CPAP Helps Glycemic Control in OSA Patients

According to research published in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine is a study believed to be the first randomized controlled trial of its kind. The study is titled “Effect of CPAP on glycemic control in patients with obstructive sleep apnea and type 2 diabetes: A randomized clinical trial.”

A randomized clinical trial for this is believed to be the first randomized controlled trial of its kind. Francisco Garcia-Rio, MD, PhD, professor of medicine at Autonoma University of Madrid and senior study author, said the research advanced understanding of the biological relationship between two major public health problems, which epidemiological studies have indicated are related.

"OSA is a public health problem of the first order, due to its high prevalence and marked morbidity and mortality, having been linked to traffic accidents, cardiovascular complications and, more recently, neoplastic diseases," he said. "Diabetes mellitus is a global epidemic. There are currently 382 million diabetics worldwide, a figure which is estimated to reach 592 million in 2035."

Dr. Garcia-Rio and his colleagues studied results from 50 patients with both OSA and sub-optimally controlled type 2 diabetes, who were assigned to CPAP intervention or control. Participants, who ranged in age from 18 to 80, did not change diabetes medications during the trial unless medically necessary, nor were they expected to change their diets or level of physical activity.

The researchers measured glucose control, changes in insulin sensitivity and resistance, inflammatory proteins and other biomarkers associate with type 2 diabetes glycemic control. Researchers found that those using CPAP showed a statistically significant:

1. • Decrease in glycated hemoglobin (HbA1c) levels at 6 months. (The decrease at 3 months was not statistically significant.)
2. • Improvement in insulin sensitivity at 3 and 6 months.
3. • Decrease in insulin resistance at 6 months.

The researchers found that CPAP participants experienced lower levels of the inflammatory molecules IL-1β and IL-6 and higher levels of the hormone adiponectin, an important glucose regulator.

Dr. Garcia-Rio said study findings suggest that "early identification of OSA in patients with type 2 diabetes, and assessment for metabolic abnormalities in those with OSA could reduce the cardiovascular disease risk of patients with these chronic diseases."

Researchers believe results are generalizable, given that patients included in the study were referred from diabetes units or primary care physicians, reflecting standard clinical practice. Study limitations include small sample size, lack of a placebo arm and medication changes that were necessary for some patients during the trial.

Deafness Has Link to Type 2 Diabetes

The author of this article is almost too timid in what she/he writes. I disagree and feel that diabetes does play a role in hearing loss at all ages. Many studies to determine hearing loss are poorly done and the authors excuse their poor design as older people have hearing loss and the effect diabetes plays as negligible. Do understand that as people age, hearing loss can become a problem, with or without diabetes. Poorly managed diabetes can accelerate hearing loss. Well managed diabetes can prevent much of the hearing loss.

A review of studies of possible linkages between type 2 diabetes and hearing impairment concludes there is compelling evidence that diabetes can damage the auditory system, and that clinicians should include hearing testing in managing type 2 diabetes.

Elizabeth Helzner, PhD, assistant professor in the Department of Epidemiology and Biostatistics in the School of Public Health at SUNY Downstate Medical Center, said, “An association between diabetes and hearing impairment in human subjects has been shown in many, but not all, studies. Direct comparison of these studies is complicated due to a lack of consistency in defining hearing impairment and other factors.” The last statement is a key.

“However, the association between diabetes and hearing impairment tends to be stronger in studies that included younger participants, perhaps because in older samples, other causes of age-related hearing impairment may mask the contribution of diabetes to the impairment. This factor in itself lends weight to the notion that type 2 diabetes can damage hearing.”

Dr. Helzner and her co-author note in the article that the epidemiologic study of the relationship between diabetes and hearing impairment is relatively new. They add that well-designed longitudinal studies are necessary in order to explore whether patients with diabetes are at increased risk of early-onset hearing impairment, and whether the progression of hearing impairment varies based on diabetes status, as well as disease management factors, after taking other known contributors to hearing sensitivity into account.

Hearing impairment is one of the most pervasive disabling conditions, affecting 16.1 % of adults in the United States. Two thirds of adults have clinically significant hearing impairment by age 70. Hearing impairment has been associated with social isolation and depression, cognitive decline and incident dementia, a higher propensity for falls and hospitalizations, and increased mortality.

I have two blogs on the different types of hearing loss here and here.

Physicians Passing on Treating Prediabetes

I am not sure the ADA actually said this. “According to the ADA, if A1C is between 5.7-6.4%, the patient is considered prediabetic and should be treated with lifestyle modifications and possibly metformin therapy.” But this is what the author of the article stated and I hope it is true, as a prediabetes diagnosis is a last call for patients to take action to possibly prevent a lifelong battle with diabetes.

