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The Liver’s Role in Blood Sugar Management

If you don’t live with type 1 diabetes (T1D), your pancreas’s beta cells produce insulin whenever your blood sugar level increases (usually after a meal). Before reaching your bloodstream and your body cells (e.g., muscle, fatty tissue), the insulin goes directly to your liver, which then stores excess glucose that will be gradually secreted back into your bloodstream in-between meals. This means that your liver plays a key role in controlling and stabilizing your blood sugar as a person who doesn’t have T1D. 

If you do have T1D, your pancreas’s beta cells were destroyed and no longer produce any insulin. You must inject insulin in your subcutaneous tissue to survive. This also means that the insulin that you inject reaches your body cells WITHOUT ever going through the liver. If it were possible to restore the primary action of insulin on your liver, you might see better glycemic control with decreased post-meal hyperglycemia and between-meal hypoglycemia. 

Could there be a workaround?

A manufacturer is currently testing a product that could artificially redirect injected insulin towards the liver first. The tested product is a group of vesicles (that act as “carriers”) that bind to insulin molecules to keep them from being used immediately by body cells. Having safely reached the liver, the freed-up insulin—the liver eliminates the vesicles—can be used by the liver first and then by other tissue. The product is formulated as an additive that could be added to any insulin cartridge, according to the manufacturer.

This video provides a detailed description.

 Does it work?

A study involving this product just completed its second phase, which means that the product’s efficacy was tested with a small-scale group of T1D patients. The additive was combined to insulin lispro (e.g., Humalog), and the effects of the resulting mixture were compared to those of regular insulin lispro.

Results show that average glycemic control, with or without the additive, was similar. However, patients who had less than optimal glycemic control (HbA1c > 8.5%) experienced fewer hypoglycemic episodes when using the additive. There are still a number of steps to be completed before the product is released, but this study shows that modifying existing insulin can reduce the risk of hypoglycemia.

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References

  • Bode, B. W., Weinstock, R. S., Garg, S. K., Klonoff, D. C., Singh, K. K., Muchmore, D. B., . . . Sanadi, C. E. (2020). 111-LB: Hepatic Insulin Delivery to Minimize Hypoglycemic Events in Persons with Type 1 Diabetes: The OPTI-1 Study. Diabetes, 69(Supplement 1). doi:10.2337/db20-111-lb
  • Klonoff, D., Bode, B., Cohen, N., Penn, M., Geho, W. B., & Muchmore, D. B. (2019). Divergent Hypoglycemic Effects of Hepatic-Directed Prandial Insulin: A 6-Month Phase 2b Study in Type 1 Diabetes. Diabetes Care, 42(11), 2154-2157. doi:10.2337/dc19-0152
  • Ph.D., M. (2020, October 05). One-of-a-Kind Technology Aims to Reduce Blood Sugar Swings. Retrieved November 04, 2020, from https://www.diabetesdaily.com/learn-about-diabetes/treatment/insulin-101/new-approach-to-insulin-delivery-may-reduce-blood-sugar-swings/
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