Journal Watch

Prepared for IDDT by Jim Young

November 2015

Elevated baseline glomerular filtration rate (GFR) is independently associated with a more rapid decline in renal function of patients with type 1 diabetes
Hilary J. Thomson et al. Journal of Diabetes and Its Complications. Doi:
Renal hyperfiltration is observed prior to the development of diabetic kidney disease (DKD) in patients with type 1 diabetes (T1DM). Because its significance remains uncertain, this study looked at the association between measured baseline glomerular filtration rate (GFR) and renal function decline in patients with T1DM. The study included 142 adult patients with T1DM who were followed up for 19 years. It found that a higher baseline measured glomerular filtration rate (mGFR) was associated with more rapid mGFR decline. This is an important finding because patients with high baseline mGFR who developed rapid mGFR decline had higher HbA1c measurements throughout the study. The authors suggest that their findings are consistent with the concept that poor glycaemic control over time may be a determining factor for the rapid renal function decline observed in some hyperfiltering patients.

LDL cholesterol is not a good marker of cardiovascular risk in Type 1 diabetes
C. Hero et al. Diabetic Medicine. Doi: 10.1111/dme.13007

LDL cholesterol (LDL–C) is considered an important cardiovascular disease (CVD) risk factor, but less is known about its significance in Type 1 diabetes. This study assessed LDL–C and also the total cholesterol to HDL cholesterol ratio (TC/HDL–C) as predictors of CVD in Type 1 diabetes. The study population was large and monitored 30,778 people with Type 1 diabetes, from a baseline of 2003–2006 through to December 2011. The findings were that LDL–C was not a good predictor of CVD. The investigators found that there was no support for an LDL–C cut-off point < 2.6 mmol/l. TC/HDL–C appeared to be a more reliable as a marker for CVD risk when considering primary prevention.


Statins are independently associated with increased HbA1c in Type 1 Diabetes
Magnus Thorsten Jensen et al. Diabetes Research and Clinical Practice. Doi:
Statin use has been associated with increased risk of developing type 2 diabetes (T2DM) and with impaired glycemic control in T2DM patients. However, the association between statin use and glycemic control in type 1 diabetes (T1DM) is unknown. In this study the association between use of statins and glycemic control in T1DM patients without known heart disease was examined. The investigation looked at 1,093 T1DM patients of mean age 49.6 years, 53% were men, and mean diabetes duration was 25.5 years. Of these patients 475 (43.5%) were receiving statins. It was also observed that statin users tended to be older, have longer diabetes duration, and have more severe kidney disease. The findings were that the use of statins was independently associated with impaired glycemic control. However, a causal relationship could not be determined from this study. The authors advise that, given the benefit of statin use on cardiovascular outcome, this should not cause patients to stop statin treatment, but may indicate a need to revisit dose of insulin when starting statin treatment.


The management of adult diabetes services in the NHS: progress review
National Audit Office.  ISBN: 9781786040084

This report from the National Audit Office alerts us to the fact that improvements in delivery of key care processes have stalled, and that “this is likely to be reflected in a halt to outcomes improvement for diabetes patients.” It alarmingly reports that there are still 22,000 people estimated to be dying each year from diabetes-related causes that could potentially be avoided. The estimated cost of diabetes to the NHS in England in 2010-11 was £5.6 billion, 69% of which was the cost of complications, such as amputation, blindness, kidney failure and stroke. Since the NAO last reported on diabetes services, the relative risk for people with diabetes developing complications has not changed or has reduced for most complications. But, the increase in the number of people with diabetes means that the absolute number of diabetes patients with complications is rising. If that was not enough, it also reports that there are significant variations across England in delivering key care processes, achieving treatment standards and improving outcomes for diabetes patients. For example, across clinical commissioning groups: the percentage of people with diabetes receiving all the recommended care processes, apart from eye screening, ranged from 30% to 76% in 2012-13; and the additional risk of death among people with diabetes within a one-year follow-up period, ranged from 10% to 65%. Worryingly, younger people with type 1 and type 2 diabetes and all people with type 1 diabetes receive fewer of the recommended care processes and are less likely to achieve all 3 treatment standards. Amongst the NAO’s recommendations is that NHS England should set out how it intends to hold clinical commissioning groups to account for poor performance in delivering key care processes, the 3 treatment standards and longer-term outcomes. The full report and a summary are available from links on the webpage.


Answers to commonly asked questions about biosimilar versions of insulin glargine
Nicola Hooke. London Medicines Evaluation Network Review.

This briefing sheet [a 9 page PDF] is intended to support prescribers by providing answers to
commonly asked questions about the introduction of these medicines. It answers such questions as: What is a biosimilar medicine? What brands of insulin glargine will be available for use? What objections are being raised about using biosimilar versions of insulin glargine? What evidence is required for the approval of biosimilars in the EU? What evidence exists to support the use of a biosimilar version of insulin glargine? If the clinical studies were conducted in adults, what evidence is there to support use of the biosimilar in children? Will there be any independent guidance available to help inform clinical practice? What is the current national guidance regarding choice of insulin Are there any potential advantages to using a biosimilar version of insulin glargine?  in patients with diabetes? Is there any guidance on switching between Lantus® and the biosimilar? Fascinating and informative reading!


