Monday, 16 January 2012

Stem Cells May Help in Type 1 Diabetes

Stem Cells May Help in Type 1 Diabetes

Therapy using the patient's lymphocytes passed through a device with cord blood stem cells may "educate" the patient's cells to provide safe, lasting treatment for patients with type 1 diabetes, according to the results of a small Chinese study.

Those patients with moderate diabetes and some residual beta cell function (Group A) exhibited improved fasting C-peptide levels at 12 and 24 weeks post-treatment, Yong Zhao, PhD, of the University of Illinois at Chicago, and colleagues reported online in BMC Medicine.

Patients with more severe disease and no residual beta cell function (Group B) also showed improvement at every follow-up.

Treatment consisted of passing lymphocytes from the patient's blood through discs containing adherent multipotent cord blood stem cells. After two or three hours, the lymphocytes were collected and returned to the patient.

No participants suffered any serious adverse events, reporting only mild discomfort during venipuncture and apheresis, which resolved at the conclusion of the procedure. There were also no significant differences at 24 hours after treatment in white blood cell counts or body temperature.

In the phase I/II open-label trial, the researchers enrolled 15 patients with type 1 diabetes (mean duration 8.5 ± 6.4 years) receiving care at the General Hospital of the Jinan Military District. Patients were enrolled if they met the 2010 diagnosis criteria of the American Diabetes Association and blood tests found at least one autoantibody to pancreatic islet beta cells.

Exclusion criteria included liver, kidney, or heart disease, pregnancy, use of immunosuppressive medications, viral diseases, or immunodeficiency diseases. After two days of hospitalization to monitor early adverse reactions, follow-ups were scheduled at 4, 12, 24, 40 weeks after treatment.

Twelve patients were divided into two groups of six according to the severity of their diabetes and whether they had any residual beta cell function. Both cohorts were given full treatments. A third group of three individuals was given a single sham treatment to serve as a process-control.

Addressing the autoimmunity that underlies type 1 diabetes has been a major impediment to using stem cells for long-term treatment. Studies in mice have shown that cord blood stem cells can be used to alter immune function and they have been shown to modulate the immune function of type 1 diabetes patient-derived islet beta cell-specific T cell clones.

The researchers wanted to know if re-educating a patient's lymphocytes had the potential to address the autoimmunity concerns in a way that reduced donor risk, minimized ethical concerns, and avoided graft-versus-host disease.

C-peptide production at baseline in Group B was less than the minimum sensitivity of the test following a 75-g oral glucose tolerance. They had marked improvement at 12 weeks that continued to 40 weeks (P=0.026). The control group showed no changes at any time.

The median daily dose of insulin was reduced by 38% at 12 weeks (36 ± 13.2 units/day versus 22 ± 1.8 units/day) and 25% in the more severe group (48 ± 7.4 units/day versus 36 ± 4.4 units/day). These were maintained through the entire 24 weeks this measure was tracked.

Median hemoglobin A1C showed similar results.

In Group A the median was lowered from 8.73% ± 2.49 at baseline to 6.82% ± 0.49 at 12 weeks after treatment (P=0.019). This measure fell 1.68% ± 0.42 at 12 weeks in Group B with no change in the controls (P=0.86). These indicated to the authors that immune education of cord blood stem cells could lead to regeneration of islet beta cell function.

They also measured changes in the CD4+CD25+Foxp3+ regulatory T lymphocytes (Tregs) to see if measures of autoimmunity were altered. The percentage of Tregs in peripheral blood was significantly increased at 4 weeks in the treatment groups but not in the sham controls (P<0.0001).

There was no evidence of transfer of the cord blood stem cells to the patients as a result of the process of treating the lymphocytes, according to the investigators.

"This trial provides powerful evidence that exposing a patient's lymphocytes to [cord blood stem cells] can achieve the two essential outcomes required to cure T1D: reversal of autoimmunity and regeneration of islet beta cells," wrote the authors. "Importantly, the trial provides additional support for the mechanisms of [cord blood stem cells]-mediated immune response and demonstrates these mechanisms are apparent and lasting in patients."

Friday, 6 January 2012

Sleep Woes Tied to Blood Sugar Levels in Diabetic Kids

Sleep Woes Tied to Blood Sugar Levels in Diabetic Kids

Children with type 1 diabetes may be more likely to have sleep problems that worsen not only their blood sugar control, but also their quality of life, researchers found.

Diabetic children with more nightly apnea events had significantly higher glucose levels and spent more time in hyperglycemia than young type 1 diabetics without sleep disturbances, Michelle Perfect, PhD, of the University of Arizona in Tucson, and colleagues reported online in Sleep.

And those who reported being sleepier during the day had more trouble in school and worse quality of life, they found.

"Despite adhering to recommendations for good diabetic health, many youth with type 1 diabetes have difficulty maintaining control of their blood sugars," Perfect said in a statement. "We found that it could be due to abnormalities in sleep, such as daytime sleepiness, lighter sleep, and sleep apnea. All of these make it more difficult to have good blood sugar control."

Some work has shown that sleep can impact glucose regulation. In particular, slow-wave, or deep sleep, may be important in glucose maintenance and insulin sensitivity, the researchers said. In fact, some studies have shown that sleep architecture may be altered in diabetes patients, and they may spend more time in lighter stages of sleep and in the REM stage, and less time in deeper sleep.

Yet most research in this area has focused on adults with type 2 diabetes, not young people with type 1 disease, they noted.

So Perfect and colleagues assessed 50 type 1 diabetes patients ages 10 to 16 -- 40 of whom had polysomnography data -- and in part of the study, compared them with 40 matched controls.

They found that kids with an apnea-hypopnea index score of 1.5 events per hour or greater had higher blood glucose levels on continuous glucose monitoring (CGM) and a spent greater percentage of time at night in hyperglycemia (P=0.021 for both).

With regard to sleep architecture, when compared with healthy controls, youth with type 1 diabetes spent more time in N2 sleep, or lighter sleep (P=0.003), and less time in N3 sleep, or deeper sleep (P=0.011), particularly during the first half of the night, Perfect and colleagues wrote.

Those with diabetes also experienced more central apnea events per hour (P=0.029), although there were no significant differences in total apnea events, the researchers said.

Perfect and colleagues found that spending less time in N3 sleep, or deep sleep, was associated with higher HbA1c levels (P=0.003), and that more time spent in N2 sleep, or a lighter sleep, was associated with higher HbA1c levels (P<0.001), higher glucose levels (P=0.014), and more time in hyperglycemia (P=0.03).

The researchers also found that self-reported daytime sleepiness was linked with compromised psychosocial functioning.

For instance, greater daytime sleepiness was significantly associated with worse grades in school (P<0.001), reduced disease-related quality of life (P=0.004), more diabetes-related worry (P=0.005), and greater depressive symptoms (P=0.027).

Self-reported sleep problems also were related to lower scores on state standardized tests of reading, the researchers found, and spending more time in N2 sleep, or lighter sleep, was associated with worse scores on state math tests.

The findings regarding school performance "should serve as an impetus for future research to better understand the role of sleep in altering school functioning in youth with diabetes," the researchers wrote.

The researchers concluded that the study "adds to the burgeoning evidence that sleep-disordered breathing may result in higher glucose levels," but that further study is needed -- particularly a longitudinal trial to discern whether sleep problems affect glucose control, or if dysregulated glucose contributes to sleep problems in young type 1 diabetics.

They added that clinicians should routinely ask about sleep habits in this population as part of routine care.

The study was limited by its small population, and because it didn't control for insulin dosage. Also, it precluded analysis of the effects of severe sleep-disordered breathing on this population.