Exenatide versus insulin glargine: a cost-effectiveness evaluation in patients with Type 2 diabetes in Switzerland.

OBJECTIVES: To investigate the long-term clinical and economic outcomes associated with exenatide versus insulin glargine as "add-on" treatments to oral therapy in individuals with Type 2 diabetes inadequately controlled with combination oral agents in the Swiss setting. METHODS: A computer simulation model of diabetes was used to project complications, life expectancy, quality-adjusted life expectancy and direct medical costs over a 35-year time horizon. Cohort characteristics and treatment effect data were derived from a 26-week randomized clinical trial comparing exenatide and insulin glargine. Modeled treatment effects included reductions in glycosylated hemoglobin (HbA1c) by -0.99% and -1.07% and in body mass index (BMI) by -0.80 and +0.55 kg/m2 with exenatide and insulin glargine respectively. Changes in systolic blood pressure and serum lipid levels were also captured. Simulations incorporated published quality of life utilities and Swiss costs from 2006. Extensive sensitivity analyses were conducted to assess the robustness of projected outcomes. Future clinical and economic outcomes were discounted at 2.5% per annum. RESULTS: In the base-case analysis exenatide was associated with comparable life expectancy (11,549 years versus 11,468 years) and an improvement in quality-adjusted life expectancy of 0.43 quality-adjusted life years (QALYs) versus insulin glargine over a 35-year time horizon. Exenatide was associated with a reduced cumulative incidence of most diabetes-related complications including an absolute reduction in myocardial infarction by 0.28%. Assuming an annual treatment cost of CHF 2,797.74 for exenatide, direct costs increased by CHF 8,378 per patient over the 35-year time horizon compared to insulin glargine. The resultant incremental cost-effectiveness ratio was CHF 19,450 per QALY gained for exenatide versus insulin glargine. CONCLUSIONS: Exenatide was associated with comparable life expectancy and an improvement in quality-adjusted life expectancy versus insulin glargine over a 35-year time horizon. Based on current standards exenatide would be a cost-effective treatment alternative to insulin glargine in Switzerland for Type 2 diabetes patients inadequately controlled on oral therapy.

Assessment of basal insulin requirement using fasting tests in insulin-treated patients with type 2 diabetes mellitus.

AIMS: Characterizing the time course of the rise of blood glucose concentrations in the fasting state during the day and night in patients with type 2 diabetes. METHODS: 40 consecutive insulin-treated patients with type 2 diabetes underwent fasting tests on two different days with either no breakfast and lunch (fasting time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering medication was stopped prior to the test according to the half-life of the medication prescribed. At the start of the fasting tests, blood glucose concentrations were lowered to below 7 mmol/L using an insulin infusion. RESULTS: 26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10 years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8 years and duration of insulin therapy had been prescribed for a mean of 6+/-6 years. During the daytime fast, plasma glucose concentrations rose by a mean of 0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly more than during the daytime fast. CONCLUSIONS: Fasting blood glucose concentrations in the majority of insulin-treated patients with type 2 diabetes increase markedly after midnight. No similar increase is observed during the day. Thus, for most patients with type 2 diabetes, an intermediate- or long-acting insulin injected at bedtime with a peak action six to eight hours after injection should be appropriate.

Economic and clinical impact of alternative disease management strategies for secondary prevention in type 2 diabetes in the Swiss setting.

PRINCIPLES: Different intervention strategies for the optimisation of disease management of diabetes exist and have been shown to increase the proportion of patients receiving screening and examinations and to improve risk factors such as HbA1c, lipids, and blood pressure. Thus, in the long-term, a decrease in diabetic complications and the associated costs could be expected. To address this question, the current analysis used a published diabetes simulation model to analyse the long-term clinical and economic implications of implementing various interventions in the Swiss setting. METHODS: Based on data from the literature, the short-term effects on clinical variables of multifactorial interventions, including screening for nephropathy and retinopathy, educational programmes and control of cardiovascular risk profile were assessed, and a cost-effectiveness analysis in comparison to standard care was performed. Life expectancy (LE) and total lifetime costs (TC) from the perspective of the health insurance payer were calculated using a long-term Markov simulation model. RESULTS: The multifactorial intervention led to an improvement in undiscounted LE of 0.56 years (LE = 10.73 and 11.29 years for standard care and multifactorial intervention respectively), and a reduction in 3%-discounted TC of CHF 7313 (10.7%) per patient compared to current standard practice. Extrapolation to the whole Swiss type 2 diabetes population (285,000) showed yearly cost savings of CHF 194 million from the multifactorial intervention. CONCLUSIONS: The implementation of multifactorial interventions, including improved control of cardiovascular risk factors, combined with early diagnosis and treatment of diabetic complications, could be both cost- and life-saving in the Swiss setting.