Insulin dose and cardiovascular mortality in the ACCORD trial
Elias S. Siraj. Et al. Diabetes Care. Doi: 10.2337/dc15-0598

In the ACCORD trial it was reported that intensive treatment of patients with type 2 diabetes and high cardiovascular (CV) risk was associated with higher all-cause and CV mortality. However, subsequent analyses have failed to implicate rapid reduction of glucose, hypoglycemia, or specific drugs as the causes of this finding. The authors of this report hypothesized that exposure to injected insulin might be quantitatively associated with increased CV mortality. They examined insulin exposure data from 10,163 participants followed-up for 5 years. Their findings were that more of the participants who were allocated to intensive treatment than standard treatment were prescribed insulin in ACCORD, with a higher total daily dose. It was reported that, after adjustment for baseline covariates, no significant association of insulin dose with CV death was observed. [A covariate is a variable that is possibly predictive of the outcome under study. A covariate may be of direct interest or it may be a confounding or interacting variable]. The conclusion was that their analyses provided no support for the hypothesis that insulin dose contributed to CV mortality in the ACCORD trial.


Depressive symptoms in youth with type 1 or type 2 diabetes
Janet Silverstein et al. Diabetes Care. Doi: 10.2337/dc15-0982

This study looked the frequency of depressive symptoms, the diagnosis and the management of depression in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D). It found that symptoms of depression were identified in 13% of T1D and 22% of T2D participants. It was also found that of these, only 4% of T1D and 9% of T2D youth had been treated by a therapist within the prior 12 months. The authors conclude that depressive symptoms are more frequent than diagnosed depression in youth with T1D or T2D, and that their results underscore the need for regular depression screening and appropriate referral for youth with diabetes.


Successful maintenance on sulfonylurea therapy and low diabetes complication rates in a HNF1A–MODY cohort
S. Bacon et al. Diabetic Medicine. Doi: 10.1111/dme.12992

The introduction to this paper says that HNF1A gene mutations are the most common cause of maturity-onset diabetes of the young (MODY) in the UK, and that persons with HNF1A–MODY display sensitivity to sulfonylurea therapy. The aim of the study was to determine the natural progression and clinical management of HNF1A–MODY diabetes with special reference to the prevalence of micro- and macrovascular complications. Sixty patients participated in the study. The results showed that following a genetic diagnosis of MODY the majority (80%) of the cohort treated with sulfonylurea therapy remained insulin independent at 84–month follow-up. It was also noted that the rate of retinopathy was significantly lower than that noted in the Type 1 diabetes mellitus group, and there was also a lower rate of microalbuminuria and cardiovascular disease. The authors posit that their study demonstrated that the majority of patients with HNF1A–MODY can be maintained successfully on sulfonylurea therapy with good glycaemic control. They also suggest that the use of appropriate therapy at early stages of the disorder may decrease the incidence of complications.


Development and validation of risk prediction equations to estimate future risk of blindness and lower limb amputation in patients with diabetes
J Hippisley-Cox. BMJ. Doi:

This study looked at the possibility of developing risk prediction equations to estimate the 10-year risk of blindness and lower limb amputation in patients with diabetes aged 25 to 84 years. It analysed routinely collected data from general practices in England. The calculations they used were based on variables that patients are likely to know or that are routinely recorded in general practice computer systems. They can be used to identify patients at high risk for prevention or further assessment. This study will enable patients with type 1 or type 2 diabetes – who are at increased risk of blindness and amputation – to accurately assess the magnitude of their individual risks.


Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections
Marcus Lind et al. BMJ. Doi:

This study looked at the effects of liraglutide, an incretin based treatment, on glycaemic control in people with type 2 diabetes treated with multiple daily insulin injections. [Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from the beta cells of the islets of Langerhans after eating]. It was carried out at 13 hospital based outpatient clinics and one primary care unit in Sweden. Patients were considered eligible for inclusion if they had type 2 diabetes and inadequate glycaemic control (HbA1c concentrations ≥58 mmol/mol (7.5%) and ≤102 mmol/mol (11.5%)), a body mass index of 27.5-45 kg/m2, and required multiple daily insulin injections. 124 participants were randomised 1:1 to receiving subcutaneous liraglutide or placebo, and the main outcome measured was change in HbA1c level from baseline to week 24. It found that liraglutide was associated with a significant reduction of 16.9 mmol/mol (1.5%) in HbA1c versus 4.6 mmol/mol (0.4%) for placebo. Body weight was also significantly reduced in participants in the liraglutide compared with placebo, and total daily insulin doses were significantly reduced, by 18.1 units and 2.3 units
It reported that neither group experienced severe hypoglycaemic events nor were there any significant differences in symptomatic or asymptomatic non-severe hypoglycaemia. The authors summarised that adding liraglutide to multiple daily insulin injections in people with type 2 diabetes improved glycaemic control without an increased risk of hypoglycaemia, and enabled patients to lower their insulin doses.