For the first time, researchers have determined how bromodomain (BRD) proteins work in type 2 diabetes, which may lead to a better understanding of the link between adult-onset diabetes and certain cancers.
The findings, which appear in PLOS ONE, show that reducing levels in pancreatic beta cells of individual BRDs, called BET proteins, previously shown to play a role in cancer, may also help patients who are obese and diabetic.
The research was led by Gerald V. Denis, PhD, associate professor of pharmacology and medicine at Boston University School of Medicine, who was the first to show that BET protein functions are important in cancer development.
Adult-onset diabetes has been known for decades to increase the risk for specific cancers. The three main members of the BET protein family, BRD2, BRD3 and BRD4, are closely related to each other and often cooperate. However at times, they work independently and sometimes against each other.
According to the researchers new small molecule BET inhibitors have been developed that block all three BET proteins in cancer cells, but they interfere with too many functions.
"The BET proteins provide a new pathway to connect adult-onset diabetes with cancer, so properly targeting BET proteins may be helpful for both," explained Denis, who is the corresponding author of the study.
He believes this discovery shows the need for deeper analysis of individual BET proteins in all human cell types, starting with boosting insulin and improving metabolism in the pancreas of adults who are obese.
"Without better targeted drugs, some ongoing cancer clinical trials for BET inhibitors are premature. These new results offer useful insight into drug treatments that have failed so far to appreciate the complexities in the BET family."
People with type 2 diabetes and obstructive sleep apnea (OSA) may not experience improved glycemic control by using continuous positive airway pressure, or CPAP, as some studies have suggested, according to the results of a randomized, controlled trial published online ahead of print in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
"Many studies have indicated that OSA may contribute towards the development and progression of type 2 diabetes," said lead study author Jonathan Shaw, MD, associate professor and head of population health at Melbourne's Baker IDI Heart and Diabetes Institute "However, proving that link, and determining if treating OSA could have benefits for glucose control, requires intervention studies. Some uncontrolled studies had reported improved glucose control after starting CPAP, but some small controlled trials did not support this."
In "The Effect of Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes," researchers in Australia and the U.S. randomly assigned 298 patients with "relatively well-controlled" type 2 diabetes and newly diagnosed OSA to either treat their sleep apnea with CPAP or receive usual care.
In addition to measuring the change in glycemic control, researchers studied changes in blood pressure, daytime sleepiness and quality of life over six months. Researchers found:
No difference between those receiving CPAP and the control group in change in glycated hemoglobin (HbA1c) at three and six months.
Greater fall in diastolic blood pressure over six months in the CPAP group compared to controls -- a finding that was statistically significant only among those who used CPAP for at least four hours a night.
Daytime sleepiness improved significantly among those using CPAP as measured by the Epworth Sleepiness Index.
Quality of life between the two groups was not statistically significant overall as measured by the RAND 36-Item Short Form Health Survey. Among those using CPAP for at least four hours a night, there was a significant difference with controls on vitality and mental health subscores.
Authors offered several possible explanations for why participants using CPAP did not experience better glycemic control. OSA may play a bigger role in the development of diabetes than in the control of established diabetes. The bar for adherence to CPAP -- set at four hours a night -- may have been set too low. And, lastly, CPAP may only benefit those with severe OSA and/or poor glycemic control. Participants with those characteristics were not well represented in the study, the authors noted.
"OSA is common in people with type 2 diabetes, and although we did not find a glycemic benefit for its treatment, clinicians should have a high index of suspicion for its presence when patients experience daytime sleepiness, snoring and resistant hypertension," Dr. Shaw said. "Identification and treatment of OSA in these patients may lead to clinically meaningful benefits."
A new study in Molecular Nutrition & Food Research found that anthocyanin-rich strawberries may improve insulin sensitivity.
Insulin resistance (IR) is a hallmark of metabolic syndrome and a risk factor for heart disease and type 2 diabetes. Typically, after a meal, the pancreas produces an appropriate amount of insulin to usher glucose from the bloodstream into the cells. People with IR have built up a tolerance to insulin, so the pancreas must churn out extra insulin to coax blood sugar into the cells. Over time, this process can lead to type 2 diabetes.
