If type 2 diabetes were an infectious disease, it is said we would be in the midst of an epidemic. This problematic disease is striking an ever-growing number of adults. With the rising rates of childhood obesity, it has become more common in youth, especially among certain ethnic groups. The good news is that prediabetes and Type 2 Diabetes are largely preventable. About 9 in 10 cases in the U.S. can be avoided by making lifestyle changes. These changes can also lower the chances of developing heart disease and some cancers. In this article, we will look at diet as a means to prevent and regulate T2DM.

1. How does what you eat affect you?

According to the Centers for Disease Control and Prevention, one out of every three American adults has prediabetes; that is 86 million people. Without intervention, up to one-third of them will go on to develop type 2 diabetes within five years

Is everything lost? Not at all! Lifestyle changes can help. While excess body fat is a recognized risk factor for diabetes (and weight loss is an important way to lower risk), specific diet patterns and foods seem to decrease or increase risk, independent of weight. The latest research suggests that diabetes risk (as well as the risk of heart disease and stroke) is largely influenced not by single nutrients but by specific foods and overall diet patterns.

Poor diet quality may influence weight and metabolic risk independent of calories: Different types of foods have different effects on satiety, glucose-insulin responses, liver fat synthesis, fat-cell function, craving and reward responses in the brain, and the creation of visceral fat.

2. So, which foods lower the risk of getting Type 2 Diabetes?

We will discuss in some detail everyday food that might either aid in the prevention of diabetes or accelerate your progress towards it. When you are making the decision of what to eat, choose wisely.

1. Choose high-fiber, slow-release carbs

Carbohydrates have a big impact on your blood sugar levels—more so than fats and proteins—so you need to be smart about what types of carbs you eat. Limit refined carbohydrates like white bread, pasta, and rice, as well as soda, candy, packaged meals, and snack foods. Focus on high-fiber complex carbohydrates—also known as slow-release carbs. They are digested more slowly, thus preventing your body from producing too much insulin.

2. Eat more plant foods.
   Minimally processed plant foods such as fruits, non-starchy vegetables, legumes, and nuts/seeds are consistently linked to better cardio-metabolic outcomes, including decreased diabetes risk.
3. How about proteins?
   While they have been studied to different extents, meat, poultry, eggs, fish, and dairy protein sources appear to impact diabetes risk differently.

In their 2011 meta-analysis, Pan and colleagues determined that red meat consumption, particularly processed red meat, is associated with an increased risk of type 2 diabetes and suggested that substituting one serving of nuts, low-fat dairy, and whole grains per day for one serving of red meat would lower diabetes risk by 16% to 35%.

4. Are fats bad for you?
Most research on fats typically looks at their impact on cardiovascular, not diabetes, risk, and fats’ association with diabetes risk is in need of clarification. Recent evidence suggests that the quality of fats consumed in the diet is more important than the total quantity of dietary fat. Some researchers point out that the source of fat is important, and possibly confounding, in studies looking at total fat intake and health effects. Although some results are controversial, it’s important to be aware of and keep an eye on emerging research. Some recent study findings include the following:

• A Mediterranean dietary pattern, which is relatively high in monounsaturated fats, may help prevent type 2 diabetes.
• High vegetable fat intake may decrease type 2 diabetes risk in females.
• Intake of high-fat, but not low-fat, dairy products is associated with a decrease in type 2 diabetes risk.
• EPA+DHA seems to provide neither harm nor benefits with regard to diabetes development. The omega-3 fatty acid ALA (alpha-linolenic acid) may be associated with modestly lower risk.10

Since fat is calorically dense (9 kcal/g as opposed to 4 kcal/g for protein or carbohydrate), it’s often the focus of weight-loss diets.

5. Should you take beverages?
   What to drink is a choice we make every day. It is important to get into healthy drinking habits.

• 100% fruit juices are generally considered safe, as long as the serving is kept to one a day.
• Both coffee (caffeinated and decaffeinated) and tea are associated with a lower risk of diabetes.
• There’s strong evidence that moderate alcohol use is associated with lower diabetes risk across diverse populations, but people who don’t currently drink alcohol shouldn’t be encouraged to do so, and drinkers should limit themselves to up to two drinks per day for men and one to 1.5 for women.

3. So, In Summary…..

Eat more

• Healthy fats from nuts, olive oil, fish oils, flax seeds, or avocados
• Fruits and vegetables—ideally fresh, the more colorful the better; whole fruit rather than juices
• High-fiber cereals and bread made from whole grains
• Fish and shellfish, organic chicken or turkey
• High-quality protein such as eggs, beans, low-fat dairy, and unsweetened yogurt

Eat less

• Trans fats from partially hydrogenated or deep-fried foods
• Packaged and fast foods, especially those high in sugar, baked goods, sweets, chips, desserts
• White bread, sugary cereals, refined pasta or rice
• Processed meat and red meat
• Low-fat products that have replaced fat with added sugar, such as fat-free yogurt

4. How to eat healthy on a normal diet

It is easier to adopt a healthy eating lifestyle than to go on a diet. A good dietary pattern to lower diabetes risk would limit red and processed meats, refined grains, sweets and Soda, and emphasize plant foods like whole grains, nuts, fruits, and leafy green vegetables. Evidence supports including coffee, tea, yogurt, vegetable fats, and possibly cheese.

Working with a dietary pattern instead of focusing on individual nutrients or “superfoods” (or vilifying particular food groups) allows greater flexibility for you. It lets you choose foods you like at times that are convenient for you.

Given the health advantages of plant foods like leafy greens and whole grains and their association with reduced diabetes risk, you should ensure your diet pattern includes a healthy serving of them at all times.

References:

1. Today’s dietician (2017): Diabetes Management & Nutrition Guide: Foods and Eating Patterns for Diabetes Prevention. Retrieved from https://www.todaysdietitian.com/newarchives/0717p40.shtml

2. Harvard School of Public Health (2019): Simple Steps to Preventing Diabetes. Retrieved from https://www.hsph.harvard.edu/nutritionsource/disease-prevention/diabetes-prevention/preventing-diabetes-full-story/

3. Health Guide (2018): The Diabetic Diet. Retrieved from https://www.helpguide.org/articles/diets/the-diabetes-diet.htm

Obesity, Prediabetes, and Diabetes Type 2 are associated with most of the diseases of modern society (cardiovascular/cerebrovascular disease, cancer, Alzheimer’s disease). These are all metabolic dysfunctions related to the malnutrition of overconsumption which leads to metabolic inflammation, or metal inflammation. This series of articles provides a recipe on how to make a healthy society, and create metal inflammation, which results in severe chronic disease and requires expensive lifelong treatment.

Whether by coincidence or concerted action, this chronic disease model produces tremendous revenue for the medical-industrial complex, big pharma, big food, and reduces upward mobility. I would even contend that generational metal inflammation is a primary driver of economic disparity and plays a significant role in violence and incarceration rates.

Type 2 Diabetes hits African American populations especially hard.

