RESUMEN
Emerging evidence indicates a bi-directional relationship between SARS-CoV-2 and diabetes. The possibility exists that SARS-CoV-2 could induce diabetes, but it is not yet clear whether this might be a fulminant-type diabetes, autoimmune diabetes, or a new-onset transient hyperglycaemia. This viewpoint discusses mechanisms by which SARS-CoV-2 might trigger type 1 diabetes mellitus (T1DM). Specifically, we looked at the role of post-translational protein modifications (PTMs) and the generation of neoepitopes as a potential mechanism in the induction of islet autoimmunity, and the pathways via which coronavirus infections might exacerbate the formation of PTMs and, in so doing, provoke the onset of T1DM.
Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 1 , Procesamiento Proteico-Postraduccional , COVID-19/epidemiología , COVID-19/metabolismo , Diabetes Mellitus Tipo 1/epidemiología , HumanosRESUMEN
AIMS: We aimed at evaluating residual ß-cell function in insulin-treated patients with type 2 diabetes (T2D) while determining for the first time the difference in C-peptide level between patients on basal-bolus compared to those on the basal insulin scheme, considered as an early stage of insulin treatment, together with assessing its correlation with the presence of complications. METHODS: A total of 93 candidates with T2D were enrolled in this cross-sectional study and were categorized into two groups based on the insulin regimen: Basal-Bolus (BB) if on both basal and rapid acting insulin, and Basal (B) if on basal insulin only, without rapid acting injections. HbA1c, fasting C-peptide concentration and other metabolic parameters were recorded, as well as the patient medical history. RESULTS: The average fasting C-peptide was 1.81 ± 0.15 ng/mL, and its levels showed a significant inverse correlation with the duration of diabetes (r = -0.24, p = 0.03). Despite similar disease duration and metabolic control, BB participants displayed lower fasting C-peptide (p < 0.005) and higher fasting glucose (P = 0.01) compared with B patients. Concentrations below 1.09 ng/mL could predict the adoption of a basal-bolus treatment (Area 0.64, 95%CI:0.521-0.759, p = 0.038, sensitivity 45% and specificity 81%). CONCLUSIONS: Insulin-treated patients with long-standing T2D showed detectable level of fasting C-peptide. Measuring the ß-cell function may therefore guide toward effective therapeutic options when oral hypoglycemic agents prove unsuccessful.
Asunto(s)
Péptido C/análisis , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/uso terapéutico , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Péptido C/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Cálculo de Dosificación de Drogas , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoRESUMEN
Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.
Asunto(s)
Adulto , Humanos , Autoanticuerpos , Péptido C , Complicaciones de la Diabetes , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diagnóstico , Inhibidores de la Dipeptidil-Peptidasa IV , Péptido 1 Similar al Glucagón , Hipoglucemiantes , Insulina , Resistencia a la Insulina , Islotes Pancreáticos , Fenotipo , Características de la PoblaciónRESUMEN
Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by a less intensive autoimmune process and a broad clinical phenotype compared to classical type 1 diabetes mellitus (T1DM), sharing features with both type 2 diabetes mellitus (T2DM) and T1DM. Since patients affected by LADA are initially insulin independent and recognizable only by testing for islet-cell autoantibodies, it could be difficult to identify LADA in clinical setting and a high misdiagnosis rate still remains among patients with T2DM. Ideally, islet-cell autoantibodies screening should be performed in subjects with newly diagnosed T2DM, ensuring a closer monitoring of those resulted positive and avoiding treatment of hyperglycaemia which might increase the rate of β-cells loss. Thus, since the autoimmune process in LADA seems to be slower than in classical T1DM, there is a wider window for new therapeutic interventions that may slow down β-cell failure. This review summarizes the current understanding of LADA, by evaluating data from most recent studies, the actual gaps in diagnosis and management. Finally, we critically highlight and discuss novel findings and future perspectives on the therapeutic approach in LADA.