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Impact of a mild decrease in fasting plasma glucose on β-cell function in healthy subjects and patients with type 2

Marta Seghieri1, Eleni Rebelos2, Brenno D Astiarraga2

  • 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; martaseghieri@gmail.com.

American Journal of Physiology. Endocrinology and Metabolism
|April 14, 2016
PubMed
Summary

Mildly lowering fasting glucose acutely impairs beta-cell function and insulin sensitivity in people with type 2 diabetes (T2D) and normal glucose tolerance (NGT). This highlights how prestimulatory glucose levels impact glucose metabolism differently in these groups.

Keywords:
arginine-stimulated acute insulin responsefasting plasma glucoseinsulin sensitivityβ-cell functionβ-cell mass

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Area of Science:

  • Endocrinology
  • Metabolic Research
  • Diabetes Mellitus Research

Background:

  • Restoring normal glucose levels (euglycemia) for extended periods improves insulin secretion in type 2 diabetes (T2D).
  • The acute impact of mild reductions in fasting plasma glucose (FPG) on beta-cell function and insulin sensitivity remains less understood.

Purpose of the Study:

  • To investigate the acute effects of mild fasting glucose decrements on beta-cell function and insulin sensitivity.
  • To compare these effects in individuals with normal glucose tolerance (NGT) and T2D.

Main Methods:

  • Employed isoglycemic (Iso) and subisoglycemic (Sub) tests in paired NGT and T2D participants.
  • Sub-test involved an insulin infusion to mildly lower FPG before a glucose challenge and arginine test.
  • Assessed beta-cell function via mathematical modeling and acute insulin response (AIR) to arginine using C-peptide levels.

Main Results:

  • The Sub-test significantly lowered FPG by 17% in NGT and 31% in T2D.
  • Total insulin release was reduced in the Sub-test for both groups.
  • Beta-cell glucose sensitivity and AIR to arginine decreased in NGT individuals but not in T2D patients.
  • Insulin sensitivity improved marginally in T2D and more so in NGT.

Conclusions:

  • Prestimulatory glucose levels acutely influence beta-cell function and insulin sensitivity.
  • These effects are distinct in individuals with NGT compared to those with T2D.
  • Mildly reduced fasting glucose acutely impairs beta-cell function and insulin sensitivity, particularly in NGT individuals.