Journal Watch

Prepared for IDDT by Jim Young

November 2013

The impact of insulin type on severe hypoglycaemia events requiring inpatient and emergency department care in patients with type 2 diabetes
Matthew D. Solomon et al. Diabetes Research and Clinical Practice. Doi: 10.1016/j.diabres.2013.09.013

In this study patients with type 2 diabetes who had recently started insulin were evaluated for severe hypoglycaemia (SHG) events. They were classified into groups based on the insulin type used. In all 8,626 patients were followed for an average of 4.0 years after insulin initiation, and of these 161 (1.9%) had a SHG event at an average of 3.1 years after insulin initiation. It was found that patients with SHG events were slightly older (56.4 vs. 53.4 years), and had more co-morbidities compared with those without SHG events. It was also discovered that premixed insulin, isophane insulin, and rapid acting insulin had significantly higher risks of SHG events compared with glargine, but no statistically significant difference in SHG events was seen with detemir. The investigators concluded that among patients with type 2 diabetes, the use of newer basal insulin analogues was associated with lower rates of SHG events requiring inpatient or emergency department care compared with users of other insulin formulations.


Non-invasive detection of microvascular changes in a paediatric and adolescent population with type 1 diabetes
Sarah P M Hosking et al. BMC Endocrine Disorders. Doi: 10.1186/1472-6823-13-41

Because the detection of microvascular damage in type 1 diabetes is difficult, and because traditional investigations do not detect changes until they are well established, the investigators evaluated the combined ability of nailfold capillaroscopy, laser Doppler flowmetry, and retinal vessel analysis to detect early microvascular changes. [In microvascular complications cells in the retina (diabetic retinopathy) or kidney (diabetic nephropathy), or nerves (diabetic neuropathy) may not get enough blood which may lead to loss of function] – [Doppler flowmetry uses a flow meter to measure the velocity of a fluid in order to calculate volume flow].The study looked at 26 patients aged between 8 and 18 years with type I diabetes and no other autoimmune conditions. It was found that participants with microvascular complications had more avascular areas on nailfold capillaroscopy [Capillaroscopy entails microscopic examination of the nail fold]. Interestingly, recent HbA1c readings were associated with the number of nailfold microhaemorrhages observed. Also a decrease in perfusion as shown by laser Doppler flowmetry was associated with an increase in the density of capillaries and an increased in the number of microaneurysms. [An aneurysm is a localized, blood-filled balloon-like bulge in the wall of a blood vessel]. The authors assert that their pilot study has shown that in children and adolescents with established type 1 diabetes, abnormal microvasculature can be detected by these investigations, and that the markers are associated with evidence of suboptimal diabetes control as assessed by HbA1c.


Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control Elsemiek E.C. Engwerda et al. Diabetes Care. Doi: 10.2337/dc13-0492

Studies have shown that the absorption and action of rapid-acting insulin are faster following injection by a jet injector than with administration by conventional pen. This study set out to determine if these pharmacokinetic changes benefit postprandial glucose control in type 1 and type 2 diabetes. [Pharmacokinetics looks at the fate of drugs administered to a patient]. In this randomized, double-blind, crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, followed by a standardized meal. [In a double-blind study the results are concealed from both the tester and the subject] – [In a crossover study each patient is randomly assigned to the sequence of treatments]. It was found that insulin administration by jet injection resulted in shorter time until peak plasma insulin level was achieved and resulted in a reduced hyperglycemic burden during the first hour when compared with conventional administration. However jet injection did not significantly reduce the hyperglycemic burden during the 5 hour period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes. The authors suggest that the improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.


Chronic kidney disease and diabetes in the National Health Service: a cross-sectional survey of the UK National Diabetes Audit
C. J. Hill et al. Diabetic Medicine. Doi: 10.1111/dme.12312

This investigation looked at the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure using data from the UK National Diabetes. Patients were stratified according to chronic kidney disease stage and albuminuria status, and 868,616 met inclusion criteria. It was found that a higher proportion of people with Type 2 diabetes had renal dysfunction compared with those with Type 1 diabetes. Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol. Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. The conclusions were that the high prevalence of chronic kidney disease and poor attainment of treatment targets highlighted a large subset of the diabetes population that were of increased risk of cardiovascular mortality or progressive kidney disease.


Thyroid autoimmunity in Type 1 diabetes
C. B. Shun et al. Diabetic Medicine. Doi: 10.1111/dme.12318

This systematic review and meta-analysis explored the incidence and evidence for screening for thyroid autoimmunity and thyroid dysfunction in Type 1 diabetes. [A meta-analysis refers to methods that focus on contrasting and combining results from different studies].Thyroid dysfunction was defined as an abnormal thyroid-stimulating hormone level. The outcomes examined were the incidence of thyroid autoimmunity and/or dysfunction, and the association between thyroid autoimmunity and dysfunction. The investigators identified 14 eligible studies that involved 2,972 young people and 789 adults with Type 1 diabetes, with the follow-up period ranging from 1 to 18 years. It was found that the risk of thyroid dysfunction was higher in those with thyroid autoimmunity and was higher in children compared with adults. The optimal method or frequency of screening could not be determined from available data. The authors suggest that future studies should examine whether screening improves clinical outcomes in this population.


