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Insulin Resistance, the silent killer and root cause of modern chronic disease.

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Insulin is much more than a blood sugar hormone. Produced by the pancreas primarily in response to carbohydrate and sugar consumption, insulin is a master anabolic signal that dictates how every cell in your body grows, uses energy, and repairs itself. When insulin levels are healthy, it keeps the body in a state of “build and store.” When insulin resistance (IR) develops, the body loses its ability to hear this signal, leading to systemic breakdown. Instead of “build and store” the body deteriorates, causing loss of muscle mass, strength, energy production, memory and cognitive function, bone strength, brain cells and connections, ability of blood vessels to relax, ability for the heart to pump blood, ability to achieve restorative sleep, ability of the liver and kidneys to clear toxins from the body, even the ability to reproduce resulting in infertility and erectile dysfunction. Visceral fat stores increase to destructive levels resulting in obesity and obesity-related complications including chronic inflammation which further drives IR to higher levels.

IR is a root cause of cardiovascular disease (heart attack, stroke, hypertension, heart failure), many kinds of cancer (directly linked to breast, prostate and colon cancer), kidney failure, heart failure, dementia, osteoporosis, osteoarthritis, and much more.  IR is causally linked or a contributor to, every chronic non-communicable disease of modern civilization.

WHAT IS INSULIN RESISTANCE?

Insulin resistance is the inability of cells and organs to respond normally to insulin signaling. Every cell of every organ has insulin receptors that initiate action by the cell and organ.

WHAT CAUSES INSULIN RESISTANCE?

There are many causes of IR. Stress hormones (cortisol, adrenaline), inflammation, and high insulin levels themselves (response to dietary sugar and refined carbohydrates), each alone and in combination, cause immediate (within minutes to hours) insulin resistance. When these conditions persist over time insulin resistance becomes a chronic state. As fat cells grow in size, they reach a point where there is inadequate blood flow to the cells themselves and macrophages (immune cells that reside between the fat cells, most prominently in visceral fat) produce inflammatory chemicals called cytokines. Cytokines flow through the blood stream and effect every organ and every cell in the body creating a state of chronic inflammation which further worsens IR, creating a vicious cycle. As IR continues the pancreas produces increasingly higher amounts of insulin to maintain normal blood sugar levels but eventually IR becomes so great that blood sugar levels move into the “pre-diabetes” and eventually the diabetes range. IR builds for years to decades before blood sugar regulation fails. By the time blood sugar levels are “abnormal” insulin resistance has done great damage throughout the body.

Most doctors tragically do not order fasting insulin levels as routine blood tests. Fasting insulin levels rise long before fasting blood sugars and hemoglobin A1c start to rise. Meanwhile the damage progresses under the radar of routine testing.

1. Metabolic Engines: Muscle and Liver

Muscle

  • Normal Action: Insulin acts as a key that opens “doors” (GLUT4 receptors) to let glucose in for fuel. it also stimulates protein synthesis. Protein synthesis is essential to maintaining and increasing muscle mass and strength.
  • Insulin Resistance Effect: The “doors” stay locked. Glucose stays in the blood, and the muscle becomes “starched,” leading to sarcopenia (muscle wasting) and fatigue. The muscle can no longer utilize dietary protein to maintain or increase muscle mass.

Liver

  • Normal Action: Tells the liver to stop producing glucose and start storing it as glycogen or converting excess into fat.
  • Insulin Resistance Effect: The liver ignores the “stop” signal and keeps pumping out glucose while simultaneously ramping up fat production. This results in Non-Alcoholic Fatty Liver Disease (NAFLD).

2. Fat Cells (Adipose Tissue)

Visceral (Deep Fat) vs. Subcutaneous (Under Skin)

  • Normal Action: Insulin promotes fat storage and inhibits the breakdown of stored fat (lipolysis).
  • Insulin Resistance Effect: Fat cells—especially visceral ones—become “leaky.” They spill free fatty acids into the bloodstream and release inflammatory cytokines. This causes weight gain that is biologically difficult to lose because high insulin levels keep the “fat-burning” switch permanently off.

3. The Vital Organs: Heart, Kidneys, and Arteries

Heart and Arteries

  • Normal Action: Insulin stimulates the release of nitric oxide, which helps arteries relax and dilate.
  • Insulin Resistance Effect: Nitric oxide production drops, causing arteries to stiffen (hypertension). High insulin also damages the endothelial lining, leading to atherosclerosis (plaque buildup). This is the primary driver of heart failure, heart attacks and strokes.

Kidneys

  • Normal Action: Helps regulate sodium reabsorption.
  • Insulin Resistance Effect: The kidneys hold onto too much salt, increasing blood pressure. Over time, high blood sugar and inflammation damage the filtering units, leading to chronic kidney disease (CKD).

4. The Brain, Memory, and Sleep

Brain and Memory

  • Normal Action: Insulin crosses the blood-brain barrier to regulate appetite and support synaptic plasticity (the basis of learning).
  • Insulin Resistance Effect: Often called “Type 3 Diabetes,” brain IR starves neurons of energy and allows amyloid plaques and neurofibrillary tangles to build up. Worse, the brain is unable to utilize glucose to meet energy demands it starts to malfunction. This is a direct pathway to Alzheimer’s disease and dementia. As the small arteries in the brain become atherosclerotic and unable to deliver adequate oxygen and nourishment to brain cells small areas of the brain become permanently damaged eventually leading to vascular dementia.

Sleep

  • Insulin Resistance Effect: IR is heavily linked to Obstructive Sleep Apnea. (OSA) High insulin affects the central respiratory drive and increases fat deposits around the neck (a major contributor to obstructive sleep apnea), disrupting sleep cycles and creating periods of inadequate oxygen flow to the brain resulting in the acute stress response and awakening with each apneic event. Even without OSA, high insulin levels impair the production of melatonin which is essential to normal-restorative sleep. Throughout the day the brain accumulates metabolic toxins that must be cleared through the glymphatic system at night during sleep. As sleep is impaired this clearance system is disrupted, contributing to structural damage and functional loss. Sleep disruption and apneic episodes are stressful events, increasing stress hormones which then worsen IR, creating another vicious cycle. One night of sleep disruption causes acute IR. Chronic sleep disruption contributes to chronic IR.

