Journal Watch

Prepared for IDDT by Jim Young

June 2017

The risk of severe hypoglycemia in type 1 diabetes over 30 years of follow-up in the DCCT/EDIC study
Rose A. Gubitosi-Klug et al. Diabetes Care. DOI: https://doi.org/10.2337/dc16-2723

During the DCCT study, intensive diabetes therapy, that achieved a mean HbA1c of about 7%, was associated with a threefold increase in the rate of severe hypoglycemia compared with conventional diabetes therapy with a mean HbA1c of 9%. After approximately 30 years of follow-up, this study looked at rates of severe hypoglycemia in the DCCT/EDIC cohort. It found that one-half of the cohort reported episodes of severe hypoglycemia. Rates of severe hypoglycemia in the former intensive treatment group fell but rose in the former conventional treatment group. It also found that a preceding episode of severe hypoglycemia was the most powerful predictor of subsequent episodes. The conclusion drawn was that rates of severe hypoglycemia have equilibrated over time between the two treatment groups in association with advancing duration of diabetes and similar HbA1c levels. However, severe hypoglycemia persists and remains a challenge for patients with type 1 diabetes across their life span.
http://care.diabetesjournals.org/content/early/2017/05/19/dc16-2723

 

Carbohydrate counting at meal time followed by a small secondary postprandial bolus injection at 3 hours prevents late hyperglycemia, without hypoglycemia, after a high-carbohydrate, high-fat meal in type 1 diabetes
Matthew D. Campbell et al. Diabetes Care. DOI: https://doi.org/10.2337/dc16-0709

Patients with type 1 diabetes are provided with guidance and structured education on adjusting their mealtime bolus insulin dose based on meal carbohydrate content. However, recent research in patients using continuous subcutaneous insulin infusion has highlighted the role of dietary fat in increasing prandial insulin requirements, particularly late into the postprandial period. It has been noted that peak insulin concentration after a premeal bolus usually occurs within the first 60 min, but the peak action is usually observed between 90 and 120 min, and this duration can vary between 4 and 6 h. However, peak postprandial lipemia occurs after 3–4 h, which can promote acute peripheral insulin resistance and increase hepatic glucose output and thus hyperglycemia. This investigation found that when a meal has a high-carbohydrate and high-fat content using the carbohydrate counting method for insulin dose adjustments at mealtime and administering additional bolus insulin units 3 h later provided similar postprandial glucose control to a meal containing negligible fat, without causing hypoglycemia. The authors suggest that patients should be advised that increasing the mealtime insulin dose alone is not an effective strategy and is an approach that may increase the risk of early postprandial hypoglycemia.
http://care.diabetesjournals.org/content/39/9/e141

 

Review of basal-plus insulin regimen options for simpler insulin intensification in people with Type 2 diabetes mellitus
D. Raccah et al. Diabetic Medicine. DOI: 10.1111/dme.13390
This investigation searched the PubMed database, systematic reviews, meta-analyses and proof-of-concept studies, for randomized clinical trials related to the progressive intensification of a basal insulin regimen to a basal-plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short-acting insulin injections/day) vs a basal-bolus regimen (basal insulin plus three short-acting insulin injections per day) in people with Type 2 diabetes. The review explored approaches that could be used to define the meal for first prandial injection with basal-plus regimens, differences among insulin titration algorithms, and the importance of self-motivation and autonomy in achieving optimum glycaemic control. It found that when compared with a basal-bolus regimen, a basal-plus insulin regimen was as effective, and was more practical, and had the best chance of acceptance and success in the real world.
http://onlinelibrary.wiley.com/doi/10.1111/dme.13390/abstract

 

Projected long-term outcomes in patients with type 1 diabetes treated with fast-acting insulin aspart versus conventional insulin aspart in the UK setting
D Russell-Jones et al. Diabetes, Obesity and Metabolism. DOI: 10.1111/dom.13026
The authors of this report state that many patients with type 1 diabetes mellitus (T1DM) fail to achieve optimal glycemic control, and mealtime insulins that more closely match physiological insulin secretion can help improve treatment. In the onset 1 trial, fast-acting insulin aspart (faster aspart) was shown to improve glycemic control in patients with T1DM compared with conventional insulin aspart (insulin aspart). In the UK, faster aspart and insulin aspart are associated with the same acquisition cost, and the analysis reported here assessed the impact of faster aspart versus insulin aspart on long-term clinical outcomes and costs for patients with T1DM in the UK setting. It concluded that faster aspart was associated with improved clinical outcomes and cost savings versus insulin aspart for patients with T1DM in the UK setting.
http://onlinelibrary.wiley.com/doi/10.1111/dom.13026/abstract

 

Efficacy and safety of incretin-based drugs in patients with type 1 diabetes mellitus: A systematic review and meta-analysis
Wen Wang et al. Diabetes Research and Clinical Practice. DOI: http://dx.doi.org/10.1016/j.diabres.2017.05.007

