High uric acid directly inhibits insulin signaling and induces insulin resistance

Accumulating clinical evidence suggests that hyperuricemia is strongly associated with abnormal glucose metabolism and insulin resistance. However, how high uric acid (HUA) level causes insulin resistance remains unclear. We aimed to determine the direct role of HUA in insulin resistance in vitro and in vivo in mice.

An acute hyperuricemia mouse model was created by potassium oxonate treatment, and the impact of HUA level on insulin resistance was investigated by glucose tolerance test, insulin tolerance test and insulin signaling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt. HepG2 cells were exposed to HUA treatment and N-acetylcysteine (NAC), reactive oxygen species scavenger; IRS1 and Akt phosphorylation was detected by Western blot analysis after insulin treatment.

Hyperuricemic mice showed impaired glucose tolerance with insulin resistance. Hyperuricemia inhibited phospho-Akt (Ser473) response to insulin and increased phosphor-IRS1 (Ser307) in liver, muscle and fat tissues. HUA induced oxidative stress, and the antioxidant NAC blocked HUA-induced IRS1 activation and Akt inhibition in HepG2 cells.

This study supplies the first evidence of HUA directly inducing insulin resistance in vivo and in vitro. Increased uric acid level may inhibit IRS1 and Akt insulin signalling and induce insulin resistance. The reactive oxygen species pathway plays a key role in HUA-induced insulin resistance.

Wisdom Wednesday: Gycohemoglobin A1c

This blood test measures the percentage of RBCs (red blood cells) saturated with glucose. RBCs live about 120 days. During that span they can slowly be glycosylated by high levels of serum glucose. Assuming the average age of an RBC to be 60 days, this test reveals what your glucose levels have averaged over the course of the past two months. By comparison, the fasting glucose only measures the glucose level after eight or more hours for fasting, with no stress on glucose metabolism.

For the past several years the A1c has been used to monitor diabetics to see how effective they are managing their disease. However, in July of 2015, the A1c was established as the medical standard for diagnosing diabetes. This big step forward that has met with either resistance or indifference from the medical community as less than half of primary care physicians currently order this test for their patients.

The new standard recommends physicians begin to test patients who are obese between the ages of 40 and 45. I have been using this test on my patient population for several years. I do not restrict the test by age or weight status. Clinically, I have found that this test often begins to elevate in patients by their late 20’s, even when they are at ideal weight.

The normal range for the A1c is 4.8 to 5.6%. However, the diagnosis of diabetes is restricted to levels at or above 6.5%. A “well controlled diabetic” will have an A1c of 7% or less. Levels between 5.6 and 6.5% are considered “pre-diabetic”. Currently, over 50% of all Americans are estimated to be either diabetic or pre-diabetic and that percentage is still increasing.

In my office, anyone exhibiting symptoms of metabolic syndrome – central obesity, hypertension, high serum lipids, hypothyroidism, or insulin resistance – is a candidate for A1c testing, regardless of age. Additionally, using the QA (Quintessential Applications) protocol, if a patient tests for sesame seed oil to block prostaglandin inflammation (PG2) I also recommend an A1c. Clinically, over 90% of patients demonstrating a need for sesame seed oil have an elevated A1c. The remaining 10% typically have altered serum lipids or hypothyroidism.

Doctors May Be Missing Chances to Treat Prediabetes

More than one-third of U.S. adults have prediabetes, which means their blood sugar levels are higher than normal, but not high enough to be diagnosed with diabetes. People with prediabetes are at risk for circulatory problems, kidney disease, and nerve and retinal damage, the study authors said.

“We know that prediabetes is considered one of the biggest risk factors for the development of diabetes, with estimates ranging from 15-30% of people with prediabetes developing diabetes within five years,” said lead investigator Arch Mainous III. Mainous is chair of the department of health services research, management and policy in the College of Public Health and Health Professions at the University of Florida.

