Vitamin D as a Biomarker of Ill Health among the Over-50s: A Systematic Review of Cohort Studies.

BACKGROUND: The association between circulating levels of vitamin D and the incidence of chronic diseases is known. The identification of vitamin D as a biomarker of physiological/pathological ageing could contribute to expanding current knowledge of its involvement in healthy ageing. METHODS: According to PRISMA guidelines, a systematic review was conducted on cohorts studying the role of 25OH-Vitamin D [25(OH)D] and 1,25(OH)2-Vitamin D [1,25(OH)2D] concentrations as biomarkers of healthy ageing. We consulted MedLine, Scopus, and Web of Science to search for studies on the association between vitamin D status in populations of originally healthy adults, and outcomes of longevity, illness, and physical and cognitive functionality. The quality of the studies was assessed using the Newcastle Ottawa scale. RESULTS: Twenty cohorts from 24 articles were selected for this review. Inverse associations were found between low 25(OH)D levels and all-cause mortality, respiratory and cardiovascular events, as well as markers relating to hip and non-vertebral fractures. Associations between 1,25(OH)2D and healthy ageing outcomes gave similar results, although of lower clinical significance. CONCLUSIONS: This systematic review pinpoints peculiar aspects of vitamin D as a multidimensional predictor of ill health in the ageing process. Further well-designed controlled trials to investigate whether vitamin D supplement results in superior outcomes are warranted in the future.

Assessment of fat-free mass from bioelectrical impedance analysis in men and women with Prader-Willi syndrome: cross-sectional study.

We have recently shown that population-specific formulae are required to estimate fat-free mass (FFM) from bioelectrical impedance analysis (BIA) in obese women with Prader-Willi syndrome (PWS) matched by age and percent fat mass (FM) to non-PWS women. The present cross-sectional study was aimed at developing generalised BIA equations that could be used in PWS subjects independently of sex and FM. We used dual-energy X-ray absorptiometry to measure FFM and BIA to measure whole-body impedance at 50 kHz (Z50) in 34 women and 21 men with PWS. The impedance index, that is, height (cm)2/Z50 (Ω), explained 77% (BCa-bootstrapped 95% CI 65 to 85%) of the variance of FFM with a root mean squared error of the estimate of 3.7 kg (BCa-bootstrapped 95% CI 3.2 to 4.5 kg). BIA can be used to estimate FFM in obese and non-obese PWS men and women by means of population-specific equations.

The relationship between resting energy expenditure and thyroid hormones in response to short-term weight loss in severe obesity.

BACKGROUND: Regulating thermogenesis is a major task of thyroid hormones (THs), and involves TH-responsive energetic processes at the central and peripheral level. In severe obesity, little is known on the relationship between THs and resting energy expenditure (REE) before and after weight loss. METHODS: We enrolled 100 euthyroid subjects with severe obesity who were equally distributed between genders. Each was examined before and after completion of a 4-wk inpatient multidisciplinary dieting program and subjected to measurement of thyroid function, REE, fat-free mass (FFM, kg) and percent fat mass (FM). RESULTS: Baseline REE was lower than predicted in 70 obese patients, and overall associated with BMI, FFM and FM but not thyroid-related parameters. By the study end, both BMI and REE decreased (5.5% and 4.1%, p<0.001 vs. baseline) and their percent changes were significantly associated (p<0.05), while no association related percent changes of REE and FFM or FM. Individually, REE decreased in 66 and increased in 34 patients irrespective of gender, BMI and body composition. Weight loss significantly impacted TSH (-6.3%), FT3 (-3.3%) and FT4 levels (3.9%; p<0.001 for all). By the study end, a significant correlation became evident between REE and FT4 (r = 0.42, p<0.001) as well as FT3 (r = 0.24, p<0.05). In stepwise multivariable regression analysis, however, neither THs nor body composition entered the regression equation for REE response to weight loss. CONCLUSIONS: In severe obesity, short-term weight loss discloses a positive relationship between REE and THs.

Analysis of Predictive Equations for Estimating Resting Energy Expenditure in a Large Cohort of Morbidly Obese Patients.

