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4. Mind map of biochemical testing of glucose metabolism disorders
This is a mind map about biochemical testing of glucose metabolism disorders, including body fluid glucose testing, glucose tolerance test, glycated protein testing, etc.
Edited at 2023-11-12 16:57:43- bacteria
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4. Mind map of biochemical testing of glucose metabolism disorders
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4. Biochemical testing of glucose metabolism disorders
4.2 Types of diabetes
Types of diabetes
② Type 2 diabetes
Insulin resistance (IR): The cellular effect of unit concentration of insulin is weakened, that is, the body's biological response to normal concentrations of insulin is reduced.
Mechanism 1
Insulin gene mutation reduces the level of pancreatic beta cells, resulting in relatively insufficient insulin secretion and elevated blood sugar.
Mechanism 2
Decreased insulin receptors, insufficient biological effects of insulin, insulin resistance, and elevated blood sugar.
Characteristics of type 2 diabetes
Obesity is common in middle-aged and elderly people over 40 years old. The onset is slow and there is a genetic tendency, but it has nothing to do with HLA genes.
The absolute value of insulin content in plasma does not decrease, but its release is delayed after sugar stimulation.
Oral hypoglycemic drugs alone can generally control blood sugar
ICA and other autoantibodies were negative
It is a metabolic syndrome characterized by fasting and postprandial hyperglycemia.
Pancreatic beta cell dysfunction
① Type 1 diabetes (immune-mediated diabetes)
Characteristics of type 1 diabetes
1. It is common in adolescents with an acute onset and prone to ketoacidosis. Genetic factors are related to HLA genotype.
3. Autoimmune damage to beta cells is the most important pathogenesis, and autoantibodies can often be detected
2. Low levels of plasma islet cells and C-peptide
4. Treatment relies mainly on insulin
Most damage is mediated by T cells, and 60% to 80% of newly diagnosed T1DM patients have autoantibodies (ICA, IAA).
autoimmune reaction Chemical material Viral infection
Pancreatic beta cells are damaged
Absolutely insufficient insulin secretion
elevated blood sugar
③Gestational diabetes
diagnosis:
A diagnosis can be made if at least two test results match or exceed the following results.
Determine plasma glucose concentration within two hours
②Measurement of fasting plasma glucose concentration
③ Take 75 grams of glucose orally
①Measurement in the morning on an empty stomach
Refers to diabetes detected during pregnancy. Including any degree of impaired glucose tolerance and onset of diabetes, but known diabetes associated with pregnancy does not exclude this type.
④Other special types of diabetes
This type of diabetes is often secondary to other diseases, with many causes but fewer patients.
type
3. Diabetes caused by islet exocrine disease
2. Diabetes caused by genetic defects in insulin action
1. Diabetes caused by defective B cell function
4. Diabetes caused by endocrine diseases
①Test items
Fasting blood glucose (FPG) (normal value 3.89∽6.11): refers to the venous plasma glucose concentration measured without any caloric intake within 8 to 10 hours.
Random blood glucose: The glucose concentration measured from blood taken as a sample at any time.
②Diabetes
1.Basic concepts
Diabetes is a group of metabolic diseases caused by insufficient insulin secretion or low insulin action. It is characterized by hyperglycemia, the typical symptoms of which are: polyuria, polyuria, and weight loss.
Hyperglycemia: fasting blood glucose concentration exceeds 7.0mmol/L
Major metabolic disorders in diabetes
①Glucometabolism disorders (hyperglycemia and glycosuria)
Hyperglycemia (exceeding the renal glucose threshold) can be excreted by the kidneys, Causes glycosuria and produces osmotic diuresis
②Lipid metabolism disorder (hyperlipidemia and hypercholesterolemia)
Due to increased production of acetoacetate and beta-hydroxybutyrate, Depletion of the blood buffer system leading to acidosis
③Protein metabolism disorder (weight loss and slow growth)
Protein and fat synthesis decrease and decomposition accelerates
complications of diabetes
Characteristics of diabetes: polydipsia, polyuria, and weight loss.
4.3 Body fluid glucose detection
③Methods for blood glucose testing
enzymatic method
Glucose oxidase method (common method)
Principle of glucose oxidase method
Characteristics of glucose oxidase method
①Applicable to serum, plasma, and cerebrospinal fluid samples, not applicable to urine and whole blood. Peroxidase has low specificity and is affected by reducing substances in the body such as uric acid, bilirubin, and Vita C. It can compete with the chromogen for hydrogen peroxide, resulting in lower results.
