Journal Watch

Prepared for IDDT by Jim Young

April 2016

National diabetes insulin pump audit report, 2013-15

The Insulin Pump Audit collects information on the number and characteristics of people with diabetes using an insulin pump and the outcomes achieved since starting the pump. The guidance states that Continuous Subcutaneous Insulin Infusion (CSII) or ‘insulin pump’ therapy is recommended as a possible treatment for adults and children 12 years and over with Type 1 diabetes mellitus if: attempts to reach target HbA1c levels with multiple daily injections result in the person having ‘disabling hypoglycaemia’, or HbA1c levels have remained high (70mmol (8.5%) or above) with multiple daily injections despite the person and/or their carer carefully trying to manage their diabetes.
The key findings were:
Either people with Type 1 diabetes are being incorrectly classified as Type 2 or a substantial number of people with Type 2 diabetes are being treated with insulin pumps outside the NICE guidance.
More people on pumps achieved HbA1c treatment targets.
The audit recommend that pump services should:
Ensure their patients get all annual care processes.
Record accurately the treatment goals for starting pump treatment.
Record reliably whether the treatment goal has been achieved, especially hypoglycaemia minimisation.
When the HbA1c is in the high risk range consider whether pump treatment remains the best option.
The 25-page PDF can be downloaded from this page:


The impact of gastroparesis on diabetes control: patient perceptions
Carol Homko, Elias S. Siraj, and Henry P. Parkman. Diabetes and Its Complications.

This study identified patient perceptions regarding the impact of gastroparesis on managing their diabetes. Gastroparetic symptom severity was assessed with the Patient Assessment of Upper GI Symptoms (PAGI-SYM) that examined the impact of gastroparesis on diabetes related symptoms and control. In total 54 diabetic patients with gastroparesis (36 with Type 1 Diabetes, 18 with Type 2 Diabetes) participated in the study, and the duration of diabetes averaged 17 years with gastroparetic symptoms for 5 years. Patients rated their most severe symptoms as postprandial fullness, early satiety, and nausea. Two thirds of diabetic subjects reported that since their diagnosis of gastroparesis, their diabetes was more difficult to control and that extra time and effort was required for care of their diabetes. Patients with T1DM, compared to those with T2DM, more often expressed that since developing gastroparesis, their blood sugars have been higher, have had more frequent episodes of hypoglycemia, and found their gastroparetic symptoms worsened if blood sugars were too high. The authors of this paper conclude that gastroparesis has a significant impact on patients’ perceived ability to self-manage and control their diabetes. They suggest that future research should focus on strategies to support self-management of patients with diabetic gastroparesis. [Gastroparesis is a partial paralysis of the stomach resulting in food remaining in the stomach for an abnormally long time].


Brain lactate concentration falls in response to hypoglycemia in patients with type 1 diabetes and impaired awareness of hypoglycemia
Evita C. Wiegers et al. Diabetes. Doi: 10.2337/db16-0068

The abstract for this paper suggests that brain lactate may be involved in the development of impaired awareness of hypoglycemia (IAH), a condition that affects approximately 25% of patients with type 1 diabetes and increases the risk of severe hypoglycemia. This study investigated the effect of acute hypoglycemia on brain lactate concentration in patients with IAH, as compared to those with normal awareness of hypoglycemia (NAH) and healthy controls. After an overnight fast, all subjects underwent a hyperinsulinemic euglycemic hypoglycemic glucose clamp. [With a hyperinsulinemic-euglycemic clamp the plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal or hypoglycemic levels]. Brain lactate concentrations were measured continuously using a specific lactate detection method. The trial demonstrated that hypoglycemia generated symptoms in patients with NAH and healthy controls, but not in patients with IAH. Brain lactate fell significantly by about 20% in response to hypoglycemia in type 1 diabetes patients with IAH, but remained stable in both healthy controls and in patients with NAH. The authors posit that the fall in brain lactate is compatible with increased brain lactate oxidation providing an alternative fuel source during hypoglycemia, and that this may contribute to impaired detection of hypoglycemia.


Meta-analysis: association between hypoglycaemia and serious adverse events in older patients
Katharina Mattishent and Yoon Kong Loke. Journal of Diabetes and Its Complications.  Doi:

This paper reports on a meta-analysis of serious adverse events (macro- and microvascular events, falls and fractures, death) associated with hypoglycaemia in older patients. The investigators searched MEDLINE and EMBASE spanning a ten-year period up to March 2015, and they selected observational studies that reported on hypoglycaemia and associated serious adverse events. The analysis included 17 studies involving 1.86 million participants. Eight of the studies demonstrated that hypoglycemic episodes were associated with macrovascular complications, and two studies with microvascular complications. Four studies demonstrated an association between hypoglycaemia and falls or fractures. Eight studies found that hypoglycaemia was associated with increased likelihood of death. The authors conclude that their meta-analysis raises major concerns about a range of serious adverse events associated with hypoglycaemia. They suggest that clinicians should prioritize individualized therapy and closer monitoring strategies to avoid hypoglycaemia in susceptible older patients.


Variability of insulin requirements over 12 weeks of closed-loop insulin delivery in adults with type 1 diabetes
Yue Ruan et al. Diabetes Care. Doi: 10.2337/dc15-2623

This study quantified the variability of insulin requirements during closed-loop insulin delivery. The investigators retrospectively analysed overnight, daytime, and total daily insulin amounts delivered during a multicenter closed-loop trial involving 32 adults with type 1 diabetes. Data was analysed from 1,918 nights, 1,883 daytime periods and 1,564 total days. The results showed that overnight insulin requirements were significantly more variable than daytime and total daily amounts. The authors suggest that this might explain why some people with type 1 diabetes report frustrating variability in morning glycemia.


