Journal Watch

Prepared for IDDT by Jim Young

March 2015

Taking Control: Supporting people to self-manage their diabetes
All-Party Parliamentary Group for Diabetes
This report from the All-Party Parliamentary Group for Diabetes examines in detail why many individuals are not getting the support they need to self-manage their diabetes and what the NHS, clinical commissioning groups, healthcare professionals and providers can do to address this. It looks at the barriers to the uptake and provision of diabetes education and support for both adults and children. Among the solutions it offers are: better commissioning, improving uptake of education and support, structured education, lifelong learning, peer support, and online resources.


Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission
Liehua Liu et al. Diabetes Research and Clinical Practice. Doi: 10.1016/j.diabres.2015.02.011

In this study intensive continuous subcutaneous insulin infusion (CSII) was applied in 104 patients with newly diagnosed type 2 diabetes. Daily insulin doses were titrated and recorded to achieve and maintain euglycemia for 2 weeks. Measurements of blood glucose, lipid profiles as well as intravenous glucose tolerance tests were performed before and after the therapy. Afterwards, patients were followed up for 1 year. It found that there was a steady decline in total daily insulin dose after euglycemia was achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and that this was also associated with a better long-term glycemic outcome.


Treatment persistence after initiating basal insulin in type 2 diabetes patients
Stefan Pscherer et al. Primary Care Diabetes. Doi: 10.1016/j.pcd.2015.01.011

This study compared persistence and its prediction in type 2 diabetes patients in 918 primary care practices, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin. Persistence was defined as proportion of patients remaining on the initial basal insulin over 2 years. It was found that in the BOT group, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively. In ICT group persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively. Heart failure was a predictor of non-persistence, whereas higher age, metformin, and sulfonylurea co-medication were associated with lower discontinuation. The authors concluded that in BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics.


Weight-based hypoglycaemia treatment protocol for adults with Type 1 diabetes
L. McTavish et al. Diabetic Medicine. Doi: 10.1111/dme.12730

In this study patients with frequent hypoglycaemia were recruited from hospital-based diabetes clinics. The treatment for each hypoglycaemic episode was randomly assigned to one of three protocols: 0.2 g/kg, 0.3 g/kg, or the internationally recommended 15-g treatment, of DextroTMglucose. Each participant received each treatment in random order for up to 15 hypoglycaemic episodes. The study recruited 34 participants aged 22–71 years. The study found that the weight-based protocol of 0.3 g/kg glucose appeared more effective for treating symptomatic hypoglycaemia in adults with Type 1 diabetes than either the most common current recommendation of 15 g glucose or a 0.2 g/kg glucose dose.


Diabetes, diabetic complications, and fracture risk
Ling Oei et al. Current Osteoporosis Reports. Doi: 10.1007/s11914-015-0260-5

Diabetes and osteoporosis are both common diseases with increasing prevalence in the aging population. There is increasing evidence corroborating an association between diabetes and bone. This review discusses why, when compared to control subjects, decreased bone mineral density (BMD) has been observed in type 1 diabetes mellitus, while on average higher BMD has been found in type 2 diabetes, and why patients with both types of diabetes are still seemingly at increased risk of fractures. The paper reports that deterioration in bone microarchitecture and an inefficient distribution of bone mass with insufficiency of repair and adaptation mechanisms appear to be factors of relevance. The authors caution that there is a highly complex and heterogeneous molecular pathophysiology underling diabetes-related bone disease that involves hormonal, immune, and perhaps genetic pathways. They posit that the detrimental effects of chronically elevated glucose levels on bone should be added to the more well-known complications of diabetes.


Predictors of progression from the appearance of islet autoantibodies to early childhood diabetes
Andrea K. Steck et al. Diabetes Care. Doi: 10.2337/dc14-2426

The authors assert that while it is known that progression to diabetes occurs in less than 10 years for 70% of children who have two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined. The Environmental Determinants of Diabetes in the Young (TEDDY) study observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months. It found that children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.


