Pre-Diabetes Metabolic Syndrome, Type 2 Diabetes and Mitochondrial Function

By Prof. Garth L. Nicolson
Department of Molecular Pathology,
The Institute for Molecular Medicine,
Huntington Beach, California

Type 2 Diabetes develops from a pre-Diabetes condition called Metabolic Syndrome (MetSynd).  MetSynd is present in over 22% of the adult U.S. population, and it is made up of several interrelated disturbances of sugar and lipid metabolism.  The major risk factors for MetSynd are: abdominal obesity, high blood sugar, increased levels of low-density lipoproteins (LDL) and reduced levels of high-density lipoproteins (HDL), elevated blood pressure, resistance to insulin and the presence of inflammatory molecules in the blood [1, 2].

Insulin resistance is one of the initial signs in the development of MetSynd [3].  Insulin is secreted into the blood by the pancreas in response to increased blood sugar levels; it assists in sugar metabolism and is essential for our development, growth and maintenance of proper blood sugar levels.  When the blood concentrations of insulin are insufficient to regulate the above processes or our cells do not respond to insulin, insulin resistance occurs. Insulin resistance is one of the primary events in the development of MetSynd, and this can ultimately lead to type 2 Diabetes.

Defects in the capacity to metabolize certain lipid components called fatty acids as well as defects in sugar metabolism are thought to play important roles in insulin resistance and MetSynd [2, 3].¬† When fatty acids are oxidized, like the oxidizing or ‚Äėrusting‚Äô of metal, they are damaged and do not function properly.¬† Fatty acid lipid components are important building blocks of cellular structure, especially the cellular membranes that enclose cells and separate compartments of each cell, such as the nuclei where genetic information is housed in the form of DNA, and the mitochondria, the little ‚Äėbatteries‚Äô inside our cells that produce the energy our cells require.

Mitochondrial Damage, Metabolic Syndrome and Type 2 Diabetes

An important event in the development of MetSynd and eventually type 2 Diabetes is damage to cellular ‚Äėbatteries‚Äô or mitochondria where energy production occurs [2, 3].¬† Various studies point to generalized mitochondrial dysfunction in MetSynd and type 2 Diabetes, and this dysfunction results in the overall feeling of fatigue and lack of energy [2].¬† Mitochondrial dysfunction has also been linked to chronic insulin resistance.¬† These changes cause gradual pancreatic and other organ dysfunction due to changes in lipid-oxidation, which results in changes in mitochondrial structure [2, 3].This damage to our mitochondria, in turn, results in loss of cellular energy production and eventually fatigue and the overall loss of energy to do normal everyday tasks.

When mitochondria function properly, the amount of oxidation produced is effectively balanced by the presence of natural antioxidants and antioxidant enzymes present inside our cells.  In MetSynd, type 2 Diabetes and associated diseases, however, excess oxidation is produced in our cells that cannot be neutralized, and this results in damage to mitochondrial and other cellular membranes and their components.

In obese, insulin-resistant, pre-Diabetic people higher amounts of damaged lipids called fatty acids accumulate. This also occurs in many elderly and obese people where oxidized fatty acids accumulate in muscle mitochondria, and eventually this causes loss of energy production and muscle fatigue [2, 3].

The Role of Mitochondria in Aging and Fatigue

Fatigue or lack of energy occurs naturally during aging and is a common condition in many clinical diagnoses, including MetSynd, type 2 Diabetes, cardiovascular diseases, respiratory, musculoskeletal and bowel conditions as well as infections and cancer [2].  Fatigue is related to reductions in the efficiency of mitochondrial energy production, and oxidative damage to mitochondrial components can impair energy production and cause fatigue in all of these conditions.

Mitochondria are critical elements in the process of aging, and they have been proposed to be one of the regulators of aging and cell death.  During aging and fatigue antioxidant enzymes, low molecular weight antioxidants and enzyme repair mechanisms cannot restore or replace enough of the oxidation-damaged molecules to maintain mitochondrial function and other functions inside cells.  Disease and infection can also result in excess oxidative damage that exceeds the abilities of cells to repair and replace damaged molecules.

Replacement of Damaged Mitochondrial Membrane Components by Lipid Replacement Therapy

Lipid Replacement Therapy plus antioxidants, such as found in NT Factor¬ģ, has been used to reverse cellular oxidative damage and increase mitochondrial function in various clinical disorders that involve loss of mitochondrial function [5]. Lipid Replacement Therapy is useful for MetSynd and type 2 Diabetes, because it replaces damaged lipids with undamaged lipids to ensure proper structure and function of cellular and mitochondrial membranes.¬† In addition, when it is combined with antioxidants, vitamins and minerals (such as in Propax with NT Factor¬ģ or Revacel with NT Factor¬ģ) it can provide additional antioxidant protection and help maintain immune function and overall health. Lipid Replacement Therapy plus antioxidants has proven to be an effective method to prevent oxidation-associated damage to mitochondrial function.¬†¬† As discussed above, antioxidants alone may not completely eliminate or reverse oxidative damage, and this is why Lipid Replacement Therapy is an important addition to dietary antioxidant supplementation [2, 5, 6].¬† NT Factor‚Äôs encapsulated lipids are protected from oxidation in the gut and can be absorbed and transported into tissues without significant oxidative damage [5].

