About 85% of the people that walk through my office doors have some degree of insulin resistance. What is “insulin resistance?” It is an over production of insulin in response to ANY form of carbohydrate intake (yes, even the “good carbs” cause an insulin over-response in a person with insulin resistance.) How do I know this? Because I routinely check insulin loads and the down stream markers of insulin on a large number of the patients that I see. I have been fascinated by the fact that a diet high in both sugar and fat [like the Standard American Diet, (SAD) diet] turn on the genetics leading to insulin resistance.
Insulin acts like a key at the glucose doorway of every cell in your body. In many people, the insulin acts like a “dull key” – not opening the glucose doorway as efficiently. So the body panics, and releases extra insulin in response to the same load of carbohydrate or glucose. People with insulin resistance will produce between 2-10 times the normal amount of insulin in response to a simple carbohydrate load. Recent studies(1,2) reveal high cholesterol and diets high in both fat and carbohydrate cause insulin resistance to progress or worsen.
So, instead of producing enough insulin to accommodate the one slice of bread or the one apple that you might eat, the insulin resistant person produces enough insulin for an entire loaf of bread or an entire bushel of apples. This excess insulin then stimulates one or all of the following:
- Weight Gain – Insulin directly stimulates weight gain by activating lipoprotein lipase to take up triglycerides into the fat cells. This causes direct storage of fat and increases your waistline. (3)
- Elevated Triglycerides – Insulin directly stimulates production of free fatty acids and triglycerides through hepatic gluconeogenesis and is even more notably amplified by the broken signaling mechanism of the FOX-01 phosphorylation mechanism in patients with insulin resistance. (4)
- Increased number of Small Dense LDL (sdLDL) particles – Low density lipoprotein (LDL, or “bad cholesterol”) is actually comprised of various sized lipoproteins including small, medium and large. As triglycerides increase, the small dense LDL particle numbers increase. Research points to the fact that it is the small dense particle that is highly atherogenic (leading to the formation of vascular plaques within the arteries). (5, 8)
- Elevated Uric Acid – Leptin resistance and insulin resistance syndromes are often found together and are suspected to have significant influence on each other. High insulin loads lead to “sick adipose cells” causing leptin resistance. This has a dramatic effect on hepatic fructose metabolism increasing the production of uric acid. Excess insulin suppresses urinary excretion of uric acid and dramatically increases serum content of uric acid and the risk of kidney stones and gout. (6, 7)
- Increased Inflammation – Increased levels of circulating insulin have a direct correlation on raising many of the inflammatory markers and hormones including TNF-alpha and IL-6 in the body (9). Any disease process that is caused by chronic inflammation can be amplified by increased circulating levels of insulin including asthma, acne, eczema, psoriasis, arthritis, inflammatory bowel and celiac disease, etc.
- Elevated Blood Pressure – Increased uric acid production from insulin resistance as noted above directly suppresses production of nitric oxide within the vasculature and increases blood pressure (7). This completes the triad of metabolic syndrome (elevated triglycerides & cholesterol, weight gain, and elevated blood pressure) found in patients with insulin resistance.
- Water Retention – We have known for many years that insulin affects the way the kidney uses sodium in the distal nephron. Insulin has a direct effect on sodium retention in the kidney. As insulin levels rise, the kidney retains increased levels of sodium (10). Water follows sodium and thereby causes fluid retention. This is the reason that many of my insulin resistant patients who have struggled with leg swelling and edema suddenly improve when they correct their diet and their high circulating insulin levels fall. It is also the reason that many of my patients show up in my office after the holidays with swollen legs and amplified swelling in their varicose veins after cheating on their ketogenic diets.
If you are plagued by any or all of these, my first suggestion is to see your doctor and get screened for insulin resistance. Having seen these signs and patterns over the last 15 years of medical practice, I am still astonished every day by the dramatic effect our diet plays on the hormonal changes within the body. Remember that the food you eat is actually the most powerful form of medicine . . . and the slowest form of pernicious poison.
- Cholesterol Elevation Impairs Glucose-Stimulated Ca2+Signaling in Mouse Pancreatic β-Cells, Endocrinology, June 2011, Andy K. Lee, Valerie Yeung-Yam-Wah, Frederick W. Tse, and Amy Tse; DOI: http://dx.doi.org/10.1210/en.2011-0124
- Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element–Binding Protein-1c in the Hepatocytes, DIABETES, VOL. 54, JUNE 2005; Seung-Soon Im, Seung-Youn Kang, So-Youn Kim, Ha-il Kim, Jae-Woo Kim, Kyung-Sup Kim and Yong-Ho Ahn
- Obesity and Insulin Resistance. J Clin Invest. 2000 Aug;106(4):473-81.Kahn BB, Flier JS
- Selective versus Total Insulin Resistance: A Pathogenic Paradox, Cell Metabolism, Volume 7, Issue 2, 6 February 2008, Pages 95–96, Michael S. Brown, Joseph L. Goldstein
- Association between small dense LDL and early atherosclerosis in a sample of menopausal women, Department of Clinical Medicine and Surgery, University “Federico II” Medical School, Naples, Italy Division of Cardiology, Moscati Hospital, Aversa, Italy A. Cardarelli Hospital, Naples, Italy, Gentile M, Panico S, et al., Clinica Chimica Acta, 2013
- Sugar, Uric Acid and the Etiology of Diabetes and Obesity. Diabetes. 2013;62(10):3307-3315, Richard J. Johnson; Takahiko Nakagawa; L. Gabriela Sanchez-Lozada; Mohamed Shafiu; Shikha Sundaram; Myphuong Le; Takuji Ishimoto; Yuri Y. Sautin; Miguel A. Lanaspa
- Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010 Sep;110(9):1307-21. doi: 10.1016/j.jada.2010.06.008. Lustig RH
- Cardiovascular Risk in Patients Achieving Low-Density Lipoprotein Cholesterol and Particle Targets. Atherosclerosis. Vol 235; 585-591, May 2014, Peter P. Toth, Michael Grabner, Rajeshwari S. Punekar, Ralph A. QuimboMark J. Cziraky c, Terry A. Jacobson
- Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS), Circulation, July 2000, 102:42-47; Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; George Howard, DrPH; Leena Mykka¨nen, MD, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD
- The Effect of Insulin on Renal Sodium Metabolism. Diabetologia. September 1981, Volume 21, Issue 3, pp 165-171. R. A. DeFronzo