Iatrogenic hyperinsulinemia in type 1 diabetes: Its effect on atherogenic risk markers

May-Yun Wang, Xinxin Yu, Young H Lee, S. Kay McCorkle, Gregory O. Clark, Suzanne Strowig, Roger H Unger, Philip Raskin

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Aims: Insulin is lipogenic and may invoke inflammation. We wished to determine if well controlled human and mice with type 1 diabetes had iatrogenic hyperinsulinemia as an explanation for the increased rate of coronary artery disease (CAD) in type 1 diabetes. Methods: Type 1 diabetic subjects with HbA1C less than 7.0% had plasma insulin measured before and one hour after a Boost® challenge and a dose of subcutaneously administered insulin. These levels were compared with non-diabetic humans. Plasma insulin levels in well controlled NOD mice with type 1 diabetes were measured 3 h and 17 h after their usual dose of insulin. Hepatic cholesterol-relevant CAD and inflammation markers were measured in the NOD mice. Result: Marked iatrogenic hyperinsulinemia was observed in patients at levels of approximately two times higher than in non-diabetic controls. Similar findings were present in the NOD mice. Hepatic CAD risk markers were increased by insulin, but did not exceed normal expression levels in non-diabetic mice with lower insulin. In contrast, insulin-mediated stimulation of pro-inflammatory mediators TNF-α and IL-1β remained significantly higher in hyperinsulinemic NOD than non-diabetic mice. Conclusion: Optimal insulin therapy in mice and humans with type 1 diabetes causes iatrogenic hyperinsulinemia and subsequently promotes pro-inflammatory macrophage response independent of hepatic cholesterol-relevant CAD markers. The tight glycemic control in type 1 diabetes may thus increase the risk for atherogenesis via inflammation.

Original languageEnglish (US)
Pages (from-to)70-74
Number of pages5
JournalJournal of Diabetes and Its Complications
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Coronary artery disease
  • Iatrogenic hyperinsulinemia
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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