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Mora M.,Universitari Of Barcelona | Serra-Prat M.,Research Unit and Ciberhep | Palomera E.,Research Unit and Ciberhep | Puig-Domingo M.,Hospital Universitari Germans Trias i Pujol
Clinical Endocrinology | Year: 2014

Objective Ageing is a physiological process that may be influenced by genetic factors as well as metabolic and hormonal determinants. The aim was to describe metabolic and hormonal factors related to survival in the cohort of non-institutionalized people aged >70 years old of the Matarõ Ageing Study. Design and methods 313 individuals were included and followed-up during 8 years. Metabolic syndrome (MS) parameters by International Diabetes Federation and ATP-III as well as hormonal factors (TSH, free-T4, growth hormone, IGF-I, ghrelin, cortisol, dehidroepiandrosterone -DHEA-, DHEAs, testosterone, SHBG, estradiol, estrone, cortisol/DHEA and cortisol/DHEAs) were studied and their relationship with survival was assessed. Results At 8 year of follow-up, 96 out of 313 subjects (30·7%) died. No association between MS and its components and survival was found. However, when abdominal perimeter was analyzed according to distribution in quartiles and categorized by gender, the lowest and highest quartile showed higher mortality (P = 0·009; waist circumference (WC) between 98-102 cm in men and 95-102 cm in women were associated to lower mortality). In men, IGF-I, estrone, cortisol/DHEA ratio and cortisol/DHEAs ratio were lower in survivors, and in women, growth hormone and ghrelin were higher in survivors and cortisol/DHEAs ratio was lower. When Cox regression was performed for survival analysis of the whole cohort (adjusting by age, gender, tobacco consumption and WC, cortisol (B = 0·036, P = 0·033), estrone (B = 0·014, P = 0·004) and cortisol/DHEA ratio (B = 0·018, P = 0·008) were significantly associated to mortality. Sequential adjustments including additionally in the model Lawton scale, MiniNutritional Assessment and MCE showed significant association to estrone (P = 0·018). Conclusions Waist circumference in a U-shaped relationship, together with hormonal factors (adrenal steroids and somatotropic axis) influenced survival in individuals participating in Matarõ Ageing Study.

Mora M.,Hospital Clinic of Barcelona | Adam V.,Genotyping and Genetic Diagnosis Unit | Palomera E.,Research Unit and Ciberhep | Blesa S.,Genotyping and Genetic Diagnosis Unit | And 9 more authors.
PLoS ONE | Year: 2015

Background The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people. Objectives We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components. Subjects and Methods 824 subjects (413 men/411 women, age 77.31±5.04) participating in the Mataró aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%. Results No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of -604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters. Conclusion Ghrelin gene variants -604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects. Copyright © 2015 Mora et al.

Mora M.,Universitari Of Barcelona | Granada M.L.,Hospital Universitari Germans Trias i Pujol | Roca M.,Hospital Universitari Germans Trias i Pujol | Palomera E.,Research Unit and Ciberhep | And 3 more authors.
Clinical Endocrinology | Year: 2013

Objective Ghrelin and obestatin have apparent opposite orexigenic and anorexigenic effects, although the latter has not been firmly demonstrated in humans. So far, little data have been reported in relation to its potential association with metabolic syndrome (MS). The objective was to study obestatin concentrations in relation to nutritional parameters and eating behaviours in old women. Design, Patients and Measurements Prospective study; a total of 110 women (age: 76·93 ± 6·32) from the Matarõ Ageing Study were included. Individuals were characterized by anthropometric variables, lipids, glucose, blood pressure, MS components (Adult Treatment Panel III criteria), anorexia and nutritional status by Mini Nutritional Assessment Short Form (MNA-SF) and re-evaluated at 2-year follow-up. Obestatin was measured by IRMA. Results 58·2% of the subjects had MS; at 2-year follow-up 24·1% had a weight loss >5%, 7·2% >10%, and 26·4% changed their MNA-SF score to risk of malnutrition category. Anorexia was present in 38·4%. Obestatin levels were not related to either change of weight, MNA-SF or anorexia, but a positive correlation was found with the absolute difference between basal and 2-year waist circumference (WC) (r = 0·429; P < 0·001) and relative difference between basal and 2-year WC (r = 0·420; P < 0·001); both remained significant after adjusting for age and body mass index. When obestatin was divided into quartiles, a significant lineal trend was observed in relation to WC (P = 0·049), absolute and relative difference between basal and 2-year WC (both P < 0·001). Obestatin was associated with glucose impairment (69·0% in 4th quartile vs 47·5% in 1st to 3rd, P = 0·047; after adjustment, P = 0·098) and MS (77·8% in 4th vs 51·3% in 1st to 3rd, P = 0·017; after adjustment, P = 0·046, OR 2·90 (1·02-8·25) 4th vs 1st to 3rd). Conclusions Obestatin is elevated in aged women bearing MS but is otherwise not associated with other nutritional parameters, weight loss or anorexia. © 2012 John Wiley & Sons Ltd.

