Topic 3 Management of Endocrine Disorders (Diabetes Mellitus) PDF

TOPIC 3: MANAGEMENT OF ENDOCRINE DISORDERS Diabetes Mellitus Thyroid Disorders Parathyroid Disorders Clinical Therapeutics I RPB40203 Nor Safwan Hadi bin Nor Afendi Lecturer Discipline of Clinical Pharmacy and Pharmacy Practice Faculty of Pharmacy and Health Sciences...

TOPIC 3: MANAGEMENT OF ENDOCRINE DISORDERS Diabetes Mellitus Thyroid Disorders Parathyroid Disorders Clinical Therapeutics I RPB40203 Nor Safwan Hadi bin Nor Afendi Lecturer Discipline of Clinical Pharmacy and Pharmacy Practice Faculty of Pharmacy and Health Sciences UniKL RCMP  Diabetic Foot Ulceration (DFU) Acanthosis nigricans Diabetic Nephropathy Diabetic Retinopathy Diabetic Neuropathy INTRODUCTION TO DIABETES MELLITUS TYPE 2 T2DM is a chronic disorder marked by high blood sugar due to insulin resistance/deficiency. Global prevalence is rising, with notable trends in developed and developing countries, including Malaysia. Insulin resistance in muscles/fat and beta-cell dysfunction in the pancreas cause hyperglycemia. Risk Factors Obesity, inactivity, high-fat diets, family history, age, and ethnicity (e.g., South Asians) are significant risk factors. Learning Point: Understanding T2DM's multifactorial nature is crucial for effective management. DIAGNOSTIC CRITERIA FOR T2DM Criteria from ADA 2024 include: ✓ FPG ≥ 7.0 mmol/L, 2-hour plasma glucose ≥ 11.1 mmol/L during OGTT, ✓ HbA1c ≥ 6.5%, and random plasma glucose ≥ 11.1 mmol/L ✓ with hyperglycemia symptoms. Pre-diabetes involves impaired fasting glucose and impaired glucose tolerance, increasing T2DM risk. Hyperglycemia symptoms: polyuria, polydipsia, weight loss, fatigue, blurred vision, frequent infections, slow healing. Learning Point: Accurate diagnosis is essential for effective management and preventing complications. GOALS OF T2DM MANAGEMENT Glycemic Targets: Aim for HbA1c < 7% for most; adjust based on patient specifics (e.g., < 6.5% for younger, healthier patients; < 8% for those older or with comorbidities). Prevention of Complications: Address both microvascular (nephropathy, retinopathy, neuropathy) and macrovascular (cardiovascular disease) issues. Quality of Life & Patient-Centered Approach: Reduce hyperglycemia symptoms and hypoglycemia risks; tailor goals to age, diabetes duration, comorbidities, and life expectancy. LIFESTYLE MODIFICATIONS Dietary Management: Focus on a balanced diet with whole grains, vegetables, lean proteins, and healthy fats. Low-carbohydrate or Mediterranean diets are advantageous; consider glycemic index and load. Physical Activity: Improve insulin sensitivity and weight control through regular physical activity. Aim for 150 minutes per week of moderate aerobic activity plus twice- weekly resistance training. Weight Management: Modest weight loss (5-10%) enhances glycemic control. Bariatric surgery may be considered for severe obesity in T2DM patients. Learning Point: Emphasize lifestyle changes as crucial in managing T2DM. PHARMACOLOGICAL TREATMENT OVERVIEW First-line therapy is Metformin unless contraindicated (CKD/ESRF/ESRD). Second-line options are tailored to patients, including sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists, and insulin. Combination therapy is often required if monotherapy does not meet target HbA1c levels. Individualized Treatment Approach Treatment considers efficacy, side effects, patient preferences, cost, and comorbid conditions. METFORMIN: THE FIRST-LINE AGENT Reduces hepatic glucose production and improves insulin sensitivity. Dosage starts at 500 mg, up to 2000-2500 mg/day. Common side effects are gastrointestinal; rare risk of lactic acidosis (DKA), especially in renal impairment. Renal function monitoring is crucial, especially for older patients or those with CKD. Preferred for its efficacy, safety, and low cost. Learning Point: Metformin remains the gold standard due to its efficacy, safety profile, and low cost. SULFONYLUREAS AND GLINIDES Stimulate insulin secretion from pancreatic beta cells. Include drugs like glimepiride, gliclazide, and repaglinide (shorter action). Risks include hypoglycemia and weight gain; less preferred due to these risks. Therapeutic Use and Cautions Used as second-line agents. Caution in patients with high hypoglycemia risk; education on low blood sugar signs is crucial. Learning Point: Use cautiously in patients with high hypoglycemia risk and educate patients about signs of low blood sugar. DPP-4 INHIBITORS Mechanism of Action: Inhibit the enzyme DPP-4, leading to prolonged incretin action (GLP-1), which increases insulin secretion and decreases glucagon release. Common Drugs: Sitagliptin, saxagliptin, linagliptin. Advantages: Weight neutral, low risk of hypoglycemia. Adverse Effects: Rare reports of pancreatitis. Dosage adjustments may be needed in renal impairment. Learning Point: These are useful in patients who cannot tolerate metformin or who are at risk for hypoglycemia. GLP-1 RECEPTOR AGONISTS Mechanism of Action: Mimics the action of incretin hormones, increasing insulin secretion, reducing glucagon levels, and slowing gastric emptying. Drugs: Liraglutide, dulaglutide, semaglutide. Benefits: Significant weight loss, cardiovascular