5. Immunity and Structural Health

Immune System

  • Action: High insulin/glucose impairs white blood cell function.
  • Effect: Chronic inflammation (high CRP levels) and a weakened defense against infections. This is why diabetics often have poor wound healing. As normal immune regulation is impaired the immune system both over-reacts and under-reacts. Under-reaction increases risk of infection. Over-reaction produces cytokine storms seen with Covid-19 and other infections. Chronic inflammation worsens IR creating another vicious cycle. Chronic inflammation contributes to most chronic diseases.

Bone and Joints

  • Action: Insulin is bone-building.
  • Effect: IR leads to poor bone quality (despite high density) and osteoarthritis due to systemic inflammation and the “glycosylation” (sugar-coating) of joint cartilage, making it brittle.

6. The Pancreas: Beta and Alpha Cells

  • Normal Action: Beta cells produce insulin; Alpha cells produce glucagon (which raises sugar). They balance each other.
  • Insulin Resistance Effect:
    • Beta Cells: Work overtime to produce massive amounts of insulin to compensate, eventually “burning out” and dying. This can produce per4manent irreversible damage to the pancreas.
    • Alpha Cells: Become resistant to insulin’s “stop” signal and keep secreting glucagon, further raising blood sugar levels which in turn cause higher insulin secretion, both of which worsen IR, creating another vicious cycle.

7. Reproductive Effects: Infertility

  • In Women: High insulin stimulates the ovaries to produce excess testosterone, which is the primary driver of Polycystic Ovary Syndrome (PCOS) and infertility.
  • In Men: IR is a leading cause of low testosterone and erectile dysfunction (due to the arterial damage mentioned above).

Summary of Systemic Effects

ConditionPrimary Mechanism of Insulin Resistance
AtherosclerosisEndothelial dysfunction, high triglycerides, low HDL, increased TG/HDL ratio, increased small dense LDL and remnant particles, increased endothelial permeability.
DementiaNeuronal glucose starvation and plaque buildup, brain small vessel disease, disruption of blood brain barrier.
Chronic InflammationRelease of cytokines from visceral fat.
Heart FailureStiffening of the heart muscle and high blood pressure.
DiabetesPancreatic beta cell and alpha cell damage

Insulin’s Role vs. Insulin Resistance (IR)

Organ/SystemNormal Insulin ActionEffects of Insulin Resistance
LiverStops glucose production; stores glucose as glycogen.The liver ignores the “stop” signal, pumping out sugar even when you haven’t eaten (fatty liver).Fatty liver disease is the greatest cause of liver failure in the US.
MusclePrimary site for glucose uptake; promotes protein synthesis.Muscles can’t take in fuel efficiently, leading to fatigue and muscle wasting (sarcopenia). Muscle cells cannot use amino acids from dietary protein to maintain or build muscle. Elderly lose muscle and strength, resulting in falls, fractures and head trauma. Loss of muscle (the major sink for blood sugar after a meal) further increases duration and degree of blood sugar and insulin rise after a meal, which in turn increases IR. (vicious cycle)
Fat (Adipose)Stores fat; inhibits the breakdown of stored fat.Fat cells leak fatty acids into the blood, leading to high triglycerides and visceral fat gain. Macrophages (immune cells) produce inflammatory cytokines which circulate through the body contributing to chronic inflammation which worsens IR, another vicious cycle.
BrainRegulates appetite, memory, and cognitive function.Linked to “Type 3 Diabetes”; impaired memory and increased risk of neurodegeneration. Brain loses ability to meet energy demands and clear toxins. Insulin resistance in the brain explains memory loss, cognitive impairment, loss of neurons and synapses, loss of neuroplasticity. BDNF (brain derived neurotrophic factor) production is decreased by IR.
ArteriesStimulates nitric oxide for vasodilation (keeps vessels flexible).Reduced nitric oxide causes vessels to stiffen, raising blood pressure and plaque buildup. This is called endothelial dysfunction, the precursor to heart attack, stroke, peripheral vascular disease and a root cause for neuropathy and amputations.
HeartRegulates fuel use (switching between glucose and fats).The heart becomes “metabolically inflexible,” increasing the risk of heart failure.
KidneyManages sodium reabsorption and filtration.High insulin causes the kidneys to hold onto salt, driving up blood pressure and damaging filters. Oxidative stress leads to kidney failure.
Immune SystemModulates inflammation and helps T-cell function.Creates a state of “chronic low-grade inflammation” and weakens the response to infections.
BoneStimulates bone-forming cells (osteoblasts).Bone quality decreases; despite higher bone density in some cases, the bones are more brittle.
JointsMaintains cartilage and reduces systemic inflammation.High insulin promotes pro-inflammatory cytokines, accelerating osteoarthritis and gout.

 A meal with sugar and refined carbohydrates causes excessive swings in blood sugar and insulin levels, creating insulin resistance and downstream damage. Alcohol consumption contributes to this process. Fat consumption does not cause a rise in blood sugar or insulin levels. Protein consumption produces a minimal rise in insulin levels in the absence of IR.

Fat storage can occur through hyperplasia (increase in number of fat cells) or hypertrophy (increase in size). Some ethnic groups are more prone to hypertrophy (south and east Asian). Hypertrophy in visceral fat (fat around the internal organs as opposed to fat under the skin) results in macrophage production of inflammatory cytokines. Eventually, the fat cells themselves can literally burst from too much volume.

 In my next post, I will discuss what we can do to prevent and reverse IR.

