Which health-related quality of life score? A comparison of alternative utility measures in patients with Type 2 diabetes in the ADVANCE trial.

BACKGROUND: Diabetes has a high burden of illness both in life years lost and in disability through related co-morbidities. Accurate assessment of the non-mortality burden requires appropriate health-related quality of life and summary utility measures of which there are several contenders. The study aimed to measure the impact of diabetes on various health-related quality of life domains, and compare several summary utility measures. METHODS: In the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) study, 978 Australian patients with Type 2 diabetes completed two health-related quality of life questionnaires at baseline: the EQ-5D and the SF-36v2, from which nine summary utility measures were calculated, and compared. The algorithms were grouped into four classes: (i) based on the EQ-5D; (ii) using fewer items than those in the SF-12 (iii) using the items in the SF-12; and (iv) using all items of the SF-36. RESULTS: Overall health-related quality of life of the subjects was good (mean utility ranged from 0.68 (+/-0.08) to 0.85(+/-0.14) over the nine utility measures) and comparable to patients without diabetes. Summary indices were well correlated with each other (r = 0.76 to 0.99), and showed lower health-related quality of life in patients with major diabetes-related events such as stroke or myocardial infarction. Despite the smaller number of items used in the scoring of the EQ-5D, it generally performed at least as well as SF-36 based methods. However, all utility measures had some limitation such as limited range or ceiling effects. CONCLUSION: The summary utility measures showed good agreement, and showed good discrimination between major and minor health state changes. However, EQ-5D based measures performed as well and are generally simpler to use

Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: results from the ADVANCE-ON study.

BACKGROUND: Peripheral arterial disease (PAD) is known to be associated with high cardiovascular risk, but the individual impact of PAD presentations on risk of macrovascular and microvascular events has not been reliably compared in patients with type 2 diabetes. We aimed to evaluate the impact of major PAD, and its different presentations, on the 10-year risk of death, major macrovascular events, and major clinical microvascular events in these patients. METHODS: Participants in the action in diabetes and vascular disease: PreterAx and DiamicroN modified-release controlled evaluation (ADVANCE) trial and the ADVANCE-ON post-trial study were followed for a median of 5.0 (in-trial), 5.4 (post-trial), and 9.9 (overall) years. Major PAD at baseline was subdivided into lower-extremity chronic ulceration or amputation secondary to vascular disease and history of peripheral revascularization by angioplasty or surgery. RESULTS: Among 11,140 participants, 516 (4.6 %) had major PAD at baseline: 300 (2.7 %) had lower-extremity ulceration or amputation alone, 190 (1.7 %) had peripheral revascularization alone, and 26 (0.2 %) had both presentations. All-cause mortality, major macrovascular events, and major clinical microvascular events occurred in 2265 (20.3 %), 2166 (19.4 %), and 807 (7.2 %) participants, respectively. Compared to those without PAD, patients with major PAD had increased rates of all-cause mortality (HR 1.35, 95 % CI 1.15-1.60, p = 0.0004), and major macrovascular events (1.47 [1.23-1.75], p < 0.0001), after multiple adjustments for region of origin, cardiovascular risk factors and treatments, peripheral neuropathy markers, and randomized treatments. We have also observed a trend toward an association of baseline PAD with risk of major clinical microvascular events [1.31 (0.96-1.78), p = 0.09]. These associations were comparable for patients with a lower-extremity ulceration or amputation and for those with a history of peripheral revascularization. Furthermore, the risk of retinal photocoagulation or blindness, but not renal events, increased in patients with lower-extremity ulceration or amputation [1.53 (1.01-2.30), p = 0.04]. CONCLUSIONS: Lower-extremity ulceration or amputation, and peripheral revascularization both increased the risks of death and cardiovascular events, but only lower-extremity ulceration or amputation increased the risk of severe retinopathy in patients with type 2 diabetes. Screening for major PAD and its management remain crucial for cardiovascular prevention in patients with type 2 diabetes (ClinicalTrials.gov number, NCT00949286)

Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus

BackgroundThe present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes.MethodsIn the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated.ResultsA total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c) and glycated albumin were 8.5% (8.0% to 9.6%) and 25.2±7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8±0.1%, P<0.001) and their postprandial glucose levels were decreased by 48.7±10.3 mg/dL (P<0.001). Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55), high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78), and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99), and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93) at baseline were independently associated with good responders whose A1c reduction was more than 0.5%.ConclusionThe authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen

Haemoglobin glycation index and risk for diabetes-related complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial

AIMS/HYPOTHESIS: Previous studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. METHODS: We studied participants in the ADVANCE trial with data available for baseline HbA1c and fasting plasma glucose (FPG) (n = 11,083). HGI is the difference between observed HbA1c and HbA1c predicted from a simple linear regression of HbA1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA1c. RESULTS: Intensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p = 0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA1c. Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14-17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA1c was a stronger predictor of these outcomes than HGI. CONCLUSIONS/INTERPRETATION: HGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA1c. Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA1c, clinical use of HGI in type 2 diabetes cannot currently be recommended

An observational study of patient characteristics and mortality following hypoglycemia in the community

Objectives: Characterize diabetes patients with severe hypoglycemia requiring emergency services intervention at home and investigate 12 month mortality. Research design and methods: Emergency services call-outs for hypoglycemia were recorded between 2005 and 2013 in an area covering 34000 patients with diabetes. Patient characteristics were documented together with capillary blood glucose (CBG), HbA1c and treatment for hypoglycemia. 12 month mortality and variables influencing survival were analysed. Results: In 1835 episodes amongst 1156 patients, 45% had type 1 diabetes (68.2% males), 44% had type 2 diabetes (49.4% males) with a minority unclassified. CBG at presentation (mean±SD) was 1.76±0.72 mmol/L in type 1 diabetes and 1.96±0.68 mmol/L in type 2 diabetes patients (p<0·0001), with higher HbA1c in the former group (8.3±1.52% (67.5±16.4 mmol/mol) and 7.8±1.74% (61.6±19.0 mmol/mol), respectively; p<0·0001). A third of type 2 diabetes patients were not on insulin therapy and displayed lower HbA1c compared with insulin users. Glucagon was used in 37% of type 1 diabetes and 28% of type 2 diabetes patients (p<0.0001). One year mortality was 4.45% in type 1 diabetes and 22.1% in type 2 diabetes. Age and type of diabetes were predictive of mortality in multivariable analysis, whereas CBG levels/frequency of hypoglycemia had no effect. Conclusions: Severe hypoglycemia in the community is common with a male predominance in type 1 diabetes. Severe hypoglycemia in non-insulin treated type 2 diabetes patients is associated with lower HbA1c compared with insulin users. Severe hypoglycemia appears to be associated with increased mortality at 12 months, particularly in type 2 diabetes. KEY MESSAGES Severe hypoglycemia in the community is common, and presents a large burden on both patients and healthcare workers. Using a large database of ambulance call-outs for hypoglycemia this study aimed to characterise those requiring the emergency services for an episode of hypoglycemia, and to investigate factors that may be associated with an increased risk of mortality. We found that a third of type 2 diabetes patients having severe hypoglycemic episodes were not using any insulin, these individuals had a lower HbA1c than those with type 2 diabetes requiring insulin treatment. 12 month mortality following an episode of severe hypoglycemia was high, especially in individuals with type 2 diabetes. More research is required to investigate the cause of death in these patient

Comparison of Vildagliptin-Metformin and Glimepiride-Metformin Treatments in Type 2 Diabetic Patients