Assessment of selective arterial calcium stimulation and hepatic venous sampling to localize insulin-secreting tumours.

OBJECTIVE: Non-invasive localization modalities such as ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) often fail to localize insulinomas smaller than 2 cm in diameter. Recent studies have shown that the selective arterial stimulation and hepatic venous sampling (ASVS) technique using intra-arterial calcium as the insulin secretagogue facilitates the regionalization of such occult insulinomas. This study assesses the sensitivity of ASVS in localizing insulin-secreting tumours. SUBJECTS AND METHODS: Eleven consecutive patients (8 women), aged 29-82 years, were studied over the past 4 years at our hospital. Hyperinsulinaemic hypoglycaemia due to an insulin-secreting tumour was proven in all patients. Calcium gluconate (0.025 mEq/kg body weight) was injected directly into the arteries supplying the pancreas and the liver. Insulin levels were measured in samples taken from the right hepatic vein before and 30, 60 and 120 s after each injection. The ASVS technique was performed in all 11 patients; the results were compared with the surgical findings in 10 patients and the autopsy findings in 1 case. The ASVS results were also compared with the findings of other, previously performed imaging modalities. RESULTS: ASVS correctly localized 4 insulin-secreting tumours to the head, 3 to the body, 1 to the tail, 2 to the tail or body of the pancreas and 1 to the liver. Thus, the sensitivity was 100% (11/11) whereas other localization techniques were less sensitive: 7/11 tumours were detected by angiography, 4/8 by endosonography, 3/8 by CT and 1/6 by MRI. Insulinomas (confirmed by histological examination), sized 4-25 mm, were found in 10 patients. All were cured by selective surgery and remained free of hypoglycaemia over the next 1-4 years of follow-up. An insulin-secreting neuroendocrine tumour in the liver was documented in 1 case at autopsy. CONCLUSIONS: Arterial stimulation and hepatic venous sampling is a very sensitive technique for preoperative localization of insulin-producing tumours. It can help to plan minimally invasive surgery and to select an appropriate strategy for patients suffering from malignant tumours in others.

10 Swiss kindreds with multiple endocrine neoplasia type 1: assessment of screening methods.

PRINCIPLES: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterised by the combined occurrence of tumours of the parathyroid glands, the enteropancreatic neuroendocrine system and the anterior pituitary gland. The genetic defect has been mapped to the long arm of chromosome 11q13, and the MEN1-gene was recently identified by positional cloning. Genetic screening for MEN1 germline mutations allows the identification of gene carriers in affected kindreds. Biochemical and radiological screening for MEN1 tumours allows an earlier diagnosis and treatment, and, thus may reduce morbidity and mortality. Since there is no consensus about the frequency and the extent of the necessary screening investigations, evaluation of proposed screening programs is of importance. METHODS: The aims of our study were to identify the MEN1-gene mutations and to detect the gene-carriers in 10 Swiss MEN1 families, as well as to assess biochemical and radiological screening methods. The study included 45 members from 10 MEN1 families. RESULTS: Every family had a different type of MEN1-gene mutation. Thirty out of 45 family members were gene mutation carriers. Twenty-two MEN1-gene carriers had typical MEN1 tumours: parathyroid, enteropancreatic and pituitary tumours were found in 21, 14 and 1 patients, respectively. Applying a defined screening program the following manifestations in asymptomatic MEN1-gene carriers were detected: 9 primary hyperparathyroidism, 3 nonfunctioning pancreatic tumours, 1 gastrinoma, 1 nonfunctioning microadenoma of the pituitary and 1 macronodular adrenal hyperplasia. CONCLUSIONS: The genetic screening facilitates the identification of individuals who carry MEN1-gene mutations, and allows one to exclude non-mutant gene carriers from further investigations. The prospective biochemical and radiological screening of gene mutation carriers allows the earlier detection of MEN1-associated tumours. Therefore, it might be expected that morbidity and mortality of the MEN1 could be reduced.

Clinical and technical evaluation of a new self-monitoring blood glucose meter: assessment of analytical and user error.

