Researchers find TZDs may pose certain health risks for diabetics
MARYLAND HEIGHTS, Mo. — According to a report in the May issue of Cell Metabolism, while drugs known as thiazolidinediones, or TZDs, are widely used in diabetes treatment, they have effects on the kidneys that lead to fluid retention as the volume of plasma in the bloodstream expands.
"TZDs usually increase body weight by several kilograms," stated George Seki of the University of Tokyo. "However, TZDs sometimes cause massive volume expansion, resulting in heart failure."
The findings may lead to the development of improved diabetes therapies.
TZDs act on a hormone receptor known as peroxisome proliferator-activated receptor γ. PPARγ is a master gene of fat cell biology and differentiation, Seki explained, making it an ideal target for diabetes treatment.
However, TZDs also lead to changes in gene expression that enhance the sodium transport system of the kidney and lead to the reabsorption of water and salt, as scientists knew. But, Seki said, that mechanism alone didn’t seem to be enough to explain the volume expansion.
Seki’s team has found that TZDs also have direct effects on channels in the kidney known as the proximal tubules. TZDs rapidly stimulate sodium-coupled bicarbonate absorption from renal proximal tubules. Inhibitors of PPARγ or other players in the pathway suppress that stimulation, they reported.
The discovery helps to explain the speed with which side effects of TZDs sometimes can arise, and may lead to strategies to improve insulin resistance without the accompanying severe cardiovascular side effects, the researchers noted. "Massive volume expansion in human subjects usually occurs after weeks of use of TZDs," they wrote. "However, it can also occur as rapidly as four days after use of TZDs, supporting the involvement of multiple mechanisms. Thus, combination therapy with different diuretics targeting both renal proximal tubules and the distal nephrons could be a therapeutic option in case of TZD-induced massive volume expansion."
The findings also raise the possibility that other small molecules might bind PPARγ in slightly different ways, leading to different biological responses, the researchers added. In fact, several selective PPARγ modulators already have been developed and appear to induce less fluid retention, at least in animals. Whether that will prove to work in humans to prevent massive fluid retention remains to be seen.
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Study finds link between insomnia, high insulin resistance among diabetics
NEW YORK — Diabetics that have trouble sleeping likely experience high insulin resistance and have a more difficult time controlling the disease, according to study findings published in the June issue of Diabetes Care.
Researchers said they monitored the sleep of 40 subjects with diabetes for a duration of six nights and also measured the subjects’ insulin and glucose levels during clinical examinations. The subjects also reported if they generally suffered from symptoms of such sleep disturbances as insomnia, snoring or sleep apnea.
Among the diabetics, poor sleepers had 23% higher blood-glucose levels in the morning, as well as 48% higher blood insulin levels. Using these numbers to estimate a person’s insulin resistance, the researchers found that poor sleepers with diabetes had 82% higher insulin resistance than normal sleepers with diabetes.
The data was collected as part of the CARDIA study, an ongoing longitudinal study of the heart health that is supported by the National Heart, Lung and Blood Institute. It has tracked thousands of people for more than 20 years, study investigators said.
"Poor sleep quality in people with diabetes was associated with worse control of their blood-glucose levels," said Kristen Knutson, assistant professor of medicine and lead author of the study. "People who have a hard time controlling their blood-glucose levels have a greater risk of complications, they have a reduced quality of life and they have a reduced life expectancy."
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Pharmacy’s role in emergency preparedness underscored in statement to House subcommittee
ALEXANDRIA — Pharmacies play a critical role in emergency preparedness. That was the key message in a statement issued this week by the National Association of Chain Drug Stores to the House of Representatives’ Homeland Security Subcommittee on Emergency Preparedness, Response and Communications.
The subcommittee held a hearing this week, titled "Taking Measure of Countermeasures: A Review of Efforts to Protect the Homeland Through Distribution and Dispensing of CBRN [chemical, biological, radiological or nuclear] Medical Countermeasures."
In the statement, NACDS outlined the ways in which pharmacies are equipped and stand ready to assist policymakers and public health officials at all levels of government in ensuring convenient access to countermeasures in a medically relevant time frame following an emergency.
NACDS discussed pharmacy’s role in extending the reach of public health during the aftermath of emergencies, such as Hurricane Katrina and during the 2009 H1N1 influenza pandemic. During these types of situations, pharmacists performed a range of services for patients and worked cooperatively with state and local partners to ensure access to high-quality patient care.
"Pharmacists have performed a range of services to targeted patient populations following emergencies, including dispensing countermeasures, administering vaccines, patient screening and triage, education of the public and monitoring for adverse events," NACDS highlighted in the statement. "Pharmacies have existing technological infrastructures that can be leveraged to triage patients, have a lot space to accommodate surges in patient demand and sell personal protective equipment and medical supplies that may also be important in preventing or treating CBRN threats."
"As the face of neighborhood health care, community pharmacies remain committed to assist public health efforts to protect our citizens through convenient access to countermeasures. We look forward to working with Congress and the public health community to ensure the nation’s community pharmacies are used to the greatest extent possible," the statement concluded.
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