Researchers observed the effect of anthocyanins on the postprandial insulin response of 21 obese adults with insulin resistance. Subjects were served a typical ‘Western-style’ meal high in carbohydrates and fat plus a beverage that contained freeze-dried whole strawberry powder. The beverages were controlled for fiber, and the amount of strawberry powder ranged from 0 grams to 40 grams (equivalent to 3 cups of fresh strawberries). When subjects drank the most concentrated beverage, they didn’t produce as much insulin as when they drank the least concentrated versions. In other words, they didn’t need as much insulin to metabolize their meal after drinking the anthocyanin-rich strawberry shake.
While the exact mechanisms are unclear, strawberry anthocyanins may alter insulin signaling at a cellular level.
These results add to the collective evidence that consuming strawberries may help improve insulin action, says study author Britt Burton-Freeman, Ph.D.
Eunyoung Park, et al. A dose-response evaluation of freeze-dried strawberries independent of fiber content on metabolic indices in abdominally obese individuals with insulin-resistance in a randomized, single-blinded, diet-controlled crossover trial. Molecular Nutrition & Food Research, February 2016.
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A multinational clinical trial led by UT Southwestern Medical Center and others found that injection of a new long-acting insulin combined with another drug improves glucose control in patients with Type 2 diabetes and, additionally, is associated with weight loss.
The trial compared glucose control of participants receiving daily injections of either basal insulin glargine or IDegLira, which is a mixture of insulin degludec and liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist. Liraglutide stimulates cells in the pancreas to produce insulin. The study findings were published today in the Journal of the American Medical Association.
"Many patients who are on an oral agent and basal insulin are unfortunately not at goal glycemia. Treatment options for such patients are to either increase the basal insulin dose or to add additional shots of insulin at mealtimes. The downside of both of these approaches is weight gain and hypoglycemia (low blood sugar)," said the study's lead author, Dr. Ildiko Lingvay, Associate Professor of Internal Medicine and Clinical Sciences at UT Southwestern. In addition, taking multiple injections per day also increases the burden on the patient.
Currently, about two-third of patients with Type 2 diabetes who are treated with basal insulin are not in good glucose control, Dr. Lingvay said.
"The clinical trial found that participants treated with the combination product had more improvement in their HbA1C (hemoglobin A1C) test than those treated with basal insulin alone, they had weight loss rather than weight gain, and they had many fewer episodes of hypoglycemia," she added.
The phase 3 trial, conducted from September 2013 to November 2014, enrolled 557 participants with uncontrolled Type 2 diabetes in 75 treatment centers located in 10 countries. At the time they enrolled, study participants were taking an oral diabetes medication, metformin, as well as basal insulin glargine. All remained on the oral medication.
Participants were then randomly assigned to continue on insulin glargine - or to switch to daily injections of IDegLira. Those who were assigned to the insulin glargine group had their insulin dose sequentially increased as high as necessary to bring their glucose levels under control. For those taking IDegLira, dosage was also increased based on glucose readings, but there was a cap on the amount their dosage could be increased because of limits on liraglutide dosage.
Participants who took the combination product saw their glucose levels drop faster. On average, the HbA1C blood sugar level for participants on IDegLira dropped from 8.4 to 6.6. On average, the HbA1C level for participants on insulin glargine dropped from 8.2 to 7.1. The HbA1C test indicates the average blood glucose level over a three-month period; participants with an HbA1C level below 7 are considered within normal range.
Those taking IDegLira lost an average of about 3 pounds compared with an average weight gain of nearly 4 pounds for the glargine group. Only 6.1 percent of participants on the combination product experienced confirmed episodes of nighttime hypoglycemia compared with 24.4 percent of the patients on the basal glargine.
"The advantage of the combination product is that the treatment burden is the same as taking a basal insulin - one shot a day - but you are getting an additional product that works through a different mechanism and addresses different pathophysiologic defects of the disease. The liraglutide affects satiety and induces weight loss, while also stimulating insulin secretion. The combination product addresses more underlying abnormalities present in this disease," said Dr. Lingvay.
Insulin degludec, which was approved last fall by the Food and Drug Administration, is the longest-acting insulin currently available.
"Patients on IDegLira did better overall, especially when factoring in weight loss and decreased hypoglycemia risk," said Dr. John Buse, Professor of Medicine at the University of North Carolina School of Medicine and senior author on the study.