The Role of Hyperglycemia-Induced Endothelial Dysfunction in Diabetes, Atherosclerosis and Inflammatory Disorders

Author: VP Grewal, MD. 2020 Apr 12

The prevalence of type 2 diabetes mellitus (T2DM) has tripled in the past three decades, with 2014 figures estimating 422 million diabetics worldwide. Additionally, half of those with diabetes are currently undiagnosed. Hyperglycemia is the primary feature of T2DM, and is most often caused by metabolic abnormalities. Pre-diabetes precedes the onset of T2DM by several years and encompasses early metabolic changes called impaired fasting glucose. Vascular complications in T2DM increase in proportion to the duration of hyperglycemia. Chronic hyperglycemia triggers endothelial dysfunction, the primary factor in the pathogenesis of diabetic vascular complications. Furthermore, emerging research has identified hyperglycemia induced endothelial disfunction to play a significant role in the pathogenesis of atherosclerosis and other inflammatory disorders.

Endothelial cells (ECs) line the internal surface of all blood vessels, and serve as a barrier between circulating blood and tissues. ECs are crucial in the regulation of vascular tone and maintenance of vascular homeostasis. Under normal physiological conditions, ECs exist in a dormant state, but under various mechanical and chemical stimuli, ECs synthesize and secrete many vasoactive substances and growth modulators. ECs are particularly sensitive to changes in blood glucose levels, and hyperglycemic conditions induce acute endothelial inflammation, and a prolonged pro-inflammatory state leading to endothelial dysfunction.

Endothelial dysfunction is characterized by a loss of balance between vasoconstrictors and vasodilators, growth promoting and inhibiting factors, pro-atherogenic and anti-atherogenic factors, and pro-coagulant and anti-coagulant factors. This disruption in vascular homeostasis is caused by reduced nitric oxide production, increased endothelial permeability, increased expression of adhesion molecules, and increased apoptosis. Endothelial dysfunction is responsible for the vascular complications associated with T2DM, and is believed to play a significant role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis, asthma, cerebral small vessel disease, and autoimmune disorders such as inflammatory bowel disease. Furthermore, emerging research has identified endothelial dysfunction as an early pivotal event preceding the development of coronary artery atherosclerosis.

Researchers hypothesize the risk of developing autoimmune diseases, diabetes, and atherosclerotic coronary artery disease to be directly related to the number, intensity and duration of hyperglycemic events. The modern diet is rampant with refined sugar products and beverages with high-fructose corn syrup which cause massive spikes in blood glucose levels. A simple dietary modification to reduce hyperglycemic episodes and associated endothelial dysfunction is to supplement sugar with low-glycemic alternatives such as vitaSWEET, an all-natural sugar alternative, that is as sweet as sugar, bakes like sugar, but without the metabolic consequences.


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Dietary Sugar and the Childhood Obesity Epidemic

Preventing childhood obesity is vital due to its association with lifelong obesity, metabolic disorders such as type-2 diabetes mellitus and hypertriglyceridemia, obesity-related cancers, in addition to psychosocial repercussions and decreased educational attainment. From 1975 to 2016, mean BMI and obesity rates in children and adolescents aged 5-19 years have increased globally and in most regions.

Added sugar consumption is the primary factor associated with childhood obesity trends, in addition to being associated with other detrimental health conditions such as dental caries, asthma, altered lipid profiles, hypertension, and cancer. A 2019 analysis of data compiled from the Centers for Disease Control and Prevention (CDC) from 2011 to 2016 revealed 98% of American toddlers and 60% of infants consume added sugar in sweetened foods and beverages. Sweet bakery products were in the top 3 sources of added sugar for both toddlers and infants. Previous studies examining sugar intake in older children (aged 2-8 years) also reported sweet bakery products to be one of the top three sources for added sugar. Fruit drinks, yogurt, and sugar-sweetened beverages were other important sources of added sugar identified by researchers. In 2015, the World Health Organization (WHO) and the American Heart Association (AHA) recommended limiting added sugars consumption to <10% of total caloric intake for children aged 2 to 19 years. In 2017, the AHA released a statement advising children less than 2 years to old to avoid consuming added sugars entirely. The most recent analysis of CDC data revealed about 70% of American children older than 2 years exceed recommendations for added sugars intake.