Engineering the gut for insulin replacement to treat diabetes
Majid Mojibian, Maria M Glavas and Timothy J Kieffer. Journal of Diabetes Investigation. Doi: 10.1111/jdi.12479

The abstract to this (full text) paper prefaces with the statement that the gut epithelium’s large surface area, its direct exposure to ingested nutrients, its vast stem cell population and its immune-tolerogenic environment make it an excellent candidate for therapeutic cells to treat diabetes. The authors point out that several attempts have been made to coax immature gut cells to differentiate into insulin-producing cells by altering the expression patterns of specific transcription factors. Furthermore, because of similarities in enteroendocrine and pancreatic endocrine cell differentiation pathways, other approaches have used genetically engineered enteroendocrine cells to produce insulin in addition to their endogenous secreted hormones, and several studies support the utility of both of these approaches for the treatment of diabetes. Converting a patient’s own gut cells into meal-regulated insulin factories in a safe and immunotolerogenic environment is an attractive approach to treat and potentially cure diabetes. This paper reviews work on these approaches and the authors indicate where they feel further advancements are required.


Long-term benefits of intensive glucose control for preventing end-stage kidney disease: ADVANCE-ON
Muh Geot Wong et al. Diabetes Care. Doi: 10.2337/dc15-2322

This study examined the long-term effects of intensive glucose control on risk of end-stage kidney disease (ESKD) in patients with type 2 diabetes. Survivors, previously randomized to intensive or standard glucose control, were invited to participate in a post-trial follow-up. ESKD was defined as the need for dialysis or kidney transplantation, or death due to kidney disease. A total of 8,494 participants in the ADVANCE study (Action in Diabetes and Vascular Disease Controlled Evaluation) were followed for 5 additional years. The findings were that in-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD persisted after 9.9 years of overall follow-up. These effects were greater in earlier-stage CKD and at lower baseline systolic blood pressure levels. The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function. The conclusions were that intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.


Promoting immune regulation in type 1 diabetes using low-dose interleukin-2
Connor J. Dwyer et al. Immunology and Transplantation. Doi: 10.1007/s11892-016-0739-1

The abstract to this paper describes how dysregulation of the immune system contributes to the breakdown of immune regulation, leading to autoimmune diseases, such as type 1 diabetes (T1D). Current therapies for T1D include daily insulin, due to pancreatic β-cell destruction to maintain blood glucose levels, suppressive immunotherapy to decrease the symptoms associated with autoimmunity, and islet transplantation. Genetic risks for T1D have been linked to IL-2 and IL-2R signaling pathways that lead to the breakdown of self-tolerance mechanisms, primarily through altered regulatory T cell (Treg) function and homeostasis.  [The interleukin-2 receptor (IL-2R) is a protein expressed on the surface of certain immune cells, such as lymphocytes, that binds and responds to a cytokine called IL-2]. [Cytokines are a broad and loose category of small proteins that are important in cell signaling. They are released by cells and affect the behaviour of other cells].In attempt to correct such deficits, therapeutic administration of IL-2 at low doses has gained attention due to the capacity to boost Tregs without the unwanted stimulation of effector T cells. Preclinical and clinical studies utilizing low-dose IL-2 have shown promising results to expand Tregs due to their high selective sensitivity to respond to IL-2. These results suggest that low-dose IL-2 therapy represents a new class of immunotherapy for T1D by promoting immune regulation rather than broadly suppressing unwanted and beneficial immune responses.


Accelerated fetal growth prior to diagnosis of gestational diabetes mellitus: a prospective cohort study of nulliparous women
Ulla Sovio, Helen R. Murphy and Gordon C.S. Smith. Diabetes Care. Doi: 10.2337/dc16-0160

This prospective cohort study of unselected nulliparous women recorded ultrasonic measurement of the fetal abdominal circumference (AC) and head circumference (HC) at 20 and 28 weeks of gestational age (wkGA). Exposures were diagnosis of GDM greater than 28 wkGA and maternal obesity. [Nulligravida is a woman who has never been pregnant]. It was found that of the 4,069 women studied, 171 (4.2%) were diagnosed with GDM at greater than 28 wkGA. There was no association between fetal biometry at 20 wkGA and subsequent maternal diagnosis of GDM. However, at 28 wkGA, there was an increased risk of AC greater than 90th percentile and HC-to-AC ratio less than 10th percentile. [A percentile is a measure used in statistics indicating the value below which a given percentage of observations in a group of observations fall. For example, the 20th percentile is the value (or score) below which 20 percent of the observations may be found]. Maternal obesity showed similar associations at 28 wkGA. The combination of GDM and obesity was associated with an approximately fivefold risk of AC greater than 90th percentile and approximately threefold risk of HC-to-AC ratio less than 10th percentile. Fetal AC greater than 90th percentile at 28 weeks was associated with an approximately fourfold risk of being large for gestational age at birth. The conclusions drawn were that a diagnosis of GDM is preceded by excessive growth of the fetal AC between 20 and 28 wkGA, and its effects on fetal growth are additive with the effects of maternal obesity.


Global report on diabetes
World Health Organisation

This new WHO report calls upon governments to ensure that people are able to make healthy choices and that health systems are able to diagnose, treat and care for people with diabetes. It encourages us all as individuals to eat healthily, be physically active, and avoid excessive weight gain.
The report is available for download as 88-page PDF