Diabetes Mellitus Overview

Diabetes Mellitus

• Type 1 diabetes involves autoimmune destruction of beta cells
• Type 2 diabetes involves both insulin resistance and beta-cell dysfunction
• Diagnostic criteria include:
  • Fasting glucose ≥126 mg/dL
  • A1c ≥6.5%
  • Random glucose ≥200 mg/dL with symptoms
• Glycemic goals (ADA) include:
  • A1c <7% for most outpatients
  • Maintaining glucose between 140-180 mg/dL for inpatients
  • Different targets are set for children, pregnant individuals, and older adults
• Glucose monitoring methods include fingerstick self-monitoring and continuous glucose monitoring
• Type 1 diabetes requires insulin therapy
• Type 2 diabetes involves using oral and injectable medications (non-insulin)
• Bolus insulins include rapid-acting (Lispro/Humalog) and short-acting (Regular/Humulin R)
• Basal insulins include intermediate (NPH/Humulin N) and long-acting (Glargine/Lantus)
• Pre-mixed insulins: Humalog Mix 75/25, Humulin 70/30
• Non-insulin medications include:
  • Biguanides (Metformin): Decreases hepatic glucose production
  • Sulfonylureas: Increases insulin secretion (risk of hypoglycemia)
  • Meglitinides: Short-acting insulin secretagogues
  • Thiazolidinediones (TZDs): Improves insulin sensitivity
  • Alpha-glucosidase inhibitors: Delays carbohydrate absorption
  • Amylin mimetics: Slows gastric emptying, reduces glucagon secretion
  • GLP-1 agonists: Enhances insulin secretion, slows gastric emptying
  • DPP-4 inhibitors: Inhibits GLP-1 breakdown
  • SGLT2 inhibitors: Promotes urinary glucose excretion
• Hypoglycemia Symptoms: Sweating, tremors, confusion, palpitations, dizziness
• Hypoglycemia Treatment: Rule of 15 (15g glucose, recheck in 15 min)
• Patient education and self-management encompasses self-monitoring, medication adherence, and lifestyle modifications
• Core components of quality diabetes care include self-management education and support (DSMES) which is provided by certified specialists (CDCESs)
• Medical nutrition therapy (MNT) involves with individualized plans developed by registered dietitians
• Physical activity improves insulin sensitivity and glucose tolerance, promoting weight loss
• Type 1 diabetes drug therapy includes multiple daily injections or an insulin pump
• Type 2 diabetes drug therapy involves oral medications, non-insulin injectables, and insulin if needed
• Insulin delivery methods include subcutaneous injections and insulin pump therapy
• Final notes to remember are regular follow-ups, monitoring complications, and individualized treatment plans

Adrenal and Thyroid Gland

• Cortisol: "Stress hormone," 1:1 glucocorticoid:mineralocorticoid effect
  • Peaks in the morning, declines throughout the day
  • Mineralocorticoid role maintains BP, increasing vessel sensitivity to catecholamines
  • Glucocorticoid role increases gluconeogenesis, proteolysis, and lipolysis, dampens immune response
• Endogenous vs. exogenous corticosteroids include:
  • Hydrocortisone which is equivalent to cortisol
  • Cortisone & Prednisone are inactive prodrugs converted in the liver
  • Prednisolone is an active form of corticosteroids that is preferred in liver disease
• Metabolic effects of supraphysiological doses include hyperglycemia, osteoporosis, and weigh gain
• Immune suppression is an effect of supraphysiological doses that increases infection risk
• Cushing syndrome causes include pituitary tumors, adrenal tumors, ectopic ACTH secretion, and chronic steroid use
• Cushing syndrome first line of treatment is surgery or chemotherapy
• Cushing syndrome pharmacotherapy includes Ketoconazole, Mitotane, Pasireotide, and Mifepristone
• Adrenal insufficiency:
  • Primary (Addison's disease) involves damage to adrenal glands, leading to glucocorticoid and mineralocorticoid deficiency
  • Secondary involves low ACTH, leading reduced cortisol, normal aldosterone
• Treatment for adrenal insufficiency:
  • Primary: Glucocorticoid + mineralocorticoid replacement
  • Secondary: Glucocorticoid replacement only
• Glucocorticoid replacement considerations include:
  • Hydrocortisone dose increases during stress, fever, and injury
  • Major illness/trauma may require 10x the usual dose
  • Fludrocortisone mineralocorticoid is used in Addison's disease
• TRH (Thyrotropin-releasing hormone) causes the releases of TSH (Thyroid-stimulating hormone) to lead to T4 & T3 production
• T4 (Thyroxine) is a prohormone and is converted to T3 in tissues
• T3 (Triiodothyronine) is an active form, and has a rapid onset with a shorter duration than T4
• Hyperthyroidism causes include Graves’ disease and pituitary tumors
• Hyperthyroidism definitive treatments include radioactive iodine therapy, and thyroidectomy
• Hyperthyroidism medical management includes:
  • Methimazole (MMI) which is a first-line medication given once daily
  • Propylthiouracil (PTU) a second-line medication given during the first trimester of pregnancy, inhibits peripheral T4 → T3 conversion
  • Beta-blockers (Propranolol, Atenolol) aid in the control of symptoms like palpitations, tremors, anxiety
• Hypothyroidism causes include autoimmune thyroiditis (Hashimoto's) and iodine deficiency
• Treatment for hypothyroidism is Levothyroxine (T4 replacement) with dosing administered once daily and requires monitoring of of TSH/T4 levels every 6 weeks after a dose change
• Cushing Syndrome: Excess cortisol → treated with surgery or pharmacotherapy
• Addison's Disease: Cortisol & aldosterone deficiency → Hormone replacement.
• Hyperthyroidism: Excess T3/T4 → Methimazole, PTU, beta-blockers.
• Hypothyroidism: T4 deficiency → Levothyroxine replacement therapy