REFERENCES

Chadt A, Al-Hasani H. Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease. Pflugers Arch. 2020 Sep;472(9):1273-1298. doi: 10.1007/s00424-020-02417-x. Epub 2020 Jun 26. PMID: 32591906; PMCID: PMC7462924.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7462924/

Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E745-54. doi: 10.1152/ajpendo.00271.2005. Epub 2006 May 16. PMID: 16705054; PMCID: PMC2804964.

https://pmc.ncbi.nlm.nih.gov/articles/PMC2804964

Vargas E, Joy NV, Carrillo Sepulveda MA. Biochemistry, Insulin Metabolic Effects. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525983/

https://www.ncbi.nlm.nih.gov/books/NBK525983/

Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in nonalcoholic fatty liver disease. Curr Pharm Des. 2010 Jun;16(17):1941-51. doi: 10.2174/138161210791208875. PMID: 20370677.

https://pubmed.ncbi.nlm.nih.gov/20370677/

Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, Panza JA. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation. 1999 Aug 24;100(8):820-5. doi: 10.1161/01.cir.100.8.820. PMID: 10458717.

https://pubmed.ncbi.nlm.nih.gov/10458717/

Ke JF, Wang JW, Zhang ZH, Chen MY, Lu JX, Li LX. Insulin Therapy Is Associated With an Increased Risk of Carotid Plaque in Type 2 Diabetes: A Real-World Study. Front Cardiovasc Med. 2021 Feb 1;8:599545. doi: 10.3389/fcvm.2021.599545. PMID: 33598483; PMCID: PMC7882504.

https://pubmed.ncbi.nlm.nih.gov/33598483/

Brosolo G, Da Porto A, Bulfone L, Vacca A, Bertin N, Scandolin L, Catena C, Sechi LA. Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney. Biomedicines. 2022 Sep 23;10(10):2374. doi: 10.3390/biomedicines10102374. PMID: 36289636; PMCID: PMC9598512.

https://pubmed.ncbi.nlm.nih.gov/36289636/

Kumar M, Dev S, Khalid MU, Siddenthi SM, Noman M, John C, Akubuiro C, Haider A, Rani R, Kashif M, Varrassi G, Khatri M, Kumar S, Mohamad T. The Bidirectional Link Between Diabetes and Kidney Disease: Mechanisms and Management. Cureus. 2023 Sep 20;15(9):e45615. doi: 10.7759/cureus.45615. PMID: 37868469; PMCID: PMC10588295.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10588295/

Banks WA, Owen JB, Erickson MA. Insulin in the brain: there and back again. Pharmacol Ther. 2012 Oct;136(1):82-93. doi: 10.1016/j.pharmthera.2012.07.006. Epub 2012 Jul 17. PMID: 22820012; PMCID: PMC4134675.

https://pubmed.ncbi.nlm.nih.gov/22820012/

Rahman MS, Hossain KS, Das S, Kundu S, Adegoke EO, Rahman MA, Hannan MA, Uddin MJ, Pang MG. Role of Insulin in Health and Disease: An Update. Int J Mol Sci. 2021 Jun 15;22(12):6403. doi: 10.3390/ijms22126403. PMID: 34203830; PMCID: PMC8232639.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8232639/

Scherrer U, Sartori C. Insulin as a vascular and sympathoexcitatory hormone: implications for blood pressure regulation, insulin sensitivity, and cardiovascular morbidity. Circulation. 1997 Dec 2;96(11):4104-13. doi: 10.1161/01.cir.96.11.4104. PMID: 9403636.

https://pubmed.ncbi.nlm.nih.gov/9403636/

Affuso F, Micillo F, Fazio S. Insulin Resistance, a Risk Factor for Alzheimer’s Disease: Pathological Mechanisms and a New Proposal for a Preventive Therapeutic Approach. Biomedicines. 2024 Aug 19;12(8):1888. doi: 10.3390/biomedicines12081888. PMID: 39200352; PMCID: PMC11351221.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11351221/

Park MH, Kim DH, Lee EK, Kim ND, Im DS, Lee J, Yu BP, Chung HY. Age-related inflammation and insulin resistance: a review of their intricate interdependency. Arch Pharm Res. 2014 Dec;37(12):1507-14. doi: 10.1007/s12272-014-0474-6. Epub 2014 Sep 20. PMID: 25239110; PMCID: PMC4246128.

https://pubmed.ncbi.nlm.nih.gov/25239110/

Hardy OT, Czech MP, Corvera S. What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes. 2012 Apr;19(2):81-7. doi: 10.1097/MED.0b013e3283514e13. PMID: 22327367; PMCID: PMC4038351.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4038351/

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

4th International Evolutionary Health Conference

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Sorry for the confusion. The website for the International Evolutionary Health Conference changed when the venue changed from Boston to Virtual. Here is the correct website link which gives a list of speakers/topics and sign up information. 

https://2023.evolutionaryhealthconference.com/

The previously published link will lead you to a site that says “canceled”. The conference is not cancelled, the venue has changed to virtual. 

Dr. Bob

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Fourth International Evolutionary Health Conference

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I’ve been asked to talk at the fourth International Evolutionary Health Conference on the topic of Cardiovascular Risk Assessment. This year the conference is virtual. Presenters include clinicians and researchers discussing many topics related to health. The underlying principle of this approach attributes modern degenerative and chronic diseases to mismatch between our evolutionary biology and present day life. You can sign up for this virtual event here.

https://2023.evolutionaryhealthconference.com/

Agenda

9:45 AM – 10:00 AM

Opening remarks

Prof. Lynda Frassetto

10:00 AM – 10:30 AM

Maladaptive cognitive/emotional processing as the cause of the stress response

Prof. Igor Mitrovic

Physiologic reserve is spare capacity activated when demand exceeds baseline, causing stress. If demand surpasses reserve, it damages the system and leads to death. The brain predicts the future to a…
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10:30 AM – 11:00 AM

How breathing patterns affect health

Dr. Michael Mew

11:00 AM – 11:15 AM

Round table with Q & A (Moderator: Darryl Edwards)

Dr. Michael Mew

Prof. Igor Mitrovic

11:15 AM – 11:45 AM

Break and Poster session

If you would like to submit a poster, please contact us at evolution.conference@nutriscience.pt

11:45 AM – 12:15 PM

Decoding The Truth: Cancer, Carbs and Cure

Darryl Edwards, MSc

1. We will delve into the extensive evidence showcasing how higher levels of physical activity can reduce the risk of various cancers. 2. While awareness of the importance of exercise exists, we will…
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12:15 PM – 12:45 PM

Influential factors on sun-induced vitamin D synthesis

Pedro Bastos, PhD candidate

Ultraviolet B radiation is absorbed in the epidermis by 7-dehydrocholesterol, giving rise to previtamin D3 and subsequently to vitamin D3. In the liver, vitamin D is converted to one of the various c…
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12:45 PM – 1:00 PM

Round table with Q & A (Moderator: Prof. Lynda Frassetto)

