Journal Watch

Prepared for IDDT by Jim Young

July 2014

Outpatient glycemic control with a bionic pancreas in type 1 diabetes
Steven J. Russell et al. NEJM. Doi: 10.1056/NEJMoa1314474

This study reports on the results from two 5-day trials, one involving adults and one involving adolescents, which tested an autonomous, wearable, bihormonal, bionic pancreas in two distinct outpatient settings. [A Bihormonal system delivers both and glucagon]. The research utilised a random-order, crossover design, where patients received therapy with a bionic pancreas for 5 days and therapy with their own insulin pump for 5 days. It was found that when compared with an insulin pump, a wearable, automated, bihormonal, bionic pancreas improved mean glycemic levels, with less frequent hypoglycemic episodes, among both adults and adolescents with type 1 diabetes mellitus.


Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes
Yves Reznik et al. Lancet. Doi: 10.1016/S0140-6736(14)61037-0

Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. The researchers aimed to resolve this uncertainty by conducting a trial at 36 hospitals, tertiary care centres, and referral centres in Canada, Europe, Israel, South Africa, and the USA. The study looked at 331 patients who were randomised (168 to pump treatment, 163 to multiple daily injections).It was found that in patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option.


MANF is indispensable for the proliferation and survival of pancreatic ß cells
Maria Lindahl et al. Cell Reports. Doi: 10.1016/j.celrep.2014.03.023

The authors of this paper remind us that all forms of diabetes mellitus (DM) are characterized by the loss of functional pancreatic β cell mass, leading to insufficient insulin secretion, and that the identification of novel approaches to protect and restore β cells is essential for the development of DM therapies. They also report that the physiological function of mesencephalic astrocyte-derived neurotrophic factor (MANF) in mammals has remained obscure. To explore this the researchers generated MANF-deficient mice that develop severe diabetes due to progressive postnatal reduction of β cell mass, caused by decreased proliferation and increased apoptosis [Cell death]. Their research demonstrated that overexpression of MANF in the pancreas of diabetic mice enhanced β cell regeneration. The authors posit that their research has demonstrated that MANF specifically promotes β cell proliferation and survival, and might constitute a therapeutic candidate for β cell protection and regeneration.


Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes
Teresa Rodriguez-Calvo et al. Diabetes. Doi: 10.2337/db14-0549

Type 1 diabetes (T1D) results from a complex interplay between genetic susceptibility and environmental factors which have been implicated in the pathogenesis of disease both as triggers and potentiators of beta cell destruction. CD8 T cells are the main cell type found in human islets and they have been shown in vitro to be capable of killing beta-cells. The authors of this paper report that CD8 T cells also infiltrate the exocrine pancreas of diabetic subjects in high numbers, and not only endocrine areas. [Exocrine glands are glands of the exocrine system that secrete their essential product by way of a duct to some environment external to itself]. They also report that people with T1D present significantly higher CD8 T cell density in the exocrine tissue. The preliminary data from subjects with T2D indicates that there might be a spontaneous inflammatory infiltration of the exocrine tissue, common to both T1D and T2D. The researchers posit that their study provides the first information on the precise tissue distribution of CD8 T cells in pancreata from subjects with T1D and T2D.


Fear of hypoglycemia in parents of children with type 1 diabetes
Colin Patrick Hawkes et al. Journal of Paediatrics and Child Health. Doi: 10.1111/jpc.12621

The aim of this study was to determine if parental fear of hypoglycaemia is associated with worse glycaemic control and increased resource utilisation and to identify risk factors for increased hypoglycaemia fear. A total of 106 parents participated in the study, and the mean patient age was 11 years, and the duration of diabetes was 4.8 years. It was found that fear of hypoglycaemia was associated with worse glycaemic control. It is highest among parents of 6 to 11 year-olds but was not affected by previous severe hypoglycaemia or associated with increased contact with the diabetes team.


A Practical Method to Measure GFR in people with type 1 diabetes
D.M. Maahs et al. Diabetes and Its Complications. Doi: 10.1016/j.jdiacomp.2014.06.001

The authors of this paper assert that improved early diagnostic methods are needed to identify risk for kidney disease in people with type 1 diabetes. They hypothesized that glomerular filtration rate (GFR) measured by iohexol clearance in dried blood spots (DBS) on filter paper would be comparable to plasma (gold-standard) and superior to estimated GFR (eGFR), and that adjustment for ambient blood glucose would improve accuracy and precision of GFR measurement. [Iohexol is a contrast agent and is commonly used during coronary angiography]. It was found that Iohexol clearance measured with DBS performed better than eGFR methods. The authors say that this method is more convenient than the gold-standard GFR method and may improve screening and diagnostic capabilities in people with type 1 diabetes.


Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes
Daniel Gordin et al. Diabetes Care. Doi: 10.2337/dc14-0065

Osteopontin (OPN) is a multifunctional protein suggested to be a player in the arterial disease of patients with type 2 diabetes. However, its role for complications in patients with type 1 diabetes (T1D) is unknown. Therefore the researchers looked at the associations between OPN and diabetic vascular complications and all-cause mortality in patients with T1D. Serum OPN was measured in 2,145 adults with T1D without end-stage renal disease as part of the Finnish Diabetic Nephropathy study. It was discovered that serum OPN was a strong predictor of incipient diabetic nephropathy, a first-ever CVD event, and all-cause mortality in patients with T1D. The authors posit that serum OPN may be of clinical significance for the risk prediction of CVD events in patients with T1D.


Diabetes overtreatment in elderly individuals: risky business in need of better management
Mary A. Andrews et al. JAMA. Doi:10.1001/jama.2014.4563

Although serious hypoglycemia is a common adverse drug event in ambulatory care, current performance measures do not assess potential overtreatment. This study looked at patients receiving insulin and/or sulfonylureas in 2009. It also assessed the rates in patients with other significant medical, neurologic, or mental comorbid illness. It was found that patients with risk factors for serious hypoglycemia represented a large subset of individuals receiving hypoglycemic agents, and that approximately one-half had evidence of intensive treatment. The authors suggest that a patient safety indicator, derived from administrative data, could identify high-risk patients for whom a re-evaluation of glycemic management might be appropriate.


Association between impaired cardiovascular autonomic function and hypoglycemia in patients with type 1 diabetes
Mamta Jaiswal et al. Diabetes Care. Doi: 10.2337/dc14-0445

The researchers studied the association between glycemic variability (GV) reflecting hypoglycemic stress and cardiovascular autonomic function in subjects with type 1 diabetes.
Forty-four type 1 diabetes patients without cardiovascular disease, dyslipidemia, or hypertension participated in this pilot study. It was found that increased GV (that promoted hypoglycemic stress) was associated with reduced heart rate variability independent of glycaemic control as assessed by HbA1c. The authors posit that these pilot data suggested that glucose variability may contribute to cardiovascular autonomic dysfunction among adults with type 1 diabetes.


Should thyroid-stimulating hormone goals be reviewed in patients with Type 1 diabetes mellitus?
M. Rodacki et al. Diabetic Medicine. Doi: 10.1111/dme.12530

This study of 1,205 individuals investigated if thyroid-stimulating hormone (TSH) levels were associated with any differences in glycaemic control or diabetes-related complications in individuals with Type 1 diabetes. Patients were separated into three groups:  0.4–2.5 mU/l; 2.5–4.4 mU/l; and ≥ 4.5 mU/l. [The normal range of TSH is 0.4 – 4.5]. It found TSH levels of 0.4–2.5 mU/l were associated with a lower risk of diabetic retinopathy and renal failure in individuals with Type 1 diabetes, independently of glycaemic control and duration of the disease.