Complications of diabetes mellitus

Diabetic nephropathy is a major cause of end stage renal disease (ESRD).

• Mesangial changes: increased permeability and hyperfiltration
• Vascular lesions: arteriolosclerosis, especially in the efferent arterioles
• Glomerular lesions:
  • Diffuse capillary basement membrane thickening is the earliest and most common finding.
  • Nodular: Kimmelstiel-Wilson nodules are pathognomonic.
• Tubular lesions: tubular glycogen deposition

Clinical features

• Often asymptomatic; patients may complain of foamy urine
• Progressive diabetic kidney disease with signs of renal failure and risk of uremia (e.g., uremic polyneuropathy)
• Arterial hypertension

Urine analysis: proteinuria

• Initially moderately increased albuminuria (microalbuminuria)  ,
• Eventually significantly increased albuminuria (macroproteinuria): nephrotic syndrome may develop.

Prevention and management

• Stringent glycemic control  
• Antihypertensive treatment
  • ACE inhibitors OR angiotensin-receptor blockers are the first-line antihypertensive drugs in patients with diabetes.
  • Second line agents to be added to ACE inhibitors or ARBs to further control hypertension include diuretics or calcium channel blockers
• Dietary modification: daily salt intake < 5–6 g/day; phosphorus and potassium intake restriction in advanced nephropathy; protein restriction

• Epidemiology
  • After 15 years with disease, approx. 90% of patients with type 1 diabetes and approx. 25% of patients with type 2 diabetes develop diabetic retinopathy.
  • The most common cause of visual impairment and blindness in patients aged 25–74 years in the US
• There are 3 main categories:
  • background or simple retinopathy - consists of microaneurysms, hemorrhages, exudates, and retinal edema
  • pre-proliferative retinopathy - with cotton wool spots
  • proliferative or malignant retinopathy - consists of newly formed vessels.

• Clinical features
  • Asymptomatic until very late stages of disease
  • Visual impairment
  • Progression to blindness
• Screening
  • Type 1 DM: initial dilated and comprehensive eye examination within 5 years after the onset of diabetes and then annually
  • Type 2 DM: initial dilated and comprehensive eye examination at the time of the diabetes diagnosis and then annually

• Often asymptomatic and found on screening exams
• Can be generalized focal, multifocal, or autonomic
• Chronic distal symmetric polyneuropathy :
  • Presents with paresthesias in a “stocking glove” sensory-loss pattern
  • Affected individuals may complain of:
    • Numbness
    • Tingling
    • Burning
    • Pain in the feet
    • Worsening at night
  • Decreased sensation to light touch/monofilament on exam
  • Loss of pain perception , leading to the potential for wounds
• Autonomic neuropathy:
  • Cardiovascular manifestations:
    • Resting tachycardia
    • Orthostatic hypotension
  • Gastroparesis due to the vagus nerve being affected:
    • Delayed gastric emptying
    • Risk of postprandial hypoglycemia
    • Nausea
    • Bloating
    • Loss of appetite
    • Can result in excess weight loss
  • Genitourinary involvement can lead to erectile dysfunction , although this condition is more likely due to a vascular etiology.
  • Cranial nerves :
    • Can lead to oculomotor nerve palsies
    • Ptosis
    • Spared pupillary function
  • Peripheral mononeuropathy: nerve palsies, such as common peroneal nerve causing foot drop
  • Mononeuritis multiplex: asymmetric neuropathy involving multiple peripheral and cranial nerves

• Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency.
• Triggering factors include inadequate insulin therapy, underlying infection, concurrent medical illness, or drug side effects.
• Diabetic ketoacidosis patients tend to be younger, with type 1 diabetes, who present with acute symptoms, including abdominal pain, nausea, and vomiting .
• Epidemiology
  • More frequently seen in younger patients
  • Mostly seen in patients with type 1 diabetes
  • Accounts for approximately 14% of all hospital admissions for diabetics
  • Mortality rate: 0.2%–2% (increased mortality in patients with coma, hypothermia , and oliguria )
• Pathophysiology
  • Hormone abnormalities:
    • Absolute insulin deficiency
    • ↑ glucagon
    • Additional hormone changes, which oppose insulin :
      • ↑ cortisol
      • ↑ growth hormone
      • ↑ catecholamines
    • Hyperglycemia results from:
      • ↓ glucose utilization by peripheral tissues
      • ↑ glycogenolysis
      • ↑ gluconeogenesis
        • ↑ amino acid delivery from muscle
        • ↑ glycerol delivery from adipose tissue
    • Severe hyperglycemia leads to:
      • ↑ osmolality → draws water out of cells → dilutes sodium concentrations
      • Glucosuria → osmotic diuresis, resulting in:
        • Water and electrolyte loss ( sodium and potassium)
        • Dehydration
        • ↑ osmolality
        • Impaired renal function
    • Ketoacidosis results from:
      • ↑ lipolysis → ↑ free fatty acids → ↑ ketone production (ketogenesis)
      • ↓ bicarbonate → consumed as a buffer → ↑ anion gap
    • Acidosis and hyperosmolality results in:
      • Potassium shifts out of cells → ↑ extracellular potassium, ↓ intracellular potassium
      • Potassium is then excreted in the urine → ↓ total body potassium
• Clinical features
  • Rapid onset of symptoms (over 24 hours): Polyuria, Polydipsia, Nausea and vomiting, Diffuse abdominal pain. and Weakness 
  • Physical exam findings:
    • Tachycardia, Hypotension, and Hypothermia
    • Rapid, deep respirations (Kussmaul respirations) → compensatory hyperventilation
    • Fruity breath → exhaled acetone
    • Evidence of severe dehydration: Dry mucous membranes, Sunken eyes, Decreased skin turgor, Anhidrosis, Decreased urine output
• Diagnostics
  • ↑ Glucose (typically 300-800 mg/dL)
  • Metabolic acidosis (bicarbonate <18 mEq/L)
  • ↑ Anion gap
  • Positive serum ketones
  • Potassium in DKA: normal or elevated (despite a total body deficit)
  • Hyponatremia is common in DKA, due to hypovolemic hyponatremia  ; and hypertonic hyponatremia  
  • Always check corrected sodium for hyperglycemia  .
  • BUN and creatinine are often elevated  .
• Severity of DKA

• Treatment
  • High-flow IV fluids (normal saline) → First-Line
    • If corrected serum sodium ≥ 135 mmol/L: 0.45% NaCl
    • If corrected serum sodium < 135 mmol/L: 0.9% NaCl
    • When serum glucose falls to < 200–250 mg/dL, add 5% dextrose to infusion  .
  • IV insulin
    • Does: 0.1 unit/kg/hr → فكرة سؤال
    • Potassium levels must be ≥ 3.3 mEq/L before insulin therapy is initiated
      • If potassium level is < 3.3 mEq/L, potassium should be repleted and rechecked prior to giving any insulin  .
      • If potassium level is < 5.3 mEq/L, the patient will likely require potassium repletion once insulin therapy is started
      • Maintain serum potassium between 4–5 mEq/L.
      • Monitor potassium levels every 2 hours while administering insulin infusion.
  • Sodium bicarbonate (NaHCO3) can be given if the patient’s pH is < 6.9.