Page not availableDrug-induced hyperglycemia is a more common complication of various treatment regimens than many physicians may realize. GC-induced hyperglycemia is the most common form of drug-induced hyperglycemia. GC treatment routes include oral, IV, intranasal, inhaled, topical, and localized injections. While all forms of GC administration carry the risk of diabetes, the oral and IV routes are by far the most commonly associated with hyperglycemia and will thus kortikosteroidi za nos the only treatment routes described in this chapter. GCs may be the most diabetogenic nph insulin for steroid induced hyperglycemia all drugs known to induce hyperglycemia.
USE OF NPH INSULIN FOR GLUCOCORTICOID-INDUCED HYPERGLYCEMIA. - PubMed - NCBI
Drug-induced hyperglycemia is a more common complication of various treatment regimens than many physicians may realize. GC-induced hyperglycemia is the most common form of drug-induced hyperglycemia. GC treatment routes include oral, IV, intranasal, inhaled, topical, and localized injections. While all forms of GC administration carry the risk of diabetes, the oral and IV routes are by far the most commonly associated with hyperglycemia and will thus be the only treatment routes described in this chapter.
GCs may be the most diabetogenic of all drugs known to induce hyperglycemia. In transplant patients, tacrolimus is more likely to result in hyperglycemia, especially in pediatric transplant recipients and African Americans, and is estimated to be 5 times as diabetogenic as cyclosporine. The risk of hyperglycemia varies among the different SGAs available on the market.
Discussion of each specific SGA is beyond the scope of this chapter and thus, unless specifically stated, SGAs will be discussed as a group.
This chapter will focus primarily on GC-induced hyperglycemia. In many pediatric oncology protocols, especially for ALL, urine is routinely screened for glucose and ketones. Transplant patients are also screened, although the exact protocol varies.
In patients with ALL , increased risk of infections is seen with hyperglycemia, and infection can be an initial presentation of hyperglycemia.
In patients who are post-transplant , especially kidney transplant recipients, the success of the graft can be compromised if hyperglycemia is present; thus, graft failure can be an initial presenting sign. In both cases, screening enables detection of hyperglycemia before serious complications occur, such as graft failure or infection. Examples of such patients include those receiving GC for rheumatologic diseases and patients with Down syndrome diagnosed with ALL.
The likely mechanism is stress hormones such as cortisol, catecholamines, and growth hormone driving increased glucose production and insulin resistance.
Dose and duration of drug exposure. These factors clearly affect the development of steroid-induced hyperglycemia and likely atypical antipsychotic-induced hyperglycemia. While many cases of L-asparaginase-induced hyperglycemia occur early even after the first dose , most episodes occur during the induction protocol, when the dose of L-asparaginase is highest.
Multiple drugs causing hyperglycemia used together. The addition of GCs to other drugs known to be diabetogenic significantly increases the likelihood of diabetes. Underlying disease and intercurrent illness. In some cases, particularly in oncology or transplant patients, the exact cause of hyperglycemia may not be known. Some authors have suggested that leukemia alone increases the likelihood of diabetes. Critical illness or sepsis also increase the risk.
In both leukemia and sepsis, cytokines may play a role in causing hyperglycemia. L-asparaginase, tacrolimus, and GCs each can cause pancreatitis, which can cause secondary hyperglycemia.
Uremia in renal failure can cause insulin resistance, and cirrhosis in hepatic failure can result in an abnormal OGGT in pre-transplant evaluation. Resolution is expected with a successful transplant, but may not if hyperglycemia causes graft dysfunction. Combination of risk factors. The risk of diabetes increases sharply when more than one risk factor is present, and appears to be proportionate to the number of risks present.
A serum glucose is mandatory. A high glucose obtained by glucometer or D-stick should be confirmed on a venous sample. A confirmatory laboratory test based on measurements of venous blood glucose must be done on another day in the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation. In patients at risk for beta cell failure, urine should be tested for ketones.
The presence of ketones implies insulin deficiency and increases the risk of diabetic ketoacidosis DKA. In patients suspected of hyperglycemic hyperosmolar syndrome HHS , a serum osmolarity should be measured directly or calculated. The diagnosis of HHS should also prompt a urine test for myoglobulin and creatine kinase CK levels for evaluation of rhabdomyolysis. A normal HbA1c, however, is not reassuring as the duration of hyperglycemia may not have been sufficient to raise the level to the diabetic threshold.
A diabetes auto-immune pane l may be drawn in cases where type 1 diabetes is also suspected. Antibodies against beta cell antigens are present as markers of disease. Anti-glutamic acid decarboxylase GAD 65 and anti-islet cell antibodies are most specific and sensitive for the diagnosis of type 1 diabetes. Anti-insulin antibodies are less specific but are also included in the panel. There are no formal decision algorithms cited in the literature specifically addressing the evaluation and confirmation of drug-induced hyperglycemia in children.
The following suggestions are based on literature and the author's best clinical reasoning: Confirm hyperglycemia see above. Exclude the possibility of other causes of hyperglycemia, particularly in those patients at risk for type 1 and type 2 diabetes and other less common types of diabetes. Ideally, patients and families should be counseled about the risk of hyperglycemia before treatment has been initiated.
