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Questions and Answers
What is the primary cause of high blood glucose levels in diabetes mellitus?
What is the primary cause of high blood glucose levels in diabetes mellitus?
Which type of diabetes is also known as juvenile diabetes?
Which type of diabetes is also known as juvenile diabetes?
What physiological process is impaired in Type 2 diabetes?
What physiological process is impaired in Type 2 diabetes?
Which hallmark symptom indicates excessive urination in diabetes mellitus?
Which hallmark symptom indicates excessive urination in diabetes mellitus?
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What percentage of individuals with diabetes are estimated to have Type 2 diabetes?
What percentage of individuals with diabetes are estimated to have Type 2 diabetes?
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Which factor contributes to gestational diabetes?
Which factor contributes to gestational diabetes?
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What was the historical term used for diabetes in the 17th century?
What was the historical term used for diabetes in the 17th century?
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What role does calcium play in normal insulin function?
What role does calcium play in normal insulin function?
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What is the primary cause of Type 2 Diabetes Mellitus?
What is the primary cause of Type 2 Diabetes Mellitus?
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What percentage of diabetes cases are attributable to Type 1 Diabetes Mellitus?
What percentage of diabetes cases are attributable to Type 1 Diabetes Mellitus?
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Which of the following is a significant risk factor for Gestational Diabetes?
Which of the following is a significant risk factor for Gestational Diabetes?
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In the Philippines, what is the projected number of individuals expected to have diabetes by 2045?
In the Philippines, what is the projected number of individuals expected to have diabetes by 2045?
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What is the leading cause of preventable blindness in Region 3 of the Philippines?
What is the leading cause of preventable blindness in Region 3 of the Philippines?
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What percentage of the U.S. population is diagnosed with diabetes, primarily Type 2?
What percentage of the U.S. population is diagnosed with diabetes, primarily Type 2?
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Which symptom is NOT commonly associated with diabetes?
Which symptom is NOT commonly associated with diabetes?
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What lifestyle factor is considered a risk for Type 2 Diabetes Mellitus?
What lifestyle factor is considered a risk for Type 2 Diabetes Mellitus?
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What characteristic differentiates Type 2 Diabetes Mellitus from Type 1 Diabetes?
What characteristic differentiates Type 2 Diabetes Mellitus from Type 1 Diabetes?
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What is the mechanism of action of insulin preparations?
What is the mechanism of action of insulin preparations?
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Which of the following is a concern when using beta-blockers in patients taking regular insulin?
Which of the following is a concern when using beta-blockers in patients taking regular insulin?
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Which rapid-acting insulin consists of a single substitution at position B28?
Which rapid-acting insulin consists of a single substitution at position B28?
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What is a common contraindication of using Technosphere (Afrezza)?
What is a common contraindication of using Technosphere (Afrezza)?
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What is the typical administration schedule for NPH insulin?
What is the typical administration schedule for NPH insulin?
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Which of the following insulin types does NOT have a peak effect?
Which of the following insulin types does NOT have a peak effect?
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What is a primary use of short-acting insulins like regular insulin?
What is a primary use of short-acting insulins like regular insulin?
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What is the primary mechanism of action for metformin in the treatment of Type 2 diabetes?
What is the primary mechanism of action for metformin in the treatment of Type 2 diabetes?
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Which of the following is a characteristic of insulin degludec?
Which of the following is a characteristic of insulin degludec?
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What is a common adverse effect of insulin therapy?
What is a common adverse effect of insulin therapy?
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What condition contraindicates the use of metformin?
What condition contraindicates the use of metformin?
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How does pioglitazone affect lipid levels?
How does pioglitazone affect lipid levels?
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What should be monitored in patients receiving insulin therapy to prevent complications?
What should be monitored in patients receiving insulin therapy to prevent complications?
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What is a potential adverse effect of thiazolidinediones?
What is a potential adverse effect of thiazolidinediones?
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How does insulin detemir differ from regular insulin?
How does insulin detemir differ from regular insulin?
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Study Notes
Diabetes Mellitus
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Diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia (high blood glucose levels) due to issues with insulin secretion, insulin action, or both.
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The word "diabetes" comes from the Greek word meaning "siphon" and "mellitus" comes from the Latin word meaning "honeyed" or "sweet."
Types of Diabetes Mellitus
- Type 1 Diabetes: Also known as juvenile diabetes or insulin-dependent diabetes. The body doesn't produce insulin due to the destruction of beta cells.
- Type 2 Diabetes: The most common type. Cells become resistant to insulin (insulin resistance). This leads to less glucose being taken up by cells, resulting in high blood sugar.
- Gestational Diabetes: Occurs during pregnancy, often due to chronic insulin resistance during gestation.
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, allowing calcium to enter 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 allowing glucose to enter the cell.
