Exercise and Intranasal Insulin in Type 2 Diabetes

Официальное название

Effects of Intranasal Insulin Plus Exercise Training on Brain Blood Flow, Neuronal Insulin Signaling, and Cognition in Adults With Type 2 Diabetes

Обзор

About 6.5 million adults in the United States who are 65 or older have dementia. While the exact cause of dementia is not known, it may be due to changes in the brain. Further, risk may be higher when the brain does not respond to insulin. Indeed, brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise may help reduce the risk of dementia by increased blood flow to the brain and help the brain respond better to insulin. In addition, giving insulin through a nose spray (called intranasal insulin) may also help with thinking and memory. However, it is unknown if using both exercise and intranasal insulin is best for the brain.

Подробное описание

This goal of this study is to find out if exercise plus an insulin nose spray works better than exercise alone for brain blood flow in older adults with Type 2 Diabetes. This study will also look at how the brain uses insulin and thinking skills. Individuals will be randomized to one of two groups. One group will exercise and use an insulin nose spray. The other group will exercise and use a saline (placebo) nose spray. Exercise training will be supervised and consist of walking or light jogging 3 times per week for 16 weeks. Brain imaging, cognition, and blood tests will be conducted before and after the intervention. Other measures include fitness tests and body composition scans.

Вмешательства

• Препарат Intranasal Insulin
  Dosage will be 20 IU of INI twice per day (40 IU in total/day). The study will use the Kurve Technology intranasal device, which delivers a 20 second stream of insulin through a nose piece into a nostril, after which the device switches off. The process will then be repeated in the other nostril.
• Препарат Intranasal Placebo
  Saline will be administered twice daily (20 seconds in each nostril) using the Kurve Technology intranasal insulin device.
• Поведенческое High Intensity Exercise
  High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk. The duration of each exercise session will be adjusted based on fitness level so that \~300 kcal will be expended per training session during weeks 1-2, 350 kcal per training session during weeks 3-4, and 400 kcal per training session during weeks 5-16. This usually equals \~60 minutes per session but c

Первичные конечные точки

• Cerebrovascular Insulin Sensitivity [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]

Вторичные конечные точки (7)

• Blood Brain Barrier Integrity [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]
• Insulin Signaling Proteins [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]
• Augmentation Index [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]
• Peripheral Insulin Sensitivity [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]
• Cognitive Function [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]
• Pulse Wave Velocity [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]
• Insulin Secretion [Срок оценки: Change from baseline to the end of the intervention at 16 weeks]

Критерии участия

Критерии включения

• Male or female 55-80 years old
• Type 2 diabetes diagnosis or confirmation HbA1c >6.5% and fasting glucose >126 mg/dl
• Individuals prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors >6 months.
• MOCA ≥26
• Body mass index (BMI) ≥25 and ≤40 kg/m2
• Not diagnosed with Type 1 diabetes
• Not currently engaged in <90 min/wk of exercise

Критерии исключения

• A diagnosis of dementia
• Neurologic disease (e.g. Parkinson's, autonomic neuropathy, etc.)
• Intolerance to insulin
• Morbidly obese patients (BMI >40 kg/m2) and lean patients (BMI <25 kg/m2)
• >2 kg weight change in past 6 months
• Participants who have been recently active (>90 min of moderate/high intensity exercise)
• Individuals who are smokers or who have quit smoking (<2 years)
• Hypertriglyceridemia (400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
• Uncontrolled Hypertensive (>160/100 mmHg)
• Participants with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety
• Pregnant (as evidenced by positive pregnancy test) or nursing women
• Participants with contraindications to participation in an exercise training program
• Major psychiatric disorders (e.g. psychosis, bipolar disorder, major depression, alcohol/substance abuse)
• History of head trauma or loss of consciousness in last 5 years.
• Known contraindications for MR imaging:

• History of head trauma or neurosurgery, or neurological disorder (other than headaches or peripheral nerve disease) as these may impact neuroimaging results.
• Ferrous material implanted in or on the body, including flakes or filings, surgical clips, bullets, or electrical devices such as a pacemaker, or nonremovable ferrous jewelry (fillings in teeth and permanent retainers are permitted).
• Fillings and permanent retainers do not provide a safety risk and are not general exclusions. However, upper retainers may cause artifacts in ventral frontal regions and therefore may be an exclusion for some studies.
• Individuals with surgical pins or plates above the neck are excluded. Surgical pins or plates below the neck are exclusions, except when the material is fixed to bone, and considered acceptable by the Reference Manual for Magnetic Resonance Safety. Implants and Devices, 2020 Edition. Almost all recent orthopedic implants are made of materials that are not ferromagnetic and therefore are safe for scanning, and even though some screws are still made of ferromagnetic materials these are firmly screwed into bone. In cases where the material is unknown or deemed unsafe for scanning by the Reference Manual for Magnetic Resonance Safety. Implants and Devices the participant will be excluded.
• History of eye injury involving metallic materials, shavings in eyes, or welding without a face mask
• Lead/iron tattoos
• Claustrophobia (history of significant anxiety in closed places).
• Back problem that would prevent the subject from laying still comfortably for up to 90 minutes.
• Deafness

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Robert Wood Johnson University Hospital Clinical Research Center — New Brunswick
• Institute for Food, Nutrition, and Health — New Brunswick
• Rutgers University Loree Gymnasium — New Brunswick
• Center for Advanced Human Brain Imaging Research — Piscataway

Публикации

• Malin SK, Battillo DJ, Beeri MS, Mustapic M, Kapogiannis D. A Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle-Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk. Compr Physiol. 2026 Apr;16(2):e70131. doi: 10.1002/cph4.70131. PMID 41876945
• Malin SK, Battillo DJ, Zald DH, Ramirez J. Appetite Perception and Cerebral Blood Flow in Aging Adults Following a Single Bout of Exercise. Nutrients. 2026 Mar 27;18(7):1072. doi: 10.3390/nu18071072. PMID 41978122
• Malin SK, Zald DH, Battillo DJ. Acute exercise reduces intranasal insulin-mediated elevations in blood pressure in aging adults with cardiometabolic risk. Am J Physiol Regul Integr Comp Physiol. 2026 Aug 1;331(2):R147-R154. doi: 10.1152/ajpregu.00119.2026. Epub 2026 Jun 15. PMID 42295834
• Malin SK, Battillo DJ, Beeri MS, Mustapic M, Delgado-Peraza F, Kapogiannis D. Two weeks of exercise alters neuronal extracellular vesicle insulin signaling proteins and pro-BDNF in older adults with prediabetes. Aging Cell. 2025 Jan;24(1):e14369. doi: 10.1111/acel.14369. Epub 2024 Oct 18. PMID 39421964

Идентификаторы

NCT: NCT07675499 · Pro2026000751 · 1R01DK147509-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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