Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus.

OBJECTIVE: Current guidelines recommend treating patients with type 1 diabetes mellitus with ACE inhibitors after the onset of microalbuminuria. Recent clinical trials have shown ACE inhibitors can affect the development of nephropathy when initiated prior to the onset of microalbuminuria. Our objective is to examine the cost effectiveness of treating adults aged over 20 years with an ACE inhibitor (captopril) immediately following diagnosis of type 1 diabetes versus treating them after the onset of microalbuminuria. DESIGN: Using a semi-Markov model, we calculated four main outcome measures: lifetime direct medical costs (discounted), QALYs, cumulative incidence of end-stage renal disease (ESRD), and number of days of ESRD over a lifetime. Medical costs are in 1999 US dollars. SETTING: All analyses were from the viewpoint of a single US payer responsible for all direct medical costs, including screening for microalbuminuria, ACE inhibitor treatment (captopril), management of major diabetic complications, and routine annual medical costs not specific to diabetes. METHODS: We applied the model to a hypothetical cohort of 10,000 persons newly diagnosed with type 1 diabetes. Distribution of sex and race/ethnicity within the cohort is representative of the general US population. RESULTS: We estimated that the incremental cost of early use of captopril for the average adult with type 1 diabetes is USD 27,143 per QALY. This level varies considerably with age and glycaemic level. When the age at onset of diabetes is 20 years and glycosylated haemoglobin (HbA(1c)) level is 9%, the cost-effectiveness ratio is USD 13,814 per QALY. When the age at onset is 25 years and HbA(1c) level is 7%, the cost-effectiveness ratio is USD 39,530 per QALY. CONCLUSION: This model, with its underlying assumptions and data, suggests that early treatment with captopril provides modest benefit at reasonable cost effectiveness, from the US single-payer perspective, in the prevention of ESRD compared with delaying treatment until diagnosis of microalbuminuria. Early treatment with other ACE inhibitors will provide similar cost effectiveness if they have equivalent efficacy, compliance and price per dose. Treatment may be considered among patients at age 20 years with new onset of type 1 diabetes. This conclusion is sensitive to the extent that ACE inhibitors delay onset of microalbuminuria. Other factors such as the patient's age and glycaemic level must be considered when deciding to initiate early treatment.

Rates of glucose change measured by blood glucose meter and the GlucoWatch Biographer during day, night, and around mealtimes.

OBJECTIVE: The purpose of this study was to characterize the distribution of the rate of change of blood glucose for a diabetic population. RESEARCH DESIGN AND METHODS: The study population consisted of 124 adults with type 1 or type 2 diabetes requiring insulin. Study participants applied a GlucoWatch Biographer during the day at home for 5 consecutive days and took finger-prick blood glucose measurements hourly. Subjects kept a diary of meals. The Biographer frequently and automatically measured glucose up to three times per hour for up 12 h. Rates of glucose change were calculated for both Biographer and blood glucose measurements. Rates of glucose change during a separate study of 134 subjects were determined for daytime and nighttime use. RESULTS: -Mean (+/-SD) rates of change of glucose of -0.36 +/- 0.95 and 0.36 +/- 0.99 mg. dl(-1). min(-1) were found before and after lunch using blood glucose data and -0.31 +/- 1.23 and 0.43 +/- 1.26 using Biographer data. For both types of diabetes, rates of glucose change exceeded 2 mg. dl(-1). min(-1) before and after meals approximately 10% of the time. Periprandial glucose patterns showed some significant differences between type 1 and type 2 diabetic subjects. Glucose levels changed more gradually at night than during the day. CONCLUSIONS: Glucose values were almost equally unstable before and after meals. Glycemic instability around dinner was different in type 1 and type 2 diabetes. The GlucoWatch Biographer was found to be effective in tracking trends in glucose levels and yielded similar results as obtained by finger-prick blood samples.

The effect of preapplication of corticosteroids on skin irritation and performance of the GlucoWatch G2 Biographer.

