Effects of KDT501 on metabolic parameters in insulin-resistant prediabetic humans

Philip A. Kern, Brian S. Finlin, Dorothy Ross, Tania Boyechko, Beibei Zhu, Neile Grayson, Robert Sims, Jeffrey S. Bland

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Context: KDT501 is an isohumulone drug that has demonstrated beneficial effects on metabolic parameters in mice. Objective: This study was intended to examine potential improvements in metabolism in humans. Design and Setting: Changes in carbohydrate and lipid metabolism, along with inflammatory markers, were evaluated in prediabetic humans in a clinical research center. Participants: Nine obese patients participated. All had prediabetes or normal glucose tolerance plus three features of metabolic syndrome. Intervention: All participants were treated with escalating doses of KDT501 to a maximum dose of 1000 mg every 12 hours for a total of 28 days. Outcome Measures: Changes in carbohydrate metabolism were measured with oral glucose tolerance, homeostatic model of insulin resistance, and euglycemic clamp; changes in plasma lipids and response to a lipid tolerance test; and changes in plasma inflammatory markers. Results: The drug was well tolerated. After KDT501 treatment, plasma triglycerides were reduced at 4 hours during a lipid tolerance test. Furthermore, plasma adiponectin and high-molecular-weight adiponectin increased significantly, and plasma tumor necrosis factor-a decreased significantly. There were no significant changes in oral glucose tolerance test results or insulin sensitivity measures. Conclusions: Despite the small sample size and the short duration of therapy, KDT501 administration reduced measures of systemic inflammation and improved postmeal plasma triglyceride levels, which may be beneficial in participants with insulin resistance or metabolic syndrome.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalJournal of the Endocrine Society
Volume1
Issue number6
DOIs
StatePublished - Jun 2017

Bibliographical note

Publisher Copyright:
© 2017 Endocrine Society.

Keywords

  • Adiponectin
  • Insulin resistance
  • KDT501
  • Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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