Diabetes Mellitus

Snapshot

• A 56-year-old woman comes to your clinic for her annual physical exam. She reports increased urinary frequency and thirst, but is otherwise feeling generally well. She is obese, does not exercise, and regularly eats fried foods. A random blood glucose is 223 ml/dL. Her hemoglobin A1c is 9.2.

Introduction

• Type 1 diabetes
  • immune-mediated destruction of β-cells and loss of insulin production by pancreas 
    • may also have antibodies against insulin
  • 10% of diabetes cases
  • classically occurs in thin people younger than 30
  • sudden onset (after about 90% β-cells destroyed)
  • result of self-reactive T-cell destruction of β-cells 
  • not necessary to have a family history
  • associated with HLA-DR3 and -DR4 
    • also seen concurrently with other autoimmune diseases (e.g., Graves’, Hashimoto, etc.)
• Type 2 diabetes
  • insulin insensitivity in peripheral organs requiring increased insulin production
    • pancreas cannot produce enough insulin
  • gradual onset
  • 90% of diabetes cases
  • typically in older individuals, though increasingly found in children with obesity
  • common to have a family history
  • associated with obesity
  • amyloid deposition in β-cells 
• Complications are due to poor glycemic control 
  • if diabetic maintains glucose in normal range prognosis is good
  • damage mediated by
    • non-enzymatic glycosylation which makes vessels more permeable
    • increased synthesis of type IV collagen in basement membrane
    • osmotic damage which is secondary to glucose conversion to sorbitol by aldose reductase 
• cause of cataracts and neuropathy 

Presentation

• Symptoms
  • type I
    • polyuria
    • polydipsia
    • polyphagia
    • fatigue
    • weight loss
    • DKA  
  • type II
    • blurry vision
    • candidal infections (especially vaginitis)
    • hyperosmolar nonketotic coma 
• acanthosis nigricans: a velvety hyperpigmentation of the skin and found in body folds

Evaluation

• Labs: 4 options 
  • hemoglobin A1c > or equal to 6.5% 
    • best single test for diabetes mellitus
  • random blood glucose of > or equal to 200mg/dL AND diabetic symptoms
  • 2 separate fasting glucoses of > or equal to 126 mg/dL (fasting means no intake for > 8 hours)
• 2-hour postprandial glucose (glucose tolerance test) of > or equal to 200 mg/dL 

Treatment

• See Diabetes pharmacology 
• Complications of treatment
  • peripheral neuropathy 
    • duloxetine (serotonin/norepinephrine reputake inhibitor), venlafaxine, tricyclic antidepressants, pregabalin, or gabapentin 
  • diabetic kidney disease
    • ACE-inhibitor 
  • gastroparesis
• metoclopramide

Prognosis, Prevention, and Complications

• Macrovascular complications
  • coronary artery disease 
    • 4 times more likely in DM patients
  • peripheral vascular disease
  • stroke
• Microvascular complications
  • nephropathy
    • arteriosclerosis leading to hypertension
    • nodular sclerosis
      • Kimmelstiel-Wilson nodules
    • progressive proteinuria
    • chronic renal failure
  • ocular
    • retinopathy
      • proliferative changes involve neovascularization of retina
      • nonproliferative changes involve microaneurysms
    • cataracts
    • glaucoma
    • blindness
  • peripheral neuropathy
    • numbness and paresthesias
    • burning sensation
    • ↓ deep tendon reflexes
    • ↓ vibration sense
  • central neuropathy
    • 3rd nerve palsy sparing the pupil
      • also CN IV and VI
  • autonomic dysfunction
    • impotence
    • bladder retention and incontinence
    • gastroparesis  
    • abnormal small bowel motility 
      • leads to small intestinal bacterial overgrowth 
    • GI discomfort
    • postural hypotension
  • skin dysfunction
    • necrobiosis lipoidica diabeticorum
      • yellow plaques on legs
  • diabetic foot
    • combination of vascular and nerve disease
    • higher likelihood of infection, pressure ulcers
    • can lead to amputation
  • infectious disease
    • urinary tract infections
      • due to increased glucose in urine
    • rhinocerebral mucormycosis
    • Pseudomonas malignant external otitis