Journal Watch

Prepared for IDDT by Jim Young

April 2014

Effects of low dose metformin in adolescents with type I diabetes mellitus
Kristen J Nadeau et al. Pediatric Diabetes. Doi: 10.1111/pedi.12140

The background to this paper noted that insulin resistance increases during adolescence in those with type 1 diabetes mellitus (T1DM), and that this complicates glycemic control and potentially increases cardiovascular disease risk. [Insulin resistance is physiological condition in which cells fail to respond to the normal actions of the hormone insulin]. The authors hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Their study looked at 74 adolescents aged 13 to 20 years with T1DM.Their findings indicated that that low-dose metformin probably improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose.


Changes in basal rates and bolus calculator settings in insulin pumps during pregnancy in women with type 1 diabetes
Jonathan M. Mathiesen et al. Journal of Maternal-Fetal and Neonatal Medicine. Doi:10.3109/14767058.2013.837444

This study examined insulin pump settings in a cohort of pregnant women with type 1 diabetes on insulin pump therapy with a bolus calculator. [A cohort is a group of people who share a common characteristic or experience within a defined period].Twenty-seven women were included in the study. At 8, 12, 21, 27 and 33 weeks, insulin pump settings and HbA1c were recorded. These results were compared with 96 women with type 1 diabetes on multiple daily injection therapy. It was found that in women with type 1 diabetes on insulin pump therapy with a bolus calculator, the carbohydrate-to-insulin ratio declined 4-fold from early to late pregnancy, whereas changes in basal insulin delivery were smaller. [Carbohydrate to insulin ratio is the number of grams of carbohydrate covered by a certain amount of bolus insulin].Throughout pregnancy, the carbohydrate-to-insulin ratio decreased at all three main meals. The most pronounced decrease was observed at breakfast, where the carbohydrate-to-insulin ratio was reduced, from median 12 in early pregnancy to 3 grams carbohydrate per unit insulin in late pregnancy.


The UK service level audit of insulin pump therapy in adults
H. D. White et al. Diabetic Medicine. Doi: 10.1111/dme.12325

The first UK-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. This paper reports the results of the adult service level audit. One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the UK, of which 178 (97.3%) participated in the audit. It records that the prevalence of continuous subcutaneous insulin infusion use in the UK falls well below the expectation of NICE (15–20%) and that of other European countries (greater than 15%) and the USA (40%). The authors posit that this may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users.


Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus
Birgit Fullerton et al. Cochrane Library. Doi: 10.1002/14651858.CD009122.pub2

Clinical guidelines differ regarding recommended blood glucose targets for patients with type 1 diabetes and recent studies on patients with type 2 diabetes suggest that aiming at very low targets can increase the risk of mortality. This study set out to assess the effects of intensive versus conventional glycaemic targets in patients with type 1 diabetes in terms of long-term complications and determine whether very low, near normoglycaemic values are of additional benefit. It was found that tight blood sugar control reduced the risk of developing microvascular diabetes complications. The evidence of benefit was mainly from studies in younger patients at early stages of the disease. The authors suggest that these benefits need to be weighed against risks including severe hypoglycaemia, and they say that patient training is an important aspect in practice. They report that the effects of tight blood sugar control seem to become weaker once complications have been manifested. The discussion suggests that there is a lack of evidence on the effects of tight blood sugar control in older patient populations or patients with macrovascular disease. Because there is no firm evidence for specific blood glucose targets,  treatment goals need to be individualised taking into account age, disease progression, macrovascular risk, as well as the patient’s lifestyle and disease management capabilities.


Results from the UK cohort of SOLVE: Providing insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice
Kamlesh Khunt et al. Primary Care Diabetes. Doi:10.1016/j.pcd.2013.11.010

The authors remind us that SOLVE was a large observational study of more than 17,000 insulin-naïve patients with type 2 diabetes, that investigated basal insulin analogue initiation in a primary care setting across a diverse geographical area. This analysis of the results compared and contrasted the results of the UK cohort with the previously published global population results. The conclusion was that it is possible to improve glycaemic control and reduce HbA1c in patients previously uncontrolled with oral antidiabetic drug therapy, in a primary setting, despite clinical inertia.


The Ipswich Touch Test: a simple and novel method to screen patients with diabetes at home for increased risk of foot ulceration
S. Sharma et al. Diabetic Medicine. Doi: 10.1111/dme.12450

The Ipswich Touch Test is a novel method to detect loss of foot sensation and involves lightly and briefly touching the tips of the first, third and fifth toes of both feet with the index finger. The authors of this study investigated whether it could be used by relatives and/or carers to detect reduced foot sensation in the setting of the patient’s home. It was found that with clearly written instructions, this simple test can be used by non-professionals to accurately assess for loss of protective sensation. The authors suggest that the test may also be a useful educational adjunct to improve awareness of diabetes foot disease in patients and relatives alike and empower them to seek appropriate care if sensation was found to be abnormal.


The cytotoxic role of intermittent high glucose on apoptosis and cell viability in pancreatic beta cells
Zhen Zhang et al. Journal of Diabetes Research. Doi: 10.1155/2014/712781

The introduction to this paper states that glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. The paper investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. [Apoptosis is the process of programmed cell death that may occur in multicellular organisms]. [Rat INS-1 cell line cultures secrete insulin in response to glucose concentrations in the physiological range]. The results from this study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG. [Cyclins are a family of proteins that control the progression of cells through the cell cycle].


Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial
Michaela Diamant et al. The Lancet Diabetes & Endocrinology. Doi: 10.1016/S2213-8587(14)70029-4

The authors recall that when patients with type 2 diabetes start their first injectable therapy, clinicians can choose between glucagon-like peptide-1 (GLP-1) receptor agonists and basal insulins. In the DURATION-3 study, exenatide once weekly was compared with insulin as first injectable therapy. The results of the final 3-year follow-up showed that the efficacy of once-weekly exenatide was sustained for 3 years, and that GLP-1 receptor agonists could be a viable long-term injectable treatment option in patients with type 2 diabetes who have not yet started taking insulin.


Microvesicles and diabetic complications – novel mediators, potential biomarkers and therapeutic targets
Ying Wang et al. Acta Pharmacologica Sinica. Doi: 10.1038/aps.2013.188

Microvesicles (MVs), also known as microparticles, are small membrane vesicles released from different cell types under different conditions. MVs have been detected in the circulation and in organs/tissues in various diseases, including diabetes. Studies have shown that MVs may contribute to the development of diabetic macrovascular and microvascular complications. In addition, changes in MV number and composition may serve as potential biomarkers for diagnostic and prognostic use. Here, the authors review the latest publications from their group and other groups that focus on the involvement of MVs in diabetic complications.


Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program
D. Dabelea et al. Diabetic Medicine. Doi: 10.1111/dme.12437

This study asked if the presence of diabetes autoantibodies predicted the development of diabetes among participants in the Diabetes Prevention Program. A total of 3,050 participants were enrolled in the study. The authors concluded that ‘diabetes autoimmunity’, as reflected by glutamic acid decarboxylase (GAD) antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes was not a clinically relevant risk factor for progression to diabetes. [Glutamic Acid Decarboxylase Autoantibodies (GAD) is used to help discover whether someone has either type 1 diabetes or Latent Autoimmune Diabetes of Adulthood]. [Insulinoma-Associated-2 Autoantibodies are autoantibodies directed against beta cells].