Lower mortality and cardiovascular event rates in patients with Latent Autoimmune Diabetes In Adults (LADA) as compared with type 2 diabetes and insulin deficient diabetes: A cohort study of 4368 patients

      Abstract

      Background

      Latent Autoimmune Diabetes in Adults (LADA) is the second most common form of diabetes, but data on its clinical course and prognosis are scarce. We compared long-term risk of mortality and cardiovascular outcomes in patients with LADA, type 2 diabetes mellitus (T2D), and insulin deficient diabetes (IDD).

      Methods

      We conducted a cohort study of 4368 adults with diabetes referred to the Department of Endocrinology, Odense University Hospital, Denmark, between 1997 and 2012. Data on comorbidity, cardiovascular outcomes and death were obtained from prospective medical databases. We compared adjusted hazard ratios (HRs) of mortality and cardiovascular outcomes for patients with LADA, T2D and IDD, respectively.

      Results

      We included 327 patients with LADA, 3539 with T2D and 502 with IDD. At diagnosis, patients with LADA were older (50 years (IQR 37–59)) than IDD patients (40 years (IQR 28–52)), but younger than patients with T2D (55 years (IQR 45–64)). During a median follow-up period of 6.6 years (IQR 3.4–9.4), patients with IDD had higher mortality than patients with LADA, age- and gender-adjusted HR 2.2 (95% CI, 1.5–3.2). T2D also conferred higher mortality than LADA, HR 1.4 (95% CI, 1.0–1.9). Compared with LADA patients, cardiovascular outcome rates were increased both with IDD, HR 1.2 (95% CI, 0.7–2.0) and T2D, HR 1.2 (95% CI, 0.8–1.8), with the strongest association observed for T2D vs. LADA and acute myocardial infarction HR 1.7 (95% CI, 0.8–3.5).

      Conclusion

      LADA seems to be associated with lower mortality and lower risk of cardiovascular events, compared with both T2D and IDD.

