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Part II

Update on Type II Diabetes in America

[Epidemiology and New Research Findings]

Introduction

In Part II a short review of new research on diabetes is provided. In the last decade thousands of studies on diabetes have been carried out in a variety of settings including hospitals, medical schools, pharmaceutical research laboratories, and universities involving both private and or public funding. As a person with Type II Diabetes the last 22 years I’ve chosen to review just a few exciting research projects involving Type II Diabetes.

One of the long-standing areas of research over the last several decades has been obesity among Type II Diabetics. Obesity appears to be growing exponentially on a global scale and has correspondingly contributed to the increase in diabetes worldwide. While treatment plans for diabetes normally involve diet, exercise, hypoglycemic medicine and various forms of insulin, there is also a lot of pending weight loss drugs in the wings from the pharmaceutical industry. In recent decades close daily monitoring of blood sugar has also helped diabetics immensely along with the usual standard treatment plans. The future for overweight diabetics is getting better all the time as new strategies are developed. However, many diabetics are not overweight and this has led to other areas of research. Nevertheless, research on why obesity is related to diabetes so intimately is still the focus of major research efforts to find a cure for diabetes.

What everyone has realized for some time is that there is a very close relationship between Type II diabetes, obesity and insulin resistance. This latter relationship between insulin resistance and obesity has been found to be connected in recent years through a new factor that has emerged in the medical research on Type II Diabetes. That factor is Inflammation. But first here is a review of what is known about insulin resistance. 

Insulin Resistance   

 All humans need energy to live. Consequently, every cell in the body needs energy, including cells in our large muscle groups. How do our cells get this energy? Normally, the foods we eat provide that energy. The food is then converted to blood glucose (blood sugar) and leads to circulation in our blood stream. The pancreas produces a hormone called insulin, and sends it into your bloodstream to travel to the various cells of the body. Insulin then attaches to a receptor on the cell’s surface and causes the cell membrane to permit blood glucose to enter. That is the normal process.

However, in Type II diabetes this system doesn’t work very well. The insulin gets to each cell; however, when it arrives, it has trouble unlocking the door to each cell and then the cell fails to permit the glucose to enter. Since glucose cannot get into the cells, it then builds up in the bloodstream. This condition is called Insulin Resistance.

The mystery of Type II diabetes has always been to find out why insulin resistance occurs. We now have a pretty good idea of the cause. So, what is the cause of Type II diabetes? Insulin’s ability to work is blocked in the human cell (like gum jamming up a lock as the metaphor suggests) by actual FAT. The cell’s receptors are blocked or jammed by fat.

Normally small amounts of fat are stored for energy in an emergency in each cell. However, in a diet (like the Western diet high in fat and cholesterol) excessive fat builds up in each cell creating the jamming process that prevents glucose from entering. If fat, called intramyocellular lipid, accumulates inside the cell it interferes with insulin’s intracellular signaling process.

Tiny organelles, called mitochondria, are supposed to burn fat. But their failure to keep up with the accumulating fat may be the origin of Type II diabetes. It turns out fatty foods actually do more than add excessive fat to each cell—they also interfere by turning off the genes that would help them create mitochondria and thus burn fat. The genes become disabled and do not allow the cells to produce the needed mitochondria. Your ability to eliminate fat inside your cells seems to slow down when you eat fatty foods.

Continue this faulty intracellular activity long enough, and guess what—you end up being diagnosed with Type II diabetes. This scenario of explanation is a good one, but new research is suggesting that other variables are involved in connecting obesity to insulin resistance. All of this leads (in this diabetic’s humble opinion) to answering the question why does the excess fat in a cell lead to the disabling of genes? What is the etiology of disabled genes in diabetics.

New Research Findings Emerge

 In November 2007 Science Daily reported that researchers at the University of California, San Diego (UCSD) School of Medicine have discovered that Inflammation provoked by immune cells called macrophages leads to insulin resistance and Type II diabetes. Their discovery may pave the way to novel drug development to fight the epidemic of Type II diabetes associated with obesity, the most prevalent metabolic disease worldwide. But, as you will shortly see, inflammation is intimately related or involved in a number of medical conditions and diseases.