The treatment of obesity requires creating an energy deficit through caloric restriction and physical activity. Energy needs are estimated assessing the resting energy expenditure (REE) that in the clinical practice is estimated using predictive equations. In the present cross sectional study, we compared, in a large cohort of morbidly obese patients, the accuracy of REE predictive equations recommended by current obesity guidelines [Harris-Benedict, WHO/FAO/ONU and Mifflin-St Jeor (MJ)] and/or developed for obese patients (Muller, Muller BC, Lazzer, Lazzer BC), focusing on the effect of comorbidities on the accuracy of the equations. Data on REE measured by indirect calorimetry and body composition were collected in 4,247 obese patients (69% women, mean age 48 ± 19 years, mean BMI 44 ± 7 Kg/m2) admitted to the Istituto Auxologico Italiano from 1999 to 2014. The performance of the equations was assessed in the whole cohort, in 4 groups with 0, 1, 2, or ≥ 3 comorbidities and in a subgroup of 1,598 patients with 1 comorbidity (47.1% hypertension, 16.7% psychiatric disorders, 13.3% binge eating disorders, 6.1% endocrine disorders, 6.4% type 2 diabetes, 3.5% sleep apnoea, 3.1% dyslipidemia, 2.5% coronary disease). In the whole cohort of obese patients, as well as in each stratum of comorbidity number, the MJ equation had the highest performance for agreement measures and bias. The MJ equation had the best performance in obese patients with ≥3 comorbidities (accuracy of 61.1%, bias of -89.87) and in patients with type 2 diabetes and sleep apnoea (accuracy/bias 69%/-19.17 and 66%/-21.67 respectively), who also have the highest levels of measured REE. In conclusion, MJ equation should be preferred to other equations to estimate the energy needs of Caucasian morbidly obese patients when measurement of the REE cannot be performed. As even MJ equation does not precisely predict REE, it should be better to plan the diet intervention by measuring rather than estimating REE. Future studies focusing on the clinical differences that determine the high inter-individual variability of the precision of the REE predictive equations (e.g., on the organ-tissue metabolic rate), could help to develop predictive equations with a better performance.

Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium-zinc-telluride camera: first clinical experience.

AIMS: To investigate the relationships between regional adrenergic innervation heterogeneity, myocardial perfusion, and contractile function obtained by means of a low-dose imaging protocol with a cadmium-zinc-telluride (CZT) dedicated camera. METHODS: Twenty-eight patients with or without ischaemic heart disease underwent (123)I-metaiodobenzylguanidine (MIBG) planar scintigraphic and CZT early and delayed evaluations followed by (99m)Tc-tetrofosmin rest gated CZT with a single-day protocol. The heart-to-mediastinum ratio and the washout rate were computed from planar (123)I-MIBG images. The summed (123)I-MIBG defect scores (SS-MIBG) were semi-quantitatively assessed from CZT images. The summed rest score (SRS), summed motion score (SMS), and summed thickening score (STS) were quantitated from (99m)Tc-tetrofosmin images. RESULTS: Sixteen patients showed a depressed left ventricular systolic function [ejection fraction (EF)<50%]. They presented higher SRS (P = 0.007), SMS (P < 0.001), STS (P < 0.001), and early SS-MIBG (P = 0.007) values than those with normal contractile function. Interestingly, higher early SS-MIBG values, index of regional sympathetic innervation heterogeneity, clustered with more elevated SRS (P = 0.023), and more impaired measures of regional and global left ventricle systolic function, i.e. SMS (P = 0.046), STS (P = 0.014), and EF (P = 0.027). At multivariate analysis, a higher SRS (P = 0.039) remained the only independent predictor of more elevated early SS-MIBG values. In the 20 of 28 ischaemic patients, the correlations between early SS-MIBG and SMS (P = 0.017) and also STS (P = 0.036) were further confirmed. The effective dose of the investigation was 4.2 ± 0.72 mSv. CONCLUSIONS: An altered early SS-MIBG, assessed with a low-dose imaging protocol and a CZT cardiac camera, identifies patients with more impaired myocardial perfusion and contractile function.

