Abstract
Objetivos
Detectar pacientes con diabetes tipo LADA (latent autoinmune diabetes of adult) tipo 1 en diabéticos adultos con sobrepeso y describir las variaciones metabólicas tras administrar metformina.
Diseño
Estudio observacional, multicéntrico, basado en una serie de casos.
Emplazamiento
Atención primaria, provincia de Barcelona.
Participantes
Diabéticos con sobrepeso u obesidad, con diagnóstico de diabetes < 2 años, entre 35 y 65 años de edad, sin complicaciones microvasculares o macrovasculares ni tratamiento farmacológico inicial antidiabético.
Intervención
Administración de metformina, 1.700 mg/día.
Mediciones
La variable de control metabólico fue la hemoglobina glucosilada (HbA1c); otras variables fueron el índice de masa corporal (IMC), la glucemia en ayunas, la insulinemia, el péptido C y la valoración de la insulinorresistencia (HOMA-IR). Para el diagnóstico de diabetes tipo LADA se determinaron los anticuerpos ICA, anti-GAD y anti-IA2.
Resultados
En la muestra de diabéticos estudiada (n = 103) se detectaron 3 casos de LADA tipo 1 (prevalencia del 2,9%; intervalo de confianza del 95%, 0,6-8,3%). Estos pacientes presentaron valores basales más elevados de HbA1c, insulina y sobre todo de HOMA-IR. El tratamiento con metformina mejoró la HbA1c en ambos grupos de pacientes (con o sin LADA de tipo 1). El descenso de la insulinemia al cabo de un año en los pacientes con LADA de tipo 1 fue más marcado que en el resto de diabéticos.
Conclusiones
Dada su frecuencia, hay que reflexionar sobre si deberían buscarse con más frecuencia anticuerpos frente a células β pancreáticas en atención primaria. Los pacientes con LADA de tipo 1 presentaron buen control de la HbA1c en tratamiento con metformina y un drástico descenso de la insulina. Faltan estudios que evalúen si la metformina mejora el control glucémico, aunque tal vez no proteja la reserva insulínica, y confrontarla con otros fármacos.
Palabras clave: Metformina, LADA, Diabetes mellitus tipo 2, Insulinorresistencia, Obesidad
Abstract
Objectives
To detect type-1 LADA (latent auto-immune diabetes in adults) in adults with overweight.To describe the metabolic variations in these patients after metformin treatment.
Design
Observational, multi-centre study based on a series of cases.
Setting
Health centres in Barcelona province, Spain.
Participants
Diabetic patients with overweight or obesity, diagnosed with diabetes for <2 years, aged between 35 and 65, and without clinical micro-macrovascular complications and without initial glycaemialowering drug treatment.
Intervention
Metformin administration (1700 mg/day).
Measurements
The metabolic control variable was HbA1c.Other variables measured were: body mass index (BMI), glucose in fast, insulinaemia, C-peptide, and insulin resistance (HOMA-IR).We determined ICA, GADAb and IA2Ab antibodies to diagnose LADAtype diabetes.
Results
In our sample of diabetics (N=103), we detected 3 type-1 LADA cases. These patients had higher levels of HbA1c, insulin and, especially, HOMA-IR. Metformin treatment for one year improved HbA1c in both groups (with and without type-1 LADA). However, the decrease in insulin one year afterwards was greater in type-1 LADA patients.
Conclusions
The percentage of type-1 LADA in our sample made us wonder whether we should search for pancreatic antibodies more often in primary care. More studies on the prevalence of type-1 LADA in our country are needed, especially in diabetic patients with overweight.Type-1 LADA patients improved their metabolic control after metformin treatment and showed a drastic decrease in insulin levels. Further studies are needed to evaluate whether metformin improves metabolic control, even though it may not protect insulin reserves, and to contrast metformin with other drugs.
