Endocrinology

Diabetes Mellitus

Clinical overview and exam mastery guide for T1DM/T2DM diagnosis, insulin and non-insulin drugs, acute emergencies (DKA/HHS), and long-term complication prevention.

T1DM
Absolute insulin deficiency
T2DM
Insulin resistance dominant
First-Line T2DM
Metformin
A1C Target
Usually under 7 percent

Type 2 DM Therapeutic Targets

Liver Metformin lowers hepatic output Kidney SGLT2 blockade glucose excretion Incretin axis GLP-1 effect satiety and insulin Cardiorenal benefit now drives regimen selection HF, CKD, and ASCVD context guide SGLT2 or GLP-1 prioritization

Modern treatment choices are glucose-focused and risk-modifying.

1. What Is Diabetes Mellitus?

Diabetes mellitus is chronic hyperglycemia caused by insulin deficiency, insulin resistance, or both. Persistent hyperglycemia drives microvascular and macrovascular complications.

2. Classification

  • Type 1 diabetes: autoimmune beta-cell destruction, absolute insulin deficiency
  • Type 2 diabetes: insulin resistance plus relative insulin deficiency
  • Gestational diabetes
  • Secondary diabetes examples: steroid-induced, pancreatitis, Cushing syndrome
  • T1DM requires lifelong insulin
  • T2DM is most prevalent form

3. Diagnostic Criteria

A1C 6.5 percent or higher Fasting glucose 126 mg/dL or higher Random glucose 200 mg/dL with symptoms 2-hour OGTT 200 mg/dL or higher
Prediabetes range: A1C 5.7 to 6.4 percent.

4. Pathophysiology of Type 2 DM

  • Insulin resistance
  • Increased hepatic glucose output
  • Progressive beta-cell dysfunction
  • Increased glucagon signaling
  • Increased renal glucose reabsorption
  • Incretin axis dysfunction

5. Goals of Therapy

Control hyperglycemia Prevent complications Reduce cardiovascular risk Individualize A1C target
Common target is A1C under 7 percent, individualized by age, comorbidity, and hypoglycemia risk.

6. Type 1 Diabetes Management

Insulin is mandatory.

Insulin

  • MOA: replaces endogenous insulin, increases glucose uptake, suppresses hepatic glucose production
  • Rapid-acting: lispro, aspart, glulisine
  • Short-acting: regular insulin
  • Long-acting: glargine, detemir, degludec
  • Side effects: hypoglycemia, weight gain, lipodystrophy
  • Contraindication: current hypoglycemia episode

7. Type 2 Diabetes Pharmacologic Therapy

Metformin is first-line unless contraindicated.
Class / Examples MOA Major Side Effects Contraindications / High-Yield Notes
Metformin (biguanide) Reduces hepatic glucose production, improves insulin sensitivity, lowers intestinal glucose absorption GI upset, B12 deficiency, rare lactic acidosis Severe renal impairment, acute metabolic acidosis
SGLT2 inhibitors (empagliflozin, dapagliflozin) Block renal SGLT2, increasing urinary glucose excretion Genital infections, volume depletion, euglycemic DKA Severe renal impairment; strong HF and CKD benefit
GLP-1 receptor agonists (semaglutide, liraglutide) Glucose-dependent insulin increase, glucagon suppression, delayed gastric emptying, satiety enhancement Nausea, vomiting, rare pancreatitis Personal/family medullary thyroid carcinoma history
DPP-4 inhibitors (sitagliptin) Prevent incretin breakdown and increase endogenous GLP-1 activity Nasopharyngitis, rare pancreatitis Dose adjust by renal function; modest efficacy
Sulfonylureas (glipizide, glyburide) Stimulate pancreatic insulin release from beta cells Hypoglycemia, weight gain Glyburide caution in renal impairment
TZDs (pioglitazone) PPAR-gamma activation improves insulin sensitivity Weight gain, edema, HF worsening Contraindicated in NYHA class III-IV heart failure

8. Acute Complications

DKA (more common in T1DM)

  • Hyperglycemia, ketonemia, metabolic acidosis
  • Management: IV fluids, IV insulin, potassium replacement

HHS (more common in T2DM)

  • Severe hyperglycemia, hyperosmolarity, minimal ketosis
  • Management parallels DKA framework with fluid-first strategy

9. Chronic Complications

Microvascular

  • Retinopathy
  • Nephropathy
  • Neuropathy

Macrovascular

  • Coronary artery disease
  • Stroke
  • Peripheral arterial disease
Aggressive glucose, blood pressure, and lipid control reduces long-term risk.

Management Recap Drill

T2DM 1: start metformin when eligible.
T2DM 2: if ASCVD/HF/CKD, prioritize SGLT2 inhibitor or GLP-1 receptor agonist.
T2DM 3: add agents if A1C remains above target.
T2DM 4: initiate insulin when uncontrolled or catabolic.
DKA: fluids, insulin, potassium.

Visual Algorithm Placeholder

[Insert ADA Diabetes Treatment Algorithm and Insulin Regimen Diagram Here During UI Integration]

Guideline References (Management)

ADA Standards of Care

https://diabetes.org

Guideline Scope

  • Treatment algorithms and A1C targets
  • Insulin initiation strategy
  • Cardiovascular and renal risk-based therapy

10. Common Exam Traps

Metformin remains first-line unless contraindicated.
SGLT2 inhibitors are strongly favored with HF or CKD.
GLP-1 receptor agonists support weight loss and ASCVD risk reduction.
Sulfonylureas increase hypoglycemia risk.
TZDs are contraindicated in advanced heart failure.

11. Quick Revision Summary

Must Remember

  • T1DM requires insulin
  • T2DM centers on insulin resistance and progressive beta-cell dysfunction
  • Metformin is foundational
  • SGLT2 and GLP-1 classes provide major cardiorenal advantages
  • DKA management is fluids plus insulin plus potassium

Practice Questions Placeholder

  • Topic: Diabetes Mellitus
  • Subtopics: T1DM, T2DM, insulin therapy, oral agents, DKA, HHS, complications