Diabetic ketoacidosis or DKA: It is commonly seen in type 1 DM and in some cases of type 2 DM who have decreased secretion of insulin. It may be precipitated by an intercurrent infection, noncompliance with insulin or illicit drug use. There is insulin deficiency along with increased glucagon, catecholamines, cortisol and growth hormone. As the body is unable to use glucose, there is increased lipolysis and release of free fatty acids, some of which are converted into ketone bodies. Acetone, acetoacetic acid and beta hydroxybutyric acid are the ketone bodies formed. Hyperglycemia leads to osmotic diuresis, dehydration and hyperosmolarity. It presents with polyuria, polydipsia, weight loss, fatigue, vomiting, nausea, abdominal pain, orthostatic hypotension, lethargy and coma. Metabolic acidosis causes Kussmaul respirations. Acetone in breath gives a fruity smell. Laboratory findings include elevated serum glucose level > 250 mg/dl, an elevated serum and urine ketone levels and high anion gap metabolic acidosis with pH < 7.3 and a serum bicarbonate level < 18 mEq/L. Urine dipstick does not measure beta hydroxybutyrate which is the predominant ketone body in DKA. Urine analysis will measure acetone and acetoacetate. Potassium levels may be normal or low. Amylase and lipase may be elevated. Chest X ray, urine and blood cultures should be done to look for foci of infection. Management includes fluid replacement with intravenous normal saline (0.9% NS) followed by half-normal saline (0.45% NS), intravenous insulin to maintain blood glucose between 150-200 mg/dl. DKA is resolved when the glucose level is <200 mg/dl, the pH is > 7.3 and the bicarbonate level is = or >18 meq/L. Hyperosmolarity may cause pseudohyponatremia. Potassium levels have to be carefully monitored. Goal is to maintain serum potassium levels between 4 to 5 meq/L. Potassium should be supplemented with the intravenous fluids. If serum potassium falls below 3 meq/L, insulin should be temporarily halted, while when the potassium is > 5 meq/L, potassium replacement can be temporarily halted. 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 like lethargy, headache, tachypnea, vomiting and incontinence. CT scan can confirm the diagnosis.
Hyperosmolar hyperglycemic state or HHS: It is seen typically in type 2 diabetics. It is characterized by severe dehydration, marked hyperglycemia, increased serum osmolarity with mild to absent ketosis. It carries a high mortality rate. Excess glucose is produced by increased glycogenolysis, gluconeogenesis and reduced peripheral glucose uptake. Resulting hyperglycemia increases osmolarity of the plasma causing osmotic diuresis and dehydration. As some amount of 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 like UTI, pneumonia etc, substance and alcohol abuse, AMI, stroke, PE, antipsychotics, glucocorticoids, diuretics etc. Many times patients with undiagnosed DM may initially present with HHS. Clinical features include low-grade fever, signs and symptoms of dehydration like decreased skin turgor, dry tongue and mucosa, weak pulse; 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, 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 there is reduction in total body potassium. 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 by intravenous fluid hydration, beginning with 0.9% saline, followed by 0.45% saline when the estimated or corrected serum sodium level is in normal range. Once the blood glucose level reaches about 300 mg/dl, fluid 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 be given preferably 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. Caution should be taken 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 from retinal ischemia and infarction, neovascularization which 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 involves peripheral nerves including sensory and motor nerves all over the body and symptoms depend on the area involved. It presents as paresthesias (numbness and tingling in 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 is with 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 it to thrombus formation and atherosclerosis.
Diabetes predisposes to malignant otitis externa (caused by Pseudomonas), candidiasis, mucormycosis and Dupuytren’s contractures.
Sign up for free to take 2 quiz questions on this topic