• African Americans are 1.7 times more likely to develop diabetes compared to non-Hispanic whites.
• The prevalence of Type 2 Diabetes among African Americans has quadrupled during the past 30 years
• African Americans with diabetes are more likely than non-Hispanic whites to develop greater diabetes-related complications such as amputations, adult blindness, kidney failure, and increased risk of heart disease and stroke due to a delay in diagnosis. Being Prediabetic starts the injury, even before becoming Diabetic five years later.
• Death rates for African Americans with diabetes are 27 percent higher than for non-Hispanic whites.

Metainflammation is the lynchpin for over 80% of human suffering and healthcare expense in the United States. Understanding the common root causes, which appear unrelated on the surface, is the first actionable step in preventing and reversing the disease and restoring health to a community.

Are Obesity, Prediabetes, and Diabetes Type 2 really a significant problem?

Obesity, Prediabetes, and Diabetes are a new phenomenon in the United States. Obesity and Diabetes type 2 in the 1940s was nearly unheard of. In the 1970s only 13% of adults and 5% of children were obese. Today 35% of adults and 17% of children are obese.

Diabetes Obesity disproportionately affects certain racial and ethnic minority groups. By 2035 nearly 100% of African American females will be overweight or obese, which is only 16 years from now.

Nearly 72% of adults in the United States are now overweight or obese. Obesity is a contributing factor to approximately 100,000–400,000 deaths in the United States per year, and directly accounts for 5% to 10% of the national health care expenditure. Obesity is the second leading cause of death and is likely to become the first (Mokdad, Marks, Stroup, & Gerberding, 2004). Statistics predict that 86% of the United States population will be overweight or obese by 2030. It is highly likely that future adults will have shorter life-spans than the current generation (Olshansky et al., 2005). Not only do obese individuals have a shorter life span, but they also have a significantly shorter health span (healthy living before getting a debilitating illness) which reduces their quality of life and worsens economic disparity. They are far more likely to suffer from stroke, breast, and colorectal cancer, osteoarthritis, and depression (Jebb, 2004).

There are 84.1 million Prediabetics in the United States (34% of the population), a condition that if left untreated leads to type 2 diabetes within five years. Less than 11 percent of adults with Prediabetes know they have it.

There are about 30.3 million diabetics in the United States (9% of the population), 23.1 million are diagnosed and 7.2 million are undiagnosed diabetics. Over 95% of all diabetics are type 2 diabetics, which is a disease created by the modern lifestyle. The American Diabetes Association currently estimates the total costs of diagnosed diabetes have risen from $245 billion in 2012 to $327 billion in 2017, a 26% increase over a five-year period. For diagnosed diabetics, the average annual medical expenditure is approximately $16,752 per year:

• hospital inpatient care (30% of the total medical cost)
• prescription medications to treat complications of diabetes (30%)
• anti-diabetic agents and diabetes supplies (15%)
• physician office visits (13%)

Statistics predict that the prevalence of diabetes will increase by 54% to more than 54.9 million Americans between 2015 and 2030; annual deaths attributed to diabetes will climb by 38%, and annual medical and societal costs will increase 53%. By 2050, nearly 1/3 of the United States population is predicted to be diabetic.

So, what exactly is diabetes?

Diabetes is a condition in which glucose sugar builds up in your blood. When you have diabetes, your body either doesn’t make enough insulin (Type 1 Diabetes) or can’t use its own insulin as well as it should (Type 2 Diabetes). Other than the fact that there is too much glucose in the bloodstream, Type 1 diabetes and Type 2 Diabetes is not the same disease.

The focus of this discussion is Type 2 Diabetes, what causes it and how to reverse it.

Our bodies normally use a combination of carbohydrates (sugars such as glucose), fats, and proteins for energy.  When the body senses that it is going to receive a carbohydrate load, the Beta cells of the pancreas release a hormone called Insulin. Insulin works through specialized receptors and transporters to clear the bloodstream of glucose, and deposit the glucose into the cells. Glucose inside the cells is rapidly converted to energy or stored for later use as glycogen or converted to fat. Insulin specifically triggers a series of enzymes to cause fat storage. Whenever you hear the word insulin, think “fat-storage hormone.”

 

As the fat cells uptake excessive circulating glucose, they overflow their capacity to use glucose for energy and their limited glycogen storage. The cells produce chemical inflammatory signaling compounds that leech into the bloodstream, activating the immune system, contributing to the onset of metal inflammation. The cell also begins to leech out stored fats as triglycerides.

If the cell becomes overwhelmed with glucose and runs out of fat storage capacity, it eventually reaches a critical size and will literally explode. This cell death also causes an inflammatory reaction or metal inflammation.

Extra glucose outside the cells quickly damages the cells by a process of glycation, making cell walls, proteins, and receptors sticky and function poorly. Imagine putting sugar into your car’s gas tank, as the clean gas is burned it would leave a sticky residue in the engine and over time your engine would seize up and all the parts would stop moving.

Insulin resistance due to glycation occurs as the cell receptors can no longer efficiently move and the circulating proteins such as insulin become sticky. We measure this as Hemoglobin A1C, which tells us how much glucose is sticking to the hemoglobin in the red blood cells, the higher the number, the greater the glycation.

It can take up to 12 years for a patient to develop decompensated diabetes until then the fasting blood sugars appear normal, but the patient is in a state of metal inflammation.

Trajectories of glycemia, insulin sensitivity, and insulin secretion before the diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 2009; 373: 2215–2221.

The body compensates by increasing the production of insulin, even more, to clear out the toxic glucose, which only leads to even more insulin production and worsening insulin resistance, and more fat storage.

Insulin resistance also occurs because of the constant stimulation of biological receptors causes the receptors to down-regulate. These transporters become fatigued if there is too much insulin or the frequency of insulin release becomes too often.

Eventually, the tremendous excessive fat storage and cell structure disruption become so great that the liver and pancreas become congested with fat, and blood flow to the pancreas decreases so insulin production is severely reduced, and the patient now becomes dependent on injected insulin.

Diabetes results in metal inflammation because your body is trying to clean out the sticky residue, or glycated parts.  Diabetes can cause serious health complications including heart disease, blindness, kidney failure, amputations, and pain. Unfortunately, the most patient does not realize they have diabetes until some significant symptom causes them to seek care, usually pain which is the common pathway of tissue damage in metal inflammation.

What is wrong with the standard of care treatment for diabetes?

Current medical guidelines specifically consider Type 2 Diabetes a chronic and progressive disease, in which the patient has little choice.

http://www.diabetes.org/diabetes-basics/myths/

The standard of care usually starts with one drug, then two, then three and sequentially increasing insulin. Most people assume that we are treating their diabetes with medications to make their disease better. It’s simply not true, we are not actually treating the disease. We are treating the symptom of diabetes, the elevated blood sugar; the disease of insulin resistance is getting worse year after year. Diabetes is getting worse, not better. The complications of diabetes track insulin resistance over time, not just the glucose level.

In fact, the American Diabetes Association almost seems to relish in this learned helplessness and dependence on insulin.

“Using insulin to get blood glucose levels to a healthy level is a good thing, not a bad one. For most people, type 2 diabetes is a progressive disease. When first diagnosed, many people with type 2 diabetes can keep their blood glucose at a healthy level with a combination of meal planning, physical activity, and taking oral medications. But over time, the body gradually produces less and less of its own insulin, and eventually, oral medications may not be enough to keep blood glucose levels in a healthy range.”

