Insulin Resistance

When blood glucose levels rise too high the body attempts to restore a healthy level by releasing insulin from the pancreas (exposure to insulin encourages cells in the body to draw glucose from the bloodstream). If, however blood glucose levels are chronically* high, meaning that cells throughout the body are chronically exposed to insulin, they lose their sensitivity to insulin's effects, and become what is called 'insulin resistant' (IR).
As the cells in the body become insulin resistant they ...

• are increasingly unable to draw glucose from the blood and
  
• become low in glucose (hypoglycaemic)
  

…leading to:

• lower energy production by the cells
  
• higher storage of fat in the body
  
• raised blood glucose, fat and insulin levels, and
  
• reduced function
  

Two examples:

• IR liver cells are less able to fulfill one of their major roles: the regulation of glucose and fat levels in the blood, resulting in even higher blood levels of both
  
• IR brain cells are less able to think and focus
  

Other symptoms of IR include:

• illnesses like obesity, diabetes and metabolic syndrome
  
• increased hunger
  
• weight gain, fat storage and difficulty losing weight
  
• intestinal bloating
  
• sleepiness, especially after meals
  
• raised blood pressure
  
• depression
  
• raised levels of pro-inflammatory cytokines*
  

The major cause of IR is almost certainly (i) the intake of excessive energy - via a diet containing high levels of the sugars glucose, fructose, galactose and sucrose (see Edi), combined with (ii) the insufficient burning of energy due to low levels of exercise. It is probably the source illness and principal cause of type 2 diabetes, obesity and other metabolic disorders (see Ediii and Ediv), and a major risk factor for cardiovascular disease
and Alzheimer’s disease (see Edvi)¹


Other risk factors for IR
There are other factors that can increase a person’s risk of developing IR. For instance:

• Excessive body fat, particularly round the belly. Fat was once considered to be only a passive form of energy storage. Now we know that certainly belly fat and perhaps other fat around the body produces hormones and other substances that can themselves promote IR, inflammation, high blood pressure, imbalanced cholesterol and cardiovascular disease (CVD). Some studies suggest that losing belly fat can reduce IR
  
• Insufficient exercise. Taking exercise insufficient in both duration and intensity promotes raised blood glucose levels, but there is more. After exercising, muscle cells become less insulin-resistant and can even absorb glucose from the blood without the presence of insulin. The more exercise and muscle a body has the more glucose it can absorb
  
• Insufficient nutrients in the body. Good levels of vitamin D, for instance, are known to promote both appropriate insulin production by the pancreas and appropriate insulin sensitivity in the cells
  
• Stress and depression. Chronic stress and depression are increasingly recognised as independent risk factors for decreased insulin sensitivity³
  
• Chemical polution. Exposure to chemical pollution (e.g. pesticides, the fumes from tobacco-based cigarettes and e-cigarettes) have been linked to IR. Endocrine-disrupting environmental toxins (sometimes called ‘obesogens’) have been linked with obesity.
  

Perhaps the true link is with IR, which leads to obesity

• Medications. Steroid hormones have been found to promote IR. Medications like psychotropic,* anti-diabetic and anti-hypertensive drugs, contraceptives, anti-histamines and anti-HIV/AIDS drugs have been shown to promote obesity. Again, is the true link with obesity or with IR?
  
• Genetic factors. Some people’s bodies cope less well with chronic high levels of insulin, or with (e.g.) exposure to various environmental toxins, than other people’s bodies because, e.g.:
  
  • genetic factors - their ancestors’ bodies were genetically less able to cope
    
  • epigenetic factors - their parents’ or grandparents’ bodies had been chronically exposed to a toxin or hardship (e.g. a famine) that had changed their genes - changes they have passed on, making the bodies of their children and grandchild less able to cope
    
  • they were exposed to health-damaging factors at critical times between conception and birth, e.g. some negative factor in their father’s sperm or mother’s egg (perhaps due to greater age), an obese mother, or exposure of the mother to a toxin
    

Editorial
(i) Sugars The word ‘sugar’ is the ‘umbrella term’ for sweet, short-chain, soluble, carbon-hydrogen-oxygen compounds (carbohydrates), many of which occur or are used in food. There are many types of sugar. Here we are concerned with ‘simple sugars’ called monosaccharides, such as glucose (also known as dextrose), fructose and galactose, and with the two-monosaccharide compound sucrose (a disaccharide) that breaks down in the body into fructose and glucose.
(ii) High fructose corn syrup (HFCS) High fructose corn syrup (called isoglucose, glucose/fructose syrup or frucose/glucose syrup in Europe) is an unnatural/artificial/refined sweetener made from corn/maize starch by modifying its sugar profile (100% glucose). The fructose content of HFCSs used to sweeten foods (e.g. breads and cakes, cereals, yogurts, soft drinks and soups) is usually either 58% glucose/42% fructose or 45% glucose/55% fructose. For comparison, the fructose content of grapes and apples is 5-10%, the fructose content of vegetables, milk and meat even lower.
HFCS can now be found in many sweetened fruit juices and processed foods bought from shops (particularly in the US). Health campaigners allege links with the rises in obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease. Not surprisingly, the refined corn industry hotly contests these. It promotes the idea that HFCS is ‘natural’ and (reminiscent of the biotech industry’s claims of ‘substantially equivalent to nature’ for its genetically-modified products) not significantly different to sugar from sugar cane or sugar beet.

