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J Diabetes Complications. 2013 Jan-Feb;27(1):70-4. doi: 10.1016/j.jdiacomp.2012.08.008. Epub 2012 Oct 15.

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

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Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.



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.


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.


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.


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.

[Indexed for MEDLINE]

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