Eating disorders are frequent causes of chronic failure of blood glucose control in young type 1 diabetic women (1) that result in a high incidence of diabetic complications (2). Moreover, severe disorders such as bulimia and binge eating are commonly associated with inappropriate compensatory behaviors to avoid weight gain, including self-induced vomiting, insulin misuse, laxative or diuretic surreptitious intake, and hyperactivity (3). Because these impulsive attitudes develop as addictions, naltrexone, an antagonist of endogenous opiates that is currently used to help weaning off alcohol, opiates, or heroin, might be considered a potentially effective therapy. Of note, recent data (4) report significant improvements obtained with naltrexone in bulimic patients, reinforcing the hypothesis of an opioid-mediated dependence.
To assess the effectiveness of naltrexone in type 1 diabetic women presenting bulimia or binge eating, we conducted an open-label, 1-year pilot trial in 10 patients affected by these eating disorders who did not respond to antidepressive drugs, behavioral therapy, and interpersonal psychotherapy. All patients volunteered and gave their informed consent to enter the trial, which was ethically approved. Mean age of the patients was 22 years (range 17–29), with type 1 diabetes history of 8 years (range 5–15). Initial BMI was 25 ± 6 kg/m2. One patient affected by binge eating presented morbid obesity (BMI 41.5 kg/m2). Blood glucose control at enrollment was very poor, as shown by HbA1c levels (mean ± SD), which were 11.6 ± 1.6% (by high-performance liquid chromatography, normal range <5.6%). Eating disorders included binge eating in three subjects (with 14, 21, and 26 episodes per week, respectively) and bulimia in seven subjects (7–18 episodes per week) and were also associated with “purging” behavior (self-vomiting) in six subjects (7–21 episodes per week), according to the Diagnostic and Statistical Manual of Mental Disorders IV classification. No psychiatric comorbidity was diagnosed. The mean history of severe eating disorders was 6 years (range 4–11). All patients received oral naltrexone 200 mg b.i.d. (Bristol Myers Squibb, Paris, France) for 1 year. Follow-up included a monthly evaluation of the weekly occurrence of impulsive eating with or without purging episodes as the main outcome and monthly measurement of body weight and HbA1c assay every 2 months as secondary outcomes. Psychological assessment by self-administered Eating Disorder Inventory 2 questionnaire was performed before and at the end of the trial.
Results after 2 months and 1 year are presented here to estimate the rapidity and maintenance of drug response. Weekly binge-eating episodes were dramatically reduced by 42, 62, and 86%, respectively, as early as in the first 2 months and remained reduced by 31, 52, and 86%, respectively, after 1 year in the three patients affected by this eating disorder. Weekly bulimic crises were reduced by 50% (range 16–88) after 2 months and by 64% (range 29–94) after 1 year, while associated purging decreased by 74% (range 50–86) and 75% (range 52–100) during the same time periods. The only patient with nonpurging bulimia reduced her weekly crises by 71% after 2 months, which was sustained after 1 year. Meanwhile, body weight decreased by 3–5% after 2 months and by 5–7% after 1 year in binge eaters, and HbA1c levels moved from 11.3, 12.1, and 14.1% to 10.4, 9.8, and 10.2% after 2 months and to 9.0, 8.7, and 9.8% after 1 year, respectively. Body weight remained stable over 1 year in bulimic patients, except in the nonpurging subject, who lost 5% of her initial weight. However, HbA1c levels (mean ± SD) improved from 11.6 ± 1.2 to 10.1 ± 0.6% after 2 months and to 9.0 ± 0.9% after 1 year in these patients. Scores of the Eating Disorder Inventory 2 questionnaire dramatically improved concerning “attitude toward impulsiveness” (data not shown, P < 0.01) and also improved at a lower level concerning “low self-esteem” (data not shown, P < 0.05), regardless of which eating disorder. No undesirable clinical or biological (liver enzymes and creatininemia) side effects were noted during the trial.
Similar to results obtained with naltrexone in nondiabetic subjects, our data show a dramatic improvement in impulsive eating disorders with this drug in our cohort of type 1 diabetic women. While average weekly occurrence of food intake crises was reduced by 50–64%, purging behaviors were improved even more by >70%. Most of the drug response was obtained after 2 months, but it was maintained or slightly improved further after 1 year. Only binge-eating crises slightly rebounded between the second and twelfth months in two patients, but remained much less frequent than the initial rate. The effect on body weight was modest because reduction of previous intentional insulinopenia and/or vomiting attenuates the impact on body weight. The highly significant improvement of diabetes control is shown, with an average HbA1c decrease of 1.5% after 2 months and 2.5% after 1 year. If maintained for years, such reductions in HbA1c levels could mean an even more impressive improvement of the incidence of diabetic complications, according to estimations from the Diabetes Control and Complications Trial (5). Beside reduction of carbohydrate intakes, psychological changes documented by the Eating Disorder Inventory 2 questionnaire likely played a role in positive behavior toward insulin treatment, which may explain the HbA1c improvement. Although we cannot exclude a nonspecific “study effect,” the encouraging results of this pilot trial warrant further assessment of naltrexone in controlled studies, especially as severe eating disorders associated with type 1 diabetes represent an often hopeless condition.