Acute Hyperglycemia Reduces Cerebrovascular Reactivity: The Role of Glycemic Variability

Giordani, Ilaria; Flaviani, Alessandra Di; Picconi, Fabiana; Malandrucco, Ilaria; Ylli, Dorina; Palazzo, Paola; Altavilla, Riccardo; Vernieri, Fabrizio; Passarelli, Francesco; Donno, Silvia; Lauro, Davide; Pasqualetti, Patrizio; Frontoni, Simona

doi:10.1210/jc.2014-1087

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…Furthermore, patients with diabetes often overcorrect for hypoglycemia leading to "yo-yoing" of glucose levels and increased glycemic variability. The impact of glycemic variability on clinical outcomes remains unclear, although a growing body of literature has shown that increased glycemic variability is associated with adverse outcomes (5)(6)(7)(8), including increased rates of cerebrovascular events (9), white matter hyperintensities (10), and cognitive decline (11). However, the underlying mechanisms for these associations remain unclear.…”

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confidence: 99%

Glycemic Variability and Brain Glucose Levels in Type 1 Diabetes

et al. 2018

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The impact of glycemic variability on brain glucose transport kinetics among individuals with type 1 diabetes mellitus (T1DM) remains unclear. Fourteen individuals with T1DM (age 35 ± 4 years; BMI 26.0 ± 1.4 kg/m2; HbA1c 7.6 ± 0.3) and nine healthy control participants (age 32 ± 4; BMI 23.1 ± 0.8; HbA1c 5.0 ± 0.1) wore a continuous glucose monitor (Dexcom) to measure hypoglycemia, hyperglycemia, and glycemic variability for 5 days followed by 1H MRS scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-h glucose clamp (target glucose concentration 220 mg/dL). Hyperglycemic clamps were also performed in a rat model of T1DM to assess regional differences in brain glucose transport and metabolism. Despite a similar change in plasma glucose levels during the hyperglycemic clamp, individuals with T1DM had significantly smaller increments in intracerebral glucose levels (P = 0.0002). Moreover, among individuals with T1DM, the change in brain glucose correlated positively with the lability index (r = 0.67, P = 0.006). Consistent with findings in humans, streptozotocin-treated rats had lower brain glucose levels in the cortex, hippocampus, and striatum compared with control rats. These findings that glycemic variability is associated with brain glucose levels highlight the need for future studies to investigate the impact of glycemic variability on brain glucose kinetics.

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Glycemic Variability and Brain Glucose Levels in Type 1 Diabetes

et al. 2018

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“…Studies have found reduced CVR 18,19 or no differences between control individuals and those with MetS. 20 Although several studies have reported reduced resting cortical blood flow using ASL-MRI 21,22 or SPECT 23 methods, no studies have looked at CVR in obese insulin-resistant individuals without MetS or T2DM.…”

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Insulin resistance among obese middle-aged is associated with decreased cerebrovascular reactivity

et al. 2017

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IR is associated with impaired CVR; the relationship appears to be driven by the degree of IR and not by obesity. These rarely reported results suggest that early forms of cerebrovascular dysfunction exist among obese middle-aged individuals with significant IR but without type 2 diabetes mellitus. These functional vascular abnormalities may help explain the associations among IR, diabetes, and dementia, and suggest that interventions aiming to improve IR or CVR may help prevent cognitive decline later in life.

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“…Controversies exist about the effect of acute hyperglycemia, as mimicked by 2-3 h of 15 mmol z L 21 hyperglycemic clamp, on cerebral blood flow in healthy humans. This hyperglycemia either decreased resting cerebrovascular reactivity to CO 2 (29) or increased resting middle cerebral artery blood flow (30), whereas it did not alter middle cerebral artery blood flow during 10-min rhythmic handgrip exercise (31). Considering the latter results, the acute hyperglycemia, present only in a small proportion of the current patients, was probably not involved in the observed relative hypoperfusion in response to maximal exercise.…”

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confidence: 75%

Regional Cerebral Hemodynamic Response to Incremental Exercise Is Blunted in Poorly Controlled Patients With Uncomplicated Type 1 Diabetes

Tagougui

Fontaine²,

Leclair

et al. 2015

Diabetes Care

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OBJECTIVE Cerebral vasoreactivity to pharmacologically induced hypercapnia is impaired in poorly controlled patients with type 1 diabetes but otherwise free from microangiopathy. However, whether this response is also compromised during exercise, a daily-life physiological condition challenging regional cerebral hemodynamics, is unknown. We aimed to investigate prefrontal cortex hemodynamics during incremental maximal exercise in patients with uncomplicated type 1 diabetes, taking into account long-term glycemic control as well as exercise- and diabetes-influenced vasoactive stimuli. RESEARCH DESIGN AND METHODS Two groups of patients (type 1 diabetes with adequate glycemic control [T1D-A], n = 8, HbA1c 6.8 ± 0.7% [51 ± 7.7 mmol/mol]; type 1 diabetes with inadequate glycemic control [T1D-I], n = 10, HbA1c 9.0 ± 0.7% [75 ± 7.7 mmol/mol]) were compared with 18 healthy control subjects (CON-A and CON-I) matched for physical activity and body composition. Throughout exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), and total hemoglobin (THb) in the prefrontal cortex. Venous and arterialized capillary blood was sampled during exercise to assess for factors that may alter prefrontal cortex hemodynamics and oxygenation. RESULTS No differences were observed between T1D-A and CON-A, but VO2max was impaired (P < 0.05) and cerebral blood volume (THb) increase blunted (P < 0.05) in T1D-I compared with CON-I. Nonetheless, O2Hb appeared unaltered in T1D-I probably partly due to blunting of simultaneous neuronal oxygen extraction (i.e., a lower HHb increase; P < 0.05). There were no intergroup differences in arterial oxygen content, Paco2, pH, [K+], and free insulin levels. CONCLUSIONS Maximal exercise highlights subtle disorders of both hemodynamics and neuronal oxygenation in the prefrontal cortex of poorly controlled patients with type 1 diabetes. These findings may warn clinicians of brain endothelial dysfunction occurring even before overt microangiopathy during exercise.

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Acute Hyperglycemia Reduces Cerebrovascular Reactivity: The Role of Glycemic Variability

Abstract: GV is increased in patients with MS but without DM and is the major predictor of CVR reduction induced by acute hyperglycemia, possibly representing the earliest cause of cerebrovascular damage in DM.

Cited by 18 publications

References 27 publications

Glycemic Variability and Brain Glucose Levels in Type 1 Diabetes

Glycemic Variability and Brain Glucose Levels in Type 1 Diabetes

Insulin resistance among obese middle-aged is associated with decreased cerebrovascular reactivity

Regional Cerebral Hemodynamic Response to Incremental Exercise Is Blunted in Poorly Controlled Patients With Uncomplicated Type 1 Diabetes

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