In clinical studies Lipid Replacement Therapy has been used to reduce fatigue and protect mitochondrial membranes. Products containing NT Factor¬ģ have been used in severely chronic fatigued patients, and it was found to reduce their fatigue approximately 40% within 8 weeks [6]. In four clinical trials NT Factor¬ģ in moderately and severely fatigued subjects was found to result in increased mitochondrial function and improved fatigue scores.¬† For example, in patients with chronic fatigue there was a 35.5% reduction in fatigue with a proportionate increase in mitochondrial function.¬† The results indicated that in moderately to severely fatigued subjects dietary Lipid Replacement Therapy plus antioxidants can significantly improve and even restore mitochondrial function and significantly improve fatigue.¬† Similar findings have been observed in Chronic Fatigue Syndrome and Fibromyalgia Syndrome patients [6]. The advantage of Lipid Replacement Therapy plus antioxidants over antioxidant mixtures alone is that further oxidative damage is reduced and damaged (oxidized) lipid components are gradually replaced, restoring function to cellular membranes and mitochondria.

Metabolic Syndrome, Atherosclerosis and Coronary Heart Disease

Atherosclerosis involves chronic inflammatory damage to blood vessels due to oxidative damage, lipid accumulation, inflammatory response, blood vessel cell death and the presence of blood clots, which can eventually result in the blockage of heart and other organ blood vessels [2].  A main cause of cardiovascular diseases and stroke, atherosclerosis is characterized by a number of risk factors, including abnormalities in lipoprotein distribution, increases in blood inflammatory proteins, and changes in vascular cell adhesion molecules.  In the cardiovascular system excess oxidation also plays a role in cardiovascular dysfunction.

The process of atherosclerosis is thought to begin with abnormalities in lipoprotein subclasses, their remnants, and low-density lipoproteins (LDL), all hallmarks of MetSynd.  In MetSynd lipoproteins and their remnants are susceptible to oxidation,and the presence of the oxidized lipoproteins is significantly associated with an abundance of inflammatory cells called macrophages in atherosclerotic lesions.

When they interact with the blood vessel wall, the oxidized lipoprotein subclasses can induce adhesion molecules on the cells lining the blood vessels, which can attract the circulating macrophages.  The adhesion and movement of the adherent macrophages to underlying tissue layers and their differentiation into fully inflammatory cells is highly associated with atherosclerotic plaques.  These plaques can break off and form blood clots that can occlude blood vessels in the heart, resulting in myocardial infarction, heart failure and stroke. They can also lodge in the brain and cause severe brain damage and death of nerve cells.

Thus the use of products containing NT Factor is an important dietary advance in helping prevent the most common diseases associated with aging.


1. Fonseca VA. The metabolic syndrome, hyperlipidemia and insulin resistance. Clin Cornerstone 2005; 7: 61-72.

2. Nicolson GL. Metabolic syndrome and mitochondrial function: molecular replacement and antioxidant supplements to prevent membrane oxidation and restore mitochondrial function. J Cell Biochem 2007; 100: 1352-1369.

3. Houston MC, Egan BM. The Metabolic Syndrome. Pathophysiology, diagnosis, clinical aspects, prevention and nonpharmacologic treatment: emphasis on lifestyle modifications, nutrition, nutritional supplements, vitamins, minerals, antioxidants, weight management and exercise.  J Am Nutraceutical Assoc 2005; 8(2): 3-83.

4. Huang H, Manton KG. The role of oxidative damage in mitochondria during aging: a review.  Front Biosci   2004; 9: 1100-1117.

5. Nicolson GL. Lipid replacement as an adjunct to therapy for chronic fatigue, anti-aging and restoration of mitochondrial function. J Am Nutraceutical Assoc 2003; 6(3): 22-28.

6. Nicolson GL, Ellithrope R. Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in chronic fatigue syndrome and other fatiguing illnesses.  J Chronic Fatigue Syndr 2006; 13(1):5 7-68.

About the Author:

Professor Garth L. Nicolson is the President, Chief Scientific Officer and Research Professor at the Institute for Molecular Medicine in Huntington Beach, California.  He is an Emeritus Professor of Pathology and Laboratory Medicine.  Professor Nicolson has published over 600 medical and scientific papers, edited 16 books, and served on the Editorial Boards of 30 medical and scientific journals and was the senior editor of four of these.  Professor Nicolson has won many awards, such as the Burroughs Wellcome Medal of the Royal Society of Medicine (United Kingdom), Stephen Paget Award of the Metastasis Research Society, the U. S. National Cancer Institute Outstanding Investigator Award, and the Innovative Medicine Award of Canada.  He is also a Colonel (Honorary) of the U. S. Army Special Forces and a U. S. Navy SEAL (Honorary) for his work on Armed Forces and veterans’ illnesses.