Percepción de la insulinoterapia por parte de pacientes con diabetes mellitus tipo 2 / Perception on Insulinotherapy by Patients with Type 2 Diabetes Mellitus

La diabetes mellitus (DM) es un importante problema de salud pública con una alta prevalencia y carga económica. En Cuba, se estima que viven 1 134 000 personas entre los 20 y 79 años con diabetes, ubicándose como la octava causa de muerte.1 A pesar de existir en el país programas para la atención integral a pacientes diabéticos, todavía existe un vacío en la educación diabetológica, afectado fundamentalmente por el tránsito del paciente entre la atención endocrinológica especializada y la atención médica brindada por los médicos de familia. El conocimiento sobre el tratamiento con insulinas entre los profesionales de la salud del primer nivel de atención es bajo, con una relación directa entre dicho conocimiento y el control glucémico.2 Se asume que un paciente bien educado en su enfermedad logrará un mejor control de esta con adecuada calidad de vida. Según varios estudios,3,4,5 la adherencia al tratamiento en pacientes con diabetes mellitus tipo 2 es baja, donde influyen, entre otros factores, el desconocimiento de la enfermedad, las opciones terapéuticas y conductas de autocuidado y la autorresponsabilidad. En este sentido, con la finalidad de conocer la percepción sobre el tratamiento con insulina por parte de pacientes con DM, se realizó un estudio observacional, descriptivo y transversal, en el Hospital Provincial Clínico-Quirúrgico Arnaldo Milián Castro de Villa Clara (Cuba), en entre enero y marzo de 2020, que fue detenido en este período ante la contingencia generada por la COVID-19. Para ellos se encuestaron 21 pacientes con DM tipo 2 que acudieron a consulta externa de Endocrinología, a los cuales se les aplicó la escala de percepción del tratamiento con insulina (Insuline Treatment Appraisal Scale [ITAS]),6,7 conformada por 16 ítems de percepción negativa y 4 ítems de percepción positiva; con un alfa de Cronbach de 0,89. La calificación de la encuesta es de 20 a 100 puntos, donde a mayor puntuación mayor es la opinión negativa (peor percepción). Del total de pacientes, 12 (57,14 por ciento) eran usuarios de insulina y el resto se trataban con antidiabéticos orales. La edad media de los participantes fue 62,38 ± 2,25 años, predominó el sexo femenino (n = 11; 52,38 por ciento) y el nivel educacional medio-universitario (n = 14; 66,66 por ciento). La media de evolución de la enfermedad fue 10,95 ± 2,25 años para la totalidad del grupo y 13,67 ± 3,28 años para los usuarios de insulina; con un promedio de la glicemia en ayunas previo a la recogida de datos de 7,79 ± 0,92 mmol/L. El 95,23 por ciento de los pacientes tenía al menos alguna complicación crónica de la diabetes y 15 (71,42 por ciento) no habían recibido educación diabetológica previa. En 13 pacientes, desde el debut, existió la necesidad de realizar cambio de tratamiento, en general de antidiabéticos orales hacia esquemas de insulina. La puntuación media global de la escala fue 60,05 ± 1,96 puntos, ligeramente superior en los usuarios de antidiabéticos orales (62,22 ± 9,06 vs. 58,42 ± 9,02), sin diferencia significativas entre ambos grupos (p = 0,95 > 0,05), no obstante, la mayor puntuación en los no usuarios de insulina indica una peor percepción sobre esta. Investigaciones previas coinciden con esta observación, donde la percepción es peor en pacientes no insulinizados.6,7,8 La atención al paciente con DM debe ser integral y, tomando en cuenta este precepto, darse prioridad a la educación diabetológica desde el momento del diagnóstico e incorporar elementos nuevos en cada consulta, sin llegar a saturar de información al paciente. Es conocido el temor que puede generar la necesidad de utilizar insulina entre la población con diabetes, es por ello que debe mostrarse al paciente las ventajas de su utilidad incluso cuando no exista la necesidad inmediata de su uso. Otra conducta extendida entre profesionales de la salud, es la ejemplificación del tratamiento con insulina como último recurso para lograr un control metabólico óptimo en caso de fallar otras terapias o las modificaciones en el estilo de vida, actitud que debe ser erradicada en las consultas de atención integral al paciente con diabetes. Actualmente, los autores de la presente carta, desarrollan una investigación para validar la ITAS en población cubana y contribuir al desarrollo de instrumentos útiles en la educación diabetológica a todos los niveles de atención. Futuros estudios pueden elaborar propuestas de programas formativos, on-line o presencial, y cualquier variedad de materiales educativos que contribuyan con el desconocimiento sobre la DM, tanto de pacientes como de profesionales de la salud(AU)

Insulin Shocks.

Some of the news about insulin is shocking. In the United States, people have died because they were rationing a life-saving medication discovered in the 1920s. How could this happen? Perhaps a better question is why anyone should be surprised. The insulin story both illustrates and challenges many understandings of the problems with insurance, treatment, payment, and politics in the US health care system. It particularly highlights consequences of structuring price discounts as rebates to health plans or government instead of as lower individual prices to patients. Perversely, this encourages higher list prices, which, for patients without insurance or with high cost sharing, make insulin less affordable than it would be without the rebates.

Histopathological and immunohistochemical analysis of the cerebral white matter after transient hypoglycemia in rat.

Patients with hypoglycemic coma show abnormal signals in the white matter on magnetic resonance imaging. However, the precise pathological changes in the white matter caused by hypoglycemic coma remain unclear in humans and experimental animals. This study aimed to reveal the distribution and time course of histopathological and immunohistochemical changes occurring in the white matter during the early stages of hypoglycemic coma in rats. Insulin-induced hypoglycemic coma of 15-30-min duration was induced in rats, followed by recovery using a glucose solution. Rat brains were collected after 6 and 24 hr and after 3, 5, 7, and 14 days. The brains were submitted for histological and immunohistochemical analysis for neurofilament 200 kDa (NF), myelin basic protein, olig-2, Iba-1, and glial fibrillary acidic protein (GFAP). Vacuolation was observed in the fiber bundles of the globus pallidus on days 1-14. Most of the vacuoles were located in GFAP-positive astrocytic processes or the extracellular space and appeared to be edematous. Additionally, myelin pallor and a decrease in NF-positive signals were observed on day 14. Microgliosis and astrogliosis were also detected. Observations similar to the globus pallidus, except for edema, were noted in the internal capsule. In the corpus callosum, a mild decrease in NF-positive signals, microgliosis, and astrogliosis were observed. These results suggest that after transient hypoglycemic coma, edema and/or degeneration occurred in the white matter, especially in the globus pallidus, internal capsule, and corpus callosum in the early stages.

Peripherally administered KP-10 prevents development of insulin-induced hypoglycemic shock in diabetic rhesus monkeys.

AIM: This study investigated whether kisspeptin-10 (KP-10) prevents diabetic rhesus monkeys from insulin-induced hypoglycemic shock. MATERIALS AND METHODS: Thirty-six adult male rhesus monkeys were used, six in each group. Diabetes was induced with streptozotocin (45 mg/kg b.w.; single dose i.v.). Groups were as: saline control, insulin alone, pre-insulin (treated with KP-10, 30 min before insulin), post-insulin (treated with KP-10, 30 min after insulin), treated with premix dose of KP-10 (50 µg) and insulin, and the group treated with the kisspeptin antagonist P234 (50 µg). Following an overnight fast, each animal was subjected to respective treatment, and blood glucose concentrations were recorded every 30-min interval for 3 h. RESULTS: Intergroup comparisons demonstrated that treatment with KP-10 prior to insulin administration and kisspeptin-insulin premix treatment allowed blood glucose levels to rise to significantly higher levels (p < 0.001) by 180 min in diabetic and healthy animals compared to treatment with insulin alone. However, intragroup comparisons revealed a significant decrease in blood glucose level in diabetic animals only. Treatment with P234 antagonist followed by insulin administration abolished the preventive action of kisspeptin, whereby blood glucose decreased significantly (p < 0.001) in both diabetic and healthy animals. KP-10 post-insulin treatment, however, remained ineffective and led, instead, to significantly decreased glucose concentrations by 180 min in both diabetic and healthy animals when compared to animals treated with insulin alone. CONCLUSIONS: KP-10 bears therapeutic potential to prevent hypoglycemic shock that may sometimes occur during intensive insulin therapy. Several pharmacological aspects of its interaction with insulin and other drugs, however, remain to be investigated.

Risk of recurrent severe hypoglycemia remains associated with a past history of severe hypoglycemia up to 4 years: Results from a large prospective contemporary pediatric cohort of the DPV initiative.

OBJECTIVES: In a contemporary cohort of youth with type 1 diabetes, we examined the interval between episodes of severe hypoglycemia (SH) as a risk factor for recurrent SH or hypoglycemic coma (HC). METHODS: This was a large longitudinal observational study. Using the DPV Diabetes Prospective follow-up data, we analyzed frequency and timing of recurrent SH (defined as requiring assistance from another person) and HC (loss of consciousness or seizures) in 14 177 youths with type 1 diabetes aged <20 years and at least 5 years of follow-up. RESULTS: Among 14 177 patients with type 1 diabetes, 72% (90%) had no, 14% (6.8%) had 1 and 14% (3.2%) >1 SH (HC). SH or HC in the last year of observation was highest with SH in the previous year (odds ratio [OR] 4.7 [CI 4.0-5.5]/4.6 [CI 3.6-6.0]), but remained elevated even 4 years after an episode (OR 2.0 [CI 1.6-2.7]/2.2 [CI 1.5-3.1]). The proportion of patients who experienced SH or HC during the last year of observation was highest with SH/HC recorded during the previous year (23% for SH and 13% for HC) and lowest in those with no event (4.6% for SH and 2% for HC) in the initial 4 years of observation. CONCLUSIONS: Even 4 years after an episode of SH/HC, risk for SH/HC remains higher compared to children who never experienced SH/HC. Clinicians should continue to regularly track hypoglycemia history at every visit, adjust diabetes education and therapy in order to avoid recurrences.

Variability of Basal Rate Profiles in Insulin Pump Therapy and Association with Complications in Type 1 Diabetes Mellitus.

BACKGROUND: Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus. MATERIALS AND METHODS: BR profiles of 3118 female and 2427 male patients from the "Diabetes-Patienten-Verlaufsdokumentation" registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The "variability index" was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate. RESULTS: The variability Index correlated positively with severe hypoglycemia (r = .06; p<0.001), hypoglycemic coma (r = .05; p = 0.002), and microalbuminuria (r = 0.05; p = 0.006). In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029) in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (ß = 0.013; p<0.001) and diabetic ketoacidosis (ß = 0.012; p = 0.017). CONCLUSIONS: Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes.

Research on Psychiatric Treatment by Psychiatrists of Chosun-Governor Hospital and Keijo Imperial University Hospital in Korea during Japanese Colonial Rule / 신경정신의학

This review describes the types of psychiatric treatment studied during the Japanese colonial period of 1910–1945 in Korea, known at the time as Chosun. Twenty-nine research papers and abstracts on psychiatric treatment were reviewed, which were published in the Shinkeigaku-zassi (Neurologia), the Seishin-shinkei-gaku zassi (Psychiatria Et Neurologia Japonica) and the Journal of Chosun Medical Association, by faculty members of the department of neuropsychiatry, Chosun-Governor Hospital and Keijo (Seoul) Imperial University School of Medicine. The major research area was biological psychiatry and biological treatment, as Japanese pioneers in psychiatry at that time had introduced German psychiatry into Japan. Professor Kubo published the most papers, followed by Dr. Hattori, Dr. Hikari, and Professor Suits. In Chosun-Governor Hospital, research on prolonged sleep therapy was an active field. In the Imperial University Hospital, malarial fever therapy, sulphur-induced fever therapy, and insulin shock treatment were the most frequent research topics. Some were tried for the first time in the Japanese Empire, which reflected the pioneering position of the university. These achievements are attributed to Professor Kubo. Six papers on psychotherapy were published. Among them, two papers were on persuasion therapy, three papers were case reports of psychoanalytic therapy, and one paper on Freud. However, this psychoanalytic therapy research seemed to be limited trials conducted following literal guidance, and no further development was noted. Generally, research was characterized by simple design, small numbers of subjects, lack of objective evaluation method, lack of statistical treatment, and especially lack of ethical consideration comparing with today's standard.

Prolonged bilateral reactive miosis as a symptom of severe insulin intoxication.

BACKGROUND: Miosis occurs following exposure to toxins that decrease the sympathomimetic tone, increase the cholinergic tone, or exert sedative-hypnotic effects, but has not been reported in insulin poisoning. CASE REPORT: A 64-year- old woman without co-morbidities was found unconscious next to an empty insulin pen. Her Glasgow Coma Scale was 3 with absent reflexes, bilateral reactive miosis, and injection marks across the abdominal wall. The patient was endotracheally intubated, mechanically ventilated, and transferred to this hospital. At admission, the blood glucose level was 34 mg/dL. Glasgow Coma Scale remained at 3, with persistent bilateral reactive miosis. The toxicology screening was negative for ethanol, barbiturates, tricyclic antidepressants, phenothiazines, amphetamines, cannabinoids, salicylates, acetaminophen, and cocaine. Cranial computed tomography with angiography and magnetic resonance imaging (MRI) did not show any structural brain lesions. Intravenous glucose was continued at 6-14 g/h for 3 days. On repeated neurological examinations, the patient remained deeply comatose, with partial loss of cranial nerve function. Bilateral reactive miosis persisted for 4 days. From day 5 on, the patient awoke progressively. At discharge, the patient was fully alert and orientated, without a focal neurological deficit. CONCLUSIONS: Prolonged bilateral reactive miosis can be a clinical symptom accompanying metabolic encephalopathy in severe insulin poisoning. Functional impairment of the pons due to relative hypoperfusion during hypoglycemia may serve as a reasonable pathophysiologic explanation for this phenomenon.