The American Diabetes Association is definitely dependent on insulin, or at least dependent on the companies who manufacture insulin and fund the Association.

Eli Lilly

Novo Nordisk

Sanofi

http://www.diabetes.org/about-us/corporate-support/our-corporate-supporters.html
and
http://www.diabetes.org/about-us/corporate-support/banting-circle-supporters.html

While the use of agents, including insulin, to reduce glucose is absolutely necessary for certain circumstances, it does not address the disease of diabetes, which is insulin resistance.

What’s wrong with conventional dietary advice of multiple small meals per day?

Conventional dietary advice suggests that patients should eat 3 meals per day plus snacks, resulting in a feeding frequency of approximately five times per day. This dietary recommendation is baseless in the normal adult population, and inconsistent from an evolutionary perspective.

Hunter-gatherer eating patterns were characterized by intermittent energy intake depending entirely upon food availability and required an extraordinarily high level of physical and mental functional capacity during the extended periods without food. These adaptations allowed for organs to rapidly uptake and store glucose when available, as fat and glycogen storage, and mobilize these reserves as needed as glucose, fatty acid, and ketones in times of need.

Less than 10,000 years ago, converting from a hunter-gatherer eating pattern to an agrarian eating pattern resulted in year-round availability of food and the current three meals per day eating pattern.

The concept of multiple snacks between meals is a modern development, which began in the 1950s and closely tracks with the loss of healthy eating patterns, food overconsumption and the epidemic of obesity, metabolic syndrome, and diabetes.  In a study conducted by the Agriculture Department and the Department of Health and Human Services on food consumption behavior, the percent of the American population eating three or more snacks a day increased from 11% to 42% between 1977 to 2002. Snacks now constitute more than 27 percent of children’s daily calories.

Adapted from the American Journal of Clinical Nutrition, March 1, 1999

In fact, there is no actual data supporting even three meals per day. Breakfast as a meal has only been advocated as the “most important meal of the day” in the media since 1917, and there is no evidence that breakfast consumption promotes weight loss or that skipping breakfast leads to weight gain. In fact, people who eat breakfast consume on average 260 calories/day more than those who skip breakfast and are heavier.

Effect of breakfast on weight and energy intake: systematic review and meta-analysis of randomized controlled trials. BMJ 2019; 364 DOI: https://doi.org/10.1136/bmj.l42 (Published 30 January 2019)

Insulin is a fat-storage that clears glucose from the bloodstream (lipogenesis). It is produced by the pancreas in anticipation of a carbohydrate load. Its primary function is to rapidly clear the bloodstream of excessive glucose after a feast, and convert it to long term fat storage for later use in a time of famine. Maintaining elevated levels of insulin, both as in terms of spikes and for a proportionate period of time, causes a continuous shunting of circulating glucose to fat storage. When insulin is decreased, the body automatically shifts to burning fat as a fuel source (lipolysis).

Insulin acts as a growth hormone, preventing the cellular stress responses involved in removing damaged cells and organelles (autophagy). Allowing dysfunctional cells and organelles to accumulate is the hallmark of aging and the common pathway for diabetes, cardiovascular/cerebrovascular disease, cancers, and Alzheimer’s disease. When insulin is decreased, autophagy is increased.

Intermittent energy restriction permits a cyclical ebb and flow which maintains insulin receptor sensitivity and minimizes excessive fat storage due to chronically elevated insulin. In other words, eating less frequently exercise your insulin system and prevents insulin resistance. Constantly eating results in lipogenesis and accumulation of cellular debris.

What’s wrong with the conventional dietary advice to consume carbohydrates?

The Dietary Guidelines for Americans published by the USDA recommends that carbohydrates make up 45 to 65 percent of total daily calories. Based upon a  2,000 calories/day, between 900 and 1,300 calories should be from carbohydrates (225 and 325 grams of carbohydrates a day). The Institute of Medicine also recommends 45 to 65 percent calorie intake as carbohydrates, with at least 130 grams of consumed carbs per day. The American Heart Association recommends that refined sugar should be limited to 6 to 9 teaspoons per day. All of these organizations suggest that there is an absolute requirement of carbohydrate necessary for human function, with the majority of nutrition coming from carbohydrates.

However, the lower limit of carbohydrate consumption is likely zero, there are no essential carbohydrates required for living.  According to the Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids (2005), the Recommended Dietary Allowance (RDA) for carbohydrate,  considered to be the average minimum amount of glucose needed by the brain or central nervous system (CNS), is 130 g/day for adults and children.

The CNS comprises less than 2% of total body weight but consumes roughly 20% of the total daily calories.  Historically the brain has been considered the only organ that required glucose as a fuel source, utilizing approximately 100-140 g glucose per day.  However, with keto-adaptation, the CNS reduces the obligatory glucose requirement by approximately 80%, resulting in a true utilization of 20-28 g glucose/d.

Traditional civilizations (Masai, the Greenland, and Alaskan Inuit and Pampas indigenous people) survive on a “minimal amount of carbohydrate for extended periods of time with no apparent effect on health or longevity“.

“In the absence of dietary carbohydrate, de novo synthesis of glucose requires amino acids derived from the hydrolysis of endogenous or dietary protein or glycerol derived from fat. Therefore, the marginal amount of carbohydrate required in the diet in an energy-balanced state is conditional and dependent upon the remaining composition of the diet.”

Endogenous glucose production through gluconeogenesis is approximately 2.8-3.6 g/kg/d, or approximately 210-270 g/d in a 70kg human, far greater than the obligatory requirement of 20-28g glucose/d of the keto-adapted human.

“The lower limit of dietary carbohydrate compatible with life apparently is zero, provided that adequate amounts of protein and fat are consumed” (pg. 275). There is no essential need for dietary carbohydrate, provided that “adequate amounts of protein and fat are consumed”.

This does not mean that patients should strive to be zero carbohydrates, what it means is that half your calories don’t need to come from carbohydrates.

What’s wrong with the conventional dietary advice to diabetics?

Newly diagnosed diabetics are instructed to eat “multiple” small meals per day to have a steady-state glucose level. This sounds reasonable until you examine what the patient is being recommended to eat.

Diabetics are often instructed to consume more than 50% of their calories as carbohydrates. They are often instructed to consume “healthy” fruits and vegetables, as if “fruits and vegetables” was a single food group. Selective breeding of plants over the last 9,000 years has resulted in fruit that is sweeter, and bigger. Modern fruits are genetically engineered to contain sugars at or above the level of soda.

Patients often think that fruit juices, or “juicing” is healthy. That’s understandable, given that it is natural and has the word “fruit” in it. Fruit juice contains just as much sugar and calories as a sugary soft drink… and sometimes even more. Minute Maid 100 percent apple contains nearly 66 grams of fructose per liter. That’s more than the 62.5 grams per liter in Coca-Cola and the 61 grams per liter in Dr. Pepper. The fructose in fruit comes with fiber, which slows down and reduces the absorption of the sugar in the body, and juicing the fruit removes the fiber. The minimal amount of vitamins and antioxidants in the juice do not make up for a large amount of sugar, and the sugars may actually prevent vitamin absorption.

https://doi.org/10.1016/S2213-8587(14)70013-0

Diabetics are often instructed to use rescue sugars when they feel light-headed. Many diabetic patients automatically consume sugar, but when you actually look at their glucose level, it’s often in the normal ranges. What’s happened is that their brain is insulin resistant. The normal or even high blood sugar can’t get from the bloodstream to the interior of the brain cell. Being lightheaded is the symptom of intracellular hypoglycemia. The temporary fix at that moment is to control the symptom of hypoglycemia by consuming a rapidly absorbed fuel source. The issue is that if you constantly use rescue sugars, the insulin resistance only worsens. The better option is to reduce medications while reducing carbohydrate consumption and consider a fuel source such as ketones as a rescue (ketones do not require insulin to get inside the cell) and excess ketones are rapidly exhaled through your breath.