Skin irritation due to iontophoresis may limit the frequency of use of devices for drug delivery or transdermal extraction of analytes of clinical interest. This study examined whether preapplication of corticosteroid preparations could reduce skin irritation from iontophoresis used by the GlucoWatch G2 Biographer (Cygnus, Inc., Redwood City, CA) in monitoring interstitial glucose levels frequently and automatically. Numerous corticosteroid preparations were screened to identify formulations that did not interfere with adhesion of the Biographer to the skin or glucose sensing. Kenalog (Westwood-Squibb Pharmaceuticals, Inc., Buffalo, NY) (triamcinolone acetonide) and Cortizone-10 Quick Shot (Pfizer, Inc., New York, NY) (hydrocortisone) sprays were selected and, in a double-masked, randomized, controlled trial, were applied to the forearms of 66 subjects with diabetes and allowed to dry. Biographers were applied and worn for 15 h, and home blood glucose measurements were taken every 30 min to assess accuracy. Irritation was assessed periodically by trained observers and study subjects. Skin irritation was reduced by both corticosteroid sprays, with the fraction of subjects who experienced moderate irritation reduced by 57% and 43% for the Kenalog and Cortizone-10 Quick Shot sprays, respectively. The treatment effect persisted at the 1-week assessment. Preapplication of these preparations did not affect the clinical utility of interstitial glucose readings. Preapplication of Kenalog or Cortizone-10 Quick Shot sprays significantly reduced skin irritation due to iontophoresis, and did not interfere with glucose measurements. This approach may enable the minority of users who experience moderate to severe skin irritation to use the Biographer more frequently for diabetes management.

Use of the Cygnus GlucoWatch biographer at a diabetes camp.

BACKGROUND: Detection and prevention of nocturnal hypoglycemia is a major medical concern at diabetes camps. OBJECTIVE: We conducted an open-label trial of the Cygnus GlucoWatch biographer to detect nocturnal hypoglycemia in a diabetes camp, a nonclinical environment with multiple activities. METHODS: Forty-five campers (7-17 years old) wore a biographer. The biographer was placed on the arm at 6:00 PM, with the low alarm set to 85 mg/dL (4.7 mmol/L). Overnight glucose monitoring occurred per usual camp protocol. Counselors were to check and record blood glucose values if the biographer alarmed. RESULTS: Biographers were worn for 154 nights by 45 campers. After a 3-hour warm-up period, 67% of biographers were calibrated, of which 28% were worn the entire night (12 hours). Thirty-four percent of readings were skipped because of: "data errors" (65%), sweat (20%), and temperature change (16%). Reported biographer values correlated with meter glucose values measured 11 to 20 minutes later (r = 0.90). Of 20 low-glucose alarms with corresponding meter values measured within 20 minutes, there were 10 true-positive alarms, 10 false-positive alarms, and no false-negative alarms. Campers reported sleep disruption 32% of the nights, and 74% found the biographer helpful. Campers reported they would wear the biographer 4 to 5 nights each week. CONCLUSIONS: Half of the biographer low-glucose alarms that had corresponding blood meter values were true-positive alarms, and the remaining were false-positive alarms. There was close correlation between the biographer and meter glucose values. The majority of campers found the biographer helpful and would use it at home.

Cost-effectiveness of use of the GlucoWatch Biographer in children and adolescents with type 1 diabetes: a preliminary analysis based on a randomized controlled trial.

OBJECTIVE: To conduct a preliminary analysis of the cost-effectiveness of the use of the GlucoWatch Biographer in the management of type 1 diabetes in children and adolescents. METHODS: The computer model used to analyze the cost-effectiveness of intensive diabetes treatment in the Diabetes Control and Complications Trial (DCCT) was modified to simulate cohorts of patients who participated in a small clinical trial at one center comparing standard and Biographer-assisted standard care. The model is a Monte Carlo simulation model that simulates the lives of individual patients. Cohorts of 10,000 patients are simulated to accumulate statistics on average treatment costs and complications. Complication and treatment costs were updated to 2002 dollars. Future costs and benefits are discounted using a rate of 3%. The perspective of the analysis is from a single payer of health care costs. RESULTS: The model predicts that use of the Biographer, if sustained for the life of the cohort, would delay the development of the first serious diabetes complication by 4.1 yr. Treating 18 subjects would prevent one case of blindness and 1.4 cases of renal failure. The intervention costs $91,059/years-of-life (YOL), $61,326/quality-adjusted life-years (QALYs), and $9930/yr free of a major complication. If the biographer ceased to be effective after age 17, the cost per QALY would increase to $103,178/QALY gained. CONCLUSIONS: Preliminary analysis of the cost-effectiveness of use of the GlucoWatch Biographer in diabetes management is encouraging. Definitive analysis will require confirmation in other studies and populations.

Use of the GlucoWatch biographer in children with type 1 diabetes.

