Journal Watch

Prepared for IDDT by Jim Young

May 2014

Variations in the quality and sustainability of long-term glycaemic control with continuous subcutaneous insulin infusion
R. Nixon et al. Diabetic Medicine. Doi: 10.1111/dme.12486

Using computerised clinic records this study looked at HbA1c changes in 35 adult people with Type 1 diabetes and an elevated HbA1c. The patients had been treated with multiple daily insulin injections and had been switched to continuous subcutaneous insulin infusion for at least 5 years. The researchers identified three subgroups with similar baseline HbA1c but different long-term responses to pump therapy: group A) those with improvement followed by deterioration (57%); group B) those with improvement that was sustained throughout the 5 years (31%); and group C) those where HbA1c did not change significantly from baseline (12%). The data was summarised as confirming improved glycaemic control with continuous subcutaneous insulin infusion maintained over 5 years by 88% of people with Type 1 diabetes. However, it was noted that there were variations in the long-term efficacy, with some people improving and worsening, others maintaining strict control and a few subcutaneous insulin infusion ‘non-responders’.


Effect of insulin analogues on risk of severe hypoglycaemia in patients with type 1 diabetes prone to recurrent severe hypoglycaemia (HypoAna trial)
Ulrik Pedersen-Bjergaard et al. The Lancet Diabetes & Endocrinology. Doi: 10.1016/S2213-8587(14)70073-7

The authors of this study state that although insulin analogues have been developed to reduce the risk of hypoglycaemia in patients with diabetes who require insulin-based treatment, their effect on this endpoint in patients with type 1 diabetes complicated by recurrent severe hypoglycaemia is unknown. This trial was conducted at seven medical centres in Denmark and looked at patients aged 18 years or over with type 1 diabetes that had been diagnosed for more than 5 years, and who had reported two or more episodes of severe hypoglycaemia in the preceding year. It was found that treatment with insulin detemir and aspart in patients with type 1 diabetes and recurrent severe hypoglycaemia resulted in a clinically significant reduced rate of severe hypoglycaemia compared with human insulin.


Effect of early multifactorial therapy compared with routine care on microvascular outcomes at 5 years in people with screen-detected diabetes
Annelli Sandbæk et al. Diabetes Care. Doi: 10.2337/dc13-1544

This study was conducted in four centers in: Denmark; Cambridge, U.K.; The Netherlands; and Leicester, U.K., and 343 general practices participated with 2,861 people with diabetes detected by screening being followed-up. Biomedical data on nephropathy were collected in 2,710 (94.7%) participants, retinal photos in 2,190 (76.6%), and questionnaire data on peripheral neuropathy in 2,312 (80.9%). It was found that compared with routine care, an intervention to promote target-driven, intensive management of patients with type 2 diabetes detected by screening was not associated with significant reductions in the frequency of microvascular events at 5 years.


Metformin vs insulin in the management of gestational diabetes
D .F. Su and X.Y. Wang. Diabetes Research and Clinical Practice. Doi:10.1016/j.diabres.2013.12.056.
This study searched four electronic databases and then two investigators independently reviewed the titles and abstracts, performed data abstraction on full articles, and assessed the quality of the study. Six randomized clinical trials involving 1,420 subjects were included. The authors report that the data suggested that using metformin in gestational diabetes subjects did not significantly increase adverse maternal outcomes and neonatal outcomes, also with less weight gain and neonatal hypoglycemia, but a higher incidence of premature birth.


Serious harm from inpatient hypoglycaemia: a survey of hospitals in the UK
R. Rajendran and G. Rayman. Diabetic Medicine. Doi: 10.1111/dme.12457

An anonymised questionnaire e-mailed to lead organisers at the 142 acute NHS Trusts that contributed to the National Diabetes Inpatient Audit 2012 found that an alarming number of serious adverse events were reported (12 serious adverse events with three deaths) over a 1-year period in 41 Trusts. The authors posit that this may be the tip of the iceberg, considering the potential under-reporting. Robust reporting mechanisms are required to determine the full extent of this serious preventable harm.


Aging is associated with increased HbA1c levels, independently of glucose levels and insulin resistance, and also with decreased diagnostic specificity
N. Dubowitz et al, Diabetic Medicine. Doi: 10.1111/dme.12459

This analysis investigated whether using HbA1c for screening and management could be confounded by age differences and whether the effects of aging have an impact on diagnostic accuracy. It reported that in two large datasets, using different methods to measure HbA1c, the association of age with higher HbA1c levels was confirmed along with reduced diagnostic specificity. The authors suggest that age should be taken into consideration when using HbA1c for the diagnosis and management of diabetes and prediabetes.


High efficient and cost-effective screening method for diabetic cardiovascular risk
Tadafumi Kajimoto et al. Diabetology & Metabolic Syndrome. Doi: 10.1186/1758-5996-6-51

After analysing five years of clinical data from 337 outpatients (196 males and 141 females) with diabetes the authors of this report developed a simple and noninvasive screening method to evaluate the possibility of ischemic heart disease in patients with diabetes. The paper itemises the laboratory data used and concludes that ischemic heart disease could be predicted in patients with diabetes using a combination of results from the conventional physical and laboratory tests used.


Diabetes-specific emotional distress in people with Type 2 diabetes: a comparison between primary and secondary care
C. H. Stoop et al. Diabetic Medicine. Doi: 10.1111/dme.12472

 This study of 774 patients from 24 primary care practices, and 526 patients from and three secondary care clinics, compared levels of diabetes distress in people with Type 2 diabetes and examined demographic and clinical correlates that may explain the potential differences between care settings. It found that in primary care, lower levels of diabetes distress were reported than in secondary care. The difference in diabetes distress between care settings can be largely, but not fully, explained by specific demographic and clinical characteristics. The authors say that their results need to be interpreted with caution because they were based on two separate studies, but they do call into question the need to screen for diabetes distress in people with Type 2 diabetes in primary care.


Combination therapy with metformin plus sulfonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality
C.Ll. Morgan et al. Diabetes, Obesity and Metabolism. Doi: 10.1111/dom.12306

This study compared the risk of major adverse cardiovascular events (MACE) and mortality for combination therapies with metformin and either sulfonylurea (SU) or DPP-4 inhibitor (DPP-4i). Data was extracted from the UK Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes treated with combination therapies comprising metformin plus SU or DPP-4i were included in the study. There were 33,983 patients prescribed SU and prescribed 7,864 DPP-4i.The co-primary endpoints were all-cause mortality and MACE (myocardial infarction or stroke).
It was discovered that there was a reduction in all-cause mortality for patients treated with metformin combined with DPP-4i versus metformin plus SU, and a similar trend for MACE.


SGLT2 inhibitors in the treatment of type 2 diabetes
Farhad M. Hasan et al. Diabetes Research and Clinical Practice. Doi:10.1016/j.diabres.2014.02.014

The abstract to this paper reminds us that the kidney plays an important role in glucose homeostasis via its production, utilization, and, most importantly, reabsorption of glucose from glomerular filtrate which is largely mediated via the sodium glucose co-transporter 2 (SGLT2). Pharmacological inhibition of SGLT2 increases urinary glucose excretion and decreases plasma glucose levels in an insulin-independent manner. Agents that inhibit SGLT2 represent a novel class of drugs, which has recently become available for treatment of type 2 diabetes. The article summarizes the rationale for use of these agents and reviews available clinical data on their efficacy, safety, and risks/benefits.