Type 2 Diabetes is a lifestyle choice that requires conscious decision making, because the default acceptance of the current nutritional recommendations has resulted in a catastrophic failure, disproportionately injuring the urban minority communities.

Today we are joined by Dr. Gurpreet Padda, a man of great learning and with a great interest in metabolic health and nutrition. He became interested in metabolic health when he noticed that, working in adult pain at the time, 91% of his patients were overweight. Through observation and experimentation, he noticed that metabolic inflammation was at the epicenter of pain, addiction, and obesity. Ever since that realization, he has continued to work toward sharing his findings and increasing his understanding of the issue. His work led him ultimately to understand that social isolation is an extremely significant factor in addiction/overeating. We also discuss in detail the metabolic impact of various foods, the importance of insulin as a marker for the disease, and the importance of achieving satiety in the process of recovering from food addiction.

We have heard a lot about the harmful effects of refined grains on our health. Interestingly, recent research seems to point in a different direction, exonerating them from the label they have held for so long. Are refined grains not so bad after all? What are the facts? In this article, we will take a closer look at why refined grains seem to have been unfairly vilified.

1. Refined grain consumption and your health

Have you been avoiding refined grains such as white bread and pasta? Do you feel bad when you do eat them? Apparently, there’s no evidence to show that refined grains are “bad” for you. Conversely, there is evidence that shows that whole grains are good for you. Somehow along the way, the message has been mixed up – putting a slice of white bread or a dish of white pasta in the same category as pie and piece of cake.

The dietary recommendation has been to make half of your grains whole grains. This does not mean “avoid all refined grains”. They too can fit into your diet.

Contrary to previous research findings, refined grain consumption is not associated with any of the adverse health effects it has been linked to, such as obesity, heart disease, and diabetes. This is according to a new study from the Healthy Lifestyles Research Center at Arizona State University (ASU) published in Advances in Nutrition. The researchers note that what counts is the number of consumed calories, not so much their source.

Analyses of existing research – including 32 publications with data from 24 distinct cohorts – showed that refined grains are not linked to increased disease risk or premature death. The study highlights that the current dietary recommendation to reduce refined grain consumption conflicts with the substantial body of published scientific evidence.

Professor Glenn Gaesser, Ph.D., Director of the Healthy Lifestyles Research Center at ASU“Simply put, refined grains are not the bad guy,” says study author, Professor Glenn Gaesser, Ph.D., Director of the Healthy Lifestyles Research Center at ASU. “Contrary to popular belief and current dietary guidance, refined grain intake is not associated with type 2 diabetes, cardiovascular disease, coronary heart disease, stroke, hypertension, cancer or death.”

Gaesser theorizes that refined grains have developed a guilt-by-association reputation. He explains that while refined grains are frequently characterized as unhealthy, this can be attributed to their inclusion in a dietary pattern that contains a range of foods that are the real culprits in the link between an unhealthy dietary pattern and an increased risk of a number of chronic diseases.

What were the results of the study?

• No association was observed between refined grain intake and cardiovascular disease or coronary heart disease.
• No association was found between refined grain intake and stroke risk. In fact, one study demonstrated a 10 percent lower reduction of stroke risk.
• No association was found between refined grain intake and risk of Type 2 diabetes.
• Cancer studies are limited. Nonetheless, one meta-analysis shows an inverse association between refined grain intake and total cancer deaths. A second meta-analysis shows that refined grain intake was not associated with the risk of rectal or colorectal cancer.
• Five out of six studies show no relationship between refined grain intake and death rate. The other study shows a statistically significant inverse association between refined grain intake and all-cause death rate.
• Three systematic reviews show no consistent relationship between refined grain intake and body mass index (BMI).

2. Is there a link between refined grains and obesity?

The demonization of refined grains has deterred people from consuming them, opting for whole grains instead. Whole grains are higher in calories but touted as more nutritionally-rich.

In reality, the association between refined grain consumption and obesity is murky, with no clear relationship. Weight gain is essentially a result of consuming more calories than you burn. It’s the number of calories that matters most, not so much the type of calories. In studies that do indicate that refined grains are associated with increased risk of weight gain, the association is “inconsequentially small.” Randomized dietary interventions of whole grains and refined grains compared head-to-head reveal no differences between the two.

Both refined grains and whole grains are important in people’s diets. Whole grains are important for health since they provide fiber and essential vitamins. Enriched/refined grains provide fiber too, and 39 percent of the dietary fiber Americans eat comes from refined grains. “As a population, US consumers still fall far short of reaching their daily goals for fiber.

It is important to note that eliminating enriched grain products will result in nutrient shortfalls. Refined grain foods that have been enriched and/or fortified help to alleviate shortfalls including B-vitamins, folic acid, thiamin, niacin, riboflavin, and iron.

A good example is that enriched grains are the largest contributor of folic acid in the American diet. This is key to preventing neural tube birth defects.

3. So, what should you eat?

To reduce disease risk and balanced nutrition, the DGA dietary recommends you eat:

• A variety of vegetables from all of the subgroups—dark green, red and orange, legumes (beans and peas), starchy, and other
• Fruits, especially whole fruits
• Grains, at least half of which are whole grains
• Fat-free or low-fat dairy, including milk, yogurt, cheese, and/or fortified soy beverages
• A variety of protein foods, including seafood, lean meats and poultry, eggs, legumes (beans and peas), and nuts, seeds, and soy products
• Oils

4. What is the future for refined grains?

Future research efforts must distinguish between staple grain foods, such as cereals, bread and pasta and indulgent grain foods, such as cakes, cookies, and donuts, according to Gaesser. Most of the studies included in the current paper did not make such distinctions, so it’s impossible to know whether the results would be different if refined grains were categorized separately as a staple or indulgent grain foods.

It is possible that the risk of chronic diseases would be different for the consumption of staple grain foods as compared to the consumption of indulgent grain foods. Randomized-comparison trials are needed to better differentiate the health effects of whole grain and refined grain foods. Most published studies have been too short and do not include enough outcome measures to draw definitive conclusions.

As currently stands, the results of randomized-comparison trials show no consistent benefits of whole-grain foods over refined grain foods. These findings are at odds with the results of large-scale observational studies, which show a clear superiority of whole grains over refined grains. This is a paradox that needs to be resolved,” Gaesser concludes.

