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


RESULTS
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.


CONCLUSIONS
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.
Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
May-Yun
MY
Wang
Xinxin
X
Yu
Young
Y
Lee
S Kay
SK
McCorkle
Gregory O
GO
Clark
Suzanne
S
Strowig
Roger H
RH
Unger
Philip
P
Raskin
D000328:Adult; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology*; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007049:Iatrogenic Disease; D007328:Insulin / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008875:Middle Aged; D012307:Risk Factors
D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin