Diabetes mellitus y covid-19: epidemiología, fisiopatología, manejo ambulatorio e intrahospitalario: revisión / Diabetes mellitus and covid-19: epidemiology, pathophysiology, outpatient and inpatient management: review

La diabetes mellitus ha sido asociado a una mayor probabilidad de enfermedad más grave por Covid-19. Los estudios epidemiológicos evidencian que los pacientes diabéticos tienen un riesgo mayor de un cuadro grave que requiera UCI, ventilación mecánica y probabilidad de morir. Un buen control metabólico parece fundamental para disminuir este riesgo. En el caso del manejo ambulatorio es importante asegurar la continuidad de los tratamientos crónicos, medir los niveles de glicemia capilar y minimizar la posibilidad de infección. En caso de infección por SARS-Cov2 el paciente diabético deberá hacer los ajustes necesarios en su tratamiento tanto para lograr un control glicémico adecuado como para disminuir los riesgos de algunos fármacos antidiabéticos. El uso de telemedicina constituye una excelente herramienta para facilitar el logro de los objetivos terapéuticos. En caso de requerir hospitalización, se ha evidenciado que los pacientes diabéticos tienen altos requerimientos de insulina y rápida tendencia a producir cetosis. Considerando la situación actual de pandemia las metas intrahospitalarias pueden ser más laxas y seguras, en especial en pacientes no críticos. En caso de pacientes críticos idealmente se debe mantener las metas glicémicas entre 140-180 mg/dL.

Diabetes mellitus has been associated with a higher probability of severe disease due to Covid-19. Epidemiological studies show that diabetic patients have an increased risk of a serious condition requiring ICU, mechanical ventilation and of course the probability of dying. Good metabolic control seems essential to reduce this risk. In the case of outpatient management, it is very important to ensure the continuity of chronic treatments, measure capillary blood glucose levels and minimize the possibility of infection. In case of SARS-Cov2 infection, the diabetic patient should make the necessary adjustments in their treatment, both to achieve adequate glycemic control and to reduce the risks of some antidiabetic drugs. Telemedicine is an excellent tool to facilitate the achievement to therapeutic goals. In case of requiring hospitalization, it has been shown that diabetic patients have high insulin requirements and rapid tendency to produce ketosis. Considering the current situation of a pandemic, intrahospital goals may be laxer and safer, especially in non-critically ill patients. In the case of critically ill patients, the glycemic goals should ideally be maintained between 140-180 mg/dL.

Cinética de muerte de linfocitos en diabetes mellitus tipo 1 y su posible asociación con miR-146a y miR-155 / Kinetics of cell death in type 1 diabetes mellitus and their possible association with miR-146a and miR-155

Aim: Analyze mi-146a and miR-155 expression and its correlation with the apoptosis of lymphocytes T in T1D and control patient. Patients and Methodology: 17 T1D patients (5 children between 8-14 yr and 12 adults between 19-29 yr). Activated and not activated peripheral mononuclear cells were studied were studied. Cellular activation with anti-CD3 and primary culture with interleukyne-2 by 5 days. Apoptosis assays through flow cytometry. miRNA through Taqman probes. Statistical analysis through Kruskal-Wallis and post-hoc Dunn's test. Results: Composition of virgin and memory T CD4 cells showed significant differences for stimulus response in control group (p = 0,0004). Increased memory cells count in control group activated by 7 days than basal (p = 0,0047). For early apoptosis differences were observed in days 3 and 7 with and without activation (p = 0,001). AICD apoptosis showed increases in control group after re-stimulation through TCR (p= 0,03). miR-146a expression was lower in recent-onset T1D children vs recent-onset DM1 adults (p = 0,0167). Conclusion: This study shows a differential miR-146a expression in T1D children with respect to T1D adult patients, diminished AICD mechanism in T1D and altered CD4+CD45RA-CD45R0+ memory cells generation in T1D adult patients.

Tabaquismo y Diabetes / Smoking and Diabetes

Resumen El tabaco ejerce daño en los pacientes con diabetes mellitus acelerando las complicaciones crónicas, incremento en el riesgo de mortalidad global y cardiovascular. Dejar de fumar produce una reducción del riesgo. Además, el tabaquismo tanto activo como pasivo incrementa la incidencia de diabetes tipo 2. La exposición al tabaco durante el embarazo también puede predisponer al desarrollo de diabetes de las hijas y diabetes gestacional en las madres. Un estudio en diabetes mellitus 1 comparó una cohorte de EE. UU. con una europea, demostró que los fumadores tienen niveles de HbA1c significativamente mayores y un perfil lipídico con mayor nivel de triglicéridos y colesterol LDL. Por todas estas razones es urgente realizar consejería breve o ABC-D, según las Primeras Guías de Práctica Clínica de Tratamiento del Tabaquismo, Chile, 2017 a todo paciente diabético ya sea en atención ambulatoria como hospitalaria.

