Journal Watch

Prepared for IDDT by Jim Young

October 2013

Perspectives from before and after the pediatric to adult care transition: a mixed-methods study in type 1 diabetes
Marisa E. Hilliard et al. Diabetes Care. Doi: 10.2337/dc13-1346

The aim of this study was to understand the concerns, expectations, preferences, and experiences of adolescents, parents and young adults when transferring from pediatric to adult care. Based on the results from questionnaires the authors found that at a mean age of 16.1 years most adolescents had not discussed the transfer of care with their parents or doctors. They also found that although many post-transition young adults reported positive and supportive interactions, several described challenges in establishing a relationship with an adult diabetes provider. In particular the timing of the transfer and early preparation were important concerns, as was maintaining family and social support, along with strategies for coordinating care between pediatric and adult providers.


A psychosocial risk index for poor glycemic control in children and adolescents with type 1 diabetes
David D Schwartz et al. Pediatric Diabetes. Doi: 10.1111/pedi.12084

The aim of this study was to develop and validate a psychosocial screening tool to predict risk for poor glycemic control in children with type 1 diabetes.  [Psychosocial relates to one’s psychological development in, and interaction with, a social environment]. The study looked at 196 children aged 3–18 years at diagnosis. The psychosocial risk index that the researchers developed predicted poor glycemic control of HbA1c of more than 9.5%; 80 mmol/mol at 1 to 4 years post diagnosis. The efficacy of the index in predicting diabetes-related emergency-room visits and diabetic ketoacidosis were also tested. The authors assert that their paper presents the first psychosocial risk index for poor glycemic control in children with newly diagnosed type 1 diabetes. They advise that it is brief, easily administered, and provides a single score which will translate directly into an estimate of risk, and that this can help guide routine diabetes care.


Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review
Markolf Hanefeld et al. Cardiovascular Diabetology. Doi: 10.1186/1475-2840-12-135

The authors remind us that although hypoglycaemia is associated with increased cardiovascular (CV) risk and mortality, the mechanistic links driving this association remain ill defined. Using a systematic review of 88 studies they summarized the data on how hypoglycaemia may affect CV risk in patients with diabetes. They found evidence indicating that hypoglycaemia mechanistically contributed to CV risk by increasing thrombotic tendency, causing abnormal cardiac repolarization, inducing inflammation, and contributing to the development of atherosclerosis [Repolarisation returns the membrane charge back to a negative value after depolarization previously changed the membrane potential to a positive value in order to conduct a nerve impulse]. They also found that these hypoglycaemia-associated risk factors were conducive to events such as unstable angina, non-fatal and fatal myocardial infarction, sudden death, and stroke in patients with diabetes. The authors remind us that although the emerging data suggests that hypoglycaemia does have an impact on CV function, that mechanistic link is multifactorial, and that further research will be needed to ascertain the full impact of hypoglycaemia on the CV system and its complications.


Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes
Hannele Yki-Järvinen et al. Diabetes Care. Doi: 10.2337/dc12-2718

This study of 1,261 patients evaluated the efficacy and long-term safety of linagliptin when added to basal insulins in type 2 diabetes that was inadequately controlled on basal insulin with or without oral agents. The participants were either on basal insulin alone or combined with metformin and/or pioglitazone. It was found that linagliptin when added to basal insulin therapy significantly improved glycemic control relative to placebo without increasing hypoglycemia or body weight.
[Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels].


A systematic review of the experience of older women living and coping with type 2 diabetes
Jiemin Li et al. International Journal of Nursing Practice. Doi: 10.1111/ijn.12135

The authors of this paper found evidence that women aged 18 and over were challenged by their multi-caregiving roles and the complexities of managing their diabetes simultaneously. They report that for female patients with diabetes, holistic care and individual psycho-education programmes appeared to facilitate more effective and successful diabetes management. [Holistic care advocates that a patient’s psychological, physical and social needs should be taken into account and seen as a whole]. In addition, the authors advocate that carer programmes should provide information that would enable family and friends to support and assist a woman with diabetes.


