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      Management of Hypoglycemia in Nondiabetic Palliative Care Patients: A Prognosis-Based Approach

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          Abstract

          Hypoglycemia due to underlying terminal illness in nondiabetic end-of-life patients receiving palliative care has not been fully studied. For example, we do not have adequate information on the frequency of spontaneous hypoglycemia in patients as occurs during the different stages of palliative care. Depending on the case-mix nature of the palliative care ward, at least 2% of palliative care patients may develop hypoglycemia near the end of life when the remaining life expectancy counts down in days. As many as 25%–60% of these patients will neither have autonomic response nor have neuroglycopenic symptoms during a hypoglycemic episode. Although it is not difficult to diagnose and confirm a true hypoglycemia when it is suspected clinically, an episode of hypoglycemic attack may go unnoticed in some patients in a hospice setting. Current trends in palliative care focus on providing treatments based on a prognosis-based framework, involving shared decision-making between the patient and caregivers, after considering the prognosis, professional recommendations, patient’s autonomy, family expectations, and the current methods for treating the patient’s physical symptoms and existential suffering. This paper provides professional care teams with both moral and literature support for providing care to nondiabetic patients presenting with hypoglycemia.

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          Most cited references17

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          Hypoglycemia as a predictor of mortality in hospitalized elderly patients.

          Hypoglycemia during hospitalization occurs in patients with and without diabetes. The aims of this study were to determine the incidence, associated risk factors, and short- and long-term outcome of hypoglycemia among hospitalized elderly patients. This is a case-control study conducted at geriatric and medicine departments. All patients 70 years or older with documented hypoglycemia hospitalized within 1 year (n = 281) were compared with a nonhypoglycemic group of 281 elderly, randomly selected patients from the same hospitalized population. Among 5404 patients 70 years or older, 281 (5.2%) had documented hypoglycemia. Compared with the nonhypoglycemic group, we found the following characteristics to be true in the hypoglycemic group: there were more women than men (58% vs 44%, P =.001); sepsis was 10 times more common (P<.001); malignancy was 2.8 times more common (P =.04); the mean serum albumin level was lower (2.8 g/dL vs 3.4 g/dL, P<.001); and the mean serum creatinine and alkaline phosphatase levels were higher (P<.001 for both). Diabetes was known in 42% of the hypoglycemic group and in 31% of the nonhypoglycemic group (P =.03); 70 patients in the hypoglycemic group were taking sulfonylureas or insulin. Multivariate logistic analysis showed that sepsis, albumin level, malignancy, sulfonyurea and insulin treatment, alkaline phosphatase level, female sex, and creatinine level were all independent predictors of developing hypoglycemia. In-hospital mortality and 3-month mortality were about twice as high in the hypoglycemic group (P<.001). Multivariate analysis of mortality found that sepsis, low albumin level, and malignancy were independent predictors, while hypoglycmia was not. Hypoglycemia was common in elderly hospitalized patients and predicted increased in-hospital 3- and 6-month cumulative mortality. However, in a multivariate analysis, hypoglycemia was not an independent predictor for mortality, implying that it is only a marker.
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            Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia.

            In type 1 diabetes, the impairment of the glucagon response to hypoglycemia increases both its severity and duration. In nondiabetic individuals, hypoglycemia activates the autonomic nervous system, which in turn mediates the majority of the glucagon response to moderate and marked hypoglycemia. The first goal of this minireview is therefore to illustrate and document these autonomic mechanisms. Specifically we describe the hypoglycemic thresholds for activating the three autonomic inputs to the islet (parasympathetic nerves, sympathetic nerves, and adrenal medullary epinephrine) and their magnitudes of activation as glucose falls from euglycemia to near fatal levels. The implication is that their relative contributions to this glucagon response depend on the severity of hypoglycemia. The second goal of this minireview is to discuss known and suspected down-regulation or damage to these mechanisms in diabetes. We address defects in the central nervous system, the peripheral nervous system, and in the islet itself. They are categorized as either functional defects caused by glucose dysregulation or structural defects caused by the autoimmune attack of the islet. In the last section of the minireview, we outline approaches for reversing these defects. Such reversal has both scientific and clinical benefit. Scientifically, one could determine the contribution of these defects to the impairment of glucagon response seen early in type 1 diabetes. Clinically, restoring this glucagon response would allow more aggressive treatment of the chronic hyperglycemia that is linked to the debilitating long-term complications of this disease.
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              Leptin-inhibited PBN neurons enhance counter-regulatory responses to hypoglycemia in negative energy balance

              Hypoglycemia initiates the counter regulatory response (CRR), in which the sympathetic nervous system, glucagon, and glucocorticoids restore glucose to appropriate concentrations. During starvation, low leptin restrains energy utilization, enhancing long-term survival. To ensure short-term survival during hypoglycemia in fasted animals, the CRR must overcome this energy-sparing program and nutrient depletion. Here, we identify in mice a previously unrecognized role for leptin and a population of leptin-regulated neurons that modulate the CRR to meet these challenges. Hypoglycemia activates leptin receptor (LepRb) and cholecystokinin (CCK)-expressing neurons of the parabrachial nucleus (PBN), which project to the ventromedial hypothalamic nucleus. Leptin inhibits these cells and Cckcre -mediated ablation of LepRb enhances the CRR. Inhibition of PBN LepRb cells blunts the CRR, while their activation mimics the CRR in a CCK-dependent manner. PBN LepRbCCK neurons represent a crucial component of the CRR system, and may represent a therapeutic target in hypoglycemia.
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                Author and article information

                Journal
                Palliat Care
                Palliat Care
                Palliative Care: Research and Treatment
                Palliative Care
                Libertas Academica
                1178-2242
                2016
                23 November 2016
                : 10
                : 1-5
                Affiliations
                [1 ]Division of Palliative Medicine, Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan.
                [2 ]Division of Medical Oncology, Cancer Center of Kuang Tien General Hospital, Taichung, Taiwan.
                [3 ]Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
                [4 ]Division of Geriatric Medicine, Department of Family Medicine, Kuang Tien General Hospital, Taichung, Taiwan.
                Author notes
                Article
                pcrt-10-2016-001
                10.4137/PCRT.S38956
                5123827
                27920549
                526bafed-52f6-4f3d-bb73-99962d4aa2d8
                © 2016 the author(s), publisher and licensee Libertas Academica Ltd.

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

                History
                : 13 September 2016
                : 26 October 2016
                : 01 November 2016
                Categories
                Review

                hypoglycemia,nondiabetic,palliative care,shared decision,lucid moments,treatment withholding,prognosis based

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