Our study aimed to validate (against the standards of the American Diabetes Association and the International Organization for Standardization) the analytical and clinical accuracy of the new MediSense Precision Plus Electrodes on the QID system when compared with a reference method using the Abbott Vision glucose analyzer. Previous studies have shown that the overall accuracy of the device also depends on the proficiency of the operator, so we also assessed the 'ease of use' of the MediSense system, by comparing the results obtained by the patient and health care professional. Accuracy of the self-monitored blood glucose measurements was evaluated over a wide range of glucose readings (2.6-20.0 mmol/l). Between-run CVs (using the manufacturer's quality control material) were found to be 7% at 2.7 mmol/l and 4.8% at 15.5 mmol/l (n=380). We used the error-grid analysis with target range blood glucose, then separated the data into different subsets. We found that 100% of all measurements were in the clinically acceptable zones of A and B. All measured values of the MediSense QID system complied with the requirements for 'blood glucose monitoring meters', as proposed by the International Organization for Standardization. The rating of the patient questionnaire showed a good to very good overall rating and acceptance with a short instruction time. The results indicate that that the MediSense QID/Precision Plus Electrodes is a reliable and easy to use device, which can be recommended for the majority of patients with diabetes mellitus.

Applying some UK Prospective Diabetes Study results to Switzerland: the cost-effectiveness of intensive glycaemic control with metformin versus conventional control in overweight patients with type-2 diabetes.

OBJECTIVE: The results of the metformin substudy of the United Kingdom Prospective Diabetes Study (UKPDS) were applied through modelling techniques to the Swiss setting, allowing a cost-effectiveness analysis of the management of overweight type-2 diabetes patients with either conventional glycaemic control or intensive control with metformin from the Swiss third-party payer perspective. METHODS: Occurrence of diabetes-related complications was simulated using a Markov model. Probabilities for complications were taken from the UKPDS, and costs were retrieved from published sources. Total direct costs (costs of diabetes therapy plus costs of treating complications) and survival over an 11-year period were determined for cohorts randomised to either conventional glycaemic control or intensive control with metformin. Changes in life expectancy were calculated for conventional versus intensive control with metformin. Extensive sensitivity analysis was performed. RESULTS: Mean costs per patient over the 11-year follow-up period (discounted at 5% per annum) were CHF 10,877 and CHF 9950 for patients randomised to either conventional control or intensive control with metformin respectively. Intensive control with metformin led to improved survival (0.43 life-years gained per patient) over the 11-year-period. Outcomes were most sensitive to variations in the acquisition costs of metformin. Changes in the event rates and costs related to myocardial infarction, renal failure, and stroke also had important impacts. CONCLUSIONS: Within the limitations of the modelling study, intensive glycaemic control with metformin was cost- and life-saving in overweight type-2 diabetes patients in the Swiss setting.

The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective.

AIMS/HYPOTHESIS: A computer model was developed to determine the health outcomes and economic consequences of different combinations of diabetes interventions in newly diagnosed patients with Type I (insulin-dependent) diabetes in Switzerland. METHODS: We modelled seven complications of diabetes: hypoglycaemia, ketoacidosis, acute myocardial infarction, stroke, lower extremity amputation, nephropathy, and retinopathy. Transition probabilities and costs were taken from published literature. The Swiss health insurance payer perspective was taken. Various combinations of diabetes management strategies, including intensive or conventional insulin therapy and screening and treatment strategies for renal and eye disease were defined. Life expectancy, cumulative incidences of complications, and mean expected total lifetime costs per patient were calculated under six different management strategies. Incremental cost-effectiveness ratios were calculated in terms of costs per life-year gained compared with conventional insulin therapy alone. RESULTS: The addition of screening for microalbuminuria and retinopathy followed by appropriate treatment, if detected, were cost saving, with reduction in cumulative incidence of end stage renal disease and blindness respectively, and, in the case of microalbulminuria screening and treatment, an improvement in life expectancy. Intensive therapy improved life expectancy but increased total lifetime costs. CONCLUSION/INTERPRETATION: Optimal management of Type I diabetic patients, including secondary and tertiary prevention, leads to reduced complications and improved life expectancy, with the increased costs of prevention offset to varying degrees by cost savings due to complications avoided.

[Assessment of hypoglycemia]. / Abklärung von Hypoglykämien.

