Journal Watch

Prepared for IDDT by Jim Young

June 2015

Twice- rather than once-daily basal insulin is associated with better glycaemic control in Type 1 diabetes mellitus 12 months after skills-based structured education in insulin self-management
H. E. Hopkinson et al. Diabetic Medicine. Doi:10.1111/dme.12806

This study investigated the relationship between basal insulin regimen and glycaemic outcomes 12months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for type 1 diabetes. It utilised a retrospective analysis of data from 892 DAFNE participants from 11 UK centres. It found that mean HbA1c12months after DAFNE was lower in those using twice- rather than once-daily basal insulin. The greatest fall in HbA1c occurred in those with less good baseline control who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1cbetween users of glargine, detemir and NPH insulin. The relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12months after DAFNE. Also the rate of severe hypoglycaemia fell from 0.82 to 0.23events/patient year in twice-daily basal insulin users. Based on the results from their study the authors concluded that after structured education in adults with type 1 diabetes mellitus, the use of basal insulin twice rather than once daily was associated with lower HbA1c, independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.


Insulin degludec: No hint of added benefit in children and adolescents
This press release from the Institute for Quality and Efficiency in Health Care (IQWiG ) summarises an examination into whether Insulin degludec (trade name: Tresiba), alone or in combination with other blood-glucose lowering drugs, offers an added benefit over the appropriate comparator therapy.It reports that there was no added benefit of insulin degludec for adolescents and children with type 1 diabetes, and that in girls there was a hint of greater harm regarding serious adverse events.It also states that in the only study presented by the manufacturer in its dossier that investigated children and adolescents with type 1 diabetes, the results showed no differences between the treatment groups regarding mortality, symptoms and complaints, as well as most side effects (discontinuation due to side effects, severe and symptomatic hypoglycaemia, ketoacidosis). Health-related quality of life was not investigated. IQWiG deduced from this that there was no hint of an added benefit of insulin degludec that could be derived for these outcomes. The press release goes on the record that neither positive nor negative effects were determined for boys. In girls with type 1 diabetes mellitus who were treated with insulin degludec, however, serious adverse events occurred more frequently than in the comparator group. There was no data for type 2 diabetes mellitus.


Effect of intensive versus standard blood glucose control in patients with type 2 diabetes mellitus in different regions of the world
Partha Sardar et al. Preventative Cardiology. Doi: 10.1161/JAHA.114.001577

In this database search study the investigators evaluated the differences between North America and the rest of the world with regard to regional variation in type 2 diabetes mellitus care. In particular they looked at variations in patients treated with intensive versus standard blood glucose control. The analysis included 34,967 patients from 17 randomized controlled trials (7 in North America and 10 in the rest of the world). It found that there were no significant differences between intensive and standard therapy groups for all‐cause mortality and cardiovascular mortality. However, for trials conducted in North America, intensive therapy compared with standard glycemic control resulted in significantly higher all‐cause mortality and cardiovascular mortality than trials conducted in the rest of the world.


Analysis of insulin pump settings in children and adolescents with type 1 diabetes mellitus
Yu Ning Lau et al. Pediatric Diabetes. Doi:10.1111/pedi.12285

This study characterized current insulin pump settings used by young patients with type 1 diabetes mellitus (T1DM) and assessed their relationship to glycemic control. It looked at patients aged 18 years old or younger with T1DM using a Medtronic pump device. The information collated included: pump data including number of blood glucose (BG) tests per day, basal and bolus insulin parameters, carbohydrate ratio (CR), and insulin sensitivity factors (ISFs). Anthropometric data and recent HbA1c were also recorded. The study concluded by reporting that insulin pump therapy required continuous adjustments and that glycemic targets were achieved by a minority. The authors believe that their study was the first study in a pediatric cohort that looked at the association between CR and ISF with glycemic control.