benefits (proven in trials). Adverse Effects: GI disturbances like nausea and vomiting, risk of thyroid tumors (in animal studies). Learning Point: These are especially beneficial in patients who need weight loss or have cardiovascular disease. SGLT2 INHIBITORS Mechanism of Action: Reduces renal glucose reabsorption, leading to glucosuria and lower blood glucose levels. Common Drugs: Empagliflozin, dapagliflozin, canagliflozin. Benefits: Cardiovascular and renal protection, weight loss. Adverse Effects: Genital mycotic infections, dehydration, risk of euglycemic diabetic ketoacidosis. Learning Point: SGLT2 inhibitors are highly beneficial for patients with cardiovascular or renal complications but require careful monitoring for adverse effects. INSULIN THERAPY IN T2DM Indications: Severe hyperglycemia (HbA1c > 10%), patients who fail to achieve control with oral agents (OHA), or during acute illness. Types of Insulin: Basal (long-acting) insulin like glargine, detemir, bolus (rapid-acting) insulin like aspart, lispro, and premixed insulins. Dosing and Titration: Start with a basal insulin at 10 units/day or 0.1-0.2 units/kg/day and titrate based on fasting glucose. Monitoring: Frequent SMBG (self-monitoring of blood glucose) and titration based on readings. Adverse Effects: Hypoglycemia, weight gain. Teaching Point: Educate patients about proper insulin injection techniques and hypoglycemia management. COMPLICATIONS OF T2DM Acute Complications: DKA (Diabetic Ketoacidosis): Rare in T2DM but possible in cases of severe insulin deficiency. HHS (Hyperosmolar Hyperglycemic State): Severe hyperglycemia without ketosis, leading to dehydration and altered mental status. Chronic Complications: Microvascular: Retinopathy (leading to blindness), nephropathy (leading to CKD), and neuropathy (leading to foot ulcers). Macrovascular: Coronary artery disease, stroke, peripheral vascular disease. Preventive Measures: Regular screening for complications (e.g., annual eye exams, renal function tests, foot care). Teaching Point: Managing blood glucose is crucial in preventing long-term complications. MONITORING AND FOLLOW-UP Key Points: SMBG: Frequency of monitoring depends on the treatment regimen. Those on insulin require more frequent checks than those on oral agents. HbA1c Testing: Every 3-6 months depending on glycemic control. Complications Monitoring: Regular foot checks, eye exams, and renal function assessments are necessary to prevent long-term damage. Learning Point: Regular follow-up is essential to adjust treatment and monitor for complications. CONCLUSION 1. Early Diagnosis is Key Emphasize the importance of early detection and diagnosis of T2DM, especially in at-risk populations (e.g., obese individuals, those with family history, or sedentary lifestyles). 2. Lifestyle Interventions are the Foundation Reinforce the role of lifestyle modifications (diet, exercise, and weight loss) as the cornerstone of T2DM management. 3. Personalized Treatment Plans Highlight that treatment of T2DM should be individualized based on patient- specific factors such as age, comorbidities, and risk of hypoglycemia. 4. Pharmacotherapy: Stepwise Approach Summarize the importance of starting with first-line therapy (e.g., metformin) and progressing to additional treatments (e.g., SGLT2 inhibitors, GLP-1 receptor agonists, insulin) as needed based on disease progression and patient response. 5. Managing Comorbidities is Critical Emphasize the need for comprehensive management of associated conditions like hypertension, dyslipidemia, and cardiovascular disease. 6. Regular Monitoring to Prevent Complications Stress the importance of ongoing monitoring (e.g., HbA1c, blood pressure, lipid levels, renal function) and regular follow-up to adjust therapy and detect early signs of complications. 7. Preventing Complications is a Priority Reiterate that preventive care (e.g., annual eye exams, foot checks, and renal function tests) is essential to avoid serious complications like retinopathy, nephropathy, and neuropathy. REFERENCES 1. American Diabetes Association (ADA) Standards of Medical Care in Diabetes – 2024. American Diabetes Association. Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Supplement 1) 2. European Association for the Study of Diabetes (EASD) and ADA Consensus Report – 2022. Davies MJ, Aroda VR, Collins BS, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. Diabetes Care. 2022;45(11):2753-2786. 3. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Edition. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Edition. New York, NY: McGraw-Hill Education; 2018. 4. Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs, 11th Edition. Alldredge BK, Corelli RL, Ernst ME, et al. Applied Therapeutics: The Clinical Use of Drugs, 11th Edition. Philadelphia, PA: Wolters Kluwer Health; 2020. 5. SGLT2 Inhibitors in the Treatment of T2DM: Cardiovascular and Renal Benefits. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine. 2015;373(22):2117-2128. 6. International Diabetes Federation (IDF) Diabetes Atlas, 10th Edition – 2021. International Diabetes Federation. IDF Diabetes Atlas, 10th Edition. Brussels, Belgium: International Diabetes Federation; 2021.