Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans

Abstract

Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor κB (NF-κB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ(2) analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, -1.37; 95% confidence interval, -2.65 to -0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury.

Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: a pilot, randomized safety and feasibility trial

“…Surprisingly, enteral and solid diets in SCI acute and sub-acute care have traditionally promoted high carbohydrate nutritional content (carbohydrate: 45%; fat: 30%, and protein: 25%). The presence of hyperglycemia on hospital admission (irrespective of past diabetes mellitus history) was found to be strongly associated with a lower probability of improvement in neurological function [25]. The ability of a KD to ameliorate the diabetic state and help stabilize hyperglycemia has been repeatedly shown in human studies [45,46].…”

“…Emerging evidence suggests that acute-phase hyperglycemia is a critical factor in the poor functional outcomes of SCI [25,26]. Surprisingly, enteral and solid diets in SCI acute and sub-acute care have traditionally promoted high carbohydrate nutritional content (carbohydrate: 45%; fat: 30%, and protein: 25%).…”

“…The presence of hyperglycemia ( ≥ 126 mg/dL) on hospital admission (irrespective of past diabetes mellitus history) was found to be strongly associated with a lower probability of improvement in motor and sensory function. Results of preclinical studies have indicated that hyperglycemia exacerbates inflammatory cytokine production, neural cell apoptosis, and demyelination during acute SCI in rodents [25]. These findings have shed light on the importance of achieving tight glycemic control in acute human SCI to obtain better neurological outcomes.…”

“…Emerging evidence also suggests that acute-phase hyperglycemia is a critical factor in the poor functional outcomes of SCI [25,26]. The presence of hyperglycemia ( ≥ 126 mg/dL) on hospital admission (irrespective of past diabetes mellitus history) was found to be strongly associated with a lower probability of improvement in motor and sensory function.…”

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair

“…[18][19][20][21][22][23] Experimental data in animals suggest that hyperglycemia may play a deleterious role in the setting of spinal cord ischemic injury; however, prospective human studies are lacking. [24][25][26] The purpose of this study was to examine the association between lower extremity weakness (LEW) and the glucose levels of blood and cerebrospinal fluid (CSF) in patients undergoing multibranched endovascular aneurysm repair (MBEVAR) of pararenal aortic aneurysms (PRAAs) and TAAAs.…”