      Keywords

      To read this article in full you will need to make a payment

      References

        • Hawa M.I.
        • Kolb H.
        • Schloot N.
        • et al.
        Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: action LADA 7.
        Diabetes Care. 2013; 36: 908-913
        • Fourlanos S.
        • Dotta F.
        • Greenbaum C.J.
        • et al.
        Latent autoimmune diabetes in adults (LADA) should be less latent.
        Diabetologia. 2005; 48: 2206-2212
        • Leslie R.D.
        • Kolb H.
        • Schloot N.C.
        • et al.
        Diabetes classification: grey zones, sound and smoke: action LADA 1.
        Diabetes Metab Res Rev. 2008; 24: 511-519
        • Leslie R.D.
        • Williams R.
        • Pozzilli P.
        Clinical review: type 1 diabetes and latent autoimmune diabetes in adults: one end of the rainbow.
        J Clin Endocrinol Metabol. 2006; 91: 1654-1659
        • Tuomi T.
        • Carlsson A.
        • Li H.
        • et al.
        Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies.
        Diabetes. 1999; 48: 150-157
        • Radtke M.A.
        • Midthjell K.
        • Nilsen T.I.
        • 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: 245-250
        • Carlsson S.
        • Midthjell K.
        • Grill V.
        Influence of family history of diabetes on incidence and prevalence of latent autoimmune diabetes of the adult: results from the Nord-Trondelag Health Study.
        Diabetes Care. 2007; 30: 3040-3045
        • Turner R.
        • Stratton I.
        • Horton V.
        • et al.
        UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group.
        Lancet. 1997; 350: 1288-1293
        • Naik R.G.
        • Brooks-Worrell B.M.
        • Palmer J.P.
        Latent autoimmune diabetes in adults.
        J Clin Endocrinol Metab. 2009; 94: 4635-4644
        • Isomaa B.
        • Almgren P.
        • Henricsson M.
        • et al.
        Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA).
        Diabetes Care. 1999; 22: 1347-1353
        • Myhill P.
        • Davis W.A.
        • Bruce D.G.
        • Mackay I.R.
        • Zimmet P.
        • Davis T.M.
        Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study.
        Diabetic Med: J Br Diabetic Assoc. 2008; 25: 1245-1250
        • Olsson L.
        • Grill V.
        • Midthjell K.
        • Ahlbom A.
        • Andersson T.
        • Carlsson S.
        Mortality in adult-onset autoimmune diabetes is associated with poor glycemic control: results from the HUNT Study.
        Diabetes Care. 2013; 36: 3971-3978
        • Romkens T.E.
        • Kusters G.C.
        • Netea M.G.
        • Netten P.M.
        Prevalence and clinical characteristics of insulin-treated, anti-GAD-positive, type 2 diabetic subjects in an outpatient clinical department of a Dutch teaching hospital.
        Neth J Med. 2006; 64: 114-118
        • Arikan E.
        • Sabuncu T.
        • Ozer E.M.
        • Hatemi H.
        The clinical characteristics of latent autoimmune diabetes in adults and its relation with chronic complications in metabolically poor controlled Turkish patients with Type 2 diabetes mellitus.
        J Diabetes Complications. 2005; 19: 254-258
        • Baum P.
        • Hermann W.
        • Verlohren H.J.
        • Wagner A.
        • Lohmann T.
        • Grahmann F.
        Diabetic neuropathy in patients with “latent autoimmune diabetes of the adults” (LADA) compared with patients with type 1 and type 2 diabetes.
        J Neurol. 2003; 250: 682-687
        • Balme M.
        • McAllister I.
        • Davis W.A.
        • Davis T.M.
        Retinopathy in latent autoimmune diabetes of adults: the Fremantle Diabetes Study.
        Diabetic Med: J Br Diabetic Assoc. 2002; 19: 602-605
        • Roh M.O.
        • Jung C.H.
        • Kim B.Y.
        • Mok J.O.
        • Kim C.H.
        The prevalence and characteristics of latent autoimmune diabetes in adults (LADA) and its relation with chronic complications in a clinical department of a university hospital in Korea.
        Acta Diabetol. 2013; 50: 129-134
        • Hawa M.I.
        • Buchan A.P.
        • Ola T.
        • et al.
        LADA and CARDS: a prospective study of clinical outcome in established adult-onset autoimmune diabetes.
        Diabetes Care. 2014; 37: 1643-1649
        • Thomsen R.W.
        • Hundborg H.H.
        • Johnsen S.P.
        • et al.
        Statin use and mortality within 180 days after bacteremia: a population-based cohort study.
        Crit Care Med. 2006; 34: 1080-1086
        • Wod M.
        • Yderstraede K.B.
        • Halekoh U.
        • Beck-Nielsen H.
        • Hojlund K.
        Metabolic risk profiles in diabetes stratified according to age at onset, islet autoimmunity and fasting C-peptide.
        Diabetes Res Clin Pract. 2017; 134: 62-71
      1. Health MotIa. Health care in Denmark. Ministry of the Interior and Health; 2008. <http://www.sum.dk/Aktuelt/Publikationer/~/media/Filer - Publikationer_i_pdf/2008/UK_Healthcare_in_dk/pdf.ashx>.

        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Pedersen C.B.
        • Gotzsche H.
        • Moller J.O.
        • Mortensen P.B.
        The Danish Civil Registration System. A cohort of eight million persons.
        Dan Med Bull. 2006; 53: 441-449
        • Lynge E.
        • Sandegaard J.L.
        • Rebolj M.
        The Danish national patient register.
        Scand J Public Health. 2011; 39: 30-33
        • Andersen T.F.
        • Madsen M.
        • Jorgensen J.
        • Mellemkjoer L.
        • Olsen J.H.
        The Danish National Hospital Register. A valuable source of data for modern health sciences.
        Dan Med Bull. 1999; 46: 263-268
        • Thomsen R.W.
        • Johnsen S.P.
        • Olesen A.V.
        • et al.
        Socioeconomic gradient in use of statins among Danish patients: population-based cross-sectional study.
        Br J Clin Pharmacol. 2005; 60: 534-542
        • Hawa M.I.
        • Thivolet C.
        • Mauricio D.
        • et al.
        Metabolic syndrome and autoimmune diabetes: action LADA 3.
        Diabetes Care. 2009; 32: 160-164
        • Mollo A.
        • Hernandez M.
        • Marsal J.R.
        • et al.
        Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain.
        Diabetes Metab Res Rev. 2013; 29: 446-451
        • Szepietowska B.
        • Glebocka A.
        • Puch U.
        • Gorska M.
        • Szelachowska M.
        Latent autoimmune diabetes in adults in a population-based cohort of Polish patients with newly diagnosed diabetes mellitus.
        Arch Med Sci. 2012; 8: 491-495
        • Schwartz S.S.
        • Epstein S.
        • Corkey B.E.
        • Grant S.F.
        • Gavin 3rd, J.R.
        • Aguilar R.B.
        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: 179-186