Hypovitaminosis D and "Metabolic" Inflammatory Status in Patients With Obesity
Condition: Hypovitaminosis D; Obesity
MeSH terms: Rickets; Obesity; Avitaminosis; Vitamin D Deficiency
Study type: Observational

Summary: 
      Since obesity is related to systemic chronic inflammatory status and hypovitaminosis D, the
      study aimed to assess the incidence of hypovitaminosis D in obese patients and the
      correlations between vitamin D levels, inflammation indices, and bioimpedance measures.

      A retrospective study was conducted on a cohort of obese patients. The inflammation-based
      prognostic scores, diagnosis of liver fibrosis, systemic inflammatory indices, and
      bioimpedance measures were analyzed. The linear relationship between vitamin D levels and
      continuous variables was assessed through the Spearman correlation coefficient, and to
      determine significant predictors of vitamin D levels a stepwise multiple linear regression
      was used.
    

Detailed description: 
      Introduction Obesity is a major health problem related to a cluster of chronic metabolic
      disorders and is associated with increased overall morbidity and mortality. Several studies
      proved that obesity is linked to a low grade of systemic chronic inflammatory status,
      considering the adipose tissue the largest metabolically active organ with endocrine,
      inflammatory, and immunological functions.

      The "metabolic" inflammatory process leads to the release of inflammatory cytokines with
      subsequent systemic effects on insulin-sensitive organs, such as the liver which markedly
      suffers from the systemic proinflammatory environment. Vitamin D (25(OH)D) plays a key role
      in the regulation of mineral homeostasis by binding the vitamin D receptors, leading to an
      adequate calcium level to promote skeletal health. Furthermore, vitamin D has
      anti-inflammatory and immunoregulatory functions. It is an indispensable nutritive component
      that regulates the inflammatory microenvironment through several mechanisms such as the
      up-regulation of Mitogen-activated protein kinases (MAPKs) and inhibition of Nuclear
      Factor-Kappa B (NF-Kb) signaling pathways.

      A low level of vitamin D in the visceral adipose tissue (VAT) induces more lipogenesis and
      less lipolysis promoting fat storage and obesity. The prevalence of vitamin D deficiency is
      24% and 35% higher in overweight and obese people, respectively, compared to the general
      population. Many hypotheses have been proposed to explain the inverse correlation between
      Vitamin D and obesity:1) the storage of this fatsoluble nutrient in the exceeded VAT; 2) the
      higher plasma dilution of the Vitamin D in the obese patient compared to the normal-weight
      population; 3) the reduced sun exposure due to the stigma of obesity; 4) the presence of
      metabolic syndrome or type 2 diabetes that often co-exist with obesity; 5) molecular
      interactions between Vitamin D and pro-inflammatory cytokines.

      Thus, hypovitaminosis D, inflammation, and obesity are three pathological conditions closely
      linked. In the literature, data explaining this relationship are still inconsistent, but
      crosstalk based on molecular signals exists.

      On this basis, patients with obesity could be a high-achieving biological model helping to
      clarify the noncalcemic effects of vitamin D in regulating inflammation.

      The first aim of the study is to assess the incidence of hypovitaminosis D in a cohort of
      obese patients; secondly, our purpose is to evaluate the correlation between hypovitaminosis
      D and inflammation's indices: inflammation-based prognostic scores, ferritin, C-reactive
      protein (CRP), inflammation grade on liver biopsy, and bioimpedance measures.

      Materials and Methods This monocentric retrospective cohort study is based on a prospective
      database of consecutive obese patients referred to the General Surgery Department at
      Cattinara University Hospital in Trieste, Italy, between January 2018 and June 2021.

      Patients were divided into three groups according to 25(OH) D levels: deficiency was defined
      as 25(OH) D levels ≤ 20 ng/mL, insufficiency between 21 and 29 ng/mL, and normal ≥ 30 ng/mL.
      The cohort was divided into three classes of obesity, according to BMI: grade I obesity
      30.0-34.9 kg/m2; grade II obesity, 35.0-39.9 kg/m2; grade III obesity ≥40.0 kg/m2.