 A Quick Definition of Inflammation and Its Relationship to Disease

 A quick definition of inflammation is needed. Inflammation is the first response by the immune system to infection or irritation. It often involves redness, heat, pain, swelling, and dysfunction of the organ involved. Chronic inflammation is an ongoing, low level of inflammation, invisible to the human eye and is associated with many diseases (this was an eye opener to me) including: Heart Disease, Cancer, Stroke, Diabetes, Metabolic Syndrome, Alzheimer’s Disease, many forms of arthritis such as Rheumatoid and Lupus, Inflammatory Bowel Disease such as Ulcerative Colitis and Crohn’s Disease, age-related Macular Degeneration, Sepsis which is infection in the blood stream, Multiple Sclerosis, hundreds of diseases ending in “itis” including Meningitis, Acne, and everyone’s favorite—Allergies. The mechanisms of Inflammation are complex, but just understand that it is controlled by fatty acids called prostaglandins. Just like cholesterol there are “good” prostaglandins and “bad” prostaglandins.

 Discovery of Inflammation and Diabetes

In recent years, it has been theorized that chronic, low-grade tissue inflammation related to obesity contributes to insulin resistance, the major cause of Type II diabetes. In research done in mouse models, the UCSD scientists proved that, by disabling the macrophage inflammatory pathway, insulin resistance and the resultant Type II diabetes can be prevented.

The findings of the research team, led by principle investigators Michael Karin, Ph.D., Professor of Pharmacology in UCSD’s Laboratory of Gene Regulation and Signal Transduction, and Jerrold Olefsky, Distinguished Professor of Medicine and Associate Dean for Scientific Affairs, were published as the feature article in an issue of Cell Metabolism.

According to Olefsky, “Our research shows that insulin resistance can be disassociated from the increase in body fat associated with obesity.” Macrophages, found in white blood cells in the bone marrow, are key players in the immune response. When these immune cells get into tissues, such as adipose (fat) or liver tissue, they release cytokines, which are chemical messenger molecules used by immune and nerve cells to communicate. These cytokines cause the neighboring liver, muscle or fat cells to become insulin resistant, which in turn can lead to Type II diabetes.

The UCSD research team showed that the macrophage is the cause of this cascade of events by knocking out a key component of the inflammatory pathway in the macrophage, JNK1, in a mouse model. This was done through a procedure called adoptive bone marrow transfer, which resulted in the knockout of JNK1 in cells derived from the bone marrow, including macrophages.

With this procedure, bone marrow was transplanted from a global JNK1 knockout mouse (lacking JNK1 in all cell types) into a normal mouse that had been irradiated to kill off its endogenous bone marrow. This resulted in a chimeric mouse in which all tissues were normal except the bone marrow, which is where macrophages originate. As a control, the scientists used normal, wild-type mice as well as mice lacking JNK1 in all cell types. These control mice were also subjected to irradiation and bone marrow transfer.

The mice were all fed a high-fat diet. In regular, wild-type mice, this diet would normally result in obesity, leading to inflammation, insulin resistance and mild Type 2 diabetes. The chimeric mice, lacking JNK1 in bone marrow-derived cells, did become obese; however, they showed a striking absence of insulin resistance — a pre-condition that can lead to development of Type 2 diabetes.

“If we can block or disarm this macrophage inflammatory pathway in humans, we could interrupt the cascade that leads to insulin resistance and diabetes,” said Olefsky. “A small molecule compound to block JNK1 could prove a potent insulin-sensitizing, anti-diabetic agent.”

The research also proved that obesity without inflammation does not result in insulin resistance. Olefsky explained that when an animal or a human being becomes obese, they develop steatosis, or increased fat in the liver. The steatosis leads to liver inflammation and hepatic insulin resistance.

The chimeric mice did develop fatty livers, but not inflammation. “Their livers remained normal in terms of insulin sensitivity,” said Olefsky, adding that this shows that insulin resistance can also be disassociated from fatty liver. “We aren’t suggesting that obesity is healthy, but indications are promising that, by blocking the macrophage pathway, scientists may find a way to prevent the Type II diabetes now linked to obesity and fatty livers,” Olefsky said.

In a related study, it was found that inflammation-causing cells in fat tissue may explain the link between obesity and diabetes. The findings came from Walter and Eliza Hall Institute researchers in Melbourne, Australia. The discovery, by Professor Len Harrison and Dr John Wentworth from the institute’s Autoimmunity and Transplantation division, opens the way for new anti-inflammatory treatments that prevent insulin resistance (where the body is unable to respond to and use the insulin it produces) and other complications associated with obesity.

“We have shown that insulin resistance in human obesity is closely related to the presence of inflammatory cells in fat tissue, in particular a population of macrophage cells,” Professor Harrison said.

Once again this research team had similar findings to those of UCSD scientists. That is, macrophages, white blood cells derived from the bone marrow, are immune cells that normally respond to infections. In obese people, macrophages move into the fat tissue where they cause inflammation and release cytokines, which are chemical messenger molecules used by immune cells to communicate. Certain cytokines cause cells to become resistant to the effects of the hormone insulin, leading to diabetes and heart disease.

My hypothesis (as a diabetic, not as a medical doctor) is that these cytokines cause the genes that produce mitochondria in our cells (especially adipose cells) to become disabled. It is only a hypothesis of mine but it would be theoretically very informative if some future research were to experimentally prove this.

 Other Studies of Importance

 It probably should be no surprise that inflammation in the body has an effect on other medical problems, including Metabolic Syndrome. Metabolic syndrome is a condition whereby a combination of medical disorders that, when occuring together, increase the risk of developing cardiovascular disease and diabetes. Some studies have shown the prevalence in the USA to be an estimated 25% of the population, and prevalence increases with age.

Individuals who are obese are at increased risk of developing a combination of medical disorders associated with type II diabetes and heart disease known as the metabolic syndrome. Recent studies have suggested that adipose (fat) tissue obesity induces an inflammatory state that is crucial to the development of the metabolic syndrome. UCLA researchers demonstrated that an over-the-counter dietary supplement may help inhibit development of insulin resistance and glucose intolerance, conditions that are involved in the development of Type II diabetes and metabolic syndrome, which affect millions worldwide.

In this early preclinical study, a naturally produced amino acid-like molecule called GABA was given orally to mice that were obese, insulin resistant and in the early stages of Type II diabetes. Researchers found that GABA suppressed the inflammatory immune responses that are involved in the development of this condition.

According to study authors, GABA helped prevent disease progression and improved glucose tolerance and insulin sensitivity, even after onset of Type II diabetes in mice. Researchers also identified the regulatory immune cells that likely direct GABA activity in inhibiting inflammation.

Researchers note that in the future, GABA taken as a supplement or related medications may provide new therapeutic agents for the treatment of obesity-related Type II diabetes and metabolic syndrome. However, like any substance science does not know what side effects there may be with GABA. Don’t run out to your health store just yet. Wait for the proper medical research to be conducted on GABA efficacy and safety. Nobody wants to wait forever for something that may work but FDA approval and the proper research protocols must be followed first. Does this mean we can’t utilize the new research to our advantage right now? No— not at all. One area we do have control over is the food we eat and the lifestyle we choose for ourselves. It’s time we all come into the 21st C entury folks. Your doctor isn’t responsible for your health—YOU ARE.

Connections

I am a 69 year old diabetic who has had diabetes since August 1991 (I was 48 years old at time of diagnosis). I ask myself, how can this new information help me? I’ve been a Vegan for two years that helped launch me down the road to successfully losing weight (16 lb weight loss in 2011, but virtually very little weight loss in 2012).