In patients with type 2 diabetes, incretin-based therapies can improve glucose control without increased weight gain or hypoglycemia. Incretin-based drugs added to insulin therapy in type 1 diabetes (T1DM) have also been tried in many studies. However, the results were controversial. This meta-analysis assessed the efficacy and safety of incretin-based therapies in patients with T1DM. It systematically searched Medline, EMBASE, and Cochrane Central Register of Controlled Trials for relevant studies published before August 25, 2016. It found that incretin-based treatment in patients with T1DM may improve glycemic control and reduce insulin dose and weight without increasing the risk of serious adverse event, such as severe hypoglycemia, ketosis or ketoacidosis. The caveat offered was that current evidence for the adverse effects, however, is weak. The authors suggest that a rigorous monitoring of these adverse events should be implemented in well-designed observational studies.
http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(17)30011-6/fulltext

 

The elusive role of B lymphocytes and islet autoantibodies in (human) type 1 diabetes
Stef J. BloemBart O. Roep. Diabetologia. DOI:10.1007/s00125-017-4284-5

The introduction to this article discusses how the role of B lymphocytes in the pathogenesis of type 1 diabetes in humans is not entirely evident. The cells are presumed to be important, but this assumption is largely based on animal models of autoimmune diabetes, where compelling evidence for the contribution of both B lymphocytes and insulin-specific autoantibodies to this disease is in place. For humans, this is much less the case; the exact way in which B lymphocytes and/or autoantibodies may contribute to type 1 diabetes is not yet known but the possibilities include a pathogenic function (‘fire’), or they may represent a surrogate of loss of immune tolerance to beta cells (‘smoke’) or, indeed, they could be a marker of an attempt at immune regulation (‘ice water’). This article adds new information but no greater clarity on the relevance of B lymphocytes in type 1 diabetes. It showed a decrease in germinal centre frequencies in donors with recent-onset type 1 diabetes compared with control donors and donors with longstanding type 1 diabetes. The authors suggest that their findings may guide the research community to design experiments to unambiguously define whether B lymphocytes or their products function as fire, smoke or perhaps ice water in the immunopathogenesis of type 1 diabetes.
https://link.springer.com/article/10.1007/s00125-017-4284-5

 

Assessing psychological insulin resistance in type 2 diabetes: a critical comparison of measures
E. Holmes-Truscott et al. Current Diabetes Reports. DOI:10.1007/s11892-017-0873-4

This study examined ‘psychological insulin resistance’ (PIR) among people with type 2 diabetes with a view to identifying relevant measures. PIR has been described as (1) the assessment of attitudes or beliefs about insulin therapy and (2) hypothetical or actual resistance, or unwillingness, to use to insulin. The authors posit that assessment of PIR should focus on the identification of negative and positive attitudes towards insulin use. Actual or hypothetical insulin refusal may be better understood as a potential consequence of PIR. This paper provides guidance on the selection of questionnaires for clinical or research purpose and the development of new, or improvement of existing, questionnaires.
https://link.springer.com/article/10.1007%2Fs11892-017-0873-4

 

How can point-of-care HbA1c testing be integrated into UK primary care consultations? – a feasibility study
J.A. Hirst et al. Diabetes Research and Clinical Practice. DOI: http://dx.doi.org/10.1016/j.diabres.2017.05.014

Point-of-care (POC) HbA1c testing gives a rapid result, allowing testing and treatment decisions to take place in a single appointment. Trials of POC testing have not been shown to improve HbA1c, possibly because of how testing was implemented. This study aimed to identify key components of POC HbA1c testing and determine strategies to optimise implementation in UK primary care. It discovered that HbA1c measurement with POC devices can be effectively implemented in primary care. This work identified when these technologies might work best, as well as potential challenges. The authors suggest that their findings could be used to inform the design of a pragmatic trial to implement POC HbA1c testing.
http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(16)31798-3/fulltext

 

SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease
Honghong Zou et al. Cardiovascular Diabetology. DOI: 10.1186/s12933-017-0547-1

This is the complete abstract for this paper and makes very interesting reading. Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents, act on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin–angiotensin–aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
https://cardiab.biomedcentral.com/articles/10.1186/s12933-017-0547-1

 

Identification and management of neonatal hypoglycaemia in the full-term infant – a framework for practice
Co-chairs Dr James Boardman, Ms Janette Westman. British Association of Perinatal Medicine.

This is a comprehensive 35-page PDF report of the findings and recommendations of a working group that met in 2016. It was convened by NHS Improvement and British Association of Perinatal Medicine (BAPM). It set out to develop a Framework for Practice (FfP) that would: address variation in practices in the identification, management and admission thresholds of babies admitted to neonatal units for hypoglycaemia; and to promote safer practices that avoid unnecessary separation of mother and baby. The target audience is: all healthcare professionals involved in the care of infants born at term during the first 48 hours after birth, and should be delivered in partnership with parents.
http://www.bapm.org/publications/Hypoglycaemia%20F4P%20May%202017.pdf