People Often Clinically Excluded From Type 2 Drug Trials

People are under intense scrutiny for selection for type 2 diabetes drug trials. This is often done to help obtain the results desired and Big Pharma does this to obtain positive results for drug approval from the FDA.

Young women of childbearing age are usually excluded. Exclusion criteria for clinical trials of type 2 medications that affect women of childbearing potential are frequently disproportionate to risk to the participant and fetus. This data is shown from a study published in Diabetes Care.

Clinical trials often exclude women of childbearing potential due to concerns about adverse fetal effects of treatment. Because of the high prevalence of diabetes among pregnant women, researchers examined the prevalence of fertility-related exclusion criteria in clinical trials for type 2 diabetes medications. They sought to determine whether these criteria are an accurate representation of type 2 diabetes drug risk.

This is why many of the women who develop diabetes while pregnant are put on insulin rather that any oral medications.

The next group is young people under the age of 18 to 20 years of age. This is mainly because of the legal process of obtaining permission for testing. The other problem is parents that pull the young from trials for capricious reasons. Most researchers avoid this by excluding them from trials.

The elderly are also excluded from trials because of other comorbid conditions that researchers do not want to deal with. Most of the time, the age excluded is 65 and older. However, people under the age of 65 are also excluded if they have other comorbid conditions or diseases.

Read my blog here about elderly discrimination and why it harms the elderly. Occasionally, a study will use limited comorbid conditions for the elderly up to the age of 74. These trials are very limited and the comorbid conditions are also limited.

This makes many clinical trials very discriminatory and possibly harmful to the classes of people mentioned above. Yet, when people in these classes are diagnosed with type 2 diabetes, the doctors prescribe the medications to people not in the clinical trials. They do this normally on the advice of drug reps of the companies making the drugs. The doctors are often unaware that these classes have been excluded from the drug trials and may be causing harm to the very patients they want to help.

Are You On the Diabetes Couch?

If you are, and are medically able, get off the couch and exercise to the limit that is available to you. I know several people with type 2 diabetes living in a nursing home and are unable to walk, yet most of them exercise every day. Granted it is upper body exercise and light weight lifting, plus most are able use their wheel chairs to move themselves around at meal times and at other times.

Granted, a sedentary lifestyle may lead to type 2 diabetes and metabolic syndrome. The researchers have correctly identified many of the factors that lead to type 2 diabetes, which has meant in the USA, at least, to slow the new cases of diabetes. There is still a lot of work to do, but at least we know that genetics, lifestyle, and environment have been linked with type 2 diabetes.

The further identification of modifiable risk factors continues to be a tool for prevention and some studies have shown that an over sedentary life can increase metabolic syndrome, weight gain, and insulin resistance.

This recent cross-sectional study investigated associations between total amount and patterns of sedentary behavior, metabolic syndrome and glucose metabolism. Participants were analyzed from the Maastricht Study, a prospective population-based cohort study of the pathophysiology, etiology and comorbidities of type 2 diabetes. Inclusion criteria mandated that all participants were between the ages of 40-75 and living in the southern Netherlands. They were recruited by means of mass media from municipal registries and diabetes registries.

This study took measures to adjust for confounding variables between study groups, but only followed patients for 1 week and could not adjust for the possibility that type 2 diabetes patients may be more sedentary due to poor health. Furthermore, by virtue of the study design, a causal relationship cannot be inferred. Though a longitudinal randomized clinical trial should be conducted to determine causation, this does not discount the findings of the current study, which has made a strong association between sedentary behavior and an increased chance of developing type 2 diabetes.

This to me is not a valid study and does mean that more studies need to be done. Yes, this is one thing many of us with type 2 diabetes know that people need to avoid. Being sedentary is something that everyone that is like this hears repeatedly “get up and move.” This is said so often that people that have problems moving and are by necessity sedentary get tired of hearing.

What Can We Do?

In the last blog, we found ourselves dealing with two individuals not wanting to share information about their diabetes. A couple of days later Brenda asked us to meet again. She said the woman was in the hospital and she was not sure what had happened. The hospital had called her and she would be the one picking up the woman's two children as she would be still be in the hospital. The hospital had called the school and a teacher would bring out the children after the buses had pulled away. She would know the car to look for and had the license number.

