Diabetes Mellitus for USMLE Step 3

Diabetes Mellitus for the USMLE Step 3 Exam

Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to impaired insulin production, insulin resistance, or both.

Types:
Type 1 Diabetes Mellitus (T1DM): An autoimmune condition that leads to the destruction of pancreatic beta cells, resulting in absolute insulin deficiency. It commonly presents in childhood or adolescence.
Type 2 Diabetes Mellitus (T2DM): Characterized by insulin resistance and progressive beta-cell dysfunction. Initially, insulin secretion increases to compensate, but over time, beta-cell failure leads to hyperglycemia. T2DM is strongly associated with obesity and lifestyle factors.
Gestational Diabetes Mellitus (GDM): Diabetes diagnosed during pregnancy, increasing the risk of future T2DM in the mother.

Type 1 DM: Presents with the classic symptoms of hyperglycemia, including polyuria, polydipsia, polyphagia, and weight loss. If untreated, it can progress to diabetic ketoacidosis (DKA).
Type 2 DM: Often asymptomatic in the early stages and is frequently diagnosed during routine screening or after the development of complications. Symptoms may include fatigue, recurrent infections, blurred vision, and polyuria.
Diabetic Ketoacidosis (DKA): A life-threatening acute complication of T1DM characterized by hyperglycemia, ketonemia, and metabolic acidosis. Patients present with dehydration, vomiting, abdominal pain, and altered mental status.
Hyperosmolar Hyperglycemic State (HHS): A complication of T2DM with severe hyperglycemia, dehydration, and hyperosmolarity without significant ketoacidosis. It typically presents with confusion or coma.

ADA Diagnostic Criteria:
Fasting plasma glucose (FPG) ≥126 mg/dL.
2-hour plasma glucose ≥200 mg/dL during a 75 g oral glucose tolerance test (OGTT).
HbA1c ≥6.5%.
Random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia (polyuria, polydipsia, unexplained weight loss).
Screening: Recommended for adults ≥45 years old and earlier in individuals with risk factors such as obesity, hypertension, and family history of diabetes.

Lifestyle Modifications:
Diet: Focus on a balanced diet with controlled carbohydrate intake. Low-calorie, low-carbohydrate diets are particularly effective for weight loss in T2DM.
Exercise: Patients are advised to engage in at least 150 minutes of moderate aerobic exercise per week, along with resistance training, to improve insulin sensitivity and overall glycemic control.
Pharmacologic Therapy:
Type 1 DM: Insulin therapy is essential. Basal-bolus insulin regimens or continuous subcutaneous insulin infusion (CSII) via insulin pumps are commonly used.
Type 2 DM:
Metformin: First-line therapy unless contraindicated (e.g., renal insufficiency). It reduces hepatic gluconeogenesis and improves insulin sensitivity.
Second-Line Agents:
GLP-1 Receptor Agonists: Promote insulin secretion, suppress glucagon, slow gastric emptying, and support weight loss.
SGLT-2 Inhibitors: Increase renal glucose excretion and reduce cardiovascular and renal events.
DPP-4 Inhibitors: Improve glycemic control by prolonging the action of incretin hormones.
Insulin: May be required in T2DM as beta-cell function declines or during periods of severe hyperglycemia or acute illness.

Microvascular Complications:
Diabetic Retinopathy: Chronic hyperglycemia damages retinal vessels, leading to vision loss. Annual dilated eye exams are recommended.
Diabetic Nephropathy: Glomerular damage from hyperglycemia can lead to proteinuria and eventually end-stage renal disease (ESRD). Screening for albuminuria and serum creatinine is necessary.
Diabetic Neuropathy: Peripheral neuropathy causes pain, numbness, and increased risk of foot ulcers. Autonomic neuropathy can lead to gastrointestinal, cardiovascular, and sexual dysfunction.
Macrovascular Complications:
Cardiovascular Disease (CVD): Patients with diabetes are at increased risk of coronary artery disease (CAD), myocardial infarction, stroke, and peripheral artery disease (PAD).
Acute Complications:
DKA: A medical emergency requiring IV insulin, fluids, and electrolyte replacement.
HHS: Requires aggressive rehydration and insulin therapy to correct hyperglycemia and prevent severe dehydration.

Key Points

Pathophysiology: T1DM involves autoimmune destruction of pancreatic beta cells, while T2DM involves insulin resistance and progressive beta-cell dysfunction. Gestational diabetes increases the future risk of T2DM.
Diagnosis: The ADA criteria include FPG ≥126 mg/dL, 2-hour OGTT ≥200 mg/dL, HbA1c ≥6.5%, or random glucose ≥200 mg/dL with symptoms.
Management: T1DM requires insulin therapy. T2DM management starts with lifestyle modifications and metformin, with additional medications (GLP-1 agonists, SGLT-2 inhibitors, insulin) as needed.
Complications: Microvascular complications include retinopathy, nephropathy, and neuropathy. Macrovascular complications involve cardiovascular disease, while acute complications include DKA and HHS.