Key words: Metformin, LADA, Type-2 diabetes mellitus, Insulin resistance, Obesity
Bibliografía
- 1.Groop L.C., Bottazzo G.F., Doniach D. Islet cell antibodies identify latent type I diabetes in patients aged 35-75 years at diagnosis. Diabetes. 1986;35:237–241. doi: 10.2337/diab.35.2.237. [DOI] [PubMed] [Google Scholar]
- 2.Pozzilli P., Di Mario U. Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention. Diabetes Care. 2001;24:1460–1467. doi: 10.2337/diacare.24.8.1460. [DOI] [PubMed] [Google Scholar]
- 3.Zimmet P.Z., Tuomi T., Mackay I.R., Rowley M.J., Knowles W., Cohen M. Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med. 1994;11:299–303. doi: 10.1111/j.1464-5491.1994.tb00275.x. [DOI] [PubMed] [Google Scholar]
- 4.Landin-Olsson M. Latent autoinmune diabetes in adults. Ann NY Acad Sci. 2002;958:112–116. doi: 10.1111/j.1749-6632.2002.tb02953.x. [DOI] [PubMed] [Google Scholar]
- 5.Zimmet P., Turner R., McCarty D., Rowley M., Mackay I. Crucial points at diagnosis. Type 2 diabetes or slow type 1 diabetes. Diabetes Care. 1999;22(Suppl 2):B59–B64. [PubMed] [Google Scholar]
- 6.LohmannF T., Kellner K., Verlohren H.J., Krug J., Steindorf J., Scherbaum W.A. Titre and combination of ICA and autoantibodies to glutamic acid decarboxylase discriminate two clinically distinct types of latent autoimmune diabetes in adults (LADA) Diabetologia. 2001;44:1005–1010. doi: 10.1007/s001250100602. [DOI] [PubMed] [Google Scholar]
- 7.Monge L., Bruno G., Pinach S., Grassi G., Maghenzani G., Dani F. A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years. Diabet Med. 2004;21:456–459. doi: 10.1111/j.1464-5491.2004.01177.x. [DOI] [PubMed] [Google Scholar]
- 8.Soriguer-Escofet F., Esteva I., Rojo-Martínez G., Ruiz de Adana S., Catala M., Merelo M.J., Diabets Group of the Andalusian Society of Endocrinology and Nutrition Prevalence of latent autoimmune diabetes of adults (LADA) in Southern Spain. Diabetes Res Clin Pract. 2002;56:213–220. doi: 10.1016/s0168-8227(02)00002-5. [DOI] [PubMed] [Google Scholar]
- 9.Naik R.G., Palmer J.P. Preservation of b-cell function in type 1 diabetes. Diabetes Reviews. 1999;7:154–182. [Google Scholar]
- 10.Pagano G., Tagliaferro V., Carta Q., Casselle M.T., Bozzo C., Vitelli F. Metformin reduces insulinrequirement on type 1 (insulin dependent) Diabetes Care. 1995;18:1050–1064. doi: 10.1007/BF00251823. [DOI] [PubMed] [Google Scholar]
- 11.Lernmark A., Kolb H., Mire-Sluis T. Towards a World Health Organization (WHO) approved standard sample for islet cell antibodies. GAD65 and IA-2 autoantibodies. Diabetologia. 1999;42:381–382. doi: 10.1007/s001250051167. [DOI] [PubMed] [Google Scholar]
- 12.Matthews D.R., Hosker J.P., Rudenski A.S., Naylor B.A., Treacher D.F., Turner R.C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419. doi: 10.1007/BF00280883. [DOI] [PubMed] [Google Scholar]
- 13.Castell C., Tresserras R., Serra J., Goday A., Lloveras G., Salleras L.L. Prevalence of diabetes in Catalonia (Spain): an oral glucose tolerance test-based population study. Diabetes Res Clin Pract. 1999;43:33–40. doi: 10.1016/s0168-8227(98)00125-9. [DOI] [PubMed] [Google Scholar]
- 14.Monclus Benet J.F., Álvarez Vera J.I., Arasa Fava M.J., Aguilar Martín C., Viñas Naranjo J.J., Curto Romeu C. Los criterios de ADA-97, prevalencia de diabetes mellitus y las comarcas más meridionales de Cataluña. Aten Primaria. 2001;27:178–182. doi: 10.1016/S0212-6567(01)78793-8. [DOI] [PMC free article] [PubMed] [Google Scholar]