Effects of Acute Insulin-Induced Hypoglycemia on Indices of Inflammation Putative mechanism for aggravating vascular disease in diabetes

Rohana J. Wright, David E. Newby, David Stirling, Christopher A. Ludlam, Ian A. Macdonald, Brian M. Frier

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE - To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes.

RESEARCH DESIGN AND METHODS - We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry.

RESULTS - In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P <= 0.02). Inflammation was triggered with CD40 expression increasing maximally at 24 h (3.13 +/- 2.3% vs. 2.06 +/- 1.0%) after hypoglycemia (P = 0.009). Both sCD40L and hsCRP (P = 0.02) increased with a nonsignificant rise in vWF and tPA, indicating a possible endothelial effect. A reduction in sCD40L, tPA, and P-selectin occurred during euglycemia (P = 0.03, P <= 0.006, and P = 0.006, respectively). In type 1 diabetes, both CD40 expression (5.54 +/- 4.4% vs. 3.65 +/- 1.8%; P = 0.006) and plasma sCD40L concentrations increased during hypoglycemia (peak 3.41 +/- 3.2 vs. 2.85 +/- 2.8 ng/ml; P = 0.03). Platelet-monocyte aggregation also increased significantly at 24 h after hypoglycemia (P = 0.03). A decline in vWF and P-selectin occurred during euglycemia (P <= 0.04).

CONCLUSIONS - Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type 1 diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury.

Original languageEnglish
Pages (from-to)1591-1597
Number of pages7
JournalDiabetes Care
Volume33
Issue number7
DOIs
Publication statusPublished - Jul 2010

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