Journal Watch

Prepared for IDDT by Jim Young

October 2016

Heart rate informed artificial pancreas (AP) system enhances glycemic control during exercise in adolescents with T1D
Mark D. DeBoer et al. Pediatric Diabetes. Doi: 10.1111/pedi.12454
This trial recruited adolescents with T1D age 13 – 18 years and on separate days they received either the unmodified UVa AP (stdAP) or an artificial pancreas system connected to a portable heart rate monitor (AP-HR) that triggered an exercise algorithm for blood glucose (BG) control. During admissions participants underwent a structured exercise regimen. Hypoglycemic events and CGM tracings were compared between the two admissions, during exercise and for the full 24-hour period. It found that heart rate signals can safely and efficaciously be integrated in a wireless AP system to inform of physical activity. While exercise contributes to hypoglycemia among adolescents, even when using an AP system, informing the system of exercise via a HR monitor improved time spent in an hypoglycaemic event. Although, it did not significantly reduce the total number of hypoglycemic events, which were low in both groups.


Long-term outcomes in patients with morbid obesity and type 1 diabetes undergoing bariatric surgery
Nuria Vilarrasa et al. Obesity Surgery. Doi: 10.1007/s11695-016-2390-y

Thirty-two patients with T1DM and initial BMI of 41.3 kg/m2 were included in this study. 18.7 % underwent duodenal switch (DS), 34.4 % gastric bypass, and 46.9 % sleeve gastrectomy and they were followed-up after surgery for 4.6 ± 2.6 years. Changes in BMI, HbA1c, insulin requirements, evolution of comorbidities, and microvascular complications were registered annually after surgery. The findings were that the benefits of weight reduction following bariatric surgery were mainly on: insulin requirements, obesity comorbidities, and some benefits in diabetes complications. However, the authors posit that it might have only minimal effect on the glycemic control in the long term.


GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes
Craig A. Beam et al. Diabetologia. Doi: 10.1007/s00125-016-4122-1

GAD is a major target of the autoimmune response that occurs in type 1 diabetes. However, clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results.
[Glutamic Acid Decarboxylase Autoantibodies (GAD) is used to help discover whether someone has either type 1 diabetes or Latent Autoimmune Diabetes of Adulthood] The investigators estimate that there is a 98% probability that 20 μg GAD with alum administered twice yields a positive biological effect, and that this effect probably results in a 15–20% reduction in the loss of C-peptide at approximately 1 year after treatment.
[C-peptide is a protein that connects insulin’s A-chain to its B-chain in the proinsulin molecule. Measuring C-peptide can help to determine how much of a patient’s own natural insulin is being produced as C-peptide is secreted in equimolar amounts to insulin]
This translates to an annual expected loss of between −0.250 and −0.235 pmol/ml in treated patients and this compares with an expected loss of −0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The authors conclude that the biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.


Type 1 diabetes in older adults: comparing treatments and chronic complications in the United States T1D Exchange and the German/Austrian DPV registries
Ruth S. Weinstock et al. Diabetes Research and Clinical Practice. Doi:

This study looked at people over 60 years old with type 1 diabetes seen during 2011-2012 in the USA T1DX and the German/Austrian DPV registries. Individuals in both registries were similar in body mass index, percent with obesity (25%) and gender (48% male). The results showed that in T1DX there was longer diabetes duration (32.3 vs. 28.8 years), greater use of antihypertensive medications (85% vs 62%), statins (68% vs 40%), aspirin (77% vs 21%), insulin pumps (58% vs. 18%), and less smoking (7% vs. 10%); lower LDL-cholesterol and lower adjusted mean systolic and diastolic blood pressures (128 vs. 136 and 68 vs. 74 mmHg); fewer myocardial infarctions (6% vs. 9%), strokes (2% vs. 8%), microvascular complications including microalbuminuria (17% vs. 44%) but increased depression (16.1% vs. 8.7%). Adjusted mean HbA1c levels were similar (7.5% 58 mmol/mol). These disparities are unsettling, and one cannot but agree with the authors suggestion that further research is needed to better understand the role of intensive therapy in improving outcomes in older adults with type 1 diabetes.


Diabetic macular edema pathophysiology: vasogenic versus inflammatory
Pedro Romero-Aroca et al. Journal of Diabetes Research. Doi:
We all know that diabetic macular edema (DME) can cause blindness in patients suffering from diabetic retinopathy (DR). In the treatment of diabetes: glycemia, arterial tension, and lipids are the gold standard for preventing DR and DME. Although angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease, this still remains to be clarified. Also it has to be ascertained whether angiogenesis following vascular endothelial growth factor (VEGF) overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. The analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. The authors assert that in the future, diagnosing the physiopathology of each patient with DME will help select the most effective drug.


