- Credits - Section Writer: Dr. Om J Lakhani - Section Editor: Dr. Om J Lakhani Support us: 1. Support us by purchasing our book - Click here for more details: [[Volume 1- THE BEST OF NOTES IN ENDOCRINOLOGY BOOK SERIES]] 2. [Support you by Becoming a YouTube member (Click here)](https://www.youtube.com/channel/UC6zQSf7dLDqfQOeM4mNUBTQ/join) Reference: Buzzetti et al^[Buzzetti R, Tuomi T, Mauricio D, Pietropaolo M, Zhou Z, Pozzilli P, Leslie RD. Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel. Diabetes. 2020 Oct;69(10):2037-2047. doi: 10.2337/dbi20-0017. Epub 2020 Aug 26. PMID: 32847960; PMCID: PMC7809717.] - Q. What are the diagnostic criteria for Latent autoimmune diabetes of Adulthood (LADA) ? - Age > 30 year - At least 1 insulin cell autoantibodies positive - Period of 6 months on insulin independence - Q. What are the expanded clinical criteria for Latent autoimmune diabetes of Adulthood (LADA) ? - Age at onset > 30 years - A family or personal history of autoimmunity - A reduced frequency of metabolic syndrome compared with people with full-on type 2 diabetes: lower HOMA, lower body mass index, lower blood pressure, normal HDL compared with people with type 2 diabetes - No disease-specific difference in cardiovascular outcomes between these patients and those with type 2 diabetes - C-peptide levels fall more slowly than in traditional type 1 diabetes - Positivity for anti-GAD antibodies is the most sensitive marker, but other autoantibodies can be found as well, just less frequently - Non–insulin-requiring at the onset - Q. Which is the preferred marker to diagnose LADA? - Anti GAD65 - Q. What are the subtypes of LADA? - LADA1 – lesser C peptide, more ketosis-prone, higher GAD antibody - LADA2- greater C peptide, less ketosis-prone, lesser GAD antibody positivity - Q. What is LADY? - Latent autoimmune diabetes in Young - Similar to LADA but age is <30 years - Q. What is the importance of a positive GAD antibody in any diabetic individual? - Positive GAD antibody in any diabetic predicts the requirement for early insulin requirement - Q. Which is the latest antibody for Type 1 Diabetes or Latent autoimmune diabetes of Adulthood (LADA) ? - Tetraspanin 7 - Q. Are there any benefits of early insulin initiation? - Yes - Early insulin initiation would help give rest to beta-cell and give overall good control - Q. Which heat shock protein has been found to reduce beta-cell destruction? - Diapep 277- a heat shock protein 60 derivative has been found to reduce the incidence of beta-cell destruction in both type 1 diabetes and LADA - Q. What vaccine has been found to retard  beta-cell damage? - Anti GAD65 vaccine – DIAMYD - Q. How do these vaccines work? - They cause a shift from pro-inflammatory Th1 cells to anti-inflammatory Th2 cells - This shift suppresses the cytokine produced by Th1 - This is a form of “acquired immune tolerance” - Q. What is the core difference between adult type 1 diabetes and LADA? - The core difference is the speed of the beta-cell destruction leading to the dependency on insulin - Adult-onset Type 1 Diabetes have more rapid beta-cell destruction unlike LADA - This is differentiated by the criteria which say 6 or more months of insulin independence after onset which is required for LADA - If insulin requirement is before 6 months - it is adult type 1 - otherwise, it is LADA - Q. Which OAD must be avoided for use in LADA? - Avoid sulphonylurea - Q. Can other OAD be used in LADA? - Yes - There are small studies for benefit of all other OADs including SGLT2i in LADA patients - Q. Should all patients with Type 2 Diabetes mellitus be screened for LADA? - Yes - According to the recent guidelines on the topic - Q. Give the algorithm for diagnosis and management of Latent autoimmune diabetes of Adulthood (LADA) -  -  -  - Q. What is the C-peptide-based approach to the management of a patient with LADA? - C-peptide - <0.9 ng/ml (0.3 nmol/l) - Patient should be on basal bolus insulin - 0.9-2.1 ng/ml (0.3-0.7 nmol/l) - Patient should be on basal insulin plus OAD - More than 2.1 ng/ml (>0.7 nmol/l) - treat with OAD and/or as per the ADA guidelines for type 2 diabetes - Q. What should be the glucose levels while performing the C-peptide assay? - 80-180 mg/dl - Q. Apart from the insulin requirement and OAD, which other factors must be kept in mind when a patient has LADA instead of Type 2 Diabetes mellitus ? - Increased risk of other autoimmune diseases - including hypothyroidism 14-Aug-2023, #update - Q. What were the conclusion from the Botnia study group published in 2010 ? - The study was done to look at the impact of GAD antibody in the future risk of diabetes in non diabetic individuals - The study found the the following: - • GADA positivity is a strong predictor of diabetes, regardless of family history. - • People with high GADA concentrations are at an increased risk of developing diabetes. - • GADA positivity tends to occur in families with type 1 diabetes or latent autoimmune diabetes in adults. - • Low or medium levels of GADA do not impact the incidence of diabetes in individuals without a family history of diabetes. - • Elevated GADA concentrations indicate an increased risk of diabetes in both relatives and control subjects. - • The risk of diabetes is influenced by age, sex, BMI, GADAs, and family history of type 1 or type 2 diabetes. - • GADA positivity significantly raises the risk of diabetes, in addition to traditional risk factors for type 2 diabetes - This flow chart summarizes this well: -  - Ref: Lundgren VM, Isomaa B, Lyssenko V, Laurila E, Korhonen P, Groop LC, Tuomi T, Botnia Study Group. GAD antibody positivity predicts type 2 diabetes in an adult population. Diabetes. 2010 Feb 1;59(2):416-22. - Q. What level of [[GAD65 antibody]] was considered as positive in this study ? - Levels about 32 IU/l were considered positive - Q. Should patients with LADA be given SU ? Does it impact long term beta-cell reserve ? - A study published in JCEM concluded that it is better to give insulin early and not [[Sulphonylurea]] in patients with LADA - Study conducted by Taro Maruyama et al. that focused on comparing the effectiveness of insulin therapy versus sulfonylurea (SU) treatment in preserving or reversing beta-cell function in patients with slowly progressive insulin-dependent diabetes or LADA. - The study was a randomized clinical trial that included 60 patients with a 5-year duration or shorter of diabetes. - The primary endpoint of the study was an insulin-dependent state defined by low levels of serum C-peptide values. - The results showed that the progression rate to an insulin-dependent state was lower in the insulin group compared to the SU group, indicating that insulin therapy may be more effective in preserving beta-cell function in LADA patients. - Ref: Maruyama T, Tanaka S, Shimada A, Funae O, Kasuga A, Kanatsuka A, Takei I, Yamada S, Harii N, Shimura H, Kobayashi T. Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus. The Journal of Clinical Endocrinology & Metabolism. 2008 Jun 1;93(6):2115-21.