As I explained in this blog, many doctors won't treat prediabetes in the hopes that they will soon have a patient with type 2 diabetes that they can treat. They use words like, “watch what you eat, as your blood sugar is elevated.” We know this is code for prediabetes and these doctors are licking their chops knowing they will soon have a captive patient to treat. I must state that not all doctors are this callus and do diagnosis prediabetes, but then fail to help the patient.

A new article published in Journal of the American Board of Family Medicine (JABFM) states that only 23% of prediabetes patients were diagnosed by their healthcare providers and started on appropriate therapy. Researchers looked at the data from the 2012 National Ambulatory Medical Care Survey, which included adults over 45 years of age with no diabetes and their A1C tested within the last 90 days. A1C results were categorized as normal, prediabetes, or diabetes and were broken down based on age, sex, race, payer type, body mass index, and prediabetes treatment.

A total of 518 visits were analyzed. The survey found that 54.6% of participants had a normal A1C, 33.6% had prediabetes, and 11.9% had diabetes. Only 23.0% of patients categorized as having prediabetes received treatment; the most common was counseling on lifestyle modifications. Rates of prediabetes were similar between men (36.5%) and women (40.0%). The most frequent primary diagnosis was hypertensive disease (16.3%). There were no noticeable differences in applied treatments based on HbA1c level range whether patients had an HbA1c level of 5.7% or 6.4%.

This proves the doctors don't have the best interests of their patients in mind and are afraid of diabetes and prediabetes. Why they won't prescribe metformin is unknown. This is a generic diabetes medication, very inexpensive, and many endocrinologists do prescribe it “off-label.” It is the safest diabetes drug available and while not FDA approved for prediabetes, it still needs to be prescribed.

Primary care physicians (PCPs) should play an active role in the lives of their patients who have prediabetes and diabetes. The increasing prevalence of diabetes is a major health problem and the American Diabetes Association recommends screening for prediabetes in all individuals over 44 years of age and children who are obese.

When patients do have elevated A1C, PCPs must intervene. By providing them counseling and medication therapy, and following up with them, PCPs can influence patients’ lives by delaying the onset of diabetes, or perhaps even preventing patients from transitioning to diabetes. Prevention is the most effective strategy to treat diabetes that we have so far, and can greatly improve the overall quality of life of an affected patient as well as help lower the total cost of healthcare for all of us.

In the last ten days, I have been in email correspondence with three individuals that actually asked for and received copies of their lab reports. All three had A1c's in the prediabetes range and asked what they should be doing. All stated that the doctor had made a statement like the one in the second paragraph above. I asked if they had insurance and explained that metformin would probably not be covered, but they should check this and testing supplies. If insurance would not cover any of this, they should investigate purchasing testing supplies from a pharmacy that was low cost and known for this. They needed to talk to their doctor about prescribing metformin ER (extended release) or even just metformin as it was a low cost generic.

Two of the individuals said their doctor would not prescribe metformin and I suggested they get a referral to an endocrinologist or lacking this, getting an appointment with one. Then they should talk to the endocrinologist about a prescription for metformin. They said they would and I have told all three that I would work with them on “eating to their meter” and learning what the meter readings were telling them.

This is one reason I promote obtaining your lab reports so that you will know what the results are and if there is need for concern and action on your part. I would suggest reading this article in Diabetes-in-Control.

SGLT2 Therapy Does Not Prevent Diabetic Bone Disease

And yet another problem with SGLT2 diabetes drugs. Doctors are being told to take bone density and history of osteoporosis into consideration when prescribing SGLT2 inhibitors. Both type 1 and 2 diabetes patients are at increased risk of bone fractures.

It is believed that the cause is the chronic hyperglycemia state that leads to a decrease in bone density, and this in turn puts diabetes patients at risk for osteopenia and osteoporosis. Osteopenia is a condition of bone in which decreased calcification, decreased density, or reduced mass occurs. Therefore, bone microarchitecture and strength could be potentially amplified by down-regulating patients’ blood glucose levels.

Using sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors), seems to lower blood glucose levels only by 0.7 to 1.0 percent which is helpful but not great in the overall blood glucose lowering needs. They work by blocking sodium-glucose cotransporter 2 in the proximal tubules of the kidneys and reducing the reabsorption of filtered glucose from the tubular lumen, which lowers glucose levels in the blood. The added benefit of this group of medications is a slight weight loss.

Paradoxically, previous studies indicated that treatment with the SGLT2 inhibitor canagliflozin could actually worsen the bone structure and increase the risk for bone fractures by 30%.

While recent studies have all be on rodents, the findings do suggest an association between the increased risk for bone fractures and using medications like canagliflozin, and caution in using them in a group of patient at high risk for bone fracture.

Because of the rodent studies, we definitely need more studies that involve human participants who would challenge these findings. The significance of the results may increase since, currently, SGLT2 inhibitors are approved by the FDA only for type 2 diabetes patients, but it may change as new studies are being conducted on type 1 patients.