Darryl Edwards, MSc

Pedro Bastos, PhD candidate

1:00 PM – 2:15 PM

Lunch Break

2:15 PM – 2:45 PM

How nutrition can impact microbiome composition/permeability/immune response

Prof. Alessio Fasano

Improved hygiene and reduced microorganism exposure are linked to the ‘epidemic’ of chronic inflammatory diseases (CID) in developed nations. This hygiene hypothesis suggests that lifestyle and envir…
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2:45 PM – 3:15 PM

Comprehensive cardiovascular risk assessment

Dr. Robert Hansen

Assessing insulin resistance is central to predicting CV risk. LDL-C and standard lipid profile is extremely limited in predictive value. A systems engineering understanding of atherosclerosis and ev…
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3:15 PM – 3:30 PM

Round table with Q & A (Moderator: Pedro Bastos)

Prof. Alessio Fasano

Dr. Robert Hansen

3:30 PM – 3:45 PM

Short Break

3:45 PM – 4:15 PM

Environmental influences on cellular senescence and aging

Prof. Peter Stenvinkel

Planetary health recognizes that human well-being depends on the health of ecosystems. Neglecting this concept has led to an anthropocentric world, causing increased greenhouse gas emissions, heat st…
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4:15 PM – 4:45 PM

Fueling a Bright Future: The Role of Diet in Preventing Childhood Obesity

Dr. Polina Sayess

Childhood obesity is a global health issue. In my presentation, I’ll explore its origins, classifications, and mitigation strategies. I’ll discuss the definitions and distinctions between “overweight…
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4:45 PM – 5:00 PM

Round table with Q & A (Moderator: Prof. Lynda Frassetto)

Prof. Peter Stenvinkel

Dr. Polina Sayess

5:00 PM – 5:30 PM

Final discussion with all speakers and moderators

Establishing future research and intervention directions.

5:30 PM – 5:45 PM

Closing remarks

Prof. Lynda Frassetto

Please join us if you can.

Dr. Bob

COVID 19 UPDATE: What have we learned?

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I was recently interviewed by a health blogger, Dmitri Konash, with specific questions about COVID 19. The podcast link is below.

Here are the questions and answer notes from the podcast.

QUESTION #1: It has been almost 4 months since Covid19 was declared a global pandemic. What are the main things which we have learned about the virus over these 4 months?

Very contagious, spread by droplet AND aerosol as well as fomites (CLOTHING, surfaces, pillows, blankets, etc). Aerosols are tiny particles suspended in the air for hours following a sneeze or cough or possibly yelling or singing. Droplets are larger particles that fall to the ground or onto surfaces. Depending on the surface the virus can remain infectious for up to 72 hours following droplet spread.

Individuals without symptoms can transmit disease (unlike most viruses) so this in combination with degree of contagion is very dangerous.

The average time from exposure to develop symptoms is 5 DAYS, 97.5% of people who develop symptoms do so within 11.5 days.

Some individuals never develop symptoms but can transmit disease for 2 or more weeks.

Infected individuals can carry the virus for up to 36 days (but we do not know how long an individual can transmit the disease) Average time to clear the virus is 14 days. (nasal PCR test)

Cough and sneeze can project 26 feet through the air, that is why masks can decrease risk but decreasing projection distance and viral load.

Masks Work, they decrease risk of disease transmission and probably decrease viral load, so if transmitted the recipient is probably less likely to develop severe complications (not proven but likely true).

Most infections are transmitted in closed spaces where many people are congregated and socializing such as parties, social gatherings, meetings, bars and restaurants.

Outdoor activity is safer.

The longer the contact between individuals the greater the risk.

The closer the contact the greater the risk.

Anyone can die from the virus but risk increases with age, diabetes, pre-diabetes, obesity, heart and lung disease, immune-compromise.

Any organ can be affected, lungs, brain, heart, kidneys, blood vessels.

Hyper-coaguable state can cause blood clots in the legs, lungs, heart and brain, any organ.

After recovering from infection individuals can suffer permanent damage to these organs.

We do not know how many people who recover will be immune or how long immunity could last. Already one case of re-infection has been reported.

The infection fatality rate (IFR) for COVID-19 IS 25 times greater than the H1N1 FLU pandemic.

A recent analysis comparing the 2009 H1N1 influenza A pandemic to COVID 19 suggested this:

 Case Fatality RateInfection Fatality Rate
2009 H1N1 Virus (flu)0.1% to 0.2%0.02%
COVID-19 New York8%0.50%
CFR is # deaths/#cases identified by nasal PCR, IFR is # deaths/actual # cases in a given population, estimated by antibody testing of a large population

For a discussion on the difference between CFR (case fatality rate) and IFR (infection fatality rate) see my previous post.

https://practical-evolutionary-health.com/2020/04/25/stanford-study-on-santa-clara-county-very-questionable-conclusions/

QUESTION #2: We reached the new high of newly diagnosed cases on June 28th. It looks like the virus is not subsiding. What is the status re drug and vaccine development?

Vaccine will likely take at least a year to develop, test, then manufacture and distribute.

Initially most vulnerable will probably take priority for vaccination. Massive vaccination will take longer.

THERE HAS NEVER BEEN A SUCCESSFUL CORONA VIRUS Vaccine. There are many corona viruses. They mutate quickly and a vaccine that works initially may become ineffective if/when new strains emerge.

Decadron (dexamethasone) IV decreases mortality rates in very sick patients.

Remdesivir shortens illness and might decrease mortality rate (the reduction compared to placebo fell short of statistical significance, p=0.059, cut-off for statistical significance is usually P=0.050)

Hydroxychloroquine and chloroquine have failed to show any benefit. A prevention trial remains underway.

There is no “cure”, just risk reduction.

QUESTION #3: What are the latest recommendations on prevention?

Social distance

Mask

Frequent hand washing

Get adequate sleep, sleep deprivation impairs immunity

Avoid alcohol which suppresses the immune system.

Get sunshine (vitamin D)

Develop a social “bubble”, limit contacts to close, reliable (responsible behavior) individuals

Exercise out of doors.

If overweight or obese, LOSE WEIGHT (Low Carb High Fat diet is MOST EFFECTIVE in combination with time restricted eating)

IF diabetes or pre-diabetes, carbohydrate restriction can rapidly achieve better blood sugar control, which is linked to risk reduction. Regular exercise can also improve insulin sensitivity, as can improved sleep habits.

QUESTION #4: There was some information recently about potential long-term impact on vital body organs for patients who had only mild symptoms. What actions do people who were tested positive for COVID19 should take to minimize long term impact to their health?

