Diabetes Mellitus for USMLE Step 1

Diabetes Mellitus for the USMLE Step 1 Exam

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

Types of Diabetes:
Type 1 Diabetes Mellitus (T1DM): An autoimmune disorder where T-cell-mediated destruction of pancreatic beta cells leads to absolute insulin deficiency. This commonly occurs in childhood or adolescence.
Type 2 Diabetes Mellitus (T2DM): Characterized by insulin resistance and relative insulin deficiency. Insulin resistance precedes beta-cell dysfunction, which leads to hyperglycemia. T2DM is more common in adults and is associated with obesity and a sedentary lifestyle.
Gestational Diabetes Mellitus (GDM): Diabetes diagnosed during pregnancy, increasing the risk for developing T2DM later in life.

Insulin is secreted by pancreatic beta cells in response to increased blood glucose levels. It promotes glucose uptake in muscle and fat cells, inhibits hepatic glucose production, and promotes glycogen synthesis.
Insulin Deficiency: Leads to hyperglycemia, increased lipolysis, proteolysis, and ketogenesis in the liver, contributing to diabetic ketoacidosis (DKA) in T1DM.
Insulin Resistance: In T2DM, insulin is less effective at stimulating glucose uptake, leading to hyperglycemia and compensatory hyperinsulinemia early in the disease.

Type 1 DM: Presents with polyuria, polydipsia, polyphagia, and weight loss due to glucose loss in the urine, dehydration, and catabolic metabolism. These symptoms often develop rapidly in children or young adults.
Type 2 DM: Often asymptomatic in the early stages, but may present with similar symptoms as T1DM over time. It is commonly discovered through screening or the onset of complications such as infections or blurred vision.
Diabetic Ketoacidosis (DKA): A life-threatening complication of T1DM characterized by hyperglycemia, ketonemia, and metabolic acidosis. Symptoms include vomiting, abdominal pain, Kussmaul breathing, and altered mental status.
Hyperosmolar Hyperglycemic State (HHS): A complication of T2DM with extreme hyperglycemia, dehydration, and hyperosmolarity without significant ketoacidosis. It typically presents with confusion or coma.

Diagnostic Criteria (ADA guidelines):
Fasting plasma glucose (FPG) ≥126 mg/dL.
2-hour plasma glucose ≥200 mg/dL during an oral glucose tolerance test (OGTT).
HbA1c ≥6.5%.
Random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia.
Monitoring: HbA1c is used to assess long-term glycemic control, with a target of <7% in most patients.

Type 1 DM:
Insulin Therapy: Required for survival. Treatment regimens include basal-bolus insulin or continuous subcutaneous insulin infusion (insulin pumps). Intensive insulin therapy is used to mimic normal insulin physiology.
Type 2 DM:
Lifestyle Modifications: Diet and exercise are first-line interventions. Weight loss and increased physical activity improve insulin sensitivity.
Pharmacotherapy:
Metformin: First-line therapy for T2DM due to its ability to decrease hepatic gluconeogenesis and improve insulin sensitivity.
Other Agents: Sulfonylureas (increase insulin secretion), GLP-1 receptor agonists (enhance insulin secretion and promote weight loss), and SGLT-2 inhibitors (promote renal glucose excretion).
Insulin: May be required as the disease progresses and beta-cell function declines.

Microvascular Complications:
Diabetic Retinopathy: Results from chronic hyperglycemia, leading to retinal vessel damage, neovascularization, and potential blindness. Routine eye exams are essential.
Diabetic Nephropathy: Glomerular damage due to hyperglycemia causes proteinuria and can progress to end-stage renal disease (ESRD).
Diabetic Neuropathy: Peripheral neuropathy leads to numbness, tingling, or pain, typically in the feet. Autonomic neuropathy can affect cardiovascular, gastrointestinal, and urogenital systems.
Macrovascular Complications:
Cardiovascular Disease (CVD): Diabetes is a major risk factor for atherosclerosis, leading to myocardial infarction, stroke, and peripheral artery disease (PAD).
Acute Complications:
DKA: Common in T1DM and can be fatal if untreated. It requires prompt IV insulin and fluid replacement.
HHS: More common in T2DM, requiring aggressive rehydration and insulin therapy.

Key Points

Types: T1DM is caused by autoimmune destruction of beta cells, leading to insulin deficiency, while T2DM involves insulin resistance and progressive beta-cell dysfunction. GDM occurs during pregnancy.
Diagnosis: FPG ≥126 mg/dL, 2-hour OGTT ≥200 mg/dL, HbA1c ≥6.5%, or random plasma glucose ≥200 mg/dL with symptoms.
Management: T1DM requires insulin therapy, while T2DM management includes lifestyle modifications and medications like metformin. Insulin may be needed in advanced T2DM.
Complications: Microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (CVD) complications are common in poorly controlled diabetes. DKA and HHS are life-threatening acute complications.