Doctors are being advised that SGLT2 inhibitors can contribute to increased risk of bone fractures in diabetes patients. In diabetes patients with a history of multiple bone fractures or osteoporosis, it may be wise to stay away from SGLT2 inhibitors and try other groups of medications first. Physicians are encouraged to report any known incidents of sudden unexpected worsening of bone density in patients who recently got started on SGLT2 inhibitor therapy.

SGLT2 Being Investigated by EMA

After the last blog, I am not surprised that the European Medicines Agency (EMA) is continuing the investigation of SGLT2 diabetes drug. This time after an increase in amputations, mostly of the toe, was observed in a large ongoing clinical trial of the drug.

Cases of lower-limb amputation occurred in both the active drug and placebo groups in the Canagliflozin Cardiovascular Assessment Study (CANVAS), which is the cardiovascular-outcomes trial for this agent and is randomizing just over 4000 type 2 diabetes patients to canagliflozin 100 mg or 300 mg daily or to placebo, slated for completion in 2017.

“The EMA Pharmacovigilance Risk Assessment Committee (PRAC) has requested more information from the company to assess whether canagliflozin causes an increase in lower-limb amputations and whether any changes are needed in the way this medicine is used in the European Union.”

The EMA notes that patients with diabetes, and especially those with poorly controlled diabetes and preexisting vascular problems are at increased risk of infection and ulceration, which result in lower-limb amputations. In 12 other completed clinical trials, there was a statistically nonsignificant increase in the number of amputations.

Both CANVAS and CANVAS-R involve patients at high cardiovascular risk. The PRAC will also ask for data on other medicines in the SGLT2 inhibitor class, which include dapagliflozin (Farxiga, Forxiga, AstraZeneca) and empagliflozin (Jardiance, Lilly/Boehringer Ingelheim).

"Based on this, the PRAC may decide to extend the scope of the review to cover these medicines," the EMA notes.

Combination products containing SGLT2 inhibitors with metformin are also available in the European Union.

While the review on canagliflozin is ongoing, healthcare professionals will receive a letter reminding them about the importance of routine foot care among diabetic patients to avoid cuts or sores of the feet and to treat them promptly should they occur to prevent infection and ulceration.

Patients at increased risk of amputation (such as those who have had a previous amputation) should be carefully monitored. As a precautionary measure, doctors may consider stopping treatment with canagliflozin in patients who develop significant foot complications.

"Patients who have any questions should speak to their doctor or pharmacist. It is important that patients with diabetes continue to take their prescribed treatment and not stop treatment without first consulting a healthcare professional," the EMA notes.

The incidence of lower-limb amputation in CANVAS is currently seven in 1000 patient-years with canagliflozin 100 mg daily and five in 1000 patient-years with canagliflozin 300 mg daily, compared with three in 1000 patient-years with placebo, EMA indicates.

Patients in the study have so far been followed up for an average of 4.5 years.

In CANVAS-R, a study on the effects of canagliflozin on renal end points in adults with type 2 diabetes, the incidence of lower-limb amputation is seven in 1000 patient-years with canagliflozin and five in 1000 patient-years with placebo. This difference is not statistically significant. Patients in this study have so far been followed up for an average of 0.75 years.

The independent data monitoring committee for CANVAS and CANVAS-R has recommended that the trials should continue.

Diabetes Ketoacidosis with SGLT2 Inhibitors

The European Medicines Agency (EMA) is alerting doctors and other healthcare professionals to the possibility of atypical cases of diabetic ketoacidosis (DKA) associated with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, a relatively new class of oral medications used to treat type 2 diabetes and some type 1 diabetes patients. The announcement follows a review, conducted by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC), and aims to help minimize the risk of DKA associated with the use of this class of drugs.

The issue initially came to light in May 2015, when the US Food and Drug Administration issued a notice on the basis of 20 cases of DKA associated with SGLT2 inhibitors reported to the agency's adverse-event reporting system. A month later, the EMA initiated its review and identified 101 cases worldwide associated with type 2 diabetes.

Diabetic ketoacidosis is a serious complication of diabetes caused by low insulin levels. The issue is of considerable concern because ketoacidosis is not typically observed in patients with type 2 diabetes. "Rare cases of this condition, including life-threatening ones, have occurred in patients taking SGLT2 inhibitors for type 2 diabetes, and a number of these cases have been atypical, with patients not having blood sugar levels as high as expected," states EMA.

Patients with type 1 diabetes who have DKA typically have very high glucose levels.

An atypical presentation of DKA can delay diagnosis and treatment, so doctors and others treating diabetes patients should therefore consider the possibility of ketoacidosis in those taking SGLT2 inhibitors who have symptoms consistent with the condition, even if blood glucose levels are not high, the EMA adds.