Tobacco exerts damage in patients with diabetes mellitus by accelerating chronic complications, increasing the risk of global and cardiovascular mortality. Quitting smoking produces risk reduction. In addition, both active and passive smoking increases the incidence of type 2 diabetes. Exposure to tobacco during pregnancy can also predispose to the development of diabetes of daughters and gestational diabetes in mothers. A study in diabetes mellitus 1 compared a US cohort with a European cohort, showed that smokers have significantly higher levels of HbAlc and a lipid profile with a higher level of triglycerides and LDL cholesterol. For all these reasons it is urgent to brief counsel or provide ABC-D, according to the First Clinical Practice Guidelines of Tobacco Treatment, Chile, 2017 for all diabetic patients, whether in outpatient or hospital care.

Síndrome de Cushing por ACTH ectópica: revisión a propósito de dos casos clínicos / Cushing syndrome caused by ectopic ACTH secretion: report of two cases

Twelve percent of Cushing syndromes (CS) are caused by ectopic ACTH secretion. We report two cases of the condition. A 57 years old woman with an ectopic CS caused by a bronchial carcinoid tumor. After the tumor excision, the patient had a favorable evolution. A 63 years old woman consulting for cough, dyspnea and weight loss causes by a small cell lung cancer. The patient presented hyperglycemia, hypokalemia and metabolic alcalosis. The laboratory showed a severe hypercortisolism with elevated ACTH levels. The metabolic condition did not subside after the first course of chemotherapy and the patient died due to an infectious complication...

Caso clí­nico: reactivación de psoriasis posterior a adrenalectomía por sí­ndrome de Cushing / Case report: psoriasis relapse following adrenalectomy for cushing syndrome

The relapse of autoimmune diseases following resolution of Cushing syndrome (CS) has been established with frequency, especially for thyroid disease. We present the case of a 39-year-old woman with a history of psoriasis vulgaris, with no other comorbidities. She presented a one-year of weight gain, high blood pressure, hypermenorrhea, pre-diabetes and dyslipidemia. During this period of time, the complete remission of psoriatic lesions was confirmed. The laboratory analysis demonstrated elevated free urinary cortisol in two opportunities, and a confirmatory low-dose dexamethasone test. Low ACTH levels were established (12,3pg/ml), and the abdominal images where compatible with a right adrenal adenoma of 3,0 x 2,3 cm, sothe patient underwent a laparoscopic right adrenalectomy with no complications. Her blood pressure, glucose and cholesterol levels improved following surgery. One month after surgery the patient developed new, generalized psoriatic plaques. The excess of glucocorticoids produced by the adrenal tumor could have controlled the immunopathogeny of psoriasis. By removing the tumor, with the consequent reduction of cortisol levels, a more severe relapse of her cutaneous disease occurred.

Osteomalacia hipofosfatémica secundaria a sarcoma de muslo: caso clínico / Hypophosphatemic osteomalacia secondary to a sarcoma: report of one case

Tumor induced osteomalacia is uncommon and is characterized by an isolated and not PTH dependent reduction in tubular phosphate reabsorption. This alteration is produced by phosphaturic factors, such as fibroblast growth factor-23 (FGF-23) that are secreted by tumors. We report a 41 years old female presenting with joint pain and progressive loss of muscle strength in the lower limbs. Initial laboratory assessment showed hypophosphatemia, elevated alkaline phosphatases, normal intact parathormone levels, low levels of 25 hydroxy vitamin D and an elevated 24 h phosphaturia. Bone mineral density showed spine and femoral neck osteopenia. A positron emission tomography (PET) revealed a right thigh tumor with lung metastases. Its biopsy disclosed a fibrosarcoma. FGF-23 levels, measured by ELISA were markedly elevated. The patient was discharged with palliative measures.