In 2012 Sciatica visited the nerves in my lower back and down my left leg, hamstring, thigh, and buttocks. The pain impacted my ability, particularly after my USA Track & Field Meets were over in July, to exercise 4-5 days a week the rest of the year. This in turn helped explain why my weight loss stood still in 2012.

With physical therapy I have been getting better and intend on returning to a good schedule of exercise in 2013. In terms of food consumption, as a tool to fight inflammation, I have decided to integrate my Vegan diet with the Anti-Inflammation Diet. For those interested in understanding the Vegan diet please read some of my earlier Blogs.

People should be asking themselves this question: If inflammation (low-grade or otherwise) plays a role in many other diseases besides Diabetes what dietary changes can I make to increase the success in lessening inflammation in the body? I’m glad you asked. Here is what I’m going to do about it. As always, see your primary care physician before undertaking any program.

Because of what is involved in using the anti-inflammatory diet and the vast amount of information available I simply, with the rest of this Blog, want to accomplish two things: (1) make the reader aware of two books I found valuable with reducing inflammation, and (2) give the reader a preview of the kinds of food one can eat right away to reduce inflammation in the body. These books are: (1) The Idiot’s Guide to The Anti-Inflammation Diet by Christopher P. Cannon, M.D., and Elizabeth Vierck., and (2) The Anti-Inflammation Diet and Recipe Book by Jessica K. Black, N.D.

 Top 10 Anti-Inflammatory and Inflammatory Foods

The above books listed go into great detail on the Anti-Inflammation Diet. In the meantime, here are some quick suggestions.

 Foods to Consume:

  • Wild Alaskan Salmon
  • Kelp
  • Extra Virgin Olive Oil
  • Cruciferous Vegetables
  • Blueberries
  • Turmeric
  • Ginger
  • Garlic
  • Green Tea
  • Sweet Potatoes

 Foods to Avoid:

  •  Sugar
  • Common Cooking Oils
  • Trans Fats
  • Dairy
  • Feedlot-Raised Meat
  • Red and Processed Meats
  • Alcohol
  • Refined Grains
  • Artificial Food Additives

 Final Advice:

      Add lots of fruits and vegetables to your diet, nuts and legumes, whole grains, take a daily multiple vitamin-mineral; and, when in the grocery store—READ THE LABELS.

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Part I

Update on Diabetes in America
[Epidemiology and New Research Findings]

Introduction

This is Part I of a two-part series on diabetes in this country. Part I will be an epidemiological look at this disease in terms of statistical estimates disaggregated by age, race, and gender.

Part II of the series will concentrate on presenting some of the new research findings as they relate to Type II diabetes, insulin resistance, obesity, and a new factor that is emerging as important—Inflammation.

2011 National Diabetes Fact Sheet

Diagnosed and undiagnosed diabetes in the United States, all ages, 2010

Total: 25.8 million people, or 8.3% of the U.S. population, have diabetes.
Diagnosed: 18.8 million people
Undiagnosed: 7.0 million people

Estimation Methods

The estimates in this fact sheet were derived from various data systems of the Centers for Disease Control and Prevention (CDC), the Indian Health Service’s (IHS) National Patient Information Reporting System (NPIRS), the U.S. Renal Data System of the National Institutes of Health (NIH), the U.S. Census Bureau, and published studies.

The estimated percentages and the total number of people with diabetes and prediabetes were derived from 2005–2008 National Health and Nutrition Examination Survey (NHANES), 2007–2009 National Health Interview Survey (NHIS), 2009 IHS data, and 2010 U.S. resident population estimates.

The diabetes and prediabetes estimates from NHANES were applied to the 2010 U.S. resident population estimates to derive the estimated number of adults with diabetes or prediabetes. The methods used to generate the estimates for the fact sheet may vary over time and need to be considered before comparing fact sheets. In contrast to the 2007 National Diabetes Fact Sheet, which used fasting glucose data to estimate undiagnosed diabetes and prediabetes, the 2011 National Diabetes Fact Sheet used both fasting glucose and hemoglobin A1c (A1c) levels to derive estimates for undiagnosed diabetes and prediabetes. These tests were chosen because they are most frequently used in clinical practice.