Follow general principles of healthy living (visit my website)

Sleep

Nutrition-anti-inflammatory diet

Exercise

Sunshine

Stress reduction

Social-community support

Minimize environmental toxin exposure (organic foods, safe personal and home-care products, visit EWG.org)

QUESTION #5: What actions should be taken by people who have been tested negative for COVID19 ? 

Same answer as question #4 above, lifestyle changes to enhance immune function and reduce systemic inflammation.

On July 10, a review article on COVID 19 was published in JAMA.

Pathophysiology, Transmission, Diagnosis, and Treatment
of Coronavirus Disease 2019 (COVID-19)

Here is the link.

https://jamanetwork.com/journals/jama/fullarticle/2768391

The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%

And here is a link to the JAMA patient information page for COVID 19.

https://jamanetwork.com/journals/jama/fullarticle/2768390

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

Chronic Inflammation, the silent killer

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I was recently interviewed by a health blogger for his podcast. The topic was chronic inflammation. Here it is.

I prepared some notes for the interview. Here are the questions and answers.

What made you so interested in the topic of chronic inflammation?

Interest in chronic inflammation:

  • Emerging evidence, source of most chronic disease including mental health (depression, etc.) is inflammation
  • family health issues experience personally
  • health care policy interest since graduate school
  •  First started to question USDA dietary advice after reading GOOD CALORIES, BAD CALORIES, by Gary Taubes,
  • Experienced Statin myopathy, researched statin drugs, bad data, financial conflicts of interest. Sought alternative approaches to Coronary Artery Disease prevention.
  • In USA, Profit driven health care system evolved from more benign not-for-profit earlier system in medical insurance and hospital system. Drug and surgery oriented. Corporate ownership of multiple hospitals, concentration of wealth and power in the industry and in society in general
  • Saw this every day: growing obesity, Metabolic Syndrome, DMII, auto-immune disease. Root causes NOT ADDRESSED.
  • While recovering from surgery attended on line functional medicine conference on auto-immune disease, covering diet, sleep, exercise, sunshine, Vitamin D, environmental toxins, gut dysbiosis, intestinal permeability (THE GATEWAY TO AUTOIMMUNITY IS THROUGH THE GUT).
  • Introduced to EVOLUTIONARY BIOLOGY and Paleo Diet by my son

What diseases does chronic inflammation typically lead to? 

  • Cancer
  • Diabetes
  • Obesity epidemic, DIABESITY
  • Hypertension
  • Metabolic Syndrome (3/5: HTN, insulin resistance/high blood sugar, abdominal obesity, high TGs, low HDL),
  • Autoimmune diseases
  • Degenerative arthritis
  • Neurodegenerative disorders (dementia, Parkinson’s, neuropathy, multiple sclerosis)
  • Works of Dale Bredesen (dementia, “The End of Alzheimer’s”), Ron Perlmutter (Grain Brain), Terry Wahls (The Wahls protocol for MS), all FUNCTIONAL MEDICINE looking at root cause of illness, common-overlapping threads.
  • Interplay between sleep, circadian rhythm, exercise, sunlight, stress, environmental toxins, diet, processed foods, nutritional deficiency, gut microbiome, endocrine disruptors, intestinal permeability, oral and skin microbiome, social disruptors, GUT BRAIN AXIS. These are all part of one large ECOSYSTEM.
  • Positive and negative feedback systems requiring a SYSTEMS ENGINEERING approach to understanding root causes.
  • Butyrate is the preferred substrate for colonocytes, providing 60-70% of the energy requirements for colonic epithelial cells1,2. Butyrate suppresses colonic inflammation,3 is immunoregulatory in the gut,4 and improves gut barrier permeability by accelerating assembly of tight junction proteins.5,6
  • Improves insulin sensitivity, increase energy expenditure, reduce adiposity, increases satiety hormones,
  • HDAC activity inhibitor, PROTECTS GENES from removal of necessary acetyl groups.
  • Butyrate also influences the mucus layer. A healthy colonic epithelium is coated in a double layer of mucus. The thick, inner layer is dense and largely devoid of microbes, protecting the epithelium from contact with commensals and pathogens alike. The loose, outer layer of mucus is home to many bacteria, some of which feed on the glycoproteins of the outer mucus layer itself. Both of these mucus layers are organized by the MUC2 mucin protein, which is secreted by goblet cells in the epithelium. Supplementation of physiological concentrations of butyrate has been shown to increase MUC2 gene expression and MUC2 secretion in a human goblet cell line.7,8

What are the population groups which have higher risk of chronic inflammation? 

  • Obese
  • Sedentary
  • Poor-urban-polluted environment dwelling (air, water, noise, crowding, violence, racism, oppression)
  • Divergence from ancestral evolutionary biology
  • Working environment: indoors, polluted, oppressive supervisors, no sunlight, noise pollution, air pollution, toxic social situations, repetitive motion, bad ergonomics,
  • night shift, disruption of circadian rhythm
  • both parents working, no time for real food and family interaction, supervision of children.
  • screen time- sedentary behavior, lack of outdoor activity
  • Stress of social inequality, food insecurity, violent neighborhoods, nutritional deserts

What are the “danger signs” or typical symptoms which may signal a chronic inflammation? 

DANGER SIGNS:

  • Waistline (waist to height ratio, BMI)
  • Sarcopenia (muscle as an endocrine organ)
  • Sleep disturbance
  • Pain
  • Headaches
  • Depression
  • Lack of joy.
  • Brain fog, fatigue

What are the typical biomarkers of chronic inflammation?

  • METABOLIC SYNDROME (3 or more of the following: high blood pressure, elevated blood sugar, elevated Triglycerides, low HDL, obesity)
  • CRP predictive of cardiovascular events,
  • ESR associated with arthritis
  • Stress hormones (morning cortisol levels)
  • Resting Heart Rate and Heart Rate Variability

What are the typical sources of systemic chronic inflammation?

