LETS TALK CARDIO METABOLIC SYNDROME AND RISK FACTORS

Uncontrolled insulin resistance and glucose levels in the blood have been well documented in the literature for many years.

Worldwide, an estimated 1.5 billion people are overweight with 300-500 million of those obese.  The places nearly a QUARTER of humanity at dramatically increased risk for diabetes, cardiovascular disease and many types of cancer. (2)

Patients with diabetes are considered high-risk patients for acquired infections, and among the risk factors is circulating glucose. It was noted that the higher the glucose, the higher the risk of infections. Additionally, most patients with diabetes develop over time, co-morbidities that increase such risks.

  • The comorbidity burden tended to increase in older age groups and was higher in men than women. The most common conditions in patients with T2DM included hypertension (HTN) in 82.1%; overweight/obesity in 78.2%; hyperlipidaemia in 77.2%; chronic kidney disease (CKD) in 24.1%; and cardiovascular disease (CVD) in 21.6%. (3)

Sterling Hill reminds us that we are seeing a cumulative effect in the form of metabolic disturbances in younger folks (e.g., type II diabetes) that were previously, typically associated with aging. It is therefore imperative to eat clean, do our best to limit exposures to chemicals, and high frequency RF signals, lower stress, and address methylation enzymatic pathway deficits. (4)

The degree of insulin resistance increases with age and may accelerate the ageing process.  Insulin resistance observed in the aging is directly linked to obesity.

A link between chronic inflammation along with obesity and insulin resistance has been related to the proinflammatory cytokine tumour necrosis factor (TNFa) which directly causes insulin resistance. Neutralisation of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity. (5)

  • Diabetic individuals are at a high risk for infection
  • The higher the glucose reading, the higher the risk of infection
  • Eventually, most patients with diabetes develop further comorbidities that increase this risk
  • Obesity, Insulin resistance and aging are associated with chronic, systemic low-grade inflammation
  • Metabolic disorders are being noted in younger population whereas it was once associated with aging

Consequences of Insulin Resistance

Factors noted in Insulin Resistance

  • Excess body weight
  • Excessive Carbohydrate intake
  • Sedentary Lifestyle
  •  Genetics

Leads to

  • Cardiomyopathy
  • Neurological changes – Urinary frequency, Light-headedness, Bloating, Heartburn, Constipation
  • Increase of Intra-abdominal Fat
  • Elevated Blood sugar
  • Hypertension (High Blood Pressure)
  • Elevated Triglycerides
  • Low HDL (good cholesterol) (needed for hormone production and synthesis)
  • Increased risk of blood clots
  • Atherosclerosis – a contributing factor of Heart Attack, Stroke and Peripheral Vascular Disease
  • Polycystic Ovarian Disease
  • Sleep apnoea
  • Inflammation of the liver, Non-alcoholic fatty liver disease (NAFLD) and Cirrhosis

Why do obese patients present a worse clinical picture than lean subjects?

Basal hormone conditions, defective response of both innate and adaptive immune system and sedentariness are major contributing factors in the severity of influenza viral infection in obese patients. Current research indicates that being overweight not only increases the risk of infection and of complications for the single obese person, but a large prevalence of obese individuals within the population might increase the chance of appearance of more virulent viral strain, prolongs the virus shedding throughout the total population and eventually might increase overall mortality rate of an influenza pandemic.

During the 2009 Influenza A virus (IAV) H1N1 pandemic, obesity was also linked to increased risk of severe disease and a risk factor for hospitalization and death.

Research findings into comorbidities state that obese and obese-diabetic subjects have an alteration at different steps of the innate and adaptive immune response, characterised by a state of chronic and low-grade inflammation. This pathway contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders.

