Tóm tắt Luận án Researching clinical features, some target organ lesions and target insulin resistance in new hypertensive patients with impaired fasting glucose

Nội dung tài liệu: Tóm tắt Luận án Researching clinical features, some target organ lesions and target insulin resistance in new hypertensive patients with impaired fasting glucose

1. MINISTRY OF EDUCATION & TRAINING MINISTRY OF NATIONAL DEFENSE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES -------- NGUYEN THI HONG VAN RESEARCHING CLINICAL FEATURES, SOME TARGET ORGAN LESIONS AND TARGET INSULIN RESISTANCE IN NEW HYPERTENSIVE PATIENTS WITH IMPAIRED FASTING GLUCOSE Major : Cardiology Code : 62720141 SUMMARY OF DOCTORAL DISSERTATION HA NOI - 2019
2. THE THESIS WAS DONE AT 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Full name of supervisor: 1. Dr. VIEN VAN DOAN 2. Associate Prof. Dr. NGUYEN VAN QUYNH Reviewer 1: Associate Prof. Dr. Nguyen Oanh Oanh Reviewer 2: Associate Prof. Dr. Vu Bich Nga Reviewer 3: Associate Prof. Dr. Vu Dien Bien This thesis will be presented at Institute Council at 108 Institute of Clinical Medical and Pharmaceutical Sciences At Day Month Year The thesis can be found at: 1. National Library of Vietnam 2. Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences
3. 1 BACKGROUND Impaired fasting glucose is a new concept developed by the American Diabetes Association in 1997 and approved by the World Health Organization in 1998 to address "pre-diabetes" as a risk factor of type 2 diabetes mellitus. In 2003, the American Diabetes Association proposed lowering the threshold to 5.6 mmol/l and impaired fasting glucose was defined when fasting glucose levels ranged from 5.6 to 6.9 mmol/l for early detection of potential risks of type 2 diabetes mellitus. The rate of prediabetes is increasing rapidly, especially in people with high cardiovascular risk factors. Although in the pre-diabetic stage, blood glucose levels increase slightly, it begins to cause damage to the target organs, especially when combined with other cardiovascular risk factors such as obesity, hypertension, etc., then the lesions appear early and more. The glucose tolerance test has not been routinely used in cases of impaired fasting glucose, therefore, many cases of diabetes are missed. On the other hand, screening for target lesions in high-risk individuals for aggressive intervention for the purpose of delaying or minimizing complications is not concerned. Therefore, this topic is researched for two goals: 1. Study clinical characteristics, target organ lesions, glucose tolerance test results and insulin resistance in patients with new hypertension associated with impaired fasting glucose. 2. Evaluate the relationship between insulin resistance and target organ lesions in patients with new hypertension associated with impaired fasting glucose.
4. 2 CHAPTER 1: OVERVIEW 1.1. CONCEPTS OF INSULIN AND INSULIN RESISTANCE 1.1.1. The concept of insulin Insulin is a hormone secreted by the pancreas β cells to maintain blood glucose levels. Insulin regulates carbohydrate metabolism, lipid and protein metabolism, promotes cell division and growth. 1.1.2. The concept of insulin resistance "Insulin resistance is a decrease in the biological response of cells, organs, and organizations to the actions of insulin." The concept of insulin resistance refers to the decline in the biological response of insulin on the target cells, which is usually expressed by an increase in insulin levels in the blood. 1.1.3. Methods to determine insulin resistance Endogenous methods - Basic fasting insulin measurement: (I0). - Oral glucose tolerance test: quantifies concentration of glucose and fasting plasma insulin (G0, I0), after 75 g of glucose intake for 5-10 minutes. After 120 minutes, blood is taken again to measure the concentration of glucose and insulin (G120, I120). Exogenous methods - The glucose “clamp”: This method is considered to be the most accurate or "gold standard". Glucose level is "clamped" or fixed at a certain level while evaluating the secretion of insulin. If the patient needs a large amount of glucose to maintain normal blood glucose levels, then it is not insulin resistant. Some indicators of insulin resistance - Index HOMA-IR (Homeostasis Model Assessment Insulin Resistance):
