Journal Watch

Prepared for IDDT by Jim Young

July 2015

Use of a basal-plus insulin regimen in persons with type 2 diabetes
Mark R. Lankisch et al. Primary Care Diabetes. Doi:

This study looked at 711 patients with a mean age of 59.9 years and a mean duration of diabetes of 11.0 years. It analysed data from those patients who had poor glycemic control on oral antihyperglycemic drugs and who were initiated on a ‘basal-plus’ regimen for up to 6 months. HbA1c, fasting blood glucose, postprandial glucose (PPG), insulin dose and demographics were measured at baseline and at the end of the study. It found that the ‘basal-plus’ regimen was associated with significant decreases in HbA1c and PPG at 6 months, an increase in glargine and glulisine doses and small changes in body weight and BMI in all patient subsets. The proportion of patients with HbA1c of less than 7% also increased in all populations studied, while the prevalence of severe hypoglycemia was low and did not significantly differ across patient groups. The authors concluded that the use of ‘basal-plus’ can achieve a good therapeutic response with a low risk of hypoglycemia and weight gain, regardless of a patient’s age or BMI.


Insulin mediated improvement in glycemic control in elderly with type 2 diabetes mellitus can improve depressive symptoms and does not seem to impair health-related quality of life
R. A. Oliveira et al. Diabetology & Metabolic Syndrome. Doi: 10.1186/s13098-015-0052-1

This study looked at the association of starting insulin therapy, depressive symptoms, and health-related quality of life (HRQoL) of elderly people with T2D. 36 participants were recruited, 26 of whom completed the follow-up. It was found that there was a reduction in the Beck Depression Inventory (BDI) score after the use of insulin, which indicated an improvement in depressive symptoms. There were no statistically significant differences in HRQoL scores. There was also a reduction in HbA1c.


Five-year metabolic, functional, and safety results of patients with type 1 diabetes transplanted with allogenic islets
Sandrine Lablanche et al. Diabetes Care. Doi: 10.2337/dc15-0094

This retrospective analysis looked at subjects enrolled two islet transplantation trials. Parameters related to metabolic control, graft function, and safety outcomes were studied, during a 5-year follow-up.[Tissue transplanted from one person to another is said to be allogenic]. It reports that islet transplantation is safe and efficient in restoring good and lasting glycemic control, and prevented severe hypoglycemia in patients with type 1 diabetes.


Practical guidance on the use of premix insulin analogs in initiating, intensifying, or switching insulin regimens in type 2 diabetes
Ted Wu et al. Diabetes Therapy. Doi: 10.1007/s13300-015-0116-0

The introduction to this paper states that premix insulin analogs are a well-established treatment for type 2 diabetes. However, there is a lack of simple, clear guidance on some aspects of their use. These include: choosing a regimen for insulin initiation, recognizing when patients need intensification of therapy, and switching from basal–bolus to a premix insulin analog when appropriate. The results from trials in both initiation and intensification of insulin showed that no single insulin or regimen was best on all endpoints, and that improved glycemic control can be expected regardless of which regimen is used. Therefore, individual patient factors and preferences become more important.


Treatment satisfaction and quality-of-life between type 2 diabetes patients initiating long- vs. intermediate-acting basal insulin therapy in combination with oral hypoglycemic agents
Norbert Hermanns et al. Health and Quality of Life Outcomes. Doi: 10.1186/s12955-015-0279-4

In this 48-week trial insulin naïve type 2 diabetes patients with blood glucose not at target on oral hypoglycemic agents had basal insulin added to their treatment regimen. A total of 343 patients were randomized to either receive insulin glargine or neutral protamine Hagedorn (NPH) insulin in period 1 (weeks 1–24) and vice versa in period 2 (weeks 25–48). The primary objective was to assess patient reported outcomes using a composite Diabetes Related Quality of Life (DRQoL). It was shown differences in the patient reported outcomes evaluated in this study were negligible between insulin glargine and NPH insulin.


Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery
Jicheng Yu et al. PNAS. Doi: 10.1073/pnas.1505405112

This fascinating paper reports on the development (tested in mice) of a novel glucose-responsive insulin delivery device that uses a painless microneedle-array patch containing hypoxia-sensitive hyaluronic acid-based vesicles [Hyaluronic acid is abundant in extracellular matrices and contributes to tissue hydrodynamics and participates in a number of cell surface receptor interactions]The vesicles quickly release encapsulated insulin under the local hypoxic environment, caused by the enzymatic oxidation of glucose in the hyperglycemic state. The authors assert that their “smart insulin patch” with a new enzyme-based glucose-responsive mechanism can regulate the blood glucose of type 1 diabetic mice to achieve normal levels, with faster responsiveness compared with the commonly used pH-sensitive formulations, and can avoid the risk of hypoglycemia. They also posit that the glucose-responsive “closed-loop” insulin delivery system mimics the function of pancreatic cells and therefore has tremendous potential to improve quality of life and health in people with diabetes.