Diagnosed and undiagnosed diabetes among people aged 20 years or older, United States, 2010

Age 20 years or older: 25.6 million, or 11.3% of all people in this age group, have diabetes.

Age 65 years or older: 10.9 million, or 26.9% of all people in this age group, have diabetes.

Men: 13.0 million, or 11.8% of all men aged 20 years or older, have diabetes.

Women: 12.6 million, or 10.8% of all women aged 20 years or older, have diabetes.

Non-Hispanic whites: 15.7 million, or 10.2% of all non-Hispanic whites aged 20 years or older, have diabetes.

Non-Hispanic blacks: 4.9 million, or 18.7% of all non-Hispanic blacks aged 20 years or older, have diabetes.

Sufficient data are not available to estimate the total prevalence of diabetes (diagnosed and undiagnosed) for other U.S. racial/ethnic minority populations.

Diagnosed diabetes in people younger than 20 years of age, United States, 2010

About 215,000 people younger than 20 years have diabetes (type 1 or type 2). This represents 0.26% of all people in this age group. Estimates of undiagnosed diabetes are unavailable for this age group.

Racial and ethnic differences in diagnosed diabetes

National estimates of diagnosed diabetes for some but not all minority groups are available from national survey data and from the IHS NPIRS, which includes data for approximately 1.9 million American Indians and Alaska Natives in the United States who receive health care from the IHS. Differences in diabetes prevalence by race/ethnicity are partially attributable to age differences. Adjustment for age makes results from racial/ethnic groups more comparable.
• Data from the 2009 IHS NPIRS indicate that 14.2% of American Indians and Alaska Natives aged 20 years or older who received care from IHS had diagnosed diabetes.

• After adjusting for population age differences, 16.1% of the total adult population served by IHS had diagnosed diabetes, with rates varying by region from 5.5% among Alaska Native adults to 33.5% among American Indian adults in southern Arizona.

• After adjusting for population age differences, 2007–2009 national survey data for people aged 20 years or older indicate that 7.1% of non-Hispanic whites, 8.4% of Asian Americans, 11.8% of Hispanics, and 12.6% of non-Hispanic blacks had diagnosed diabetes. Among Hispanics, rates were 7.6% for both Cubans and for Central and South Americans, 13.3% for Mexican Americans, and 13.8% for Puerto Ricans.

• Compared to non-Hispanic white adults, the risk of diagnosed diabetes was 18% higher among Asian Americans, 66% higher among Hispanics, and 77% higher among non-Hispanic blacks. Among Hispanics compared to non-Hispanic white adults, the risk of diagnosed diabetes was about the same for Cubans and for Central and South Americans, 87% higher for Mexican Americans, and 94% higher for Puerto Ricans.

New cases of diagnosed diabetes among people aged 20 years or older, United States, 2010

About 1.9 million people aged 20 years or older were newly diagnosed with diabetes in 2010.

New cases of diagnosed diabetes among people younger than 20 years of age, United States, 2002–2005

SEARCH for Diabetes in Youth is a multicenter study funded by CDC and NIH to examine diabetes (type 1 and type 2) among children and adolescents in the United States. SEARCH findings for the communities studied include the following:
• During 2002–2005, 15,600 youth were newly diagnosed with type 1 diabetes annually, and 3,600 youth were newly diagnosed with type 2 diabetes annually.

• Among youth aged

• Non-Hispanic white youth had the highest rate of new cases of type 1 diabetes (24.8 per 100,000 per year among those younger than 10 years and 22.6 per 100,000 per year among those aged 10–19 years).

• Type 2 diabetes was extremely rare among youth aged 9%) were 2.9 times more likely to have severe periodontitis than those without diabetes. The likelihood was even greater (4.6 times) among smokers with poorly controlled diabetes.

• About one-third of people with diabetes have severe periodontal disease consisting of loss of attachment (5 millimeters or more) of the gums to the teeth.

Complications of pregnancy
• Poorly controlled diabetes before conception and during the first trimester of pregnancy among women with type 1 diabetes can cause major birth defects in 5% to 10% of pregnancies and spontaneous abortions in 15% to 20% of pregnancies. On the other hand, for a woman with pre-existing diabetes, optimizing blood glucose levels before and during early pregnancy can reduce the risk of birth defects in their infants.

• Poorly controlled diabetes during the second and third trimesters of pregnancy can result in excessively large babies, posing a risk to both mother and child.

Other complications
• Uncontrolled diabetes often leads to biochemical imbalances that can cause acute life-threatening events, such as diabetic ketoacidosis and hyperosmolar (nonketotic) coma.

• People with diabetes are more susceptible to many other illnesses. Once they acquire these illnesses, they often have worse prognoses. For example, they are more likely to die with pneumonia or influenza than people who do not have diabetes.

• People with diabetes aged 60 years or older are 2–3 times more likely to report an inability to walk one-quarter of a mile, climb stairs, or do housework compared with people without diabetes in the same age group.

• People with diabetes are twice as likely to have depression, which can complicate diabetes management, than people without diabetes. In addition, depression is associated with a 60% increased risk of developing type 2 diabetes.

Preventing diabetes complications

As indicated above, diabetes can affect many parts of the body and can lead to serious complications such as blindness, kidney damage, and lower-limb amputations. Working together, people with diabetes, their support network, and their health care providers can reduce the occurrence of these and other diabetes complications by controlling the levels of blood glucose, blood pressure, and blood lipids, and by receiving other preventive care practices in a timely manner.

Glucose control
• Studies in the United States and abroad have found that improved glycemic control benefits people with either type 1 or type 2 diabetes. In general, every percentage point drop in A1c blood test results (e.g., from 8.0% to 7.0%) can reduce the risk of microvascular complications (eye, kidney, and nerve diseases) by 40%. The absolute difference in risk may vary for certain subgroups of people.

• In patients with type 1 diabetes, intensive insulin therapy has long-term beneficial effects on the risk of cardiovascular disease.

Blood pressure control
• Blood pressure control reduces the risk of cardiovascular disease (heart disease or stroke) among people with diabetes by 33% to 50%, and the risk of microvascular complications (eye, kidney, and nerve diseases) by approximately 33%.

• In general, for every 10 mmHg reduction in systolic blood pressure, the risk for any complication related to diabetes is reduced by 12%.

• No benefit of reducing systolic blood pressure below 140 mmHg has been demonstrated in randomized clinical trials.

• Reducing diastolic blood pressure from 90 mmHg to 80 mmHg in people with diabetes reduces the risk of major cardiovascular events by 50%.
Control of blood lipids
• Improved control of LDL cholesterol can reduce cardiovascular complications by 20% to 50%.

Preventive care practices for eyes, feet, and kidneys
• Detecting and treating diabetic eye disease with laser therapy can reduce the development of severe vision loss by an estimated 50% to 60%.

• About 65% of adults with diabetes and poor vision can be helped by appropriate eyeglasses.

• Comprehensive foot care programs, i.e., that include risk assessment, foot-care education and preventive therapy, treatment of foot problems, and referral to specialists, can reduce amputation rates by 45% to 85%.

• Detecting and treating early diabetic kidney disease by lowering blood pressure can reduce the decline in kidney function by 30% to 70%. Treatment with particular medications for hypertension called angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is more effective in reducing the decline in kidney function than is treatment with other blood pressure lowering drugs.

• In addition to lowering blood pressure, ARBs and ACEIs reduce proteinuria, a risk factor for developing kidney disease, by about 35%.

Post Script

In Part I, data were presented on diabetes in order to give the reader an epidemiological look at this disease. In Part II data will be presented on some of the research looking to understand, or at least better treat, this dreadful disease. It is hoped that as each year passes, researchers will eventually find the cure for diabetes.

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