OBJECTIVE The comparative neuroprotective effects of different antidiabetes drugs have not been characterized in randomized controlled trials. Here, we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Thirty-six patients with type 2 diabetes inadequately controlled with metformin monotherapy were randomized to receive liraglutide, dapagliflozin, or acarbose treatment for 16 weeks. Brain functional MRI (fMRI) scan and a battery of cognitive assessments were evaluated pre- and postintervention in all subjects. RESULTS The 16-week treatment with liraglutide significantly enhanced the impaired odor-induced left hippocampal activation with Gaussian random field correction and improved cognitive subdomains of delayed memory, attention, and executive function (all P < 0.05), whereas dapagliflozin or acarbose did not. Structural equation modeling analysis demonstrated that such improvements of brain health and cognitive function could be partly ascribed to a direct effect of liraglutide on left hippocampal activation (β = 0.330, P = 0.022) and delayed memory (β = 0.410, P = 0.004) as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all P < 0.05). CONCLUSIONS Our head-to-head study demonstrated that liraglutide enhanced impaired brain activation and restored impaired cognitive domains in patients with type 2 diabetes, whereas dapagliflozin and acarbose did not. The results expand the clinical application of liraglutide and provide a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.
Few studies have investigated the associations between diabetic peripheral neuropathy (DPN) and cognitive decline. Olfactory impairment is related to neurodegenerative diseases and type 2 diabetes mellitus (T2DM); however, the cognitive alterations of patients with DPN and the role of olfactory function in DPN are not known. We explored alterations in cognition with DPN and the associations of neuropathy parameters with cognition and olfaction. Methods: Healthy controls (HCs) and patients with T2DM underwent nerve-conduction tests, detailed cognitive assessment, olfactory-behavior tests, and odor-induced functional magnetic resonance imaging (fMRI). T2DM patients were divided into two groups (non-DPN [NDPN] and DPN). Olfactory brain regions showing different activation between the two groups were selected for functional connectivity (FC) analyses. A structural equation model (SEM) was also generated to demonstrate the association among cognition, olfactory, and neuropathy parameters. Results: One hundred individuals (36 HCs, 36 NDPN, and 28 DPN) were matched for age, sex, and educational level. Compared with the NDPN group, the DPN group had significantly lower scores for memory and processing speed, as well as lower olfactory identification and memory scores, decreased activation of the left frontal lobe, and reduced seed-based functional connectivity in the right insula. The nerve conduction velocity in patients with T2DM was associated with cognitive functions. The association between nerve conduction and executive function was mediated by olfactory behavior. Conclusion:Patients with DPN had worse cognition than the NDPN patients in the domains of memory and processing speed. Cognitive dysfunction could be predicted by olfactorybehavior tests and electrophysiological examination.
Introduction The clinical characteristics and outcomes of small fiber neuropathy (SFN) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been thoroughly described. In this study, we investigated the metabolic and neurological indexes and the prognosis of patients with T2DM based on skin biopsy. Methods A total of 34 healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intra-epidermal nerve fiber density (IENFD), and 89 patients with T2DM attending the Nanjing Drum Tower Hospital were evaluated at baseline. Of these 89 patients, 17 with pure SFN and nine with mixed diabetic polyneuropathy (DPN) were reassessed at the end of the follow-up. Results Glycated hemoglobin and postprandial blood glucose levels were lower ( P = 0.005 and P = 0.041, respectively) and postprandial C-peptide and insulin levels were higher ( P = 0.001 and P = 0.019, respectively) in the pure SFN group than in the mixed DPN group. A partial correlation study showed that there was a negative correlation between IENFD of the distal leg and cardiovascular autonomic reflex test (CART) scores ( r = − 0.513, P = 0.001) after adjusting for age and duration of diabetes. Only vitamin B12 level ( P = 0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve ( P = 0.045) were increased in the patients with pure SFN at the final visit while MCVs of the common peroneal nerve ( P = 0.025) and tibial nerve ( P = 0.047) were decreased in the mixed DPN group at the final visit. Conclusion Better islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. The metabolic and neurological indexes remained relatively stable in the patients with pure SFN during the follow-up. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01111-0.
<b>Objective:</b> <a></a><a>The comparative neuroprotective effects of different anti-diabetic drugs have not been characterized in randomized controlled trials. Here, </a><a>we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes.</a> <p> </p> <p><b>Research design and methods: </b>Thirty-six patients with type 2 diabetes inadequately controlled with metformin monotherapy were randomized to receive liraglutide, dapagliflozin, or acarbose treatment for 16 weeks. Brain functional magnetic resonance imaging (fMRI) scan and a battery of cognitive assessments were evaluated <a>pre- and postintervention</a> in all subjects.</p> <p> </p> <p><b>Results: </b>The 16-week treatment with liraglutide significantly enhanced the impaired odor-induced left hippocampal activation with GRF correction, and improved cognitive subdomains of delayed memory, attention, and executive function (all <i>P</i> < 0.05), whereas dapagliflozin or acarbose did not. Structural equation modeling analysis demonstrated that such improvements of brain health and cognitive function could be partly ascribed to a direct effect of liraglutide on left hippocampal activation (<i>β</i> = 0.330, <i>P</i> = 0.022) and delayed memory (<i>β</i> = 0.410, <i>P</i> = 0.004), as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all <i>P</i> < 0.05).</p> <p> </p> <p><b>Conclusions:</b> <a>Our head-to-head study demonstrated that liraglutide</a> enhanced impaired brain activation and restored impaired cognitive domains in patients with type 2 diabetes, whereas dapagliflozin and acarbose did not. The results expand the clinical application of liraglutide and provide <a>a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.</a><b></b></p>
<b>Objective:</b> <a></a><a>The comparative neuroprotective effects of different anti-diabetic drugs have not been characterized in randomized controlled trials. Here, </a><a>we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes.</a> <p> </p> <p><b>Research design and methods: </b>Thirty-six patients with type 2 diabetes inadequately controlled with metformin monotherapy were randomized to receive liraglutide, dapagliflozin, or acarbose treatment for 16 weeks. Brain functional magnetic resonance imaging (fMRI) scan and a battery of cognitive assessments were evaluated <a>pre- and postintervention</a> in all subjects.</p> <p> </p> <p><b>Results: </b>The 16-week treatment with liraglutide significantly enhanced the impaired odor-induced left hippocampal activation with GRF correction, and improved cognitive subdomains of delayed memory, attention, and executive function (all <i>P</i> < 0.05), whereas dapagliflozin or acarbose did not. Structural equation modeling analysis demonstrated that such improvements of brain health and cognitive function could be partly ascribed to a direct effect of liraglutide on left hippocampal activation (<i>β</i> = 0.330, <i>P</i> = 0.022) and delayed memory (<i>β</i> = 0.410, <i>P</i> = 0.004), as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all <i>P</i> < 0.05).</p> <p> </p> <p><b>Conclusions:</b> <a>Our head-to-head study demonstrated that liraglutide</a> enhanced impaired brain activation and restored impaired cognitive domains in patients with type 2 diabetes, whereas dapagliflozin and acarbose did not. The results expand the clinical application of liraglutide and provide <a>a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.</a><b></b></p>
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