L14 Diabetes (Students) PDF - Lecture Notes

D I A B E T E S M E L L I TU S Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk fac...

D I A B E T E S M E L L I TU S Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors and diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management. Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management.  Diabetes is a chronic disease characterized by elevated levels of Definition blood glucose, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves. Type 1 Diabetes Mellitus (T1DM) Types Type 2 Diabetes Mellitus (T2DM) Gestational Diabetes Mellitus (GDM) Idiopathic Diabetes Mellitus Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management.  T1DM T2DM Autoimmune reaction where own Progressive decline in β-cells function immune cells attack β-cells associated with low level of insulin Pathophysiology results in no/zero insulin secretion and insulin resistance in production. muscle and adipose tissue *β-cells are insulin producing cells at islet of Langerhan’s in pancreas*  Features of T1DM & T2DM Features T1DM T2DM Onset Sudden Gradual Age of Onset Any age mostly young Mostly in adults Body Thin or normal Often obese Ketoacidosis Common Rare Autoantibodies Usually present Absent Endogenous insulin Zero/no/low Insufficient/resistance Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management. Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors and diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management.  Increasing age Smoking Obese African-Carribean, Black African or Risk History of cardiovascular South Asian Factor disease/GDM/PCOS/mental Physical inactivity and sedentary health condition lifestyle Family history of DM Drugs eg long-term use of corticosteroid, atypical antipsychotic drugs For screening: Confirm diagnosis Fasting capillary blood symptomatic individual + any one abnormal value or glucose ≥ 5.6mmol/L asymptomatic individual + two abnormal value Random capillary Diagnosis blood glucose ≥ Abnormal value 7.8mmol/L HbA1c ≥ 6.3% Fasting venous plasma glucose ≥ 7.0mmol/L (fasting for at least 8 hours) Random venous plasma glucose ≥ 11.1mmol/L *HbA1c = a test that measure the average blood glucose level over the past 3 months* Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management. Acute complications Chronic complications Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management.  Diet Physical activity Non- pharmacologic Weight reduction for overweight Smoking cessation for smokers al treatment  Diet Physical activity Low calorie diet (reduce calorie Aim 150min/week moderate intake) intensity exercise Reduced carbohydrate intake Moderate intensity exercise – “suku-suku separuh” – quarter exercise using 50-70% maximum carbohydrate, quarter protein, heart rate half vegetables and fruits Example: fast walking, cycling on Avoid snacking/binge eating ground level and gardening Non- pharmacologic Weight reduction for overweight Smoking cessation for smokers al treatment Monitor body weight regularly Set quit date Aim normal BMI = 18.5 – 23kg/m2 Recognize triggering factors and 5-10% body weight reduction in 6 avoid them months Social supports from family Repeat until normal BMI reached members and friends Via low calorie diet, increase Seek pharmacological treatment physical activity, intermittent from clinic/pharmacy fasting Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management.  Antidiabetic Drugs Classes Examples Biguanides Metformin Sulphonylureas (SU) Gliclazide, Glibenclamide, Glimepiride Meglitinides Repaglinide, Nateglinide Will not be discussed as they Thiazolidinediones (TZD) Pioglitazone are not widely used in Malaysia Alpha glucosidase inhibitors (AGI) Acarbose Dipeptidyl-peptidase 4 inhibitor Sitagliptin, Vildagliptin, Linagliptin (DPP4-i) Glucagon-like peptide-1 receptor Exenatide, Liraglutide, Lixisenatide, Dulaglutide, agonist (GLP1-RA) Semaglutide (incretin mimetics/ GLP analogues) Sodium-glucose transporter 2 Empagliflozin, Dapagliflozin, Canagliflozin inhibitors (SGLT2-i)  Biguanides Example Metformin (Glucophage®) Reduce gluconeogenesis (production of glucose from glycogen) Mechanism of Increase insulin sensitivity in cells Action Reduce absorption of glucose in small intestines Most common: Nausea and vomiting, diarrhea, GI discomfort Long term use of MTF decrease absorption of B12 deficiency in GI that Side effects causes peripheral neuropathy Lactic acidosis in renally impaired patients. MTF excreted by kidneys, so impaired kidney cause MTF accumulation that indirectly cause high lactate production and reduced lactate clearance Formulations Immediate release tab Extended-release tab Strengths 500mg 850mg 750mg 1000mg  Biguanides Counseling Points Most common side effects may be minimized by: - taken MTF together with meals/after meals - change MTF to XR formulation - low dose/ increase dose of MTF gradually For XR formulation; swallow tablet whole do not crush, best taken after dinner General Information Normally the first-line treatment for T2DM Dose beyond 2000mg/day do not confer any further glycemic benefits Safe in pregnancy and breastfeeding May result in mild weight loss. Can be combined with any other antidiabetic drugs Sulphonylureas (SU) Examples Gliclazide (Diamicron®), Glimepiride (Amaryl®) Mechanism of Action Increase insulin production in pancreas Hypoglycemia Side effects Weight gain Formulations Immediate extended-release tab Strengths Tablet = 80mg MR = 30mg and 60mg  Sulphonylureas (SU) Counseling Points Most common side effects are hypoglycemia and weight gain – counseled on management of hypoglycemia and monitor body weight Gliclazide should be taken 30 minutes before breakfast and dinner (avoid hypo) Gliclazide MR may be taken immediately before or after breakfast General