Journal Watch

Prepared for IDDT by Jim Young

August 2015

Hypoglycaemia in adults with insulin-treated diabetes in the UK: self-reported frequency and effects
M. Frier et al. Diabetic Medicine. Doi: 10.1111/dme.12878

In this survey adults aged over 15 years with Type 1 diabetes or insulin-treated Type 2 diabetes completed 4 weekly questionnaires. Respondents with Type 2 diabetes were grouped by insulin regimen: basal-only, basal–bolus and ‘other’. A total of 1,038 respondents (466 with Type 1 diabetes, 572 with Type 2 diabetes) completed 3,528 questionnaires. Mean numbers of non-severe events per week were 2.4 for Type 1 diabetes and 0.8 for Type 2 diabetes; 23% and 26% of non-severe events occurred at night, respectively. In the week following an event, respondents’ blood glucose measurements (tests per week) increased by 4.3 for Type 1 diabetes (12% increment) and 4.2 for Type 2 diabetes (21% increment). Most respondents rarely or never informed healthcare professionals about events. The authors conclude that non-severe hypoglycaemia is common in adults with insulin-treated diabetes in the UK, with consequent health-related and economic effects. They also noted that communication about non-severe hypoglycaemia is limited and therefore the burden of hypoglycaemia may be underestimated.


Interventions that restore awareness of hypoglycemia in adults with type 1 diabetes
Ester Yeoh et al. Diabetes Care. Doi: 10.2337/dc15-0102

Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia (SH) sixfold and affects 30% of adults with type 1 diabetes (T1D). This systematic review and meta-analysis looked at the educational, technological, and pharmacological interventions aimed at restoring hypoglycemia awareness (HA) in adults with T1D. Educational interventions included structured diabetes education on flexible insulin therapy, including psychotherapeutic and behavioral techniques. These were able to reduce SH and improve glycemic control, with greater benefit from the latter two techniques in improving IAH. Technological interventions (insulin pump therapy, continuous glucose monitoring, and sensor-augmented pump) reduced SH, improved glycemic control, and restored awareness when used in combination with structured education and frequent contact. Pharmacological studies included four insulin studies and one noninsulin study, but with low background SH prevalence rates. The review provides evidence for the effectiveness of a stepped-care approach in the management of patients with IAH, initially with structured diabetes education in flexible insulin therapy, which may incorporate psychotherapeutic and behavioral therapies, progressing to diabetes technology, incorporating sensors and insulin pumps, in those with persisting need.

Chronic comorbidities in children with type 1 diabetes: a population-based cohort study
Soulmaz Fazeli Farsani et al. BMJ. Doi: 10.1136/archdischild-2014-307654

This study looked at patients in the Dutch PHARMO database (1998–2010). All patients (915) were younger than 19 years with T1D (the T1D cohort) and a group of age- and sex-matched children without diabetes (the reference cohort). The main outcome measured was the incidence of nine common chronic comorbidities that needed treat pharmacologically and/or resulted in hospital admission. It was found that incidences of six chronic diseases were significantly higher in T1D children during the early years of developing this disease compared with the reference children.


Inhaled Technosphere insulin compared with injected prandial insulin in type 1 diabetes
Bruce W. Bode et al. Diabetes Care. Doi: 10.2337/dc15-0075

This trial compared the change in HbA1c from baseline to week 24 of prandialTechnosphere insulin (TI) with that of subcutaneous aspart, both with basal insulin, in patients with type 1 diabetes and HbA1c 7.5–10.0% (56.8–86.0 mmol/mol). It found that the mean change in HbA1c from baseline was noninferior to that in aspart patents, with less hypoglycemia, less weight gain, but increased incidence of cough.


Metformin versus insulin for gestational diabetes mellitus
Li-Ping Zhao et al. British Journal of Clinical Pharmacology. Doi: 10.1111/bcp.12672

The investigators conducted searches of databases, including PubMed, Embase and the Cochrane Central Register of Controlled Trials, for randomized controlled trials (RCTs) that compared metformin and insulin treatments in women with gestational diabetes GDM. They analysed eight studies involving 1,592 subjects. Their research showed that metformin had statistically significant effects on pregnancy-induced hypertension. However, its effects on neonatal hypoglycaemia, rate of large-for-gestational age infants, respiratory distress syndrome and perinatal death were not significant. The authors suggest that there is no clinically relevant difference in efficacy or safety between metformin and insulin; however, metformin may be a good choice for GDM because of the lower risk of pregnancy-induced hypertension.