The nursing role in the use of insulin coma therapy for schizophrenia in Britain, 1936-1965.

AIM: To explore the nursing role in the use of insulin coma therapy for schizophrenia in Britain, 1936-1965. BACKGROUND: The only history of mental health nursing in Britain published to date gives a minor role to insulin coma therapy and emphasizes nursing opposition to it. DESIGN: An historical study using documentary and oral history sources obtained in 2003-2008 and supplemented by material drawn from interviews in 2010. METHOD: Historical method was used involving the collection and analysis of primary documentary and oral history material, together with relevant secondary sources. FINDINGS: A range of contemporary sources suggest that nurses in Britain were generally supportive of this treatment regime. The scope for using physical nursing skills was particularly attractive, while the emphasis on close interaction with patients also laid the foundation for later developments in social therapy. The debates surrounding its evidence base are also examined. Faced with a lack of rigorous research findings, clinicians preferred to rely on their clinical judgement. The issue of whether the treatment was abandoned as worthless or merely superseded by still more effective regimes is also explored. CONCLUSION: A nuanced account of the rise and fall of insulin coma therapy provides a lens through which to examine the development of mental health nursing and a case study of the challenges involved in implementing care based on the best evidence.

Resolution of electroconvulsive therapy refractory major depressive disorder with unintentional hypoglycemic seizure: a case report.

We report a 74-year-old white woman with type 1 diabetes and major depressive disorder refractory to multiple medications who received 15 electroconvulsive therapy treatments with minimal improvement. After an accidental hypoglycemic seizure, the patient's symptoms completely resolved. In conclusion, the present case reveals an instance where electroconvulsive therapy-induced seizures appeared to be minimally effective, whereas a single accidental hypoglycemia-induced seizure was incredibly effective for the resolutions of depressive symptoms. Although this case presents a single efficacious use of accidental insulin coma therapy, the applicability is limited because of the known risks of insulin coma therapy.

Severe hypoglycaemia in drug-treated diabetic patients needs attention: a population-based study.

OBJECTIVE: To study one-year incidence and risk factors of severe hypoglycaemias (SH) in adult drug-treated diabetic patients living in two Finnish communities. DESIGN: The episodes of SH and their risk factors were identified from local ambulance registers, from the databases of local health care units, and from patient questionnaires. SETTING: The target population consisted of all drug-treated diabetic patients from the two middle-sized communities in southern Finland, altogether 1776 patients. The study was retrospective. SUBJECTS: A total of 1469 patients (82.7% of the target population) gave informed consent for the use of their medical records and 1325 patients (74.6% of the target population) returned the detailed 36-item questionnaire. RESULTS: Of type 1 and type 2 insulin-treated diabetic patients, 14.6% and 1.0%, respectively, needed ambulance or emergency room care (incidence of 30.5 and 3.0 per 100 patient years). However, 31.0% of type 1 and 12.3% of type 2 diabetic patients reported at least one episode of SH (incidence of 72.0 and 27.0 per 100 patient years). Of all insulin-treated patients, 53 (7.8%) reported three or more episodes of SH. Significant independent risk factors for SH were depression, daily exercise, and nephropathy but not glycaemic control. CONCLUSION: The incidence of SH was high in both types of insulin-treated diabetic patients. However, the recurrent episodes of SH were clustered in a small minority of insulin-treated patients with diabetes. The risk of SH should be considered when assessing the treatment target for an individual diabetic patient.

The effects of hypoglycemic and alcoholic coma on the blood-brain barrier permeability.

In this investigation, the effects of hypoglycemic coma and alcoholic coma on the blood-brain barrier (BBB) permeability have been compared. Female adult Wistar albino rats weighing 180-230 g were divided into three groups: Control group (n=8), Alcoholic Coma Group (n=18), and Hypoglycemic Coma group (n=12). The animals went into coma approximately 3-4 hours after insulin administration and 3-5 minutes after alcohol administration. Evans blue (4mL/kg) was injected intravenously as BBB tracer. It was observed that the alcoholic coma did not significantly increase the BBB permeability in any of the brain regions when compared to control group. Changes in BBB permeability were significantly increased by the hypoglycemic coma in comparison to the control group values (p<0.01). Our findings suggest that hypoglycemic and alcoholic coma have different effects on the BBB permeability depending on the energy metabolism.

