33.79±0.91 vs 33.21±1.14; p=0.003), eosinophils (0.300±0.253 vs 0.196±0.197; p=0.014), and platelet (347.1±81.7 vs 319.0±65.9; p=0.042) were detected for boys. There was no statistically significant difference between the groups in terms of neutrophil/lymphocyte ratios as well as HOMA-IR values (p ≥ 0.05). Statistically significant gender-based differences were found for hemoglobin as well as mean corpuscular hemoglobin concentration and hence, separate reference intervals for two genders should be considered for these parameters. Eosinophils may contribute to the development of thrombus in acute coronary syndrome. Eosinophils are also known to make an important contribution to mechanisms related to thrombosis pathogenesis in acute myocardial infarction. Increased platelet activity is observed in patients with MetS and these individuals are more susceptible to CVDs. In our study, elevated platelets described as dominant contributors to hypercoagulability and elevated eosinophil counts suggested to be related to the development of CVDs observed in boys may be the early indicators of the future cardiometabolic complications in this gender.

Keywords: Children, complete blood count, gender, metabolic syndrome.

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Authors: Climstein Mike, Walsh Joe, John Best, Heazlewood Ian Timothy, Burke Stephen, Kettunen Jyrki, Adams Kent, DeBeliso Mark

Abstract:

Recently, the health of retired National Football League players, particularly lineman has been investigated. A number of studies have reported increased cardiometabolic risk, premature ardiovascular disease and incidence of type 2 diabetes. Rugby union players have somatotypes very similar to National Football league players which suggest that rugby players may have similar health risks. The International Golden Oldies World Rugby Festival (GORF) provided a unique opportunity to investigate the demographics of veteran rugby players. METHODOLOGIES: A cross-sectional, observational study was completed using an online web-based questionnaire that consisted of medical history and physiological measures. Data analysis was completed using a one sample t-test (<50yrs versus >50yrs) and Chi-square test. RESULTS: A total of 216 veteran rugby competitors (response rate = 6.8%) representing 10 countries, aged 35-72 yrs (mean 51.2, S.D. ±8.0), participated in the online survey. As a group, the incidence of current smokers was low at 8.8% (avg 72.4 cigs/wk) whilst the percentage consuming alcohol was high (93.1% (avg 11.2 drinks/wk). Competitors reported the following top six chronic diseases/disorders; hypertension (18.6%), arthritis (OA/RA, 11.5%), asthma (9.3%), hyperlipidemia (8.2%), diabetes (all types, 7.5%) and gout (6%), there were significant differences between groups with regard to cancer (all types) and migraines. When compared to the Australian general population (Australian Bureau of Statistics data, n=18,000), GORF competitors had a Climstein Mike, Walsh Joe (corresponding author) and Burke Stephen School of Exercise Science, Australian Catholic University, 25A Barker Road, Strathfield, Sydney, NSW, 2016, Australia (e-mail: [email protected], [email protected], [email protected]). John Best is with Orthosports, 160 Belmore Rd., Randwick, Sydney,NSW 2031, Australia (e-mail: [email protected]). Heazlewood, Ian Timothy is with School of Environmental and Life Sciences, Faculty Education, Health and Science, Charles Darwin University, Precinct Yellow Building 2, Charles Darwin University, NT 0909, Australia (e-mail: [email protected]). Kettunen Jyrki Arcada University of Applied Sciences, Jan-Magnus Janssonin aukio 1, FI-00550, Helsinki, Finland (e-mail: [email protected]). Adams Kent is with California State University Monterey Bay, Kinesiology Department, 100 Campus Center, Seaside, CA., 93955, USA (email: [email protected]). DeBeliso Mark is with Department of Physical Education and Human Performance, Southern Utah University, 351 West University Blvd, Cedar City, Utah, USA (e-mail: [email protected]). significantly lower incidence of anxiety (p<0.01), arthritis (p<0.06), depression (p<.01) however, a significantly higher incidence of diabetes (p<0.03) and hypertension (p<0.01). The GORF competitors also reported taking the following prescribed medications; antihypertensive (13%), hypolipidemics (8%), non-steroidal anti-inflammatory (6%), and anticoagulants (4%). Significant differences between groups were observed in antihypertensives, anticoagulants and hypolipidemics. There were significant (p<0.05) differences between groups (<50yrs versus >50yrs) with regard to height (180 vs 177cm), weight (97.6 vs 93.1Kg-s), BMI (30 vs 29.7kg/m2) and waist circumference (85.7 vs 93.1cm) however, there were no differences in subsequent parameters of systolic blood pressure, diastolic blood pressure, total cholesterol, HDL-C, LDL-C, triglycerides-C or fasting plasma glucose. CONCLUSIONS: This represents the first collection of demographics on this cohort. GORF participants demonstrated increased cardiometabolic risk with regard to the incidence of hypercholesterolemia, hypertension and type 2 diabetes. Preventative strategies should be developed to reduce this risk with education of these risks for future participants.

Keywords: Masters athlete, rugby union, risk factors, chronic disease.

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