Start Insulin at Lower Dose for Diabetes Patients with Renal Insufficiency

In a randomized trial, the authors saw a trend toward less hypoglycemia in patients who were started on lower doses.

Dr. David Baldwin from Rush University, Chicago, stated that, "Chronic renal failure has profound effects on the pharmacokinetics of injected insulin." "In order to avoid excess hypoglycemia, one needs to reduce initial insulin dosing in this patient group."

Dr. Baldwin and colleagues compared the effects of starting with a standard 0.5 U/kg/day dose or a reduced dose of 0.25 U/kg/day, in 107 adults with type 2 diabetes and a glomerular filtration rate below 45 mL/min. The patients in this study were not critically ill. Doses were adjusted based on four-times-daily blood glucose measurements on each of the six study days. Patients stopped receiving any oral diabetes medications when they were admitted.

Mean blood glucose was similar with the standard dose and the reduced dose on study day one (196.1 vs 196.9 mg/dL) and all subsequent days. The two groups were also similar in the percentage of blood glucose values that fell within the target range of 100 to 180 mg/dL during each of the six study days.

In contrast, more patients in the standard-dosage group (30%) than in the reduced-dose group (15.8%) experienced hypoglycemic episodes (p=0.08). Also, at least one severe hypoglycemic episode (blood glucose <50 mg/dL) occurred in 6% of the standard-dosage group, compared with 1.8% of the reduced-dosage group.

"Current guidelines for insulin dosing in hospitalized patients do not suggest specific modifications depending on the level of GFR," the researchers note. "Our study is the first to provide direct evidence for the benefit of a dose reduction for such patients."

"We believe that our findings apply to all patients with renal insufficiency who begin insulin in the hospital," Dr. Baldwin said. "Although we used two insulins, glargine and glulisine, in our study, we believe that the results are applicable to the use of other insulins as well, such as NPH, detemir, aspart, regular, and lispro. Remember that all patients stopped their oral anti-diabetic agents on hospital admission."

Dr. Baldwin said, "It is important to assess kidney function and the degree of renal failure by calculating the estimated GFR." "Relying on simple serum creatinine levels will often underestimate the degree of renal dysfunction, especially in older individuals."

He added, "Another fundamental question facing physicians who care for in-patients with diabetes is what anti-diabetic therapy to send them home on when they are ready to be discharged. Extrapolation from outpatient guidelines would suggest that HBA1C be checked on every patient with diabetes admitted to the hospital and that this HBA1C level be used to guide discharge therapy for diabetes, including initiation and continuation of insulin therapy. We hope to launch a prospective study to evaluate the long-term benefits of this approach."

Diabetes Care Online June 14, 2012