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Diabetes Mellitus, Type 2

Basics

  • Caused by progressive insulin secretory defect in the setting of insulin resistance.
  • Associated with obesity, visceral adiposity, dyslipidemia, hypertension, gut microbiome changes.
  • Drug-induced causes include glucocorticoids, antiretroviral therapy, atypical antipsychotics, immunosuppressants.
  • Geriatric patients require less aggressive glucose targets, dose adjustments, and hypoglycemia monitoring.
  • Pediatric incidence rising with obesity epidemic.
  • Pregnancy: diet, metformin, glyburide, insulin are treatment options; postpartum screening recommended.

Epidemiology

  • Estimated 37.3 million Americans affected (11.3% prevalence).
  • 90-95% of diabetes cases likely T2DM.

Etiology and Pathophysiology

  • Peripheral insulin resistance plus defective insulin secretion.
  • Genetic: polygenic with rare monogenic forms (e.g., PPARγ and insulin gene mutations).
  • Strong familial predisposition.

Risk Factors

  • Family history of T2DM.
  • History of gestational diabetes or macrosomia (>4 kg birth weight).
  • PCOS.
  • Dyslipidemia (high triglycerides, low HDL).
  • Ethnic risk: African American, Latino, Native American, Asian, Pacific Islander.
  • Sedentary lifestyle, visceral obesity.

General Prevention

  • Weight maintenance or loss (~7% body weight).
  • Carbohydrate and calorie reduction.
  • Moderate exercise (~150 min/week).
  • Metformin, α-glucosidase inhibitors, TZDs, GLP-1 receptor agonists for prediabetes.

Commonly Associated Conditions

  • Hypertension, dyslipidemia, metabolic syndrome.
  • Fatty liver disease, PCOS.
  • Acanthosis nigricans.
  • Hemochromatosis.

Diagnosis

History

  • Polyuria, polydipsia, polyphagia, weight loss, fatigue, blurry vision, neuropathy, infections.
  • Many are asymptomatic.

Physical Exam

  • BMI, waist circumference.
  • Fundus, oral, cardiopulmonary, abdominal, neurologic, foot exam.

Differential Diagnosis

  • Type 1 DM (autoantibodies, low C-peptide, ketosis).
  • Endocrine disorders (Cushing syndrome, acromegaly, glucagonoma).

Diagnostic Tests

  • HbA1c ≥6.5%
  • Random plasma glucose ≥200 mg/dL with symptoms.
  • Fasting plasma glucose ≥126 mg/dL.
  • 2-hour OGTT glucose ≥200 mg/dL.
  • Repeat testing if equivocal.

Treatment

General Measures

  • Lifestyle: diet, exercise, CV risk control (BP, lipids).
  • Individualized HbA1c targets:
  • ADA: <7.0% for most, less stringent for limited life expectancy or comorbidities.
  • ACP: target 7-8% for most.
  • ADA glucose targets: preprandial 80-130 mg/dL, postprandial <180 mg/dL.
  • High-risk cardiorenal patients: start with GLP-1 RA or SGLT2 inhibitors with proven benefits.

Medication

First Line

  • Metformin 500-2000 mg/day (divided or extended-release).
  • Mechanism: reduces hepatic gluconeogenesis.
  • Advantages: high efficacy, safety, low hypoglycemia risk, weight neutral, low cost.
  • Avoid in severe acute illness, renal impairment (eGFR <30), caution in elderly.

Second/Third Line

  • Choose agents based on comorbidities, side effects, cost.
  • GLP-1 receptor agonists (exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide).
  • CV benefit, weight loss, low hypoglycemia risk.
  • Contraindicated in personal/family history of medullary thyroid cancer or MEN2.
  • SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin).
  • Reduce CV mortality, renal protection.
  • Risks: genital infections, euglycemic DKA, fractures.
  • DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin).
  • Weight neutral, low hypoglycemia risk.
  • No CV risk reduction proven.
  • Sulfonylureas (glipizide, glyburide, glimepiride).
  • High hypoglycemia risk, weight gain, inexpensive.
  • Use cautiously with renal/liver disease.
  • Thiazolidinediones (pioglitazone, rosiglitazone).
  • Increase insulin sensitivity.
  • Risk: heart failure worsening, fractures.

Insulin

  • Consider if HbA1c >10%, catabolic symptoms, ketosis.
  • Basal insulin start 0.1-0.3 U/kg/day, titrate; add prandial insulin if needed.
  • Rapid-acting analogs preferred for less hypoglycemia.
  • Premixed insulin formulations available.

Other Agents

  • Amylinomimetic (pramlintide).
  • α-Glucosidase inhibitors (acarbose, miglitol).
  • Meglitinides (repaglinide, nateglinide).

Surgery

  • Bariatric surgery if BMI >35 kg/m².

Ongoing Care

  • Diabetes self-management education.
  • Regular foot, eye, renal monitoring.
  • Manage comorbid conditions (hypertension, dyslipidemia).
  • Promote healthy lifestyle.

Prognosis

  • Normal lifespan with good management.
  • Prevention of microvascular and macrovascular complications critical.

Complications

  • Atherosclerotic cardiovascular disease (ASCVD), peripheral vascular disease, stroke.
  • Foot ulcers, Charcot joints.
  • Neuropathy, retinopathy, diabetic kidney disease.
  • Nonalcoholic fatty liver disease, gastroparesis.

ICD10 Codes:
- E11.329 Type 2 diabetes mellitus with mild nonproliferative diabetic retinopathy without macular edema
- E11.331 Type 2 diabetes mellitus with moderate nonproliferative diabetic retinopathy with macular edema
- E11.359 Type 2 diabetes mellitus with proliferative diabetic retinopathy without macular edema

Clinical Pearls:
- Individualize HbA1c targets by patient comorbidities and life expectancy.
- Hypoglycemia poses greater immediate risk than hyperglycemia.
- GLP-1 RAs and SGLT2 inhibitors recommended early in patients with CV or renal disease.