In the supplement to Green Health Watch Magazine 28 we reported a small study by Karen Teff and colleagues at the University of California’s Monell Chemical Senses Center. It found that the human body appeared to react to glucose and fructose differently. Twelve women of normal weight were given meals identical in terms of calories, fats, carbohydrates and protein content for two days. With each meal they were given a soft drink sweetened with equal amounts of either fructose or glucose.

• The women who drank the fructose-sweetened drinks experienced:
  
  • temporary reductions in circulating levels of insulin and leptin, the principal hormones controlling appetite stimulation or suppression
    
  • temporary reductions of ghrelin, another appetite-stimulating hormone
    
  • a long-lasting increase of triglycerides*
    

Fructose researchers George Bray and Barry Popkin contended that the added sweetness may actually stimulate the appetite rather than satisfy it.²
(iii) Metabolic disorders The most common ‘metabolic disorders’ are type 2 diabetes, obesity, impaired glucose tolerance, high blood insulin, cholesterol or fat levels (dyslipidemia), high blood uric acid levels (hyperuricemia), high blood triglyceride levels (hypertriglyceridemia) and hypertension. Metabolic disorders are not to be confused with ...
(iv) Metabolic syndrome Metabolic syndrome (previously called ‘syndrome X’) is the umbrella term for a cluster of conditions - high blood pressure, high blood sugar level, excessive body fat around the waist and raised blood cholesterol and/or triglycerides and/or insulin levels - that occur together in various combinations, increasing the risk of developing heart disease, stroke and diabetes. You need to have at least two of the conditions listed above to have ‘metabolic syndrome’. It is now thought to affect 24% of UK and US adults.⁴
(v) Average fasting blood insulin levels According to the US National Health and Nutrition Examination (NHANES) III survey,⁵ the average fasting blood insulin level in the US is around 8.8 microInternational Units per millilitre (microIU/mL) for men and 8.4microIU/mL for women. A study that compared the fasting blood insulin levels of Swedes and the Kitavan islanders⁶ found average levels of 4-10microIU/mL in male and female Swedes, but only levels of 3-6microIU/mL when the fasting levels of the Kitavans were considered in isolation. Kitavans are lean and have extremely low rates of heart attack and stroke.
Obesity researcher Stephan Guyenet (a neurobiologist) feels that 2-6microIU/mL is within our environmental template (healthy).⁷
(vi) Insulin resistance and Alzheimer’s disease There is growing evidence (i) of raised levels of insulin resistance in people with Alzheimer’s disease, and (ii) that insulin abnormalities and insulin-resistant brain cells contribute to Alzheimer’s disease.
Many brain functions need and use insulin, including:

• the formation and functioning of memory
  
• cognitive functioning*
  
• the regulation of amyloid precursor protein and its derivative* beta-amyloid (Abeta), the main component of the amyloid plaques found in the brains of Alzheimer patients
  

The increased occurrence of insulin resistance in Alzheimer’s disease and the numerous mechanisms through which insulin may affect clinical and pathological aspects of the disease suggest that improving insulin effectiveness may have therapeutic benefit for patients with Alzheimer’s disease, concluded one study.¹


Definitions
Chronic - (in medicine) persistent and long-lasting (usually at least three months)
Cognitive function - e.g. working memory, comprehending and producing language, calculating, reasoning, problem solving and decision-making
Cytokines, pro-inflammatory - small proteins that promote systemic* inflammation
Derivative - a substance the body makes from another substance, e.g. cholesterol derivatives are substances the body makes from pure cholesterol
Plaque, senile - deposits of beta amyloid in the gray matter of the brain
Psychotropic drug - any drug that crosses the blood-brain barrier and affects brain function, resulting in alterations in perception, mood, consciousness, cognition and behaviour, e.g. anti-depressants, analgesics, anti-convulsants, anti-Parkinson’s disease and recreational drugs
Systemic - (medical) affecting the whole body, or at least multiple organ systems
Triglycerides - the major form of fat stored by the body (in the blood)

References
http://wholehealthsource.blogspot.co.uk/2011/11/what-causes-insulin-resistance-part-i.html
http://eatingacademy.com/nutrition/gravity-and-insulin-the-dynamic-duo
¹ e.g. The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. Watson,GS and Craft,S. CNS Drugs 2003;17(1):27-45 PMID: 12467491
http://www.ncbi.nlm.nih.gov/pubmed/12467491
² Bray,GA et al. American Journal of Clinical Nutrition 2004;79(4):537-43
³ Acute psychological stress results in the rapid development of insulin resistance. Li,L et al. Journal of Endocrinology 2013; 217:175-184
⁴ Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population. Harris,M et al. Diabetes Metab Res Rev. 2002 Mar-Apr;18(2):149-55. PMID: 11994907
⁵ NHANES III http://www.cdc.gov/nchs/nhanes/nh3data.htm
⁶ Low serum insulin in traditional Pacific Islanders--the Kitava Study. Lindeberg,S et al. Metabolism 1999;48(10):1216-9 PMID: 10535381
⁷ Stephan Guyenet. Whole Health Source December 2009
http://wholehealthsource.blogspot.co.uk/2009/12/whats-ideal-fasting-insulin-level.html

(16752)  Nick Anderson. Green Health Watch Magazine 47   (9.9.2014)