References

1. Nutritioninsight (2019): Let us eat cake? Refined grains “falsely” linked to obesity and chronic disease risk. Retrieved from https://www.nutritioninsight.com/news/let-us-eat-cake-refined-grains-falsely-linked-to-obesity-and-chronic-disease-risk.html

2. Rust Nutrition (2019): Refined Grains Redefined. Retrieved from https://rustnutrition.com/blog/2019/07/03/refined-grains-redefined/

3. NCBI (2019): Perspective: Refined Grains and Health: Genuine Risk, or Guilt by Association? Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520038/

4. Baking Business.com (2019): Study disputes negative health claims surrounding refined grains. Retrieved from https://www.bakingbusiness.com/articles/48376-study-disputes-negative-health-claims-surrounding-refined-grains

We have been looking at metabolic inflammation and its role in the development of obesity, diabetes and other chronic diseases. Does overnutrition contribute to metabolic inflammation? How?

1. Some background on overnutrition….

It is estimated that by 2020, two-thirds of the global burden of the disease will be due to chronic non-communicable diseases, most of which are associated with diet. While hunger is a tremendous global health concern that cannot be minimized, overnutrition should similarly be given concentrated attention. Malnutrition affects up-to 1 billion people. Even though undernutrition is the main cause of malnutrition, people who are overweight could also be malnourished.

The “double burden of malnutrition” is a term coined by the World Health Organization (WHO) to describe a situation which is characterized by “the coexistence of undernutrition along with overweight and obesity, or diet-related non-communicable diseases, within individuals, households and populations, and across the life course. Globally, the problem is not the availability of food resources, but the allocation and consumption of food.

1. What is overnutrition?

Overnutrition is defined as the overconsumption of nutrients and food to the point at which health is adversely affected. Overnutrition can develop into obesity, which increases the risk of serious health conditions, including cardiovascular disease, hypertension, cancer, and type-2 diabetes.

Until recently, overnutrition had been viewed as a problem that only affected developed nations. However, this has been reviewed to affect most populations. The prevalence of obesity is increasing in developing countries with the introduction of fast food and refined sugars.

While once considered the disease of the rich, low-income groups in richer countries are also being affected by this condition.

2. What is overnutrition induced inflammation?

Inflammation is a biological response launched by the immune system against dangerous assaults that threaten the integrity and normal physiology of an organism. Chronic nutrient overload causes an increase in adipose irregularities in that, if adipose tissue expandability is low, there will be an increased presence of thickened tissue. This condition would lead to a pro-inflammatory state that can trigger insulin resistance, the release of macrophage chemoattractant proteins, and in chronic inflammation, even the death of the thickened adipose tissue itself. This creates cyclic an action that extends the insulin resistance to all adipose tissue.

An important characteristic of overnutrition-induced diseases is chronic low-grade inflammation caused by nutritional excess. Overnutrition-induced inflammation is thought to occur in the brain and thus plays an extensive and steering role in overnutrition-induced diseases.

3. Overnutrition and the metabolic syndrome

The metabolic syndrome is a constellation of metabolic risk factors including high cholesterol, elevated blood pressure, insulin resistance, and elevated serum glucose, a pro-inflammatory state, and a prothrombotic state.

Most persons with metabolic syndrome are obese and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed of by lipid oxidation.

When obesity is present, adipose tissue becomes inflamed. This inflammation may result in a pro-inflammatory state, which could contribute to both ASCVD and diabetes.

4. What is carbohydrate overnutrition?

Most evidence supports the concept that fatty acids represent the final common pathway to tissue nutrient overload. Less attention has been given to the possible negative effects of excessive intake of carbohydrates.

Chronic overstimulation of insulin secretion induced by dietary carbohydrates could have the following adverse effects:

• The β-cell function may be impaired by chronic glucotoxicity
• Carbohydrate-induced hyperinsulinemia may suppress muscle insulin sensitivity.

Furthermore, high-carbohydrate intakes can prompt lipogenesis in the liver; fatty acids produced in this way can feed into the final common pathway of ectopic lipid accumulation. There is thus a need to look further into the role of carbohydrate overnutrition in the development of the metabolic syndrome.

5. What factors Contribute to Overnutrition?

Obesity in the United States has reached startling heights. The National Center for Health Statistics at the Centers for Disease Control and Prevention (CDC) estimated that in 2015-2016, the prevalence of obesity in the United States was 39.8% in adults and 18.5% in youth.

While obvious factors including genetics, drugs, and other medical conditions may contribute to obesity, the behavior is perhaps the most common contributor. Healthy weight on an individual level is associated with a healthy diet and regular physical activity. Restaurants serve incredibly caloric meals, with some meals containing as much as 2,000 calories. The sedentary lifestyle practiced by most adds to the epidemic.

Unfortunately, this obesogenic culture has spread to other nations, including many developing countries. China, for example, now has more than 5,000 Kentucky Fried Chicken (KFC) restaurants in 1,100 cities. Similarly, McDonald’s expects to have 4,500 restaurants in China by 2022, up from 2,500 in 2017. A growing number of Chinese households also own television sets, personal vehicles, and other technologies that reduce physical activity and facilitate weight gain.

It is of note that economic inequality in developing nations is a primary cause of both overnutrition and undernutrition. Studies conducted in India show that income inequality had the same effect on the risk of being overweight as it did on the risk of being underweight; specifically, for each standard deviation increase in income inequality, the odds of being underweight increased by 19% and the odds of being obese increased by 21%.

While some people have the resources to purchase amounts of food beyond their daily caloric requirements, others cannot meet their recommended caloric intake. However, increasing numbers of poor people are becoming overweight in more nations, as these individuals consume affordably, yet highly caloric meals, such as fast food and processed foods.

6. What then should be done to avoid overnutrition?

An approach to understanding the effects of overnutrition on the metabolic profile is through overfeeding studies. These indicate that overnutrition produces a deterioration of metabolic status. Variability in individual response is, however, is expected. Such investigations are potentially useful for identifying those who are particularly susceptible to the development of metabolic risk factors.

The host of genetic factors likely acts at tissue levels to influence the response to nutrient excess. Different people may react differently to the accumulation of fat. However, overnutrition is generally considered to trigger metabolic disorders and predispose one to chronic conditions like Type 2 Diabetes. When choosing what to eat, one should be careful to ensure they choose balanced meals rich in fiber and nutrients and avoid the modern-day fast-food craze, as there cost of bad eating is too high.

References

1. Unite for Sight (2018): Module 4: Overnutrition. Retrieved from http://www.uniteforsight.org/hunger/module4
2. NCBI (2009): From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19171470
3. NCBI(2013): Neuroinflammation in Overnutrition-induced Diseases. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389772/
4. American Federation for Medical Research (2016): Overnutrition, ectopic lipid, and metabolic syndrome. Retrieved from https://jim.bmj.com/content/jim/64/6/1082.full.pdf 
5. NCBI (2009): From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19171470

Soybean oil not only leads to obesity and diabetes but could also affect neurological conditions such as:

maternal-child bonding
autism
Alzheimer’s disease
anxiety
depression

A previous study published in 2015 suggested that soybean oil-induced obesity, diabetes, insulin resistance, and fatty liver in mice. A more recent 2020 study published in the journal Endocrinology, compared mice fed diets high in fat: soybean oil, a polyunsaturated fat vs. coconut oil, a saturated fat.