Protective effects of d-3-hydroxybutyrate and propionate during hypoglycemic coma: clinical and biochemical insights from infant rats.

BACKGROUND: d-3-hydroxybutyrate (3OHB) is an alternative energy substrate for the brain during hypoglycemia, especially during infancy. Supplementation of 3OHB during sustained hypoglycemia in rat pups delays onset of burst suppression coma, but is associated with white matter injury and increased mortality. The biochemical basis for this ambivalent effect is not known. It may be related to an anaplerotic or gluconeogenetic deficit of 3OHB. METHODS AND RESULTS: We studied clinical alertness, EEG and brain metabolites (acyl-carnitines, amino acids, glycolytic and pentose phosphate intermediates) in 13 day-old rat pups during insulin induced hypoglycemic coma and after treatment with 3OHB alone or in combination with the anaplerotic substrate propionate. Clinically, treatment with 3OHB and propionate resulted in an alert state and EEG improvement, while treatment with 3OHB alone resulted in an improved EEG but animals remained clinically comatose. Biochemically, both treatments resulted in correction of cerebral glutamate and ammonia levels but not of gluconeogenetic substrates and pentose phosphate metabolites. CONCLUSION: 3OHB treatment restores glutamate metabolism but cannot restore a glycolytic or pentose phosphate pathway deficit. Additional treatment with propionate significantly improved the clinical protective effect of 3OHB in hypoglycemic coma.

Frequent reoccurrence of hypoglycemia in a type 2 diabetic patient with insulin antibodies.

BACKGROUND: Insulin antibody (IAb) may be produced in patients receiving long-term, animal-derived insulin, leading to insulin resistance or hypoglycemia. There have been very few reports of hypoglycemia caused by IAb in patients taking recombinant human insulin. CASE REPORT: We report the case of an 82-year-old male patient with type 2 diabetes mellitus who suffered repeated episodes of severe hypoglycemia-related symptoms (including coma) prior to admission. The patient had been taking Novolin 30R, a premixed human insulin. The patient's IAb level was markedly elevated, and hypoglycemia caused by recombinant human insulin treatment-induced IAb production was diagnosed. Acarbose and metformin were prescribed, and the patient recovered uneventfully. The patient ceased taking these medications, and he was subsequently treated with recombinant human insulin to combat hyperglycemia. This was followed by reoccurrence of hypoglycemic coma. The patient was advised to avoid taking recombinant human insulin for the rest of his life and to control hyperglycemia with acarbose and metformin. CONCLUSIONS: Although rare, hypoglycemia caused by recombinant human insulin-induced IAb production should be considered in patients with type 2 diabetes who experience repeated episodes of hypoglycemia.

Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study.

OBJECTIVE A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy. RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model. RESULTS Of the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95% CI 0.91-3.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38-4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.

Utility values for symptomatic non-severe hypoglycaemia elicited from persons with and without diabetes in Canada and the United Kingdom.

OBJECTIVE: To elicit societal and patient utilities associated with diabetic symptomatic non-severe hypoglycaemia for three health states: 1) rare (quarterly), 2) intermittent (monthly), 3) and frequent (weekly) hypoglycaemia episodes. METHODS: Using validated health states, time trade-off utilities were elicited from 51 Canadian respondents with diabetes, and 79 respondents in Canada and 75 respondents in the United Kingdom (UK) without diabetes. RESULTS AND DISCUSSION: Each hypoglycaemic episode was associated with a reduction in utility and persons with diabetes consistently reported slightly higher utility values than respondents without diabetes. The utility for diabetes without hypoglycaemia ranged from 0.88 to 0.97, the mean utility for rare hypoglycaemic events (quarterly) ranged between 0.85 and 0.94. The utility for the intermittent state (monthly) ranged from 0.77 to 0.90 and from 0.66 to 0.0.83 for the frequent state (weekly). Differences were observed between respondents without diabetes in Canada and the UK. Using a multivariate linear OLS regression, the estimated utilities associated with a single hypoglycaemic event were -0.0033 and -0.0032 for respondents with diabetes and without diabetes, respectively. CONCLUSION: Among respondents with and without diabetes, there was a demonstrable utility loss associated with hypoglycaemia. Considering a utility loss of 0.03 as a minimum clinically important difference for persons with diabetes, the evidence from this study indicates that as low as ten symptomatic non-severe hypoglycaemic episodes per year may be of clinical importance and that the importance increases with frequency of episodes. Integrating directly elicited utility values such as those reported here will improve the quality and applicability of economic evaluations of diabetes treatment.