Investigating the Insulin Resistance in Individuals With Type 2 Diabetes

Official title

Investigating the Central and Peripheral Insulin Resistance in Individuals With Type 2 Diabetes

Overview

Numerous studies have provided evidence of a correlation between Type 2 Diabetes Mellitus (T2DM) and cognitive dysfunction, specifically in the realms of complex attention, information processing, and executive function. These impairments have been observed in middle-aged and elderly individuals with T2DM, with longer diabetes duration, suboptimal glycemic control, and the presence of diabetic complications being contributing factors. Recent research in young adults and adolescents diagnosed with T2DM has revealed cognitive and brain structural alterations in this growing demographic, suggesting that early disease mechanisms, rather than solely vascular and age-related neurodegeneration, contribute to pathogenesis. However, there remains uncertainty regarding the interplay between central and peripheral insulin resistance and its impact on cognitive dysfunction in individuals with T2DM. This study aims to investigate central insulin resistance in T2DM, elucidating its association with peripheral insulin resistance and the effects on cognitive impairments.

Detailed description

Participants screened through inclusion and exclusion criteria will accept cross-sectional evaluation. The information of demographic data, medical history, previous and current medication regimen, details of complications, and family history regarding metabolic diseases will be collected. The assessments includes physical examination, anthropometry, blood test(blood routine, liver function, renal function, blood lipids, fasting blood glucose, serum insulin，thyroid function and glycosylated hemoglobin A 1c), MRI scan( High-resolution T1-weighted Anatomical Images, Diffusion Tensor Imaging, Resting-state functional MRI and Arterial Spin Labeling) and psychiatry scales(Hamilton Depression Scale, Young Mania Rating Scale and Self-reporting Inventory-90); cognitive function will be assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS) Consensus Cognitive Battery; biological samples also will be collected and stored to explore related mechanisms.

Interventions

• Drug 160 units nasal insulin spray
  Initially, a series of MRI scans, including high-resolution T1-weighted anatomical images, diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling, will be conducted. Subsequently, 160 units of nasal insulin spray will be administered, followed by a second round of MRI scans after a 30-minute interval, encompassing high-resolution T1-weighted anatomical images, resting-state functional MRI, and arterial spin labeling.

Primary outcome measures

• The difference of changes of brain cerebral blood flow by arterial spin labeling between type 2 diabetes and healthy volunteers. [Time frame: Baseline]
• The difference of the level of insulin signaling in Extracellular Vesicles of neuronal origin isolated from blood between type 2 diabetes and healthy volunteers. [Time frame: Baseline]
• The difference of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery between type 2 diabetes and healthy volunteers. [Time frame: Baseline]
• The difference of c-fMRI between type 2 diabetes and healthy volunteers. [Time frame: Baseline]

Secondary outcome measures (1)

• The difference of Diffusion Tensor Imaging scanned by MRI between type 2 diabetes and healthy volunteers [Time frame: Baseline]

Eligibility criteria

Inclusion criteria

• Meeting the diagnostic criteria for Type 2 diabetes: typical symptoms of diabetes plus random blood glucose level of ≥11.1 mmol/l, or fasting blood glucose level of ≥7.0 mmol/l, or 2-hour post-OGTT (Oral Glucose Tolerance Test) blood glucose level of ≥11.1 mmol/l, or HbA1c level of ≥6.5%; for those without typical symptoms of diabetes, re-examination on a different day is required for confirmation.

Exclusion criteria

• Having history of substance dependence or abuse or whose symptoms are caused by diagnosable mental disorders;
• Having history of traumatic brain injury, seizures or other known neurological or organic diseases of the central nervous system;
• Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be manage in an inpatient setting;
• Taking drugs that could affect cognitive function.
• The routine blood tests showing significant abnormal renal, liver function or other somatic disease.
• Pregnant or lactating women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Screening

Study locations

China · 1 center

• Department of Psychiatry, National Clinical Research Center for Mental Disorders, and Nati — Changsha

Identifiers

NCT: NCT06428968 · T2DM2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