Information Generally used as add-on therapy suitable for non-obese patient Contraindicated with basal-bolus insulin regimen (insulin treatment)  Alpha-glucoxidase Inhibitors (AGI) Examples Acarbose (Glucobay®) Delay digestion of carbohydrates Mechanism of Action Slow down glucose absorption in small intestine Bloating Side effects Abdominal discomfort Diarrhea Flatulence Formulations Immediate release chewable tablet Strengths 50mg, 100mg Alpha-glucoxidase Inhibitors (AGI) Counseling Points Acarbose must be taken orally with little liquid or chewed with the first mouthful of food every heavy meal. Taking Acarbose earlier render it useless as it is rapidly degraded by bacteria in the gut May cause increase flatulence, diarrhea, abdominal discomfort and bloating – may need to use sanitary pad General Information Can be combined with any antidiabetic agents Contraindicated in inflammatory bowel disease, colonic ulcerations, intestinal obstruction.  Dipeptidyl-peptidase 4 Inhibitors (DPP4-i) Examples Sitagliptin, Vildagliptin, Linagliptin Inhibits the breakdown of incretin secreted during meals. Mechanism of Incretin functions: increase insulin secretion, reduce glucagon Action secretion, slows gastric emptying (slowing glucose absorption) and promotes satiety GI discomfort Side effects diarrhea Hypoglycaemia Formulations Immediate release tablet (for all) Sitagliptin (Januvia®) = 25mg/50mg/100mg Strengths Vildagliptin (Galvus®) = 50mg Linagliptin (Trajenta®) = 5mg Dipeptidyl-peptidase 4 Inhibitors (DPP4-i) General Information Can be combined with any antidiabetic agents Weight neutral  Glucagon-like Peptide-1 Receptor Agonists Examples Exenatide, Liraglutide, Lixisenatide, Dulaglutide, Semaglutide Mimic the effects of incretin Mechanism of Incretin functions: increase insulin secretion, reduce glucagon secretion, Action slows gastric emptying (slowing glucose absorption) and promotes satiety Nausea &Vomiting Side effects Diarrhea Weight loss Formulations Injection Exenatide IR (Byetta®) = 5μg/20μL, 10μg/40μL (OD dosing) Exenatide XR (Bydureon®) = 2mg (weekly dosing) Strengths Liraglutide (Saxenda®) = 6mg/mL (OD dosing) Lixisenatide (Adlyxin®) = 50μg/mL, 100μg/mL (OD dosing) Dulaglutide (Trulicity®) = 0.75mg, 1.5mg (weekly dosing) Glucagon-like Peptide-1 Receptor Agonists Counseling Points Nausea and vomiting are common side effects and must be adequately counseled Counseled on injection techniques General Information Can be combined with other antidiabetic Licensed for weight reduction  Sodium-Glucose Transporter 2 Inhibitors Examples Empagliflozin, dapagliflozin, canagliflozin Selectively inhibits SGLT-2 inhibitors at proximal convoluted tubule in Mechanism kidney of Action Reduce glucose reabsorption back into blood vessels Increase glucose excretion in urine Significantly increases risk of UTI Weight loss Side effects Dehydration and Mild hypotension - volume depletion via osmotic diuresis Formulations Immediate release tab Strengths Empagliflozin (Jardiance®) = 10mg and 25mg Dapagliflozin (Forxiga®) = 5mg and 10mg Canagliflozin (Invokana®) = 100mg and 300mg Sodium-Glucose Transporter 2 Inhibitors Counseling Points Dehydration – drink a lot of water Increase risk of UTI – proper hygiene Postural hypotension – get up slowly General Information SGLT2i is cardioprotective, Reno-protective and now indicated for heart failure too! Contraindicated in severe renal impairment  Insulins Mechanism of Action Insulin facilitate glucose uptake by body cells from blood vessel Hypoglycemia Side effects Weight gain Lipodystrophy (Lipohypertrophy): The accumulation of fat tissue, causing lumps or thickened areas under the skin at injection sites. Formulations Injection Strengths 3ml of 100UI/ml (all except Toujeo) 4.5ml of 300UI/ml (Toujeo) Some terms used for insulins Common insulin regimen Insulin may be given once up to five times Continuous insulin infusion daily. The most favorable regimen that mimics normal insulin secretion is the basal-bolus regimen, which involves: 1x long-acting or intermediate-acting insulin (typically at night) to provide basal coverage. 3x rapid-acting or short-acting insulin (before each main meal) to manage post-meal blood sugar spikes. Insulin Counseling Points Counseling on injection techniques Site of administration injected subcutaneously into abdominal area, thigh and arm Rotate site rotation to reduce lipodystrophy Usually injected at 90⁰. 45 ⁰ for thin people Storage – unused insulin pen/cartridge in refrigerator (2-8 ⁰C), opened cartridge/insulin pen at room temperature (discard after 4weeks for Toujeo, 6weeks for others) General Information Can be combined with all agents except sulphonylureas Safe in pregnancy Combination Antidiabetics Drugs Glucovance Janumet Galvusmet Xigduo Invokamet Glyxambi Kombiglyze XR Objectives At the end of this lecture, students should be able to: 1. Understand the definition of diabetes mellitus (DM) and state the types of DM 2. Differentiate pathophysiology and features of T1DM and T2DM. 3. Identify the symptoms of DM 4. State the risk factors, diagnosis of DM 5. Identify the complications of DM 6. Identify non-pharmacological treatment of DM 7. Differentiate the antidiabetic drugs (classifications, mechanism of actions, side effects, generic and trade names) 8. Understand the general information regarding DM management. General Information Management of Hypoglycemia Helps patients to recognize symptoms of hypoglycemia – palpitation, sweating, tingling, feeling hungry, trembling, drowsiness, vision changes) Blood glucose level 7 mmol/L (fasting) or >11.1 mmol/L (random). Drink water, administer insulin or adjust medication as prescribed, and consider exercise (after consulting a healthcare provider). Antidiabetic effects on weight and safety in pregnancy?