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April 2017

Treatment of diabetic ketoacidosis (DKA)/hyperglycemic hyperosmolar state (HHS): novel advances in the management of hyperglycemic crises (UK Versus USA)
Ketan K. Dhatariya and Priyathama Vellanki. Current Diabetes Reports. DOI: 10.1007/s11892-017-0857-4

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. However, large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK. Unlike the USA, the UK has separate guidelines for DKA and HHS. Although there is considerable overlap, important differences remain between the UK and USA guidelines for the management of DKA and HHS. The authors assert that further research needs to be done to delineate a unifying diagnostic and treatment protocol. One would have thought that this was a matter of urgency.


Are the results from the 2014 UK national survey on the management of diabetic ketoacidosis applicable to individual centres?
M. Varadarajan et al. Diabetes Research and Clinical Practice. DOI: http://dx.doi.org/10.1016/j.diabres.2017.03.004

In 2013, the Joint British Diabetes Societies (JBDS) published an update to their 2010 guideline on the management of diabetic ketoacidosis (DKA). In 2014, a national survey was conducted to assess the management of DKA across the UK using the JBDS or local guidelines. Hospitals were invited to submit data on 5 people presenting with DKA. These data were published in 2016. However, whether those national results were applicable to individual hospitals was unknown. In this study, the investigators collected information on 40 subjects (a total of 52 admissions) admitted with DKA between April 2014 and July 2015. They discovered that the management of DKA was best during the first few hours after admission, then biochemical and physical monitoring frequency decreased. The number of people who developed hypokalaemia and hypoglycaemia were very similar to the national data. Rates of biochemical improvement were slightly better locally. The authors conclude that the data from the national DKA survey, even though based on a maximum of 5 people per hospital from across the UK are applicable at a hospital level. This open access paper provides all the details.


Acute kidney injury in children with Type 1 Diabetes hospitalized for diabetic ketoacidosis
Brenden E. Hursh et al. JAMA Pediatrics. DOI: :10.1001/jamapediatrics.2017.0020

Acute kidney injury (AKI) in children is associated with poor short-term and long-term health outcomes; however, surprisingly, the frequency of AKI in children hospitalized for diabetic ketoacidosis (DKA) has not been previously examined. This study from the USA determined the proportion of children hospitalized for DKA who develop AKI and hoped to identified the associated clinical and biochemical markers of AKI. The main outcome studied was acute kidney injury, and it sought to identify potential factors associated with AKI. It found that of the 165 children hospitalized for DKA, 106 (64.2%) developed AKI (AKI stage 1, 37 [34.9%]; AKI stage 2, 48 [45.3%]; and AKI stage 3, 21 [19.8%]). Two children required hemodialysis. A serum bicarbonate level less than 10 mEq/L was associated with a 5-fold increase in the odds of severe (stage 2 or 3) AKI. Also, each increase of 5 beats/min in initial heart rate was associated with a 22% increase in the odds of severe AKI. Initial corrected sodium level of 145 mEq/L or greater was associated with a 3-fold increase in the odds of mild (stage 1) AKI. Happily, there were no cases of mortality in patients with or without AKI. The authors assert that their study is the first to document that a high proportion of children hospitalized for DKA develop AKI. Acute kidney injury was associated with markers of volume depletion and severe acidosis. They caution that acute kidney injury is concerning because it is associated with increased morbidity and mortality as well as increased risk of chronic renal disease, a finding that is especially relevant among children who are already at risk for diabetic nephropathy. They posit that strategies are needed to improve the diagnosis, management, and follow-up of AKI in children with type 1 diabetes.


Faster insulin action is associated with improved glycemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy in adults with type 1 diabetes
Yue Ruan et al. Diabetes, Obesity and Metabolism. DOI: 10.1111/dom.12956

This retrospective study analysed data from a multicenter randomized control trial involving 32 adults with type 1 diabetes receiving day-and-night closed-loop insulin delivery and sensor-augmented pump therapy over 12 weeks. Estimated time-to-peak insulin action and insulin sensitivity during both interventions were recorded. It was found that faster insulin action is associated with improved glycemic control during closed-loop insulin delivery and sensor-augmented pump therapy.


Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4)
Vanita R Aroda et al. The Lancet Diabetes & Endocrinology. DOI: http://dx.doi.org/10.1016/S2213-8587(17)30085-2

This trial was conducted at 196 sites in 14 countries. Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea. Participants were randomly assigned (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide or once-daily insulin glargine for 30 weeks. In all treatment groups, previous background metformin and sulfonylurea treatment was continued throughout the trial.

 The primary endpoint was change in mean HbA1c from baseline to week 30 and the secondary endpoint was the change in mean bodyweight from baseline to week 30. It was reported that compared with insulin glargine, semaglutide resulted in greater reductions in HbA1c and weight, with fewer hypoglycaemic episodes, and was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists.


Who should be considered for islet transplantation alone?
Nantia Othonos and Pratik Choudhary. Current Diabetes Reports. DOI: 10.1007/s11892-017-0847-6

Episodic hypoglycemia is an almost inevitable consequence of exogenous insulin treatment of type 1 diabetes, and in up to 30% of patients, this can lead to impaired awareness of hypoglycemia. This predisposes to recurrent severe hypoglycemia and has a huge impact on quality of life. Although many patients can get resolution of severe hypoglycemia through novel education and technology, some patients continue to have ongoing life-threatening hypoglycemia. Islet transplantation offers an alternative therapeutic option for these patients, in whom these conventional approaches have been unsuccessful. This review discusses the selection process of identifying suitable candidates based on recent clinical data. Results from studies of islet transplantation suggest the optimal recipient characteristics for successful islet transplantation include age over 35 years, insulin requirements less than 1.0/kg, and weight over 85 kg. Islet transplantation can completely resolve hypoglycemia and near-normalize glucose levels, achieving insulin independence for a limited period of time in up to 40% of patients. The selection of appropriate candidates, optimising donor selection, the use of an optimised protocol for islet cell extraction, and immunosuppression therapy have been proved to be the key criteria for a favorable outcome in islet transplantation.


Comparison of insulin pump therapy and multiple daily injections insulin regimen in patients with Type 1 Diabetes during Ramadan fasting
Reem Alamoudi et al. Diabetes Technology and Therapeutics. DOI: :10.1089/dia.2016.0418

Although fasting during Ramadan carries a high risk for patients with type 1 diabetes (T1DM), data on the optimum insulin regimen in these patients are limited. This study compared glucose profiles in patients with T1DM who use continuous subcutaneous insulin infusion (CSII) compared with those who use multiple daily injections (MDI) insulin regimen during Ramadan fast. The primary outcome was rates of hypoglycemia. Other outcomes included glycemic control, number of days needed to break fasting, and acute glycemic complications. A total of 156 patients were recruited, 61 on CSII and 95 on MDI. It was found that there was no difference in the rate of mild hypoglycemia or of severe hypoglycemia in both groups. There was no difference in the number of days that patients have to stop fasting. However, glucose variability was significantly better in CSII group.


Risk factors and outcome differences in hypoglycaemia-related hospital admissions
Francesco Zaccardi et al. Diabetes, Obesity and Metabolism. DOI: 10.1111/dom.12941

This study evaluated risk factors for hospital admissions for hypoglycaemia and compared the length of hospitalisation, inpatient mortality, and hospital readmission between hypoglycaemia and non–hypoglycaemia–related admissions. The study used all admissions for hypoglycaemia in people with diabetes to English NHS hospital trusts between 2005 and 2014 (101,475 case admissions) and three random admissions per case in people with diabetes without hypoglycaemia (304,425 control admissions). The interesting findings were that a U–shaped relationship between age and risk of admission for hypoglycaemia was observed until the age of 85 years: compared to the nadir at 60 years, the risk was progressively higher in younger and older patients and steadily declined after 85 years. Social deprivation (positively) and comorbidities (negatively) were associated with the risk of admission for hypoglycaemia. Length of hospitalisation was 26% shorter while risk of rehospitalisation was 65% higher in people admitted for hypoglycaemia. Compared to admissions for hypoglycaemia, risk of inpatient mortality was 50% lower for unstable angina but higher for acute myocardial infarction (3 times), acute renal failure, or pneumonia.


Research digest: the risks of type 2 diabetes at a young age
Naveed Sattar and David Preiss. The Lancet Diabetes & Endocrinology. DOI: http://dx.doi.org/10.1016/S2213-8587(17)30117-1

This is an interesting Research Digest. If asked which diabetes type is more harmful in younger people, we expect that many healthcare professionals would choose type 1 diabetes because they know that it is a condition caused by pancreatic beta cell failure that requires insulin injections. Yet, in terms of the risk of complications, the opposite seems to be true. The SEARCH for Diabetes in Youth registry study those with type 2 diabetes were at substantially elevated risk of almost all outcomes compared to their counterparts with type 1 diabetes. The authors’ sobering conclusion was that 8 years after developing diabetes as teenagers or young adults, 72% of those with type 2 diabetes had evidence of at least one early diabetes-related complication, whereas only 32% of those with type 1 diabetes had such evidence. These findings, in turn, add to earlier data which showed a doubling of mortality risk in individuals who developed type 2 diabetes aged 15–30 years in comparison with age-matched individuals who developed type 1 diabetes. Part of the reason for the discrepancy probably lies in the fact that people who develop type 2 diabetes at a young age are typically heavier than people who develop type 2 diabetes later in life, or indeed type 1 diabetes at any age. The likelihood of not just preventing, but even reversing, diabetes might seem overly optimistic. However, increasing evidence shows that substantial weight loss can achieve this goal, at least in the short term. Greater and sustained weight loss seems to be needed for long term success. The key question going forward is whether initial weight loss and metabolic benefit achieved with a very low calorie diet intervention in a research setting can be sustained in a real-life primary care setting. The DiRECT randomised trial will test this hypothesis and will report in 2017.


Improvement of insulin injection technique
Geralyn Spollett et al. Diabetes Educator. DOI: https://doi.org/10.1177/0145721716648017

We are all aware that correct insulin injection technique is a crucial aspect of diabetes management. The purpose of this article was (1) to outline the medical literature, including patient-based studies and surveys, surrounding the type of issues and problems that patients encounter with injectable insulin therapy and the degree to which correct insulin technique is being applied and (2) to review the latest recommendations for insulin injection technique and discuss the key aspects that diabetes educators and other health care professionals should be communicating to their patients to ensure that injection technique is optimized. You might find this detailed and illustrated exposition a useful revision of injection techniques.

InDependent Diabetes Trust