Diabetic ketoacidosis or DKA: DKA is most commonly seen in type 1 DM and can also occur in some patients with type 2 DM who have decreased insulin secretion. It may be precipitated by an intercurrent infection, noncompliance with insulin, or illicit drug use.
In DKA, there is insulin deficiency along with increased counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Because the body can’t use glucose effectively, lipolysis increases and free fatty acids are released. Some of these fatty acids are converted into ketone bodies:
Hyperglycemia causes osmotic diuresis, leading to dehydration and hyperosmolarity.
Clinical features include polyuria, polydipsia, weight loss, fatigue, vomiting, nausea, abdominal pain, orthostatic hypotension, lethargy, and coma. Metabolic acidosis causes Kussmaul respirations. Acetone in the breath produces a fruity odor.
Laboratory findings include:
A key limitation is that the urine dipstick does not measure beta hydroxybutyrate (the predominant ketone body in DKA). Urinalysis measures acetone and acetoacetate.
Potassium levels may be normal or low. Amylase and lipase may be elevated. Chest X ray, urine cultures, and blood cultures should be done to look for foci of infection.
Management includes:
DKA is considered resolved when:
Hyperosmolarity may cause pseudohyponatremia.
Potassium management must be done carefully. The goal is to maintain serum potassium between 4 to 5 meq/L.
Intravenous bicarbonate replacement is recommended when the pH is < 6.9. Phosphate and magnesium replacement may be required.
Cerebral edema is a dreaded complication of DKA and is more common in children and in severe cases. It results from a shift of water from the extracellular space into the intracellular compartment due to rapid correction of hyperosmolarity in DKA. Hyponatremia is a contributory factor. Early signs include decrease in heart rate, changes in sensorium (such as lethargy), headache, tachypnea, vomiting, and incontinence. CT scan can confirm the diagnosis.
Hyperosmolar hyperglycemic state or HHS: HHS is typically seen in type 2 diabetics. It is characterized by severe dehydration, marked hyperglycemia, increased serum osmolarity, and mild to absent ketosis. It carries a high mortality rate.
In HHS, excess glucose is produced due to increased glycogenolysis, gluconeogenesis, and reduced peripheral glucose uptake. The resulting hyperglycemia increases plasma osmolarity, causing osmotic diuresis and dehydration. Because some insulin is still present in HHS, lipolysis and ketogenesis are suppressed (compare and contrast with DKA).
Precipitating factors include non-compliance with antidiabetic medications, stress, infections (UTI, pneumonia, etc.), substance and alcohol abuse, AMI, stroke, PE, antipsychotics, glucocorticoids, diuretics, etc. Patients with undiagnosed DM may initially present with HHS.
Clinical features include low-grade fever and signs of dehydration (decreased skin turgor, dry tongue and mucosa, weak pulse), as well as headache, changes in sensorium, disorientation progressing to coma, seizures, abdominal pain, nausea, and vomiting.
Laboratory features (see table below) include hyperglycemia, hyperosmolarity, absence of ketones in serum or urine, and normal blood pH or mild metabolic acidosis. HHS, by itself, does not cause a high anion gap metabolic acidosis. Creatinine, BUN, and hematocrit will be elevated. Serum potassium is normal or elevated, although total body potassium is reduced. Serum lipase and amylase may be elevated.
| DKA | HHS |
| High anion gap | Variable anion gap |
| Severe metabolic acidosis seen | pH > 7.3, mild to absent metabolic acidosis |
| Serum osmolarity variable | Serum osmolarity very high , often > 320 mOsm/kg |
| High plasma glucose >250 mg/dl | Very high plasma glucose > 600 mg/dl |
| Serum bicarbonate low | Serum bicarbonate > 15 meq/l |
| Urine and serum ketones present | Urine and serum ketones often absent or present in traces |
Management is with intravenous fluid hydration, beginning with 0.9% saline, followed by 0.45% saline when the estimated or corrected serum sodium level is in the normal range. Once the blood glucose level reaches about 300 mg/dl, fluids should be changed to 5% dextrose with 0.45% saline.
Serum osmolarity should be decreased gradually, especially in children, to prevent cerebral edema. Insulin should preferably be given as an infusion to slowly decrease the blood sugar level to 200-300 mg/dl; subcutaneous insulin can be used after that.
Electrolyte management, including potassium, phosphate, and magnesium, is similar to DKA. Use caution in the presence of full-blown renal failure. Antibiotics should be given if an infection is present. Patients with HHS are at increased risk of thrombo-embolic complications and rhabdomyolysis.
Diabetic retinopathy: Both proliferative and nonproliferative retinopathy are seen in DM. It begins with small microaneurysms, dot and blot hemorrhages, hard exudates from leaky capillaries, and macular edema with loss of visual acuity. “Cotton wool” exudates result from retinal ischemia and infarction. Neovascularization may involve the vitreous and optic disc, causing visual loss, retinal detachment, and cataracts.
Diabetic nephropathy: It begins as microalbuminuria, followed a few years later by overt proteinuria, hypertension, nephrotic syndrome, and ESRD. End-stage renal disease is characterized by small, atrophic kidneys with diffuse glomerulosclerosis.
Diabetic neuropathy: Diabetes can involve peripheral nerves, including sensory and motor nerves throughout the body, so symptoms depend on the area involved. It may present as paresthesias (numbness and tingling in a glove and stocking distribution), hypoaesthesia, burning pain,
peripheral vascular, weakness, sensory loss, slowing of gastrointestinal motility, diarrhea, impotence, retrograde ejaculation, urinary incontinence, dizziness, resting tachycardia, postural hypotension, cranial nerve palsies, absent reflexes, and carpal tunnel syndrome.
Treatment of sensorimotor neuropathies includes gabapentin, pregabalin, carbamazepine, TCAs, SSRIs and SNRIs, phenytoin, lidocaine, and topical capsaicin. Gastroparesis is treated with metoclopramide and erythromycin. Neuropathy and microvascular changes causing ischemia lead to diabetic ulcers.
Cardiovascular complications: Coronary artery disease is more common in diabetics than non-diabetics and occurs at a younger age. It is associated with nephropathy. Vascular endothelium is damaged by glycosylation, which predisposes to thrombus formation and atherosclerosis.
Diabetes predisposes to malignant otitis externa (caused by Pseudomonas), candidiasis, mucormycosis, and Dupuytren’s contractures.
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