Cardiovascular Autonomic Neuropathy Is Associated With Increased Glucose Variability in People With Type 1 Diabetes.

OBJECTIVE: We investigated the association between the cardiovascular autonomic neuropathy (CAN) diagnosis and glucose variability (GV) in type 1 diabetes (T1D), as autonomic dysfunction previously has been associated with increased GV. RESEARCH DESIGN AND METHODS: CAN was assessed by three recommended cardiovascular reflex tests (CARTs). Glucose metrics were obtained from 10-day blinded continuous glucose monitoring (CGM). Between-group differences in GV indices were assessed by regression analyses in 24 participants with T1D with CAN and 24 matched control subjects without CAN. RESULTS: The CAN diagnosis was associated with 4.9% (95% CI 1.0, 8.7) higher coefficient of variation (CV) (P = 0.014), 0.7 mmol/L (0.3, 1.1) higher SD (P = 0.002) of glucose, and 1.4 mmol/mol (0.0, 2.7) higher mean amplitude of glycemic excursions (P = 0.047). Lower measures of CARTs were associated with higher CV, SD, and time above range values. CONCLUSIONS: The CAN diagnosis associates with a significantly higher GV in T1D, despite a high prevalence of routine CGM use.

Non-invasive assessment of temporal changes in myocardial microvascular function in persons with type 2 diabetes and healthy controls.

BACKGROUND: Cardiac Rubidium-82 (82 Rb) positron emission tomography/computed tomography (PET/CT) provides a measure of the myocardial blood flow and the myocardial flow reserve, which reflects the function of both large epicardial arteries and the myocardial microcirculation. Knowledge on changes in the myocardial microvascular function over time is lacking. METHODS: In this cohort study, we recruited 60 persons with type 2 diabetes and 30 non-diabetic controls, in 2013; all free of overt cardiovascular disease. All underwent a cardiac 82 Rb PET/CT scan. In 2019, all survivors (n = 82) were invited for a repeated cardiac 82 Rb PET/CT scan using the same protocol, and 29 with type 2 diabetes and 19 controls participated. RESULTS: Median duration between visits was 6.2 years (IQR: 6.1-6.3). In the total cohort, the mean age was 66.4 years (SD: 9.3) and 33% were females. The myocardial flow reserve was lower in persons with type 2 diabetes compared to controls (p = 0.002) but there was no temporal change in the myocardial flow reserve in participants with type 2 diabetes: mean change: -0.22 (95% CI: -0.47 to 0.02) nor in controls: -0.12 (-0.49 to 0.25) or when comparing type 2 diabetes to controls: mean difference: -0.10 (95% CI: -0.52 to 0.31). The temporal reduction in stress-induced myocardial blood flow did not differ within the groups but was more pronounced in type 2 diabetes compared to controls: mean difference: -0.30 (95% CI: -0.55 to -0.04). CONCLUSION: The myocardial microvascular function was impaired in persons with type 2 diabetes compared to controls but did not change significantly in either of the groups when evaluated over 6 years.

Intraganglionic injection of a nitric oxide donator induces afferent mechanical sensitization that is attenuated by palmitoylethanolamide.

AIM: The aim of this article is to investigate whether the nitric oxide (NO) donator diethylenetriamine/nitric oxide (DETA/NO) affects trigeminal sensory processing through the trigeminal ganglion in part by activating trigeminal satellite glial cells (SGCs) and whether this effect is attenuated by the anti-inflammatory compound palmitoylethanolamide (PEA). METHODS: DETA/NO was administered to isolated rat trigeminal SGCs in vitro, and injected into the rat trigeminal ganglion in vivo, in the presence or absence of PEA. RESULTS: Administration of DETA/NO (1000 µM) increased the release of prostaglandin E2 by SGCs. PEA (1 and 10 µM) significantly attenuated prostaglandin E2 release. Two intraganglionic injections of DETA/NO (10 mM, 3 µl) or prostaglandin E2 at a 30-minute interval did not evoke discharge in trigeminal ganglion neurons that innervate the rat jaw-closer muscles, but did reduce the mechanical activation threshold of their peripheral endings by 30%-50%. Intravenous administration of PEA (1 mg/kg) or ketorolac (0.5 mg/kg) prevented DETA/NO-induced afferent mechanical sensitization. CONCLUSIONS: Elevation of NO in the trigeminal ganglion results in the sensitization of the peripheral endings of masticatory muscle nociceptors to mechanical stimulation through a mechanism that involves prostaglandin E2 release from SGCs. Attenuation of this sensitization by PEA suggests a possible option for acute management of craniofacial pain and headache.

Development of a novel lipophilic, magnetic nanoparticle for in vivo drug delivery.

The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4) cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro.