L3 _Glucose Tolerance and Glycemic Control_2024-25 SEM1(1).pdf

2k¥ Glucose tolerance and glycemic control , 9 June 2024 Huige LIN Learning outcome In this lecture, students shall learn: Pathophysiology of diabetes mellitus (DM) Laboratory diagnosis of DM DM monitoring...

2k¥ Glucose tolerance and glycemic control , 9 June 2024 Huige LIN Learning outcome In this lecture, students shall learn: Pathophysiology of diabetes mellitus (DM) Laboratory diagnosis of DM DM monitoring & prevention of complications Complications of DM Laboratory diagnosis & monitoring of diabetic nephropathy  Importance of glucose Common and abundant simple sugar from dietary carbohydrates Can be synthesized from protein or triglyceride Storage as glycogen in the liver Tsp hymen of glume - All tissues use glucose: as energy source for precursors in the biosynthesis of amino acids, lipids and nucleic acids Skeletal muscle use glycogen and blood glucose for energy production in heavy exercise Brain and red blood cells use glucose almost exclusively as the major source of energy; hypoglycemia impairs cerebral function The brain mainly depend on glucose for energy; low blood glucose impairs brain function Hak Fasting blood glucose (FPG) for non-diabetes: 3.9 – 5.6 mmol/L Blood glucose >renal threshold (around 10 mmol/L), blood glucose spills into the urine (glycosuria) When glucose is not readily available, body metabolize fat as energy source; with ketone production and resulting in ketoacidosis b glucose → ☒ lol → by ketone Reference Intervals EXTRA FPG levels no sex difference Increase with age from the third to the sixth decade does not increase significantly after age 60  Regulation of blood glucose Insulin produced from- cells of the pancreas after meal Stimulates uptake of glucose from blood to liver, muscle after meals. Hence insulin decrease blood glucose levels. Joe Synthesis of glycogen in liver and muscle for storage Insulin Inhibits glucagon release Glucagon produced from cells of the pancreas; increasing blood glucose levels in fasting state → Normal blood glucose Stimulate liver glycogenolysis (breakdown of liver glycogen to release glucose to blood stream) ◦ Stimulates gluconeogenesis (the formation of glucose from lactate → & amino acids & fat) to maintain blood glucose levels. Other hormones that increase blood glucose: growth hormone (GH), adrenaline, cortisol, adrenocorticotropichormone (ACTH) and thyroid hormones Post meal insulin and glucagon response Blood glucose homeostasis 8 In a fed state, insulin dominates In a fasting state, glucagon dominates  Causes of hyperglycemia Hyperglycemia (increased blood glucose concentration), is the most frequently encountered disorder of carbohydrate metabolism. *As An FA ① Diabetes mellitus (DM): Metabolic disorder characterized by hyperglycemia (high blood glucose) due - to problems making or using insulin ← Endocrine disorders – increased levels of growth hormone (GH), adrenaline, cortisol, thyroid hormones and adrenocorticotropichormone (ACTH) ③ Medication: glucocorticoids (corticosteroids) for allergic, inflammatory, and autoimmune disorders ④ Prolonged stress state -> increased stress hormones (prolactin, cortisol, adrenaline)  Pathophysiology & types of diabetes mellitus (DM) Diabetes: a Silent Killer and Global Epidemic Type 1 Insulin dependent diabetes mellitus (IDDM) or juvenile onset DM gkn%Bf-msntm.ua 5% to 10% of DM is Type 1 Caused by autoimmune disease; resulting in cell destruction and complete lack of insulin; associated with histocompatibility leukocyte antigen (HLA) in 40-50% of familial type 1 DM. Some have increased islet cell antibodies & insulin antibodies antigen *↓Éy Some caused by infectious agent e.g enteroviruses Autoimmune cell [ reaction Need life-long treatment with insulin injections destroyed ✓ insulin cell h Br antibodies Feature cell Acute onset -814¥ Mostly affect: children and young adults Insulin dependent Metabolism of fat causes ketoacidosis that may induce coma  Pathophysiology & types of diabetes mellitus (DM) Type 2: previously called non-insulin dependent diabetes mellitus (NIDDM). These names are invalid as insulin is often used in the management of type 2 diabetes. 90% of DM is Type 2 Due to progressive loss of -cell insulin secretion and/or insulin @ resistance (body cells can not respond to insulin efficiently) Associated with sedentary lifestyles, obesity, diet, and polygenic factors Insidious (gradual, subtle) presentation a- Mostly affect: Middle aged, elderly. Management Oral hypoglycemic drugs (metformin, sulfonylurea, insulin) Lifestyle management: exercise, diet control  Pathophysiology & types of diabetes mellitus (DM) Gestational (GDM) BOX 57.1 Classification of Diabetes Mellitus defined as any degree of glucose intolerance I. Type 1 diabetes during pregnancy II. Type 2 diabetes Affecting both the baby and the mother. III. Gestational diabetes mellitus Most patients shall returns to normal after IV. Other specific types delivery. A. Genetic defects of -cell function B. Genetic defects in insulin action C. Diseases of the exocrine pancreas Frequency range from less than 1% to 28% D. Endocrinopathies E. Drug or chemical induced 40% of GDM patients may have Type 2 DM F. Infections G. Uncommon forms of immune-mediated diabetes later in life. H. Other genetic syndromes sometimes associated with diabetes From the American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care S81–90.  Diagnostic Tests for diabetes Fasting blood glucose: Blood sample taken when the patient has not eaten for a specific period of time (fasting; e.g. 8 hours) Convenient Serves as the screening test Oral glucose tolerance test (OGTT) for diagnosis of DM Procedure: Patient ( overnight fast 8 hours ) – take blood for 0 time. Consume g anhydrous glucose dissolve in water. Take blood for glucose measurement at 1 hour and 2 hours. Time-consuming.  OGTT Glucose load is LAG Curve Fasting glucose level is normal. Rises rapidly in the 1/2 to 1 hour and exceeds the renal threshold; urine specimens glucose + The return to normal value is more rapid than normal This curve is obtained in : Hyperthyroidism Post gastroenterosectomy During Pregnancy Early diabetes ☆ Earthy American Diabetes Association (ADA) 2024 diagnostic criteria for DM in non-pregnant individuals 2 hours post- OR Classic symptoms of hyperglycemia or hyperglycemic crisis with a HbA1c  American Diabetes Association (ADA) 2024 o Diagnostic criteria for prediabetes in non-pregnant individuals Prediabetes is an intermediate state between normoglycemia and diabetes; it is clearly a significant risk factor for progression to diabetes Fasting (8 hours) plasma glucose 5.6 – 6.9 mmol/L; OR - test (OGTT); OR HbA1c – 6.4%  Diagnostic tests for diabetes FPG OGTT-2h-PG Diagnostic results mmol/L mmol/L Normal glucose tolerance mmol/L -11.1 mmol/L Impaired glucose tolerance 6.1- mmol/L mmol/L Impaired fasting glycemia mmol/L 11.1 mmol/L DM  Gestational DM (GDM) qh¥* BAE Diabetes during pregnancy increases fetal and maternal morbidity (subject to disease state) and mortality (subject to death) Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset of pregnancy In women with pre-existing DM, when they are pregnant, it is called DM in pregnancy → - A*cb*FbK¥☒ Diagnosis of GDM (HK College of O&G; 2016) ONE or more of the venous plasma glucose values are met or exceeded: ISLET Fasting: 5.1 – 6.9 mmol/L 2 hour: 8.5 – 11.0 mmol/L  Glucose Monitoring Important for preventing or delaying complications GOD-POD method Determination of glucose: methods: enzymatic: e.g. glucose oxidase (GOD-POD method)or hexokinase principles: photometry or amperometry Home glucose meters (Point of care testing- POCT) Laboratory tests for diabetic monitoring & management: - Glycated hemoglobin, i.e. HbA1c Urinary albumin excretion (microalbumin) – is the early indicator of diabetic kidney damage (nephropathy) Glycated albumin  Glycated hemoglobin (HbA1c) tf ☆ Hemoglobin is the oxygen-carrying pigment that gives blood its red color At least 96% of hemoglobin in the whole blood is hemoglobin A (HbA; the "A" stands for ⊖ adult type) Art Approximately 6 % of hemoglobin A (HbA) is made up of minor components that are glycated and chemically slightly different. These minor components are hemoglobin A1c (~5%), A1b, A1a1, and A1a2. Hemoglobin A1c (HbA1c) is a minor component of hemoglobin to which glucose is bound, i.e. glycated → bind with 8k¥ prop > HbA1c levels depend on the blood glucose concentration, i.e. the higher glucose concentration in blood, the higher level of HbA1c. - Levels of HbA1c: not influenced by daily fluctuations in blood glucose level, but reflect the average glucose levels over the average of life-span of RBC of 2 – -12 weeks.  Chemical reaction in glycation of hemoglobin Nonenzymatic reaction between the glucose and the N- -chain of Hb, forms a reversible Schiff base The second step is irreversible, Schiff base is converted into the stable Amadori product Correlation between HbA1c and fasting - - blood - glucose in type 2 DM patients  Glycated hemoglobin (HbA1c) HbA1c serves as: useful indicator of long-term blood glucose level in the recent past 2- -12 weeks to monitor the effects of diet, exercise, and drug treatment long term titty the 2-3 months In non-diabetics, the HbA1c level is