5. 3 HOMA- IR = - QUICKI index: Quantitative Insulin Sensitivity Check Index. QUICKI = 1 / log (I 0 + G 0 ) - ß cell function Homeostasis Model Assessment based on Matthew D. + HOMA -% ß = 1.1.4. The pathology and clinical syndrome associated with insulin resistance 1.4.1.1 The role of insulin resistance in type 2 diabetes Insulin resistance is a prerequisite in glucose metabolism disorder. Forms of insulin resistance are also abundant including: decreased ability to inhibit glucose production in the liver, reduced ability of glucose uptake in peripheral tissues and reduced ability to use glucose in organs. The early phase of insulin secretion is reduced in both impaired fasting glucose and glucose tolerance disorders. In the late phase of insulin secretion, people with impaired fasting glucose are normal while glucose tolerance disorder are reduced. Impaired fasting glucose In 2003, the American Diabetes Association proposed lowering the threshold to 5.6 mmol/l (100/mg/dl) and impaired fasting glucose is determined when fasting plasma glucose level from 5.6 to 6.9 mmol/l. This standard is widely applied today. Glucose tolerance disorder Glucose tolerance disorder is a concept adopted by the World Health Organization in 1980 for use in pre-diabetes and the regulation of oral glucose tolerance testing for diagnosing and quantifying fasting plasma glucose level, followed by 75 g of glucose dissolved in 250 - 300 ml of drinking water within 5 - 15
6. 4 minutes. After 120 minutes, blood is taken again to quantify glucose level to evaluate results. - Glucose level after 2 hour glucose tolerance testing is <7.8 mmol/l: normal glucose tolerance. - If the glucose level after 2 hour glucose tolerance testing is 7.8 - 11 mmol/l: glucose tolerance disorder. - If the glucose level after 2 hour glucose tolerance testing is ≥ 11.1 mmol/l: diabetes. 1.1.4.2. The role of insulin resistance and hypertension The relationship between insulin resistance in hypertension is still a challenge for scientists. Coexistence of insulin resistance and hypertension can be seen in the causal relationship (insulin resistance causes hypertension and vice versa) or the independent relationship of the same metabolic disorder (cumulative calcium accumulation) due to changes in phosphorylation of glucose transporters and other intracellular substrates. Studies also report that free Ca ++ levels in the plasma of patients with hypertension are higher than in those with normal blood pressure, and that Ca ++ levels are closely related not only to blood pressure but also to increased blood insulin. Or, insulin resistance is a genetic marker in the pathogenesis of various metabolic abnormalities commonly associated with hypertension. Treatment by long-term insulin injections does not cause hypertension and hyperinsulinemia patients due to pancreatic islet beta cells are not reported with hypertension. 1.2. TARGET ORGAN LESIONS IN HYPERTENSIONS WITH IMPAIRED FASTING GLUCOSE 1.2.1. Endothelial dysfunctions Endothelial dysfunction includes the alteration of anticoagulants and anti-inflammatory agents in endothelial cells, defects in the regulation of vascular growth factors, prevention of vascular recovery, reduction of NO production and other vasodilators (endothelin-1, thromboxane A2, and angiotensin II). Under basic conditions, the biological effect of NO in the body plays a role in lowering blood pressure due to vasodilatation. Endothelial cells also release acetylcholine, P, serotonin, prostacyclin, etc.
7. 5 1.2.2. Lesions of large blood vessel system Hypertrophy of myocardial cells, restoration of cardiac muscle, left ventricular dysfunction, heart failure Myocardial ischemia, acute coronary syndrome. Lesions of cerebral vascular system lesions of aortic system, lower limb artery 1.2.3. Lesions of small blood vessels Renal failure: Structural and renal dysfunction are almost present in hypertensive patients with features of arterial injury to glomerular, but are not specific because they are found in renal vascular diseases. The artery wall thickening occurs first, followed by hyaluronation, medial fibrosis in coming arteries and arteries in the glomerulus. Hypertension causes kidney damage includes two forms: malignant and benign kidney disease. Eye lesions: Self-regulation of blood flow helps to stabilize blood flow to organizations even when there is a change in flow pressure. When the blood pressure rises or falls, the arteries will contract or relax to adjust the flow. However, this self-regulation becomes less effective when blood pressure exceeds the threshold because the contraction and relaxation of the arterioles are to a certain degree. CHAPTER 2 RESEARCH