Acute and chronic complications of diabetes
1. What are the acute complications of diabetes?
Hyperglycemia and hypoglycemia; both are the result of an imbalance between medications (insulin or oral diabetic agents) and the patient’s food intake and exercise.
2. Describe the symptoms of hyperglycemia.
Initial symptoms are increased thirst (polydipsia), increased urination (polyuria), fatigue, and blurry vision. If uncorrected, hyperglycemia may eventually lead to diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic syndrome (HHS). Rather than distinct entities, DKA and HHS represent a spectrum of a disease process characterized by varying degrees of insulin deficiency, overproduction of counterregulatory hormones, and dehydration. In some situations, features of both DKA and HHS may occur concurrently.
DKA is a state of uncontrolled catabolism triggered by a relative or absolute deficiency in circulating insulin. The DKA triad is hyperglycemia (blood glucose [BG] usually > 250 mg/dL), metabolic acidosis (pH < 7.35), and ketonuria. Insulin deficiency is accompanied by a reciprocal elevation in counterregulatory hormones (glucagon, epinephrine, growth hormone, and cortisol), which causes increased glucose production by the liver (gluconeogenesis) and catabolism of fat (lipolysis). Lipolysis provides the substrate (free fatty acids) for the uncontrolled production of ketones by the liver. The production of ketones then leads to metabolic acidosis.
Any disorder that alters the balance between insulin and counterregulatory hormones can precipitate DKA. A minority of cases occurs in people not previously diagnosed with diabetes, but most cases (up to 80%) occur in people with previous diagnoses. DKA is most often associated with type 1 diabetes; however, it may also occur in older patients with type 2 diabetes, particularly when associated with a major intercurrent illness.
5. What illnesses may trigger DKA?
Infection and myocardial infarction are the illnesses most commonly known to trigger DKA. Even localized infections, such as urinary tract infections and prostatitis, have precipitated DKA. Other triggers are severe emotional stress, trauma, medications (i.e., corticosteroids), and hormonal changes (i.e., preovulation) in women. Nonadherence and improper insulin self-management during an intercurrent illness are other common causes of DKA. Both represent a lack of knowledge and may be remediated through appropriate education (sick day rules to frequently measure glucose/ketones) or psychological intervention.
6. What are the signs and symptoms of DKA?
Nausea and vomiting, generalized abdominal pain, dehydration, rapid (Kussmaul) respirations, and a sweet (acetone) odor on the breath represent the classic clinical picture. In addition, patients may have an altered mental status and symptoms due to their possible precipitating illness.
DKA should be suspected if the patient presents with marked hyperglycemia (BG > 250 mg/dL) and metabolic acidosis (pH < 7.35). An elevated anion gap (> 13 mEq/L) is usually, but not always, present. The finding of elevated ketones in the blood or urine confirms the diagnosis.
8. Is the ketone test result always positive with DKA?
No. If blood or urine ketone results are negative and DKA is strongly suspected, treatment with fluids and insulin should still be initiated. During the course of treatment, the blood and urine ketones test results will become positive. This “delay” in positivity for measured ketones is due to a limitation of the laboratory test for ketones, which detects only acetoacetate. The predominant ketone in untreated DKA is beta-hydroxybutyrate. As DKA is treated, acetoacetate becomes the predominant ketone, causing the test for ketones to turn positive.
9. What lab tests are recommended in the first hour of treatment for DKA?
Baseline electrolytes, blood urea nitrogen (BUN), creatinine, and glucose measurements, anion gap calculation, urinalysis, urine and blood ketone measurements, and electrocardiogram (ECG) should be performed.
Fluid intake, urine output, and progression of laboratory changes should be recorded.
10. Summarize the strategy for fluid and potassium administration in the first hour.
11. How should insulin treatment be started with DKA?
An initial IV bolus of 10 to 20 units of regular insulin should be followed by a continuous infusion of 0.5 units/mL of regular insulin mixed in normal saline at a rate of 5 to 10 units per hour (0.1 unit/kg/h).
12. Summarize the strategy for clinical assessment, and fluid and potassium administration in the second hour of treatment.
Fluids: Continue normal saline at approximately 1 L/h.
Potassium: Adjust or add KCl to IV fluids to maintain serum potassium at 4 to 5 mEq/L.
Repeat measurements of electrolytes, BG, and urine and blood ketones. Calculate anion gap.
13. How should insulin be adjusted during treatment?
If the serum glucose drops to less than 250 mg/dL, fluids should be changed to a 5% to 10% dextrose–containing solution. The insulin infusion rate may be doubled if the serum glucose does not decline after the first hour. The optimal rate of glucose decline is 100 mg/dL/h. The glucose level should not be allowed to fall to less than 250 mg/dL during the first 4 to 5 hours of treatment.
14. Summarize the basic strategy after the second hour of treatment.
Assess the patient and repeat previously discussed lab tests hourly.
Potassium: Continue to adjust to a goal serum value of 4 to 5 mEq/L.
Insulin: Continue IV infusion as long as acidosis is present; supplement with dextrose as necessary.
15. When can the insulin infusion be discontinued?
When the anion gap corrects to normal, the pH is 7.3 or greater, or the serum bicarbonate is 18 mEq/L or greater, the patient can be given a subcutaneous dose of regular insulin or a short-acting insulin analog (lispro, aspart, glulisine) to cover a meal. The infusion should be stopped 30 minutes after the subcutaneous insulin is given. If the patient is unable to eat, give 5 units of regular or a short-acting insulin analog, continue the IV dextrose solution, and give supplemental short-acting insulin every 4 hours on the basis of the glucose level.
