Prevention and Therapy of Steroid-Induced Diabetes

Fig. 64.1

Suggested screening and treatment algorithm for glucocorticoid-induced DM

64.4 Prediabetes

Thus far, we have discussed the pathophysiology and recognition of overt diabetes mellitus. However, it is important to recognize that, while some patients may not meet the requirements for diagnosis of DM, they may have levels of hyperglycemia that increase their risk for DM relative to the rest of the population. These individuals are said to have prediabetes, which may be diagnosed when there is one of the following [8]:

Impaired fasting glucose – fasting plasma glucose of 100–125 mg/dL (5.6–6.9 mmol/L)
Impaired glucose tolerance with 2-h OGTT – plasma glucose levels of 140–199 mg/dL (7.8–11.1 mmol/L)
Hemoglobin A1C 5.7–6.4 %

These patients are also at greater risk for developing cardiovascular disease; therefore, early screening and intervention is strongly recommended.

Patients diagnosed with prediabetes should receive diabetic counseling. In addition, these patients should have a goal of losing 7 % of their body weight and 150 min of moderate exercise each week [8]. Several large-scale studies have shown that lifestyle intervention alone can reduce the rate of conversion to overt diabetes. One study found this reduction to be 43 % at 7 years [12]. Lifestyle modification has been found to be more effective than metformin in some studies, but the ADA cites other studies to support the use of metformin in patients with BMI >35 kg/m², those with a history of gestational diabetes, and those with severe hyperglycemia [8].

64.5 Management

Although it is unlikely that the same practitioner implementing glucocorticoid therapy will also initiate and manage diabetic therapy, it is important for all practitioners involved in the care of AIBD to be aware of treatment options for glucocorticoid-induced diabetes. While the literature describes several different approaches to the treatment of glucocorticoid-induced diabetes, the practitioner must ultimately choose a medication regimen that is safe, effective in controlling hyperglycemia, and easy to follow.

First, it is important to ensure patients are on the lowest steroid dose possible that allows proper control of their AIBD. Doing so will lower the incidence of diabetes as the risk of glucocorticoid-induced diabetes increases with increasing dose. Diet and exercise, while effective in treating other forms of DM, may be less feasible in glucocorticoid-induced diabetes since diet may be hampered by the increase in appetite seen with steroid use, and patients with severe, extensive AIBD may be unable to participate in exercise due to the number and location of open lesions [3]. For these reasons, it is likely that the patient will require medication in addition to lifestyle modification.

64.5.1 Medical Intervention: Oral Hypoglycemics

Therapy is often initiated with oral hypoglycemic agents with selection based on the glucose levels of the patient and the side effect profile of the medication.

The only biguanide available in the USA is metformin. Metformin decreases hepatic gluconeogenesis and increases peripheral insulin sensitivity [4]. It is associated with only a small risk of hypoglycemia (when used as monotherapy) and promotes modest weight loss. Gastrointestinal side effects, such as nausea, abdominal pain, and diarrhea, may be avoided by starting with a low dose and slowly increasing as tolerated [4]. There is a rare but potentially life-threatening side effect of lactic acidosis in patients with chronic kidney disease and heart failure. However, there is a lack of long-term studies to determine the safety of this medication in this population.

Sulfonylureas inhibit the ATP-dependent potassium channel of beta cells, thereby increasing the release of insulin. These agents have a fast onset of action and are recommended for cases of mild hyperglycemia. Long-acting forms such as glyburide can cause hypoglycemia, especially in patients with chronic kidney disease. Glipizide may be a safer alternative. In addition, older sulfonylureas have been linked to increased mortality following myocardial infarction. Meglitinides, such as repaglinide, act in a manner similar to sulfonylureas and they too can cause hypoglycemia.

Thiazolidinediones bind to PPARγ (peroxisome proliferator activator) receptors, causing transcription of genes involved in glucose metabolism. These medications require several weeks to take effect, making them a poor choice in cases of short-term steroid therapy. In addition, they have now been linked to edema, congestive heart failure exacerbations, and increased cardiac events in diabetic patients with heart disease.

DPP-4 inhibitors (gliptins) cause an increase in GLP-1 and GIP concentration, ultimately causing increased insulin secretion and decreased glucagon secretion. Gliptins are advantageous in that they have a low risk of hypoglycemia and a weight neutral profile. However, they produce smaller decreases in A1C than other hypoglycemic, and there have been several reports of gliptin-related pancreatitis.

GLP-1 agonists, such as exenatide, bind to GLP-1 receptors in β[beta] cells and in the brain to cause increased insulin secretion, decreased glucagon secretion, increased satiety, and slowed gastric emptying. GLP-1 agonists promote weight loss to an even greater degree than metformin. However, they can also cause nausea, vomiting, and diarrhea.

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