Journal Watch

Prepared for IDDT by Jim Young

September 2014

Increase in the pharmacological management of Type 2 diabetes with pay-for-performance in primary care in the UK
N. Gallagher et al. Diabetic Medicine. Doi: 10.1111/dme.12575

The authors of this paper conducted an analysis of data from the General Practice Research Database for the years 1999 to 2008 looking at the treatment patterns of 21,197 people newly diagnosed with Type 2 diabetes. They sought to determine whether the financial incentives for tight glycaemic control, introduced in the UK as part of a pay-for-performance scheme in 2004, increased the rate at which people with newly diagnosed Type 2 diabetes were started on anti-diabetic medication. They found that the proportion of people with newly diagnosed diabetes managed without medication 12 months after diagnosis was 47% and after 24 months it was 40%. The conclusion was that the introduction of financial incentives in 2004 has effected a change in the management of people newly diagnosed with diabetes. They report that a greater proportion of people with newly diagnosed diabetes are being initiated on medication within 1 and 2 years of diagnosis as a result of the introduction of financial incentives for tight glycaemic control.


Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus
Pernille Kähler et al. BMJ Open. Doi: 10.1136/bmjopen-2014-004806

This study assessed the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. The study looked at randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes. It was found that there was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control, but the risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets. However, the authors posit that there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy.


Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes
P. Bjornstad et al. Diabetic Medicine. Doi: 10.1111/dme.12572

This study looked at 81 people aged 30 to 48 years with albuminuria and then re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate greater than 20 μg/min, and regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate less than 20μg/min) at follow-up. It was found that estimated insulin sensitivity was significantly higher at both baseline and at follow-up in people who had regression of albuminuria vs those who did not. The authors suggest that improving insulin sensitivity in people with Type 1 diabetes is a potential therapeutic target to increase rates of regression of albuminuria.


A qualitative synthesis of diabetes self-management strategies for long term medical outcomes and quality of life in the UK
Julia Frost et al. BMC Health Services Research. Doi: 10.1186/1472-6963-14-348

The aim of this research was to identify the ways in which self-management strategies are perceived by people with T2DM as being either supportive or unsupportive over time. The researchers conducted a systematic review of qualitative literature, published between 2000 and 2013. The findings were that people with T2DM both construct and draw upon causal accounts as a resource, and a means to counter their inability to balance medical outcomes and quality of life. These accounts can be mediated by the provision of timely and tailored information and support which would allow people to develop a flexible regimen that can facilitate both quality of life and medical outcomes.


Quantification of the glycemic response to microdoses of subcutaneous glucagon at varying insulin levels
Joseph El Youssef et al. Diabetes Care.  Doi: 10.2337/dc14-0803

Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. The authors report that here are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose. This study recruited 11 subjects with type 1 diabetes and examined the endogenous production of glucose by glucagon (EGP) at four doses and at three insulin infusion rates. It was found that at low insulin levels, EGP rose proportionately with glucagon dose, whereas at high levels, there was no increase in glucose output. The conclusion being that EGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates. However, high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas.


The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in Type 1 Diabetes
Hussein A. Rajab et al. Diabetes and Its Complications. Doi: 10.1016/j.jdiacomp.2014.08.004
In this study levels of biomarkers for clotting/fibrinolysis, inflammation and endothelial dysfunction were measured in 1,391 subjects with type 1 diabetes to determine whether their levels predicted increased risk to develop or accelerated progression of retinopathy during 16 years of follow-up.
It was found that high levels of sE-selectin and PAI-1 were associated with the development of retinopathy in patients with uncomplicated type 1 diabetes. [sE-selectin is a soluble cell adhesion molecule that may be an important biomarker for inflammatory processes] [PAI-1 is an inhibitor of fibrinolysis, the physiological process that degrades blood clots].


FDA allows marketing of first ZnT8Ab autoantibody test to help diagnose type 1 diabetes
U.S. Food and Drug Administration

This press release from the U.S. Food and Drug Administration announced that they have allowed the marketing of the first zinc transporter 8 autoantibody (ZnT8Ab) test that can help determine if a person has type 1 diabetes and not another type of diabetes. It asserts that when used with other tests and patient clinical information, the test may help some people with type 1 diabetes receive timely diagnosis and treatment for their disease. The report says that the immune system of many people with type 1 diabetes produces ZnT8Ab, but patients with other types of diabetes (type 2 and gestational) do not. The agency reviewed data from a clinical study of 569 blood samples – 323 from patients with diagnosed type 1 diabetes and 246 samples from patients diagnosed with other kinds of diabetes, other autoimmune diseases, and other clinical conditions. The test was able to detect the ZnT8 autoantibody in 65 percent of the samples from patients with diagnosed type 1 diabetes and incorrectly gave a positive result in less than two percent of the samples from patients diagnosed with other disease. The statement issues the caveat that a negative result from the test does not rule out a diagnosis of type 1 diabetes, and that the test should not be used to monitor the stage of disease or the response to treatment.


Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes
M. Blanco et al. Diabetes & Metabolism. Doi: 10.1016/j.diabet.2013.05.006

This study investigated the frequency of lipohypertrophy (LH) and its relationship to site rotation, glucose variability, hypoglycaemia and use of insulin. [Lipohypertrophy refers to a lump under the skin caused by accumulation of extra fat at the site of many subcutaneous injections of insulin]. The study included 430 outpatients injecting insulin who filled out a wide-ranging questionnaire regarding their injection technique. A diabetes nurse then examined their injection sites for the presence of LH. It was found that nearly two-thirds (64.4%) of patients had LH, and that there was a strong relationship between the presence of LH and non-rotation of sites, with correct rotation technique having the strongest protective value against LH. Of the patients who correctly rotated sites, only 5% had LH while, of the patients with LH, 98% either did not rotate sites or rotated incorrectly. Also, 39.1% of patients with LH had unexplained hypoglycaemia and 49.1% had glycaemic variability compared with only 5.9% and 6.5%, respectively, in those without LH. The authors concluded that correct injection site rotation appears to be the critical factor in preventing LH, which is associated with reduced glucose variability, hypoglycaemia, insulin consumption and costs.


Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study
Sune F Nielsen and Børge G Nordestgaard. The Lancet Diabetes & Endocrinology. Doi: 10.1016/S2213-8587(14)70173-1

Because the role of statins in the development of microvascular disease in patients with diabetes is unknown the investigators tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes. The study looked at all patients living in Denmark who were aged 40 years or older and were diagnosed with incident diabetes between 1996, and 2009. 15,679 individuals were randomly selected from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47,037 individuals who had never used statins before diagnosis (non-statin users). The conclusions from the study were that use of statins before diagnosis of incident diabetes was not associated with an increased risk of microvascular disease. Whether statins are protective against some forms of microvascular disease – a possibility raised by these data – will need to be addressed in other studies.


HbA1c, comorbid conditions and all-cause mortality in older patients with diabetes
David Grembowski et al. Diabetes Research and Clinical Practice. Doi: 10.1016/j.diabres.2014.07.017

This study examined whether HbA1c levels and comorbid conditions were related to all-cause mortality in patients with type 1 or 2 diabetes. In patients with comorbid congestive heart failure (CHF), the investigators asked if greater HbA1c values were associated with lower risk of mortality. It was found that patients with HbA1c scores less than 6.4% had significantly higher all-cause mortality. CHF was a major determinant of all-cause mortality; however, adults with comorbid CHF and high HbA1c scores had lower all-cause mortality.