Soybean oil produced pronounced effects on the hypothalamus, which regulates body weight via metabolism, maintains body temperature, is critical for reproduction and physical growth as well as response to stress. Surprisingly, mice fed soybean oil downregulated the gene which produces oxytocin in the hypothalamus, the hormone responsible for mother-child bonding and is also known as the “love” hormone.

Nearly an additional 100 other genes were also affected by the soybean oil diet, which may have ramifications not just for energy balance, but also for brain function and diseases such as autism.

One day we will view industrial seed oils with the same disdain as cigarette smoking…

BTW: Soybean oil is polyunsaturated fat and is often touted as a healthy option over saturated fats, but the saturated fat from coconut oil, produced very few changes in the hypothalamic genes.

Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice. Endocrinology, 2020; DOI: 10.1210/endocr/bqz044.

The interplay between immunity, inflammation, and metabolic changes is a growing field of research. Exciting new evidence is emerging with regard to their role in the regulation of metabolism and the activation of inflammatory pathways during the progression of metabolic disorders such as Type 2 Diabetes and Atherosclerosis.

1. The innate immune system

The innate immune system is an evolutionarily conserved system that senses and defends against infection and irritation. Innate immune signaling is a complex cascade that quickly recognizes infectious threats through multiple germline-encoded cell surface or cytoplasmic receptors and transmits signals for the deployment of proper countermeasures through adaptors, kinases, and transcription factors, resulting in the production of cytokines.

As the first response of the innate immune system to pathogenic signals, inflammatory responses must be rapid and specific to establish a physical barrier against the spread of infection and must subsequently be terminated once the pathogens have been cleared. Long-lasting and low-grade chronic inflammation is a distinguishing feature of type 2 diabetes and cardiovascular diseases, which are currently major public health problems.

2. How does the innate immune system work?

The ability of organisms to mount a response to infectious challenge without prior exposure is regulated by the coordinated interaction of components of the innate immune system. This preformed system is important to respond to exogenous stimuli such as bacterial, viral, and fungal infections. Beyond the initial response to a stressor, the innate immune system coordinates the resolution of inflammation, tissue repair, and the activation of the adaptive immune system to provide memory for future challenges.

While much of our understanding of innate immunity comes from models of infection, it is also clear that immune responses can be triggered by endogenous stimuli. Such mechanisms play a wide role in health and disease from the response to tissue injury, the direction of tissue remodeling, and the response to tumors.

3. The Innate Immune Response to Obesity

The increased prevalence of obesity and overweight in adults continues to rise and contributes to morbidity and mortality that is estimated to cost $147 billion dollars a year in the U.S. (Finkelstein et al., 2009) and up to 0.6% of the gross domestic product of European countries (Muller-Riemenschneider et al., 2008). More ominous is the high rates of childhood obesity which is a strong predictor of adult obesity (Lee et al., 2009). This has also shifted the prevalence of adult diseases such as type 2 diabetes and pre-diabetes into childhood and has generated new treatment and prevention challenges (Lee, 2006; Lee et al., 2006). Relevant to this review, increases in inflammatory biomarkers such as C-reactive Protein (CRP) and neutrophilia are seen in obese children as young as 3 years of age (Skinner et al., 2010). This indicates that many of the origins of obesity-induced inflammation may actually be initiated during childhood. Therefore, many people will face a lifetime threat to health from obesity.

The long term duration of obesity-induced inflammation makes it challenging to describe this unique type of inflammatory activation based on classical models of innate immunity. Applying such models may be inaccurate and insufficient to encompass the events that are triggered by obesity in metabolic tissues such as fat. Furthermore, it is clear that the inflammation generated by obesity is not as high in amplitude as those seen in acute infectious settings (Hotamisligil, 2006). These unique challenges have led to the coining of the term “metal inflammation” to describe the chronic low-grade inflammatory events that occur in obesity and its associated diseases.

A frequently asked question is why would obesity trigger an immune response? For the most part, this question remains unanswered, but one answer to this may lie in the fact that many of the key regulators of metabolism also play critical roles in regulating inflammatory responses.

4. Inflammation as a link between obesity and disease

The interest in obesity-induced inflammation relates to the understanding that inflammatory mechanisms are central to the pathogenesis of diseases such as heart disease that is modified by obesity.

It is impossible to cover the scope of all of these diseases so we will focus our attention on the inflammatory mechanisms of fatty liver disease and Type 2 Diabetes-related diseases with fundamental alterations in nutrient control derived from pro-inflammatory inputs. This will set the stage for future discussion of the innate immune components activated in obesity. I will highlight both clinical and pre-clinical studies in animal models of obesity that have built our understanding of the mechanisms that drive obesity-associated diseases.

4.1 Non-alcoholic Fatty Liver Disease (NAFLD)

The liver plays a critical role in the regulation of glucose and lipids levels in the blood. Obesity generates a number of physiologic changes in hepatocyte glucose production as well as lipid oxidation and storage. Unusual hepatic lipid accumulation is connected to many obesity-associated illnesses that include non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome. The metabolic changes that occur with hepatic lipid accumulation include hepatic insulin resistance which is related to inflammatory cytokine signals.

4.2 Type 2 Diabetes (T2D)

The regulation of glucose metabolism is securely coordinated between nutrient inputs regulated by the liver and gut, nutrient utilization and storage in muscle and fat, insulin secretion by the pancreas, and central signals from the hypothalamus that coordinate these responses. The dysregulation of almost all of these processes with obesity is now known to be associated with the activation of innate pro-inflammatory pathways. The net result of this is the generation of systemic insulin resistance and hyperglycemia.

5. Why obesity affects the innate immune system

The blend of a sedentary lifestyle and surplus energy intake has led to an increased occurrence of obesity which constitutes a major risk factor for several comorbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system.

Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling.

Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity-induced chronic inflammation. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities.

References:

1. Journal of Biological Chemistry (2013): How Metabolism Generates Signals during Innate Immunity and Inflammation. Retrieved from http://www.jbc.org/content/288/32/22893.full.html
2. Physiological Reviews (2018): Innate Immune Signaling and Its Role in Metabolic and Cardiovascular Diseases. Retrieved from https://www.physiology.org/doi/abs/10.1152/physrev.00065.2017
3. NCBI (2012): Innate Immune Activation in Obesity. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888776/
4. NCBI (2015): Metabolic signals and innate immune activation in obesity and exercise. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25825956

Obesity is a disease that has plagued the modern-day man in recent times. Access to highly processed foods and a decrease in physical activity are key contributors to this ailment. Researchers are hard at work looking into what other underlying factors lead to obesity, especially given its relationship with the onset of Type 2 Diabetes, Cardiovascular diseases, and liver disease. We will take an in-depth look at metabolic inflammation and its role in the onset of obesity in this article. Let’s dive in.

1. What is obesity?

Obesity is characterized by a low-grade chronic state of inflammation in which the level of pro-inflammatory cytokines such as TNF-α, IL-6, and CRP are increased. It is a state in which there is an over-accumulation of subcutaneous and/or abdominal adipose tissue. This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation.

Obesity is diagnosed when your body mass index (BMI) is 30 or higher. To determine your body mass index, divide your weight in pounds by your height in inches squared and multiply by 703. Or divide your weight in kilograms by your height in meters squared.

BMI	Weight status
Below 18.5	Underweight
18.5-24.9	Normal
25.0-29.9	Overweight
30.0 and higher	Obesity

For most people, BMI provides a reasonable estimate of body fat. However, BMI doesn’t directly measure body fat, so some people, such as muscular athletes, may have a BMI in the obesity category even though they don’t have excess body fat.

2. What is Diabesity?

‘Diabesity’ is the term for diabetes occurring in the context of obesity. This form of obesity-dependent diabetes has emerged as a major public health problem in recent times. Though it is basically explained by insulin resistance and pancreatic beta-cell dysfunction, new patterns have evolved to explain these modifications in the context of the modern spates of obesity and diabetes.

3. Is obesity an inflammatory condition?

The connection between obesity and inflammation has been often come up in debate in the recent past. Unbeknownst to many, the link between these conditions was made decades ago. Over a century ago, high doses of a class of anti-inflammatory compounds including aspirin called salicylates were used to treat Type 2 diabetes. In some cases, the symptoms of diabetes totally disappeared. Unfortunately, this treatment was discontinued due to the serious side effects caused by the high doses of salicylates.

We will now look at the questions of our topic today in-depth; Does obesity cause inflammation, or is inflammation caused by something secondary to obesity (like high blood sugar or triglycerides)? How about diabesity? Does diabesity cause inflammation, or does inflammation cause diabesity? How and why does the body initiate an inflammatory response to diabesity? Let us tackle each item separately.

4. How does Inflammation Cause Diabesity?

We look at some lines of evidence that show that inflammation directly causes obesity and diabesity.

• The development of diabesity has been shown to follow inflammation. Raised levels of inflammatory cytokines predict impending weight gain. In a study carried out, the infusion of inflammatory cytokines into healthy, normal-weight mice caused insulin resistance. This concept is also illustrated by the fact that people with other chronic inflammatory conditions are at higher risk of developing Type2 Diabetes, for example, about one-third of chronic Hepatitis C patients develop T2DM, and those with rheumatoid arthritis are also at higher risk.
• In obesity, inflammation has been noted to start in the fat cells themselves. As fat mass expands, inflammation increases. An explanation for this may be the dysfunction of the mitochondria (the “power plant” of our cells) caused by the increased stress obesity puts on cellular function. Another mechanism may be oxidative stress. As more glucose is delivered to the fat cells, they produce an excess of reactive oxygen species (ROS) which in turn starts an inflammatory cascade within the cell.
• Further, inflammation of the fat tissue causes insulin resistance, which is the primary feature of T2DM. TNF-α, a cytokine (small protein) released during the inflammatory response, has been repeatedly shown to cause insulin resistance. Several other proteins involved with inflammation, such as MCP-1 and C-Reactive protein, have also been shown to cause insulin resistance.
• Also, inflammation of the brain (specifically the hypothalamus) causes leptin resistance, which often precedes and accompanies insulin resistance and T2DM. Leptin is a hormone that regulates appetite and metabolism. It does this through its effect on the hypothalamus. When the hypothalamus becomes resistant to leptin, glucose and fat metabolism are impaired and weight gain and insulin resistance result.
• When there is inflammation of the gut, there arises leptin and insulin resistance. This may occur via an increase in lipopolysaccharide (LPS), an endotoxin produced by Gram-negative bacteria in the gut. LPS has been shown to cause inflammation, insulin resistance in the liver and weight gain.

5. How does Diabesity Cause Inflammation?

In the past, fat was considered an inactive tissue with no biological action. It wasn’t considered for much other than storing energy. It has now emerged that fat tissue is a metabolically active endocrine organ that secretes hormones and inflammatory cytokines such as IL-6 and TNF-α. This metabolic activity of fat is the key to understanding its role in diabesity.

6. Why would obesity cause inflammation?

The first theory is that obesity-induced inflammation a protective mechanism that prevents the body from losing mobility or fitness. Fat storage is an anabolic process, which means it builds up the organs and tissues. Inflammation, on the other hand, is a catabolic process. Catabolism breaks down organs and tissues. It’s possible that the activation of catabolism via inflammation is the body’s attempt to keep weight within acceptable bounds. Evidence that experimentally induced local inflammation in fat tissue improves insulin resistance and causes weight loss supports this theory.

The second theory is that obesity-induced inflammation is simply a malfunction that was never selected against human evolution. Obesity and its related disorders have been extremely rare throughout human history, and have only become common in the past 40 years. The surplus of modern, processed foods that accompanies diabesity is also a relatively new phenomenon. It’s possible that the stresses of obesity are similar enough to the stresses of an infection that the body reacts to obesity in the same way it would to an infection: via inflammation. Supporting this theory is evidence that the same intracellular, inflammatory stress pathways are activated in both obesity and infection.

7. Tackling Inflammation in the control of diabesity

We can, therefore, conclude that inflammation is both the cause and the result of diabesity. Once obesity and/or insulin resistance have been established, each can further stimulate the production of inflammatory cytokines, forming a vicious cycle of inflammation and diabesity.
Reduction of inflammation is a major key in preventing and treating diabesity. Focusing exclusively on regulating blood sugar and fat hormones without addressing other potential causes of inflammation is bound to produce inferior results.

References

1.    NCBI (2003): Diabesity: an inflammatory metabolic condition. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14598860

2.    NCBI (2013): Obesity, Inflammation, and Diet. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819692/

3.    NCBI(2006): Inflammation and insulin resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483173/

4.    Chris Kessler (2019): How Inflammation Makes You Fat and Diabetic (And Vice Versa). Retrieved from https://chriskresser.com/how-inflammation-makes-you-fat-and-diabetic-and-vice-versa/

Nearly 77% of the US population is now overweight. This dramatic change in the last 50 years is correlated with the availability of highly processed foods, and with a dramatic increase in chronic pain.

In a mouse model, high-calorie foods, which induces a dopamine release, disrupted normal feeding schedules, resulting in overconsumption.

Additionally, the “knockout” mouse model which had dopamine signaling disrupted, didn’t seek the dietary “rewarding pleasure,” maintained a normal eating schedule, and did not become obese.

Practical Conclusion:

Diet-induced obesity requires dopamine (DA)-Drd1 signaling

Avoid eating outside a normal eating window, typically less than eight hours out of 24, allowing glycogen depletion in the liver and preventing insulin resistance.

How is this relevant to chronic pain:

I practice in the field of interventional pain, addiction, and obesity/ metainflammation.
1. Patients with chronic pain have a signaling mechanism, whether induced by medications or their endogenous pain, that causes them to seek out dopaminergic stimulation, to relieve their pain.

2. Some of these dopaminergic stimulation can be substituted by dietary intake.

3. Excessive non-nutritive dietary intake leads to obesity and visceral adipose tissue accumulation, which is inflammatory.

4. Excessive inflammatory mediators aggravate pain, and the cycle repeats.

A growing body of data shows that type 2 diabetes is at least in part rooted in inflammation. The higher a person’s body mass index, the more pro-inflammatory macrophages they have in their adipose tissue, and the higher their chances of developing T2D. In this article, we will highlight the emerging role of inflammation in the pathophysiology of diabetes. We will also analyze the implicated inflammatory pathways and biomarkers of inflammation in diabetes and metabolic diseases.

