Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes.

BACKGROUND: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria five years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. METHODS: In 1,826 participants with newly diagnosed, screen-detected diabetes without albumiuria, we explored associations between risk of new albuminuria (≥2.5 mg mmol(-1) males and ≥3.5 mg mmol(-1) females) and: 1) baseline cardio-metabolic risk factors and 2) changes from baseline to one year in systolic blood pressure (∆SBP) and glycated haemoglobin (∆HbA1c ) using logistic regression. RESULTS: Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in the five years after detection of diabetes. In a model adjusted for age, gender, and baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5 mmHg decrease in SBP during the first year were independently associated with lower risks of albuminuria (Odds Ratio (OR), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively). Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHBA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. CONCLUSIONS: Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria four years later. Established multifactorial treatment for diabetes applies to cases identified through screening.Individual centres in Denmark, the Netherlands and the United Kingdom were responsible for funding. ADDITION-Denmark has been given unrestricted grants from Novo Nordisk AS, Novo Nordisk Scandinavia AB, Novo Nordisk U.K., AstraZeneca Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark A/S, and HemoCue Denmark A/S. Part of the grant from Novo Nordisk was transferred to the other centers. ADDITIONNetherlands was supported by unrestricted grants from Novo Nordisk, GlaxoSmithKline, and Merck. ADDITION-Cambridge was supported by the Wellcome Trust (grant reference no: G061895) and the Medical Research Council (grant reference no: G0001164), the National Institute for Health Research (NIHR) Health Technology Assessment Programme (grantcare.diabetesjournals.org Sandbæk and Associates 2021 reference no: 08/116/300), and National Health Service research and development support funding (including the Primary Care Research and DiabetesResearch Networks), and the NIHR under its Programme Grants for Applied Research scheme (RP-PG-0606-1259). ADDITION-Leicester was supported by the Department of Health and Support for Sciences, the NIHR Health Technology Assessment Programme (grant reference no: 08/116/300), National Health Service research and development support funding (including the Primary Care Research and Diabetes Research Networks Leicestershire, Northamptonshire and Rutland Collaborative for Leadership in Applied Health Research and Care) and the NIHR Leicester Loughborough Lifestyle Biomedical Research Unit. ADDITION-Netherlands was supported by the Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht and by unrestricted grants from Novo Nordisk and Glaxo Smith Kline

Estimated morbidity and mortality in adolescents and young adults diagnosed with Type 2 diabetes mellitus

Aims  To estimate remaining life expectancy (RLE), quality‐adjusted life expectancy (QALE), causes of death and lifetime cumulative incidence of microvascular/macrovascular complications of diabetes for youths diagnosed with Type 2 diabetes. Methods  A Markov‐like computer model simulated the life course for a hypothetical cohort of adolescents/young adults in the USA, aged 15–24 years, newly diagnosed with Type 2 diabetes following either conventional or intensive treatment based on the UK Prospective Diabetes Study. Outcomes included RLE, discounted QALE in quality‐adjusted life years (QALYs), cumulative incidence of microvascular/macrovascular complications and causes of death. Results  Compared with a mean RLE of 58.6 years for a 20‐year‐old in the USA without diabetes, conventional treatment produced an average RLE of 43.09 years and 22.44 discounted QALYs. Intensive treatment afforded an incremental 0.98 years and 0.44 discounted QALYs. Intensive treatment led to lower lifetime cumulative incidence of all microvascular complications and lower mortality from microvascular complications (e.g. end‐stage renal disease (ESRD) death 19.4% vs. 25.2%). Approximately 5% with both treatments had ESRD within 25 years. Lifetime cumulative incidence of coronary heart disease (CHD) increased with longer RLE and greater severity of CHD risk factors. Incorporating disutility (loss in health‐related quality of life) of intensive treatment resulted in net loss of QALYs. Conclusions  Adolescents/young adults with Type 2 diabetes lose approximately 15 years from average RLE and may experience severe, chronic complications of Type 2 diabetes by their 40s. The net clinical benefit of intensive treatment may be sensitive to preferences for treatment. A comprehensive management plan that includes early and aggressive control of cardiovascular risk factors is likely needed to reduce lifetime risk of CHD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90578/1/j.1464-5491.2011.03542.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90578/2/DME_3542_sm_Technical_ReportS1.pd

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

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

BackgroundSitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.MethodsWe obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.ResultsWe classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.ConclusionIn Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders

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 <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

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

Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea

BackgroundTo investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.MethodsWe analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.ResultsA total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.ConclusionWe identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia

Indirect estimation of a discrete-state discrete-time model using secondary data analysis of regression data

Multi-state models of chronic disease are becoming increasingly important in medical research to describe the progression of complicated diseases. However, studies seldom observe health outcomes over long time periods. Therefore, current clinical research focuses on the secondary data analysis of the published literature to estimate a single transition probability within the entire model. Unfortunately, there are many difficulties when using secondary data, especially since the states and transitions of published studies may not be consistent with the proposed multi-state model. Early approaches to reconciling published studies with the theoretical framework of a multi-state model have been limited to data available as cumulative counts of progression. This paper presents an approach that allows the use of published regression data in a multi-state model when the published study may have ignored intermediary states in the multi-state model. Colloquially, we call this approach the Lemonade Method since when study data give you lemons, make lemonade. The approach uses maximum likelihood estimation. An example is provided for the progression of heart disease in people with diabetes. Copyright © 2009 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63056/1/3599_ftp.pd