RESUMEN
Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.
Asunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Acidosis Láctica/inducido químicamente , Acidosis Láctica/epidemiología , Acidosis Láctica/virología , Betacoronavirus/fisiología , COVID-19 , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Enfermedad Crítica/epidemiología , Enfermedad Crítica/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Cetoacidosis Diabética/inducido químicamente , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/virología , Humanos , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Metformina/uso terapéutico , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/terapia , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Estado Prediabético/complicaciones , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiología , Estado Prediabético/terapia , Sistema Renina-Angiotensina/fisiología , Factores de Riesgo , Gestión de Riesgos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Privación de TratamientoRESUMEN
OBJECTIVES: Clinical disorders occurring in HIV-infected patients on antiretroviral therapy (ART) have been linked to mitochondrial dysfunction, for example, lactic acidosis and lipodystrophy. Mitochondrial membrane potential (delta psi m) is the most direct measure of the state of energization of the mitochondria. We analysed delta psi m, of peripheral blood mononuclear cells (PBMCs) in HIV-negative, healthy subjects (n=8), HIV-infected, treatment-naive patients (n=30), and HIV-infected patients on ART (n=58). The influence of ART was analysed in six patients who started their first regimen. METHODS: The delta psi m of PBMC was measured by flow cytometry using the dye JC-1. RESULTS: The delta psi m was significantly lower in HIV-infected patients than in HIV-negative controls. This difference was detected in both treated (P = 0.0001) and untreated patients (P = 0.001). The delta psi m of PBMCs was highly correlated with CD4+ T-cell count in therapy-naive patients (P = 0.002, r = 0.546) and in treated patients (P = 0.028, r = 0.288). The delta psi m increased significantly in therapy-naive patients after starting ART (P = 0.001). Patients with lipoatrophy had significantly lower delta psi m than patients without lipodystrophy or with lipohypertrophy (P = 0.023). CONCLUSIONS: In HIV-infected persons delta psi m is significantly reduced. Patients with lipoatrophy have significantly reduced delta psi m. This is the first study showing that the delta psi m of PBMCs is highly correlated with CD4+ T-cell count in HIV infection.
Asunto(s)
Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Leucocitos Mononucleares/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Enfermedades Mitocondriales/inducido químicamente , Acidosis Láctica/sangre , Acidosis Láctica/inducido químicamente , Acidosis Láctica/inmunología , Acidosis Láctica/virología , Adulto , Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/virología , Estudios Transversales , Hígado Graso/sangre , Hígado Graso/inducido químicamente , Hígado Graso/inmunología , Hígado Graso/virología , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Síndrome de Lipodistrofia Asociada a VIH/sangre , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Síndrome de Lipodistrofia Asociada a VIH/inmunología , Síndrome de Lipodistrofia Asociada a VIH/virología , Humanos , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Mitocondrias/virología , Enfermedades Mitocondriales/sangre , Enfermedades Mitocondriales/inmunología , Enfermedades Mitocondriales/virología , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate progressive, severe neuromuscular weakness associated with lactic acidosis in some HIV-infected patients after exposure to nucleoside reverse transcriptase inhibitors (NRTI). METHODS: HIV-associated neuromuscular weakness syndrome (HANWS) was retrospectively identified and classified based on the level of diagnostic certainty: possible (progressive weakness owing to neuromuscular disease), probable (progressive neuromuscular weakness with documented exclusion of confounding causes), or definite (progressive weakness and electrophysiological or pathological evidence of neuromuscular pathology). RESULTS: Of 69 patients identified with HANWS, 27 had definite HANWS, 19 probable, and 23 possible. In 44 patients with documented follow-up, 16 required intubation and nine died. There was a marginal association between death and hyperlactatemia (P = 0.061). At onset of neurological symptoms, 68 were receiving antiretroviral therapy, including stavudine for 61 (89.7%). Serum lactate level was elevated (> 2.2 mmol/l) in 30/37 (81%), with a trend towards an association between hyperlactatemia and stavudine usage (P = 0.087). In 25, neurological symptoms occurred after antiretroviral therapy discontinuation (median, 14 days). Electrophysiological studies (n = 24) indicated sensorimotor neuropathy in 20 patients and myopathy in three. Nerve biopsy (n = 9) revealed axonal degeneration and inflammation in three, mixed axonal and demyelinating lesions in three, and primary axonal neuropathy in three. Of 15 muscle biopsies, three revealed inflammation and four mitochondrial abnormalities. CONCLUSIONS: A severe neuromuscular weakness syndrome may occur in HIV-infected individuals. The association with hyperlactatemia and NRTI exposure supports mitochondrial toxicity as a pathogenesis. In some, the onset of neurological symptoms lagged significantly after discontinuation of antiretroviral therapy, suggesting that different etiological mechanisms may underlie these cases.
Asunto(s)
Acidosis Láctica/virología , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Debilidad Muscular/virología , Enfermedades Neuromusculares/virología , Adulto , Femenino , Infecciones por VIH/complicaciones , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Humanos , Masculino , Enfermedades Mitocondriales/virología , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/efectos adversos , SíndromeRESUMEN
OBJECTIVE: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. METHODS: Systematic review of cases reported in the medical literature. RESULTS: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. CONCLUSIONS: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.