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  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

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Reference: Buzzetti et al^[1]

• 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.