Clinical inertia to insulin initiation and intensification in the UK: A focused literature review

Kamlesh Khunti and David Millar-Jones. Primary Care Diabetes. DOI: http://dx.doi.org/10.1016/j.pcd.2016.09.003

The benefit of glycaemic control in T2DM has been shown in the UKPDS study where reduced microvascular disease after 10 years and macrovascular disease in the decade after were shown in the intensive control arm. This has also been shown in other studies including VADT. Furthermore, the progressive nature of T2DM due to β cell failure is well recognised as is the requirement to monitor the effect of hypoglycaemic agents and intensify treatment when necessary. This is reinforced in the 2015 NICE guidance with an HbA1c of 7.5% being set as an intensification threshold. Patients are often reluctant to intensify their treatment, especially when insulin is introduced including changes to insulin regime and number of injections. The UK is one of the worse countries in Europe for this ‘clinical inertia’ as shown in the SOLVE study where the UK cohort had a mean HbA1c of 9.8% v 8.9% in the global population at insulin initiation despite a shorter duration of disease. Reasons for this inertia include fear of injections and hypoglycaemia as well as lack of confidence by clinicians – given that routine management is moving into primary care.

http://www.primary-care-diabetes.com/article/S1751-9918(16)30099-7/fulltext

 

Bariatric surgery in women of childbearing age, timing between an operation and birth, and associated perinatal complications

Brodie Parent et al. JAMA Surgery. DOI: 10.1001/jamasurg.2016.3621

The rise in obesity has led to increasing numbers of bariatric procedures being performed in women of child bearing age. Obesity has a significant impact on pregnancy, being associated with fetal macrosomia, hypertension and gestational diabetes. Given the metabolic changes that happen after surgery, patients are advised not to become pregnant for 2 years after the procedure especially as this time of rapid weight loss and metabolic changes can result in nutritional deficiencies. This retrospective study looked at the relationship between perinatal outcomes in pregnancies occurring shortly after surgery. Compared with women without a history of surgery, ‘post-operative mothers’ had a higher incidence of prematurity, low Apgar scores and admissions to NICU. Women whose pregnancy occurred less than 2 years after surgery had a higher rate of these complications than those whose pregnancies occurred more than 4 years after surgery. Given the improved fertility associated with weight loss, the need to postpone pregnancy for some time after a bariatric procedure should be reinforced pre-operatively.

http://jamanetwork.com/journals/jamasurgery/fullarticle/2569812

 

Attitudes towards insulin initiation in type 2 diabetes patients among healthcare providers: a survey research

Javier Escalada et al. Diabetes Research and Clinical Practice. DOI: http://dx.doi.org/10.1016/j.diabres.2016.10.003

‘Clinical inertia’ is a buzz phrase in diabetes, highlighting slow escalation of hypoglycaemic therapy in patients with poorly controlled type 2 diabetes (T2DM). Published studies typically assess routinely collected data and these are nowhere near as robust as clinicians are led to believe. For example, whilst databases allow for assessment of HbA1c at the time of initiation of a new class of hypoglycaemic agent, they do not capture treatment escalation within a class. Given that the first two default therapies for T2DM (metformin and sulphonylureas) have several dose steps (up to ten), this is a major limitation. One thing that is not in doubt is that insulin initiation occurs at much higher HbA1c levels than are recommended in any guideline (typically 86 mmol/mol [10%] in the UK). This observational study from Spain highlights that GPs and non-specialists delay insulin starts for longer than endocrinologists and initiate at higher HbA1c levels – no surprises here. However, it also shows that only a minority of endocrinologists follow guidelines for insulin initiation. This may imply lack of ‘buy-in’ to the treatment targets rather than inertia?

http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(16)30503-4/fulltext

 

Mechanistic modeling of hemoglobin glycation and red blood cell kinetics enables personalized diabetes monitoring

Roy Malka et al. Science Translational Medicine. DOI: 10.1126/scitranslmed.aaf9304

Practicing clinicians are familiar with the concept of a ‘normal range’ when they receive the results of investigations. Almost all routinely requested biochemistry tests have variation which is clinically acceptable and this includes the haemoglobin A1c (HbA1c) …. until a patient is diagnosed with diabetes. At this point, variability ceases to exist and one value applies to all. The HbA1c target is 6.5% (48mmol/mol) or 7.5% (58mmol/mol) or whatever is individualised for the patient but it is never a range between ‘X’ and ‘Y’. This is clearly a nonsense. This complex mathematical paper provides theoretical support for this contention. The authors examine the relationship between HbA1c and average blood glucose concentration and report substantial glucose-independent variation in HbA1c that limits its precision. They then combined a mechanistic mathematical model of hemoglobin glycation and red blood cell kinetics with large sets of within-patient glucose measurements. Mean red blood cell age was found to explain all the glucose-independent variation. It is unlikely that this methodology will be introduced into clinical practice but hopefully it will make clinicians think about HbA1c targets.

http://stm.sciencemag.org/content/8/359/359ra130.full

 

Current perspectives on cardiovascular outcome trials in diabetes

Oliver Schnell et al. Cardiovascular Diabetology. DOI: 10.1186/s12933-016-0456-8

There are now three published cardiovascular outcome trials (CVOTs) which have demonstrated superiority of glucose-lowering therapies versus placebo. The first examined the SGLT-2 inhibitor, empagliflozin, whilst the latter two used the GLP-1 receptor agonists, liraglutide and semaglutide. This review highlights some of the issues that remain unanswered. The authors point out that components of the primary end-point have different aetiologies (e.g. thrombosis for myocardial infarction, arrhythmias for CV death) and also focus on the need to closely examine heart failure. They highlight the difficulty of extrapolating results from high-risk CV patients included in these studies to the general T2DM population. The relatively short duration of the studies is noted, with the suggestion that this could be addressed by the use of routinely collected data. The lack of active comparators is seen as a weakness and the authors suggest that more detailed analysis of microvascular complications should be included in future protocols. Finally, they observe that the most commonly used hypoglycaemic agents, metformin and sulphonylureas, have not be exposed to the scrutiny of a CVOT – and probably never will be.

http://cardiab.biomedcentral.com/articles/10.1186/s12933-016-0456-8