Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06115356 |
| Other study ID # |
Vit D Obesity |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2018 |
| Est. completion date |
June 30, 2021 |
Study information
| Verified date |
November 2023 |
| Source |
University of Trieste |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