      Measurements of body composition were conducted with Bioelectrical Impedance Analysis (BIA)
      technique, asking the participants to stand on the device barefoot to complete the analysis.
      Among all parameters, BMI, phase angle (PhA), total body water (TBW), extracellular (ECW) and
      intracellular water (ICW), body fat index, and fat and muscular mass were recorded. The PhA
      cutoff was not clearly defined in the literature, a value between 7.0 and 6.0 are found to be
      optimal in adulthood. Before surgery, the systemic inflammatory indices recorded were
      ferritin plasma level, CRP, and the following inflammation-based prognostic scores were
      considered for analysis: Glasgow Prognostic Score/modified Glasgow Prognostic Score
      (GPS/mGPS), Prognostic Nutritional Index (PNI), Neutrophil-to-Lymphocyte Ratio (NLR),
      Platelet-to-Lymphocyte ratio (PLR), Lymphocyte-to-monocyte ratio (LMR), Systemic immune
      inflammation index (SII). CRP values≥ 5 mg/dL were considered pathological.

      During the bariatric surgery, a liver biopsy was performed and analyzed by a single
      experienced pathologist blinded to all clinical and laboratory parameters. Patients with
      other forms of chronic liver disease, including suspected/confirmed hepatocellular carcinoma,
      alcoholic liver disease (>25 g/day alcohol consumption), or known hepatitis B virus,
      hepatitis C virus, and human immunodeficiency virus positivity were excluded. The
      histological diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis according to
      Kleiner-Brunt classification was detected. NASH was defined as a total no alcoholic fatty
      liver disease (NAFLD) activity score ≥ 5.

      The study was conducted according to the STROBE Guidelines.

      Statistical Analysis Continuous normal variables were expressed as mean ± standard deviation
      (SD); continuous non-normal variables as median and range (25 percentile-75 percentile). The
      Shapiro-Wilk test was performed to assess normality. Kruskal-Wallis non-parametric test was
      performed to identify differences in continuous variables of interest among the three groups.
      Post-hoc tests, and pair-wise comparisons using Mann-Whitney test, were conducted and
      corrected using the Holm method Categorical variables were expressed as absolute frequency
      and percentages and compared with Chi-Squared or Fisher-Exact Test when appropriate. The
      linear relationship between 25(OH) D levels and study continuous variables was assessed
      through the Spearman correlation coefficient. The most significant individual variables have
      been incorporated into a stepwise multiple linear regression (stepwise selection based on
      Akaike information criterion) to determine significant predictors of 25(OH) D levels. Two
      multiple linear regression analysis models were performed: 1) to estimate the predictive
      values of the bioelectrical impedance analysis and 2) to estimate the predictive values of
      inflammatory parameters. Beta and the standard error of Beta were reported as linear model
      results. P-Values ≤ 0.05 were considered statistically significant.

      Data were analyzed using the R Statistical Software.
    

Intervention name(s): Vitamin D Plasma Level; Bioelectrical Impedance Analysis (BIA) technique; Ferritin; C reactive protein (CRP); Inflammation-based prognostic scores; Liver biopsy
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Other
Intervention description(s): Blood test measured in ng/ml; Measurements of body composition were conducted with Bioelectrical Impedance Analysis (BIA) technique, asking the participants to stand on the device barefoot to complete the analysis. Among all parameters, BMI, phase angle (PhA), total body water (TBW), extracellular (ECW) and intracellular water (ICW), body fat index, and fat and muscular mass were recorded.; Ferritin plasma levels were measured in μg/L; CRP plasma levels were measured in mg/L; Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/mGPS), Prognostic Nutritional Index (PNI), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte ratio (PLR), Lymphocyte-to-monocyte ratio (LMR), Systemic immune-inflammation index (SII) were calculated using blood test results; A liver biopsy was used to study nonalcoholic steatohepatitis (NASH) and fibrosis according to the Kleiner-Brunt classification
Intervention MeSH terms: Vitamin D
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with obesity eligible for bariatric surgery
      
Biospecimen description: 
      Liver biopsies were studied to analyze fibrosis and inflammation grade
    
Keywords: Hypovitaminosis D; Obesity; Bariatric surgery; Inflammation