③Measurement is faster (within 30 seconds) and uses less blood (less than 5 microliters)
② Mutarotase is required to convert α-type D-glucose into β-type
Hexokinase method (HK, reference method)
The generation rate of NADPH is proportional to the glucose concentration. The laser intensity increase rate is detected at a wavelength of 340nm to calculate the glucose concentration in the serum.
Features:
① High specificity, mild hemolysis, lipemia, jaundice, etc. do not affect the results
②Reference method for glucose measurement
Glucose ATP, coupled to oxidized coenzyme II, generates reduced coenzyme II (maximum absorption peak at 340nm)
inorganic chemistry
Folin Wu Method (Pioneer Method)
organic chemistry method
o-Toluidine method (deprecated method)
④Clinical significance of detection
2. The fasting blood glucose level reflects the ability to secrete insulin. If the FPG concentration is higher than 7.0mmol/L in two repeated tests, diabetes can be diagnosed.
4. Pathological hypoglycemia is seen in pancreatic beta cell hyperplasia or pancreatic beta cell tumor, etc., causing excessive secretion of insulin.
3. Physiological hyperglycemia can be seen after ingesting high-sugar foods or when adrenal gland secretion increases due to emotional stress.
1. Fasting blood glucose is the most commonly used test for diabetes.
Does high blood sugar necessarily lead to diabetes?
Not necessarily. Diabetes will occur in normal people only when the blood sugar concentration exceeds the renal glucose threshold (10mmol/L).
①The concept of blood sugar
See above
②The source and outlet of blood sugar
See above
⑤Blood sugar two hours after a meal
subtopic
4.1 Human body’s blood sugar regulation mechanism
②The source and outlet of blood sugar
The path of blood sugar
Oxidative decomposition→ATP
① Anaerobic glycolysis: glucose → pyruvate → lactic acid (produces a small amount of ATP)
②Aerobic oxidation: glucose → pyruvate → acetyl CoA (generating carbon dioxide, water and most of ATP)
Synthesis of liver and muscle glycogen
convert to fat
gluconeogenesis
The meaning of blood sugar balance
① Blood sugar is the main energy substance for human life activities. Blood sugar balance ensures sufficient energy supply for various human tissues and organs.
②Insufficient blood sugar will lead to insufficient energy supply in the human body.
③ Diabetes may occur when blood sugar concentration is too high.
Source of blood sugar
Digestion and absorption of sugars in food
Conversion of fats and other non-sugar substances
hepatic glycogenolysis
③Things to do with blood sugar balance
regulation of body fluids
Alpha cells (increase blood sugar) → secrete glucagon → promote the decomposition of liver glycogen into glucose and the conversion of non-sugar substances into glucose
Beta cells (lower blood sugar) → secrete insulin
①Promote cells to absorb glucose
③Promote sugar oxidation and decomposition
④The effect of preventing gluconeogenesis
②Promote glycogen synthesis
⑤Reduce fat mobilization
regulation of liver
The liver is the main organ that regulates blood sugar concentration
Hyperglycemia: blood sugar → glucose 6 phosphate → glycogen
Hypoglycemia: liver glycogen→G-P-6→glucose
The liver is also the main organ for gluconeogenesis
regulation of the nervous system
Lateral hypothalamic nucleus→pancreatic beta cells→insulin
ventromedial hypothalamic nucleus
pancreatic alpha cells → glucagon
Splanchnic nerves → adrenal medulla → epinephrine
①Concept of blood sugar
glucose in blood
3.89∽6.11mmol/L (70∽110mg/dl)
4.4 Glycated protein detection
④Detection method
2. Enzyme method
Methodological evaluation: It has high precision, good specificity, simple operation, suitable for fully automatic biochemical analysis, and low cost.
Detection principle: Hemoglobin beta chain (protease)—→N-terminal-glycylglutamine Glycylglutamine (FPOX)—→H₂O₂
reference interval HbA₁c4%~6% (HPLC method)
1. Ion exchange chromatography
Detection principle: GHb and HbA can be eluted in stages using phosphate buffers of different pH. The corresponding Hb chromatogram was obtained and expressed as a percentage.
Methodological evaluation: Ion exchange HPLC method is the gold standard for HbA₁C detection. The cation exchange resin micro-column method is mainly used in China
Specimen: Venous plasma (EDTA/oxalate/sodium fluoride anticoagulation)
③Chromatography (ion exchange or affinity chromatography)
①High performance liquid chromatography (HPLC)
②Immunoanalysis
④Electrophoresis
②Composition
HbA₁c is true glycated hemoglobin, It is the main component of HbA₁ and its concentration is relatively stable, so HbA₁c can better reflect blood sugar levels.
The glycosylation site in HbA is in the β chain, which is divided into HbA₁a, HbA₁b, and HbA₁c, collectively referred to as HbA₁
Hemoglobin: HbA(97%), HbA₂(2.5%), HbF(0.5%)
The product of the reaction that occurs on the alpha chain is called HbAo
HbA: consists of 4 chains, α₂β₂
③Clinical significance
Evaluate blood sugar control: reflects the average blood sugar concentration in the past 6 to 8 weeks and is a reliable laboratory indicator. Glycated hemoglobin concentration is related to the lifespan of red blood cells and the average concentration of blood sugar during that period.
HbA₁c is an independent predictive risk factor for cardiovascular events in patients with diabetes
For diagnosis of diabetes
HbA₁c≥6.5% Diabetes
5.7%~6.4% prediabetes
Predicting chronic complications of diabetes
8%~9% control is not ideal
Greater than 9%, blood sugar control is poor
① Glycated hemoglobin
Definition: The product formed by the non-enzymatic reactive combination of hemoglobin and glucose in the presence of high concentrations of blood sugar for a long time. This is a slow, irreversible process. The glycosylation site is the valine residue at the N terminus of the hemoglobin β chain. Its production is related to blood glucose concentration and the duration of hyperglycemia.
Glucose can irreversibly combine with amino groups in many proteins in the body in the form of covalent bonds. To form glycated protein, this process does not require the participation of enzymes. The reaction speed mainly depends on the concentration of glucose. The use of glycated proteins to diagnose or track the development of the disease has unique clinical significance.
4.5 Glucose tolerance test
Blood sugar two hours after a meal.
clinical significance
③Blood sugar two hours after a meal can better reflect the amount of food eaten and whether the use of hypoglycemic drugs is appropriate. It cannot be replaced by checking fasting blood sugar.
②Blood sugar >11.1mmol/L two hours after a meal is prone to chronic complications of diabetes such as eyes, kidneys, and nerves.
①Reflects the reserve function of pancreatic islet β cells and the ability of pancreatic islet β cells to secrete insulin after eating.
Detection method
Glucose tolerance test after oral administration of 75 g anhydrous glucose
Eat 100g of steamed buns
reference interval
Blood sugar <7.8mmol/L two hours after a meal
summary
①OGTT can understand the function of pancreatic beta cells and the body’s ability to regulate glucose.
③When blood sugar is abnormally elevated but has not yet reached the diagnostic criteria for diabetes, this test can be used to determine whether it is diabetes.
②OTGG recognized as the gold standard for diagnosing diabetes
④The OGTT test is more sensitive than FPG, but has many influencing factors and is not recommended for routine clinical use.
Detection method
Test method: WHO recommends standardized OGTT test method
Preparation before experiment: Three days before the test, the sugar content in the daily food should not be less than 150 grams, and normal activities should be maintained. Drugs that may affect the test should be stopped three days before the test, and an empty stomach should be fasted for 10 to 16 hours before the test.
Experimental procedure: Within 5 minutes after taking blood while seated, drink 250 ml of sugar water containing 75 grams of anhydrous glucose. After that, blood was taken every 30 minutes for a total of 4 times. Finally draw a glucose tolerance curve. Collect urine every 1 hour for glycosuria measurement
Test items
Test item basis
Give subjects a certain loading dose orally or intravenously After glucose, by measuring the blood glucose concentration at different times, Understand the subject's ability to regulate blood sugar.
Including OGTT and IGTT
Clinical biochemistry test items in Application in the diagnosis and treatment of glucose metabolism disorders.
Application principles: Differential diagnosis of slowly progressive autoimmune diabetes in adults; Kidney or pancreas transplantation; evaluation of differential diagnosis of 1-DM and 2-DM in women with GDM
screening index ①Blood sugar: FPG, OGTT, 2h blood sugar ②Immune markers: IAA, ICA, anti-GAD ③ Gene markers: 1-DM: HLA related genes 2-DM: Multiple genes related to glucose metabolism ④Insulin secretion: fasting secretion, pulse secretion, glucose-stimulated secretion
Hypoglycemia
hypoglycemia
Cause: Imbalance between glucose uptake, endogenous glucose production and utilization.
type
Symptoms of hypoglycemia in newborns and infants
Fasting hypoglycemia in adults
diabetic hypoglycemia
postprandial hypoglycemia
During hypoglycemia, due to increased secretion of hormones such as adrenaline, Causes sweating, palpitations, hunger, dizziness, increased heart rate, etc. When it is less than 1.7mol/L, it will cause severe damage to the central nervous system.
Definition: Blood glucose concentration is lower than the lower limit of the fasting blood glucose reference level, Generally, 2.78mmol/L is used as the lower reference limit (50mg/dl)
Summarize