Dataset Information

Reversibility of brain glucose kinetics in type 2 diabetes mellitus.

ABSTRACT:

Aims/hypothesis

We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by ¹H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA_1c normalise intracerebral glucose levels.

Methods

Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m² and HbA_1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent ¹H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.

Results

Following the intervention, mean ± SD HbA_1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA_1c (r = 0.71, p=0.048).

Conclusion/interpretation

These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control. Trial registration ClinicalTrials.gov NCT03469492.

SUBMITTER: Sanchez-Rangel E

PROVIDER: S-EPMC8960594 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Reversibility of brain glucose kinetics in type 2 diabetes mellitus.

Sanchez-Rangel Elizabeth E Gunawan Felona F Jiang Lihong L Savoye Mary M Dai Feng F Coppoli Anastasia A Rothman Douglas L DL Mason Graeme F GF Hwang Janice Jin JJ

Diabetologia 20220305 5

<h4>Aims/hypothesis</h4>We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by <sup>1</sup>H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA<sub>1c</sub> normalise intracerebral glucose levels.<h4>Methods</h4>Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m<sup>2</sup> and HbA<sub>1c</sub> 84.1 ± 16.2 mmo ...[more]

PMID: 35247067

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Project description:Background Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross-sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance ( IR ), β-cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Methods and Results Homeostatic model assessment of IR ( HOMA 2- IR ) and HOMA 2-β were used to estimate IR and β-cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti-diabetic medication use at follow-up. Linear regression was used to examine cross-sectional associations of aldosterone with fasting plasma glucose, HOMA 2- IR and HOMA 2-β; Cox regression was used to estimate hazard ratios ( HR ) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non-Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log-aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA 2- IR and 6% higher HOMA 2-β ( P<0.01). A 1- SD increase in log-aldosterone was associated with a 44% higher risk of incident diabetes mellitus ( P<0.01) with the greatest increase of 142% ( P<0.01) observed in Chinese Americans ( P for interaction=0.09 versus other ethnicities). Similar cross-sectional findings for log-plasma renin activity existed, but log-plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Conclusions Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.

Dataset Information

Reversibility of brain glucose kinetics in type 2 diabetes mellitus.

Aims/hypothesis

Methods

Results

Conclusion/interpretation

Publications

Reversibility of brain glucose kinetics in type 2 diabetes mellitus.

Similar Datasets

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