Changes in time to insulin initiation in type 2 diabetes patients: A retrospective database analysis in Germany and UK (2005–2010)
Karel Kostev et al. Primary Care Diabetes. Doi:10.1016/j.pcd.2013.03.003

This study analyzed longitudinal data from general practices in Germany and UK from 1995 to 2010. [A longitudinal study is research that involves repeated observations of the same variables over long periods of time]. It looked at the time from the first diabetes diagnosis to starting insulin treatment. It included 6,368 patients (age: 68 years) in Germany and 1,998 patients (age: 64 yrs) in UK.
The data showed that the time to insulin therapy had increased in type 2 diabetes patients from 2005 to 2010 in both Germany and the UK. It was also noted that the average HbA1c values before insulin therapy also slightly increased during this period.


Basal insulin analogues in the management of diabetes mellitus: What progress have we made?
David R. Owens et al. Diabetes/Metabolism Research and Reviews. Doi: 10.1002/dmrr.2469

The authors remind us that insulin remains the most effective and consistent means of controlling blood glucose levels in diabetes, and this paper reviews recent advances in basal insulin analogues, including a critical appraisal of the degludec trials. In the 1980s recombinant DNA modifications to the insulin molecule resulted in the soluble long-acting insulin analogues, glargine and detemir. [Recombinant DNA molecules are formed in the laboratory by bringing together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms]. Both exhibit a lower risk of hypoglycaemia due to improved time-action profiles and reduced day-to-day glucose variability. Glargine is indicated for administration once daily and detemir once or twice-daily. Degludec is the latest prolonged acting insulin which forms long subcutaneous molecules that delay absorption. Recent Phase III trials in type 1 and type 2 diabetes show that degludec was non-inferior to comparators (predominantly glargine) with a minimal although inconsistent reduction in overall hypoglycaemia and a small absolute difference in nocturnal hypoglycaemia. [Phase III trials involve testing of drug on patients to assess efficacy and safety — Non-inferiority trials are designed to demonstrate that a treatment is at least not appreciably worse than another]. Newer agents are under developmental with more prolonged time-action profiles.


Early Diabetic Nephropathy – A complication of reduced insulin sensitivity in type 1 diabetes
Petter Bjornstad et al. Diabetes Care. Doi: 10.2337/dc13-0631

The authors of this paper hypothesized that baseline insulin sensitivity would predict development of diabetic nephropathy (DN) over 6 years.[Insulin sensitivity describes how sensitive the body is to the effects of insulin]. To explore this they assessed the relationship between the insulin sensitivity (IS) at baseline and development of early microalbuminuria and rapid renal function decline in 449 subjects with diabetes and 565 without diabetes. It was found that the IS was lower in subjects with diabetes than in those without diabetes, and that higher IS at baseline predicted lower odds of developing diabetic nephropathy. In conclusion they suggest that there is a relationship between IS and early manifestations of DN which is a major cause of mortality in type 1 diabetes.


Choice of early treatment regimen and impact on ß-cell preservation in type 2 diabetes
S. Mudaliar.  International Journal of Clinical Practice. Doi: 10.1111/ijcp.12154

In the preamble to this paper the authors remind us that the progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) results from insulin resistance combined with the ongoing loss of β-cell function, and that β-cell function continues to decline despite treatment with commonly prescribed antihyperglycaemic medications. They posit that interventions to address the early decline in β-cell function could potentially alter the course of T2DM and prevent or delay its onset and would decrease the incidence of complications. To examine this they identified original research papers and review articles and found that certain antihyperglycaemic medications may preserve or enhance β-cell function. The medications included the thiazolidinediones [The thiazolidinediones increase insulin sensitivity by acting on adipose, muscle, and liver to increase glucose utilization and decrease glucose production], the glucagon-like peptide-1 (GLP-1) agonists [Glucagon-like peptide-1 (GLP-1) agonists are incretin mimetics – a group of gastrointestinal hormones that cause an increase in the amount of insulin released after eating], the dipeptidyl peptidase-4 (DPP-4) inhibitors [DPP-4 inhibitors increase incretin levels (GLP-1 and GIP) which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels] and insulin. The implication is that early initiation of antihyperglycaemic agents that preserve β-cell function might reverse or delay progression to T2DM in those with prediabetes, and may confer more durable glucose control and perhaps reduce/delay the incidence of diabetic complications.


Insulin degludec for Type 1 and Type 2 diabetes
National Institute for Health and Care Excellence (NICE)

These two documents from NICE open with a summary of the key points including effectiveness and safety. The multi-page in-depth evaluations that follow included a review of the evidence, clinical effectiveness, safety, and an estimation of the impact on the NHS.