Respiratory and Allergy

• Viral rhinitis & sinusitis is a self-limiting condition that be managed symptomatically
• Allergic rhinitis is IgE-mediated, histamine release which triggers symptoms
• Pharmacologic treatments include:
  • Analgesics: Acetaminophen (max 4000mg/day) or Ibuprofen (max 1200mg/day)
  • Antihistamines:
    • First-generation: Diphenhydramine (Benadryl), Promethazine (sedating)
    • Second-generation: Cetirizine (Zyrtec), Loratadine (Claritin) (less sedating)
    • Nasal: Azelastine (Astepro), Olopatadine (Patanase)
  • Intranasal Corticosteroids: Fluticasone (Flonase), Budesonide (Rhinocort)
  • Decongestants:
    • Oral: Pseudoephedrine (Sudafed), Phenylephrine (Sudafed PE)
    • Nasal Spray: Oxymetazoline (Afrin) (limit to 3 days)
  • Antitussives:
    • Dextromethorphan (Delsym): Depresses medullary cough center.
    • Benzonatate (Tessalon Perles): Peripheral anesthetic effect.
    • Opioids (Codeine, Hydrocodone): Reserved for severe cases.
  • Expectorants: Guaifenesin (Mucinex) (must hydrate)
  • Mucolytics: Acetylcysteine, for acetaminophen overdose
• Herbal Supplements:
  • Vitamin C may reduce severity if taken consistently
  • Zinc is effective if started within 24 hours of symptom onset
• Asthma is chronic and a reversible airway inflammation
• Asthma triggers: Allergens, infections, exercise, air pollutants
• Asthma symptoms: Cough, wheezing, dyspnea, chest tightness
• Asthma pathophysiology: Bronchoconstriction, mucus hypersecretion, inflammation
• Asthma Pharmacologic Treatment:
  • Rescue (Reliever): SABA (Albuterol) PRN
  • Mild (Step 1-2): PRN ICS/Formoterol or daily ICS
  • Moderate (Step 3): Low-dose ICS + LAВА
  • Severe (Step 4-5): Medium/High-dose ICS/LABA + Biologics
  • Adjuncts: Montelukast (Singulair) (Leukotriene receptor antagonist), Mast Cell Stabilizers, Monoclonal Antibodies (Omalizumab, Mepolizumab)
• COPD is a chronic, and an irreversible airflow limitation
• COPD causes: Smoking, occupational exposure
• COPD symptoms: Chronic cough, sputum production, dyspnea
• COPD Pharmacologic Treatment:
  • First-line: Long-acting bronchodilators (LABA, LAMA)
  • Severe: Triple therapy (ICS/LABA/LAMA for high-risk patients)
  • Exacerbations: Short-term steroids (Prednisone 5-7 days), SABAs, antibiotics if indicated
  • Adjuncts: PDE-4 inhibitors (Roflumilast for severe cases)
• Bronchodilators:
  • Beta-2 Agonists (SABA/LABA): Albuterol (SABA), Salmeterol (LABA)
  • Anticholinergics (SAMA/LAMA): Ipratropium (SAMA), Tiotropium (LAMA)
  • Methylxanthines: Theophylline (limited use)
• Smoking Cessation 5 A's Approach:
  1. Ask about tobacco use
  2. Advise to quit
  3. Assess readiness
  4. Assist with resources
  5. Arrange follow-up
• Smoking Cessation Pharmacologic Treatments:
  • Nicotine Replacement Therapy (NRT): Patches, gum, lozenges, inhalers
  • Varenicline (Chantix): Partial nicotine receptor agonist, reduces cravings
  • Bupropion (Zyban): Antidepressant, reduces withdrawal symptoms
• Patient Education & Monitoring includes use of proper inhaler technique and follow ups