Impact of fat, protein, and glycemic index on postprandial glucose control in type 1 diabetes: implications for intensive diabetes management in the continuous glucose monitoring era
Kirstine J. Bell et al. Diabetes Care. Doi:10.2337/dc15-0100

This systematic review of relevant biomedical databases looked at research on the effects of dietary fat, protein, and glycemic index (GI) on acute postprandial glucose control in type 1 diabetes and prandial insulin dosing strategies for these dietary factors. All of the studies that examined the effect of fat, protein, and GI indicated that these dietary factors modified postprandial glycemia. It showed that late postprandial hyperglycemia was the predominant effect of dietary fat; however, in some studies, glucose concentrations were reduced in the first 2–3 h, possibly due to delayed gastric emptying. With regard to optimal bolus delivery pattern the studies indicated that high-fat/protein meals require more insulin than lower-fat/protein meals with identical carbohydrate content. The authors posit that their studies have important implications for clinical practice and patient education and point to the need for research focused on the development of new insulin dosing algorithms based on meal composition rather than on carbohydrate content alone.


Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4)
Lawrence Blonde et al. Lancet. Doi:

For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal–bolus insulin regimen is often recommended. This study compared the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes. [Glucagon-like peptide-1agonists(GLP-1agonists) are a class ofdrugsfor the treatment oftype 2 diabetes. They are known as the "incretinmimetics"]. It found that Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment.


The Streetlight Effect in Type 1 Diabetes
Manuela Battagli andMark A. Atkinson. Diabetes. Doi:10.2337/db14-1208

Here is the complete abstract from this thought provoking open access article:
In the nearly 100 years since the discovery of therapeutic insulin, significant research efforts have been directed at finding the underlying cause of type 1 diabetes (T1D) and developing a “cure” for the disease. While progress has clearly been made toward each of these goals, neither vision has been fulfilled. With increasing pressure from both public and private funders of diabetes research, growing impatience of those with T1D at the lack of practical discoveries, increased competition for research funds, uncertainties on the reproducibility of published scientific data, and questions regarding the value of animal models, the current research environment has become extraordinarily difficult to traverse from the perspective of investigators. As a result, there is an increasing pressure toward performance of what might be considered “safe” research, where the aim is to affirm existing dogmas rather than to pioneer efforts involving unconventional thought. Psychologists refer to this practice as “observational bias” while cartoonists label the process the “streetlight effect.” In this Perspective, we consider notions in T1D research that should be subject to bold question and provide additional concepts, many somewhat orphan to research efforts, whose investigation could lead to a means for truly identifying the cause of and a cure for T1D.


Type 1 Diabetes at a Crossroads!
William T. Cefalu et al. Diabetes Care. Doi:10.2337/dc15-0615

This article ties in well with the previous item and asks: “What then are the major advances in type 1 diabetes? How close are we to realizing an intervention that can delay or prevent type 1 diabetes? Are we any closer to a cure today than we were 10 years ago?“


Glycated albumin and the risk of micro- and macrovascular complications in subjects with Type 1 Diabetes
Hye-jin Yoon et al. Cardiovascular Diabetology. Doi: 10.1186/s12933-015-0219-y

This research investigated the relationship between the glycemic indices glycated albumin (GA) and glycated hemoglobin (HbA1c) and the progression of diabetic vascular complications [diabetic nephropathy (DN) and carotid artery atherosclerosis (CAA)] in subjects with type 1 diabetes (T1D). It found that mean GA levels were more closely associated with DN progression than mean HbA1cin subjects with T1D. However, they were not associated with the CAA.


Going mobile with diabetes support: a randomized study of a text message–based personalized behavioral intervention for type 2 diabetes self-care
Korey Capozza et al. Diabetes Spectrum. Doi:10.2337/diaspect.28.2.83

Because patients with type 2 diabetes often fail to achieve self-management goals, this study tested the impact on glycemic control of a two-way text messaging program that provided behavioral coaching, education, and testing reminders to enrolled individuals with type 2 diabetes in the context of a clinic-based quality improvement initiative. It also examined patient interaction and satisfaction with the program. The study recruited ninety-three adult patients with poorly controlled type 2 diabetes (HbA1C greater than 8%) from 18 primary care clinics in three counties for a 6-month study.  At 90 and 180 days, HbA1C data were obtained from the electronic health record and analyzed to determine changes from baseline for both groups. An exit survey was used to assess satisfaction.  The study demonstrated a practical approach to implementing and monitoring a mobile health intervention for self-management support across a wide range of independent clinic practices.