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- Almby, Kristina E., et al.
(author)
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Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
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Journal article (peer-reviewed)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
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- Lundqvist, Martin H., et al.
(author)
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Altered hormonal and autonomic nerve responses to hypo- and hyperglycaemia are found in overweight and insulin-resistant individuals and may contribute to the development of type 2 diabetes
- 2021
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:3, s. 641-655
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Results from animal models and some clinical work suggest a role for the central nervous system (CNS) in glucose regulation and type 2 diabetes pathogenesis by modulation of glucoregulatory hormones and the autonomic nervous system (ANS). The aim of this study was to characterise the neuroendocrine response to various glucose concentrations in overweight and insulin-resistant individuals compared with lean individuals.Methods: Overweight/obese (HI, n = 15, BMI ≥27.0 kg/m2) and lean (LO, n = 15, BMI <27.0 kg/m2) individuals without diabetes underwent hyperinsulinaemic euglycaemic–hypoglycaemic clamps and hyperglycaemic clamps on two separate occasions with measurements of hormones, Edinburgh Hypoglycaemic Symptom Scale (ESS) score and heart rate variability (HRV). Statistical methods included groupwise comparisons with Mann–Whitney U tests, multilinear regressions and linear mixed models between neuroendocrine responses and continuous metabolic variables.Results: During hypoglycaemic clamps, there was an elevated cortisol response in HI vs LO (median ΔAUC 12,383 vs 4793 nmol/l × min; p = 0.050) and a significantly elevated adrenocorticotropic hormone (ACTH) response in HI vs LO (median ΔAUC 437.3 vs 162.0 nmol/l × min; p = 0.021). When adjusting for clamp glucose levels, obesity (p = 0.033) and insulin resistance (p = 0.009) were associated with elevated glucagon levels. By contrast, parasympathetic activity was less suppressed in overweight individuals at the last stage of hypoglycaemia compared with euglycaemia (high-frequency power of HRV, p = 0.024). M value was the strongest predictor for the ACTH and PHF responses, independent of BMI and other variables. There was a BMI-independent association between the cortisol response and ESS score response (p = 0.024). During hyperglycaemic clamps, overweight individuals displayed less suppression of glucagon levels (median ΔAUC −63.4% vs −73.0%; p = 0.010) and more suppression of sympathetic relative to parasympathetic activity (low-frequency/high-frequency power, p = 0.011).Conclusions/interpretation: This study supports the hypothesis that altered responses of insulin-antagonistic hormones and the ANS to glucose fluctuations occur in overweight and insulin-resistant individuals, and that these responses are probably partly mediated by the CNS. Their potential role in development of type 2 diabetes needs to be addressed in future research.
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