We said that was good and she and Sue would need to attempt to find out the cause for the hospital admission. Was it for hypoglycemia, possibly for hyperglycemia, or another cause? Brenda said that is the plan. Brenda needed to leave then and Sue said she would meet her at the hospital and report back later.

Jason said that he and Ben had another meeting with the other fellow, but did not have any more information. He refuses to discuss anything about diabetes. I suggested bringing another member and pushing him a little. Ben was hesitant, but said it may drive him away completely. Jason agreed, but felt that it would be better to drive him completely away than not talk to us. We need to convince him that talking would be a benefit to him and management of his diabetes. I suggested taking Allen with them and Jason said good.

Two days later, Brenda had us together again and said that a lot of progress was made with the woman. Sue had talked with her doctor and he agreed with her need to educated the eldest daughter and said he would lead the discussion. Yes, it was an episode of hypoglycemia that had put her in the hospital and the doctor really emphasized to the patient for not educating the oldest child and teaching her what to do when an episode of hypoglycemia happens.

This time she was fortunate that the oldest daughter called 911 and the ambulance crew thought to check her blood glucose. The woman said she did not want her children to know about her diabetes. The doctor asked if she wanted to die and the children blaming themselves for not knowing what to do. Brenda said the woman still refused to tell her children. The doctor then asked her if her youngest daughter developed cancer, should that be withheld from her. With that, the woman blew and said that was very different. The doctor said it was still family and being an adult or a child was a small difference.

The woman asked Brenda what she would do. Brenda said she would tell her children which is what she had done as soon as she went on insulin and never thought twice about this. Brenda said she felt better, when the family knew and what to do in cases she could not act. She then told the woman that she had obeyed her wishes when they asked what was wrong with their mother. This shows they are concerned and want to know. If the doctor had not called her and instead called a neighbor, what would they have said if they had heard the ambulance people talking about her blood glucose levels.

The woman said she would have to think about this as she had not even told her parents. She said her husband knew, but outside of her doctor and the hospital doctor, she was not aware of anyone else but the two of them. Her doctor said that she should consider talking to her children as they would ask more questions of her and then more probing questions of their dad and her repeatedly. They know something is wrong and they will want to know more now that you have been in the hospital.

No Need to Be Ashamed of Your Diabetes

Yes, there is not a need to be ashamed of your diabetes. However, many people are and some go out of their way to avoid even being known as having diabetes whether it is type 1 or type 2.

We are having a discussion among several of our members as Ben and Jason have both encountered people hiding their diabetes in the last two weeks. We needed to bring Sue and Brenda into the discussion as one of the two was a woman, and she refused to talk with Jason.

Ben said that before he met the group, he was somewhat ashamed, but could only hide it from a few of us, as several others knew he had type 2 diabetes. He said he was not ashamed of his having diabetes, but did not like talking about it with others. He stated that he was always cautious around people he did not know because of the stigma that some attached to diabetes.

We told him that we did not understand as he was not overweight and seemed healthy otherwise. He said that was true, but if we remembered back, it was Allen and a few others that had taken him to the hospital when he was in severe depression. We said we remembered, and Ben said we had never made a thing about that or his diabetes. We had just helped him and made him feel welcome in the support group. Jason said we did the same for your sister, Sue when her husband outed her.

Ben said these are things that we need to remember when dealing with the two people Jason and I have met. They are near ideal weight, both have type 2 diabetes and both are on insulin. That is why we wanted Brenda and Sue since Brenda uses insulin. We asked if this was a couple and Jason said no, they had been met separately.

Brenda then said she and Sue had met with the woman and after they had gotten past the contention and the secrecy, the discussion had been fairly productive. Her concern, once she found out that there is a large diabetes support group, was how to avoid the members. She would not consider even coming to a meeting Sue said.

Allen asked if she would be accepting help from them. Brenda stated she was not sure as she would not answer many questions from them and while she admitted having type 2 diabetes, that was about all she would say other than she did not trust her doctor and would not take statins. Brenda stated that she was taking an antidepressant and another medication for blood pressure. Sue said they had a phone number and email address, but were discouraged from using them, as she did not want her children to know she had diabetes.

