Diabetes Mellitus (USMLE Step

Cheatsheet Content

### Definition Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. ### Types - **Type 1 Diabetes (T1DM):** - Autoimmune destruction of pancreatic $\beta$-cells, leading to absolute insulin deficiency. - Typically presents in childhood or adolescence. - Requires exogenous insulin for survival. - **Type 2 Diabetes (T2DM):** - Progressive loss of $\beta$-cell insulin secretion often on the background of insulin resistance. - Strong genetic predisposition and associated with obesity, sedentary lifestyle. - Usually adult-onset, but increasing in children. - **Gestational Diabetes Mellitus (GDM):** - Diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. - Often resolves after delivery but increases risk for T2DM later in life for mother and child. - **Other Specific Types of Diabetes:** - Monogenic diabetes (e.g., MODY - Maturity-Onset Diabetes of the Young). - Diseases of the exocrine pancreas (e.g., pancreatitis, cystic fibrosis). - Drug- or chemical-induced diabetes (e.g., glucocorticoids, HIV/AIDS treatment). ### Pathophysiology #### Type 1 Diabetes - **Autoimmune Destruction:** T-cell mediated destruction of pancreatic $\beta$-cells. - **Genetic Predisposition:** Associated with HLA-DR3/DR4. - **Insulin Deficiency:** Leads to hyperglycemia, osmotic diuresis, dehydration, and ketoacidosis (due to increased lipolysis and hepatic ketogenesis). #### Type 2 Diabetes - **Insulin Resistance:** Target tissues (muscle, liver, adipose) fail to respond adequately to insulin. - **$\beta$-cell Dysfunction:** Pancreas initially compensates by increasing insulin secretion (hyperinsulinemia), but eventually $\beta$-cells fail, leading to relative insulin deficiency. - **Glucagon Excess:** Increased hepatic glucose production. - **Adipokines:** Adipose tissue secretes hormones (e.g., leptin, adiponectin, resistin) that influence insulin sensitivity. ### Symptoms (Often "3 Ps") - **Polyuria:** Frequent urination (due to osmotic diuresis). - **Polydipsia:** Increased thirst (due to dehydration). - **Polyphagia:** Increased hunger (especially in T1DM, due to inability to utilize glucose). - **Weight loss:** (Especially T1DM, due to catabolism of fat and protein). - Fatigue, blurry vision, numbness/tingling in extremities, slow-healing sores, recurrent infections. ### Diagnosis - **Fasting Plasma Glucose (FPG):** $\ge 126 \text{ mg/dL}$ (no caloric intake for at least 8 hours). - **2-hour Plasma Glucose (OGTT):** $\ge 200 \text{ mg/dL}$ during an Oral Glucose Tolerance Test (75g glucose load). - **HbA1c:** $\ge 6.5\%$ (reflects average blood glucose over 2-3 months). - **Random Plasma Glucose:** $\ge 200 \text{ mg/dL}$ in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis. - **Prediabetes:** FPG $100-125 \text{ mg/dL}$, 2-hour PG $140-199 \text{ mg/dL}$, or HbA1c $5.7\%-6.4\%$. ### Clinical Treatment #### Type 1 Diabetes - **Insulin Therapy:** Basal-bolus regimens, insulin pumps. - **Diet and Exercise:** Important for glucose management. #### Type 2 Diabetes - **Lifestyle Modifications:** Diet, exercise, weight loss are foundational. - **Pharmacotherapy:** - **Metformin:** First-line. Decreases hepatic glucose production, increases insulin sensitivity. - **Sulfonylureas (e.g., Glipizide, Glyburide):** Stimulate insulin secretion from $\beta$-cells. - **GLP-1 Receptor Agonists (e.g., Liraglutide, Semaglutide):** Increase glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying. - **SGLT2 Inhibitors (e.g., Canagliflozin, Empagliflozin):** Block glucose reabsorption in kidneys, increasing glucose excretion. - **DPP-4 Inhibitors (e.g., Sitagliptin, Saxagliptin):** Inhibit breakdown of GLP-1, increasing insulin secretion. - **Thiazolidinediones (TZDs) (e.g., Pioglitazone, Rosiglitazone):** Increase insulin sensitivity in peripheral tissues. - **Insulin Therapy:** May be required as disease progresses. ### Side Effects / Complications - **Acute Complications:** - **Diabetic Ketoacidosis (DKA):** (Primarily T1DM) Hyperglycemia, ketonemia, acidosis. Caused by severe insulin deficiency. - **Hyperosmolar Hyperglycemic State (HHS):** (Primarily T2DM) Severe hyperglycemia, hyperosmolarity, dehydration, absence of significant ketosis. - **Hypoglycemia:** Too much insulin or oral hypoglycemic agents, inadequate food intake, excessive exercise. - **Chronic Microvascular Complications:** - **Retinopathy:** Leading cause of blindness in adults. - **Nephropathy:** Leading cause of end-stage renal disease. - **Neuropathy:** Peripheral (stocking-glove sensory loss), autonomic (gastroparesis, orthostatic hypotension, erectile dysfunction). - **Chronic Macrovascular Complications:** - **Cardiovascular Disease:** Myocardial infarction, stroke. - **Peripheral Artery Disease:** Leading to amputations. - **Other:** Infections, skin complications, cataracts, glaucoma.