Results of publications maintain that obese subjects have chronically higher leptin (a pro-inflammatory adipokine) and lower adiponectin (an anti-inflammatory adipokine) concentrations. This unfavourable hormone condition also contributes to a dysregulation of the immune response and can contribute to the development of obesity-linked complications. In addition to the obvious positive effect of weight loss, caloric restriction activates AMP-kinase, potentiating the immunomodulatory effect of physical exercise (6)

  • Historically, obesity is linked to increased risk of severity and risk factor for hospitalisation and death during viral pandemics
  • Current research indicates obesity increases the risk of infection and complications
  • Obesity within the population may increase the virulence of a viral strain, prolong the viral shedding and may increase overall mortality of rate of a pandemic
  • Obese and diabetic population have an alteration in both innate and adaptive immune responses
  • Obese & diabetic subjects exhibit a state of chronic and low grade inflammation leading to systemic metabolic dysfunction
  • Imbalanced hormones contribute to a dysregulated immune response contributing to the development of obesity-linked complications
  • Immune modulation effect activated by weight loss, caloric restriction following the implementation physical exercise

METABOLIC SYNDROME TNF-A IL-6, ADIPONECTIN

Metabolic syndrome is a complex of clinical features, the most important of which is an increased visceral (ORGAN) fat deposition. Obesity results in a proinflammatory state starting in the metabolic cells (adipocyte, hepatocyte, or myocyte) and also recruiting immune cells with the consequent release of inflammatory cytokines (TNF-α, IL-6, adiponectin, etc.). It has been hypothesised that the obesity-induced inflammatory process may lead to complications such as hypertension, atherosclerosis, dyslipidaemia, insulin resistance, and diabetes mellitus, all characteristic of metabolic syndrome. (Il-6 is produced by Macrophages)

The link between obesity and inflammation has been derived from the finding that proinflammatory cytokines are overexpressed in obesity.

With obesity and progressive adipocyte enlargement, the blood supply to adipocytes may be reduced with consequent hypoxia. Hypoxia has been proposed to be an instigator of necrosis (cell death) and macrophage infiltration into adipose tissue that leads to an overproduction of proinflammatory factors like inflammatory chemokines.

The result is localised inflammation in adipose (fat) tissue that propagates an overall systemic inflammation TNF-α. It is a proinflammatory cytokine that exerts numerous effects in adipose tissue including lipid metabolism and insulin signalling whose circulating levels are increased with obesity and decreased with weight loss associated with the development of obesity-related comorbidities.

An increase in TNF-α promotes the secretion of other proinflammatory cytokines IL-6 and TNF-α, and reduces anti-inflammatory cytokines like adiponectin. Evidence suggests that TNF-α induces adipocytes apoptosis, and promotes insulin resistance by the inhibition of the insulin receptor substrate 1 signalling pathway.

The primary source of circulating IL-6 is macrophages that have infiltrated WAT; IL-6 has an important role in the regulation of whole-body energy homeostasis and inflammation.

Adiponectin regulates lipid and glucose metabolism, increases insulin sensibility, regulates food intake and body weight, and protects against chronic inflammation. Weight loss has been shown to increase adiponectin levels.  Human studies show that hypoadiponectinemia is associated with insulin resistance, hyperinsulinemia, and the possibility of developing type 2 diabetes, independent of fat mass. (7)

High levels of inflammatory markers have been associated with increased morbidity and mortality in older persons. In addition, higher interleukin-6 (IL-6) levels in community-dwelling elderly persons have been associated with physical disability.

Medical conditions such as diabetes mellitus, cancer, (subclinical) atherosclerosis, congestive heart failure and rheumatoid arthritis and lifestyle factors such as smoking all have been associated with higher levels of proinflammatory cytokines.

In conclusion, higher plasma concentrations of IL-6 and TNF-a are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels may contribute to the loss of muscle mass and strength with aging also called sarcopenia. (8)

  • Metabolic syndrome may lead to complications such as high blood pressure, hardening of the arteries, increased lipid profiles, insulin resistance and diabetes
  • High levels of inflammatory markers increase morbidity and mortality in the elderly
  • High levels of proinflammatory cytokines have been noted in many medical conditions, including diabetes, cancer, atherosclerosis, heart failure, RA
  • Proinflammatory cytokines are overexpressed in obesity and Covid-19

UFORIA

Key Genes: TNF-a

Inflammatory Response Gene or TNF- ars1800629

WHAT IS THE PURPOSE OF THE TNF-a

The TNF-a gene helps regulate a healthy inflammatory response.

WHY IS THIS GENE IMPORTANT?

TNF-a gene regulates the production of TNF-a, a chemical messenger (cytokine) of the immune system that plays a role in inflammatory processes.

Inflammation is the body’s immune system response to attack from various sources such as pathogens, damaged cells, or irritants. Aging also results in an increased level of cytokines. TNF-a mobilizes white blood cells in response to infections and injuries.