OBJECTIVE: To determine whether use of the GlucoWatch biographer improves glucose control in children and adolescents with type 1 diabetes. METHODS: Forty children in poor glucose control (glycohemoglobin [HbA1c] >8%) were randomized to diabetes management with or without glucose monitoring using the biographer. Conventional glucose monitoring was performed 4 times daily in both groups. Those randomized to the biographer group were asked to wear the device 4 times per week for 3 months (intervention phase) and to perform blood glucose monitoring if the biographer alerted them that glucose was < or =70 mg/dL (3.9 mmol/L) or > or =300 mg/dL (16.7 mmol/L). After 3 months, all patients received biographers and were followed for 6 months (observation phase). HbA1c values were determined at baseline and after 1, 3, 6, and 9 months. RESULTS: The median HbA1c was 8.6% and 8.9% (control versus biographer) at baseline and was significantly lower in the biographer group after 3 months (8.4% vs 9%). More hypoglycemia was detected when subjects were wearing the biographer, especially at night. No severe hypoglycemia occurred. During the observation phase, HbA1c values at 6 months were 8.5% and 8.3% and at 9 months were 8.6% and 8.4% in the control and biographer groups, respectively. Two children dropped out of the study, 1 because of skin irritation from using the device. CONCLUSIONS: The GlucoWatch biographer was well tolerated by children and adolescents and significantly improved glucose control compared with standard therapy. The use of the biographer with an alarm to detect nocturnal hypoglycemia has the potential to increase the safety of diabetes management in children.

Use of the GlucoWatch biographer in children and adolescents with diabetes.

OBJECTIVE: This study was done to evaluate the accuracy and safety of measuring glucose with the GlucoWatch biographer in children and adolescents with diabetes. METHODS: Accuracy was assessed by comparing biographer glucose measurements with hourly blood glucose measurements using the HemoCue (Aktiebolaget Leo, Helsingborg, Sweden) Photometer for up to 12 h of monitoring. Safety was evaluated by examining the biographer application sites immediately upon removal of the devices, and then at regular intervals. RESULTS: Sixty-six subjects each wore three biographers at sites including the forearm, upper arm, leg, and torso. For forearm biographers, the mean absolute relative difference between biographer readings and blood glucose was 21%. Ninety-five per cent of biographer readings fell into the A or B regions of the Clarke error grid, and 97.3% into the A or B regions of the consensus error grid. Data from biographers worn at the alternative sites were similar to data from the forearm biographers. Two strong reactions to the adhesive pad of the biographer AutoSensor were observed. Most skin reactions were mild. CONCLUSIONS: The GlucoWatch biographer is well tolerated by children and adolescents with diabetes. Performance is similar when the device is worn at different anatomical sites, and is similar to the performance on the forearm, previously reported in adults.

Can diabetes mellitus be prevented? - abstract

Many secondary and tertiary interventions have proven effective in preventing the complications of diabetes mellitus. Of note, The Diabetes Control and Complications Trial has established that intensive treatment of diabetes mellitus with the goal of normo-glycaemia delays the development and slows the progression of renal failure. Screening and photocoagulation for macular oedema and proliferative retinopathy are highly effacious at reducing the progression of these complications to blindness. It is estimated that more than half of the non-traumatic amputations in diabetics can be prevented by appropriate education, footcare and early intervention for trauma, ulcer and infection. Patients and purveyors of care to patients with diabetes mellitus should institute these interventions in their patients to reduce the long-term effects of hyperglycaemia. At present, however, there are no interventions which have been proven to prevent development (primary prevention) of diabetes mellitus. Several large scale trials (Diabetes Prevention Trial - Type 1 Diabetes (DPT-1), European Nicotinamide Diabetes Intervention Trial (ENDIT), European Insulin Trial (EUROINS) are underway to try and prevent IDDM by administration of nicotinamide or insulin to individuals with increased risk of developing diabetes mellitus. Large scale studies of primary prevention studies of NIDDM are planned or are underway. Primary prevention of diabetes mellitus is intuitively attractive. Chronic disease models indicate that the delaying of the onset of diabetes mellitus enhances the effect of intensive treatment on reducing complications, and that the combined approach is more effective than either alone. It is appropriate to allocate research resources to large-scale clinical trials of diabetes primary prevention at this time. Trials of immunomodulation of the natural history of IDDM is supported by work in animals and pilot studies in man. Epidemiological studies suggest that lifestyle interventions such as diet and exercise may prevent development of NIDDM in susceptible individuals, and drugs that affect insulin secretion and/or action are also potential candidates for primary prevention of NIDDM (AU)