Latent Autoimmune Diabetes in Adults
Kiara Torres García
PGY1 Pharmacy Resident
Saint Joseph Health System
Analyze the diagnostic challenges Evaluate current treatment
and clinical implications of LADA strategies and explore recent
within the spectrum of diabetes advancements in the
management of LADA
1 Epidemiological Significance
4 Management Challenges
2 Diagnostic Precision
5 Recent Advances in Care
3 Pathophysiology
What are the latest evidence-based strategies for
pharmacists to optimize LADA management?
Demographics PMH
Social History
22 Dec. 22 • C-peptide lab done 1 Mar. 23
• Admitted with
27 Dec. 22
hyperglycemia and leg pain • Follow-up with PCP
• Started on insulin inpatient • Diagnosed with LADA
• A1c done • Glipizide discontinued,
• GAD-65 lab done started on Trulicity
• Prescribed glipizide and
metformin for outpatient
Results
Definition
• LADA is a form of diabetes that Epidemiology
exhibits characteristics of both
Type 1 and Type 2 diabetes
• LADA accounts for up to 10% of
• Occurs in adulthood, typically in all diabetes cases.
individuals over 30 years old.
Pathophysiology:
• Key Features: Islet cell destruction by autoimmunity and insulin resistance.
• Metabolic Syndrome (MetS) prevalence.
Diagnostic Criteria:
• Age usually ≥30 years at diagnosis
• Positive for at least one of four autoantibodies (GAD, IA-2, IAA, or ZnT8)
• Not treated with insulin within the first 6 months after diagnosis.
Feature LADA Type 1 Diabetes Type 2 Diabetes
Present; evidenced Present; marked by Absent; primarily
Autoimmune
by autoantibodies like an autoimmune attack insulin resistance and beta-
Component
GAD65, IA-2, ZnT8. on beta cells. cell dysfunction.
Positive for at least
Presence Commonly positive Lacks
one specific autoantibody
of Autoantibodies for multiple autoantibodies. pancreatic autoantibodies.
(e.g., GAD65).
May not initially May be managed with
Insulin require insulin but often Immediate and lifelong insulin oral agents initially; insulin
Dependence becomes necessary as the dependence. may become necessary as
disease progresses. the condition progresses.
Variable; some beta-
Beta-Cell
cell function remains, Rapid and severe loss Gradual loss of beta-
Function at
but progressive decline of beta-cell function. cell function over time.
Diagnosis
observed.
Studies using HOMA-IR and
Influences treatment approaches
QUICKI-IR indices show LADA's
like the use of insulin sensitizers.
insulin resistance is akin to T2DM’s.
• Chronic inflammation:
⚬ Marked by elevated levels of C-reactive protein and pro-inflammatory cytokines,
linked to both T2DM and LADA.
• Environmental factors:
⚬ Including lifestyle choices like smoking and dietary habits, influence LADA risk and its
pathogenesis through insulin resistance modulation.
• Decrease in the abundance of acid-producing bacteria
and contents of gut metabolites was associated with:
⚬ Islet autoantibodies and function
⚬ Glucose metabolism
⚬ Inflammatory cytokines
• New avenues for therapeutic interventions
Current guidelines highlight the importance of C-peptide
measurement for guiding treatment decisions, emphasizing
a tailored approach based on residual beta-cell function.
As of October 2020,
• Insulin therapy is essential for patients with significant insulin deficiency.
• Metformin and other glucose-lowering agents like DPP-4 inhibitors and
GLP-1 receptor agonists may be beneficial.
• The study aims to evaluate the efficacy of various therapeutic agents
for LADA by comparing their effects on multiple clinical indicators.
• A comprehensive search across PubMed, Cochrane
Library, Embase, and Web of Science databases,
collecting data from RCTs on glucose-lowering drugs
for LADA.
• Data from 14 RCTs involving various treatments for
LADA, with a total of 15 treatment regimens analyzed.
• Insulin showed the most significant effect on HbA1c
change.
• Insulin combined with DPP-4 inhibitors was best for
reducing FBG and BMI.
• TZDs were most advantageous for controlling HbA1c,
fasting C-peptide, and postprandial C-peptide.
’
• Combinations of insulin with DPP-4 inhibitors or thiazolidinediones
could be effective options to maintain islet function and control blood
glucose.
Strengths Limitations
• Comprehensive analysis • Small sample sizes
• Broad evaluation of treatments: • Varying study quality
• Efficacy ranking • Diverse interventions and
methodologies
• Underscores the necessity for personalized treatment plans for LADA, considering
the effectiveness and ranking of various therapies.
• Highlights the importance of early intervention and the potential benefits of specific
therapies in preserving beta-cell function and managing blood glucose levels.
• Calls for more high-quality, long-term RCTs to establish conclusions about the
optimal management strategies for LADA.
What would be the
best treatment plan for
this patient?
8 Aug. 23
31 Mar. 23
16 Feb. 24
• Started “Keto Hybrid" diet
• Decreased weight from
• Lost 42lbs since Oct of the
181 to 178 lbs
year prior
• BMI: 24.9
Screening Results:
Screening Results:
• A1c: 5.9
• A1c: 5.7
• C-peptide: 0.73
Treatment Decision:
• GAD-65: 5.7
• Continue metformin and
Trulicity
Treatment Decision:
• Continue metformin
• Consider CGM
• Achieve early and accurate diagnosis of LADA for optimal
management and treatment planning.
• Tailor treatment plans to individual patient characteristics,
considering factors like age, comorbidities, and screening results.
• Use multi-faceted approach to management, including lifestyle
modifications, glycemic control, and monitoring for
complications.
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clinical score for identifying patients with high risk of latent autoimmune adult diabetes (LADA):
The LADA primary care-protocol study. PLoS One. 2023;18(2):e0281657. Published 2023 Feb 9.
doi:10.1371/journal.pone.0281657
2.Pan N, Yang S, Niu X. Latent Autoimmune Diabetes in Adults and Metabolic Syndrome-A Mini
Review. Front Endocrinol (Lausanne). 2022;13:913373. Published 2022 Jun 28.
doi:10.3389/fendo.2022.913373
3.O'Neal KS, Johnson JL, Panak RL. Recognizing and Appropriately Treating Latent Autoimmune
Diabetes in Adults. Diabetes Spectr. 2016;29(4):249-252. doi:10.2337/ds15-0047
4.Raffaella Buzzetti, Tiinamaija Tuomi, Didac Mauricio, Massimo Pietropaolo, Zhiguang Zhou, Paolo
Pozzilli, Richard David Leslie; Management of Latent Autoimmune Diabetes in Adults: A
Consensus Statement From an International Expert Panel. Diabetes 1 October 2020; 69 (10):
2037–2047. https://doi.org/10.2337/dbi20-0017
5.Wang W, Huang F, Han C. Efficacy of Regimens in the Treatment of Latent Autoimmune Diabetes
in Adults: A Network Meta-analysis. Diabetes Ther. 2023;14(10):1723-1752. doi:10.1007/s13300-
023-01459-5
