Falla autonómica asociada a hipoglucemia / Hypoglycemia associated autonomic failure

La hipoglucemia inadvertida (HI) es una complicación del tratamiento de la diabetes mellitus tipo 1 (DM1) y DM2 tratada con insulina o sulfonilureas, que se caracteriza por una capacidad reducida para percibir el inicio de los episodios de hipoglucemia. En general, coexiste con una insuficiente respuesta hormonal contrarreguladora a la hipoglucemia denominada falla autonómica asociada a la hipoglucemia (FAAH). El desarrollo de HI y de falla contrarreguladora a la hipoglucemia aumentan significativamente el riesgo de hipoglucemias severas. Se han desarrollado escalas de puntuación para identificar, en la consulta clínica, a este grupo de personas con elevado riesgo de hipoglucemias severas. La piedra angular del tratamiento consiste en evitar las hipoglucemias mediante una intervención multifactorial de cuidados clínicos y educación estructurada.

Hypoglycemia unawereness is a complication of type 1 diabetes treatment and of type 2 diabetes treatment treated with insulin or sulfonylureas, characterized by a reduced ability to perceive the onset of episodes of hypoglycemia. In general, it coexists with an insufficient counterregulatory hormonal response to hypoglycemia called: hypoglycemia associated autonomic failure (HAAF). The development of hypoglycemia unawereness and counterregulatory failure to hypoglycemia significantly increase the risk of severe hypoglycemia. Scoring scales have been developed to identify this group of people at high risk of severe hypoglycemia in the clinic. The cornerstone of treatment is to avoid hypoglycemia through a multifactorial intervention of clinical care and structured education.

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes

ABSTRACT This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs.77%, respectively, p = 0.03).

Hipoglicemia grave e fatores de risco em pessoas com diabetes em unidade de internação: estudo caso controle / Severe hypoglycemia in people with diabetes in an inpatient unit: a case-control study

A hipoglicemia é uma das principais complicações frente ao manejo inadequado do diabetes, com destaque para a hipoglicemia grave que configura-se como um problema relevante para a manutenção da qualidade de vida dos indivíduos. Os objetivos do presente estudo foram caracterizar os episódios de hipoglicemia grave em pacientes com diabetes em unidades de internação clínica; analisar a associação entre os fatores de risco e os episódios de hipoglicemia grave de pacientes com diabetes em unidade de internação; estimar o tempo de sobrevida até o episódio hipoglicêmico grave. A metodologia empregada para esse estudo considerou casos episódios hipoglicêmicos graves, definidos por valores glicêmicos abaixo de 50 mg/dL. Foram considerados controles os episódios hipoglicêmicos não graves definidos por valores glicêmicos entre 51 a 70mg/dl. Considerou-se como fatores associados à hipoglicemia grave variáveis propostas pela revisão integrativa de literatura realizada para a construção dessa pesquisa. Ainda, também foi analisado o diagnóstico de enfermagem risco de glicemia instável da nomenclatura NANDA-I e sua pertinência quanto aos fatores de risco associados à ocorrência de episódios de hipoglicemia grave. A coleta de dados desenvolveu-se através de análise documental retrospectiva. Foram observados 47 episódios de hipoglicemia grave e 60 episódios de hipoglicemia não grave, respectivamente caso e controle. Os fatores de risco para hipoglicemia grave com evidências na literatura e que foram validados neste estudo caso- controle foram: escolaridade; terapia insulínica; uso de insulinas associadas; modificação recente da dose; insuficiência renal; outras comorbidades; episódio hipoglicêmico anterior e habilidade deficiente para o autocuidado. Identificou-se que o tempo de sobrevida até o episódio hipoglicêmico configura-se em uma curva descendente.A média de tempo que uma pessoa sobrevive até o desfecho de hipoglicemia grave mostrou que o paciente que tem diabetes e está internado tem chances progressivamente maiores de desenvolver episódio de hipoglicemia grave logo nos primeiros dias de internação. Frente aos resultados obtidos, sugere-se que novos estudos sejam realizados com o objetivo descrever aprofundadamente os mecanismos de associação destas variáveis com o episódio hipoglicêmico grave. A identificação da magnituddos fatores de risco para hipoglicemia grave, apresentada através do estudo caso-controle, fornece bases para a construção de instrumentos padronizados de avaliação adequada de pacientes com diabetes em unidades de internação.