“We also know that 90% of people who have prediabetes don’t know they have it. So the question becomes, where is the doctor in all this? Is the doctor identifying people with prediabetes, telling them about it and providing treatment? That’s what we wanted to find out,” he said in a university news release.

Mainous and his colleagues analyzed 2012 federal government survey data on people aged 45 and older who had doctor-ordered blood tests within the past 90 days. About 34% of them had blood sugar levels that indicated prediabetes.

However, very few of those patients were told they had prediabetes and only 23% of them began treatment for the condition, such as lifestyle changes or drug therapy, according to the study. The findings were published March 8 in the Journal of the American Board of Family Medicine.

“Even with blood test results in front of them, physicians weren’t detecting prediabetes in their patients in terms of making a diagnosis or providing some sort of management or treatment,” Mainous said.

Can Certain ‘Poor Carb’ Diets Raise Nonsmokers’ Lung Cancer Risk?

Even people who’ve never smoked can get lung cancer, and a new study suggests their risk for the disease may rise if they eat a diet rich in certain carbohydrates.

These so-called “high glycemic index” diets – regimens that trigger higher levels of insulin in the blood – tend to be heavy in refined, “poor quality” carbs, one expert explained.

“The glycemic index and glycemic load are methods to estimate the quality and quantity of dietary carbohydrates,” said Dr. Rishi Jain, a medical oncologist at Fox Chase Cancer Center in Philadelphia. “Examples of foods with a high glycemic index include white bread and white potatoes.”

Jain explained that as rates of obesity and heart risk factors rise in the United States, so does the number of Americans with “insulin resistance,” a precursor to diabetes. And he said insulin-linked disorders, which are often tied to high-glycemic diets, “have been implicated as potential contributors to a variety of chronic conditions, including certain cancers.”

Could lung cancer be one of those malignancies? Dr. Xifeng Wu, chair of cancer prevention at the University of Texas MD Anderson Cancer Center in Houston, conducted the new study to help answer that question.

Overall, people who registered in the top fifth in terms of a high-glycemic diet had a 49% greater risk of developing lung cancer versus those in the bottom fifth, Wu’s team reported.

But the trend was even stronger when the study focused on people who had never smoked. In that group, those who scored highest in terms of a high-glycemic diet had more than double the odds of lung cancer compared to never-smokers who had the lowest glycemic index scores.

Wu and her colleagues reported their finding March 4 in the journal Cancer Epidemiology, Biomarkers & Prevention.

Nearly 3 in 10 Americans with Diabetes Don’t Know It

Almost 8 million Americans have diabetes but don’t know it, a new study shows.

That’s despite the fact that about two-thirds of those with undiagnosed diabetes have seen a doctor two or more times in the past year, according to the researchers.

The study also found that among those who were diagnosed with diabetes, only about one –quarter met three important goals for people with diabetes: managing blood sugar, blood pressure and cholesterol levels.


“Out of 28.4 million people with diabetes, more than a quarter don’t know [it],” said study author Dr. Mohammed Ali, an assistant professor of public health at Emory University School of Medicine in Atlanta.

“About 80% of those people are linked to a health care provider, and two-thirds are seeing them twice a year or more. So, through whatever means, they aren’t being identified with diabetes,” Ali explained.

Symptoms of type 2 diabetes, which may be subtle and come on slowly, include fatigue, blurred vision, slow-healing cuts and scrapes, and the need to urinate more often, according to Dr. Robert Ratner, chief scientific and medical officer for the ADA.

Despite greater awareness in recent years, diabetes remains a major cause of death and disability in the United States. It’s a leading cause of adult-onset blindness, kidney failure and limb amputations, according to the researchers.

MY TAKE:
This is a prime example of a failing heath care system – over 5 million undiagnosed diabetics are seen by a physician a least twice a year, but not properly diagnosed.

As a clinician, you are responsible for the total health of your patient, regardless of their chief complaint on entry. If a patient seeks my help for acute low back pain and they also happen to be an undiagnosed diabetic, I am responsible to diagnose, properly treat, and/or refer that patient for their diabetes.