Associations between glycemic control, depressed mood, clinical depression, and diabetes distress before and after insulin initiation
Haya Ascher-Svanum et al. Diabetes Therapy. Doi: 10.1007/s13300-015-0118-y

Although depression is often associated with poor glycemic control in patients with type 2 diabetes mellitus (T2DM), this observation has been inconsistent. This analysis investigated the associations between depression and glycemic control in a study that evaluated glycemic response following insulin initiation for T2DM. The investigators analyzed data from a 24-month, observational study in 985 patients with T2DM who initiated insulin therapy in 5 European countries. Secondary measures included patient-reported diagnosis of depression at baseline, severity of depressed/anxious mood and diabetes-related distress. The latter two measures were assessed at baseline and 5 time points throughout the study. It was found that patients with higher depression parameters or distress at baseline had significantly higher rates of microvascular complications at baseline. Patients with a history of diagnosed depression or high diabetes-related distress had higher HbA1c than patients without. The proportion of patients with depressed mood declined after insulin initiation, whereas the proportion of patients with high diabetes-related distress did not significantly change. HbA1c improved following insulin initiation, regardless of presence/absence of studied depression/distress parameters at baseline.


Efficacy and safety of once weekly glucagon-like peptide 1 receptor agonists for management of type 2 diabetes
Thomas Karagiannis et al. Diabetes, Obesity and Metabolism. Doi: 10.1111/dom.12541

This systematic review and meta-analysis of randomised controlled trials compared any glucagon-like peptide 1 receptor agonists (GLP-1 RA) given once weekly (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. The authors searched Medline, Embase, the Cochrane Library and grey literature through December 2014. The review included 33 trials with 16,003 participants. It found that compared with other antidiabetic agents once weekly GLP-1 RAs outperformed sitagliptin, daily exenatide, and insulin glargine in terms of HbA1c lowering. The main adverse effects of treatment included gastrointestinal and injection site reactions. The authors concluded that given their dosing scheme and overall efficacy and safety profile once weekly GLP-1 RAs are a convenient therapeutic option as add-on to metformin.


Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes
Sanjoy K Paul et al. Cardiovascular Diabetology. Doi: 10.1186/s12933-015-0260-x

This paper reports on a retrospective cohort study of 105,477 patients carried out using United Kingdom Clinical Practice Research Datalink, including type 2 diabetes(T2DM) patients diagnosed from 1990 with follow-up data available until 2012. Mean HbA1c was 8.1% (65 mmol/mol) at diagnosis, 11% had a history of cardiovascular disease, and 7.1% experienced at least one cardiovascular event (CVE) during 5.3 years of median follow-up. The findings were that in patients with HbA1c consistently above 7 to 7.5% (53 to 58 mmol/mol) during 2 years post diagnosis, 22% never received any intensification (IT). Compared to patients with HbA1c less than 7% (53 mmol/mol), patients with HbA1c greater than 7% (53 mmol/mol) a 1 year delay in receiving IT was associated with significantly increased risk of myocardial infarction, stroke, heart failure. A one year delay in IT in interaction with HbA1c above 7.5% (58 mmol/mol) was also associated with similar increased risk of CVE.


Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes
Tao Xu et al.  Diabetes Care. Doi: 10.2337/dc15-0658

This study evaluated the effect of metformin treatment on metabolite concentrations by quantifying 131 metabolites in fasting serum samples. The study looked at 151 patients with T2D treated with metformin (mt-T2D). Additionally, in 912 patients they investigated the effects of metformin on blood lipid profiles. The study found significantly lower concentrations of three metabolites when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. Furthermore, the investigators observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years’ follow-up. The authors posit that their findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.


Type 1 Diabetes is associated with an increased risk of fracture across the life span
David R. Weber et al. Diabetes Care. Doi: 10.2337/dc15-0783

This population-based cohort study used data from The Health Improvement Network (THIN) in the U.K. (data from 1994 to 2012), in which 30,394 participants aged 0 to 89 years with type 1 diabetes were compared with 303,872 randomly selected age-, sex-, and practice-matched participants without diabetes. It was found that type 1 diabetes was associated with increased risk of incident fracture that began in childhood and extended across the life span. Participants with type 1 diabetes sustained a disproportionately greater number of lower extremity fractures. The authors posit that their findings have important public health implications, given the increasing prevalence of type 1 diabetes and the morbidity and mortality associated with hip fractures.