Sources of Chronic Inflammation:

Diet

  • N6/N3 FA ratio determined by too much Refined Easily Oxidized Vegetable Oils, not enough marine sources of N3 FA,  grain fed vs grass fed/finished ruminant meat. Loren Cordain research wild game FA composition = grass fed. Margarine vs Butter. Fried foods using Vegetable oils. Oxidized fats/oils, oxy-sterols in diet.
  • Sugar excess leading to insulin resistance
  • Refined carbs leading to insulin resistance (dense acellular….)
  • Disturbance of gut  microbiome from poor nutrition (sugar, refined carbs and vegetable oils all disrupt the microbiome)
  • Gut brain axis.
  • Food ADDITIVES AND PRESERVATIVES
  • Trans Fats (finally banned)

Endocrine disruptors/ BIOACCUMULATION

  • Plastics (microparticles in our fish, food and bottled water)
  • Plastic breakdown products
  • Phthalates added to plastics to increase flexibility ( also pill coatings, binders, dispersants, film formers, personal care products, perfumes, detergents, surfactants, packaging, children’s toys, shower curtains, floor tiles, vinyl upholstery, it is everywhere) 8.4 million tons of plasticizers produced annually. EWG.org
  • Pesticides, herbicides, glyphosate (Monsanto), DIRTY DOZEN, CLEAN FIFTEEN EWG.org
  • Medications
  • ABSORBED skin, eat, drink, breath,
  • BPS is as bad as the BPA it replaced
  • Polychlorinated biphenyls used in INDUSTRIAL COOLANTS AND LUBRICANTS
  • Flame retardants (PBDEs, polybrominated dipheyl ethers) are ubiquitous in furniture and children’s clothing. Also linked to autoimmune disease
  • Dioxins
  • PAHs (polycyclic aromatic hydrocarbons
  • Sunblock
  • CUMULATIVE BURDEN, INTERACTIONS, SYNERGY?

SLEEP DEPRIVATION CHRONIC IN OUR SOCIETY

Eating late vs time restricted eating

Gut Microbiome disrupted by

  • 1/3 of prescribed medications disrupt the microbiome AND increase intestinal permeability
  • Stress
  • Sleep deprivation
  • Sugar
  • Refined carbs
  • Refined veg oils
  • Over exercise and Under exercise, both are bad.
  • Environmental toxins

Gut dysbiosis and infections include (often chronic, low grade, not diagnosed)

  • Pathogenic bacteria, infection or overgrowth/imbalance
  • SIBO
  • Parasites
  • Viruses
  • BAD bugs > good bugs
  • Good bugs make vitamins and SCFAs required for colonocyte energy
  • Gut-Brain axis huge topic, VAGUS NERVE COMMUNICATION both ways, SCFA in gut and in CIRCULATION (butyrate, propionate, acetate), NEUROTRANSMITTER PRODUCTION (SEROTONIN, OTHERS), enterochromaffin cells producing > 30 peptides.
  • Overuse of antibiotics in medicine
  • AND use of antibiotics in raising our food.
  • Vaginal delivery vs C-section
  • Breast feeding vs bottle feeding

INCREASED INTESTINAL PERMEABILITY:

  • Caused by all factors above
  • Leads to higher levels of circulating LPS-endotoxin, bacterial products that create an immune-inflammatory response.
  • Incompletely digested proteins with AA sequences overlapping our own tissue causing autoimmunity/inflammation through molecular mimicry

Heavy Metal toxicity

  • Lead
  • Mercury
  • Cadmium
  • Arsenic

MOLD TOXICITY (> 400 identified mycotoxins, can cause dementia, asthma, allergies, auto-immunity)

  • At home
  • At work

What are the most efficient natural (non-medication) ways to address chronic inflammation?

  • Anti-inflammatory Diet, real whole food that our ancestors ate through evolutionary history (grass fed/finished ruminant meat, free range poultry, antibiotic free, and pesticide free food, wild seafood (low mercury varieties), organic vegetables and fruit, nuts, fermented foods, eggs)
  • Low mercury fish and seafood for omega three fatty acids
  • Sleep hygiene
  • Exercise, not too much, not too little, rest days, out of doors, resistance training, walking, yoga, Pilates, tai chi, chi gong, dancing, PLAYING!!!!!!!!!!!!!
  • Stress reduction: meditation, mindful living, forest bathing, sunlight, Playing, music, praying, SOCIAL CONNECTION, laughter, comedy, quit the toxic job, quit the toxic relationship, SAUNA/SWEAT, heat shock proteins, exercise
  • Vitamin D, sunshine, check levels
  • PLAY, PLAY, PLAY, LAUGH, DANCE, ENJOY, LOVE
  • Be aware of potential dangers of EMF, WiFi, hand held devices, blue tooth headphones.
  • Address environmental justice
  • Address social inequality, food insecurity
  • Tobacco addiction
  • Ethanol
  • Other substance abuse
  • Agricultural subsidies in US distort the food supply
  • Loss of soil threatens food supply
  • Suppression of science (global warming, environment, etc.,) worsens environmental degradation, creating an EXISTENTIAL THREAT.
  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

The Broken Brain Docuseries is now re-running

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Due to popular demand the producers of this terrific series are making it available again  on line this weekend. If you have not taken advantage of this information you can do it here:

Replay (YouTube) | Broken Brain

Enjoy

Bob Hansen MD

Cartoon humor: A Prescription for Health!

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prescription-for-exercise-cropped

Hat tip to Tommy Wood MD, PhD for introducing me to this great cartoon.

So what would happen if your doctor prescribed this? Would you be shocked? Would you follow the advice? Sadly few doctors make such recommendations as explicitly as this cartoon and fewer patients follow the advice.

How important are the elements in this advice?

They are essential. We too often focus on dietary concerns at the expense of ignoring other important low hanging fruit. Early morning  outdoor exercise with exposure to natural light in a green space, even on a cloudy or rainy day, is essential for health. Why? There are many reasons. Click the link above to read fitness expert Darryl Edward’s discussion with references. In fact outdoor exercise in a greenspace is more beneficial than the same exercise indoors. The reasons are many, including but not limited to Vitamin D production.

Early daytime exposure to natural outdoor light helps to maintain our Circadian rhythm and align the biologic clock in all of our cells and organs with the central biological Circadian clock in our brain. Most folks do not know that we have a biologic clock deep within our brain and that all the organs and cells of our body also have clocks. They all need to be synchronized with each other and with the sun for optimal health. When they are not synchronized bad things happen. Night shift workers and other folks with disturbed sleep have higher rates of cancer , depression ,  hypertension, heart attack and stroke.

