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MINISTRY OF EDUCATION MINISTRY OF DEFENSE AND TRAINING MILITARY MEDICAL ACADEMY DOAN VIET CUONG STUDY ON THE RELATIONSHIPS BETWEEN RESITIN, VISFATIN AND SOME METABOLIC CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH TYPE DIABETES MELLITUS Speciality: Internal medicine Code: 9720107 SUMMARY OF PHD DISSERTATION HA NOI - 2022 download by : skknchat@gmail.com THIS THESIS WAS COMPLETED AT MILITARY MEDICAL ACADEMY Scientific supervisor: Associate Professor Hoang Trung Vinh, MD PhD Professor Nguyen Linh Toan, MD, PhD Reviewer 1: Associate Professor Vu Thi Thanh Huyen Reviewer 2: Associate Professor Pham Dang Khoa Reviewer 3: MD, PhD Nguyen Vinh Quang The thesis will be examined and assessed by termination Council at: hour date month year It can be found at: National Library The Library of Military Medical Academy download by : skknchat@gmail.com INTRODUCTION Diabetes is one of the 10 most common causes of death worldwide Cardiovascular risk factors associated with type diabetes often combine with other factors such as insulin resistance, hyperglycemia, dyslipidemia, hypertension, hyperinsulinemia, systemic inflammation, and secreted factors from adipose tissue In the past, adipose tissue was considered as a passive energy reserve, recently it has been shown to be an important endocrine organ secreting many highly bioactive peptides involved in the regulation of many physiological processes and metabolism The adipocytokines include: adiponectin, leptin, MCP-1, TNF-α, resistin and visfatin Resistin belongs to the family of cysteine-rich protein molecules (cysteine rich) also known as resistin-like molecules or FIZZ (found in inflammatory zone) Resitin is associated with insulin resistance, overweight, obesity, and type diabetes Visfatin called PBEF (pre-ß cell colony-enhancing factor) acts on the Nampt enzyme (nicotinamide phosphoribosyltransferase) Visfatin has been found to be associated with visceral fat mass, the association of visfatin with insulin resistance, overweight, obesity and diabetes and its role in predicting diabetes risk remains unclear Resistin may be a biomarker associated with cardiovascular diseases and restenosis after coronary intervention Visfatin is considered an inflammatory mediator, is expressed in macrophages, atheroma and can secrete matrix metalloproteinase (MMP)-9 in monocytes Visfatin plays an important role in the pathogenesis of vasculitis and increases the risk of cardiovascular disease in patients with type diabetes Research on the relationship between resistin and visfatin levels with overweight, obesity, insulin resistance, type diabetes, their role in the pathogenesis of insulin resistance, type diabetes and metabolic cardiovascular risk factors still has many disagreements Visfatin has a cardioprotective role and has insulin-like effects It is necessary to elucidate the role of visfatin in the pathogenesis of diabetes and its clinical applicability The research question is how the concentration of resistin, visfatin and the relationship between resistin, visfatin levels with cardiovascular - metabolic risks in patients with type diabetes? In Vietnam, there have been some studies on adipokines, but studies on visfatin, resistin and the relationship with insulin resistance, overweight, obesity, type diabetes and the relationship with metabolic cardiovascular risk factors has not been studied much Therefore, we download by : skknchat@gmail.com conducted the topic: "Study on the relationships between resistin, visfatin with some metabolic cardiovascular risk factors in patients with type diabetes mellitus" with the following two objectives: Investigation of serum resistin and visfatin concentrations in patients with type diabetes Determining the relationship between serum resistin and visfatin levels with some cardiovascular-metabolic risk factors in patients with type diabetes THE NEW MAIN SCIENTIFIC CONTRIBUTION OF THE THESIS Determination of serum resistin and visfatin levels in patients with type diabetes To determine the relationship between serum resistin and visfatin levels with some cardiovascular-metabolic risk factors in patients with type diabetes STRUCTURE OF THE THESIS The thesis consists of 148 pages (excluding appendices and references) Introduction pages, overview 40 pages, objects and methods 23 pages, results 42 pages, discussion 35 pages, conclusion pages, recommendations page Includes 175 references in English and Vietnamese Chapter : OVERVIEW 1.1 Type diabetes and its