Gestational diabetes mellitus in early pregnancy: evidence for poor pregnancy outcomes despite treatment
Arianne N. Sweeting et al. Diabetes Care. Doi: 10.2337/dc15-0433
The recognition that women with diabetes have adverse pregnancy outcomes has been known for many years – indeed, addressing this was one of the pillars of the 1989 St Vincent declaration. As a result, over the last few years, reinforced in the 2015 NICE guidance, increasing attention has been given to managing women with dysglycaemia in pregnancy – both those with pre-existing diabetes and identifying those with gestational diabetes (GDM). This US study examined pregnancy outcomes in women with pre-existing T2DM and those identified with GDM at <12 (early), 12-23 and >24 weeks. Adverse outcomes including pre-eclampsia, pre-term delivery and neonatal jaundice were more prevalent in women with pre-existing T2DM and early (<12 weeks) GDM than those identified with GDM later in pregnancy. There was no difference in outcomes between early GDM and T2DM indicating the need to proactively treat hyperglycaemia in early pregnancy. However, experience suggests that significant numbers of patients with ‘early GDM’ actually have pre-existing T2DM which reinforces the need to confirm a women’s glycaemic status post partum.
Diabetes medications with cardiovascular protection in the wake of EMPA-REG OUTCOME
Robert EJ Ryder and Ralph A Defronzo. British Journal of Diabetes. Doi: http://dx.doi.org/10.15277/bjdvd.2015.045
Reducing the elevated risk of cardiovascular disease in T2DM is the main aim of patient treatment. Whilst certain treatments are well established, specifically statins and anti-hypertensive’s, the benefit of hypoglycaemic agents is more controversial. The benefits of Metformin were clearly established in the UKPDS study where a reduction in cardiovascular death was demonstrated in patients with early T2DM – although this did not become apparent for several years. The PROACTIVE study demonstrated the benefit of Pioglitazone in reducing CV death, myocardial infarction and stroke. It also reduces carotid intimal thickness, suggesting a slowing down of the atherosclerotic process. More recently, the EMPA-REG study demonstrated a reduction in CV death in high risk patients – but not non-fatal MI or stroke, signifying a different mechanism to that of Pioglitazone. Furthermore, the diuretic effect of Empagliflozin may mitigate the fluid retention of Pioglitazone. As a result, a combination of Metformin, Pioglitazone and Empagliflozin may be an effective combination of agents for patients with T2DM at high CV risk. However, given that both Metformin and Pioglitazone are off patent, it is unlikely that this combination will be tested by clinical trial.
Standards of medical care in diabetes
American Diabetes Association. January 2016; 39 (Supplement 1)
For the whole of 2015, healthcare professionals in the UK observed the agonies of the National Institute for Health and Care Excellence (NICE) as it struggled to produce new guidelines for the management of type 2 diabetes. This was an update of the NICE clinical guideline published in 2008 (with a glycaemic therapy revision in 2009). Contrast this with the situation in the United States, where the American Diabetes Association (ADA) produces an annual update of its ‘Standards of Medical Care in Diabetes’, a comprehensive suite of documents dealing with all aspects of the condition. Back in 2009, there was a much greater consensus between UK and US practice, with similar targets for HbA1c, blood pressure, lipids and aspirin use. Today, significant divergence is beginning to emerge. In the US, HbA1c targets are less prescriptive, whilst options for pharmacotherapy are much more flexible. Lipid management remains focused on LDL-cholesterol, whereas in the UK non-HDL-cholesterol has become the focus. Use of aspirin is also encouraged, whereas NICE now precludes its use for primary prevention. Same evidence, different recommendations….
Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study
Douglas H.J. Elde et al. European Journal of Heart Failure. Doi: 10.1002/ejhf.455
Interest in heart failure (HF) and type 2 diabetes (T2DM) was rekindled in 2013 following the publication of two cardiovascular (CV) safety trials of DPP-4 inhibitors. The SAVOR-TIMI 53 study reported a significant increase in hospitalisation for HF with saxagliptin (3.5% vs. 2.8% placebo; P=0.007). The EXAMINE study, compared alogliptin with placebo and whilst there was no significant increase in HF, a trend was observed. These results had several impacts. Cardiologists argued that HF should be included as a CV outcome (previously composites of myocardial infarction, stroke +/- angina had been used) and some clinicians no longer prescribed DDP4is. There was also a hypothesis that all glucose-lowering strategies might increase HF risk, as glucose might be the major energy substrate for the failing heart. Reassurance came when the TECOS trial of sitagliptin showed no increase in HF and this publication from Scotland supports that concept that tight glycaemic control in itself is not a risk. However, a U-shaped mortality curve was seen for time-weighted mean HbA1c suggesting that certain therapies (insulin and sulphonylureas) may be harmful; the jury is still out.
Association between use of warfarin with common sulfonylureas and serious hypoglycemic events
John A Romley et al. BMJ. Doi: http://dx.doi.org/10.1136/bmj.h6223
Debate around the safety of the sulphonylurea (SU) class of antidiabetic agents continues to rage. Whilst no-one doubts the association with hypoglycaemia and weight gain, the question of whether these side-effects (and/or others) lead to an increase in cardiovascular (CV) mortality is unresolved. This is despite reassuring results from the United Kingdom Prospective Diabetes Study (UKPDS) in 1998, a trial which was specifically designed to address this issue. So, over the last few years, there have been several meta-analyses suggesting increased CV risk, and SUs have slowly moved down the treatment algorithm for type 2 diabetes (including the most recent guideline from NICE). This retrospective cohort analysis from the US of 465,918 patients prescribed SUs reports that those receiving warfarin medication were more likely to attend secondary care due to hypoglycaemia, consistent with an adverse drug interaction. Whilst this type of analysis cannot attribute cause-and-effect (for example, being on warfarin might imply worse renal function, hence increased hypoglycaemia risk), it does suggest that co-prescribing with SUs should be avoided. More ammunition for the anti-SU lobby.