Liver and Kidney

• Liver disease transplant patients common causes: Alcohol-related liver disease, Metabolic-associated steatohepatitis (MASH)
• Liver functions: Metabolism, detoxification, protein synthesis, bile production
• Hepatic encephalopathy (HE) is a cirrhosis complication with ammonia accumulation which alters neurotransmission
• Hepatic encephalopathy treatment includes:
  • Lactulose which enhances ammonia elimination
  • Rifaximin which reduces ammonia production by targeting urease-producing bacteria
• Varices and variceal bleeding:
  • Primary prevention is using non-selective beta-blockers to reduce portal pressure
  • Acute variceal bleed is treated with octreotide infusion or endoscopic therapy
• Ascites:
  • Antibiotics (Ceftriaxone) prevent peritonitis
  • Management includes, fluid and sodium restriction, diuretics
  • Refractory cases involves large-volume paracentesis with albumin replacement
• Spontaneous bacterial peritonitis (SBP) is treated with antibiotics, albumin infusion, and fluoroquinolones for prevention
• Hepatorenal syndrome (HRS) pathogenesis is when peripheral vasodilation reduces renal perfusion
• Hepatorenal syndrome (HRS) treatment:
  • Discontinue diuretics & nephrotoxic drugs
  • Midodrine + Octreotide, Norepinephrine + Octreotide, Terlipressin
  • Albumin to improve perfusion
• Coagulopathy in liver disease causes decreased platelet production and clotting factor synthesis
• Coagulopathy treatment includes use of Thrombopoietin Receptor Agonists (Avatrombopag , Eltrombopag)
• Medication considerations: Impaired drug metabolism and increased volume of distribution & altered protein binding
• Definitive treatment: Liver transplantation
• Chronic kidney disease prevalence is over 697 million affected worldwide
• Chronic kidney disease (CKD) causes include diabetic kidney disease, hypertension, nephrotoxic medications
• Chronic kidney disease (CKD) complications lead to an increased mortality risk, and dialysis dependence
• Kidney functions:
  • Excretory: Removes waste, regulates electrolytes
  • Endocrine: Produces erythropoietin, activates vitamin D
  • Metabolic: Gluconeogenesis, insulin degradation
• Kidney Disease Assessment markers of function: Serum creatinine, Cystatin C, eGFR
• Kidney disease can be assessed with urinalysis by measuring albuminuria an proteinuria
• Kidney disease symptoms in the late-stage are fatigue, nausea, edema, shortness of breath, confusion
• Slowing progression of CKD can be aided by:
  • ACE Inhibitors & ARBs
  • SGLT-2 Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Non-DHP CCBs
• Anemia of kidney disease pathogenesis involves decreased erythropoietin production and increased RBC destruction with a target hemoglobin less than 11 g/dL
• Anemia treatment include supplementing iron and injecting erythropoiesis-stimulating agents and HIF Prolyl Hydroxylase Inhibitors
• Goal for Mineral & Bone Disorder in CKD: Prevent bone disease and cardiovascular complications by administering Phosphate Binders and Vitamin D
• Hyperkalemia management consists of decreasing risk factors by monitoring kidney and dietary risks
• Hyperkalemia treatment includes emergency drugs, and potassim binders

Gastrointestinal

• Diarrhea causes changes in active ion transport, motility, osmolarity, hydrostatic pressure
• Diarrhea Non-Pharmacologic Treatment: Oral Rehydration Solutions
• Diarrhea Pharmacologic Treatment: Opiate derivatives or Bismuth Subsalicylate
• Constipation causes include low fiber intake, hypothyroidism, medication side effects
• Constipation Non-Pharmacologic Treatment: Increased fluid intake, dietary fiber, exercise, bowel routine
• Constipation Pharmacologic Treatment: Bulk-forming, Osmotic, Stimulants
• Irritable Bowel Syndrome (IBS) Diagnosis: Rome IV criteria with recurrent pain and changes in stool
• IBS Treatment: Constipation-Predominant with osmotic laxatives and linaclotide, Diarrhea-Predominant with loperamide, rifaximin, eluxadoline, serotonin-3 antagonists
• Nausea & Vomiting Causes: Mechanical obstruction, pancreatitis, gastroparesis, pregnancy, chemotherapy
• Pathophysiology: Vomiting Center (VC) receives signals from the chemoreceptor trigger zone or the GI tract
• Treatment: Antiemetics and/or Non-Pharmacologic Treatment
• Gastroesophageal Reflux Disease (GERD) Symptoms: Heartburn, regurgitation, dysphagia, hypersalivation
• GERD Risk Factors: Obesity, smoking, alcohol, medications, pregnancy
• GERD Non-Pharmacologic Treatment: Weight loss, dietary changes, smoking cessation
• GERD Pharmacologic Treatment: Proton Pump Inhibitors, H2-Receptor Antagonists, Antacids, Cytoprotective Agents
• Peptic Ulcer Disease (PUD) Causes: Helicobacter pylori infection, NSAID use, stress, smoking, alcohol
• Peptic Ulcer Disease (PUD) Symptoms: Epigastric pain
• Peptic Ulcer Disease (PUD) is diagnosed with Endoscopy, H. pylori testing
• Peptic Ulcer Disease (PUD) Treatment:
  • Acid Reduction by using PPI therapy
  • H. pylori Eradication: Triple or Quadruple Therapy
• Stress-Related Mucosal Damage (SRMD) Risk Factors: Critical illness, burns, shock, mechanical ventilation
• Stress-Related Mucosal Damage (SRMD) can be Prevented by providing treatment with PPIs, H2RAs