Diabetes Mellitus Type 2

Endocrine & Metabolic

Description

Type 2 diabetes mellitus is a progressive metabolic disorder defined by chronic hyperglycemia resulting from a combination of insulin resistance in peripheral tissues and an inadequate compensatory insulin secretory response from pancreatic β-cells; it accounts for roughly 90 % of all diabetes cases worldwide and is a major driver of cardiovascular disease, renal failure, blindness, non-traumatic amputations and premature mortality.

Symptoms

Many individuals are asymptomatic for years; classic manifestations include polyuria, polydipsia, nocturia, unexplained weight loss, blurred vision, fatigue, slow-healing wounds, recurrent genital or cutaneous infections, and acanthosis nigricans on neck or axilla. Hyperosmolar hyperglycemic state may present with profound dehydration, altered mental status and plasma glucose > 600 mg/dL.

Risk Factors

Age ≥ 40 years but increasingly youth onset, family history in a first-degree relative, overweight or obesity (BMI ≥ 25 kg/m² or ≥ 23 kg/m² in Asian ancestry), waist circumference > 102 cm in men or > 88 cm in women, physical inactivity, high-energy dense diet, gestational diabetes or macrosomic baby (> 4 kg), polycystic ovary syndrome, hypertension, dyslipidemia (triglycerides ≥ 150 mg/dL or HDL < 40 mg/dL in men < 50 mg/dL in women), non-alcoholic fatty liver disease, obstructive sleep apnea, long-term glucocorticoid or antipsychotic therapy, low socioeconomic status, and certain ethnicities (South Asian, African American, Hispanic, Pacific Islander, Indigenous peoples).

Diagnosis

Diabetes is confirmed by any of the following on two occasions or once with unequivocal hyperglycemia: fasting plasma glucose ≥ 126 mg/dL after 8-h fast, HbA1c ≥ 6.5 % (48 mmol/mol) using NGSP-certified assay, 2-h plasma glucose ≥ 200 mg/dL during 75-g OGTT, or random plasma glucose ≥ 200 mg/dL plus symptoms. Autoantibody testing (GAD, IA-2, ZnT8) and fasting C-peptide differentiate from type 1 or LADA when clinical context is unclear. Baseline labs include lipid panel, liver enzymes, creatinine/eGFR, urine albumin-to-creatinine ratio and thyroid-stimulating hormone in women over 50. Fundoscopic exam, foot monofilament/vibration testing and blood-pressure measurement complete initial evaluation.

Treatment

Cornerstone therapy is individualized medical nutrition (calorie deficit 500–750 kcal/d if overweight, Mediterranean or DASH pattern, < 10 % total calories from added sugar), 150 min/week moderate-vigorous aerobic plus resistance training, 7–10 % weight loss and structured sleep/stress management; first-line pharmacologic agent is metformin 500 mg daily titrated to 1000 mg twice daily absent contraindications (eGFR < 30 mL/min/1.73 m²). If HbA1c remains above individualized target (generally < 7 %), choose additional agents based on comorbidities: GLP-1 receptor agonists (semaglutide 0.5–2 mg weekly, tirzepatide 5–15 mg weekly) or SGLT2 inhibitors (empagliflozin 10–25 mg, dapagliflozin 5–10 mg) preferred for atherosclerotic cardiovascular disease, heart failure or CKD; sulfonylureas or thiazolidinediones for cost concerns; DPP-4 inhibitors when GLP-1 contraindicated; basal insulin (glargine or degludec) initiated if HbA1c > 9 % with symptoms or after triple-oral therapy failure, advancing to basal-plus or full basal-bolus if needed. Continuous glucose monitoring or flash sensors assist dose titration. Bariatric metabolic surgery (sleeve gastrectomy, Roux-en-Y) indicated for BMI ≥ 35 kg/m² (≥ 30 kg/m² in Asian ancestry) with inadequate medical control, often achieving long-term remission. Antihypertensive (ACEi/ARB first-line), statin regardless of baseline LDL in those ≥ 40 y or with ASCVD, low-dose aspirin for secondary prevention, and GLP-1/SGLT2 combo for additive cardiorenal benefit.

Outlook

Tight glycemic control (mean HbA1c < 7 %) reduces microvascular endpoints by ~ 35 %, intensive multifactorial risk-factor management halves cardiovascular events; however, progressive β-cell failure necessitates medication intensification every 3–5 years. Life expectancy is reduced by ~ 6 years, but declines markedly with smoking, uncontrolled blood pressure or lipid levels. Remission is feasible through ≥ 15 % weight loss via intensive lifestyle or metabolic surgery, especially within first 6 years of diagnosis.

Complications

Non-proliferative and proliferative retinopathy, macular edema, diabetic kidney disease progressing to ESRD, distal symmetric polyneuropathy, autonomic neuropathy (gastroparesis, orthostatic hypotension), foot ulceration and amputation, myocardial infarction, stroke, heart failure with preserved or reduced EF, NAFLD/NASH, depression, cognitive decline and higher infection risk (pneumonia, severe COVID-19) are major sequelae.

Prevention

Population strategies include taxation of sugar-sweetened beverages, urban walkability, promotion of whole-grain plant-forward diets, breastfeeding support, and vaccination against COVID-19/influenza to limit metabolic decompensation. Individually, 5–7 % weight loss, 150 min/week activity, Mediterranean diet, adequate sleep, smoking cessation and metformin 850 mg twice daily or GLP-1 analogues in high-risk prediabetes prevent or delay onset.

Support

Monitor glucose at least twice daily if on insulin or sulfonylurea, record readings and carbohydrate intake, use smartphone apps or CGM to identify patterns, carry glucose tablets or gel for hypoglycemia (< 70 mg/dL), follow sick-day rules (check glucose and ketones q4 h, maintain hydration, continue basal insulin), schedule quarterly HbA1c checks, annual eye and foot exams, and renal labs. Family can aid by preparing balanced meals, joining exercise sessions, spotting hypoglycemia signs (sweating, tremor, confusion) and administering glucagon 3 mg nasal spray in severe lows.