Association between obesity and inflammation among diabetic polyneuropathy patients
Corresponding author: Dr. Gholamreza Askari, School of Nutrition and Food Science
Isfahan University of Medical Sciences, Isfahan, Iran, E-mail: Askari@ mui.ac.ir
Inflammation is defined as a physiological response to physical, chemical and biological stimuli . Inflammation is linked to obesity , characterized by increased levels of CRP and ESR [3, 4]. Obesity is related to different risk factors such as increased consumption of energy and reduced physical exercise [5, 6]. The source of inflammation in obesity is known , however, obesity- related inflammation is followed by the immune system activation . Obesity is associated with chronic diseases such as DPN . The pathogenesis of DPN is not completely known. Inflammation, oxidative stress, and mitochondrial dysfunction have been involved in the pathogenesis of DPN . About 50% of diabetic patients are expected to observe symptoms of diabetic neuropathy . Diabetic neuropathy can be attributed to disability related to foot ulceration, amputation, walking disturbance  and reduced of quality life . The high concentrations of inflammatory markers among obese patients seems to be effective in the progression of diabetic polyneuropathy .
Recently, researchers have found an increased interest in the relationship between inflammation and obesity [12, 13]. However, there are only a few studies in literature on the field. No studies have been conducted to investigate the relationship between inflammation and obesity among DPN patients. The objective of the present article is to investigate associations between inflammation and obesity among DPN patients.
Keywords: Body Mass Index, Obesity, Inflammation, C-Reactive Protein, Blood Sedimentation
Subjects and methods
Study population: The present study was approved by the ethical committee in University Isfahan of medical sciences. Baseline started in 4st March 2017 and ended in 23st October 2017. A total of 50 patients were excluded due to missing values for BMI (n=10), CRP (n=20), ESR (n=15), and other variables (n=5). Finally, 200 patients were entered in the final analysis.
Assessment process and data collection: Participants attended the Isabn-e-Maryam clinic after an overnight fasting. Currently smoking and education were reported by self-report. Hypertension was expressed as systolic/diastolic blood pressure equal to or greater than 140/90mm Hg or using antihypertensive medication. Diabetes was expressed as fasting blood sugar equal to or greater than 7.0 mmol / liter or using antidiabetic treatment. Height and weight were measured to the nearest 0.1cm and 0.01kg, using a Secascale and height gauge, respectively. Body mass index was defined as body weight in kilograms divided by height squared in meters. Venous blood samples were collected on admission after a 12-h overnight fast and were immediately sent to laboratory for analysis based on the clinical routine. Two hundred patients undergoing electromyography and nerve conduction velocity (EMG-NCV) for diagnosis of DPN were selected in the present study. CRP was measured with enzyme-linked immunosorbent assay (ELISA) method. ESR was determined using Westergren method.
Statistical analysis: Statistical analyses were performed using STATA, version 13 software (StataCorp). P values <0.05 were considered significant. Quantitative variables were expressed as meanSD and qualitative variables were expressed as percentage. Multiple linear regression analysis was used to evaluate the relationship between groups.
A total of 200 patients (101 men) with a mean age of 58.76 years were included in this cross-sectional study. Nine percent of the participants reported a history of smoking. The mean years of education for patients were 5.61 years. The prevalence of hypertension, coronary heart disease, hyperlipidemia and non-proliferative diabetic retinopathy among all diabetic patients were 40%, 31.5%, 75%, and 37%, respectively. The demographic characteristics and clinical examination of the patients are demonstrated in (Table 1).
Table 1: Demographic and clinical characteristics of patients with diabetic neuropathy.( *2-hpp: two-hour postprandial)
From these participants, 75 patients with DPN treated with insulin, 85 patients in combinations of insulin and oral antidiabetic drugs and 40 with oral antidiabetic drugs. CRP and ESR concentration among patients with diabetic neuropathy were 9.81mg/dl and 49.2 mg/dl, respectively. Patients with higher BMIs had high level of CRP and ESR.
The multivariate linear regression model indicated that CRP and ESR were positively related to BMI. After adjusting for age, education, sex and smoking (model-1), the β coefficient levels of CRP and ESR for 1unit increase in BMI were 0.73 and 4.99, respectively(p<0.001) (Table 2). The relationship remained significant after adjustment for other variables in the models 2 and 3 (Table II).
Table 2: Relationship between BMI and levels of CRP and ESR.
* Model 1: Adjusted for age, education, sex and smoking.
** Model 2: Model 1+ HbA1C, FBS, BS(2-hpp),TG,HDL,LDL, Chol ,Alb and chronic disease such as CHD,HLP,HTN, NDPR.
†β coefficient was interpreted as change of CRP and ESR for each kg/m2 increase in BMI.
SE = standard error.
***CRP: C−reactive protein.
****ESR: Erythrocyte sedimentation rate.
The present study demonstrates a positive association between BMI and serum levels of CRP and ESR among patients with diabetic polyneuropathy. Obese patients demonstrated significantly higher inflammation.
The finding is consistent with findings of cross-sectional studies [12, 14, 15, 16]. Although, the relationship might be confounded using covariate variable such as chronic diseases. Therefore chronic diseases such as coronary heart disease, hypertension, hyperlipidemia, non-proliferative diabetic retinopathy and related other factors were controlled for in the model-2. Also, the existence of medical features related to inflammation was excluded.
Increased serum levels of inflammatory markers play important role among diabetic patients with higher BMI . However, the mechanism of relationship between CRP and blood sugar remains unclear . In fact, adipose tissue as a producer tissue of inflammatory markers indicates the positive association between higher BMI and
inflammation . Adipose tissue as inflammatory markers can increase lipogenesis [19, 20, 21, 22] and response of the systemic inflammatory phase .
The sources of inflammation activated by hyperglycemia and metabolic disease are immune cells such as increased macrophage, mast cells and natural killer T cells that contribute for expression of tissue cytokine [17, 24]. Obesity increases metabolic stress related to the immune system activation and inflammation , as a risk factor for cardiovascular disease, colon cancer, breast cancer, dementia and depression . Also, inflammation is related to increased intake of calorie and other nutrients such as intake of high fat and carbohydrate . Increased of proinflammatory macrophages are inversely related to sensitivity insulin .
Studies have demonstarated that weight loss is related to decreased inflammatory markers [28, 29]. Also, weight loss among people with gastric bypass indicate decreased levels of inflammatory markers .
These findings about association between obesity and increased levels of CRP and ESR highlight obesity patients are susceptible to various outcomes of inflammation such as chronic diseases .
The present study has several strengths. First, our study is the first cross-sectional study about the association between inflammation and obesity among diabetic neuropathy in Iran, Isfahan. Second, the results of present study have been controlled for covariate variables. Besides, this study has several limitations. First, design of present study is cross-sectional and could not determine causal relationship for these factors. Second, two inflammatory markers were considered in this study for assessment of inflammation.
In conclusion, increased levels of CRP and ESR were related to obesity among diabetic polyneuropathy, indicating important role of inflammatory markers among diabetic polyneuropathy.
This meta-analysis was supported by Isfahan University of Medical Sciences, Isfahan, Iran. The authors are responsible for the content and writing of this paper.
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