Diabetes Mellitus - Exercise 6 PDF

Exercise 6: DIABETES MELLITUS GROUP 1 AGENDA Discuss Diabetes Discuss the given case Answer guide questions PART 1: DISCUSSION OF THE DISEASE INTRODUCTION According to the World Health Organization (WHO), diabetes mellitus is a chronic metabolic disease marked by persistent hyperg...

Exercise 6: DIABETES MELLITUS GROUP 1 AGENDA Discuss Diabetes Discuss the given case Answer guide questions PART 1: DISCUSSION OF THE DISEASE INTRODUCTION According to the World Health Organization (WHO), diabetes mellitus is a chronic metabolic disease marked by persistent hyperglycemia (high blood glucose levels) due to issues with insulin secretion, insulin action, or both. INTRODUCTION Greek word "diabetes," meaning "siphon" (to pass through), and the Latin word "mellitus," meaning "honeyed" or "sweet." In the 17th century, diabetes was referred to as the "pissing evil" due to its symptoms. INTRODUCTION Types of Diabetes Mellitus Type 1 diabetes - a.k.a. juvenile diabetes or insulin-dependent diabetes Type 2 diabetes - most common Gestational diabetes - occurs during pregnancy PHYSIOLOGY PHYSIOLOGY PHYSIOLOGY PATHOPHYSIOLOGY NORMAL INSULIN FUNCTION: Glucose enters beta cells through GLUT2 transporters. Glucose is metabolized to produce ATP (energy). Increased ATP closes potassium channels, causing cell depolarization. Depolarization opens calcium channels, and calcium enters the cell. Calcium triggers the release of insulin from beta cells into the bloodstream. Insulin binds to receptors on cells (like muscle or fat cells). This activates pathways that move GLUT4 transporters to the cell membrane. GLUT4 allows glucose to enter the cell and be used for energy (glycolysis). PATH OPH YSIO LOGY PATHOPHYSIOLOGY IN DIABETES Type 1: The body doesn’t produce insulin (due to destruction of beta cells) Type 2: Cells become resistant to insulin (insulin resistance) Even though insulin is present, GLUT4 doesn’t move tp the cell membrane properly. This leads to less glucose being taken up by cells, causing high blood sugar. Gestational Diabetes Idiopathic. May be due to chronic insulin resistance during gestation. PATHOPHYSIOLOGY HALLMARKS SIGNS OF DIABETES MELLITUS Polyuria Polydipsia Polyphagia EPIDEMIOLOGY Global: 537 million adults (aged 20-79) were living with diabetes in 2021. 1 in 10 people have diabetes ( 10.5% of the world's population.) Almost 50% of individuals with diabetes are unaware they have the condition. Over 90% of individuals with diabetes have type 2 diabetes. Mainly caused by socio-economic, demographic, environmental, and genetic factors. 6.7 million deaths attributed to diabetes in 2021. ( 1 every 5 seconds ) $966 billion spent on diabetes care in 2021 783 million adults are expected to have diabetes by 2045. (1 in 8 adults = 46% increase compared to 2021)  Top 10 COUNTRIES WITH HIGHEST RATE OF DIABETES (IDF 2021) EPIDEMIOLOGY Philippines: Estimated 4.3 million Filipinos (ranging 20-79 y/o) were diagnosed with diabetes (1 out of 14 adults) 2.8 million are undiagnosed as of 2021 Leading cause of preventable blindness in Region 3 Contributes to 38% of kidney disease cases in the country 5th leading cause of death in the Philippines in 2021, with 48,267 deaths recorded (21% increase from 2020) 6.8 million expected to have diabetes by 2045 DIABETES REPORT OF THE PHILIPPINES (2000-2045) IN 1000S EPIDEMIOLOGY Type 1 Diabetes Mellitus: About 5-10% of all diabetes cases. Approximately 45% diagnosed before age 10 (Gradually increases from birth.) Type 2 Diabetes Mellitus: Accounting for about 90-95% of all cases. More common in older adults, but increasingly prevalent in younger people, largely due to rising obesity rates. About 9% of the total population in US are diagnosed Increases up to 25% of population (65 y/o and older) ETIOLOGY Type 1 Diabetes Mellitus: Causes: Autoimmune Destruction Genetic Predisposition Environmental Triggers Risk Factors: Family history Genetics Geography Age ETIOLOGY Type 2 Diabetes Mellitus: Causes: Genetic Predisposition Environmental Triggers Insulin Resistance Lifestyle Factors Impaired Insulin Secretion Risk Factors: Family history Unhealthy Lifestyle Age Ethnicity History of gestational diabetes ETIOLOGY Gestational Diabetes: Causes: Hormonal changes during pregnancy Risk Factors: Obesity Family history of diabetes Previous gestational diabetes Age over 25 Ethnicity SIGNS & Sx Increased thirst (polydipsia) and dry mouth Frequent urination (polyuria) Excessive hunger (polyphagia) Fatigue