Altered Hierarchy of Protective Responses Against Severe Hypoglycemia in Normal Aging in Healthy Men

Matyka, Krystyna; Evans, Mark L.; Lomas, J.; Cranston, Iain; Macdonald, I. A.; Amiel, S

doi:10.2337/diacare.20.2.135

Cited by 173 publications

(130 citation statements)

References 34 publications

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“…Age itself can be a very important factor. A study has shown that neurological symptoms are important in hypoglycaemia in elderly diabetic people [104], and in our own laboratory-based studies, whereas older men showed no diminution of catecholamine responses to induced controlled hypoglycaemia, they reported markedly fewer autonomic symptoms and a greater propensity to visual disturbance and showed a greater slowing of psychomotor performance [105]. At the other end of the scale, children who have more vigorous counterregulatory hormone responses than adults [106], nevertheless seem more likely to present with behavioural and mood disturbances in hypoglycaemia than adults [107].…”

Section: The Effects Of Ageing On Hypoglycaemia Unawarenessmentioning

confidence: 63%

Hypoglycaemia unawareness and the brain

Smith

Amiel

2002

Diabetologia

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The intention of this paper is to critically review the current state of knowledge of the role of the brain in the syndrome of hypoglycaemia unawareness.Both the role of the brain in the detection of hypoglycaemia and initiation of the counterregulatory responses and the function of the cerebral cortex during acute hypoglycaemia are considered. The evidence for and against the brain as the primary site of mammalian hypoglycaemia sensing and the mechanisms whereby such sensing may occur and change in hypoglycaemia unawareness are discussed.Current evidence supports a major role for the central nervous system in hypoglycaemia sensing and there is increasing understanding of the mechanisms of counterregulatory failure and cognitive dysfunction in hypoglycaemia unawareness. More needs to be done to expand this understanding and translate it into therapeutic strategies to defend against severe hypoglycaemia in diabetes therapy. [Diabetologia (2002) -002-0877-7 Hypoglycaemia unawareness and the brainDiabetologia (2002) 45:949-958 DOI 10.1007/s00125 D. Smith, S. A. AmielGuy's, King's and St Thomas' School of Medicine, London, UK subjects. As blood glucose decreases, pancreatic insulin secretion decreases and glucagon secretion increases, stimulating endogenous glucose production and slowing the blood glucose fall. Later, sympathetic activation and catecholamine secretion, with release of growth hormone and adrenocorticotrophin, driving release of adrenal cortical steroids, contribute by supporting endogenous glucose production and reducing consumption of glucose by peripheral tissues. An associated complex of symptoms, including hunger, encourages an eating response. The functional anatomy of these responses indicate a central coordinating structure involving the regions around the hypothalamus, hippocampus and caudate nuclei. Failure of some or all of these counterregulatory mechanisms allows a more severe decrease in plasma glucose concentrations, resulting in cortical dysfunction. Thus counterregulatory failure is associated with impaired awareness of hypoglycaemia and an increased risk of severe hypoglycaemia, in which cognitive function is so disturbed that the patient can become drowsy, unco-ordinated, confused or even comatose. This is a Iatrogenic hypoglycaemia was described in the very first days of insulin therapy and hypoglycaemia without subjective awareness was described shortly thereafter. The British pioneer of diabetes therapy, R.D. Lawrence, himself diabetic, gave a clear account of neuroglycopenic hypoglycaemia with reduced subjective awareness more than 60 years ago [1]. Over 20 years ago the site of coordination of glucoregulatory responses was located in the hypothalamus [2].Hypoglycaemia sufficient to cause clinically significant cortical dysfunction does not occur in healthy

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Section: The Effects Of Ageing On Hypoglycaemia Unawarenessmentioning

confidence: 63%

Hypoglycaemia unawareness and the brain

Smith

Amiel

2002

Diabetologia

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“…Así, el envejecimiento disminuye la capacidad de aumentar la glucosa circulante en respuesta a catecolaminas y con ello la capacidad de aumentar el suministro para la función cognitiva en situaciones de estrés 8 . Este efecto del envejecimiento normal, aumentaría el riesgo de hipoglicemia severa en pacientes añosos tratados con sulfonilureas o insulina 9 .…”

Section: Discussionunclassified

Hipoglicemia recurrente como causa reversible de síndrome demencial en adultos mayores diabéticos, a propósito de un caso

