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Objective: The purpose of this study was to investigate the preferences of people with diabetes for liraglutide vs other glucose lowering drugs, based on outcomes of clinical trials. Methods: Willingness to pay (WTP) for diabetes drug treatment was assessed by combining results from a recent WTP study with analysis of results from the Liraglutide Effect and Action in Diabetes (LEAD) programme. The LEAD programme included six randomised clinical trials with 3967 participants analysing efficacy and safety of liraglutide 1.2 mg (LEAD 1-6 trials), rosiglitazone (LEAD 1 trial), glimepiride (LEAD 2-3 trials), insulin glargine (LEAD 5 trial), and exenatide (LEAD 6 trial). The WTP survey used discrete choice experimental (DCE) methodology to evaluate the convenience and clinical effects of glucose lowering treatments. Results: People with type 2 diabetes were prepared to pay an extra €2.64/day for liraglutide compared with rosiglitazone, an extra €1.94/day compared with glimepiride, an extra €3.36/day compared with insulin glargine, and an extra €0.81/day compared with exenatide. Weight loss was the largest component of WTP for liraglutide compared with rosiglitazone, glimepiride, and insulin glargine. Differences in the administration of the two drugs was the largest component of WTP for liraglutide (once daily anytime) compared with exenatide (twice daily with meals). A limitation of the study was that it was based on six clinical trials where liraglutide was the test drug, but each trial had a different comparator, therefore the clinical effects of liraglutide were much better documented than the comparators. Conclusions: WTP analyses of the clinical results from the LEAD programme suggested that participants with type 2 diabetes were willing to pay appreciably more for liraglutide than other glucose lowering treatments. This was driven by the relative advantage of weight loss compared with rosiglitazone, glimepiride, and insulin glargine, and administration frequency co

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10−11). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

OBJECTIVES: This study aimed to investigate the most important consequences of diabetes medication, as measured by the patients' willingness to pay (WTP). RESEARCH DESIGN AND METHODS: People in Sweden were recruited using existing nationwide e-mail panels if they were adults (>or=18 years) with type 2 diabetes and were receiving pharmacological anti-diabetes treatment(s). Data were collected electronically and results were analysed using a standard statistical model designed for choice games (conditional logit). Six characteristics relating to treatment of diabetes were examined: weight (gain or loss), mean glycated haemoglobin level (HbA(1c)), hypoglycaemic events, nausea, need for injections (with or independently of meals), and blood glucose testing. RESULTS: A total of 461 people with type 2 diabetes (291 males; 170 females) completed an internet questionnaire and were eligible for inclusion. Participants placed high value on weight loss and nausea avoidance; they would pay 176 Swedish Krona (SEK)/euro15.61 per month to lose 1 kg, and would pay SEK 560 (euro49.67) per month to avoid nausea completely. Patients wanting to reduce the number of hypoglycaemic events from three per month to none were willing to pay SEK 419 (euro37.17) per month. Patients valued a 1 percentage point reduction in HbA(1c) at SEK 414 (euro36.72) per month. Participants preferred taking tablets to injections and required a compensation of SEK 376 (euro33.35) to accept one injection/day. Injections independent of meals were preferred to injections with meals (WTP: SEK 140/euro12.42 per month). Potential limitations of this study are that the preferences expressed may not match preferences in real-life situations, and bias through the use of electronic questionnaire, which restricted participation to those with access to, and experience with, the internet. CONCLUSION: People with type 2 diabetes were willing to pay a considerable amount of money each month to lose weight, reduce or avoid, Research funder:Novo Nordisk A/S, Bagsværd, Denmark

Udgivelsesdato: 1998-null, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both synthesized by tubular cells in the distal part of the nephron and excreted with the urine. The present study examines the urinary excretion rates of the two peptides in relation to functional tubular markers in patients with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR had been accounted for by multiple variance analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy.

Udgivelsesdato: 1998-null, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both synthesized by tubular cells in the distal part of the nephron and excreted with the urine. The present study examines the urinary excretion rates of the two peptides in relation to functional tubular markers in patients with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR had been accounted for by multiple variance analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy.

Udgivelsesdato: 1998-null, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both synthesized by tubular cells in the distal part of the nephron and excreted with the urine. The present study examines the urinary excretion rates of the two peptides in relation to functional tubular markers in patients with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration rate (GFR) as an indicator for the general renal function, lithium clearance (C(Li)) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR had been accounted for by multiple variance analyses, the excretion rates of the two peptides were still associated with ADR(Na) but not with C(Li). In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy.

Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are synthesized in the kidneys by the distal tubular cells and excreted into urine. The urinary excretion of these peptides has been suggested as a potential index for distal tubular function. The urinary excretion rates of EGF and THP were examined in three groups of rats with increased renal excretion of urine: uninephrectomy, non-osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled in uninephrectomy when compared to controls. There was a seven-fold increase in urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria, as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all affected the urinary excretion of EGF and THP differently. The EGF excretion in uninephrectomized rats was 60-80% of that of the controls, whereas THP excretion was unchanged, indicating that EGF excretion varied with renal tissue mass. Non-osmotic polyuria caused a five-fold increase in THP excretion but no change in EGF excretion. THP excretion in the diabetic rats was increased three-fold after 21 days when compared to controls, whereas EGF excretion was decreased when expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP were colocalized in the thick ascending limbs of Henle's loops and distal tubules in all five groups of rats. In conclusion, the EGF excretion appears to follow renal tissue mass and seems independent of urinary volume, whereas THP excretion is dependent mainly on urinary volume. This has implications for the use of EGF and/or THP excretion rates as an indicator for distal tubular function.

Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are synthesized in the kidneys by the distal tubular cells and excreted into urine. The urinary excretion of these peptides has been suggested as a potential index for distal tubular function. The urinary excretion rates of EGF and THP were examined in three groups of rats with increased renal excretion of urine: uninephrectomy, non-osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled in uninephrectomy when compared to controls. There was a seven-fold increase in urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria, as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all affected the urinary excretion of EGF and THP differently. The EGF excretion in uninephrectomized rats was 60-80% of that of the controls, whereas THP excretion was unchanged, indicating that EGF excretion varied with renal tissue mass. Non-osmotic polyuria caused a five-fold increase in THP excretion but no change in EGF excretion. THP excretion in the diabetic rats was increased three-fold after 21 days when compared to controls, whereas EGF excretion was decreased when expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP were colocalized in the thick ascending limbs of Henle's loops and distal tubules in all five groups of rats. In conclusion, the EGF excretion appears to follow renal tissue mass and seems independent of urinary volume, whereas THP excretion is dependent mainly on urinary volume. This has implications for the use of EGF and/or THP excretion rates as an indicator for distal tubular function.