- Glucose is used for energy (glycolysis).
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), and GLUT4 doesn't move to the cell membrane properly. This leads to less glucose being taken up by cells, causing high blood sugar.
- Gestational Diabetes: May be due to chronic insulin resistance during gestation.
Hallmark Signs of Diabetes Mellitus
- Polyuria (frequent urination)
- Polydipsia (increased thirst)
- Polyphagia (excessive hunger)
Epidemiology
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Global:
- 537 million adults (aged 20-79) lived 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 of their condition.
- Over 90% of individuals with diabetes have type 2 diabetes.
- Diabetes is primarily caused by socio-economic, demographic, environmental, and genetic factors.
- 6.7 million deaths were attributed to diabetes in 2021 (1 every 5 seconds).
- $966 billion was 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).
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Philippines:
- Estimated 4.3 million Filipinos (20-79 y/o) were diagnosed with diabetes (1 out of 14 adults) in 2021.
- 2.8 million Filipinos are undiagnosed.
- It is the leading cause of preventable blindness in Region 3.
- Diabetes contributes to 38% of kidney disease cases in the country.
- It was the 5th leading cause of death in the Philippines in 2021, with 48,267 deaths recorded (21% increase from 2020).
- 6.8 million Filipinos are expected to have diabetes by 2045.
Type 1 Diabetes Mellitus
- Accounts for about 5-10% of all diabetes cases.
- Approximately 45% are diagnosed before age 10.
Type 2 Diabetes Mellitus
- Accounts for about 90-95% of all cases.
- More common in older adults but increasingly prevalent in younger people due to rising obesity rates.
- About 9% of the total US population is diagnosed.
- Increases up to 25% of the population aged 65 years and older.
Etiology of Type 1 Diabetes Mellitus
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Causes:
- Autoimmune destruction of beta cells.
- Genetic predisposition.
- Environmental triggers.
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Risk Factors:
- Family history.
- Genetics.
- Geography.
- Age.
Etiology of Type 2 Diabetes Mellitus
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Causes:
- Genetic predisposition.
- Environmental triggers.
- Insulin resistance.
- Lifestyle factors.
- Impaired insulin secretion.
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Risk Factors:
- Family history.
- Unhealthy lifestyle.
- Age.
- Ethnicity.
- History of gestational diabetes.
Etiology of Gestational Diabetes
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Causes:
- Hormonal changes during pregnancy.
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Risk Factors:
- Obesity.
- Family history of diabetes.
- Previous gestational diabetes.
- Age over 25.
- Ethnicity.
Signs and Symptoms
- Increased thirst (polydipsia) and dry mouth.
- Frequent urination (polyuria).
- Excessive hunger (polyphagia).
- Fatigue.
- Blurred vision.
- Unexplained weight loss.
- Numbness or tingling in hands or feet.
- Slow-healing sores or cuts.
- Frequent skin and/or vaginal yeast infections.
Signs and Symptoms of Type 1 Diabetes
- Individuals tend to be thin and may develop diabetic ketoacidosis (DKA) which is life-threatening.
- DKA requires immediate medical treatment.
- Symptoms of DKA include vomiting, stomach pains, fruity-smelling breath, and labored breathing.
Signs and Symptoms of Type 2 Diabetes
- Individuals may be asymptomatic and overweight or obese.
- Acanthosis nigricans (darkening and thickening of skin in folds) may be present
Treatment Interventions
- Pharmacological
Insulin Preparations
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Mechanism of action:
- 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.
Short Acting Insulins
- Regular insulin (Humulin R, Novolin R):
- Drug interactions:
- Corticosteroids (e.g. prednisone): May induce hyperglycemia.
- Beta-blockers (e.g. propranolol): Can mask the adrenergic symptoms of hypoglycemia.
- Other antihyperglycemic agents (e.g. insulin with sulfonylureas): Potentiate the risk of hypoglycemia.
- Available formulations: Injectable solution, intravenous (IV) administration, inhaled powder.
- Drug interactions:
Rapid Acting Insulins
- Insulin lispro (Humalog, Admelog): Single substitution of aspartic acid at position B28.
- Insulin Aspart (NovoLog): Proline at position B28 is replaced with aspartic acid.
- Insulin Glulisine (Apidra): Asparagine at position B3 is replaced with lysine, and lysine at position B29 is replaced with glutamic acid.
- Technosphere (Afrezza): Dry powder that is inhaled using a special inhaler. Taken 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).
- Contraindications (C/I): Chronic lung disease (Asthma, COPD), Smoking, Acute lung problems (Bronchitis, Pneumonia), Hypersensitivity.
Intermediate Acting Insulins
- 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.
- Contraindications: Hypoglycemia, Hypersensitivity.
Long Acting Insulin
- Insulin glargine (Lantus):
- Peakless insulin.