Aizman

Iruretagoyena

et al. 2010

Rev. méd. Chile

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Cognitive impairment probably related to repeated episodes of hypoglycemia.Report of one case Menos de 10% de las causas de demencia se consideran reversibles. Entre estas condiciones se cuentan alteraciones tiroideas, déficit de vitamina B12, hidrocéfalo normotensivo, hematoma subdural crónico, neurosífilis, VIH y desórdenes psiquiátricos como la pseudodemencia depresiva 1 . We report a 78 year-old diabetic woman, treated with gliburide and met-formin, consulting in the emergency room for a non fluctuating impairment in conscious-Una causa poco reconocida es el deterioro cognitivo producido por hipoglicemias recurrentes. Presentamos un caso clínico que destaca la importancia de reconocer dicho diagnóstico, especialmente considerando los objetivos de metas terapéuticas estrictas preconizados por las guías actuales y por la potencial reversión de los sín-tomas y la prevención de daño cognitivo crónico que implicaría su oportuno diagnóstico y manejo. Caso clínicoMujer de 78 años, autovalente, independiente en actividades de la vida diaria, con escolaridad completa, tiene antecedentes de hipertensión arterial, hipotiroidismo, hipoacusia y diabetes mellitus tipo 2 (DM 2) manejada con glibenclamida 10 mg y metformina 1.700 mg al día, con lo cual lograba glicemias capilares adecuadas.Fue llevada por familiares al Servicio de Urgencia, para evaluación por compromiso cualitativo de conciencia, no fluctuante, de más de 24 hrs de evolución, sin signos de focalización y con recuperación espontánea completa. Su familia señaló

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“…19,20 Older patients also have often organ dysfunction age related, which alters insulin sensitivity and drug metabolism, resulting in the enhancement of hypoglycemic events. 10 Elderly people show symptoms of hypoglycemia at a considerably lower glycemic threshold compared to the young (54+3.6 mg/dL vs 65+1.8 mg/dL) 9 and frequently for their altered mental conditions are not able to communicate their symptoms. In diabetic patients, the most obvious risk factor for hypoglycemia is the exogenous administration of insulin or the stimulation of insulin secretion by secretagogues containing drugs.…”

Section: Risk Factors Of Hypoglycemiamentioning

confidence: 99%

“…8,9 In addition, hospital patients may exhibit only neuroglycopenic signs, without any preceding autonomic symptoms. This is due to many factors including the polypharmacy, multiorgan dysfunction and the presence of long lasting diabetes, all factors usually present in the internal medicine patient.…”

Section: Definition and Prevalence Of Hypoglycemiamentioning

confidence: 99%

The clinical impact of hypoglycemia in hospitalized patients

Borzı̀

Fontanella

2015

Ital J Med

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Hypoglycemia is a very common problem, mostly in frail, severely ill, older hospitalized patients. Hypoglycemia has been implicated in the development of adverse clinical outcomes, including an increased mortality. Fear of iatrogenic hypoglycemia remains an obstacle to adequate inpatient glycemic control. It may be considered as a marker of disease, rather than cause in itself of undesirable events. Several factors, such as treatment with exogenous insulin, mismatch between insulin administration and meal intake with the loss of normal counter regulatory responses, place patients with diabetes at higher risk for hypoglycemia than the ones without diabetes. In this review we discuss the causes and predictors of hypoglycemia in non-critically ill hospitalized patients and how to prevent them. Subcutaneous insulin with basal-bolus regimen rather than sliding scale and the use of analogues may minimize hypoglycemic events. In-patient glycemic management should be patient-centered, following the current guidelines, and aimed to prevent hypoglycemic events.Correspondence: Andrea Fontanella, Dipartimento di Medicina, Ospedale del Buon Consiglio Fatebenefratelli, via Manzoni 220, 80123 Napoli, Italy. E-mail: andreafontanella52@gmail.com Key words: hypoglycemia, diabetes, non-critical illness, inpatients.Received for publication: 6 October 2014. Accepted for publication: 3 December 2014.This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).

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Altered Hierarchy of Protective Responses Against Severe Hypoglycemia in Normal Aging in Healthy Men

Cited by 173 publications

References 34 publications

Hypoglycaemia unawareness and the brain

Hypoglycaemia unawareness and the brain

Hipoglicemia recurrente como causa reversible de síndrome demencial en adultos mayores diabéticos, a propósito de un caso

The clinical impact of hypoglycemia in hospitalized patients

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