Blurred vision Unexplained weight loss Numbness or tingling in your hands or feet Slow-healing sores or cuts Frequent skin and/or vaginal yeast infections SIGNS & Sx Type 1 Diabetes Mellitus: Thin and may develop diabetic ketoacidosis. DKA is life-threatening and requires immediate medical treatment. Sx. include vomiting, stomach pains, fruity-smelling breath and labored breathing. Type 2 Diabetes Mellitus: Asymptomatic and overweight or obese. Acanthosis nigricans LABORATORY AND DIAGNOSTIC TEST  TREATMENT INTERVENTIONS PHARMACOLOGICAL INSULIN PREPARATIONS MOA: Mimics the body’s natural insulin response to meals Rapidly binds to insulin receptors on muscle and fat cells Promotes glucose uptake by facilitating GLUT4 translocation to the cell membrane Enhances glycogen synthesis in the liver Inhibits hepatic glucose production INSULIN PREPARATIONS SHORT ACTING INSULINS A. Regular insulin (Humulin R, Novolin R) Drug Interactions: Corticosteroids (eg. prednisone): May induce hyperglycemia. Beta-blockers (e.g. propranolol): Can mask the adrenergic symptoms of hypoglycemia. Other Antihyperglycemic Agents (eg. insulin with sulfonylureas): potentiate the risk of hypoglycemia. Available Formulations: Injectable Solution, Intravenous (IV) Administration, Inhaled Powder INSULIN PREPARATIONS RAPID ACTING INSULINS A. Insulin lispro (Humalog, Admelog) single substitution of asparticacid at position B28 B. Insulin Aspart (NovoLog) Proline at position B28 is replaced with aspartic acid C. Insulin Glulisine (Apidra) Asparagine at position B3 is replaced with lysine, and lysine at position B29 is replaced with glutamic acid INSULIN PREPARATIONS RAPID ACTING INSULINS D. Technosphere (Afrezza) dry powder that is inhaled iusing a special inhaler. taken at the before meals or within 20 minutes after meals. PRECAUTIONS It's NOT a substitute for long-acting insulin. People with type 1 diabetes must still use long-acting insulin. It's NOT used to treat diabetic ketoacidosis (DKA). C/I: Chronic lung disease (Asthma, COPD), Smoking, Acute lung problem (Bronchitis, Pneumonia), Hypersensitivity INSULIN PREPARATIONS INTERMEDIATE ACTING INSULINS A. NPH (Neutral Protamine Hagedorn or Isophane) Complex insulin and protamine Frequently used with a rapid-acting or short-acting insulin given 2-4x a day for INSULIN REPLACEMENT Helps control blood sugar levels between meals and overnight. C/I: Hypoglycemia, Hypersensitivity INSULIN PREPARATIONS LONG ACTING INSULIN A. Insulin glargine (Lantus) Peakless Insulin Administration: Once daily C/I: Hyperglycemia, Hypersensitivity B. Insulin detemir (Levemir) Longest acting insulin Administration: Once or twice daily C/I: Hypoglycemia, Hypersensitivity INSULIN PREPARATIONS LONG ACTING INSULIN C. Insulin degludec (Tresiba) Flat, peakless Insulin Lower affinity than human soluble insulin Administration: Once daily C/I: Hyperglycemia, Hypersensitivity INSULIN PREPARATIONS ADVERSE EFFECTS OF INSULIN Hypoglycemia (Low Blood Sugar) Treatment: Glucose (15-20 grams), Dextrose IV, Glucagon IM (1 gram) Weight Gain Lipodystrophy Treatment: Rotate injection sites consistently. Hypokalemia Treatment: Monitor potassium levels. Potassium supplements as needed Allergic Reactions (some patients) INSULIN SENSITIZERS Biguanides MOA: Reduce hepatic gluconeogenesis -> lowered glucose levels A. Metformin (Glucophage®) Drug of choice, first-line of therapy for Type 2 diabetes Euglycemic agent; does not cause hypoglycemia Dose not cause weight gain Elimination: Renal tubular secretion C/l: patients with renal insufficiency (estimated GFR of lowered glucose levels A. Metformin (Glucophage®) Drug interactions: Cimetidine: competes with renal tubular secretion of metformin Vitamin B12-intrinsic factor - metformin interferes with its Ca-dependent absorption --> Vitamin B12 deficiency (Anemia) Increased Ca intake may prevent Vitamin B12 malabsorption INSULIN SENSITIZERS Thiazolidinediones ("-glitazone")| MOA: Activates PPAR-y (peroxisome proliferator-activated receptor y) PPAR-y is involved in insulin signal transduction, lipid and glucose metabolism, adipocyte and other tissue differentiation. Increased expression of GLUT 1 and GLUT 4 ADR: Fluid retention C/I: ALT 2.5 times greater than normal - risk of liver failure 1. Pioglitazone (Actos®) - can decrease triglyceride levels and increase HDL, no effect on total cholesterol 2. Rosiglitazone (Avandia®) - can increase total cholesterol (HDL, LDL), no effect on triglycerides INSULIN SECRETAGOGUES Sulfonylureas (