I suggested that she be encouraged to tell her oldest child depending on their ages. Sue said the oldest as they understood was 13 and the next was 11. Both were actively involved is school activities. Brenda said I can understand why, especially if she were to have an episode of hypoglycemia. Brenda admitted that that may not be possible, but would try to work to have this done.

Jason said that the person he and Ben had talked to kept cutting them off and did not want to talk about diabetes at all. Ben continued that all they knew was that he had type 2 diabetes and was taking insulin. He would not talk about family or give us any more information. We agreed that patience would be required. We told the four to continue and we would support them as needed.

Diabetes Education Must Include Hypoglycemia

This was not anything that was included in any meetings with a certified diabetes educator. If it were not for Gretchen Becker and her book The First Year - Type 2 Diabetes, New York, Marlow & Company, 312 pages, by Gretchen Becker, and the information in this book - Diabetes Type 2 Complete Food Guide Management Program, New York, Three Rivers Press, 350 pages, by Sherri Shafer, I might not have known what to do to treat hypoglycemia and how to prevent it.

In addition, these two resources helped with hyperglycemia.

Elizabeth R. Seaquist, MD talks about hypoglycemia and gets serious about it. In this case, I can say that she is doing those of us using insulin a good service. She says this is an enormous problem for our patients, because it really limits how well they can control their blood sugars. Every patient with diabetes knows that he/she needs to keep their blood sugars at a near-normal level to reduce their risk for microvascular complications, but this frequently comes at the cost of hypoglycemia, which is really the factor that limits how well they control their blood sugars.

People can have episodes of hypoglycemia that cause them to lose consciousness, have seizures, and die from hypoglycemia. Elderly people with type 2 diabetes who have an episode of severe hypoglycemia that requires the assistance of another person have an increased risk for mortality in the subsequent year.

Even though all of us should know this, Dr. Seaquist repeats this. When you see any patient who is on insulin or a sulfonylurea, you need to wonder about their risk for hypoglycemia. You need to ask them about their hypoglycemia: when it happens, if it is happening. Don't assume that those patients with a high A1c, who you know frequently have high sugars, are free of hypoglycemia. People with very high A1c's have the same risk for hypoglycemia as people with low A1c's. We need to be aware of it at all times.

What do we do when we talk with our patients about hypoglycemia? First, I usually look at their glucose logs, meters, or CGM (continuous glucose monitor) to see if they are having hypoglycemia. Hurrah for her! However, I also ask them about undocumented episodes of hypoglycemia, because they don't always check.

I then ask them how low their blood sugar has to get before they have symptoms of hypoglycemia. That's a very important question, because if people have to get down to 50 or 40 before they have any symptoms, and that tells me that they have experienced frequent episodes of hypoglycemia. This tells me, we need to make a change. People who experience recurrent hypoglycemia in a short period of time develop "hypoglycemia unawareness." There is a real problem that you need to address.

We need to help our patients understand how to pick a rational dose of insulin for every mealtime, every time they're eating, and how to best adjust their insulin for exercise. If we can do that and use the tools that are available to us, we can help avoid hypoglycemia. As doctors, we need to sit down and talk with our patients, and think about what tools we can give them to help manage this problem of hypoglycemia.

If we can avoid hypoglycemia, we can prevent patients from developing hypoglycemia unawareness, which really puts them at risk for mortality, accidents, and disruptions to their everyday life. If we can avoid hypoglycemia, we can help patients achieve better glucose control because they won't be so fearful, which will help them control their diabetes overall.

Her approach to hypoglycemia is more rational and thought out than any doctor that I have dealt with and she carefully says what doctors need to do, questions to ask, and how to deal with patients positively. You may want to read the full article here.

Is This That Important?

This is not about diabetes at the start, but some of the nonsense on the Internet and why doctors think this is good.

The message is for the tweet of the week. They selected one that shows an image of a medical alert bracelet with the medical alert symbol on one side and the second image is the message on the reverse, which reads “DELETE MY BROWSER HISTORY.”

The title is - “Tweet of the Week: Medical Bracelet for Millennials.” Then they say in the subtitle - “No internet user will want to be without it.”

