Abstract
Latent Autoimmune Diabetes in Adults (LADA), although formally classified as Type 1 Diabetes (T1D), very often (at least in Western countries) appear clinically with Type 2 Diabetes (T2D)-like features as overweight and insulin resistance. LADA patients do not need exogenous insulin at the time they are diagnosed with diabetes, but a large percentage will within a few years develop need for such treatment. The decline in beta cell function progresses much faster in LADA than in T2D, presumably because of the ongoing autoimmune assault in LADA, and therefore necessitates insulin therapy much earlier in LADA than in T2D. Despite high prevalence of LADA (about 10% of the total diabetic population in many countries), the treatment of LADA patients is far less elucidated than is the case for T1D and T2D. Finding a treatment strategy for LADA from the time of diagnosis, that can reduce the decline of beta cell function, ensure adequate metabolic control and thereby reduce the risk of diabetic complications is thus an important clinical challenge. Conclusions from the randomized treatment studies so far do not indicate an optimal treatment strategy in LADA. This review aims to give an overview of current practices for the medical treatment of LADA as well as an update on results from recent studies on the treatment of the disease.
Keywords: LADA, GADA, treatment, randomized clinical trials, residual beta cell function, metabolic control.
[1]
Pipi E, Marketou M, Tsirogianni A. Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus. World J Diabetes 2014; 5(4): 505-10.
[2]
Ostergaard JA, Laugesen E, Leslie RD. Should there be concern about autoimmune diabetes in adults? Current evidence and controversies. Curr Diab Rep 2016; 16(9): 82.
[3]
Laugesen E, Østergaard JA, Leslie RD. Danish Diabetes Academy Workshop and Workshop Speakers. Latent autoimmune diabetes of the adult: Current knowledge and uncertainty. Diabet Med 2015; 32(7): 843-52.
[4]
Kumar A, de Leiva A. Latent autoimmune diabetes in adults (LADA) in Asian and European populations. Diabetes Metab Res Rev 2017; 33(5)
[5]
Muazu SB, Okpe I, Anumah F. The prevalence and characteristics of latent autoimmune diabetes in adults subset among type two diabetes mellitus patients in Northern Nigeria. Ann Afr Med 2016; 15(4): 163-70.
[6]
Maddaloni E, Lessan N, Al Tikriti A, Buzzetti R, Pozzilli P, Barakat MT. Latent autoimmune diabetes in adults in the united arab emirates: clinical features and factors related to insulin-requirement. PLoS One 2015; 10(8): e0131837.
[7]
Schwartz SS, Epstein S, Corkey BE, Grant SF, Gavin JR III, Aguilar RB. The time is right for a new classification system for diabetes: rationale and implications of the beta-cell-centric classification schema. Diabetes Care 2016; 39(2): 179-86.
[8]
Brophy S, Davies H, Mannan S, Brunt H, Williams R. Interventions for latent autoimmune diabetes (LADA) in adults. Cochrane Database Syst Rev 2011; 9: CD006165.
[9]
Leslie RD, Palmer J, Schloot NC, Lernmark A. Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment. Diabetologia 2016; 59(1): 13-20.
[10]
Fourlanos S, Dotta F, Greenbaum CJ, et al. Latent autoimmune diabetes in adults (LADA) should be less latent. Diabetologia 2005; 48(11): 2206-12.
[11]
Hawa MI, Buchan AP, Ola T, et al. LADA and CARDS: A prospective study of clinical outcome in established adult-onset autoimmune diabetes. Diabetes Care 2014; 37(6): 1643-9.
[12]
Clauson P, Linnarsson R, Gottsäter A, Sundkvist G, Grill V. Relationships between diabetes duration, metabolic control and beta-cell function in a representative population of type 2 diabetic patients in Sweden. Diabet Med 1994; 11(8): 794-801.
[13]
Ludvigsson J. The clinical potential of low-level C-peptide secretion. Expert Rev Mol Diagn 2016; 16(9): 933-40.
[14]
Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 2003; 26(3): 832-6.
[15]
Sjöberg S, Gunnarsson R, Gjötterberg M, Lefvert AK, Persson A, Ostman J. Residual insulin production, glycaemic control and prevalence of microvascular lesions and polyneuropathy in long-term type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1987; 30(4): 208-13.
[16]
Buzzetti R, Pozzilli P, Frederich R, Iqbal N, Hirshberg B. Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA). Diabetes Metab Res Rev 2016; 32(3): 289-96.
[17]
Jones AG, McDonald TJ, Shields BM, et al. Markers of beta-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes. Diabetes Care 2016; 39(2): 250-7.
[18]
Thunander M, Thorgeirsson H, Törn C, Petersson C, Landin-Olsson M. Beta-cell function and metabolic control in latent autoimmune diabetes in adults with early insulin versus conventional treatment: A 3-year follow-up. Eur J Endocrinol 2011; 164(2): 239-45.
[19]
Brophy S, Davies H, Dunseath G, et al. Experience of the introduction of routine antibody testing in primary care and of running a trial for latent autoimmune diabetes in adults (LADA). Diabetes Res Clin Pract 2011; 93(1): e49-52.
[20]
Andersen CD, Bennet L, Nyström L, et al. Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy. Diabetologia 2013; 56(2): 252-8.
[21]
Sørgjerd EP, Skorpen F, Kvaløy K, Midthjell K, Grill V. Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: The HUNT study, Norway. Diabetologia 2012; 55(5): 1310-8.
[22]
Gale EA. Latent autoimmune diabetes in adults: a guide for the perplexed. Diabetologia 2005; 48(11): 2195-9.
[23]
Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Cardiol 2017; 120(1S): S4-S16.
[24]
Itariu BK, Stulnig TM. Autoimmune aspects of type 2 diabetes mellitus - a mini-review. Gerontology 2014; 60(3): 189-96.
[25]
Shimada A, Shigihara T, Okubo Y, Katsuki T, Yamada Y, Oikawa Y. Pioglitazone may accelerate disease course of slowly progressive type 1 diabetes. Diabetes Metab Res Rev 2011; 27(8): 951-3.
[26]
Radtke MA, Midthjell K, Nilsen TI, Grill V. Heterogeneity of patients with latent autoimmune diabetes in adults: linkage to autoimmunity is apparent only in those with perceived need for insulin treatment: Results from the Nord-Trondelag Health (HUNT) study. Diabetes Care 2009; 32(2): 245-50.
[27]
Agardh CD, Lynch KF, Palmér M, Link K, Lernmark A. GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes. Diabetologia 2009; 52(7): 1363-8.
[28]
Zhao Y, Yang L, Xiang Y, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin maintains beta-cell function in patients with recent-onset latent autoimmune diabetes in adults: One year prospective study. J Clin Endocrinol Metab 2014; 99(5): E876-80.
[29]
Awata T, Shimada A, Maruyama T, et al. Possible long-term efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, for slowly progressive type 1 diabetes (spiddm) in the stage of non-insulin-dependency: An open-label randomized controlled pilot trial (SPAN-S). Diabetes Ther 2017; 8(5): 1123-34.
[30]
Maruyama T, Tanaka S, Shimada A, et al. Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus. J Clin Endocrinol Metab 2008; 93(6): 2115-21.
[31]
Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: A randomised, double-blind, non-inferiority trial. Lancet 2012; 380(9840): 475-83.
[32]
Johansen OE, Boehm BO, Grill V, et al. C-peptide levels in latent autoimmune diabetes in adults treated with linagliptin versus glimepiride: exploratory results from a 2-year double-blind, randomized, controlled study. Diabetes Care 2014; 37(1): e11-2.
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