And "patients taking any of these medicines should be aware of the symptoms of DKA, including rapid weight loss, nausea or vomiting, abdominal pain, excessive thirst, fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odor to urine or sweat."

If they have any of these symptoms, patients should contact a healthcare professional. If DKA is suspected or confirmed, treatment with the SGLT2 inhibitor should be stopped immediately, and should not be restarted unless another cause for the ketoacidosis is identified and resolved.

For their part, when considering SGLT2 therapy, EMA says, “medical perscribers should exercise caution in patients with risk factors for ketoacidosis and inform patients of the risk factors.”

These include low reserve of insulin-secreting cells, conditions that restrict food intake or can lead to severe dehydration, a sudden reduction in insulin, or an increased requirement for insulin due to illness, surgery, or alcohol abuse.

In addition, the PRAC recommends temporarily stopping SGLT2-inhibitor treatment in patients in the hospital for major surgical procedures or due to serious illness.

European Medicines Agency, Published February 12, 2016. This can be read here.

Second April 2016 Meeting

Several of us had been asking for a second meeting as we were feeling pressure from some of the newer members to stop promoting our way of eating. Tim had been hesitant to do this, but then he had some of the same pressure and sent out an email saying that we would have a second meeting to discuss our way of eating.

Everyone was present when the meeting started and Tim said that several of the members were not happy with our promotion of low carb high fat (LCHF) way of eating. He asked them to speak up about why they were against this. The first person that spoke up said he could not believe in high fat and had problems with eating fat. He said for years we have been told fat was a factor in heart disease and he still believed this. Tim asked him if it was just his objection or if he had actual problems in eating fat. He answered it just his objection.

Next Tim asked the second person, the answer was the same, and that she did not believe fat was good for us. Then Tim asked for a show of hand of those that agreed with this. Five more hands were raised. Tim then asked Allen what he would do. Allen said that if they felt that way, they should consider forming their own support group and leaving our group. Jason made a motion stating, “That those that opposed our way of eating should form their own support group and leave our group.”

Brenda seconded the motion and Tim asked for a show of hands. Except for the seven, it was unanimous in agreement. Tim asked them to leave our group and do what they wanted. Allen added whether they formed a support group was up to them, but they were not welcome in our group for the pressure they caused for promoting their cause. Brenda added that we have found what works for us and that high fat did work for us and studies have proven that fat was not the cause of heart disease. They were free to believe what they wanted, but we would not change our way of eating for a few members.

Tim added this is our desire and we are in agreement and would not change. With that, Tim asked them to leave. Slowly they left and one asked if they changed their mind could they ask to be reinstated. The answer was almost in unison – NO! Tim asked if there was anyone else that wanted to leave and two more left. Now we were back under 50 members and Barry asked if we should consider not adding any new members for a few months. Allen said he had one possible new member, and I said I have a possible new member later this year. I added that this has caused us some concern and that we did not like the pressure being applied to us by those that left and I don't think any of us wanted this to happen again. I continued that I agreed with stopping membership, but that we should think about this until the next meeting.

Jason added that generally we have all agreed on many things and don't get upset when someone disagrees with us, but this time the pressure they put on us to change our way of eating was not something we could agree to and we knew what worked for us.

Tim said he thought we were just complaining until they started to put pressure on him to have a meeting and demand that we change our way of eating. Tim then surprised us when he said Greg, the leader of the other group, said he would not put up with members of our group putting pressure on them to change their way of eating. Tim said they were told to leave their members alone and they did not want to follow their recommendations.

A.J said that they were obviously on a mission to promote their way of eating and were not afraid to talk to anyone. Then Tim said that even the group that Dr. Tom leads was approached and they were told to stay away from their members. Tim said he was asked to do something, as they would not be too happy if this continued. Tim said he would notify the other groups of our action and who the people were so that they would not be involved with them. Tim then thanked us for our vote and severing ourselves from them.

Tim then added that we have never needed to take action like this before and did not like being this way, but we did not need to obtain a reputation that was not liked by other groups. Tim received a short applause for this and he asked if there was anything else that needed to be discussed. Sue said we did something tonight that needed to be done and she did not feel we could have done anything differently.

Tim said he had nothing else and that the meeting was over. Several of the newer members were asking questions and were surprised that we had taken this action. Allen explained that we have found that low carb high fat worked for us and with the help of the two nutritionists were able to balance our vitamin and mineral needs and even with several of us unable to absorb some nutrients from our food for which they recommended supplements. One of them asked why they had problems with increasing their fat intake and Jason suggested that they increase their salt intake for a few days and see if this didn't help.

Another asked what they should do when they reached their ideal weight. A.J said that you will stop losing weight. Tim said that is what happened for him and Brenda said she had stopped just a couple of pounds under her ideal weight and that they should not be concerned about changing what they were eating as they approach ideal weight. This seemed to satisfy most of them and we left.