Journal Watch

Prepared for IDDT by Jim Young

July 2013


Screening intervals for diabetic retinopathy and incidence of visual loss
J. B. Echouffo–Tcheugui et al. Diabetic Medicine. Doi: 10.1111/dme.12274

This systematic review [literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question] of 25 studies from PubMed and EMBASE assessed the incidence and prevalence of sight-threatening diabetic retinopathy in relation to screening frequency. The screening intervals ranged from 1 to 4 years in people with no retinopathy. The overall tendency observed in these programmes was that 2-year screening intervals among people with no diabetic retinopathy at diagnosis were not associated with high incidence of sight-threatening diabetic retinopathy. The authors suggest that a 2-year screening interval for people with no sight-threatening diabetic retinopathy at diagnosis may be safely adopted. For patients with pre-existing diabetic retinopathy, a shorter interval of ≤ 1 year is warranted.


Threshold-based insulin-pump interruption for reduction of hypoglycemia
Richard M. Bergenstal et al. NEJM. Doi: 10.1056/NEJMoa1303576

The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. This study evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in type 1 diabetes patients with nocturnal hypoglycemia. The findings were that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values.


Do lifestyle changes reduce serious outcomes in diabetes?
Hertzel C. Gerstein, NEJM. Doi: 10.1056/NEJMe1306987

The primary results of this large, randomized, controlled trial [RCT are often used to test the efficacy and/or effectiveness of various types of medical intervention within a patient population] of the long-term effects of an intensive lifestyle intervention on cardiovascular outcomes in patients with type 2 diabetes was reported in the NEJM. The Look AHEAD (Action for Health in Diabetes) study recruited 5,145 overweight or obese patients with type 2 diabetes. It was found that the intervention had a neutral effect on cardiovascular outcomes, a finding that was consistent across all reported subgroups, although the use of reportedly cardioprotective drugs might have been a contributive factor. But lifestyle interventions may have a real, if modest effect on cardiovascular outcomes that require more than 10 years to become apparent. The article suggests that investigators might consider using a diabetes-related outcome [outcomes of health care practices] that is linked to cardiovascular outcomes but that may have a quicker response – with growing evidence suggesting that the progression of diabetic retinopathy may be one such reliable outcome. The take away message for clinicians is that they can reassure their patients that intensive lifestyle interventions are unlikely to cause harm and that the importance of lifestyle changes will continue to be one of the foundations of modern diabetes care.


Insulin-deficient diabetes-induced bone microarchitecture changes – the preventive effects of metformin
María José Tolosa et al. Diabetes Research and Clinical Practice. Doi:10.1016/j.diabres.2013.05.016

The authors of this research remind us that diabetes mellitus is associated with metabolic bone disease and increased low-impact fractures. They also assert that insulin-sensitizer metformin possesses osteogenic effects. The study use a rat model to evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture. The effect of metformin on the osteogenic potential of bone marrow progenitor cells (BMPC) was also studied. Their conclusions were that partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.


A propensity score matched comparison of different insulin regimens 1 year after beginning insulin in people with type 2 diabetes
N. Freemantle et al. Diabetes, Obesity and Metabolism. Doi: 10.1111/dom.12147

This observational study [draws inferences about the possible effect of a treatment on subjects] compared the outcomes of beginning insulin therapy with basal, premix, meal-time + basal or meal-time insulin. The CREDIT (Cardiovascular Risk Evaluation in people with Type 2 Diabetes on Insulin Therapy) study analysed data from 3,031 people. The findings were that comparing insulin regimens between individuals matched by propensity scores indicated differences in hypoglycaemia and body weight change, despite similar HbA1c reductions. The authors assert that their findings are consistent with those from randomised controlled trials [RCT are often used to test the efficacy and/or effectiveness of various types of medical intervention within a patient population].


Obesity and kidney disease in type 1 and 2 diabetes: an analysis of the National Diabetes Audit
C.J. Hill et al. QJM. Doi: 10.1093/qjmed/hct123

Althoughobesity is a major risk factor for the development of type 2 diabetes its relationship with diabetic kidney disease (DKD) remains unclear. This retrospective cross-sectional study [a research study that involves repeated observations of the same variables over long periods of time] looked at data from the National Diabetes Audit and included both Type 1 and 2 diabetes patients (58,791 Type 1 and 733,769 Type 2 diabetes patients). DKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, albuminuria or both. The study found a strong association between obesity and kidney disease in Type 1 diabetes and confirmed their association in Type 2 diabetes.


The diabetes ‘Breathalyzer’
University of Pittsburgh.

This interesting article describes how chemists at the University of Pittsburgh have demonstrated a sensor technology that could significantly simplify the diagnosis and monitoring of diabetes through breath analysis alone. The researchers combined titanium dioxide with carbon nanotubes to produce an electrical semiconductor. The sensor was able to measure electrical resistance which could be activated with light to produce an electrical charge. Under ultraviolet light the sensor could measure acetone vapours. They posit that if such a sensor could be developed and commercialized, it could transform the way patients with diabetes monitor their glucose levels. The team is currently working on a prototype of the sensor, with plans to test it on human breath samples soon.

Insulin resistance and risk of incident heart failure
Dipanjan Banerjee et al. Circulation: Heart Failure. Doi: 10.1161/​CIRCHEARTFAILURE.112.000022

Patients with heart failure (HF) have higher fasting insulin levels and a higher prevalence of insulin resistance, and this can lead to structural abnormalities in the heart, such as increased left atrial size, left ventricular mass, and alterations in transmitral velocity that can precede the diagnosis of HF. However, it is not known whether insulin resistance precedes the development of HF or whether insulin resistance is present among adults with HF caused by nonischemic heart disease. This study recruited 4,425 participants to estimate the relative risk of incident HF associated with fasting insulin. It was found that fasting insulin levels were positively associated with the risk of incident HF. Measures of left atrial size, left ventricular mass, and peak A velocity were also associated both with fasting insulin levels and with HF. The overall conclusion was that fasting insulin was positively associated with adverse echocardiographic features and risk of subsequent HF.


Outcome of review of new safety data on insulin glargine
European Medicines Agency. EMA/329790/2013
On 30 May 2013, the European Medicines Agency completed a review of new data on the cancer risk with insulin glargine-containing medicines. The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that the data do not show an increased risk of cancer and that the balance of the medicine’s benefits and risks remained unchanged. In 2009, the publication of four registry studies raised concerns of a possible link between insulin glargine and cancer, particularly breast cancer. Following the publication, the CHMP carried out an in-depth review and concluded, in July 2009 that, due to some limitations in the way the studies were conducted, a link between insulin glargine and cancer could not be confirmed or excluded from the results. The CHMP requested that the company that markets the medicine provide further data. The company subsequently carried out further studies and submitted the results to the CHMP for review. Based on the assessment of the population-based studies, the CHMP concluded that overall the data did not indicate an increased risk of cancer with insulin glargine, noting that there is no known mechanism by which the insulin glargine would cause cancer and that a cancer risk has not been seen in laboratory studies.


Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal–bolus treatment with mealtime insulin aspart in Type 1 diabetes
B. W. Bode et al. Diabetic Medicine. Doi: 10.1111/dme.12243

The aim of this open-label trial [a type of clinical trial in which both the researchers and participants know which treatment is being administered] was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period. It was found that the rate of nocturnal hypoglycaemia was 25% lower with insulin degludec than with insulin. Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar. It was also found that despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients.