Diabetes is more common in older adults, has a high prevalence in long-term care (LTC) facilities, and is associated with significant disease burden and higher cost. The heterogeneity of this population with regard to comorbidities and overall health status is critical to establishing personalized goals and treatments for diabetes. The risk of hypoglycemia is the most important factor in determining glycemic goals due to the catastrophic consequences in this population. Simplified treatment regimens are preferred, and the sole use of sliding scale insulin (SSI) should be avoided. This position statement provides a classification system for older adults in LTC settings, describes how diabetes goals and management should be tailored based on comorbidities, delineates key issues to consider when using glucose-lowering agents in this population, and provides recommendations on how to replace SSI in LTC facilities. As these patients transition from one setting to another, or from one provider to another, their risk for adverse events increases. Strategies are presented to reduce these risks and ensure safe transitions. This article addresses diabetes management at end of life and in those receiving palliative and hospice care. The integration of diabetes management into LTC facilities is important and requires an interprofessional team approach. To facilitate this approach, acceptance by administrative personnel is needed, as are protocols and possibly system changes. It is important for clinicians to understand the characteristics, challenges, and barriers related to the older population living in LTC facilities as well as the proper functioning of the facilities themselves. Once these challenges are identified, individualized approaches can be designed to improve diabetes management while lowering the risk of hypoglycemia and ultimately improving quality of life.
The present study tested two hypotheses: (1) that a receptor for extracellular Ca2+ (Ca2+ receptor [CaR]) is located in the perivascular sensory nerve system and (2) that activation of this receptor by physiological concentrations of extracellular Ca2+ results in the release of vasodilator substance that mediates Ca2+-induced relaxation. Reverse transcription-polymerase chain reaction using primers derived from rat kidney CaR cDNA sequence showed that mRNA encoding a CaR is present in dorsal root ganglia but not the mesenteric resistance artery. Western blot analysis using monoclonal anti-CaR showed that a 140-kD protein that comigrates with the parathyroid CaR is present in both the dorsal root ganglia and intact mesenteric resistance artery. Immunocytochemical analysis of whole mount preparations of mesenteric resistance arteries showed that the anti-CaR-stained perivascular nerves restricted to the adventitial layer. Biophysical analysis of mesenteric resistance arteries showed that cumulatively raising Ca2+ from 1 to 1.25 mol/L and above relaxes precontracted arteries with an ED50 value of 2.47+/-0.17 mmol/L (n=12). The relaxation is endothelium independent and is unaffected by blockade of nitric oxide synthase but is completely antagonized by acute and subacute phenolic destruction of perivascular nerves. A bioassay showed further that superfusion of Ca2+ across the adventitial surface of resistance arteries releases a diffusible vasodilator substance. Pharmacological analysis indicates that the relaxing substance is not a common sensory nerve peptide transmitter but is a phospholipase A2/cytochrome P450-derived hyperpolarizing factor that we have classified as nerve-derived hyperpolarizing factor. These data demonstrate that a CaR is expressed in the perivascular nerve network, show that raising Ca2+ from 1 to 1.25 mol/L and above causes nerve-dependent relaxation of resistance arteries, and suggest that activation of the CaR induces the release of a diffusible hyperpolarizing vasodilator. We propose that this system could serve as a molecular link between whole-animal Ca2+ balance and arterial tone.