16. What other interventions may be necessary in the treatment of DKA?
If the initial serum phosphorus is less than 1.0 mg/dL, consider giving 10 to 20 mEq/h potassium phosphate in the IV fluids.
Bicarbonate (in the form of sodium bicarbonate) replacement is not recommended unless other causes of severe acidosis are present (e.g., sepsis, lactic acidosis) or the arterial pH is less than 6.9. If used, sodium bicarbonate should be diluted in the IV fluids and given over 1 hour.
17. What is hyperosmolar hyperglycemic syndrome?
Formerly known as hyperosmolar hyperglycemic nonketotic syndrome or coma, and described first in 1957 by Sament and Schwartz, hyperosmolar hyperglycemic syndrome (HHS) is a constellation of hyperglycemia, hyperosmolarity, and altered level of consciousness, most typically in the absence of acidosis.
18. Who is at risk for HHS and why?
Elderly patients, with or without a history of type 2 diabetes, are at particular risk for HHS because of a higher rate of impaired thirst perception and increased prevalence of impaired renal function. Precipitating factors, such as infection, myocardial infarction, cerebrovascular events, pancreatitis, gastrointestinal hemorrhage, and use of exogenous medications, may also be present.
19. What are the signs of HHS?
Marked hyperglycemia (BG > 600 mg/dL)
Hyperosmolarity (serum Osm > 320 mOsm/L)
Hyperglycemia, once triggered, leads to glycosuria, osmotic diuresis, hyperosmolarity, cellular dehydration, hypovolemia, shock, coma, and, if untreated, death.
20. Why is ketoacidosis typically not seen in HHS?
Although glucose levels are generally higher in HHS than in DKA, the residual insulin secretory capacity of type 2 diabetics likely prevents severe acidosis and ketosis in HHS. The presence of circulating insulin or lower levels of counterregulatory hormones (or both) prevents lipolysis and significant ketone production. Lactic acidosis may be seen, however.
21. What are the symptoms of HHS?
Polyuria and polydipsia often occur days to weeks before manifestation of HHS. Patients are unable to drink enough to match a brisk osmotic diuresis, exacerbating the hyperglycemia. The imbalance of fluid intake and output eventually results in impairment of renal function, decrease in glucose excretion, and further worsening of hyperglycemia. Profound dehydration is typical. Fever is not part of the syndrome and, if present, suggests an infectious component. Focal neurologic defects may be seen in patients, including bilateral or unilateral hyporeflexia or hyperreflexia, seizures, hemiparesis, aphasia, presence of Babinski sign, hemianopsia, nystagmus, visual hallucinations, acute quadriplegia, and dysphagia.
22. What is the most common presenting symptom of HHS?
Altered mental status occurs in approximately 90% of cases and is the most common reason that patients are brought to the hospital. An effective osmolarity higher than 340 mOsm/L is required for coma to be attributed to HHS and is present in 10% of patients upon presentation. Effective osmolarity refers to the true osmolarity seen by the cells and is calculated by means of the following equation:
23. What is the hallmark laboratory finding in patients with HHS?
Marked hyperglycemia (BG > 600 mg/dL and often > 1000 mg/dL) is characteristic: The serum sodium concentration is often factitiously low. To correct for the hyperglycemia, the following formula is used:
Other laboratory abnormalities include elevated BUN and creatinine, hypertriglyceridemia, and leukocytosis.
24. What is the first step in treating HHS?
Aggressive volume resuscitation is imperative and should be addressed before insulin administration to avoid intracellular fluid shifts (from falling glucose levels) that may worsen systemic perfusion. The fluid deficit is typically severe—on the order of 9 to 12 L. In patients with renal insufficiency or cardiac disease, central venous access may be necessary to monitor the response to therapy, and patients with altered mental status may require an indwelling urinary catheter.
25. Should isotonic or hypotonic fluids be used?
There is controversy regarding this issue; however, isotonic (0.9%) saline at a rate of approximately 1 to 2 L over the first hour is generally recommended. After the first hour, fluids may be changed on the basis of the serum sodium concentration: If serum Na is between 145 and 165 mEq/L, a change to half-normal saline (0.45%) may be considered; if serum Na is lower than 145 mEq/L, isotonic saline should be continued. Replacement of one half of the calculated fluid deficit over the initial 5 to 12 hours is recommended, with the balance of the deficit replaced over the subsequent 12 hours.
26. What role does insulin play in the treatment of HHS?
Continuous IV insulin infusion, as previously described for DKA, is helpful to reduce glucose levels at a predictable rate. Patients may be transitioned directly from IV to subcutaneous insulin as described for DKA. Because the presence of HHS suggests a significant insulin deficiency, most patients require discharge after being started on an insulin regimen, with the appropriateness of oral agents determined in the outpatient setting.
27. Describe the signs and symptoms of hypoglycemia.
To be defined as hypoglycemia-induced, Whipple’s triad (low blood glucose, symptoms consistent with hypoglycemia, and resolution of symptoms by raising blood glucose) must be present. Symptoms can be divided into adrenergic and neuroglycopenic symptoms (Table 2-1
