Chiara Marocco

Negative association between trunk fat, insulin resistance and skeleton in obese women

AIM To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. METHODS In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m(2)) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD; at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. RESULTS Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005).Multivariate analysis demonstrated that only vitamin D was independent of TF variable. CONCLUSION In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship.

Psoriasis and bone mineral density: Implications for long‐term patients

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti‐psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty‐three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual‐energy X‐ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T‐score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.

Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/ β -Catenin Dependent Mechanism.

Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by obesity and sarcopenia (OS), and (4) affected by obesity, sarcopenia, and low BMD (OOS) as compared to subjects with normal body weight and normal BMD (CTL). Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/β-catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered β-catenin cellular compartmentalization and GSK3β phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis.

Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects

Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity (V˙O2peak) in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI: 36.6 ± 4.1 kg·m−1) and sixteen SO subjects (BMI: 37.0 ± 7.3 kg·m−1) were compared with sixteen T2DM subjects (BMI: 37.7 ± 5.6 kg·m−1). All groups performed an incremental exercise test on a treadmill according to their physical ability. V˙O2peak, %HRmax, and maximal metabolic equivalent (METmax) were evaluated at maximal effort. Moreover, V˙O2ivt, %V˙O2peak, %HRmax, %HRR, ΔHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort (V˙O2peak, %HRmax, and METmax) in all groups. On the contrary, V˙O2ivt, %V˙O2peak, %HRmax, %HRR, ΔHR, and METivt were significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (p < 0.05). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions.

Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects

PurposeObesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals.MethodsThe study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers.ResultsIn this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r2 = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r2 = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r2 = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r2 = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r2 = 0.03) and femoral site (p < 0.04, r2 = 0.03).ConclusionsIn conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.

Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity

Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol. To this aim, obese women were evaluated at time 0 and after 4, 6, and 12 months of individualized prescribed physical activity and hypocaloric diet. Dual-energy-X-ray absorptiometry measurements were performed at each time point, as well as blood was collected at the same points. Cells were incubated with sera of subjects before and after physical activity as described: obese at baseline and after for 4, 6, and 12 months of physical activity and nutritional protocol intervention. Osteoblasts exposed to sera of patients, who displayed increased lean and decreased fat mass (from 55.5 ± 6.5 to 57.1 ± 5.6% p ≤ 0.05; from 44.5 ± 1.1 to 40.9 ± 2.6% p ≤ 0.01 respectively), showed a time-dependent increase of Wnt/β-catenin signaling, versus cells exposed to sera of obese patients before intervention protocol, suggesting recovery of osteoblast homeostasis upon improvement of body composition. An increase in β-catenin nuclear accumulation and nuclear translocation was also observed, accompanied by an increase in Adiponectin receptor 1 protein expression, suggesting positive effect on cell differentiation program. Furthermore, a decrease in sclerostin amount and an increase of type 1 procollagen amino-terminal-propeptide were depicted as compared to baseline, proportionally to the time of physical activity, suggesting a recovery of bone remodeling modulation and an increase of osteoblast activity induced by improvement of body composition. In conclusion, our results show for the first time that sera of obese sedentary women who increased lean mass and decreased fat mass, by physical activity and hypocaloric diet, rescue osteoblasts differentiation and activity likely due to a reactivation of Wnt/β-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity.

Nutrition and Skeletal Health

During the last decades, in industrialized countries was observed a significant increase in average life expectancy with a gradual aging of the population. The prolonged life expectancy, lifestyle and improper eating behaviors have contributed to increase the incidence of illnesses, often resulting of well-being, such as obesity, dysmetabolism, cardiovascular disease, osteoporosis, which contribute heavily to both quality of life of those affected and significant increase in social costs.

Validity of the self- mini nutritional assessment (Self- MNA) for the evaluation of nutritional risk. A cross- sectional study conducted in general practice

IntroductionMalnutrition is a frequent condition in the elderly especially in hospitals and in nursing homes, and even among the free-living elders the prevalence is not negligible (5-10%). Awareness towards malnutrition is still limited. The lack of time for nutritional assessment by the overcommitted healthcare personnel, including the general practitioners (GPs), may represent one possible explanation for limited recognition of malnutrition. Therefore, a self-administered instrument could be useful in raising alert on the GPs and allow early detection of malnutrition and early care provision. The aim of the present study was to analyze the validity of the Self-MNA that takes cue from the Mini Nutritional Assessment-Short Form (MNA-SF) and has been adapted to be self-administered by free-living elderly subjects.MethodsParticipants were recruited from patients referring to the GP offices in Italy. Nutritional evaluation was performed through the administration of Full-MNA, MNA-SF and Self-MNA. The comorbidity level was assessed through the Cumulative Illness Rating Scale (CIRS). The level of difficulty in filling out the test was reported by the participants, and the time spent to complete the Self-MNA was also registered.ResultsA total of 226 subjects, 125 women and 101 men (75.1 ± 8 and 75.3 ± 8 years old, respectively; p=0.89) were enrolled, and 214 (94.7%) of them completed the Self-MNA. According with the Full-MNA test score, 8.4% of women and 3.5% of men were classified as malnourished, whereas 32.7% of women and 31.4% of men were at risk of malnutrition. Agreement between Self-MNA and Full-MNA, and Self-MNA vs. MNA-SF was classified as “moderate” (k = 0.476 and 0.496 respectively; p < 0.001). Self-MNA showed a fair predictive value compared to the Full-MNA and MNA-SF tests (76.6 and 79.9%, respectively) with a barely adequate sensitivity (70.9 and 75.4%, respectively). The analysis of the characteristics of FN (false negative: subjects who were considered at risk of malnutrition or malnourished at Full-MNA but not at Self-MNA) showed that the clinical and functional aspects of these subjects (age, comorbidity and severity, time necessary to complete the Self-MNA, decrease in food intake, severe illness in the past 3 months, dementia and depression, fluid intake, need for feeding assistance, arm and calf circumferences) were very similar to the characteristics of true positive subjects. Patients required 6.7 ± 4.5 minutes to complete the test and 25 subjects (11.7%) needed more than 10 minutes, up to a maximum of 30 minutes. Patients who stated a greater difficulty were older (79.8 ± 7 vs. 73.5 ± 7 years; p< 0.001), they were more «malnourished» at Full-MNA (10.7 vs. 1,7%; p= 0.006) and clinical status was characterized by a higher severity index (1.72 ± 0.6 vs. 1.41 ± 0.4; p= 0.008).ConclusionIn the present study we investigated the validity of the Self-MNA in a sample of free-living elderly subjects. The results obtained confirm the validity of the test that may represent a useful tool for the GPs, although some important limitations need to be considered, limiting its use in clinical practice.

Response to: Comment on “Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects”

(i) In 2.2. Clinical Evaluation. Shimamoto et al. [3] studied seasonal variations in body composition and anthropometric characteristics during a weight loss program. The aim of our study was to examine cardiorespiratory parameters at IVT and peak exercise capacity, and it was not to evaluate the effects of a weight loss program on body composition in obese subjects. However, the season (January 2013 to June 2013) and time of the day (morning) are stated in the text, and the precise day and hour of the morning were randomly distributed between the three studied groups.