Diabetes is an easy diagnosis. Occult cancers like breast, lung, and prostate are much more challenging. This is why a good history is so important. I recently had a new patient who was being treated for anemia with iron supplementation by her MD. She had a microcytic anemia, so iron probably would be effective. However, her history included breast cancer. As a clinician, you must assume this patient has metastatic carcinoma until you prove otherwise. You can not just treat the anemia and ignore the potentially fatal diagnosis. My new patient was referred to her oncologist for further evaluation and treatment.

Every patient in my office is evaluated for signs of metabolic syndrome, the precursor to diabetes and heart disease. The signs are central obesity (weight gain around the belly), high blood pressure, high serum lipids, low thyroid function, and insulin resistance. I see these signs all day long. Look around you or maybe look at yourself and you will see them too.

THE BOTTOM LINE:
The fasting glucose only shows how well your body handles sugar without the stress of food for the past 8 hours. You are diabetic long before the fasting glucose is elevated on your lab test.

I recommend all my patients have laboratory testing each year as a preventative tool. Included in that panel of tests is a glycohemoglobin A1c. This test measures the percent of RBCs (red blood cells) that are saturated with glucose. That number should be below 5.7%. Please ask your physician to run an A1c. Don’t wait for your MD to diagnose you as a diabetic.

Source: National Institutes of Health -Tuesday, November 18, 2014

Wisdom Wednesday: Inflammation – Part 4

Insulin, the hormone produced by the pancreas to escort glucose into the cells of the body, can stimulate inflammation. It is the most insidious inflammatory pathway and very difficult to reverse.

Most cells in the body require adequate insulin in the blood stream to facilitate glucose absorption. However, a majority of Americans are now insulin resistant. They eat too much and too much of the wrong foods – refined carbohydrates. As the pancreas increases the output of insulin to control glucose levels, the body slowly becomes insulin resistant. This occurs long before the eventual diagnosis of Type II diabetes. It is estimated that by the year 2050, over half of all Americans will be diabetic.

Today, many of these young Americans are already insulin resistant and pre-diabetic. The systemic inflammation caused by excess insulin production is evidenced by our inability to process omega 6 fatty acids, like olive oil.

Most nutritionists recommend against supplementing omega 6 fatty acids. They claim that the omegas 6’s are abundant in our diet and that they can be pro-inflammatory. Although both of those claims are true, I disagree with their recommendations. First, the omega 6 fatty acids in our diet need to be converted to GLA (gamma linolenic acid) and many people can not make that conversion. Secondly, it’s only the people who are insulin resistant that take healthy omega 6 fatty acids and convert them to inflammatory compounds. I recommend fixing the chemistry rather than denying the body an essential fatty acid. Essential means just that, your body can not make it, it is essential to the diet.

The key, of course, is cleaning up the diet, reversing all the factors associated with metabolic syndrome – central obesity, high blood pressure, low thyroid function, high serum lipids, and insulin resistance. In the meantime, the addition of sesame seed oil, and possibly GLA, to the diet will support healthy utilization of omega 6 fatty acids and effectively block the conversion to inflammatory compounds.

I have seen uncontrolled type II diabetics, on multiple medications, cut their medication by 75% with the simple addition of sesame seed oil and GLA, while reducing their blood sugar levels from over 250mg/dL to 85mg/dL in less than 3 weeks. Simultaneously, their inflammatory complaints – IBS, musculoskeletal pain, headaches, etc. also improve markedly.

In my office, as soon as I see impaired chemistry on the omega 6 fatty acids, I suspect insulin resistance as the cause. Fortunately, the glycohemoglobin A1c is a simple blood test that tells us what your blood sugar has been averaging for the past 60 days. I mention this test often in my blogs and I advise you to have this test run annually.

