DIABETIC KETOACIDOSIS (DKA)

Definition and Pathophysiology

• Triad: Hyperglycemia, anion gap metabolic acidosis, and ketonemia.
• Primarily seen in type 1 diabetes mellitus (severe insulin deficiency).
• Mechanisms:
  • Insulin deficiency + excess counterregulatory hormones (glucagon, catecholamines, cortisol, GH).
  • → Glycogenolysis, gluconeogenesis, decreased glucose disposal.
  • → Excessive lipolysis, increased fatty acid oxidation → excess ketone production.

Clinical Presentation

• Onset: Can occur rapidly over 24 hours; often preceded by polyuria, polydipsia, weight loss.
• Symptoms:
  • Nausea, vomiting, abdominal pain.
  • Lethargy, Kussmaul respirations (slow, deep breathing).
  • Fruity (acetone) odor on breath.
• Signs: Hypotension, tachycardia, tachypnea, dehydration, decreased skin turgor, dry mucous membranes.

Laboratory Findings

• Low serum bicarbonate (<10 mEq/L).
• High anion gap (>20 mEq/L).
• High serum glucose (500–900 mg/dL).
• Low arterial pH (<7.3).
• Increased ketones (acetoacetate, β-hydroxybutyrate).

Differential Diagnosis

• Other causes of metabolic acidosis with high anion gap:
  • Lactic acidosis, starvation ketosis, alcoholic ketoacidosis, uremia, salicylates, etc.

Treatment and Management

1. Fluids:
   • Normal saline 1 L in first hour → 200–500 mL/hr guided by clinical/lab response.
2. Insulin Administration:
   • IV bolus (10 U) + continuous infusion (0.1 U/kg/hr).
   • Target: decrease serum glucose by 50–75 mg/dL/hr.
   • Reduce insulin infusion rate when glucose ~200 mg/dL to avoid hypoglycemia & cerebral edema.
3. Electrolytes:
   • Potassium often shifts from intracellular to extracellular space, but total body K+ is low.
   • Add K+ if serum K+ <5.3 mEq/L.
4. Monitoring:
   • ICU setting, hourly blood glucose & potassium checks, frequent electrolytes (Ca2+, Mg2+, phosphate).
   • Correction period usually 12–36 hrs.
5. Identify Underlying Cause:
   • Often poor insulin compliance in known type 1 diabetes.
   • Can be triggered by infection, MI, stroke, pancreatitis.

DIABETIC RETINOPATHY

Overview

• Microvascular complication of hyperglycemia → 25× higher risk of blindness.
• Vision Loss Mechanisms: Retinal hemorrhage, macular edema, retinal detachment, neovascular glaucoma.
• Nearly all with type 1 and >50% with type 2 diabetes develop it within 20 years of diagnosis.

Pathogenesis

• Chronic hyperglycemia → abnormal retinal vessel permeability + vascular occlusion → ischemia.
• Mechanisms:
  • Impaired autoregulation of retinal blood flow.
  • Increased advanced glycation end products, sorbitol.
  • Microaneurysms form from pericyte loss.
  • Triggered growth factors (VEGF, etc.) → neovascularization.

Nonproliferative Retinopathy (NPDR)

• Key Findings:
  • Microaneurysms, intraretinal hemorrhages (dot-and-blot, flame-shaped), cotton-wool patches (nerve fiber infarcts), hard exudates (lipid).
  • Macular edema = main cause of vision loss here.
• Risk of Progression:
  • Mild NPDR: ~5%/year to proliferative.
  • Very severe NPDR: ~75%/year to proliferative.

Proliferative Retinopathy (PDR)

• Defining Feature: Neovascularization (new vessels from retinal vessels/optic disc).
• Complications: Vitreous hemorrhage, preretinal hemorrhage, traction retinal detachment → severe vision loss.
• Diagnosis: Fundus exam ± fluorescein angiography (to detect leak/ischemia).

Macular Edema

• Retinal thickening ± edema at or near macula → most common cause of diabetic vision loss.
• Clinically significant macular edema: thickening threatens central visual function.

COMPLICATIONS OF PROLIFERATIVE DIABETIC RETINOPATHY

Clinical Course

• Neovascularization → high risk vitreous or preretinal hemorrhage, fibrosis, traction detachment.
• Untreated severe PDR → ~60% risk of vision loss within 5 years.

Management

• Annual screening crucial; retinopathy often asymptomatic until advanced.
• Tight glycemic control slows progression.
• Laser photocoagulation:
  • Panretinal (scatter) for severe PDR (~1200–1800 burns).
  • Focal for clinically significant macular edema.
• Adjuncts: Intravitreal anti-VEGF agents under study.
• Surgery (vitrectomy) for nonresolving vitreous hemorrhage or traction detachment.

DIABETIC NEPHROPATHY

Overview

• Major cause of morbidity/mortality in both type 1 and type 2 diabetes.
• Leading cause of end-stage renal disease (ESRD).
• Classic triad: Proteinuria, hypertension, renal impairment.

Stages of Nephropathy

1. Hyperfiltration: Elevated GFR, glomerular hypertrophy.
2. Silent Stage: Normal GFR, no proteinuria, but basement membrane thickening, mesangial expansion.
3. Incipient Nephropathy: Microalbuminuria (30–300 mg/24 hr), often with hypertension.
4. Overt Nephropathy: Macroalbuminuria (>300 mg/24 hr), rising creatinine.
5. Uremia: ESRD requiring renal replacement therapy.

Pathogenesis

• Chronic hyperglycemia → thickened glomerular basement membrane, mesangial expansion, nodular/diffuse glomerulosclerosis.
• Hypertrophy → glomerular hyperfiltration → progressive damage.
• Microangiopathy can cause tubulopathy, type IV RTA, hyperkalemia, hypoaldosteronism.

Treatment

• Glycemic control: slows onset/progression.
• Blood pressure management: ACE inhibitors/ARBs are first-line for renoprotection (↓ albuminuria).
• Avoid nephrotoxins: NSAIDs, contrast dyes, etc.
• ESRD: Options include hemodialysis, peritoneal dialysis, kidney ± pancreas transplantation.

DIABETIC NEUROPATHY

General Features

• ~50% prevalence in those with ≥25 years diabetes.
• Not one single entity → multiple patterns: focal, proximal, distal, autonomic.

Focal Neuropathies

• Mononeuropathies in older patients:
  • Sudden onset, self-limited (2 months).
  • Commonly CN III, VI, VII, or peripheral nerves (ulnar, peroneal).
• Polyradiculopathy: severe pain along nerve roots ± muscle weakness.

Proximal Motor Neuropathies

• Diabetic amyotrophy → older type 2 patients.
• Thigh/pelvic girdle pain, quad atrophy, marked weakness in proximal lower limbs.
• Often weight loss, depression.

Distal Symmetric Polyneuropathy (DSPN)

• Most common form.
• Slow onset, symmetric, “stocking-and-glove.”
• Small-fiber neuropathy → burning pain, hyperalgesia, allodynia.
• Large-fiber neuropathy → decreased vibration/proprioception, muscle weakness, absent reflexes.
• Risk of foot ulcers, Charcot arthropathy.

Autonomic Neuropathy

• Pervasive sympathetic & parasympathetic involvement →
  • Pupillary changes, orthostatic hypotension, gastroparesis, nocturnal diarrhea, neurogenic bladder, erectile dysfunction, sweat disturbances, hypoglycemic unawareness, silent MI.

ATHEROSCLEROSIS IN DIABETES

Overview

• Macrovascular complications more extensive and faster progression than in nondiabetics.
• Diabetes = CHD “risk equivalent,” same approach as known CHD.
• Pathophysiology:
  • Insulin resistance → ↑ free fatty acids → ↑ VLDL → dyslipidemia (low HDL, high small dense LDL).
  • Insulin & hyperglycemia potentiate platelet-derived growth factor → vascular smooth muscle proliferation.
  • ↑ plasminogen activator inhibitor 1, decreased nitric oxide.
  • Mönckeberg arteriosclerosis (medial calcific sclerosis) more common.

Cardiovascular Risk Reduction

• Lifestyle: weight loss, exercise, stop smoking.
• Optimal glycemic control and BP <130/80.
• Lipid management (statins).
• Aspirin for primary/secondary prevention.
• ACE inhibitors/ARBs reduce CHD events in patients with diabetes.

Myocardial Infarction in Diabetes

• 2× higher fatality rate vs. nondiabetics.
• Mechanisms: more severe underlying disease, microvascular involvement, less collateral flow, autonomic dysfunction, maladaptive remodeling.
• Glycemic control can shift myocardial substrate use from fatty acids to glucose, improving efficiency.
• Post-MI care: ACE inhibitors, cardioselective β-blockers, aspirin.

VASCULAR INSUFFICIENCY IN DIABETES: THE DIABETIC FOOT

Epidemiology

• Foot ulcers in ~10% of diabetics; ~1% need amputation.
• Neuropathy + vascular disease major contributors.

Pathogenesis

1. Neuropathy:
   • Sympathetic → decreased sweating → dry, cracked skin → infection risk.
   • Motor → small muscle atrophy → deformities (claw toes) → pressure points.
   • Sensory → decreased pain/proprioception → unnoticed trauma/ulcers.
2. Vascular Insufficiency:
   • Peripheral arterial disease more severe, accelerated by diabetes-related endothelial dysfunction, atherosclerosis.

Prevention & Screening

• Annual foot exams:
  • Check pulses (dorsalis pedis, posterior tibial), skin temperature, dependent rubor.
  • Inspect foot architecture for calluses, deformities (hammer/claw toes), dryness.
  • Monofilament testing (Semmes-Weinstein 5.07 for protective sensation).
  • Check vibration (128-Hz tuning fork), reflexes, color changes.
• Foot Care:
  • Smoking cessation, avoid walking barefoot, test bath water temp, trim nails properly, daily inspection for lesions, well-fitting footwear.

Diabetic Foot Ulcer Classification (Wagner Classification)

• Grade 0: No ulcer; high risk (deformity, callus).
• Grade 1: Superficial ulcer (full-thickness).
• Grade 2: Deeper ulcer (tendons, not bone).
• Grade 3: Osteitis/osteomyelitis (bone involvement).
• Grade 4: Partial gangrene (e.g., toes/forefoot).
• Grade 5: Whole foot gangrene.

Management of Foot Ulcers

1. Correct arterial insufficiency if present.
2. Treat infection aggressively (culture, antibiotics).
3. Offload pressure (removable cast boot, orthotics).
4. Debride devitalized tissue.
5. Imaging for suspected osteomyelitis → plain X-ray, MRI, bone scan.
6. Surgical resection for infected bone or extensive gangrene.
7. Self-amputation may occur if localized, noninfected necrosis (e.g., toe tip). Larger gangrene → urgent vascular, orthopedic consult.