Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans.
Level 3 - non-randomized controlled study
Controlled human clamp physiological study without explicit randomization described in the abstract.
PubMed 27445005 · doi:10.1016/j.jdiacomp.2016.06.030
What was done
The authors evaluated the acute effects of moderate hyperglycemia and hypoglycemia on endothelial function and pro-inflammatory/pro-atherothrombotic biomarkers in 45 healthy non-diabetic participants. Subjects were compared during four glucose clamp conditions: euinsulinemic hyperglycemia (plasma glucose 11.1 mmol/L with pancreatic clamp), hyperinsulinemic hyperglycemia (plasma glucose 11.1 mmol/L with pancreatic clamp), hyperinsulinemic euglycemia (plasma glucose 5.1 mmol/L), and hyperinsulinemic hypoglycemia (plasma glucose 2.9 mmol/L). Brachial artery endothelial function was measured using two-dimensional Doppler ultrasound.
What was found
Insulin concentrations were 194 ± 23 pmol/L during euinsulinemic hyperglycemia and 850 ± 49 to 988 ± 114 pmol/L across hyperinsulinemic protocols. VCAM-1, ICAM-1, E-selectin, P-selectin, PAI-1, and IL-6 responses significantly increased (p < 0.05 to p < 0.0001) during euinsulinemic hyperglycemia and hypoglycemia relative to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia. PAI-1 increased significantly more during hypoglycemia than euinsulinemic hyperglycemia (p < 0.04), and TNF-α responses increased during hypoglycemia compared to hyperinsulinemic euglycemia or hyperglycemia (p < 0.05). In vivo endothelial function was similarly blunted by moderate hyperglycemia and hypoglycemia.
Why it matters
This study demonstrates that acute moderate hypoglycemia causes endothelial dysfunction and pro-atherothrombotic activation comparable to or exceeding that of moderate hyperglycemia in healthy humans. It also indicates that hyperinsulinemia prevents these adverse vascular and inflammatory changes during hyperglycemia, but fails to prevent them during hypoglycemia.
Limits
The abstract does not specify whether clamp protocols were randomized or conducted using a crossover versus parallel-group design. The sample size is modest (n = 45), only acute short-term effects were assessed, and the findings in healthy non-diabetic individuals may not directly translate to patients with diabetes.
Cited by
- supports Elevated blood sugar damages the single-cell endothelial lining of blood vessels within a short period, leading to inflammation and clotting.