Diabetes

Diabetes is a chronic and progressive disease affecting an ever-increasing number of individuals. More than 49% of people in NC (Burden of DM in NC [ADA]) (35.1% in the US) (1) have DM or prediabetes.  Those patients with diabetes use about 25% of the healthcare dollars spent in the US. (2).

Because of the complexity of DM, there has been a push to develop more medications and treatments for the disease.  Several new classifications of pharmaceuticals have been developed in the past 15 years.  GLP-1 agonists, dipeptidyl peptidase 4 inhibitors, and α glucosidase inhibitors all work by separate mechanisms to reduce blood glucose with the hope of slowing end organ damage. Patients are now taking these new medications along with Metformin and with insulin.  But no matter how complex the treatments get, nearly all treatment algorithms for DM specify that “healthy eating” or “improved diet” should be the first course of treatment and prevention. There can be some confusion, however, because there is not a definitive way to describe what constitutes a “healthy” diet. As we learn more about how the components of food affect the bioprocesses in our bodies, we are able to understand how to better compose diets that can improve and prevent disease.

Physiology

  • GLP-1 is an incretin hormone that is released from L-cells in the small and large intestines as food is ingested.  GLP-1 goes on to signal for the release of insulin from the â cells in the pancreas. GLP-1 is only active for a short time because it is deactivated by dipeptidyl peptidase 4 (DPP-4). Those with DM often have decreased levels of the GLP-1 hormone.
  • DPP4 is a protein on the surface of most cells. It degrades the GLP-1 hormone, many times within minutes of GLP-1’s excretion from L-cells.
  • á-glucosidase is a protein that aids carbohydrates in the passage across the brush border of the intestine into the blood stream.

Pharmacology

DM is such a complex disease. Pharmaceutical treatment goes by way of several mechanisms of action to provide a manner of reducing hyperglycemia.

  • GLP-1 agonists (Byetta, Victoza, Trulicity, Adlyxin and others) imitate the function of the GLP-1 hormone in the body, thereby increasing insulin release from the pancreas.
  • DPP4 inhibitors (Januvia, Tradjenta among others) keep the DPP4 protein from breaking down GLP-1 hormone.
  • á-glucosidase inhibitors prevent absorption of carbohydrates in the small intestine thus attenuating post prandial blood sugar rise.

Phyto Rx

            The Standards of Medical Care in Diabetes-2019 are now including the statement “higher intakes of nuts, berries, yogurt, coffee, and tea are associated with reduced diabetes risk”.(7)  Polyphenols found in blueberries, blackberries and other dark red and purple berries as well as cinnamon are a good choice for DM.

  • Increased insulin sensitivity has been reported with multiple fruits in this class. (4, 6, 11, 12)
  • Polyphenols increase secretion of GLP-1 from L-cells in the small intestine. (3)
  • Anthocyanins found in berries actively bind to the DPP4 enzyme restricting the degradation of the GLP-1 hormone. (3,5)
  • Anthocyanins found in blueberries and black currants may work in similar mechanism as á-glucosidase inhibitors by preventing glucose transport across the intestinal membrane into the bloodstream. (10)
  • Cinnamon suppresses expression of genes that signal for gluconeogenesis in the liver and thereby decreasing blood glucose. (14)

Anthocyanins also work as a prebiotic helping to maintain a healthy gut microbiome. They tend to provide the most beneficial activity when the gut is healthy. (13)

  1. https://www.niddk.nih.gov/health-information/communication-programs/ndep/health-professionals/practice-transformation-physicians-health-care-teams/why-transform/current-burden-diabetes-us
  2. Economic Costs of Diabetes in the U.S. in 2017 American Diabetes Association Diabetes Care May 2018, 41 (5) 917-928; DOI: 10.2337/dci18-0007
  3. Domínguez Avila, J., Rodrigo García, J., González Aguilar, G., & de la Rosa, L. (2017). The antidiabetic mechanisms of polyphenols related to increased glucagon-like peptide-1 (GLP1) and insulin signaling. Molecules22(6), 903.
  4. Skates, E., Overall, J., DeZego, K., Wilson, M., Esposito, D., Lila, M. A., & Komarnytsky, S. (2018). Berries containing anthocyanins with enhanced methylation profiles are more effective at ameliorating high fat diet-induced metabolic damage. Food and chemical toxicology, 111, 445-453.
  5. Fan, J., Johnson, M. H., Lila, M. A., Yousef, G., & de Mejia, E. G. (2013). Berry and citrus phenolic compounds inhibit dipeptidyl peptidase IV: Implications in diabetes management. Evidence-Based Complementary and Alternative Medicine, 2013.
  6. Lila, M. A. (2011). Impact of bioflavonoids from berry fruits on biomarkers of metabolic syndrome. Functional Foods in Health and Disease, 1(2), 13-24.
  7. Standards of Medical Care in Diabetes—2019 Abridged for Primary Care Providers American Diabetes Association. Clinical Diabetes. January 2019, 37 (1) 11-34.
  8. Tsuda, T. (2016). Recent progress in anti-obesity and anti-diabetes effect of berries. Antioxidants, 5(2), 13.
  9. Tsuda, T. (2012). Dietary anthocyanin‐rich plants: biochemical basis and recent progress in health benefits studies. Molecular nutrition & food research, 56(1), 159-170.
  10. Alvarado, J. L., Leschot, A., Olivera-Nappa, Á., Salgado, A. M., Rioseco, H., Lyon, C., & Vigil, P. (2016). Delphinidin-rich maqui berry extract (Delphinol®) lowers fasting and postprandial glycemia and insulinemia in prediabetic individuals during oral glucose tolerance tests. BioMed research international, 2016.
  11. Amiot, M. J., Riva, C., & Vinet, A. (2016). Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review. Obesity Reviews, 17(7), 573-586.
  12. Solverson, P., Rumpler, W., Leger, J., Redan, B., Ferruzzi, M., Baer, D., … & Novotny, J. (2018). Blackberry feeding increases fat oxidation and improves insulin sensitivity in overweight and obese males. Nutrients10(8), 1048.
  13. Esposito, D., Damsud, T., Wilson, M., Grace, M. H., Strauch, R., Xi, X., … & Komarnytsky, S. (2015). Black currant anthocyanins attenuate weight gain and improve glucose metabolism in diet-induced obese mice with intact, but not disrupted, gut microbiome. Journal of agricultural and food chemistry, 63(27), 6172-6180.
  14. Cheng, D. M., Kuhn, P., Poulev, A., Rojo, L. E., Lila, M. A., & Raskin, I. (2012). In vivo and in vitro antidiabetic effects of aqueous cinnamon extract and cinnamon polyphenol-enhanced food matrix. Food chemistry, 135(4), 2994-3002.
  15. Clegg, M. E., Pratt, M., Meade, C. M., & Henry, C. J. K. (2011). The addition of raspberries and blueberries to a starch-based food does not alter the glycaemic response. British journal of nutrition, 106(3), 335-338.
  16. Różańska, D., & Regulska-Ilow, B. (2018). The significance of anthocyanins in the prevention and treatment of type 2 diabetes. Adv Clin Exp Med, 27(1), 135-142.
  17. Curtis, P. J., van der Velpen, V., Berends, L., Jennings, A., Feelisch, M., Umpleby, A. M., … & Cassidy, A. (2019). Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome—results from a 6-month, double-blind, randomized controlled trial. The American journal of clinical nutrition, 109(6), 1535-1545.