Compromiso endocrinológico en el síndrome de POEMS: revisión a propósito de un caso / Secondary amenorrhea and hypothyroidism in a women with POEMS syndrome: report of one case

POEMS is an acronym for a syndrome characterized by osteosclerotic myeloma: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. Hypothyroidism, hypogonadism, diabetes mellitus and adrenal failure can be associated to POEMS syndrome. We report a 39 years old women with monoclonal gammopathy and paraparesis caused by a polyneuropathy, in whom a POEMS syndrome was diagnosed and treated with dexamethasone. The patient had a secondary amenorrhea and a clinical hypothyroidism with negative antithyroidal antibodies. Substitutionwith levothyroxine was started.

[Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis associated to the use of propylthiouracil. Report of four cases]. / Vasculitis ANCA-positivo en pacientes hipertiroideos usuarios de propiltiouracilo: Report of four cases.

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is an uncommon complication of the use of propylthiouracil. When it occurs, it affects multiple organs as any systemic vasculitis. We report three females and one male, aged 30, 40, 43 and 41 years respectively, that after a lapse of 12 to 28 months of propylthiouracil use, presented clinical signs of vasculitis. All had high titers of ANCA against myeloperoxidase. In three patients, a skin biopsy confirmed the diagnosis. The condition subsided when propylthiouracil was discontinued, but one female patient required the use of prednisone.

Vasculitis ANCA-positivo en pacientes hipertiroideos usuarios de propiltiouracilo: Report of four cases / Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis associated to the use of propylthiouracil

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is an uncommon complication of the use of propylthiouracil. When it occurs, it affects multiple organs as any systemic vasculitis. We report three females and one male, aged 30, 40, 43 and 41 years respectively, that after a lapse of 12 to 28 months of propylthiouracil use, presented clinical signs of vasculitis. All had high titers of ANCA against myeloperoxidase. In three patients, a skin biopsy confirmed the diagnosis. The condition subsided when propylthiouracil was discontinued, but one female patient required the use of prednisone.

[Fetal growth restriction and insulin resistance. New findings and review of the literature]. / Restricción del crecimiento fetal e insulinorresistencia. Nuevos hallazgos y revisión de la literatura.

There is a strong association between low birth weight and insulin resistance. The thrifty phenotype hypothesis, which postulates fetal programming for adaptation to an adverse intrauterine environment, resulting in a lower insulin sensitivity in utero, is one of the hypothesis to explain this association. Later in life, syndrome X may develop, featuring hypertension, dyslipidemia, central obesity and type 2 diabetes, associated to an excessive food intake. Our investigation during the first three years of life in a prospective cohort of small (SGA) or appropriate for gestational age newborns, demonstrated that a significant increase of insulin levels is detected in SGA, as early as during the first year of life, but only when catch up growth (CUG) occurs. Orexigenic peptides such as Ghrelin appear to participate in this CUG phenomenon. We also sought to determine whether these associations were observed in individuals born with very low birth weight. We found that in utero as well as postnatal growth rates were independent determinants of insulin sensitivity and secretion. Education about feeding practices and physical activity in SGA children, is a future challenge to prevent the onset of syndrome X in this predisposed population.

Restricción del crecimiento fetal e insulinorresistencia: Nuevos hallazgos y revisión de la literatura / Fetal growth restriction and insulin resistance: New findings and review of the literature

There is a strong association between low birth weight and insulin resistance. The thrifty phenotype hypothesis, which postulates fetal programming for adaptation to an adverse intrauterine environment, resulting in a lower insulin sensitivity in utero, is one of the hypothesis to explain this association. Later in life, syndrome X may develop, featuring hypertension, dyslipidemia, central obesity and type 2 diabetes, associated to an excessive food intake. Our investigation during the first three years of life in a prospective cohort of small (SGA) or appropriate for gestational age newborns, demonstrated that a significant increase of insulin levels is detected in SGA, as early as during the first year of life, but only when catch up growth (CUG) occurs. Orexigenic peptides such as Ghrelin appear to participate in this CUG phenomenon. We also sought to determine whether these associations were observed in individuals born with very low birth weight. We found that in utero as well as postnatal growth rates were independent determinants of insulin sensitivity and secretion. Education about feeding practices and physical activity in SGA children, is a future challenge to prevent the onset of syndrome X in this predisposed population.