Why do I think this is nonsense? What do Millennials do on the Internet that this needs to be promoted? Drugs? Porn? Looking for Dr. Google advice? Yes, I can understand the doctors wanting the last information deleted from the browser as they all think that the internet does not contain trust worthy information.

I have had a couple of doctors tell me to not read about diabetes on the Internet. I surprise them when I say that I generally avoid the ADA site and the AACE site because most of the information is unreliable and for doctors that have little common sense.

This gets their attention and makes them ask why I would say this. I tell them that if they want the complications of diabetes, follow the ADA site and you will develop the complications. You will be less likely to rapidly develop the diabetes complications if you follow the AACE site, but even there, you may find bad information.

One doctor challenged me and I needed to show him the bad information on the ADA site. I asked him what the fasting range was and he said 100 to 130 mg/dl. I said that was right according to the ADA, but was too high. He asked what I follow and I said 80 to 110 mg/dl. He said was would be more in danger of having lows (hypoglycemia) and I said that may be, but hypoglycemia starts at 70 mg/dl and I seldom go that low.

I then asked what the number was at bedtime and he said 180 mg/dl. I said this is why the complications will start as this level encourages the complications. I said that it should not be more than 140 mg/dl postprandial and preferably not more that 120 mg/dl.

Then he asked what I ate, I told him low carb high fat, and he shook his head. He asked next how many carbs and I said about 30 to 50 grams of carbohydrates per day. He countered that I should be eating a minimum of 180 grams of carbohydrates per day.

I asked if he had heard of Dr, Bernstein and his “law of small numbers” and what that meant. He admitted that he had not and I explained that this meant that he was eating 30 grams of carbohydrates per day (9-12-12) and needed very small amounts of insulin even as a person with type 1 diabetes.

At that, he ended the discussion and said he would be testing me in three months to find out if I was eating enough to stay healthy. I said I work with a nutritionist to balance my diet and cover certain nutrients with a dietary supplement when I have malabsorption as I do for vitamin B12.

Type 2 Patients Receiving Delayed Treatment

While this is a British study, it applies to the USA as well. Type 2 diabetes patients are mistreated when it comes to receiving the medication increase when needed. This applies to increased dosage, adding another medication, or changing to insulin.

Yes, people with Type 2 diabetes are being “let down” because they are being forced to wait for further treatment when needed. Research has shown the average waiting time for increased treatment from the start of insulin is 3.7 years.

Previous evidence has shown that maintaining tight management of blood glucose levels in people with type 2 diabetes can lead to significant reductions in related complications.

“Clinical inertia.” is the term applied to the delay of increasing medication needed by patients and is preventing this from happening, according to a study published in the Diabetes, Obesity and Metabolism journal. The research was carried out by NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East Midlands, an organization that turns research into cost-saving and high-quality care through cutting-edge innovation.

Professor Kamlesh Khunti, Director of CLAHRC East Midlands and Professor of Primary Care Diabetes & Vascular Medicine at the University of Leicester based at the Leicester Diabetes Centre, said: "Of the 11,000 patients we studied, only a third of those needing further medication were actually given it.

"Clinical inertia” is a global phenomenon, which is putting people with Type 2 diabetes at further risk of preventable complications associated with the diabetes.

"Failure by healthcare professionals to intensify medication in the pursuit of tighter glycemic control is due to a number of complex reasons related to patient and health care professional factors. However, we need to make great efforts to reverse these trends and improve patients reaching tight glucose targets from diagnosis of diabetes."

The study concluded that more should be done to avoid clinical inertia and patients should have their treatment intensified where appropriate. Long-term complications and mortality associated with Type 2 diabetes can be significantly reduced if therapies are initiated earlier.

Salt Continues to Be Controversial

The shame of this is the lack of science being applied to salt needs of the body. Each side proclaims their agenda, but cannot show any definitive science to prove their claims. This article is one of the better articles and applies reason in place of lack of science.

If you have tried to find science to help you figure the best salt intake, you have probably read some of the controversy. "The less the better,” has been the message for the last 30-40 years. That dogma is not being challenged. This is also the reason that the low carb diet may be affecting the amount of salt we need. To understand some of this, we need to examine the controversy.

