Diabetes

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The Problem
Type 2 diabetes is the primary chronic disease associated with increased insulin resistance.  Currently, about 30 million Americans have type 2 diabetes, and another 100 million Americans have pre-diabetes.  High levels of insulin resistance characterize both conditions.  Insulin resistance represents the inability of a cell to remove glucose from the blood. About 50 percent of this action is orchestrated by AMPK.  Thus, any decrease in AMPK activity will increase insulin resistance (1). 

The Traditional Medical Approach
The primary drug used in treating type 2 diabetes is metformin, which is known to activate AMPK (2, 3).  More potent drugs to treat type 2 diabetes, such as thiazolidinediones (TZDs), also work by increasing AMPK activity (4).  Newer medications, such as injectable GLP-1 agonists, also increase AMPK activity (5).  However, these drugs also have numerous side effects associated with long-term use.

The Metabolic Engineering® Approach
Many drugs used to treat type 2 diabetes work through AMPK activation.  Thus, the consistent use of Metabolic Engineering® works in concert with any drug therapy for type 2 diabetes treatment to help reprogram your metabolism by activating AMPK.  Using only the Zone diet as a single dietary intervention resulted in significant reductions of HbA1c (the primary marker of the severity of type 2 diabetes) and a significant decrease in the use of their diabetic medications in 12 weeks (6).  Adding the omega-3 fatty acids and polyphenols only adds to the AMPK-activating benefit of the Zone diet, as they are indirect activators of AMPK (7).



References
1. Saha AK, Xu XJ, Balon TW, Brandon A, Kraegen EW, Ruderman NB. Insulin resistance due to nutrient excess: Is it a consequence of AMPK downregulation? Cell Cycle. 2011; 10:3447-51. doi: 10.4161/cc.10.20.17886.

2. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action.  J Clin Invest. 2001; 108:1167-74. doi: 10.1172/JCI13505.

3. Goel S, Singh R, Singh V, Singh H, Kumari P, Chopra H, Sharma R, Nepovimova E, Valis M, Kuca K, Emran TB. Metformin: Activation of 5′ AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action.  Front Genet. 2022; 13:1022739. doi: 10.3389/fgene.2022.1022739.

4. LeBrasseur NK, Kelly M, Tsao TS, Farmer SR, Saha AK, Ruderman NB, Tomas E. Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues.  Am J Physiol Endocrinol Metab. 2006; 291:E175-81. doi: 10.1152/ajpendo.00453.2005. 

5. Reis-Barbosa PH, Marcondes-de-Castro IA, Marinho TS, Aguila MB, Mandarim-de-Lacerda CA. The mTORC1/AMPK pathway plays a role in the beneficial effects of semaglutide (GLP-1 receptor agonist) on the liver of obese mice.  Clin Res Hepatol Gastroenterol. 2022; 46:101922. doi: 10.1016/j.clinre.2022.101922.

6. Hamdy O and Carver C. The Why WAIT program: improving clinical outcomes through weight management in type 2 diabetes.  Curr Diab Rep. 2008; 8:413-20. doi: 10.1007/s11892-008-0071-5.

7. Sears B and Saha AK.  Dietary control of inflammation and resolution.  Front Nutr. 2021; 8:709435. doi: 10.3389/fnut.2021.709435.