Test de estimulación intraarterial selectiva con calcio en el diagnóstico de localización de insulinomas: Casos clínicos / Selective intra arterial calcium stimulation for the localization of insulinomas: Report of two cases

Insulinoma is the most common neuroendocrine tumor. Its clinical manifestations are frequently confounded with neuropsychiatric symptoms, and definitive diagnosis can be delayed for a long time. These tumors are usually small, of less than 2 cm. Thus, their preoperative localization is difficult. We report two patients with a clinical diagnosis of insulinoma, in whom the preoperative imaging study was negative. Both fulfilled diagnostic criteria, with high serum insulin levels in the presence of a blood glucose of less than 45 mg/dl. The imaging study, including abdominal computed tomography and pancreatic endoscopic ultrasonography did not disclose the location of the tumor. A pancreatic angiography with selective stimulation with intra arterial calcium and venous sampling for insulin measurements, was performed in both patients. This test allowed the exact localization of the tumors and their successful excision. A review of other localization diagnostic tests is done (Rev Méd Chile 2004; 132: 71-5).

Subtipos no clásicos de diabetes mellitus / Non classical subtypes of diabetes mellitus

Background: Some adult, obese and diabetic patients, initiate their disease with a severe diabetic ketoacidosis without a precipitating factor and do not require insulin thereafter. These patients are classified as having a non classical diabetes mellitus. Aim: To study the clinical, immunological, genetic and metabolic features of patients with non classical diabetes mellitus. Patients and methods: Ten patients (9 men, aged 45ñ12 years old) with non classical diabetes mellitus were studied. Anti islet and anti glutamic acid decarboxylase antibodies (ICA and anti GAD), HLA DQ a arginine 52 and non aspartic ß57 were measured. Insulin secretion was measured by C peptide after glucagon injection and with the minimal model of Bergman. The latter model was also used to determine insulin sensitivity. Results: Three patients were immunologically classified as type 1, since they had positive ICA or antiGAD antibodies and type 1 genetics (neutral or susceptible HLA DQ a and ß). They had insulin secretion after glucagon stimulus (C peptide ranging from 2.2 to 7.5 pmol/ml), but an almost absent response to a glucose load. They were also insulin resistant (a sensitivity index ranging from 0.05 to 1.67 x 10-4 min/µU x ml). These three cases could be categorized as latent type 1. The other seven patients were ICA negative and antiGAD negative. Five had a susceptible HLA genotype for type 1 diabetes and two were neutral. All had insulin secretion after glucagon stimulation and a variable response to glucose. Six were insulin resistant (sensitivity index ranging from 0.32 to 1.29 x 10-4 min/µU x ml). One patient was insulin sensitive (sensitivity index of 3.83 x 10-4 min/µU x ml). Therefore all these patients were classified as type two diabetics with an atypical debut. Conclusions: Not all diabetics presenting with a severe diabetic ketoacidosis are type I. Among these, there are subjects with a latent type 1 diabetes or with an atypical type 2 diabetes

Excreción urinaria de albúmina en diabéticos no insulino-dependientes: efecto de un inhibidor de la enzima convertidora de angiotensina / Albumin urinary excretion in non insulin dependent diabetic patients: effects of an angiotensin converting enzyme inhibitor

Microalbuminuria in diabetic patients is diagnostic of early renal involvement and angiotensin converting enzyme inhibitors reduce albumin excretion in these subjects. To asses the effect of ACEI on urinary albumin excretion, non insulin dependent diabetic patients with normal blood pressure were randomly assigned to receive enalapril 10 mg/day or placebo and followed during 18 months. Those with high blood pressure were randomly assigned to receive enalapril or acebutolol in doses necessary to normalize blood pressure and followed during 12 months. Every 3 month, urinary albumin excretion was measured in a 4 hour urine sample by radioimmunoassay. One hundred fifty two patients were recruited for the study and 46 were lost from follow up. In 17 subjects with normal blood pressure initial urinary albumin excretion below cutoff values (30 mg/24 h) and treated with enalapril, this parameter did not change; in 20 treated with placebo, it incresed from 5.8ñ6.1 to 18.2ñ7.5 mg/24 h. In 11 patients with normal pressure and initial urinary albumin, this parameter did not change with enalapril and increased in 10 with placebo from 87.3ñ75.1 to 253.6ñ61.1 mg/24 h. In hypertensive patients with normal urinary albumin excretion, no changes in this parameter were observed in those treated with acebutolol (n=10) or enalapril (n=14). In hypertensive with high urinary albumin excretion, it decreased from 119.2ñ8.5 to 40.0ñ4.7 mg/24 h with enalapril treatment (n=12) and no change was observed in those treated with acebutolol (n=11). In Conclusion, enalapril decreases urinary albumin excretion in non insulin dependent diabetic patients