Journal Watch

Prepared for IDDT by Jim Young

November 2014

BMI is an important driver of beta cell loss in type 1 diabetes upon diagnosis in 10-18 year old children
Angelo Lauria et al. European Journal of Endocrinology. Doi: 10.1530/EJE-14-0522

This study investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. [Body mass index (BMI) it is defined as the individual’s body mass divided by the square of their height – with the value being given in units of kg per square metre]… [C-peptide is a protein that connects insulin’s A-chain to its B-chain in the proinsulin molecule. Measuring C-peptide can help to determine how much of a patient’s own natural insulin is being produced as C-peptide is secreted in equimolar amounts to insulin].The multicentre longitudinal study collected data from 7 diabetes centres in Europe.  In individuals diagnosed between 0-5 years, 5-10 years and those diagnosed over 18 years the investigators found no association between BMI and C-peptide decline. However, in patients aged 10-18 years higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1-year. The authors suggest that this should be considered in studies of beta-cell function in type 1 diabetes.


Therapeutic inertia: underdiagnosed and undertreated hypertension in children
Bimota Nambam et al. Pediatric Diabetes. Doi: 10.1111/pedi.12231
The authors remind us that reduction of cardiovascular risk in children with type 1 diabetes requires aggressive management of hypertension (HTN). However they also report that the frequency of diagnosing and effectively treating HTN in youth with type 1 diabetes has not been established. To address this question, they used the data collected in over 9,000 youths with type 1 diabetes who enrolled in the T1D Exchange Clinic Registry in the USA. They found that HTN was diagnosed in only 1% of participants; whilst elevated BP was recorded at one of the two visits in 17% and at both visits in 4%. Among those with diagnosed HTN, only 52% were receiving ACE-I/ARB therapy and only 32% of those treated were at goal BP. It also found that children with diagnosed HTN had higher HbA1c and higher BMI when compared with children without HTN.


New Insulin Glargine 300 Units/mL versus Glargine 100 Units/mL in People with Type 2 Diabetes Using Oral Agents and Basal Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 2)
Hannele Yki-Järvinen et al. Diabetes Care. Doi: 10.2337/dc14-0990

This multicenter study looked at adults receiving basal insulin plus oral antidiabetic drugs. The participants were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point in the study was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed or severe hypoglycemic event from week 9 to month 6. It was found that Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day.


Is insulin the most effective injectable antihyperglycaemic therapy?
J. B. Buse et al. Diabetes, Obesity and Metabolism. Doi: 10.1111/dom.12402

The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly and liraglutide once-daily, with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline. The authors conclude that HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. They also suggest that liraglutide and exenatide may be appropriate alternatives to basal insulin in type 2 diabetes, including when baseline HbA1c is very high.


Initial choice of oral glucose-lowering medication for diabetes mellitus
Seth A. Berkowitz et al. JAMA Internal Medicine. Doi:10.1001/jamainternmed.2014.5294

This study set out to determine the effect of initial oral glucose-lowering agent class on subsequent need for treatment intensification. It looked at initiation of treatment with metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor. The main criterion recorded was the time to addition of a second oral agent or insulin, hypoglycemia, other diabetes-related emergency department visits, and cardiovascular events. A total of 15,516 patients were included in the study of whom 8,964 (57.8%) started therapy with metformin. It was found that medications other than metformin were significantly associated with an increased risk of adding a second oral agent or insulin. It was also found that the alternatives to metformin were not associated with a reduced risk of hypoglycemia, emergency department visits, or cardiovascular events. The authors posit that the findings have significant implications for quality of life and medication costs.


Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes? A retrospective case–control study
Anna Lena Brorsson et al. Pediatric Diabetes. Doi: 10.1111/pedi.12209

This study compared 216 patients starting continuous subcutaneous insulin infusion (CSII) with children and adolescents treated with multiple daily injections (MDI). It investigated the long-term effects on glycaemic control, ketoacidosis, serious hypoglycaemic events, insulin requirements, and body mass index in children and adolescents with type 1 diabetes. The findings showed that treatment with CSII resulted in an improvement in HbA1c levels up to 1 yr and decreased the number of severe hypoglycaemic events, but the frequency of ketoacidosis increased. The authors posit that the major challenge is to identify methods to maintain the HbA1c improvement, especially among older children and teenagers, and reduce the frequency of ketoacidosis.


Facilitating global development of biosimilars
European Medicines Agency

The European Medicines Agency (EMA) has published its revised overarching guideline on biosimilars. [Biosimilars are officially approved subsequent versions of innovative biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the original product].The main change brought by this new guidance is the possibility for medicines developers to use a comparator authorised outside the European Economic Area (EEA) during the clinical investigation of a biosimilar. This new concept is expected to facilitate the global development of biosimilars and to avoid unnecessary repetition of clinical trials. A biosimilar is granted a marketing authorisation only if the developer has demonstrated in studies that it is as safe and effective as the reference medicine. The overarching guidelines are complemented by product-specific guidelines, which give more detailed guidance to applicants in relation to the respective class of products.


Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people
Anoop Dinesh Shah et al. Lancet Diabetes & Endocrinology. Doi: 10.1016/S2213-8587(14)70219-0

The authors state that the contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. Their study looked at associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. They used records from linked primary care, hospital admission, disease registry, and death certificates taken from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. People who were 30 years or older and free from cardiovascular disease were included in the study. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. The study included 1,921,260 individuals, of whom 1,887,062 (98·2%) did not have diabetes and 34,198 (1·8%) had type 2 diabetes. The study found that heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes.


Macular dysfunction is common in both type 1 and type 2 diabetic patients without macular edema
De Benedetto et al. Retina. Doi: 10.1097/IAE.0000000000000205
This study looked at retinal function in asymptomatic patients with Type 1 and Type 2 diabetes with nonproliferative diabetic retinopathy (NPDR) and no clinical signs of diabetic macular edema.
It found that a significantly reduced sensitivity in both nonproliferative diabetic retinopathy groups without diabetic macular edema compared with healthy controls, and that this reduction was greater in Type 2 diabetic patients. It was also noted that central foveal thickness was increased in all diabetic patients compared with healthy controls, despite the absence of diabetic macular edema


CD247, a novel T cell–derived diagnostic and prognostic biomarker for detecting disease progression and severity in patients with type 2 diabetes mellitus
Roy Eldor et al. Diabetes Care. Doi: 10.2337/dc14-1544

The authors recall that chronic inflammation results in immunosuppression associated with CD247 downregulation in T lymphocytes, and that type 2 diabetes mellitus (T2DM) is known to be associated with chronic inflammation. [CD247 (Cluster of Differentiation 247) is a protein that in humans is encoded by the CD247 gene.] Their study set out to examine CD247 expression levels in patients with T2DM and to assess whether it can serve as a diagnostic and prognostic biomarker for disease complications and outcomes. Based on their findings they suggest that CD247 should be used as a biomarker in patients with diabetes for evaluating the state of chronic inflammation that contributes to morbidity and mortality in this disease and for the prediction of future cardiovascular events.