Dataset Information

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

ABSTRACT:

Background

Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects.

Methods

In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function.

Results

In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs.

Conclusions

In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

SUBMITTER: Femminella GD

PROVIDER: S-EPMC7890851 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

Femminella Grazia Daniela GD Livingston Nicholas R NR Raza Sanara S van der Doef Thalia T Frangou Eleni E Love Sharon S Busza Gail G Calsolaro Valeria V Carver Stefan S Holmes Clive C Ritchie Craig W CW Lawrence Robert M RM McFarlane Brady B Tadros George G Ridha Basil H BH Bannister Carol C Walker Zuzana Z Archer Hilary H Coulthard Elizabeth E Underwood Ben B Prasanna Aparna A Koranteng Paul P Karim Salman S Junaid Kehinde K McGuinness Bernadette B Passmore Anthony Peter AP Nilforooshan Ramin R Macharouthu Ajayverma A Donaldson Andrew A Thacker Simon S Russell Gregor G Malik Naghma N Mate Vandana V Knight Lucy L Kshemendran Sajeev S Tan Tricia T Holscher Christian C Harrison John J Brooks David J DJ Ballard Clive C Edison Paul P

Alzheimer's research & therapy 20210217 1

<h4>Background</h4>Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects.<h4>Methods</h4>In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with ar ...[more]

PMID: 33597002

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Project description:BackgroundWe demonstrated in experimental studies that hypercholesterolaemia enhances the proliferation of haematopoietic stem cells and the subsequent differentiation to neutrophils, whereas HDL-cholesterol inhibits these processes. To translate our experimental findings to clinical practice, we investigated in Chinese type-2 diabetic patients and in Flemish non-diabetic people the independent and joint associations of insulin resistance with markers of dyslipidaemia and inflammation, while looking for consistency between ethnicities and across the spectrum of insulin resistance.MethodsWe studied 798 Chinese patients with type-2 diabetes (53.6% women; mean age, 60.6 years) admitted to a tertiary referral centre and 1060 white Flemish (50.5%; 51.1 years) randomly recruited in Northern Belgium. Fasting insulin resistance (HOMA-IR) was derived from C-peptide in Chinese and from insulin in Flemish using the Homeostasis Model of Assessment algorithm. In multivariable-adjusted analyses, HOMA-IR was regressed on triglycerides, HDL-cholesterol and neutrophil count.ResultsIn Chinese patients, the percentage changes in HOMA-IR associated with triglycerides, HDL-cholesterol and neutrophils (per 1-SD increment) amounted to 8.1 (95% confidence interval, 3.0 to 13.4; p = 0.0015), -8.7 (-13.0 to -4.2; p = 0.0002) and 5.6 (1.0 to 10.4; p = 0.017). In non-diabetic Flemish, the corresponding estimates were 11.7 (8.3 to 15.1; p<0.0001), -1.7 (-4.6 to 1.4; p = 0.28) and 3.3% (0.5 to 6.3; p = 0.022), respectively. None of the interaction terms between the three explanatory variables reached significance in Chinese or Flemish (p?0.10).ConclusionsInsulin resistance increases with the serum level of triglycerides and the blood neutrophil count, but decreases with serum HDL-cholesterol concentration. These associations were consistent in Chinese type-2 diabetic patients and non-diabetic Flemish people and were independent from one another. The clinical implications are that future studies should focus on intervening with serum triglyceride and HDL-cholesterol levels or controlling inflammation as a way to prevent or treat insulin resistance.

Dataset Information

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

Background

Methods

Results

Conclusions

Publications

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

Similar Datasets

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