1. The metabolic syndrome and metabolic Inflammation

Metabolic syndrome often precedes type 2 diabetes and cardiovascular disease. It is characterized by high blood pressure, a large waist circumference, elevated fasting glucose and triglycerides, and low HDL cholesterol.

Metabolic inflammation is currently a hot research topic, wherein peculiarities in metabolic and inflammatory pathways are looked into for their possible contribution to atherosclerosis, Type 2 diabetes and insulin resistance (IR). In MI, insulin signaling is impeded by inflammation caused by obesity. Metabolically activated macrophages are key cells in the process. They are believed to spike both pro- and anti-inflammatory pathways in reaction to lipid spillover from adipocytes.

Diabetes is a complex metabolic disorder affecting the glucose status of the human body. The main clinical diagnostic features are impaired glucose tolerance and hyperglycemia. These occur as the result of an absolute or relative insulin deficiency or resistance to its action. Chronic hyperglycemia associated with diabetes can result in end-organ dysfunction and failure which can involve the retina, kidneys, nerves, heart and blood vessels. There is a  clinical relationship between diabetes and atherosclerotic cardiovascular disease, with the risk for cardiovascular disease (CVD) being significantly elevated in patients with diabetes.

Typically, CVD occurs one to two decades earlier in people with diabetes, with the more aggressive, severe and diffuse distribution. The first WHO Global report on diabetes published in 2016 demonstrates that the number of adults living with diabetes has almost quadrupled since 1980 to 422 million adults and this is expected to rise to 552 million by 2030. There is, therefore, a need for effective novel therapeutic approaches for the treatment and/or prevention of diabetes and atherosclerotic disease.

Various proposals and hypotheses have been developed to describe the mechanisms involved in the propagation of diabetes, mainly focusing on T2D. The increase in the prevalence of the condition has been related to well-recognized risk factors, such as the adoption of a western lifestyle, sedentary lives, lack of physical activity and an energy-dense diet.

Genetic predisposition, ethnicity, and aging are not modifiable risk factors for T2D. Other factors such as being overweight or obese, an unhealthy diet, insufficient physical activity and smoking are modifiable through behavioral and environmental changes. However, increasing evidence has shown that inflammatory pathways are common in both modifiable and non-modifiable factors.

2. When was inflammation first thought to cause diabetes?

Observational studies provided the first evidence for the possible association between inflammation and diabetes. Over a century ago, the administration of high doses of sodium salicylate led to decreased glycosuria in people with a suspected or definite diagnosis of diabetes.  Later studies on the role of inflammation in diabetes revealed that this hypoglycaemic action was related to the inhibition of the serine kinase IkappaB kinase-beta (IKKbeta), which correlates with the post-receptor action of insulin.

A landmark study to correlate inflammation with diabetes was conducted in animal models by Hotamisiligil et al., in 1993 and it revealed that the role of tumor necrosis factor-alpha (TNF-alpha) in obesity and particularly in insulin resistance and diabetes. Epidemiologic associations of inflammation with obesity and T2D were made when circulating concentrations of markers and mediators of inflammation and acute-phase reactants including fibrinogen, C-reactive protein, interleukin (IL)-6, plasminogen activator inhibitor-1, sialic acid, and white cells, have been shown to be elevated in these conditions.

Over the next decades, numerous studies on human and animal models provided further supporting evidence for the role of inflammation in the initiation and progression of diabetes. Accumulative evidence suggests that chronic activation of pro-inflammatory pathways in target cells of insulin action may contribute to obesity, insulin resistance and related metabolic disorders including T2D. The identification of potential pathways connecting inflammation to diabetes has produced growing interest in targeting inflammation to help prevent and control diabetes and related conditions, as well as improving risk stratification for diabetes by using inflammatory biomarkers as potential indexes.

3. What is the relationship between Metabolic Disorders and Inflammation in Type 2 Diabetes?

In several pathophysiological studies carried out, our understanding of insulin resistance and secretion in the course of disease onset and progression has been expanded. Subjects at risk of T2D display an initial state of insulin resistance compensated by hypersecretion of insulin in the beta cells. In the clinical course of the disease this pancreatic functional reserve is eventually unable to cope with the required insulin secretion and by the time diabetes is diagnosed, beta cells are no longer able to secrete enough insulin.

Although the relative contribution of beta-cell dysfunction and insulin resistance can vary in people with T2D, it is generally accepted that abnormal insulin sensitivity precedes the clinical diagnosis of diabetes by up to 15 years. Therefore, along with mechanistic studies investigating mechanisms forming the basis of insulin resistance, more recent research has also focused on the pathways leading to beta-cell failure.

4. Is there evidence of Inflammation in Other Organs in People with Type 2 Diabetes?

There is inconclusive evidence that the inflammatory state in T2D can spread to other organs such as the liver, the neural system and possibly skeletal muscle. More research is needed to support this evidence.

5. What are the Future Perspectives for the Treatment of Diabetes?

Below are some of the approaches currently being investigated.

1. Innovative approaches on T2D to gauge anti-inflammatory diets and moderate an individual’s microbiome are under study.
2. Clinical trials examining the effects of vitamin D supplementation on serum levels of inflammatory markers have provided inconsistent results, with no evidence of effects in most trials, or effects on selected markers in others.
3. There are also studies investigating whether antagonists of leukotriene production enzymes – 5-lipoxygenase (5-LO), 5-LO-activating protein and LTA4 hydrolase – or receptor binding BLT1 have cardiometabolic outcome benefits, however, these results have not yet been reported.
4. The potential for targeting cholinergic pathways, immune modulation or other mediators of inflammation such as JNK and toll-like receptors (TLRs) are also being researched.
    

6. What is the future of understanding metabolic inflammation as a cause of diabetes?

Given the increasing prevalence of diabetes, it is crucial that research focuses on its prevention as well as its treatment. Heart disease, metabolic syndrome and type 2 diabetes (T2D) all have in common the increased concentration of circulatory cytokines as a result of inflammation. Inflammatory cytokines are produced by different cell types and secreted into the circulation, where they regulate different tissues through their local, central and peripheral action.

An improved understanding of the mechanisms linking inflammation to diabetes and related complications has stimulated interest in targeting inflammatory pathways as part of the strategy to prevent or control diabetes and its complications.

T1D is considered to be more of an immunological response rather than a metabolic disorder and the preliminary results of trials using anti-inflammatory and immunomodulatory medication are promising. These treatments in combination with the possible use of stem cells to regenerate pancreatic beta cells could potentially be the key to the permanent treatment of T1D. Therefore, after a holistic review of the possible mechanisms that lead to T1D and T2D and the numerous already described inflammation pathways that are involved, it becomes more and more clear that future research should focus on simultaneous suppression of various inflammatory response pathways rather than focusing on one pathway at a time.

References

1. NCBI (2017): Nutritional modulation of metabolic inflammation. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28710289

2. EM-Consulte (2012): Inflammation and type 2 diabetes. Retrieved from https://www.em-consulte.com/en/article/735580

3. ECR (2019): The Role Of Inflammation In Diabetes: Current Concepts And Future Perspectives. Retrieved from https://www.ecrjournal.com/articles/role-inflammation-diabetes-concepts-future