In July 2015, before the 2015 Dietary Guidelines were released, the Guidelines for Americans say that the “general population” should restrict their sodium intake to 2300 mg (about a teaspoon of salt). However, about half the population is not apparently in the "general population", as people over 50, African-Americans, and others in groups at a risk for high blood pressure are told to restrict their intake to 1500 mg. The American Heart Association maintains that everyone should stay at 1500 mg.

However, no one does this, as this is very difficult to do! We could have a long conversation as to whether it is a good idea to recommend something that only a small number of people worldwide can attain.

But instead, let's turn to the science). The reason for recommending salt intake is that there is an association between eating a lot of salt and high blood pressure. However, there are a couple of caveats:

1) While going from a high-salt intake to a moderate-salt intake does tend to lower blood pressure, for most people going from a moderate intake to a low intake does very little good.

After looking into the matter, in 2013 the Institute of Medicine reported that there is no evidence that reducing sodium intake below 2300 mg provides benefit. Other recent analyses have shown little correlation in the general population between blood pressure and salt intake, although there are definitely people who do benefit, which brings us to:

2) The people who benefit the most from salt reduction are what is called "salt sensitive", which is thought to be about 10-20% of the general population.

Older people, African-Americans, and people who have high blood pressure are more likely to be salt sensitive.

If you are salt sensitive, it is probably good to know it, although the only real way to find out is to wait until you have high blood pressure and then see if reducing salt helps. But, there is actually evidence that people who are salt sensitive are at a greater risk for heart disease even if their blood pressure is kept normal. One thought is that whatever is causing the salt sensitivity may be causing inflammation and possibly other bad effects. There is much to learn about this.

What is considered a moderate salt intake? There is a lot of controversy on this point! Some experts say that the average amount of sodium people tend to eat (around 3500 mg, or 3.5 grams) is way too much, while others say that this is the very definition of moderate.

If you cook from scratch and mostly eat at home, you are probably eating a moderate or lowish amount of salt by any definition. But if you eat out a lot and/or eat prepared and packaged foods, the grams can add up fast! According to the Centers for Disease Control and Prevention, the average person in the United States gets about 3/4 of their sodium from restaurants, prepackaged, and processed foods, while only 5% is added during home cooking and 6% from the salt shaker at the table.

Okay, now we need to ask about what are the dangers from too little salt. There is little research about this, but some observational studies have shown increased "cardiovascular mortality" or "all-cause mortality" for people eating a low-salt diet. However, complicated interactions can always be in the mix, for example, sick people may eat less food, which means they eat less salt.

Why is it dangerous to eat too little salt? Blood and many other bodily fluids (lymph, sweat, and fluid around our organs) are fairly salty, for good reasons. Our bodies use salt in many ways, and it is easy to imagine that things could go awry if we don't have enough of it. One of the more interesting observations is that a low-salt diet could increase insulin resistance in the muscles of some people. The researchers of the diabetes study point out that interference in metabolic and neurohormonal pathways that could result from a low-salt diet, at least in some people, but admit that we know very little at this point.

Could eating a low-carb diet impact our need for salt? Some experts think so in some people. Particularly in the first two weeks of a very low-carb (ketogenic) diet, the body lets go of a lot of water, and some electrolytes such as sodium and potassium along with it. Some physicians who are familiar with working with low-carb diets in their patients actually advise their patients to consume more salt during this time to help mitigate the "Atkins flu," i.e., feeling sickly in the first week or so. They often advise drinking a couple of cups of bullion or broth each day during this time.

Other experts, notably Stephen Phinney and Jeff Volek, feel that people on long-term ketogenic diets may need more salt on an ongoing basis, particularly if they are athletes or very active. They point to evidence that people on ketogenic diets tend to excrete more sodium. In The Art and Science of Low Carbohydrate Living, they advise that such people add 2-3 grams of sodium to the diet each day, particularly if they are feeling lightheaded or poorly with exercise.

As those of us who benefit from low-carb diets know very well, recommendations from the government or large health organizations are not always the best for the individual! It's up to you to find out what works for you. Make sure your blood pressure gets checked. Stay away from processed foods. If your blood pressure is high, make sure you're following a healthy low-carb diet, which has been shown to help normalize blood pressure for many people. If that doesn't do the job, try cutting back on salt.