BackgroundThe present study investigated the efficacy and safety of vildagliptin-metformin treatment compared to those of glimepiride-metformin treatment for type 2 diabetes.MethodsIn a randomized, open-label, comparative study, 106 patients with type 2 diabetes were enrolled. The primary endpoint was a reduction in HbA1c from baseline and secondary endpoints included fasting plasma glucose (FPG) or 2-hour postprandial glucose (2h-PPG) reduction from baseline, as well as HbA1c responder rate and HbA1c reduction according to baseline HbA1c category.ResultsComparable HbA1c reduction was observed with a mean±standard deviation change from baseline to the 32-week endpoint of -0.94±1.15% in the vildagliptin group and -1.00±1.32% in the glimepiride group. A similar reduction in 2h-PPG (vildagliptin group 3.53±4.11 mmol/L vs. the glimepiride group 3.72±4.17 mmol/L) was demonstrated, and the decrements in FPG (vildagliptin group 1.54±2.41 mmol/L vs. glimepiride group 2.16±2.51 mmol/L) were not different between groups. The proportion of patients who achieved an HbA1c less than 7% at week 32 was 50.1% in the vildagliptin group and 56.0% in the glimepiride group. An average body weight gain of 2.53±1.21 kg in the glimepiride group was observed in contrast with the 0.23±0.69 kg weight gain noted in the vildagliptin group. A 10-fold lower incidence of hypoglycemia was demonstrated in the vildagliptin group, in addition to an absence of severe hypoglycemia.ConclusionVildagliptin-metformin treatment provided blood glucose control efficacy comparable to that of glimepiride-metformin treatment and resulted in better adverse event profiles with lower risks of hypoglycemia and weight gain

Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study

Aim: The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long-Acting insulin (HEELA) study was designed to examine whether the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, could improve HbA1c (≤7.4%) with minimal weight gain (≤1 kg) compared with insulin glargine

The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): a short‐term cost‐effectiveness analysis in the UK setting

Aim: To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. Methods: A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c &lt;7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed. Results: IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. Conclusions: IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK

Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program

BackgroundThe Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years.MethodsThis study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics.ResultsAmong the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects.ConclusionThe prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females

Clinical, metabolic and psychological outcomes and treatment costs of a prospective-randomized trial based on different educational strategies to improve diabetes care (PRODIACOR)

Aim To evaluate the effect of system interventions (formalized data collection and 100% coverage of medications and supplies) combined with physician and/or patient education on therapeutic indicators and costs in Type 2 diabetes. Methods Randomized 2x2 design in public health, social security or private prepaid primary care clinics in Corrientes, Argentina. Thirty-six general practitioners and 468 adults with Type 2 diabetes participated. Patients of nine participating physicians were selected randomly and assigned to one of four structured group education programmes (117 patients each): control, physician education, patient education and both, with identical system interventions in all four groups. Outcome measures included glycated haemoglobin, body mass index, blood pressure, fasting glucose, lipid profile, drug consumption, resource use and patient well-being at baseline and every 6 months up to 42 months. Results Glycated haemoglobin decreased significantly from 0.34 to 0.84% by 42 months (P < 0.05); the largest and more consistent decrease was in the groups where patients and physicians were educated. Blood pressure and triglycerides decreased significantly in all groups; the largest changes were recorded in the combined education group. The WHO-5-Lowe score showed significant improvements, without differences among groups. The lowest treatment cost was seen in the combined education group. Conclusions In a primary care setting, educational interventions combined with comprehensive care coverage resulted in long-term improvement in clinical, metabolic and psychological outcomes at the best cost-effectiveness ratio. Trial registration NCT01456806 Keywords Type 2 diabetes management, patient and healthcare provider education, quality of care, patient satisfaction, psychological impactFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Lapertosa, Silvia. Ministerio de Salud de la Provincia de Corrientes; ArgentinaFil: Pfirter, Guillermina . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Villagra, Mirta. Ministerio de Salud de la Provincia de Corrientes; ArgentinaFil: Caporale, Joaquín E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Gonzalez, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Elgart, Jorge Elgart. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Cernadas, C.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Rucci, Enzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Clark, C.. Indiana University; Estados Unido