Hypoglycemia is characterized by a set of symptoms, but is not a diagnosis in itself. Initial attention should focus on documentation of the condition by typical symptoms (low blood sugar and disappearance of symptoms after glucose ingestion) before further testing is considered. To evaluate acute hypoglycemia, it is important to make an initial classification into one of three categories based on history: medication- or toxin-induced, fasting (not specifically associated with meals and usually occurring over 4 hours from the last meal) or postprandial hypoglycemia. A pathophysiologic approach to well-documented hypoglycemia leads to a straightforward strategy and to a diagnosis in most cases. True fasting hypoglycemia is almost invariably associated with a significant pathology, whereas postprandial hypoglycemia is not. An observed fast over 48-72 hours is diagnostic in nearly 100%. The diagnosis rests on several simultaneous features: hypoglycemia < 2.2 mmol/l, neuroglycopenic symptoms, and inappropriately elevated plasma insulin (> 30-40 pmol/l) and C-peptide levels (> 200 pmol/l) to document endogenous insulin release. Once the diagnosis of hyperinsulinism has been established, localization of the causative insulinoma (solitary adenomas in 80-90%) has traditionally been by means of the surgeon's fingers at laparotomy. In expert hands most tumors can be accurately located and removed. Although virtually every imaging technique has been advocated for preoperative localization of insulinomas, none has proved sufficiently reliable and surgical exploration is necessary even in the presence of a negative preoperative localization. Most patients who seek evaluation of reactive hypoglycemia describe a postprandial syndrome, which occurs with some regularity 2-4 hours after meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.

[Evaluation of a strip test (Micral test) for the semi-quantitative assessment of microalbuminuria in clinical practice]. / Evaluation eines Streifentests (Micral-Test) zur semiquantitativen Erfassung der Mikroalbuminurie in der Praxis.

Microalbuminuria (AER 20-200 micrograms/min) is the earliest clinical sign of incipient diabetic nephropathy. Current methods for measuring urinary albumin are not suitable for use in an office setting. A test strip (Micral-Test, Boehringer Mannheim [D]) based on immunochemical principles has recently been developed which allows semiquantitative detection of urinary albumin concentrations. In this study Micral-Test results were compared with conventional immunoturbidimetric laboratory measurement. 65 single-void urine samples of diabetic patients were analyzed (38 type 1, 27 type 2). Urinary albumin values as obtained from Micral-Test and laboratory measurement showed a significant correlation (r = 0.85, p less than 0.001). An interclass correlation was performed for normal urinary albumin values (less than 20 micrograms/ml) and for microalbuminuric values (20-200 micrograms/ml) and resulted in correlation coefficients of 0.56 and 0.81 respectively. Interindividual variation was checked by three observers reading the same 13 urine samples. The values obtained from the three observers correlated significantly (r greater than 0.95, p less than 0.001). The test strip must be evaluated after precisely 5 minutes in order to avoid false pathological results. In conclusion, the Micral-Test is a good screening method for easy and quick detection of microalbuminuria in an office setting.

[The practical assessment of micro-albuminuria as a marker for beginning diabetic nephropathy in: which urine sampling method?]. / Erfassung der Mikroalbuminurie als Marker für die beginnende diabetische Nephropathie in der Praxis: welche Urinsammelmethode?

Microalbuminuria, i.e. elevated urinary albumin excretion rate between 20 and 200 micrograms/min, is a strong predictor of subsequent overt diabetic nephropathy. Screening for microalbuminuria is essential, since it has been shown that development of overt nephropathy can be delayed or even prevented by therapeutic measures such as strict metabolic control, early aggressive antihypertensive treatment, or restriction of protein intake. Several urine collection methods for the measurement of microalbuminuria have been proposed. In a prospective study with 40 diabetic outpatients we have compared albumin excretion in urine collected over 24 h, during a timed overnight period, and in a spot urine sample collected at random while the patient attended the outpatient clinic. In addition, the reproducibility of the three urine collection methods was assessed. For this purpose, each patient underwent 3 consecutive collections at an interval of at least 4 weeks. Our data indicate that calculation of an albumin/creatinine quotient in a spot urine probe is a reliable screening test for microalbuminuria. If this quotient is increased (greater than 2), timed overnight collection should be performed.

Magnetic resonance imaging for the assessment of lingual thyroid.

A 43-year-old woman was evaluated because of a round tumor at the base of the tongue. Scintigraphy with 131I showed radionuclide uptake over the posterior part of the tongue but no uptake at all at the usual pretracheal location. Magnetic resonance imaging revealed a well defined round mass of high signal intensity, which was clearly delineated from adjacent muscular tissue.

[Risk and severity of alpine ski accidents and their social significance]. / Risiko- und Schweregradentwicklung der alpinen Skiunfälle und deren soziale Bedeutung.

The alpine ski accidents have been studied for the last ten years in the Region of Davos-Klosters, Switzerland. Possibilities of prevention were analyzed. The accident risk has drastically decreased for immobilizing injuries of the lower extremities. Simultaneously, however, the pattern of injuries moved to the upper extremities. The accidents became, according to several criteria, less severe. Future preventive measures should be aimed primarily at reducing fall frequency and intensity.