Deconvolution-based assessment of pituitary GH secretion stimulated with GHRH+arginine in Prader-Willi adults and obese controls.

OBJECTIVE: The assessment of GH deficiency in adult patients with Prader-Willi syndrome (PWS) has been previously assessed through the evaluation of quantitative parameters, such as the peak value of GH response to exogenous stimuli. A comprehensive description of the pattern of secretory response obtainable by deconvolution analysis is still lacking. The aim of our study was to characterize the time evolution of responses of PWS subjects compared with obese controls. DESIGN AND SUBJECTS: GH responsiveness was measured following the combined administration of GHRH+arginine to 65 PWS adults (24 males, 41 females) aged 18-41·2 years, and 17 age-, gender- and body mass index-matched obese controls. PWS subjects were analysed considering the stratification on different genotypes. MEASUREMENTS: GH response to GHRH+arginine was analysed in terms of peak values, standard area under the curves (AUCs), AUCs due to the stimulus, AUCs of the Instantaneous Secretion Rate signal and Secretion Response Analysis. RESULTS: In terms of both peak values and AUC, GH responses were statistically different between PWS UPD15 and PWS DEL15 subjects as well as between PWS UPD15 and obese controls. PWS subjects showed a lower and a more delayed GH response compared with obese controls. Moreover, PWS UPD15 subjects had the most delayed GH response. CONCLUSIONS: Our findings demonstrate that impaired GH secretion in PWS subjects compared with obese controls regards not only amplitude parameters such as peak value and AUC, but also the shape of the secretory response, which is more delayed, especially for UPD15 subjects.

Evaluation of a multisensor armband in estimating energy expenditure in obese individuals.

OBJECTIVE: To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals. RESEARCH METHODS AND PROCEDURES: Energy expenditure was assessed during rest with the SWA and IC in 142 obese adults (37 men and 105 women, BMI = 42.3 +/- 7.0) and in 25 lean and overweight adults (BMI = 25.3 +/- 3.2) who were used as a comparison group. Twenty-nine of the obese adults also participated in three separate short exercise sessions including cycle ergometry, stair stepping, and treadmill walking. RESULTS: The repeatability of SWA estimates in obese subjects was high (r = 0.88, p < 0.001). The SWA generally underestimated the resting energy expenditure (REE) (1811 +/- 346 vs. 1880 +/- 382 kcal/d) and highly overestimated the energy expenditure during the exercise sessions in obese individuals. REE estimations by SWA were significantly correlated with fat-free mass (r = 0.88, p < 0.001). Bland-Altman plots based statistical analysis for the estimated REE, and measured IC showed a low agreement (Total Error > 20% but Systematic Error < 5%) between the two methods in obese subjects, although they showed a high correlation and a very good agreement in lean and overweight patients. DISCUSSION: The SWA is an easy to handle, practical, new portable device for measuring energy expenditure. The accuracy of the SWA appeared to be poor in the obese subjects we examined, especially those with high REE both in rest and exercise. We believe that it is necessary to incorporate new, obesity-specific algorithms in the relative software.

Baseline/postnitrate tetrofosmin SPECT for myocardial viability assessment in patients with postischemic severe left ventricular dysfunction: new evidence from MRI.