Renal interstitial fluid Ca(2+) concentration ([Ca(2+)](isf)) was measured in anesthetized Wistar rats by using in situ microdialysis. During perfusion of 20 cm of the proximal small intestine with Ca(2+)-free buffer, renal [Ca(2+)](isf) was 1.63 +/- 0.19 mmol/l in the cortex (n = 6) and 1.93 +/- 0.12 mmol/l in the medulla (n = 5, P = 0.223). When Ca(2+) in the intestinal lumen was increased to 3 mmol/l, no change was seen in total or ionized serum Ca(2+) (S(Ca)), urinary Ca(2+) excretion (U(Ca)), or Ca(2+) in a microdialysate of the kidney cortex. Increasing intestinal Ca(2+) further, to 6 mmol/l, was without effect on S(Ca) but significantly increased U(Ca) by 38% and microdialysate Ca(2+) by 36% (1.25 +/- 0.0.09 vs. 1.70 +/- 0. 14 mmol/l, n = 4, P < 0.05). Intravenous infusion of 28 ng. kg(-1). min(-1) of parathyroid hormone for 1 h during perfusion of the intestinal lumen with 1 mmol/ Ca(2+)caused a 7-10% rise in S(Ca), a 40% fall in U(Ca), and a 32% increase in microdialysate Ca(2+) (1.32 +/- 0.13 vs. 1.74 +/- 0.13 mmol/l, n = 6, P < 0.05). Interlobar arteries with a mean diameter of 120 microm were studied by using a wire myograph to determine whether changes in extracellular Ca(2+) affect muscle tone. When precontracted with 5 micromol/l serotonin, the arteries relaxed in response to cumulative addition of Ca(2+) (1-5 mmol/l) with an ED(50) value for Ca(2+) of 3.30 +/- 0.08 mmol/l, n = 3. These data demonstrate that [Ca(2+)](isf) changes dynamically during manipulation of whole-animal Ca(2+) homeostasis and that intrarenal arteries relax in response to extracellular Ca(2+) varied over the range measured in vivo.
We recently described a perivascular sensory nerve-linked dilator system that can be activated by interstitial Ca2+([Formula: see text]). The present study tested the hypothesis that [Formula: see text] in the rat duodenal submucosa varies through a range that is sufficient to activate this pathway. An in situ microdialysis method was used to estimate [Formula: see text]. When the duodenal lumen was perfused with Ca2+-free buffer, [Formula: see text] was 1.0 ± 0.13 mmol/l. [Formula: see text] increased to 1.52 ± 0.04, 1.78 ± 0.10, and 1.89 ± 0.1 when the lumen was perfused with buffer containing 3, 6, and 10 mmol/l Ca2+, respectively ( P < 0.05).[Formula: see text] was 1.1 ± 0.06 mmol/l in fasted animals and increased to 1.4 ± 0.06 mmol/l in free-feeding rats ( P < 0.05). Wire myography was used to study isometric tension responses of isolated mesenteric resistance arteries. Cumulative addition of extracellular Ca2+-relaxed serotonin- and methoxamine-precontracted arteries with half-maximal effective doses of 1.54 ± 0.05 and 1.67 ± 0.08 mmol/l, respectively ( n = 5). These data show that duodenal[Formula: see text] undergoes dynamic changes over a range that activates the sensory nerve-linked dilator system and indicate that this system can link changes in local Ca2+ transport with alterations in regional resistance and organ blood flow.
We recently reported that Ca2+-induced relaxation could be linked to a Ca2+ receptor (CaR) present in perivascular nerves. The present study assessed the effect of chronic sensory denervation on Ca2+-induced relaxation. Mesenteric resistance arteries were isolated from rats treated as neonates with capsaicin (50 mg/kg), vehicle, or saline. The effect of cumulative addition of Ca2+ was assessed in vessels precontracted with 5 μM norepinephrine. Immunocytochemical studies showed that capsaicin treatment significantly reduced the density of nerves staining positively for calcitonin gene-related peptide (CGRP) and for the CaR (CGRP density: control, 51.1 ± 3.9 μm2/mm2; capsaicin treated, 31.4 ± 2.8 μm2/mm2, P = 0.01; control CaR density, 46 ± 4 μm2/mm2, n = 7; capsaicin-treated CaR density, 24 ± 4 μm2/mm2, n = 8, P = 0.002). Dose-dependent relaxation to Ca2+ (1–5 mM) was significantly depressed in vessels from capsaicin-treated rats (overall P < 0.001, n = 6 or 7), whereas the relaxation response to acetylcholine remained intact. These data support the hypothesis that Ca2+-induced relaxation is mediated by activation of the CaR associated with capsaicin-sensitive perivascular neurons.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.