Mora M.,Hospital Clinic i Universitari of Barcelona | Granada M.L.,Hospital Universitari Germans Trias i Pujol | Palomera E.,Research Unit and Ciberhep | Serra-Prat M.,Research Unit and Ciberhep | Puig-Domingo M.,Hospital Universitari Germans Trias i Pujol
Age | Year: 2013

Obestatin has been proposed to have anorexigenic and anti-ghrelin actions. The objective was to study obestatin concentrations in relation to handgrip strength, functional capacity and cognitive state in old women. The prospective study included 110 women (age, 76.93±6.32) from the Mataró Ageing Study. Individuals were characterized by anthropometric variables, grip strength, Barthel and assessment of cognitive impairment [Mini Cognoscitive Examination (MCE) Spanish version], depressive status by the Geriatric Depression Scale (GDS) and frailty by the Fried criteria. Obestatin was measured by IRMA. Obestatin showed negative correlation to handgrip at basal time point (r= -0.220, p=0.023) and at 2-year follow-up (r=-0.344, p=0.002). Obestatin, divided into quartiles, showed a negative lineal association with handgrip: 11.03± 4.88 kg in first, 8.75±4.08 kg in second, 8.11±3.66 kg in third and 7.61±4.08 kg in fourth quartile (p=0.018). Higher obestatin levels were associated to increased weakness (categorized by handgrip of frailty criteria): 2.24±0.42 ng/ml in weak vs. 1.87±0.57 ng/ml in nonweak (p=0.01). The decrease of either MCE or Barthel scores at 2-year follow-up was significantly higher in individuals in the fourth quartile of obestatin in comparison with individuals in the first quartile (p=0.046 and p=0.019, respectively). No association was found between obestatin and GDS score and neither with frailty as a condition. Obestatin is associated to low muscle strength, and impaired functional and cognitive capacity in old women participating in theMataró Ageing Study. © American Aging Association 2012.

Mora M.,Hospital Clinic iversitari Of Barcelona | Mansego M.L.,University of Navarra | Mansego M.L.,Hospital Clinico Universitario Of Valencia | Serra-Prat M.,Research Unit and Ciberhep | And 4 more authors.
Aging Clinical and Experimental Research | Year: 2014

Background and aims: Cognitive state and brain volume have been related to body mass index, abdominal fat, waist-hip ratio, components of metabolic syndrome (MS) and ghrelin. Genetic variations within the ghrelin gene have been recently associated to MS. The aim of our study was to investigate cognitive state by Mini-Mental State Examination (MMSE) in relation to MS components (ATP-III criteria) and ghrelin gene polymorphisms in dwelling individuals aged ≥70. Methods: 280 subjects (137 men/143 women, age 77.03 ± 5.92) from the Mataró Ageing Study were included. Individuals were phenotypically characterized by anthropometric variables, lipids, glucose, blood pressure and MMSE. SNPs -501AC (rs26802), -994CT (rs26312), -604GA (rs27647), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene were studied. Genotypes were determined by polymerase chain reaction and SNapshot minisequencing. Results: 22.1% had MMSE <24. MMSE <24 was associated with age (p < 0.001), female gender (p = 0.016), low education (p < 0.001) and glucose impairment or diabetes (p = 0.040). MMSE was influenced by obesity, central obesity, MS and glucose impairment. This latter association remained significant after adjustment by gender, age, alcohol, educational level, GDS and ApoE genotype (p = 0.009). Ghrelin SNPs were associated to MMSE: M72L C/A genotype showed lower score than C/C (p = 0.032, after adjusting for confounders 0.049); L90G A/T genotype showed lower score than A/A (p = 0.054, after adjusting 0.005). MMSE <24 was associated to L90G (39.1% in A/T genotype vs 19.3% in A/A, p = 0.026, after adjusting for confounders p = 0.002, OR 6.18 CI 1.93-21.75). Conclusions: Glucose impairment and L90G Ghrelin gene variant influence cognitive function in old dwelling individuals participating in the Mataró Ageing Study. © Springer International Publishing 2014.

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