THE BOTTOM LINE:
Diabetes is epidemic in our county and is not only preventable, but often time’s reversible. The vast majority of pre-diabetics are undiagnosed. The odds are at least half of you reading this blog are pre-diabetic. Get an A1c performed. If you have any of the characteristics of metabolic syndrome and you suffer from inflammation, chances are your pain is being driven by insulin.

Glucosamine Fails to Prevent Deterioration of Knee Cartilage or Decrease Pain

A short-term study found that oral glucosamine supplementation is not associated with a lessening of knee cartilage deterioration among individuals with chronic knee pain.
Tuesday, March 11, 2014

Findings published in Arthritis & Rheumatology, a journal of the American College of Rheumatology (ACR) journal, indicate that glucosamine does not decrease pain or improve knee bone marrow lesions – more commonly known as bone bruises and thought to be a source of pain in those with osteoarthritis (QA).

According to the ACR, 27 million Americans over 25 years of age are diagnosed with OA – the most common form of arthritis and the primary cause of disability in the elderly. Patients may seek alternative therapies to treat joint pain and arthritis, with prior research showing glucosamine as the second most commonly used natural product. In fact, a 2007 Gallup poll reports that 10% of individuals in the US over the age of 18 use glucosamine, with more than $2 billion in global sales of the supplement.

For this double-blind, placebo-controlled trial, Dr. C. Kent Kwoh from the University of Arizona in Tucson, enrolled 201 participants with mild to moderate pain in one or both knees. Participants were randomized and treat daily with 1500mg of glucosamine hydrochloride in a 16-ounce bottle of diet lemonade or placebo for 24 weeks. Magnetic resonance imaging (MRI) was used to assess cartilage damage.

Trial results show no decrease in cartilage damage in participants in the glucosamine group compared to the placebo group. Researchers report no change in bone marrow lesions in 70% of knees, 18% of knees worsened and 10% improved. The control group had greater improvement in bone marrow lesions compared to treated participants, with neither group displaying a worsening of the bone marrow lesions. Dr. Kwoh concludes, “Our study found no evidence that drinking a glucosamine supplement reduced knee cartilage damage, relieved pain, or improved function in individuals with chronic knee pain.”

MY TAKE:
Glucosamine Sulfate was the first supplement I recommended to patients 38 years ago. Clinically, 80% of my patients with chronic low back pain experienced reduction in symptoms within 30 days. I quickly realized that about half of the patients that did not respond favorably were diabetic.

Today, we have uncovered the chemistry behind glucosamine sulfate. Basically, it requires good glucose metabolism and good sulfur metabolism to function. That explains why my diabetic patients failed to respond. Sulfur metabolism depends on the ability of the body to strip sulfur from sulfur bearing amino acids.

Please read my recent Wisdom Wednesday: Vitamin B6 blog post for information on this process.

The first flaw in this study is the use of glucosamine hydrochloride, not glucosamine sulfate. Without adequate sulfur, the chemistry just doesn’t work. They also failed to identify participants that may have impaired glucose metabolism. As I have frequently written, insulin resistance is epidemic in this country. Finally, glucosamine sulfate, MSM, and chondrotin sulfate all help form ground substance which is necessary to repair connective tissue. None of these chemical are inherently anti-inflammatory in nature. If you do not reduce inflammation first, healing can not occur.

I still use glucosamine sulfate in my practice today. However, I first address inflammation, sulfur amino acid metabolism, and glucose metabolism prior to supplementation. Most of the time, correcting these three chemical pathways solves the problem and direct supplementation of sulfur and glucose in not necessary or desired.

THE BOTTOM LINE:
If you want to take one of these supplements, at least take one that contains both glucose and sulfur. Better yet, have your glucose and sulfur metabolism evaluated. A simple blood test, the glycohemoglobin A1c will assess your metabolism of sugar for the past two months. If eating cruciferous vegetables, like broccoli, cauliflower, or cabbage, gives you gas, then your sulfur amino acid metabolism is suspect.