association with cardiovascular-metabolic risk factors 1.1.1 Epidemiology According to the International Diabetes Federation (IDF), by 2045, the number of people with diabetes will be 629 million, an increase of 48% compared to 425 million in 2017 1.1.2 Type diabetes risk factors Type diabetes is a common disease, which is the result of the interplay between endogenous and environmental factors such as genes, overweight, obesity, sedentary lifestyle, etc 1.1.3 The pathogenesis of type diabetes includes: impaired β-cell function and insulin resistance Sites of insulin resistance: in the liver, in peripheral tissues, other internal organs, insulin resistance in cells The role of α and glucagon cells, download by : skknchat@gmail.com the role of incretin, increased reabsorption in the kidney, dysfunction of neurotransmitters in the brain 1.1.4 Diabetes mellitus and its association with cardiovascularmetabolic risk factors Cardiovascular-metabolic risk factors include modifiable risk groups or markers that increase the risk of cardiovascular disease (myocardial infarction, stroke, peripheral artery disease) and diabetes Street Cardiovascular-metabolic risk factors including: insulin resistance, hypertension, elevated LDL-c, elevated triglycerides, decreased HDL-c and abdominal obesity are clinically recognizable risks Other factors such as increased oxidative stress, vascular endothelial dysfunction, and microalbuminuria are difficult to recognize, and the evaluation criteria are also more difficult, so they should only be used in studies Identification of cardiovascular-metabolic risk factors Hypertension, abdominal obesity, decreased HDL-c, increased triglycerides, increased blood glucose are components of HCCH (ATPIII), additional factors: smoking, increased LDL-cholesterol, markers of inflammation and insulin resistance, disorders insulin secretion Adipose tissue dysfunction is the underlying process leading to cardiovascular diseases Disturbances in the secretion of adipokines by adipose tissue participate in the pathogenesis of obesity and its comorbidities including: dyslipidemia, impaired glucose metabolism, altered satiety, increased inflammatory response, and dyslipidemia, coagulopathy, hypertension and cardiovascular dysfunction 1.2 Overview of adipose tissue and the role of adipocytokines 1.2.1 Endocrine function of adipose tissue The concept of adipose tissue as a passive energy storage site is no longer accurate Effects of adipose tissue on neighboring tissues (paracrine), systemic effects (endocrine) Resistin, visfatin are cytokines secreted from adipose tissue cells and some cells of other organs The structure and physiological function of these cytokyines are related to many different physiological and pathological states 1.2.2 Structure and function of resistin 1.2.2.1 Structure, origin Human resistin is a polypeptide with a molecular weight of 12.5 kDa with 108 amino acids Resistin was first discovered in 2001 by Steppan et al., in rodents, resistin is secreted mainly from adipose tissue, which is believed to play a role in the link between obesity and insulin resistance Resistin is distributed in many organs and tissues in the human body such download by : skknchat@gmail.com as: adrenal gland, pituitary gland, hypothalamus, subcutaneous adipose tissue (white fat), brown fat, white blood cells, spleen, skeletal muscle, placenta, gastrointestinal tract, pancreas, synovial fluid, plasma and many other organs 1.2.2.2 Function of resistin The role of resistin in insulin resistance, dyslipidemia, blood pressure regulation, and resistin's role in atherosclerosis In vascular endothelial cells, resistin increases the expression of proinflammatory cytokines including MCP-1, endothelin-1, and endothelial adhesion molecules such as ICAM-1, VCAM-1 and P-selectin The role of resistin in inflammation, atherosclerosis, and cardiovascular diseases shows that Resistin levels are correlated with inflammatory markers and are a predictor of coronary atherosclerosis independent of CRP Resistin has been associated with cardiovascular disease 1.2.2.3 Factors affecting the expression of resistin Nutritional factors deficiency of vitamin E, vitamin D, treatment of diabetes with rosiglitazone (RSG) reduces reisistin concentration Women with polycystic ovary syndrome, periodontitis in diabetic patients 1.2.3 Visfatin structure and function 1.2.3.1 Origin and structure of visfatin Visfatin is an adipokine first identified in 2004, produced and secreted primarily from visceral adipose tissue