Cerebral blood flow in type II diabetes mellitus patients with impaired awareness of hypoglycemia: a cross-sectional study

Cerebral blood flow is maintained and regulated through various homeostatic mechanisms. It is maintained even during hypoglycemia in patients with type 1 diabetes mellitus, but appears to increase in those with impaired awareness of hypoglycemia. However, experiments are lacking to clarify these findings. Thus, this study was conducted to investigate whether cerebral blood flow increases in type 2 diabetes mellitus patients with impaired awareness of hypoglycemia by using Doppler sonography. This was a cross-sectional study conducted from July 2021 to June 2022 in the emergency department (ED) of Inje University Busan Paik Hospital, Busan, South Korea. Patients with type 2 diabetes with complaints of various symptoms of hypoglycemia (defined as blood glucose level <60 mg/dL) were evaluated for this study after obtaining their informed consent. First, we assessed each patient’s awareness of hypoglycemia using the Gold method. Cerebral blood flow was then measured on Doppler sonography. The primary outcome was blood flow in both internal carotid arteries, and secondary outcomes included the diameter and time-averaged maximum velocity of both internal carotid arteries. A total of 132 patients were enrolled in the study, but 11 patients were excluded from analysis. Hypoglycemia was associated with increased cerebral blood flow in those with impaired awareness of hypoglycemia, but this association was not observed in other groups. The blood flow in the left internal carotid artery was significantly higher compared to the right side, perhaps due to the anatomical differences between the two arteries. The increased cerebral blood flow could be due to an adaptive response to hypoglycemia to enhance nutrient supply to the brain. However, given that this was a cross-sectional study, causality could not be determined. Thus, as in type 1 diabetes mellitus, hypoglycemia is associated with an increased cerebral blood flow in type 2 diabetes mellitus as well.

Hypoglycemia; Cerebral blood flow; Diabetes mellitus

[1] Armstead WM. Cerebral blood flow autoregulation and dysautoregulation. Anesthesiology Clinics. 2016; 34: 465–477.

[2] Lie SL, Hisdal J, Høiseth LØ. Cerebral blood flow velocity during simultaneous changes in mean arterial pressure and cardiac output in healthy volunteers. European Journal of Applied Physiology. 2021; 121: 2207–2217.

[3] Wiegers EC, Becker KM, Rooijackers HM, von Samson-Himmelstjerna FC, Tack CJ, Heerschap A, et al. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. Journal of Cerebral Blood Flow & Metabolism. 2017; 37: 1994–2001.

[4] Zhu L, Ang LC, Tan WB, Xin X, Bee YM, Goh S, et al. A study to evaluate the prevalence of impaired awareness of hypoglycaemia in adults with type 2 diabetes in outpatient clinic in a tertiary care centre in Singapore. Therapeutic Advances in Endocrinology and Metabolism. 2017; 8: 69–74.

[5] Reddy M, Jugnee N, El Laboudi A, Spanudakis E, Anantharaja S, Oliver N. A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with type 1 diabetes and impaired awareness of hypoglycaemia. Diabetic Medicine. 2018; 35: 483–490.

[6] Alkhatatbeh MJ, Abdalqader NA, Alqudah MAY. Impaired awareness of hypoglycaemia in insulin-treated type 2 diabetes mellitus. Current Diabetes Reviews. 2019; 15: 407–413.

[7] Albayrak R, Degırmencı B, Acar M, Haktanır A, Colbay M, Yaman M. Doppler sonography evaluation of flow velocity and volume of the extracranial internal carotid and vertebral arteries in healthy adults. Journal of Clinical Ultrasound. 2007; 35: 27–33.

[8] Schopman JE, Geddes J, Frier BM. Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes. Diabetes Research and Clinical Practice. 2010; 87: 64–68.

[9] Tarumi T, Zhang R. Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. Journal of Neurochemistry. 2018; 144: 595–608.

[10] Steinback CD, Poulin MJ. Influence of hypoxia on cerebral blood flow regulation in humans. Advances in Experimental Medicine and Biology. 2016; 18: 131–144.

[11] Thrall SF, Tymko MM, Green CLM, Wynnyk KI, Brandt RA, Day TA. The effect of hypercapnia on regional cerebral blood flow regulation during progressive lower-body negative pressure. European Journal of Applied Physiology. 2021; 121: 339–349.

[12] Olesen ND, Fischer M, Secher NH. Sodium nitroprusside dilates cerebral vessels and enhances internal carotid artery flow in young men. The Journal of Physiology. 2018; 596: 3967–3976.

[13] GERICH JE, MOKAN M, VENEMAN T, KORYTKOWSKI M, MITRAKOU A. Hypoglycemia unawareness. Endocrine Reviews. 1991; 12: 356–371.

[14] de Galan BE, Tack CJ, Lenders JW, Pasman JW, Elving LD, Russel FG, et al. Theophylline improves hypoglycemia unawareness in type 1 diabetes. Diabetes. 2002; 51: 790–796.

[15] Nwokolo M, Amiel SA, O’Daly O, Byrne ML, Wilson BM, Pernet A, et al. Impaired awareness of hypoglycemia disrupts blood flow to brain regions involved in arousal and decision making in type 1 diabetes. Diabetes Care. 2019; 42: 2127–2135.

[16] Fukuhara T, Hida K, Manabe Y, Munemasa M, Matsubara H, Akao I, et al. Reduced flow velocity in the internal carotid artery independently of cardiac hemodynamics in patients with cerebral ischemia. Journal of Clinical Ultrasound. 2007; 35: 314–321.