Infants and children around the world exhibit a heightened preference for sweetness, most likely a biological underpinning to confer advantage in environments of scarcity. Moreover, emerging research has shown significant similarities in neurochemistry and behavior between consumption of added sugars and drug-like effects, including bingeing, craving, tolerance, withdrawal, cross-sensitization, cross-dependence, reward and opioid effects. Sugar addiction appears to develop as a result of natural endogenous opioids released upon sugar consumption. The opioid-like pain reducing properties of sugar are evident from birth. A sweet solution placed in a newborns mouth, elicits facial relaxation, often accompanied with a smile. Furthermore, something sweet placed on the tongue of a crying newborn produces an instantaneous calming effect. In another study, sucrose consumption delayed pain reporting in children aged 8 to 11 years old undergoing a cold-induced pain stimulus test, whilst having no effect in adult. Evolutionary driven taste preferences, coupled with heightened response to natural endogenous opioids produced upon sugar consumption make infants and children more vulnerable to sugar addiction than adults.

While it may not be reasonable to eliminate sweet foods entirely from a child’s diet, substitution of sugar with an all-natural sweetener such as vitaSWEETis a practical approach to abate the rising trends in childhood obesity and other detrimental health ailments associated with added sugar consumption. vitaSWEET is as sweet as sugar, zero calories, has no effect on blood glucose levels, and is safe for children.




vitaSWEET – an ancient alternative as sweet as sugar, but without the metabolic consequences

Much of illness afflicting modern society can be attributed to changes in eating patterns.  In the past 160 years the amount of sugar consumed by society has exploded, attributed to the mechanization of sugar production.  This trend is not limited to the developed world, but has impacted almost every country on the planet.  Sugar is not only found in obvious foods such as deserts, it has also become a hidden ingredient in many foods available on the market today.  In recent years, financial incentives have driven companies such as Pepsi and Coca Cola to replace sugar with sugar with high-fructose corn syrup in certain products, such as soft drinks and processed foods.

Both sugar and high-fructose corn syrup are very high on the glycemic index, meaning that they cause blood glucose levels to rise rapidly.  This shocks the body, which responds by releasing massive amounts of insulin to drive the excess sugar into the cells of the body.  Over time, a constant elevation of blood glucose and insulin levels, leads to a the development of insulin resistance, a compensatory response in which the cells remove insulin receptors from their membrane. The subsequent effect is an even greater amount of insulin required to return blood glucose levels to normal amounts.  Eventually this leads to the development of diabetes mellitus.

In addition to diabetes, recent literature has correlated elevated blood glucose levels and insulin resistance with a wide array of health problems, including obesity, metabolic syndrome, hypertension, dyslpidemia, and hepatic steatosis. Furthermore, a high baseline insulin level is also highly inflammatory and can worsen autoimmune conditions such as arthritis, inflammatory bowel disease, multiple sclerosis, and vasculitis.

vitaSWEET is a natural alternative to table sugar and high fructose corn syrup, that is 0 on the glycemic index, meaning that it has no effect on blood glucose levels.

vitaSWEET is formulated with two simple ingredients: monk fruit and erythritol.  Monk fruit or luo han guo is native to southern China and northern Thailand, and has almost 300 times natural sweetness than that of sugar.  It has been used for centuries in traditional Chinese medicine, first mentioned in the records of 14th century Chinese monks.  Erythritol is a naturally occurring sugar alcohol derived from fruits and plants.  Vita Columbia’s unique blend of both monk fruit and erythritol is as sweet as sugar and can be used as a 1-to-1 replacement in recipes.

Sugar Consumption in the United States 1822 - 2016

United States Sugar Consumption, 1822-2016

“In addition to diabetes, recent literature has correlated elevated blood glucose levels and insulin resistance with a wide array of health problems, including obesity, metabolic syndrome, hypertension, dyslpidemia, and hepatic steatosis.”

World Sugar Consumption 1960 – 2006

Sugary Drink Consumption by CountrySales of sugary drinks by country