Commentary

Death during Intensive Glycemic Therapy of Diabetes: Mechanisms and Implications

The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers.

The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.

This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes.

This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Stress can be classified as either psychosocial or physiologic. Physiologic stress refers to stresses due to acute illness, trauma, pain, hypoglycemia, and sleep deprivation–much less is known regarding its health consequences. This review focuses on hypoglycemia as a model to further investigate physiological stress. Experimental mild to moderate hypoglycemia is a paradigmatic physiological stress that evokes autonomic, neuroendocrine, and immune responses. Hypoglycemic stress is an ideal model to examine the interactions and consequences of physiological stress on the autonomic nervous system. Acute hypoglycemia has been demonstrated to increase inflammatory markers, prolong QTc, and impair cardiac-vagal baroreflex sensitivity. Some of these consequences may not reverse completely when euglycemia is restored. For example, there is attenuation of the cardiac-vagal baroreflex, attenuation of the vascular sympathetic baroreflex (muscle sympathetic nerve activity response to transient hypotension), and attenuation of the catecholamine response to lower body negative pressure that is present the next day after hypoglycemia has resolved.

To assess the risk of hospitalization and mortality within 1 year of severe hypoglycaemia and theirs clinical predictors.

We retrospectively examined 399 admissions for severe hypoglycemia in adults with DM at the Emergency Department (ED) of the University Hospital of Novara (Italy) between 2012–2017, and we compared the clinical differences between older (aged ≥65 years) and younger individuals (aged 18–64 years). A logistic regression model was used to explore predictors of hospitalization following ED access and 1-year later, according to cardiovascular (CV) or not (no-CV) reasons; 1-year all-cause mortality was also detected.

The study cohort comprised 302 patients (median [IQR] age 75 [17] years, 50.3% females, 93.4% white, HbA_1c level 7.6% [1.0%]). Hospitalization following ED access occurred in 16.2% of patients and kidney failure (OR 0.50 [95% CI 1.29–5.03]) was the only predictor of no-CV specific hospitalization; 1-year hospitalization occurred in 24.5% of patients and obesity (OR 3.17 [95% CI 1.20–8.12]) and pre-existing heart disease (OR 3.20 [95% 1.20–9.39]) were associated with CV specific hospitalization; 1-year all-cause mortality occurred in 14.9% of patients and was associated with older age (OR 1.12 [95% CI 1.07–1.18]) and pre-existing heart disease (OR 2.63 [95% CI 1.19–6.14])

Severe hypoglycemia is associated with risk of hospitalization and mortality mainly in elderly patients and it may be predictive of future cardiovascular events in diabetic patients with pre-existing heart disease and obesity.

La hipoglucemia es el principal factor limitante para alcanzar los objetivos de control glucémico en pacientes con diabetes tipo 1. La hipoglucemia grave conlleva riesgo de daño, e incluso de muerte. Tener hipoglucemias repetidas se relaciona con la aparición de hipoglucemias inadvertidas, las cuales incrementan el riesgo de hipoglucemias graves. Algunos metaanálisis recientes estiman una prevalencia del 35% de hipoglucemia grave en pacientes con diabetes tipo 1.

Conocer la prevalencia de hipoglucemia grave en una cohorte de pacientes con diabetes tipo 1 y evaluar la dependencia entre las variables hipoglucemia grave e inadvertida evaluada mediante el test de Clarke.

Se ha estudiado una cohorte de pacientes con diabetes tipo 1 para analizar la edad, sexo, tiempo de evolución de diabetes, tratamiento (múltiples dosis o infusión subcutánea continua de insulina), autocontrol glucémico, HbA1c, episodios de hipoglucemia grave sin pérdida de conciencia, episodios de hipoglucemia grave con pérdida de conciencia e hipoglucemias inadvertidas.

El 39,8% de los pacientes presentaron hipoglucemias graves sin pérdida de conciencia (últimos 6 meses) y el 11,4%, con pérdida de conciencia (últimos 12 meses). El 40,9% presentaban hipoglucemias inadvertidas y se descartó la independencia entre estas y las hipoglucemias graves. La presencia de hipoglucemias graves con pérdida de conciencia se asoció a mayor edad y mayor tiempo de evolución; las hipoglucemias inadvertidas, con una mayor edad y una menor HbA1c.

Se confirma el elevado porcentaje de pacientes con diabetes tipo 1 afectos de hipoglucemia grave e inadvertida.

Hypoglycemia is the major limiting factor in the glycemic management of type 1 diabetes. Severe hypoglycemia puts patients at risk of injury and death. Recurrent hypoglycemia leads to impaired awareness of hypoglycemia and this increases the risk of severe hypoglycemia. Recent studies have reported rates for severe hypoglycemia of 35% in type 1 diabetic patients.

To assess the prevalence of severe hypoglycemia in type 1 diabetes mellitus patients and to evaluate the relationship between this and impaired awareness of hypoglycemia according to the Clarke test.

The following data were collected from a cohort of type 1 diabetic patients: age, gender, duration of type 1 diabetes, treatment (multiple daily insulin injection or continuous subcutaneous insulin infusion), glycemia self-control, HbA1c, episodes of severe hypoglycemia and impaired awareness of hypoglycemia.

Of the participants, 39.8% had had at least one episode of severe hypoglycemia (in the previous 6 months), 11.4% with loss of consciousness (in the previous 12 months). According to the Clark test, 40.9% had impaired awareness of hypoglycemia. Older age and longer duration of diabetes were associated with a higher prevalence of severe hypoglycemia with unconsciousness; older age and a lower level of HbA1c were associated with impaired awareness of hypoglycemia.

Our study allows us to confirm the high rate of severe hypoglycemia and impaired awareness of hypoglycemia in patients with type 1 diabetes.