Effects of acute and antecedent hypoglycemia on endothelial function and markers of atherothrombotic balance in healthy men
Nino G. Joy et al: Diabetes. Doi: 10.2337/db14-1729

The aim of this study was to determine the effects of single and repeated episodes of hypoglycemia on fibrinolytic balance, pro-inflammatory biomarkers, pro-atherothrombotic mechanisms and endothelial function. It found that acute moderate hypoglycemia impaired fibrinolytic balance, increases pro-inflammatory responses, platelet activation and coagulation biomarkers and reduced nitric oxide (NO) mediated endothelial function in healthy individuals. Repeated episodes of hypoglycemia further impaired vascular function by additionally reducing exogenously NO mediated endothelial function and increasing coagulation biomarkers. The investigators conclude that antecedent hypoglycemia results in greater endothelial dysfunction and an increased pro-atherothrombotic state as compared to a single acute episode of hypoglycemia.


Improving diabetes prevention with benefit based tailored treatment
Jeremy B Sussman et al. BMJ. Doi: 10.1136/bmj.h454

This analysis of the Diabetes Prevention Program set out to determine whether some participants were more or less likely to benefit from metformin or a structured lifestyle modification program.
The participants were 3,060 people without diabetes but with evidence of impaired glucose metabolism. The intervention groups received metformin or a lifestyle modification, and the main outcome measured was the development of diabetes. It found that 21% of participants with impaired glucose metabolism at baseline progressed to diabetes over a median 2.8 years’ follow-up. Although the lifestyle intervention provided a sixfold greater absolute risk reduction in the highest risk quarter than in the lowest risk quarter, patients in the lowest risk quarter still received substantial benefit. The benefit of metformin, however, was seen almost entirely in patients in the top quarter of risk of diabetes. No benefit was seen in the lowest risk quarter. The authors concluded that patients at high risk of diabetes have substantial variation in their likelihood of receiving benefit from diabetes prevention treatments. They posit that using this knowledge could decrease overtreatment and make prevention of diabetes far more efficient, effective, and patient centered, provided that decision making is based on an accurate risk prediction tool.


The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes
Siri Fredheim et al. Diabetologia. Doi: 10.1007/s00125-014-3486-3

This study investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes. The findings were that postprandial glucagon levels increased 160% from 1 to 60 months after diagnosis. A doubling in postprandial plasma glucose (PG) corresponded to a 21% increase in postprandial glucagon levels, whereas a doubling in total GLP-1 levels corresponded to a 33% increase in glucagon levels. [Glucagon-like peptide-1 (GLP-1) is an incretin and the major source of GLP-1 in the body is the intestine. GLP-1 has a half-life of less than 2 minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4. It is a potent antihyperglycemic hormone, inducing glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion]. The study also found that postprandial glucagon was associated negatively with postprandial C-peptide, where a doubling in postprandial glucagon corresponded to a 3% relative increase in HbA1c levels. [C-peptide is a protein that connects insulin’s A-chain to its B-chain in the proinsulin molecule. Measuring C-peptide can help to determine how much of a patient’s own natural insulin is being produced as C-peptide is secreted in equimolar amounts to insulin]. The overall conclusions were that postprandial glucagon levels were associated with deterioration of glycaemic control and declining beta cell function in the first 5 years after diagnosis of type 1 diabetes. The positive association of glucagon with total GLP-1 and PG suggests that physiological regulation of alpha cell secretion in type 1 diabetes is seriously disturbed.


National Paediatric Diabetes Audit
Royal College of Paediatrics and Child Health

The National Paediatric Diabetes Audit annual report is a 68-page PDF covering 2013-14. The executive summary states that while overall there are some very positive improvements in the quality of care and outcomes demonstrated within the report, the clear variability of care which exists across the country urgently needs addressing at both regional and local level … ongoing quality improvement will require the continuation of adequate service funding, effectively managed clinical networks and a robust quality surveillance programme.