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Observations LETTERS introducing detemir. However, we can- might worsen glycemic control (1) OBSERVATIONS not exclude that an excipient rather than whereas some of them might be neutral insulin detemir itself could be responsible (2) or improve glycemic control (3), and for this allergy. Nevertheless, the only ad- their effects on glucose metabolism are ditive present in detemir preparation and controversial. Pitavastatin, an HMG-CoA Type III Allergy to not in glargine or aspart preparations is reductase inhibitor, has been available in Insulin Detemir mannitol, and allergy to mannitol is ex- Japan since 2003 (4) and the Republic of ceptional and related to IgE-mediated Korea since 2005, and its effect on glucose anaphylaxis (type I reaction) (2). To our metabolism in diabetic patients remains llergy to insulin has become rare knowledge, we report here the first case of unknown. Since safe use of statins is im- with human recombinant insulin or allergy with insulin detemir. portant for patients, we evaluated the ef- A its analogs, with an estimated inci- fects of pitavastatin on lipid and glucose Ͻ 1 dence of 1%. The most common clini- PATRICE DARMON, MD metabolism in this study. 1 cal situation is related to the type I allergic VIRGINIE CASTERA, MD A total of 79 type 2 diabetic patients 2 reaction in the Gell and Coombs classifi- MARIE-CHRISTINE KOEPPEL, MD (47 men and 32 women; mean age Ϯ SD 1 cation and usually consists of a local CATHY PETITJEAN, MD 61.7 Ϯ 12.1 years; BMI 26.7 Ϯ 4.2 kg/ 1 2 wheal-and-flare eruption at injection site ANNE DUTOUR, MD, PHD m ) with hypercholesterolemia who had with induration, pruritus, and burning never been treated with statins and at- sensation that appear a few minutes after From the 1Department of Endocrinology, Hoˆpital 2 tended one of five outpatient diabetic the injection and last for 1–2 h; this reac- Nord, Marseille, France; and the Department of clinics were enrolled. Informed consent tion is rarely systemic, with urticaria, an- Dermatology, Hoˆpital Nord, Marseille, France. Address correspondence to Dr. Patrice Darmon, was obtained from all subjects. This study gioedema, or anaphylactic shock. Insulin Service d’Endocrinologie, des Maladies was designed as an 8-week intervention can also be infrequently responsible for a Me´taboliques et de la Nutrition, CHU Nord, 13915 period with new administration of late type III Arthus’ reaction, character- Marseille, France. E-mail: [email protected]. pitavastatin (1 or 2 mg/day). Fasting ized by the development of subcutaneous © 2005 by the American Diabetes Association. plasma glucose, HbA1c, LDL cholesterol, nodules at the injection site 2–6 h after ●●●●●●●●●●●●●●●●●●●●●●● HDL cholesterol, triglycerides, aspartate administration (1). And last, insulin al- aminotransferase, alanine aminotransfer- lergy may be rarely related to a type IV References ase, ␥-glutamyl-transferase, and creatine T-cell–mediated delayed reaction that ap- 1. Silva ME, Mendes MJ, Ursich MJ, Rocha phosphokinase levels were measured DM, Brito AHM, Fukui RT, Ruggeri GB, pears 8–12 h after injection, peaks at both before and after 8 weeks of pitava- 24 h, and lasts for several days with pain- Nery M, Wajchenberg BL: Human insulin allergy-immediate and late type III reac- statin treatment. Differences in these pa- ful, itchy, local mononuclear infiltration. tions in a long-standing IDDM patient. rameters pre- and posttreatment were To our knowledge, we report the first Diabetes Res Clin Pract 36:67–70, 1997 analyzed using Wilcoxon’s matched-pair case of type III allergy to the new long- 2. Hedge VL, Venkatesh YP: Anaphylaxis to signed-rank test. acting insulin analog detemir. A 31-year- excipient mannitol: evidence for an im- Pitavastatin treatment resulted in a old man with type 1 diabetes for 20 years munoglobulin E-mediated mechanism. significant decrease in LDL cholesterol was admitted for uncontrolled diabetes. Clin Exp Allergy 34:1602–1609, 2004 levels (from 4.28 Ϯ 0.69 to 2.70 Ϯ 1.03 He had no history of any allergy. He had mmol/l, P Ͻ 0.0001) and triglyceride lev- been treated by glargine (Lantus; Sanofi- els (from 1.71 Ϯ 0.76 to 1.54 Ϯ 1.09 Aventis) once daily and aspart (No- Efficacy of mmol/l, P Ͻ 0.0001), whereas the change vorapid; Novo Nordisk) before each meal Pitavastatin, a New in HDL cholesterol levels did not reach for 2 years. We decided to switch insulin HMG-CoA Reductase statistical significance (from 1.29 Ϯ 0.32 glargine for detemir to optimize glycemic to 1.33 Ϯ 0.33 mmol/l, P ϭ 0.055). Con- control. Six hours after the first injection Inhibitor, on Lipid cerning glycemic control, changes in fast- of detemir, the patient presented a subcu- and Glucose ing plasma glucose levels (from 8.20 Ϯ taneous small, subdermal, nonprurigi- Ϯ Metabolism in 2.71 to 8.27 2.10 mmol/l) and HbA1c nous, slightly painful nonerythematous levels (from 7.25 Ϯ 1.60 to 7.27 Ϯ nodule with central hematoma at injec- Patients With Type 2 1.47%) were not statistically significant. tion site (left arm). On the 2 following Diabetes Changes in other available parameters days, the same localized reaction oc- were also not statistically significant. No curred 4–6 h after the detemir injection subject terminated the trial because of ad- (right arm, left thigh), although no reac- ype 2 diabetes is one of the risk fac- verse events. tion to aspart was noticed. Local factors tors for macrovascular disease. Our results showed that pitavastatin such as poor injection technique, misuse T Treatment of hypercholesterolemia is a potent agent for lowering LDL cho- of insulin injector, or use of impure alco- is important in patients with type 2 dia- lesterol level and that it does not affect hol were ruled out. Detemir was then betes to prevent macrovascular disease. glycemic control in patients with diabe- switched back for glargine. The nodules The 3-hydroxy-3-methyl glutaryl- tes. Although statins have been widely spontaneously disappeared in ϳ48 h. coenzyme A (HMG-CoA) reductase in- prescribed all over the world and are re- We did not perform skin tests be- hibitors (statins) are key drugs to lower garded as the first choice for hyper- cause of the explicit clinical presentation the cholesterol level not only in nondia- cholesterolemia, physicians must pay of a type III allergy and because of the betic patients but also in patients with attention to the adverse effects of these potential risk of serum sickness after re- type 2 diabetes. However, some statins agents, e.g., myotoxicity, liver dysfunc- 2980 DIABETES CARE, VOLUME 28, NUMBER 12, DECEMBER 2005.
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