In , a consensus development conference was held to address the issue of diabetes and obesity in patients treated with SGAs. No specific definition of diabetes was proposed; however, recommendations were made about screening for diabetes in patients treated with an SGA. Baseline BMI, family history, fasting glucose, BP and lipid profiles are suggested, and continued frequent monitoring of weight is recommended.
A fasting glucose level should be measured every 3 months and then annually. In addition, they suggested that health care professionals, patients, families, and caregivers should be informed about the signs and symptoms of diabetes, especially those suggestive of metabolic decompensation such as DKA.
There were no recommendations specific to the use of an SGA in children. Diabetes Care ;27 2: Treatment should be initiated urgently and is identical to the treatment of DKA or HHS in children with either type 1 or type 2 diabetes. The type and dose of insulin should be determined based on the patient's clinical status, blood sugars, and age.
The various types of insulin available are the same as those used in patients with type 1 diabetes. Attention should be paid to the timing of the peak glucose with an aim to choose an insulin best suited to minimize glucose excursions while avoiding hypoglycemia and minimizing the number of daily injections.
GC given IV or PO often results in hyperglycemia hours after dosage administration, which can be treated with an insulin whose peak of action also occurs hours after administration, such as regular or neutral protamine Hagedorn NPH insulin.
In most patients, an initial starting dose of 0. Subsequent doses of insulin are determined by blood sugars. The frequency of monitoring of blood glucose levels depends on the type of insulin therapy chosen. Management of hyperglycemia in oncology patients: The goal of therapy is focused on avoiding extreme hyperglycemia to prevent development of DKA or HHA, and to stop the continued loss of fluids and calories in the urine. Strict glucose control can be dangerous, because insulin requirements vary greatly depending on the timing of steroid and L-asparaginase administration.
Hyperglycemia resolves spontaneously in most cases. Insulin doses should thus be decreased rapidly in response to lowered glucose levels. In some cases, GC or L-asparaginase doses can be decreased, but this decision should be made in consultation with the treating oncology team. Dietary modification may provide additional therapeutic benefits, but precautions should be taken with patients receiving chemotherapy because adequate protein and calorie intake are necessary to prevent the lean body mass loss associated with chemotherapy.
For patients with persistent hyperglycemia managed as outpatients, exercise and dietary modifications may be sufficient. Insulin therapy is added if these measures fail to adequately control hyperglycemia. The choice and dose of insulin, and frequency of blood glucose monitoring are based on the same considerations as in the inpatient setting.
HbA1c levels are not usually necessary because the goals of therapy are different than for patients with other types of diabetes. If levels are measured, consideration of recent blood transfusions is necessary during interpretation of results.
Patients receiving insulin as outpatients must be counseled about the signs, symptoms and treatment of hypoglycemia. A prescription and instruction on the emergency use of glucagon for severe hypoglycemia should be included. Patients and families should also be taught to check urine for ketonuria under the conditions described above.
The period after reperfusion post transplant is critical for graft survival. A normal metabolic milieu promotes graft performance and decreases the incidence of peri-operative infections. The dose of GC should be reduced as early as possible post transplant. A reduction in calcineurin inhibitor CNI dosage or a switch from tacrolimus to cyclosporine should also be considered. An individualized titration of agents and close blood monitoring to ensure optimum immunosuppression is essential.
Patients should also be monitored carefully for clinical evidence of rejection. A similar approach is reasonable in children although the glycemic targets may differ because of the increased risks associated with hypoglycemia in children. See section on type 1 diabetes treatment goals.
In adults, non-pharmacologic interventions such as lifestyle modification are the first step and can be done safely in children. The age of the patient may determine the choice of pharmacologic agents used in subsequent steps. The precise intervention to achieve optimal glycemic control will vary with each individual patient. The choice of insulin, dose of insulin, and frequency of blood glucose monitoring are based on the same considerations as in the inpatient setting.
With the initiation of insulin therapy, patients and families should be educated about hypoglycemia and ketonuria as described above. Self-blood glucose monitoring should performed with age-based glycemic targets similar to that used in children with type 1 diabetes.
If treatment is non-pharmacologic or is limited to metformin monotherapy, a measurement 2 hours after the largest carbohydrate-containing meal should be sufficient. Once insulin treatment is initiated, the monitoring schedule is determined by the specific type of insulin used.
HbA1c levels should be monitored but should not be drawn for at least 3 months post transplant because of the high likelihood of transfusion in the peri-operative period. HbA1c goals should be age-based as per ADA recommendations of treatment of diabetes in children link to section on type 1 diabetes treatment goals. Decrease the dose of GC. Even small decrements can produce significant reduction in blood glucose levels enabling decreased doses of insulin or even cessation of treatment.
If mild hyperglycemia in the outpatient setting persists despite GC dose adjustment and the patient is older than 10 years of age, one could consider treatment with metformin using the same doses as used in children with type 2 diabetes.