UNLABELLED: The aim of this study was to compare (99m)Tc-tetrofosmin SPECT with contrast-enhanced MRI (ceMRI), a new direct sign of myocardial fibrosis. METHODS: We studied 21 patients (age, 60 +/- 11 y; 19 male) with previous myocardial infarction and severe left ventricular dysfunction (ceMRI EF, 29% +/- 6%). All patients underwent resting and postnitrate (intravenous isosorbide dinitrate) (99m)Tc-tetrofosmin gated SPECT as well as ceMRI. Scintigraphic analysis was performed using quantitative perfusion SPECT (QPS), providing the percentage radiotracer uptake and defect severity in a 20-segment model. Hyperenhancement was defined by the increase of ceMRI signal intensity 20 min after intravenous injection of gadolinium-diethylenetriaminepentaacetic acid and its regional extension as the percentage of the total segment area. RESULTS: In ceMRI dysfunctional segments, the correlation between the extent of hyperenhancement and both (99m)Tc-tetrofosmin uptake and defect severity was significantly better after nitrate administration rather than at rest (P < 0.0001). Using a ceMRI cutoff below 40%, 102 of 196 (52%) segments were viable, whereas 94 (48%) segments were not viable. According to receiver-operating characteristic curve analysis, diagnostic accuracies were higher for postnitrate (99m)Tc-tetrofosmin uptake as well as perfusion defect severity than using resting data (0.84 vs. 0.71, P < 0.001; 0.89 vs. 0.76, P < 0.001, respectively). CONCLUSION: After nitrate administration, (99m)Tc-tetrofosmin uptake and perfusion defect severity were closely related to ceMRI, demonstrating, in vivo, the existence of an inverse correlation between the transmural distribution of fibrosis and tracer delivery to the myocardium.

Baseline/post-nitrate Tc-99m tetrofosmin mismatch for the assessment of myocardial viability in patients with severe left ventricular dysfunction: comparison with baseline Tc-99m tetrofosmin scintigraphy/FDG PET imaging.

BACKGROUND: Positron emission tomography (PET) flow/metabolic mismatch is considered the nuclear medicine gold standard for the assessment of myocardial viability. The aim of this study was to investigate whether baseline/nitrate technetium 99m tetrofosmin single photon emission computed tomography (SPECT) mismatch may provide equivalent clinical information. METHODS AND RESULTS: We studied 23 patients (aged 62 +/- 10 years, 19 men) with previous myocardial infarction (16 anterior, 4 inferior, and 3 anterior plus inferior) and postischemic heart failure (gated SPECT [G-SPECT] ejection fraction, 26% +/- 8%). All patients underwent Tc-99m tetrofosmin G-SPECT at rest and after nitrates (intravenous isosorbide dinitrate, 0.2 mg/mL, 10 mL/h) as well as a fluorine 18 fluoro-2-deoxy-d-glucose (FDG) PET scan. Regional wall motion analysis was performed with quantitative G-SPECT (QGS). Myocardial dysfunction was defined as a regional QGS score of 2 or greater. Regional perfusion was assessed by quantitative perfusion score (QPS) providing percent Tc-99m tetrofosmin uptake in a 20-segment model. Semiquantitative analysis of FDG uptake was performed by use of polar maps generated by Siemens ECAT HR + software. In areas with a perfusion rate lower than 80%, PET viability was identified by a normalized FDG percent uptake/baseline Tc-99m tetrofosmin percent uptake ratio greater than 1.2. We analyzed 460 segments; 298 (64%) were dysfunctional by QGS analysis. Of these, 170 were viable by PET imaging whereas 128 were nonviable. Regional Tc-99m tetrofosmin uptake was higher in viable than in nonviable segments both at rest (60% +/- 24% vs 42% +/- 12%, P <.01) and after nitrates (67% +/- 20% vs 41% +/- 18%, P <.01). According to receiver operating characteristic curve analysis, a cutoff value of 63% for resting as well as post-nitrate G-SPECT provided the highest diagnostic accuracy for the detection of myocardial viability (67% and 72% at rest and after nitrates, respectively). When the same algorithm used for the comparison with PET (normalized nitrate percent uptake/baseline percent uptake) was applied to G-SPECT, we obtained the highest agreement with PET (accuracy, 93%; sensitivity, 95%; specificity, 92%). CONCLUSIONS: In patients with severe left ventricular dysfunction, perfusion data alone, both at rest and after nitrates, do not allow an accurate estimate of myocardial viability. In dysfunctioning segments, the analysis of rest/post-nitrate Tc-99m tetrofosmin mismatch provides results similar to those obtained by PET flow/metabolic mismatch.

Systemic complications of acromegaly: epidemiology, pathogenesis, and management.

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.

The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure.

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.