While that response is helpful in the short term, if the inflammatory response becomes unbalanced (too much TNF-a), it can negatively affect the cells, tissues, and ultimately, the organs. An optimal inflammatory response requires a healthy balance of TNF-a.

DIETARY RECOMMENDATIONS FOR TNF-a GENE:

The TNF-a SNP is supported by ingredients that specifically help regulate TNF-a levels, support a healthy inflammatory response and help fight the increased production of free radicals caused by high levels of TNF-a and aging.

Polyphenols from Green Tea, Grape Seed, and Pomegranate Extracts • Increased polyphenol consumption supports overall health and healthy aging, reduce the expression of TNF-a as shown in both in vitro studies and animal studies and humans, modulate inflammatory response in humans.

• Polyphenols in pomegranate support modulation of inflammatory cell signalling by suppressing TNF-a induction of various inflammatory proteins. • Polyphenol compounds in grape seed extract, known as proanthocyanidins or OPCs, help reduce the expression of the vascular cell adhesion molecule-1 gene (VCAM-1),71 which plays a critical role in healthy inflammatory responses. VCAM-1 is induced by TNF-a.

Milk Thistle Extract (Silymarin)

• Silymarin helps reduce TNF-a induced activation of NF-kB. NF-kB is a nuclear transcription factor which regulates the expression of various genes involved in the inflammatory response, helps protect against TNF-a induced production of reactive oxygen species in lipid peroxidation, supports the inhibition of TNF-a gene expression,.

Individuals with a SNP in this gene can benefit from supplementation with ingredients that:

• Inhibit TNF-a activity

• Fight the increased production of free radicals caused by high TNF-a

• Support a healthy inflammatory response

UFORIA

Healthy Immune System or IL6

rs1800795

WHAT IS THE PURPOSE OF THE

IL6 GENE?

IL-6. Interleukin 6 is a well-known pro-inflammatory cytokine. It is produced by macrophages and adipocytes (fat cells). Increased levels of IL-6 are found in obese people. IL-6 crosses the blood brain barrier and can lead to increased body  temperature.

WHY IS THIS GENE IMPORTANT?

IL-6 is associated with a whole host of chronic diseases including diabetes, atherosclerosis and Alzheimer’s disease. In addition, IL-6 is associated with many autoimmune disorders such as rheumatoid arthritis.

Under stress, our cortisol levels rise as do IL-6 levels. Chronically increased IL-6 increases the susceptibility to viral and other infections.

DIETARY RECOMMENDATIONS FOR

IL6 GENE:

Turmeric Root Powder

• Turmeric contains a yellow coloured curcuminoid compound called curcumin. In addition to being used as a spice for thousands of years, turmeric has been used as well as a medicinal herb for its strong anti-inflammatory properties as well as its

value as an antioxidant.

• Curcumin in turmeric also blocks NF-kB, a nuclear transcription factor which regulates the expression of various genes involved in the inflammatory response.

Individuals with a SNP in this gene can benefit

from supplementation with ingredients that:

• Support immune function

• Support a healthy inflammation response

1.            Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020:1-8.

2.            Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804-14.

3.            Iglay K, Hannachi H, Joseph Howie P, Xu J, Li X, Engel SS, et al. Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus. Curr Med Res Opin. 2016;32(7):1243-52.

4.            Sterling Hll Compiled by Cynthia Smith B, JD, With contributions by Sterling Hill Erdei and Carolyn Ledowsky N. SNPBit Compendium 2019.

5.            Hotamisligil G, Shargill N, Spiegelman B. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87-91.

6.            Luzi L, Radaelli MG. Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic. Acta diabetologica. 2020.

7.            Emanuela F, Grazia M, Marco de R, Maria Paola L, Giorgio F, Marco B. Inflammation as a Link between Obesity and Metabolic Syndrome. Journal of nutrition and metabolism. 2012;2012:476380.

8.            Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, et al. Relationship of Interleukin-6 and Tumor Necrosis Factor-N1 With Muscle Mass and Muscle Strength in Elderly Men and Women: The Health ABC Study. The Journals of Gerontology: Series A. 2002;57(5):M326-M32.

9.            Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. LID – 10.23812/20-Editorial-Kritas [doi]. (0393-974X (Print)).