OBJECTS AND METHODS 2.1. RESEARCH SUBJECTS The study was conducted from October 2011 to October 2014 at Bach Mai Hospital Clinic on 472 objects who met the selection criteria and exclusion criteria , divided into 3 groups: 2.1.1. Group of diseases Criteria for selecting patients The study group consisted of 218 people with primary hypertension first discovered with BP> 140/90 mmHg and with impaired fasting glucose according to standards of American Diabetes Association 2003 when the fasting plasma glucose level was 5, 6 mmol/L - 6.9 mmol/L. * Exclusion criteria Patients with a history of hypertension, diabetes or hypoglycemic agents, acute pathological conditions: Myocardial
8. 6 infarction, unstable angina, acute stroke, etc., Patients who were or are under treatment for chronic diseases such as renal failure, severe liver failure, etc. patients taking certain drugs that affect test results such as glucocorticoid group, thiazide diuretics, lipid lowering drugs. 2.1.2. Group of pathological symptoms * Criteria for selecting patients The study population consisted of 119 people with primary hypertension first discovered with BP> 140/90 mmHg and with fasting plasma glucose of < 5.6mol/L. Exclusion criteria are the same as the exclusion criteria in the preceding group. 2.1.3. Control group: The control group included 55 people of the same age who were healthy, without hypertension, with fasting plasma glucose <5.6 mmol/L and the same exclusion criteria as the exclusion criteria in the upper group. Control group is used to find out limit index. 2.2. RESEARCH METHODOLOGY Cross-sectional method, descriptive method, controlled study method 2.2.1. History: Family history, smoking habits, alcohol use, physical activity, concomitant diseases, drugs used. 2.2.2. Physical examination: Measurement of height, weight, waist circumference, hip circumference, BMI, blood pressure measurement, ophthalmology and ophthalmoscopy. 2.2.5. Biochemical Tests - Functional Probe: * Blood glucose, blood insulin, blood lipids, oral glucose tolerance test, urine test. * Calculation of glucose tolerance disorder and insulin resistance indices: Fasting plasma glucose (G0) at 120 minutes after glucose tolerance test (G120); fasting insulin level (I0) and at 120 minutes after glucose tolerance test (I120); HOMA-IR, QUICKI. * Evaluate cell functions  by the formula: HOMA -  = 20 x I0/(G0 - 3,5) * Heart Doppler ultrasound 2.3. RESEARCH DATA PROCESSING : SPSS for windows.
9. 7 CHAPTER 3 RESEARCH FINDINGS 3.1. CLINICAL CHARACTERISTICS, TARGET ORGAN LESIONS, GLUCOSE TOLERANCE TESTS, INSULIN RESISTANCE OF RESEARCH OBJECTS 3.1.1. Clinical characteristics Table 3.2. Characteristics of age groups Group of Group of Age pathological diseases distribution symptoms p (n = 218) 5-10%/year (n = 199) n % n % 0,05 50-59 40 20,1 55 25,2 p>0,05 60-69 95 47,8 106 48,6 p>0,05 ≥70 54 27,1 49 22,5 p>0,05 The average age 63,9 ± 8,2 63,5 ± 7,9 p>0,05 Comment: The mean age of respondents was 63 years. Age group 60-69 was the highest in both groups, (p> 0,05). Table 3.4. Anthropometric characteristics between the two research groups Group of Group of pathological diseases symptoms Parameter (n = 218) p (n = 199) n % n % Average BMI 22,68 ± 2,25 23,07 ± 2,23 p>0,05 BMI 0,05 BMI: 18.5 - 22.9 108 54,3% 111 50,9% p>0,05 BMI: 23 - 24.9 63 31,7% 68 31,2% p>0,05 BMI: 25-29.9 21 10,6% 35 16,1% p>0,05 BMI ≥ 30 2 1% 1 0,5% p>0,05 Average WHR 0.89 ± 0.05 0.91 ± 0.04 p <0.05 ↑ WHR 139 6-8 181 83% p <0.05
10. 8 Comment: The mean WHR in group of disease is higher than that in group of pathological symptoms (p <0.05). The proportion of patients with increased WHR is 83% in the group of disease and 69.8% in Group of pathological symptoms (p <0.05). Table 3.9. Rate of left ventricular hypertrophy between the two study groups Group of Group of pathological p diseases symptoms Parameter (n = 218) (n = 199) n % n % Increased LVMI 64 32,2 83 38,1 p>0,05 RWT ≥ 0.42 46 23,1 51 23,4 p>0,05 Comment: The proportion of increased LVMI in group of disease is higher than that in group of pathological symptoms (p>0,050). Table 3.10. Classification of kidney lesions between two study groups Group of Group of pathological diseases symptoms Parameter (n = 218) p (n = 199) n % n % MAU (-) 181 91 169 77,5 p <0.01 MAU (+) 18 9 49 22,5 average eGFR 80,00 ± 23,51 77,45 ± 16,34 p> 0.05 Average ACR 13,74 ± 15,13 22,99 ± 21,81 p <0.01 Comment: MAU (+) in group of disease is higher than MAU (+) group of pathological symptoms, (p <0.01)