OBJECTIVE Type 2 diabetes is characterized by insulin resistance, which is involved in the development of Alzheimer disease. This study aims to investigate the relationship between abnormal resting-state brain functional connectivity and insulin resistance in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 30 patients with type 2 diabetes and 31 healthy well-matched volunteers were prospectively examined. Resting-state brain functional connectivity analysis was used to examine the correlation between the posterior cingulate cortex (PCC) and whole-brain regions. The possible relationships between functional connectivity measures and insulin resistance were evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS Compared with healthy controls, we observed significantly decreased functional connectivity of the PCC within some selected regions, including the right middle temporal gyrus (MTG), left lingual gyrus, left middle occipital gyrus, and left precentral gyrus; increased functional connectivity of the PCC was detected in the left cerebellum posterior lobe, right superior frontal gyrus, and right middle frontal gyrus. A significant negative correlation was found between the PCC-right MTG connectivity and HOMA-IR in type 2 diabetic patients (P = 0.014; r = −0.446). CONCLUSIONS Type 2 diabetic patients develop aberrant functional connectivity of the PCC, which is associated with insulin resistance in selected brain regions. Resting-state connectivity disturbance of PCC–MTG may be a central role for evaluating the cognitive dysfunction in type 2 diabetes.

Objectives Type 2 diabetes mellitus is associated with increased risk for dementia. Patients with impaired cognition often show default-mode network disruption. We aimed to investigate the integrity of a default-mode network in diabetic patients by using independent component analysis, and to explore the relationship between network abnormalities, neurocognitive performance and diabetic variables. Methods Forty-two patients with type 2 diabetes and 42 well-matched healthy controls were included and underwent resting-state functional MRI in a 3 Tesla unit. Independent component analysis was adopted to extract the default-mode network, including its anterior and posterior components. Z-maps of both sub-networks were compared between the two groups and correlated with each clinical variable. Results Patients showed increased connectivity around the medial prefrontal cortex in the anterior sub-network, but decreased connectivity around the posterior cingulate cortex in the posterior sub-network. The decreased connectivity in the posterior part was significantly correlated with the score on Complex Figure Test-delay recall test (r = 0.359, p = 0.020), the time spent on Trail-Making Test-part B (r = -0.346, p = 0.025) and the insulin resistance level (r = −0.404, p = 0.024). Conclusion Dissociation pattern in the default-mode network was found in diabetic patients, which might provide powerful new insights into the neural mechanisms that underlie the diabetes-related cognitive decline. Key points • Type 2 diabetes mellitus is associated with impaired cognition • Default- mode network plays a central role in maintaining normal cognition • Network connectivity within the default mode was disrupted in type 2 diabetes patients • Decreased network connectivity was correlated with cognitive performance and insulin resistance level • Disrupted default-mode network might explain the impaired cognition in diabetic population

This study aimed to examine the efficacy of a nanocarrier (polyethyleneimine [PEI]-superparamagnetic iron oxide nanoparticle [SPIO]), composed of a core of iron oxide and a shell of PEI, in the systemic delivery of therapeutic siRNA to experimental arthritic joints. PEI-SPIO/siRNA nanoparticles were synthesized and characterized in vitro. Nanoparticles were administered intravenously to arthritic rats to analyze cellular uptake, tissue distribution and the therapeutic effect of a siRNA against the IL-2/-15 receptor β chain (IL-2/IL-15Rβ). PEI-SPIOs loaded with siRNA displayed negligible cytotoxicity, improved siRNA stability, efficient uptake by macrophages and the ability to induce specific gene silencing in vitro. PEI-SPIO-delivered siRNA accumulated easily in inflamed joints and was efficiently taken up by joint macrophages and T cells. Although IL-2/IL-15Rβ siRNA-loaded PEI-SPIOs alone were efficacious in the treatment of experimental arthritis, combination therapy with both PEI-SPIO/IL-2/IL-15Rβ siRNA and a magnetic field displayed an additive anti-inflammatory effect. PEI-functionalized SPIOs can be employed for systemic siRNA delivery in rheumatoid arthritis and enhanced therapeutic benefit can be achieved by the use of an external magnetic field.