Know the Facts - Metabolic Dysfunction / Dysregulation is The Root Cause of Most Chronic Disease and a Reduced Lifespan
The American Health system is failing!
Approximately 85–90% of U.S. healthcare spending is on the management of chronic diseases such as Coronary Artery Disease, Diabetes, Obesity, Dementia, Sleep Apnea, and Cancer.
- 6 in 10 adults in the U.S. have a chronic disease.
- 4 in 10 have two or more.
- 1.1 Trillion dollars a year are spent on the management of (not the cure) these diseases
- Life expectancy is reduced by approximately 7–12 years for individuals with metabolic syndrome compared to metabolically healthy counterparts.
At the core of it all this disease, reduced lifespan, disability, and wasted money is a common denominator - Metabolic Dysfunction!
Metablic Dysfunction or Dysregulation is characterized by impaired regulation of glucose, lipids, insulin, and inflammation. This diseased regulation state has wide-reaching effects on nearly every organ system, and It plays a central role in the development of numerous chronic diseases, often creating a vicious cycle that worsens overall health and accelerates aging.
The US health system separates each of these disease states into nicely segregated silos, each treated by a different physician with different (often expensive) pharmaceuticals. The problem is that these physicians do not communicate with one another, they often have blinders on - oblivious to the to root cause of these disease states. Of the physicians that do see the association, they often feel powerless to change the flawed system in which they practice.
These statistics underscore the opportunity for Preventative, Lifestyle-oriented, and Integrative care models like Marshall Lifestyle Medicine to reduce costs while improving outcomes.
Here's a system-by-system overview of Metabolic Dysfunction
· Core features: Insulin resistance, hyperinsulinemia, chronic inflammation, mitochondrial dysfunction, and ectopic fat deposition.
· Common drivers: Poor diet (high sugar, refined carbs), sedentary lifestyle, chronic stress, poor sleep, environmental toxins, genetic predisposition, epigenetic expression, ignorance, fragmentation of care.
The Dysfunction of Metabolism leads to Disease Manifestation in almost every Organ System:
Brain
Diseases: Alzheimer’s disease (often called “type 3 diabetes”), depression, cognitive decline, stroke.
Mechanisms:
- Insulin resistance impairs neuronal glucose uptake.
- Chronic inflammation and oxidative stress damage neurons.
- Vascular dysfunction increases the risk of ischemia.
Cardiovascular System
Diseases: Atherosclerosis, hypertension, coronary artery disease, heart failure.
Mechanisms:
- Dyslipidemia (↑triglycerides, ↓HDL, ↑small dense LDL).
- Endothelial dysfunction from oxidative stress.
- Chronic inflammation accelerates plaque formation.
- Hyperinsulinemia stimulates sympathetic nervous system and sodium retention → hypertension.
Liver
Diseases: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis.
Mechanisms:
- Ectopic fat deposition from insulin resistance and lipogenesis.
- Hepatic inflammation and mitochondrial dysfunction.
Pancreas
Diseases: Type 2 diabetes, beta-cell exhaustion.
Mechanisms:
- Chronic insulin demand leads to beta-cell stress and apoptosis.
- Glucotoxicity and lipotoxicity worsen insulin secretion over time.
Adipose Tissue
Diseases: Obesity, lipedema, metabolic syndrome.
Mechanisms:
- Adipocyte hypertrophy → hypoxia → inflammation.
- Dysfunctional adipokine signaling (e.g., low adiponectin, high leptin resistance).
Musculoskeletal System
Diseases: Sarcopenia, osteoporosis, osteoarthritis.
Mechanisms:
- Insulin resistance impairs muscle protein synthesis.
- Chronic inflammation degrades bone matrix.
- Advanced glycation end products (AGEs) weaken connective tissue.
Endocrine System
Diseases: PCOS, hypogonadism, thyroid dysfunction.
Mechanisms:
- Insulin resistance disrupts hormonal feedback loops.
- Elevated insulin suppresses sex hormone-binding globulin (SHBG), altering sex hormone levels.
- Chronic stress and cortisol affect HPA axis regulation.
Immune System
Diseases: Autoimmune diseases, impaired immunity.
Mechanisms:
- Meta inflammation (metabolic inflammation) activates innate immunity.
- Dysregulated nutrient sensing alters immune cell function.
Renal System
Diseases: Chronic kidney disease (CKD), nephropathy.
Mechanisms:
- Hyperglycemia and hypertension damage glomeruli.
- Uric acid and AGEs contribute to renal endothelial injury.
Clinical Implications:
There are Early signs of this Phenomena: Midsection Fat Accumulation (Central obesity), Difficulty losing weight, Fatigue, Malaise, Aches and Pains, Elevated Blood Pressure, Poor Sleep, Hormonal Issues
There are Specific Screening Tests to Identify Metabolic Syndrome:
- Insulin Resistance Score (IR)
- fasting insulin Level
- TG / HDL ratio
- HbA1c
- Adiponectin Level
- Leptin Level
- hs-CRP
- Testosterone (Total and Free)
- Estradiol
- Sleep Study
Prevention/Treatment:
- The Hallmark of Prevention and Reversal of Metabolic Syndrome is Lifestyle changes. This is why Marshall Lifestyle Medicine puts so much emphasis on the 12 Pillars of Lifestyle Modification.
- Medications / Hormones - Metformin, GLP-1 agonists, Testosterone Replacement
- CPAP for treatment of Sleep Apnea
- Education – Understanding the connection between lifestyle and disease is paramount to ending this paradigm.
- Specific Nutraceuticals
- Collaborative and Personalized Treatment Plans involving physicians educated in Metabolic Dysfunction, Lifestyle Medicine, and Proper Hormone Therapy are critical to success.
Take Home:
Disease is not inevitable. Most Disease is Preventable and/or Reversible. Seek treatment in a practice that is Preventative, Lifestyle-centric, and is an Integrative Care Model. Do not accept the Specialist Referral Roulette. Take Charge of your Health and know that aging is inevitable, but it does not have to involve chronic disease management, suffering and disability. Know the facts! Chronic Disease Management is big business. Why would that business want to give up its cash cow???
Witten By:
John Marshall Mullins, MD