Maintaining our circadian rhythm is vital to achieving adequate high quality restorative sleep. In turn, obtaining adequate restorative sleep contributes to lower cardiovascular disease risk in addition to four traditional lifestyle risk factors.

Exposure to artificial light at night disrupts our circadian rhythm and impairs the onset of sleep.

In medical school I learned that our retina has two cell types, rods and cones. But advances in science have revealed a  third cell type called retinal ganglionic cells. 

These cells are  particularly sensitive to blue light and directly connected to our central biological clock . Exposure to artificial light, especially from TV screens, computers, cell phones and other electronic devices after sunset disrupts our sleep cycle and delays the onset of sleep. That is why wearing blue light filtering glasses in the evening helps many folks to improve their sleep quality and duration.

Sleep deprivation for even one night causes elevation in interleukin 6 levels the following day. Interleukin 6 suppresses immune function and excessive levels cause bone and tissue damage (especially cardiovascular). Sleep deprivation  increases  Stress hormones (cortisol, adrenalin), decreases prolactin and Growth hormone , and decreases the nightly production of ATP .

Melatonin , often called the sleep hormone, is produced most abundantly during restorative sleep and essential for tissue healing, immune function, cancer prevention, and defense against tissue oxidation. These are just a few of the roles melatonin and sleep cycles play in determining our health..

So exercise outdoors in a green space daily to help synchronize your biologic clock with the sun, dim the lights in the evening and if you must watch TV or work on electronic devices before bed wear Blue Light filter glasses .

Of course eating an abundance of colorful fresh organic vegetables and fruits, and practicing some stress reduction techniques every day are equally important and essential to health and functional status.

Finally, not mentioned in the cartoon above is another healthy lifestyle choice, intermittent fasting (IF). IF will be discussed in the next post.

Until then, sleep well, exercise regularly out doors in a green space environment, eat clean, learn and practice some regular stress reduction techniques and read the next post about IF.

Bob Hansen MD

Functional Medicine: Getting to the Root Causes of Illness, A cure for Alzheimer’s

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Today I watched a great TED talk by Dr. Rangan Chaterjee discussing his own journey in the discovery and implementation of a functional medicine approach to caring for his patients. The concept of using basic science and clinical science to diagnose and treat the root causes of illness, rather than treating symptoms, has been around for more than two decades.  This approach has recently started to attract more attention, especially within the community of younger physicians who have become more dissatisfied with the frustrations of traditional allopathic medicine.

Here is the talk. Dr. Chatterjee covers lots of ground in a passionate and informative talk.

Enjoy this talk. If you would like to learn about how a functional medicine approach can CURE ALZHEIMER’S DISEASE then watch this video of Dr. Bredesen who gave this lecture at a meeting of the American College of Nutrition.

Doctor Bredesen, an acclaimed neuroscientist, researcher, and more recently a brilliant clinician, has been criticized by the academic research community for implementing a clinical research protocol that addresses more than one variable at a time! Unfortunately, medical science has been handcuffed by the drug-model of clinical research wherein only one variable (drug vs. placebo for example) is studied. But if an illness has many potential contributing root causes, changing only one variable is doomed to failure, as Dr. Bredesen explains in this lecture.

Sleep well, eat clean, get outdoors every morning to help keep your circadian rhythm and biological clock in order.

Bob Hansen MD

Sugar Industry paid Harvard researchers to trash fat and exonerate sugar!

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By now most of you have already heard about the study published in JAMA that reveals an unsavory historical scenario wherein the sugar industry  funded an academic review paper that diverted the medical community’s attention from sugar as a vector for disease and erroneously placed it on saturated fat and cholesterol consumption. You can read about it by clicking on the following link.

How the Sugar Industry Shifted Blame to Fat – The New York Times

Here is a quote from the above cited article in the NY times:

The internal sugar industry documents, recently discovered by a researcher at the University of California, San Francisco, and published Monday in JAMA Internal Medicine, suggest that five decades of research into the role of nutrition and heart disease, including many of today’s dietary recommendations, may have been largely shaped by the sugar industry.

Here is the abstract of the article published in JAMA (Journal of the American Medical Association).

Sugar Industry and Coronary Heart Disease Research:  A Historical Analysis of Internal Industry Documents | JAMA Internal Medicine | JAMA Network

Early warning signals of the coronary heart disease (CHD) risk of sugar (sucrose) emerged in the 1950s. We examined Sugar Research Foundation (SRF) internal documents, historical reports, and statements relevant to early debates about the dietary causes of CHD and assembled findings chronologically into a narrative case study. The SRF sponsored its first CHD research project in 1965, a literature review published in the New England Journal of Medicine, which singled out fat and cholesterol as the dietary causes of CHD and downplayed evidence that sucrose consumption was also a risk factor. The SRF set the review’s objective, contributed articles for inclusion, and received drafts. The SRF’s funding and role was not disclosed. Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD. Policymaking committees should consider giving less weight to food industry–funded studies and include mechanistic and animal studies as well as studies appraising the effect of added sugars on multiple CHD biomarkers and disease development.

This disturbing conspiracy reveals yet another industry sponsored distortion of science which had great impact on the health of our nation. The impact is accelerating today as the epidemics of obesity and diabetes rage out of control. But sugar consumption has not just been tied to obesity, diabetes, heart attacks and strokes. Sugar added foods and beverages have likely contributed to dementia,  many forms of cancer and other chronic debilitating diseases. Sugar and refined carbohydrates mediate these effects by increasing systemic inflammation and contributing to insulin resistance. Inflammation and insulin resistance are pathways to many disease processes. Metabolic syndrome (pre-diabetes) is the hallmark combination of multiple abnormalities with insulin resistance as the underlying root cause. Prolonged insulin resistance leads to type 2 diabetes and contributes to heart attacks, strokes,  cancer and dementia. In fact dementia is often referred to as type 3 diabetes, mediated in large part by insulin resistance in the brain.

Here are links to discussions and videos relevant to these topics.

Preventing Alzheimer’s Disease Is Easier Than You Think | Psychology Today

How to Diagnose, Prevent and Treat Insulin Resistance [Infographic] – Diagnosis:Diet

Reversing Type 2 diabetes starts with ignoring the guidelines | Sarah Hallberg | TEDxPurdueU – YouTube

I have previously provided links to the YouTube lectures given by the brilliant Dr. Jason Fung, These are worth mentioning again.

The Aetiology of Obesity Part 1 of 6: A New Hope

Insulin Toxicity and How to Cure Type 2 Diabetes

How to Reverse Type 2 Diabetes Naturally

Nina Teicholz is also worth a watch.

Nina Teicholz: The Big Fat Surprise – (08/07/2014)

And here is an important talk about sugar, refined carbohydrates and cancer.

Plenty to chew on.

We did not evolve to eat lots of sugar! It is dangerous stuff.

Bob Hansen MD

 

 

 

Still want a doughnut or cereal for breakfast?

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A recent study has demonstrated that brain deterioration detected by MRI scan seems to be linked to higher blood sugar levels even within the “normal range”.

Here are some important quotes from a Medscape discussion:

“Previous studies have shown that T2D (type 2 diabetes) is associated with brain atrophy, cognitive deficits, and increased risk for dementia. Elevated plasma glucose levels still within the normal range increase the risk for T2D.”

“Studies showed that in apparently healthy individuals, atrophy of the amygdala and hippocampus increased as FPG (fasting plasma glucose) within the normal range increased.”

“You start having abnormalities in the brain even at levels that are within the normal range. This is important because, should we be defining normal glucose levels for different purposes?”

Bottom line, as discussed by neurologist David Perlmutter in his book Grain Brain, even “normal” blood sugars as defined by measurements in our society many not be healthy. If a whole modern culture has higher blood sugars, higher blood pressures, fatter waistlines compared to our healthy hunter gatherer ancestors, then the “normal range” may not really be “normal”. If we define “normal” as individuals within 1 or 2 standard deviations of the mean, but a large portion of the population is unhealthy, is normal healthy?

Do you want to spend your last day in diapers drooling in a nursing home or do you want to go out hiking in the woods and enjoying grandchildren?

The choice is yours, but the next time you have a doughnut or cereal for breakfast, consider the long term consequences.

Live clean and prosper.

Bob Hansen MD

Here is the whole Medscape article for those interested in the nitty-gritty details.

White Matter Lesions Linked to Rising Plasma Glucose

SANTIAGO, Chile — Higher fasting plasma glucose (FPG) levels are associated with a higher burden of brain white matter hyperintensities (WMH), particularly in the frontal lobes.

The association is especially strong in individuals with type 2 diabetes (T2D), a new study shows.

Lead author Nicolas Cherbuin, PhD, and colleagues in the Centre for Research on Ageing, Health and Wellbeing of the Australian National University in Canberra used data from the Personality and Total Health (PATH) Through Life Project, a large, longitudinal, population-based study investigating the time course and determinants of cognitive aging and mental health.

The study findings were presented here at the XXII World Congress of Neurology (WCN).

The PATH Through Life Project aims to follow approximately 7500 randomly selected adults in the greater Australian capital area over 20 years.

From an older age cohort (60 to 64 years; n = 2551), 401 community-living individuals were available for analysis. All were free of neurologic disorders, stroke, and gross brain abnormalities and had a Mini-Mental State Examination (MMSE) score of 27 or greater.

Using linear regression analysis, the researchers tested the association between FPG and WMH volumes, controlling for covariates of age, sex, intracranial volume, education, smoking, hypertension, body mass index (BMI), diabetes, and interactions of diabetes and sex.

Plasma glucose was measured after an overnight fast and was categorized as normal, defined as less than 5.6 mmol/L (<100.8 mg/dL), impaired (5.6 to 7 mmol/L [100.8 to 126 mg/dL]), or T2D (≥7 mmol/L [≥126 mg/dL] or self-report of T2D).

Patient groups with normal FPG (n = 276), impaired FPG (n = 86), or T2D (n = 39) were similar in age (approximately 63 years), education (14 years), and MMSE scores (29.26 to 29.45). BMI was higher in the impaired FPG and T2D groups than in the normal FPG group. There was also more hypertension in the T2D group.

WMH Mostly in Frontal and Temporal Lobes

Dr Cherbuin reported that among the entire cohort, higher FPG was associated with a higher burden of WMH in the right hemisphere (P = .02) but not in the left hemisphere. The effect was most prominent in the frontal and temporal lobes.

These findings were largely attributable to participants with impaired FPG or T2D, and the effect was most pronounced for participants with T2D.

Table. WMH Volumes per FPG Level

Location Normal FPG (n = 276) Impaired FPG (n = 86) T2D (n = 39)
Left hemisphere WMH (mm3) 2343.68 ± 2311.72 2331.07 ± 2528.34 2800.62 ± 2152.87
Right hemisphere WMH (mm3) 2379.59 ± 2645.19 2414.98 ± 2609.72 3199.79 ± 4031.47
Values are expressed as mean ± standard deviation.

 

Previous studies have shown that T2D is associated with brain atrophy, cognitive deficits, and increased risk for dementia. Elevated plasma glucose levels still within the normal range increase the risk for T2D.

Studies showed that in apparently healthy individuals, atrophy of the amygdala and hippocampus increased as FPG within the normal range increased. Striatum volumes decreased several years later in line with higher FPG or occult T2D. Functionally, poorer performance of fine motor skills is evident with higher FPG.

Session chairman Samuel Wiebe, MD, professor of neurology at the University of Calgary, Alberta, Canada, commented to Medscape Medical News that the present study intrigued him because it addresses the fact that the definition of normal glucose “maybe doesn’t apply to everything…. You start having abnormalities in the brain even at levels that are within the normal range. This is important because, should we be defining normal glucose levels for different purposes?”

Higher levels of glucose even within the normal range may affect facets that are just beginning to be understood, such as white matter changes. “That’s just one aspect. There could be other areas,” he said. “So I think that that’s an intriguing finding that deserves further study.”

Dr Wiebe said the greater effect of elevated glucose seen in the frontal lobes may be related to some degree to their sheer size or to blood flow. “I think that the truth is that it is a spectrum. It begins to have an impact at a range of values that are lower than the cutoff” for traditional interventions, he said.

He feels it would be interesting to follow up this study with assessments that go beyond WMH volume measurements, such as tractography or connectivity studies that look at brain function.

There was no commercial funding for the study. Dr Cherbuin and Dr Wiebe have disclosed no relevant financial relationships.

XXII World Congress of Neurology (WCN). Abstract 434. Presented November, 2, 2015.