Skip to main content
CartClose Cart

Unlocking Optimal Health: A Guide to Metabolic Restoration Part 1 of 3 Introduction, Diagnosis, Pathophysiology, By Dan Carter, ND

By September 11, 2024Blog10 min read

There are many reasons for the modern age decline of human health, but they fit into three main categories:

  • The pharmaceutical take-over of medicine, medical education, hospitals and our whole health system
  • The degradation of our food supply into the commonly available choices of highly processed high sugar consumables
  • The normalization of very little physical movement with extended periods of sitting

 

What results from this combination of circumstances is metabolic disease, in particular, metabolic syndrome. Metabolic syndrome is a combination of three or more of the following five medical conditions: central obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Insulin resistance negatively effects these five conditions. From 1999 to 2018, the prevalence of metabolic syndrome among US adults increased significantly from 36.2% to 47.3%. (1)

The diagnosis of metabolic syndrome (MetS) requires the presence of 3 or more metabolic abnormalities:

  • A waist circumference of more than 40 inches in men and 35 inches in women
  • Serum triglycerides 150 mg/dL or greater
  • Reduced high-density lipoprotein cholesterol, less than 40 mg/dL in men or less than 50 mg/dL in women
  • Elevated fasting glucose of l00 mg/dL or greater
  • Blood pressure values of systolic 130 mm Hg or higher or diastolic 85 mm Hg or higher (2)

Pathophysiology

The pathophysiology of MetS encompasses several complex mechanisms. The debate as to whether the different elements of MetS form by themselves distinct pathologies or fall under a common, broader pathogenic process is shifting to the former. Although there are genetic and epigenetic factors contributors (3), lifestyle and environmental habits such as overeating and lack of physical activity are the major contributors to the development of MetS. A causative role can be given to high caloric intake, particularly carbohydrates, since visceral adiposity has been shown to be an important trigger that activates most of the pathways of MetS (4). Among the proposed mechanisms, insulin resistance, chronic inflammation, and neurohormonal activation seem to be essential players in the progression of MetS and its subsequent transition to CVD and T2DM. Another pathology that is present with visceral obesity is non-alcoholic fatty liver disease (NAFLD), although a move is currently underway to change the name nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD); this makes sense as MASLD better reflects the etiology. MASLD is considered to be the liver manifestation of metabolic syndrome, and 50 to 70% of people with diabetes, and 80-90% of obese adults (5), are found to have the disease on performance of liver ultrasound.

Modifiable Risk Factors

 

The risk factors for metabolic disease are all related to diet and lifestyle. By understanding the pathophysiology of causality, the practitioner can work with the patient to effectively make sustainable diet and lifestyle choices.

 

What, exactly, causes each of the metabolic abnormalities?

 

  • Insulin resistance – Recent studies suggest that hyperinsulinemia associated with excess carbohydrate intake and obesity drives the metabolic dysfunction associated with insulin resistance. There are other contributors, but none as basic. The metabolic consequences of insulin resistance include hyperglycemia, hypertension, dyslipidemia, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, a prothrombotic state and dementia. Insulin resistance is primarily an acquired condition related to excess body fat. (6) Several clinically useful surrogate measures of insulin resistance include HOMA-IR, HOMA2, QUICKI, serum triglyceride, triglyceride/HDL ratio and lipoprotein insulin resistance.

 

Sidebar: Hyperuricemia occurs in humans, birds, reptiles and great apes due to lack a liver enzyme called uricase which breaks down and regulates uric acid. Blood uric acid levels may rise due to increased purines (organ and other meats, beer – hops) and excess fructose intake; think HFCS. Fructose -> liver -> liver metabolizes fructose to xanthine which is metabolized to uric acid. Uric acid contributes to increased hunger -> obesity -> insulin resistance. Gout can result from high uric acid levels; most people who experience gout have metabolic disease. Males are 3X more likely to have gout than females. Henry VIII, king of England (1509-1547) was famous for being obese and having gout.

 

  • Central obesity – Overall and central obesity are assessed using BMI, waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR). Normal-weight central obesity is defined as CO among individuals with normal weight, as assessed by BMI (skinny-fat). CO is significantly associated with hypertension but not associated with diabetes among those with normal weight. Central obesity is common to metabolic syndrome, with mediating factors of insulin resistance, dyslipidemia and systematic inflammation. It plays an important role in the pathogenesis of cardiovascular diseases (CVD) and certain cancers. (7) Visceral fat deposition is high in both normal and high BMI patients due to hyperinsulinemia and insulin resistance. (8) Studies show a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on increased inflammation common to MetS. (de Heredia, 2012)

 

  • Hypertension – Historically, primary (essential) hypertension was described as high blood pressure that is multi-factorial and doesn’t have one distinct cause. (9) One of the causes listed by Cleaveland is too much salt in diet. I would posit that primary hyperaldosteronism is the cause of hypertension in MetS, and many cases of primary hypertension in people not identified with MetS. Aldosterone increases with insulin resistance as the main driver, so unsurprisingly, it is high in obesity and type 2 diabetes. (10). High aldosterone results in sodium retention causing hypertension. When insulin resistance is corrected, aldosterone drops and blood pressure can return to normal because the kidneys allow increased sodium excretion.

 

  • Hyperglycemia – Diabetes and its complications are among the leading causes of organ failure. It is imperative that timely, patient-centered care is provided to avoid microvascular and macrovascular damage. (12)

 

  • Hyperglycemia upregulates markers of chronic inflammation and contributes to increased reactive oxygen species (ROS) generation, both of which cause vascular dysfunction. Increased oxidative stress and inflammation are strongly related to insulin resistance and impaired insulin secretion. (13)

 

  • The hyperglycemia associated with MetS is caused by too high carbohydrate intake, leading to blood glucose spikes, hyperinsulinemia, hypertriglyceridemia, obesity, and insulin resistance. Insulin is the main anabolic hormone, promoting carbon energy deposition in the body; in other words, insulin causes energy/fat storage in adipose tissues, liver, and muscle. (14) The presence of high insulin or insulin resistance prevents the release of fats from adipocytes, so the obese person cannot eliminate body fat.