The molecular weight is about 52 kDa and the gene encodes 491 amino acids Visfatin is distributed in many tissues and cells in which predominance from adipose tissue including subcutaneous adipose tissue (WAT) and visceral adipose tissue (VAT), white blood cells, vascular endothelial cells, tissue mammary gland fat, gastrointestinal mucosa, liver, kidney, brain, lung, synovial membrane and in plasma The effects of visfatin can be endocrine, parasecretory as well as autocrine 1.2.3.2 Receptors of visfatin Visfatin has been described as an adipocytokine secreted from visceral adipose tissue with insulin-like effects Visfatin is involved in immune, metabolic, and stress responses dependent on both extracellular (cytokine-like) as well as intracellular (enzymatic activity) effects 1.2.3.3 Functions of visfatin: The main functions of visfatin in physiology and pathology: PBEF/Nampt/Visfatin is a pro-inflammatory cytokine, immunomodulatory factor, enzyme function Visfatin has insulin-like effect and anti-apoptosis function download by : skknchat@gmail.com 1.3 Study on the relationship between resistin and visfatin levels with some cardiovascular-metabolic risk factors in patients with type diabetes in the world and in Vietnam The study of resistin concentration in patients with type diabetes showed an increase in comparison with those without diabetes, positively correlated with fasting blood glucose concentration Resistin concentration had a significant positive correlation with waist circumference, weight, insulin and HOMA-R index in obese type diabetic patients The concentration of resistin increased significantly in the group of type diabetes with hypertension, positively correlated with the blood pressure value in patients with type diabetes with hypertension Resistin concentration has a positive correlation between BMI and HOMA-IR index in patients with type diabetes The concentration of resistin, visfatin, ghrelin in saliva increased higher than in the group of patients with type diabetes associated with overweight and obesity in healthy people, newly diagnosed type diabetes without overweight and obesity and overweight and obesity (p12 μU/mL for both men and women according to Tohidi M et al (2014) - Calculate the index of insulin resistance: + Index HOMA-IR: Index of insulin resistance according to the formula of Matthews Insulin resistance was determined when HOMA-IR>2.6 according to Yin, Jinhua QUICKI (Quantitative insulin Sensitivity Check Index) was calculated according to the formula of Kazt et al (2000) β-cell function evaluation index (HOMA-β): Assess the insulin-secreting ability of β-cells (Matthews formula) HOMA-β index is normal: >116.65% + McAuley index Mc auley index = e (2.63-0.28 ln (I0)–0.31 ln (TAG0) TAG0 fasting triglyceride concentration, I0: fasting blood insulin concentration, Normal Mc Auley index 4.65 2.2.4.5 Quantification of resistin concentration Principle: Based on the specific reaction between the antibody attached to the bottom of the ELISA well with the resistin antigen present in the patient's serum combined with the specific substrate color change in the ELISA reaction The patient's test results were determined as: Normal when resistin concentration was in the range > lower quartile and less than upper quartile of the control group Increase when resistin concentration is greater than upper percentile of control group, decrease when resistin concentration is less than lower percentile of control group 2.2.4.6 Quantification of visfatin The principle and method of quantification are similar to that of resistin The way to analyze the results, units, gain, loss, normal is similar to the evaluation of resistin download by : skknchat@gmail.com (TPV25TPV75) 12 (1,13–1,57) (0,99 – 1,34) 3,11 ± 1,00 3,03 ± 2,45 > 0,05* ( Χ ± SD) LDL-Cho Median 3,20 3,00 ** (mmol/l) (TPV25(2,50–3,70) (2,30 – 3,50) > 0,05 TPV75) * compare mean of independent groups by T-test ** compare mean of independent groups using Mann-Whitney test Increase in triglycerides, decrease in HDL-Cho in patients with type diabetes compared with the control group had statistical significance p < 0.01 3.1.3 Some indices of insulin resistance, hyperinsulinemia, cardiovascular risk indicators – Metabolism Table 3.18 Comparison of insulin resistance indexes between the control group and the disease group (calculated by HOMA-IR) Control group Study group n= 133 n= 257 Variables P*P** ( Χ ± SD) ( Χ ±SD) 1,70 ± 0,94 4,29 ± 4,63 Χ ± SD) ( HOMA
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