Effect of statin therapy on vaspin levels in type 2 diabetic patients
Al-Azzam SI et al. Clinical Pharmacology: Advances and Applications.

Vaspin is an emerging adipokine with important insulin-sensitizing, cardioprotective, and anti-atherosclerotic properties in patients with diabetes. [Adipokines are cell signalling proteins secreted by adipose tissue]. This randomized controlled clinical trial evaluated the effect of statin therapy on vaspin levels in patients with type 2 diabetes mellitus. The trial found that after 8 weeks of treatment vaspin levels were increased in patients treated with simvastatin but not in patients who were not treated with simvastatin. In addition, the lipid-lowering effect of simvastatin was reflected in a statistically significant reduction in total cholesterol in the study group and in a statistically significant reduction in triglyceride. The authors assert  that their results indicate that statin therapy increases plasma vaspin levels in addition to having a lipid-lowering effect, and that this could be a mechanism underlying their cardioprotective and antiatherosclerotic effects.


Improving depression screening for adolescents with type 1 diabetes
Sarah D. Corathers et al. Pediatrics. Doi: 10.1542/peds.2013-0681

This research set out to provide a self-administered electronic version of the Children’s Depression Inventory (CDI) for depression screening of youth aged 13 to 17 years with type 1 diabetes. The study recruited 528 eligible adolescents and the process was tested and refined in over 1,200 patient encounters.  Use of the depression inventory resulted in an increase in depression screening rates from less than 5% to 85% over the initial 12 months. Elevated CDI scores were found in 8% of the sample, moderate scores in 12% of the sample, and low risk scores in 80% of the sample. It was also found that higher CDI scores correlated with lower blood glucose monitoring frequency and higher hemoglobin HbA1c which confirmed the link between more depression symptoms and poorer diabetes management and control. The authors suggest that systematic depression screening in adolescents with type 1 diabetes can be reliably implemented with clinically significant results.


Both dietary protein and fat increase postprandial glucose excursions in children with type 1 diabetes, and the effect is additive
Carmel E.M. Smart et al. Diabetes Care. Doi: 10.2337/dc13-1195

This study looked at the separate and combined effects of high-protein (HP) and high-fat (HF) meals, with the same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT). Thirty-three subjects aged 8 to 17 years were given 4 test breakfasts with the same carbohydrate amount but varying protein and fat quantities. An individually standardized insulin dose was given for each meal and postprandial glycemia was assessed by 5 hour continuous glucose monitoring. It was found that meals high in protein or fat increase glucose excursions in youth using IIT from 3 to 5 hours postmeal, and that protein and fat have an additive impact on the delayed postprandial glycemic rise. It was also discovered that protein had a protective effect on the development of hypoglycemia.


Efficacy of carbohydrate counting in type 1 diabetes: a systematic review and meta-analysis
Kirstine J Bell et al. The Lancet Diabetes & Endocrinology. Doi: 10.1016/S2213-8587(13)70144-X

The authors of this paper remind us that although carbohydrate counting is the recommended dietary strategy for achieving glycaemic control in people with type 1 diabetes, the advice is based on narrative. To explore this they used a systematic review and meta-analysis to assess the efficacy of carbohydrate counting on glycaemic control in adults and children with type 1 diabetes. [Systematic review is literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question] – [A meta-analysis refers to methods that focus on contrasting and combining results from different studies]. Change in glycated haemoglobin (HbA1c) concentration was the primary outcome studied. The investigators found seven eligible trials, of 311 potentially relevant studies, comprising 599 adults and 104 children with type 1 diabetes. It found that overall there was no significant improvement in HbA1c concentration with carbohydrate counting versus usual care. However, in five studies in adults there was a 0·64% point (7·0 mmol/mol) reduction in HbA1c with carbohydrate counting versus a control group. The authors posit that although there is some evidence to support the recommendation of carbohydrate counting over alternate advice or usual care in adults with type 1 diabetes, additional studies are needed to support promotion of carbohydrate counting over other methods of matching insulin dose to food intake.


Safety of nighttime 2-hour suspension of basal insulin in pump-treated type 1 diabetes even in the absence of low glucose
Jennifer L Sherr et al. Diabetes Care. Doi: 10.2337/dc13-1608

In the introduction to this research paper the authors describe how an integrated sensor-augmented pump system have been introduced that interrupt basal insulin infusion for 2 hours if patients fail to respond to low glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low sensor glucose levels could lead to diabetic ketoacidosis. The authors hypothesized that the random suspension of basal insulin for 2 hours in the overnight period would not lead to clinically important increases in blood β-hydroxybutyrate (BHB) levels despite widely varying glucose values prior to the suspension. [β-hydroxybutyrate is a ketone produced in Ketoacidosis]. Seventeen type 1 diabetes subjects were enrolled in the study. It was found that systems that suspend basal insulin for 2 hours were safe and did not lead to clinically significant ketonemia even if BG is elevated at the time of the suspension.