 

  • Dyslipidemia (high serum triglycerides) – Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology, although lifestyle factors predominate. (15) Chronic high blood glucose signals the liver to convert the sugar to triglycerides, which are then transported by lipoproteins for tissue storage. The initial and most valuable approach for eliminating HTG is an adjustment in lifestyle contributors to HTG. These include management of diet, obesity, and the non-TG components of MetS.

 

  • Low serum high-density lipoprotein (HDL) – Low HDL has been described in the different forms of familial lipid disorders and as a part of MetS. (16) Low HDL is <40 mg/dL for males and <50 mg/dL for females. HDL should be 60 mg/dL or higher. HDL is composed of cholesterol, triglycerides, and various apolipoproteins. HDL is known for its antiatherogenic and antiinflammatory properties, because of its uptake and return of cholesterol stored in the foam cells of atherosclerotic plaques to the liver. (17) HDL transports triglycerides and, when triglyceride levels are high, HDL will undergo changes that cause it to break down faster, leading to a lower level. (18)

Upcoming Blog Posts

Part 2: Primary treatments for metabolic disease

Part 3:  Secondary treatments for metabolic disease

 

Citations

  • Martin SS, Aday AW, Almarzooq ZI, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation. 2024 Feb 20;149(8):e347-e913. doi: 10.1161/CIR.0000000000001209. Epub 2024 Jan 24. Erratum in: Circulation. 2024 May 7;149(19):e1164. PMID: 38264914.
  • Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018 Feb 26;20(2):12. doi: 10.1007/s11906-018-0812-z. PMID: 29480368; PMCID: PMC5866840.
  • Fathi Dizaji B. The investigations of genetic determinants of the metabolic syndrome. Diabetes Metab Syndr. 2018 Sep;12(5):783-789. doi: 10.1016/j.dsx.2018.04.009. Epub 2018 Apr 11. PMID: 29673926.
  • Matsuzawa Y, Funahashi T, Nakamura T. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. J Atheroscler Thromb. 2011;18(8):629-39. doi: 10.5551/jat.7922. Epub 2011 Jul 8. PMID: 21737960.
  • Kudaravalli P, John S. Nonalcoholic Fatty Liver. [Updated 2023 Apr 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541033/
  • Freeman AM, Acevedo LA, Pennings N. Insulin Resistance. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507839/
  • Owolabi EO, Ter Goon D, Adeniyi OV. Central obesity and normal-weight central obesity among adults attending healthcare facilities in Buffalo City Metropolitan Municipality, South Africa: a cross-sectional study. J Health Popul Nutr. 2017 Dec 28;36(1):54. doi: 10.1186/s41043-017-0133-x. PMID: 29282137; PMCID: PMC5745975.
  • Huang H, Zheng X, Wen X, Zhong J, Zhou Y, Xu L. Visceral fat correlates with insulin secretion and sensitivity independent of BMI and subcutaneous fat in Chinese with type 2 diabetes. Front Endocrinol (Lausanne). 2023 Feb 27;14:1144834. doi: 10.3389/fendo.2023.1144834. PMID: 36909323; PMCID: PMC9999013.
  • From the website: https://my.clevelandclinic.org/health/diseases/22024-primary-hypertension-formerly-known-as-essential-hypertension. Accessed 08.01.2024.
  • Zavatta G, Casadio E, Rinaldi E, Pagotto U, Pasquali R, Vicennati V. Aldosterone and type 2 diabetes mellitus. Horm Mol Biol Clin Investig. 2016 Apr 1;26(1):53-9. doi: 10.1515/hmbci-2015-0065. PMID: 26876814.
  • de Heredia FP, Gómez-Martínez S, Marcos A. Obesity, inflammation and the immune system. Proc Nutr Soc. 2012 May;71(2):332-8. doi: 10.1017/S0029665112000092. Epub 2012 Mar 20. PMID: 22429824.
  • Kreider KE, Gabrielski AA, Hammonds FB. Hyperglycemia Syndromes. Nurs Clin North Am. 2018 Sep;53(3):303-317. doi: 10.1016/j.cnur.2018.04.001. PMID: 30099998.
  • Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol. 2019 Dec;70(6). doi: 10.26402/jpp.2019.6.01. Epub 2020 Feb 19. PMID: 32084643.
  • Tokarz VL, MacDonald PE, Klip A. The cell biology of systemic insulin function. J Cell Biol. 2018 Jul 2;217(7):2273-2289. doi: 10.1083/jcb.201802095. Epub 2018 Apr 5. PMID: 29622564; PMCID: PMC6028526.
  • Santos-Baez LS, Ginsberg HN. Hypertriglyceridemia-Causes, Significance, and Approaches to Therapy. Front Endocrinol (Lausanne). 2020 Sep 2;11:616. doi: 10.3389/fendo.2020.00616. PMID: 32982991; PMCID: PMC7492386.
  • Mora S, Glynn RJ, Ridker PM. High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation. 2013 Sep 10;128(11):1189-97.
  • Bailey A, Mohiuddin SS. Biochemistry, High Density Lipoprotein. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549802/
  • Stadler JT, Marsche G. Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function. Int J Mol Sci. 2020 Nov 26;21(23):8985. doi: 10.3390/ijms21238985. PMID: 33256096; PMCID: PMC7731239.

 

Leave a Reply