Hypoglycemia is one of the main complications in the face of inadequate management of diabetes, where severe hypoglycemia is a relevant problem in terms of maintaining the quality of life of individuals. The objectives of the study were to characterize episodes of severe hypoglycemia in patients with diabetes in clinical inpatient units; to analyze the association between risk factors and episodes of severe hypoglycemia in patients with diabetes in the inpatient unit; estimate the survival time until the severe hypoglycemic episode. The methodology used for this study considered cases of severe hypoglycemic episodes, defined by glycemic values below 50 mg / dL. Non-severe hypoglycemic episodes were defined as controls defined by glycemic values between 51 to 70mg / dl. Factors associated with severe hypoglycemia were considered as variables proposed by the integrative literature review carried out for the construction of this research. Still, the Nursing Diagnosis Risk of Unstable Glycemia of the NANDA-I Nomenclature and its relevance regarding the risk factors associated with the occurrence of episodes of severe hypoglycemia were also analyzed. Data collection was developed through retrospective document analysis. 47 episodes of severe hypoglycemia and 60 episodes of non-severe hypoglycemia were analyzed, case and control, respectively. The risk factors for severe hypoglycemia with evidence in the literature that were validated in this case-control study were: education; insulin therapy; use of associated insulins; recent dose modification; renal insufficiency; other comorbidities; previous hypoglycemic episode and deficient ability for self-care. It was identified that the survival time until the hypoglycemic episode is configured in a descending curve. The average time that a person survives until the outcome of severe hypoglycemia showed that the patient who has diabetes and is hospitalized has a progressively greater chance of developing an episode of severe hypoglycemia in the first days of hospitalization. In view of the results obtained, it is suggested that further studies be carried out in order to describe in depth the mechanisms of association of these variables with the severe hypoglycemic episode. The identification of the magnitude of risk factors for severhypoglycemia, presented through the case-control study, provides the basis for the construction of standardized instruments for adequate assessment of patients with diabetes in inpatient units.

La hipoglucemia es una de las principales complicaciones ante el manejo inadecuado de la diabetes, donde la hipoglucemia severa es un problema relevante en cuanto al mantenimiento de la calidad de vida de los individuos. Los objetivos del estudio fueron caracterizar episodios de hipoglucemia severa en pacientes con diabetes en unidades de internación clínica; analizar la asociación entre factores de riesgo y episodios de hipoglucemia severa en pacientes con diabetes en la unidad de internación; Estime el tiempo de supervivencia hasta el episodio de hipoglucemia grave. La metodología utilizada para este estudio consideró casos de episodios hipoglucémicos graves, definidos por valores glucémicos inferiores a 50 mg / dL. Se consideraron controles los episodios hipoglucémicos no graves definidos como valores glucémicos entre 51 y 70 mg / dl. Los factores asociados a la hipoglucemia severa fueron considerados como variables propuestas por la revisión integradora de la literatura realizada para la construcción de esta investigación. Aún así, también se analizó el Diagnóstico de Enfermería Riesgo de Glucemia Inestable de la Nomenclatura NANDA-I y su relevancia con respecto a los factores de riesgo asociados a la ocurrencia de episodios de hipoglucemia severa. La recolección de datos se desarrolló a través del análisis retrospectivo de documentos. Se analizaron 47 episodios de hipoglucemia severa y 60 episodios de hipoglucemia no severa, caso y control, respectivamente. Los factores de riesgo de hipoglucemia severa con evidencia en la literatura que fueron validados en este estudio de casos y controles fueron: educación; terapia con insulina; uso de insulinas asociadas; modificación reciente de la dosis; insuficiencia renal; otras comorbilidades; episodio hipoglucémico previo y capacidad deficiente para el autocuidado. Se identificó que el tiempo de supervivencia hasta el episodio hipoglucémico se configura en una curva descendente. El tiempo promedio que una persona sobrevive hasta el resultado de una hipoglucemia severa mostró que el paciente que tiene diabetes y está hospitalizado tiene una probabilidad progresivamente mayor de desarrollar un episodio de hipoglucemia severa en los primeros días de hospitalización. A la vista de los resultados obtenidos, se sugiere realizar más estudios con el fin de describir en profundidad los mecanismos de asociación de estas variables con el episodio de hipoglucemia grave. La identificación de la magnitud de los factores de riesgo de hipoglucemia severa, presentada a través del estudio de casos y controles, proporciona la base para la construcción de instrumentos estandarizados para la evaluación adecuada de pacientes con diabetes en unidades de internación.