- Administration: Once daily.
- Contraindications: Hyperglycemia, Hypersensitivity.
- Insulin detemir (Levemir):
- Longest acting insulin.
- Administration: Once or twice daily.
- Contraindications: Hypoglycemia, Hypersensitivity.
- Insulin degludec (Tresiba):
- Flat, peakless insulin.
- Lower affinity than human soluble insulin.
- Administration: Once daily.
- Contraindications: Hyperglycemia, Hypersensitivity.
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 may experience allergic reactions.
Insulin Sensitizers
Biguanides
- Mechanism of action: Reduce hepatic gluconeogenesis, leading to lowered glucose levels.
- Metformin (Glucophage®):
- Drug of choice, first-line of therapy for Type 2 diabetes.
- Euglycemic agent; does not cause hypoglycemia.
- Does not cause weight gain.
- Elimination: Renal tubular secretion.
- Contraindications: Patients with renal insufficiency (estimated GFR of less than 30 mL/min).
- 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.
Thiazolidinediones ("-glitazones")
- Mechanism of action: Activates PPAR-y (peroxisome proliferator-activated receptor y), which is involved in insulin signal transduction, lipid and glucose metabolism, adipocyte and other tissue differentiation.
- Increased expression of GLUT 1 and GLUT 4.
- Adverse reactions (ADR): Fluid retention.
- Contraindications: ALT 2.5 times greater than normal, risk of liver failure.
- Pioglitazone (Actos®): Can decrease triglyceride levels and increase HDL, no effect on total cholesterol.
- Rosiglitazone (Avandia®): Can increase total cholesterol (HDL, LDL), no effect on triglycerides.
Insulin Secretagogues
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Sulfonylureas (e.g., glipizide, glyburide):
- Mechanism of action: Stimulate insulin release from beta cells.
- Adverse reactions (ADR): Hypoglycemia, weight gain.
- Contraindications: Individuals with diabetic ketoacidosis, hypersensitivity to sulfonylureas, severe hepatic or renal insufficiency.
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Meglitinides (e.g., repaglinide, nateglinide):
- Mechanism of action: Stimulate insulin release from pancreatic beta cells in a glucose-dependent manner.
- Adverse reactions (ADR): Hypoglycemia, weight gain.
- Contraindications: Individuals with diabetic ketoacidosis, severe hepatic or renal insufficiency.
Alpha-Glucosidase Inhibitors
- Acarbose (Precose), miglitol (Glyset):
- Mechanism of action: Delays the digestion and absorption of carbohydrates in the small intestine.
- Adverse reactions (ADR): Gastrointestinal side effects (diarrhea, abdominal pain, flatulence).
- Contraindications: Individuals with inflammatory bowel disease, severe hepatic or renal insufficiency.
GLP-1 Receptor Agonists
- Exenatide (Byetta), liraglutide (Victoza), semaglutide (Ozempic):
- Mechanism of action: Stimulate the release of insulin and inhibit glucagon secretion.
- Adverse reactions (ADR): Gastrointestinal side effects (nausea, vomiting), pancreatitis.
- Contraindications: Individuals with diabetic ketoacidosis, severe gastroparesis.
DPP-4 Inhibitors
- Sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina):
- Mechanism of action: Inhibit dipeptidyl peptidase-4 (DPP-4) enzyme, which degrades incretin hormones. This prolongs the action of incretin hormones, which stimulate insulin release and suppress glucagon secretion.
- Adverse reactions (ADR): Hypoglycemia, allergic reactions.
- Contraindications: Hypersensitivity to the drug, diabetic ketoacidosis.
Sodium Glucose Co-transporter 2 (SGLT2) Inhibitors
- Canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance):
- Mechanism of action: Block the reabsorption of glucose in the kidneys, resulting in increased urinary glucose excretion.
- Adverse reactions (ADR): Hypoglycemia, urinary tract infections, genital mycotic infections.
- Contraindications: Severe renal impairment, diabetic ketoacidosis.
Lifestyle Modification
- Regular physical activity.
- Weight loss if needed.
- Balanced diet.
- Stress management.
Complications of Diabetes
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Acute:
- Diabetic ketoacidosis (DKA).
- Hyperosmolar hyperglycemic state (HHS).
- Hypoglycemia.
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Chronic:
- Retinopathy (damage to the blood vessels in the retina).
- Nephropathy (damage to the blood vessels in the kidneys).
- Neuropathy (damage to the nerves).
- Cardiovascular disease.
- Foot ulcers and amputations.
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Description
Explore the fundamentals of diabetes mellitus, a chronic metabolic disease characterized by high blood glucose levels. This quiz covers the different types of diabetes, including Type 1, Type 2, and gestational diabetes, along with the normal function of insulin in the body.