Association between HbA1c variability and risk of microvascular complications in adolescents with type 1 diabetes
Sohaib A. Virk et al. Journal of Clinical Endocrinology & Metabolism. Doi:

This study investigated the association between HbA1c variability and risk of microvascular complications in adolescents with Type 1Diabetes. A total of 1706 adolescents were included in the study. The main outcome measured were: Glycemic variability, retinopathy, renal function (albumin excretion rate), peripheral neuropathy, and cardiac autonomic neuropathy (CAN). The study found that greater HbA1c variability predicted retinopathy, early nephropathy, and CAN, in addition to established risk factors. The authors posit that minimizing long-term fluctuations in glycemia may provide additional protection against the development of microvascular complications.


Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes
Jan Bolinder et al. Lancet. Doi:

This study assessed whether a factory-calibrated, sensor-based, flash glucose-monitoring system, when compared with self-monitored glucose testing, reduced exposure to hypoglycaemia in patients with type 1 diabetes. The trial enrolled 328 adult patients with well controlled type 1 diabetes from 23 European diabetes centres. During the trial no device-related hypoglycaemia or safety issues were reported. 13 adverse events were reported by ten participants related to the sensor—four of allergy events (one severe, three moderate); one itching (mild); one rash (mild); four insertion-site symptom (severe); two erythema (one severe, one mild); and one oedema (moderate). There were ten serious adverse events (five in each group) reported by nine participants; none of which were related to the device. The overall findings were that novel flash glucose testing reduced the time adults with well controlled type 1 diabetes spent in hypoglycaemia. The authors suggest that further studies are needed to assess the effectiveness of this technology in patients with less well controlled diabetes and in younger age groups.


Sweet bones: the pathogenesis of bone alteration in diabetes
Mohammed Al-Hariri. Journal of Diabetes Research. Doi:

This abstract (to a full, open-access paper) provides an intriguing look at an often neglected topic. People with diabetes have increased risk of fracture. The pathogenesis underlying the status of bone alterations in diabetes mellitus is not completely understood but is multifactorial. The major deficits appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts due to abnormal insulin signaling pathway. Other prominent features of diabetes mellitus are an increased urinary excretion of calcium and magnesium, accumulation of advanced glycation end products, and oxidative stress leading to sweet bones (altered bone’s strength, metabolism, and structure).
[Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars]
The authors suggest that every diabetic patient should be assessed for risk factors for fractures and osteoporosis. The pathogenesis of the bone alterations in diabetes mellitus as well as their molecular mechanisms needs further study.


Initiation and intensification strategies in type 2 diabetes management: A comparison of Basal Plus and Premix Regimens
Michelle Downie et al. Diabetes Therapy. Doi: 10.1007/s13300-016-0199-2

The aim of this review was to examine published clinical evidence that has directly compared two recommended treatment approaches in patients with type 2 diabetes (T2D):
(1) a ‘basal plus’ regimen, whereby 1–2 injections of prandial insulin are added to basal insulin; or
(2) the use of once- or twice-daily premix insulin analogs, which contain both basal and prandial insulin in a single injection.
Available evidence suggests that both basal plus and premix regimens are comparable in terms of efficacy and safety when used for insulin initiation in insulin-naïve patients and intensification in patients who have failed on basal insulin; instances of greater glycemic control are observed with premix insulin; however, these are often accompanied by increases in hypoglycemia and/or weight relative to basal plus treatment, and results should be interpreted within the context of total insulin doses used. This review notes that relatively low numbers of patients achieved glycemic control when both regimens were used for insulin intensification following failure of basal insulin, suggesting that a full basal–bolus regimen and/or the use of different treatments is clinically indicated in certain patients. In summary, the review argues that both basal plus and premix insulin regimens are relatively efficacious and safe options for patients with T2D during both insulin initiation in insulin-naïve patients and intensification in patients who have failed on basal insulin. This emphasizes the important role of patient-centered factors in clinical decision-making.


Patterns of anti-diabetic medication use in patients with type 2 diabetes mellitus in England and Wales
Preeti Datta-Nemdharry et al. Pharmacoepidemiology and Drug Safety. Doi: 10.1002/pds.4092
The purpose of this study was to characterise how Type 2 Diabetes Mellitus (T2DM) is treated in England and Wales and whether this adheres to 2009 National Institute for Health and Care Excellence (NICE) guidance on management of T2DM. To do this, data for T2DM patients aged 18+ years prescribed at least one anti-diabetic drug between 2000 and 2012 were extracted from the Clinical Practice Research Datalink. The cohort of 123,671 patients included: 56% males, 95% aged 40+ and 79% with at least one recorded HbA1c level. Metformin was the first prescription for 98,957 (80%) patients, with mean HbA1c of 8.68% prior to initiation. A total of 19,890 (16%) patients received sulphonylureas first-line. 1,402 (12%) insulin users were prescribed insulin first-line. A total of 96,895 (78%) patients were managed in line with one of the treatment pathways recommended by NICE. Patients prescribed insulin second-line after metformin had a mean HbA1c of 10.11% prior to first prescription of insulin and 9.98% at baseline. Both values were significantly higher than other groups initiating new treatment. So, in over three-quarters of patients, anti-diabetic drugs were being prescribed per NICE guidance. When insulin was used earlier than recommended, there appeared to be a need for urgent and rapid glycaemic control.