Effect of Recurrent Severe Hypoglycemia on Cognitive Performance in Adult Patients with Diabetes: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the existence and extent of cognitive impairment in adult diabetes mellitus (DM) patients with episodes of recurrent severe hypoglycemia,by using meta-analysis to synthesize data across studies.PubMed,EMBASE and Cochrane library search engines were used to identify studies on cognitive performance in DM patients with recurrent severe hypoglycemia.Random-effects meta-analysis was performed on seven eligible studies using an inverse-variance method.Effect sizes,which are the standardized differences between the experimental group and the control group,were calculated.Of the 853 studies,7 studies met the inclusion criteria.Compared with control subjects,the adult DM patients with episodes of recurrent severe hypoglycemia demonstrated a significantly lowered performance on memory in both types of DM patients,and poor performance of processing speed in type 2 DM patients.There was no significant difference between adult DM patients with and those without severe hypoglycemia in other cognitive domains such as general intelligence,executive function,processing speed and psychomotor efficiency.Our results seem to confirm the hypothesis that cognitive dysfunction is characterized by worse memory and processing speed in adult DM patients with a history of recurrent severe hypoglycemia,whereas general intelligence,executive function,and psychomotor efficiency are spared.

Analysis of 71 cases of insulin autoimmune syndrome / 中国免疫学杂志

Objective:To know the clinical features of insulin autoimmune syndrome to improve diagnostic level. Methods:Focused oninsulin autoimmune syndrome ( IAS ), to make retrospective analysis by summarizing medical history, clinical manifestations,insulin levels,treatment and prognosis of 71 IAS cases recently fifteen years reported in the literature on CNKI. Results:Among the 71 IAS cases,there were 40 cases with a history of hyperthyroidism,31 cases taking methimazole before onset and 43 cases with hypoglycemic episodes with clear regularity, of which 30 cases hypoglycemic episodes occurred during the night or on early morning. 35 cases had disorders of consciousness and such patients had lower blood glucose level and higher insulin level; 36 cases received hormone therapy with shorter time for IAA turning negative,and 26 cases only stopped taking the causative drug;69 cases have a remission,1 case prognosis was unknown due to auto-discharge,and 1 case dies of combined pleural endotheliomas. Conclusion:IAS is one of the important causes of severe spontaneous hypoglycemia and is clinically relatively rare. It often combines with autoimmune diseases,induced by hydroxyl drug and vulnerable to disturbance of consciousness. Patients who have disorders of consciousness should be treated with hormonotherapy in time. Early identification and appropriate treatment generally lead to good prognosis.

Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes

BACKGROUND: We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes. METHODS: The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis. RESULTS: Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use. CONCLUSION: We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.

Baseline-Corrected QT (QTc) Interval Is Associated with Prolongation of QTc during Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus

BACKGROUND: We investigated an association between baseline heart rate-corrected QT (QTc) interval before severe hypoglycemia (SH) and prolongation of QTc interval during SH in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2004 and June 2014, 208 patients with T2DM, who visited the emergency department because of SH and underwent standard 12-lead electrocardiography within the 6-month period before SH were consecutively enrolled. The QTc interval was analyzed during the incidence of SH, and 6 months before and after SH. QTc intervals of 450 ms or longer in men and 460 ms or longer in women were considered abnormally prolonged. RESULTS: The mean age and diabetes duration were 68.1±12.1 and 14.1±10.1 years, respectively. The mean QTc intervals at baseline and SH episodes were 433±33 and 460±33 ms, respectively (P<0.001). One hundred and fourteen patients (54.8%) had a prolonged QTc interval during SH. There was a significant decrease in the prolonged QTc interval within 6 months after SH (QTc interval prolongation during SH vs. after recovery, 54.8% vs. 33.8%, P<0.001). The prolonged QTc interval was significantly associated with baseline QTc interval prolongation (odds ratio, 2.92; 95% confidence interval, 1.22 to 6.96; P=0.016) after adjusting for multiple confounders. CONCLUSION: A prolonged QTc interval at baseline was significantly associated with prolongation of the QTc interval during SH in patients with T2DM, suggesting the necessity of QTc interval monitoring and attention to those with a prolonged QTc interval to prevent SH.

Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes

BACKGROUND/AIMS: To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. METHODS: Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. RESULTS: A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia ( 100 beats per minute) and severe hypertension (> or = 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. CONCLUSIONS: During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.

Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes

BACKGROUND: To investigate whether a history of prior cardiovascular disease (CVD) is associated with severe hypoglycemia (SH) in patients with type 2 diabetes. METHODS: We conducted a prospective cohort study from January 2001 to December 2012 with a median follow-up time of 9.5 years (5,814 person-years). Patients aged 25 to 75 years with type 2 diabetes and without chronic kidney disease were enrolled (n=894), and 624 patients completed follow-up. SH was defined as hypoglycemic episodes requiring hospitalization or medical care in an emergency department. We used the Cox proportional hazards regression analysis to test associations between SH episodes and potential explanatory variables. RESULTS: Among the 624 participants who completed follow-up, 60 patients (9.6%) had previous CVD. Compared to patients without CVD, patients with previous CVD were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline. During follow-up, 62 patients (9.9%) experienced at least one SH episode (incidence of 1.33 per 100 patient-years). The development of SH was associated with a history of CVD (hazard ratio, 1.99; 95% confidence interval, 1.07 to 3.72; P=0.031) after adjusting for sex, age, diabetic duration, hypertension, hemoglobin A1c levels, diabetic complications, cardiovascular autonomic neuropathy, and insulin use. CONCLUSION: A history of CVD was an independent risk factor for the development of SH in patients with type 2 diabetes mellitus. For patients with CVD, modulation of glycemic targets and diabetic education for the prevention of hypoglycemia should be implemented.

Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes

Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.

Corrected QT Interval Prolongation during Severe Hypoglycemia without Hypokalemia in Patients with Type 2 Diabetes

BACKGROUND: To evaluate the effects of severe hypoglycemia without hypokalemia on the electrocardiogram in patients with type 2 diabetes in real-life conditions. METHODS: Electrocardiograms of adult type 2 diabetic patients during the episodes of severe hypoglycemia and the recovered stage were obtained and analysed between October 1, 2011 and May 31, 2012. Patients who maintained the normal serum sodium and potassium levels during the episodes of severe hypoglycemia were only selected as the subjects of this study. Severe hypoglycemia was defined, in this study, as the condition requiring active medical assistance such as administering carbohydrate when serum glucose level was less than 60 mg/dL. RESULTS: Nine type 2 diabetes patients (seven men, two women) were included in the study. The mean subject age was 73.2+/-7.7 years. The mean hemoglobin A1c level was 6.07%+/-1.19%. The median duration of diabetes was 10 years (range, 3.5 to 30 years). Corrected QT (QTc) intervals were significantly increased during the episodes of severe hypoglycemia compared to the recovered stage (447.6+/-18.2 ms vs. 417.2+/-30.6 ms; P<0.05). However, the morphology and the amplitude of the T waves were not changed and ST-segment elevation and/or depression were not found during the episodes of severe hypoglycemia. CONCLUSION: In this study, QTc interval prolongation during the episodes of severe hypoglycemia was observed without hypokalemia. Therefore, the distinct alterations in cardiac repolarization during the episodes of severe hypoglycemia may not be associated with hypokalemia.

Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea

BACKGROUND: To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects. METHODS: We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009. RESULTS: A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69+/-12 years, mean duration of diabetes was 13.8+/-9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users. CONCLUSION: We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

Severe hypoglycemia in the elderly diabetes

BACKGROUND: Hypoglycemia is the most common therapeutic complication of diabetes mellitus and especially in elderly diabetic patients with diminished cardiac and cerebral circulation can cause serious tissue damage. Though many studies have attempted to evaluate hypoglycemia in IDDM or adult diabetic patients, few studies in the elderly. We have compared clinical characteristics of severe hypoglycemia in elderly diabetes with adult diabetes. METHODS: This study include 56 severe hypoglycemic patients who have admitted to emergency department of National Medical Center from march 1, 1992 to december 31, 1997. they are divided two group (adult group; 21, elderly group; 35) and authors investigate the cause, the symptom, the time of severe hypoglycemia, degree of education, treatment method in each group. RESULTS: 1) DM education was not well done in severe hypoglycemic patients. 2) The frequency of severe hypoglycemia in the elderly was more than adult (adult: 21 (38%), elderly 35 (62%)). 3) In both population, the most common symptom of severe hypoglycemia was neuroglycopenic symptom, especially in the elderly (adult: 57%, elderly: 77%). 4) Decreased food intake (49%) in the elderly and overdose of insulin (38%) in the adult were the most common cause of severe hypoglycemia. 5) Severe hypoglycemia occurred more often between midnight and 6 AM in the adult, between noon and 6 PM in the elderly. 6) The treatment of diabetes mellitus is insulin (71%) and oral hypoglycemic agent (29%) in the adult, oral hypoglycemic agent (51%) and insulin (49%) in the elderly. CONCLUSION: For prevention of severe hypoglycemia, we should emphasize the importance of DM education and especially elderly diabetic patients should be educated about the symptoms of hypoglycemia, the self-management of hypoglycemia, the need for a regular carbohydrate intake and more easy and effective diet program is require in elderly diabetes.