A Randomized Trial of Continuous Subcutaneous Insulin Infusion and Intensive Injection Therapy in Type 1 Diabetes for Patients With Long- Standing Poor Glycemic Control J. HANS DEVRIES, MD 1 FRANK J. SNOEK, PHD 2 PIET J. KOSTENSE, PHD 3 NATHALIE MASUREL, RN 1 ROBERT J. HEINE, MD, PHD 1 ON BEHALF OF THE DUTCH INSULIN PUMP STUDY GROUP OBJECTIVE — To assess in a randomized crossover trial the efficacy of continuous subcu- taneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-standing poor glycemic control. RESEARCH DESIGN AND METHODS — A total of 79 patients in 11 Dutch centers were randomized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order. Glycemic control was assessed by HbA 1c , self-reported hypoglycemic events, and blood glucose memory meter read outs. Changes in quality of life were assessed by self-report questionnaires administered at baseline and 16 weeks. RESULTS — As the drop-out rate after crossover was high (17 of 79 patients [22%]), we analyzed the trial as a parallel clinical trial, using data of the first half of the crossover phase only. At 16 weeks, mean HbA 1c was 0.84% (95% CI -1.31 to -0.36) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group (P = 0.002). Stability of blood glucose self-measurement values, expressed as SD of the nine-point blood glucose profiles, improved in the insulin pump group by 29.3  41.1 vs. 8.2  36.5% in the injection group (P = 0.039). The number of mild hypoglycemic episodes per patient-week was 0.99 (95% CI 0.11–1.87) higher in the insulin pump group (P = 0.028). Weight gain was similar in both groups. Scores on the Short-Form 36-Item subscales ‘general health’ and ‘mental health’ improved in the continuous subcutaneous insulin infusion group, compared with stable values in the injection group (P = 0.048 and 0.050, respectively). CONCLUSIONS — Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control. Diabetes Care 25:2074 –2080, 2002 R apid-acting insulin analogs have been shown to result in moderately lower HbA 1c values as compared with unmodified human insulin, both when used as mealtime insulin in multi- ple injection therapy (1–7) and as insulin for continuous subcutaneous insulin in- fusion (8 –11). With the use of rapid- acting insulin analogs, two relatively small trials thus far have compared con- tinuous subcutaneous insulin infusion and multiple injection therapy. The first, a crossover study in 40 patients found a 0.35% lower HbA 1c with insulin pump treatment as compared with injection therapy (12). However, patients had been on insulin pump therapy using unmodi- fied human insulin for a mean of 5.5 years before entering the trial, limiting the ex- ternal validity of this study. The second, a parallel clinical trial, found no difference in HbA 1c , with a follow-up of 9 months (13). Thus, the evidence supporting the widespread and rapidly increasing use of continuous subcutaneous insulin infu- sion by an estimated 200,000 type 1 dia- betic patients (14) seems relatively scarce. The aim of our study was to compare efficacy in improving glycemic control and quality of life of continuous subcuta- neous insulin infusion and intensive in- jection therapy in patients with long- standing poor glycemic control. The reason for selecting poorly regulated pa- tients, who have often been excluded from participation in clinical trials, is that they are the most obvious candidates for treatment intensification. Moreover, the relationship between HbA 1c and the de- velopment of long-term diabetic compli- cations, as shown in the Diabetes Control and Complications Trial (DCCT), is steeper where HbA 1c is higher (15). Thus, a lowering in HbA 1c results in a greater absolute benefit in terms of prevention of long-term diabetic complications when baseline HbA 1c is high. Poor glycemic ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Department of Endocrinology, Diabetes Center, Research Institute for Endocrinology, Reproduc- tion and Metabolism, VU University Medical Center, Amsterdam, the Netherlands; the 2 Department of Medical Psychology, Diabetes Center, Research Institute for Endocrinology, Reproduction and Metabolism, VU University Medical Center, Amsterdam, the Netherlands; and the 3 Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands. Address correspondence and reprint requests to J. Hans DeVries, MD, Department of Endocrinology 1 OBU 42, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: hans.devries@vumc.nl. Received for publication 5 April 2002 and accepted in revised form 14 August 2002. R.J.H. has received honoraria for membership on an advisory panel and speaking engagements from Novo Nordisk Farma Denmark/The Netherlands. Abbreviations: DCCT, Diabetes Control and Complications Trial; SF-36, 36-Item Short-Form Survey; SMBG, self-monitoring of blood glucose. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. See accompanying editorial on p. 2100. Pathophysiology/Complications O R I G I N A L A R T I C L E 2074 DIABETES CARE, VOLUME 25, NUMBER 11, NOVEMBER 2002 Downloaded from http://diabetesjournals.org/care/article-pdf/25/11/2074/588749/dc1102002074.pdf by guest on 13 June 2022