Association of Blood Glucose and Clinical Outcome after Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Elevated blood glucose levels following acute ischemic stroke have been associated with adverse clinical outcomes in thrombolytic and nonthrombolytic treated patients. The current study examined multiple blood glucose parameters and their association with modified Rankin Scale (mRS) score at 3 months following mechanical thrombectomy and hospital discharge. METHODS: Acute ischemic stroke patients undergoing mechanical thrombectomy with a retrievable stent at two stroke centers were studied. Admission blood glucose level, maximum blood glucose during the hospital stay, and serial blood glucose measurements within the first 24 h of hospital admission were recorded. Variability in blood glucose level was represented by the standard deviation of the serial measurements within the first 24 h. The following demographic and clinical data was also collected: age, sex, baseline NIHSS score, onset-to-reperfusion times, hemoglobin A1c, and stroke mechanism. RESULTS: 79 patients were identified; at 3 months, 35 patients had an mRS score of 0-2 and 44 had had an mRS of 3-6. Among the blood glucose variables, standard deviation of blood glucose in the first 24 h following admission and maximum blood glucose during hospital stay were significantly higher in the mRS 3-6 group. In multivariate logistic regression analysis, only the standard deviation of blood glucose remained significant (OR = 1.07, 95% CI = 1.02-1.11, p = 0.003) in a model that adjusted for admission NIHSS score (p = 0.016) and number of stent retriever passes (p = 0.042). CONCLUSIONS: Greater blood glucose variability following acute ischemic stroke is associated with worse clinical outcome in patients undergoing mechanical thrombectomy.

Mechanisms of C-peptide-mediated rescue of low O2-induced ATP release from erythrocytes of humans with type 2 diabetes.

The circulating erythrocyte, by virtue of the regulated release of ATP in response to reduced oxygen (O2) tension, plays a key role in maintaining appropriate perfusion distribution to meet tissue needs. Erythrocytes from individuals with Type 2 diabetes (DM2) fail to release ATP in response to this stimulus. However, the administration of C-peptide and insulin at a 1:1 ratio was shown to restore this important physiological response in humans with DM2. To begin to investigate the mechanisms by which C-peptide influences low O2-induced ATP release, erythrocytes from healthy humans and humans with DM2 were exposed to reduced O2 in a thin-film tonometer, and ATP release under these conditions was compared with release during normoxia. We determined that 1) low O2-induced ATP release from DM2 erythrocytes is rescued by C-peptide in the presence and absence of insulin, 2) the signaling pathway activated by C-peptide in human erythrocytes involves PKC, as well as soluble guanylyl cyclase (sGC) and 3) inhibitors of cGMP degradation rescue low O2-induced ATP release from DM2 erythrocytes. These results provide support for the hypothesis that both PKC and sGC are components of a signaling pathway activated by C-peptide in human erythrocytes. In addition, since both C-peptide and phosphodiesterase 5 inhibitors rescue low O2-induced ATP release from erythrocytes of humans with DM2, their administration to humans with DM2 could aid in the treatment and/or prevention of the vascular disease associated with this condition.