Alterations in intestinal microbiota correlate with susceptibility to type 1 diabetes
Aimon K. Alkanani et al. Diabetes. Doi: 10.2337/db14-1847

In this interesting paper the investigators tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). The study was performed in subjects with islet autoimmunity living in the United States. It found that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs). [The microbiome is the aggregate of microorganisms that reside on the skin, in saliva and the oral mucosa, the conjunctiva, and in the gastrointestinal tract.]. Further analysis suggested that the gut microbiomes of autoantibody positive individuals and seronegative FDRs clustered together but were separate from those of new onset patients and unrelated healthy controls. The authors assert that their observations suggest that altered intestinal microbiota may be associated with disease susceptibility.


Frequent use of an automated bolus advisor improves glycemic control in pediatric patients treated with insulin pump therapy
Ralph Ziegler et al. Pediatric Diabetes. Doi: 10.1111/pedi.12290

This study assessed the impact of frequent and persistent bolus advisor (BA) use on glycemic control among pediatric patients with type 1 diabetes. The 6-month study recruited 104 children who were using the Accu-Chek Aviva Combo insulin pump. Frequency of BA use, HbA1c, hypoglycemia, therapy changes, mean blood glucose, and glycemic variability was assessed at baseline and at 6 months. The findings were that frequent use of the Accu-Chek Aviva Combo insulin pump BA feature was associated with improved and sustained glycemic control with no increase in hypoglycemia.


Cardiovascular mortality in type 2 diabetes patients with incident exposure to insulin glargine
Sorin Ioacara et al. Journal of Diabetes Research. Doi:

In this study all consecutive diabetes patients aged over 40 years were screened at their first diabetes outpatient visit – where the exclusion criteria restricted the cohort to 4,990 incident insulin users. The study ran from 2001 and 2008 and participants were followed up for death until 2011. It found that there were 887 deaths (of which 521 were cardiovascular) and that glargine cumulative time exposure significantly lowered overall cardiovascular and myocardial infarction mortality but not stroke mortality. Glargine cumulative dose exposure significantly lowered cardiovascular mortality but not for myocardial infarction and stroke. The conclusion was that both cumulative dose and time exposure to insulin glargine were associated with lower cardiovascular mortality. The effect was mostly driven by myocardial infarction end point, and these finding supported the concept of macrovascular benefit for basal analogue insulin use in type 2 diabetes.


Management of hyperglycemia and enteral nutrition in the hospitalized patient
Patricia Davidson et al. Nutrition in Clinical Practice. Doi: 10.1177/0884533615591057

There has been increased attention on the importance of identifying and distinguishing the differences between stress-induced hyperglycemia (SH), newly diagnosed hyperglycemia (NDH), and hyperglycemia in persons with established diabetes mellitus (DM). Inpatient blood glucose control is now being recognized as not only a cost issue for hospitals but also a concern for patient safety and care. The reasons for the increased incidence of hyperglycemia in hospitalized patients include preexisting DM, undiagnosed DM or prediabetes, SH, and medication-induced hyperglycemia with resulting transient blood glucose variability. It is clear that identifying and documenting hyperglycemia in hospitalized patients with and without a previous diagnosis of DM and initiating prompt insulin treatment is important. Agreement on the optimum treatment goals for hyperglycemia remains quite controversial, and the benefits of intensive glucose management may be lost at the cost of hypoglycemia in intensive care unit patients. Nutrition support in the form of enteral nutrition (EN) increases the risk of hyperglycemia in both critical and non–critically ill hospitalized patients. Reasons for beginning a tube feeding are the same whether a person has NDH or DM. What differs is how to incorporate EN into the established insulin management protocols. The risk for hyperglycemia with the addition of EN is even higher in those without a previous diagnosis of DM. This review discusses the incidence of hyperglycemia, the pathogenesis of hyperglycemia, factors contributing to hyperglycemia in the hospitalized patient, glycemic management goals, current glycemic management recommendations, and considerations for EN formula selection, administration, and treatment.