Type 1.5 diabetes, also called latent autoimmune diabetes in adults (LADA), is a condition that shares characteristics of both type 1 and type 2 diabetes.
Latent Autoimmune Diabetes in Adults (LADA), is a form of diabetes characterized by adult onset, the presence of islet autoantibodies (most frequently glutamic acid decarboxylase antibody, GADA), and a slow progression to insulin dependence.
LADA is diagnosed during adulthood, and it sets in gradually, like type 2 diabetes.
But unlike type 2 diabetes, LADA is an autoimmune disease and isn’t reversible with changes in diet and lifestyle.
The diagnosis of LADA is typically based on three criteria: age at onset greater than 30–35 years, presence of at least one islet autoantibody (most commonly GADA), and absence of insulin requirement for at least six months after diagnosis.
The prevalence of LADA varies by population and diagnostic criteria, accounting for approximately 5–14% of adults initially diagnosed with type 2 diabetes in Europe, North America, and Asia.
The majority of antibody-positive patients have GADA.
Other islet autoantibodies (IA-2, ZnT8, insulin) are less common.
The frequency of high-risk HLA-DR/DQ alleles is increased compared to type 2 diabetes but lower than in type 1 diabetes.
Non-HLA loci such as PTPN22, INS VNTR, and CTLA4 are also associated with LADA, but with attenuated effect sizes compared to type 1 diabetes.
Beta cells stop functioning much more quickly if you have type 1.5 diabetes than if you have type 2.
It’s estimated that 10 percent of people who have diabetes have LADA.
Type 1.5 diabetes can easily be — and is often — misdiagnosed as type 2 diabetes.
Importantly, LADA is distinguished from classic type 1 diabetes by the presence of type 2 diabetes risk alleles, most notably TCF7L2, which is increased in LADA to a similar extent as in type 2 diabetes.
LADA is more prevalent than classic adult-onset type 1 diabetes in many regions.
Risk factors for LADA include genetic susceptibility (notably HLA class II alleles such as DRB103:01-DQB102:01 and DRB104:01-DQB103:02), family history of autoimmune disease, intermediate BMI, and features of both type 1 and type 2 diabetes.
Other type 2 diabetes loci (ZMIZ1, KCNQ1, HHEX, MTNR1B, SLC30A8, FTO, PPARG, HNF1A) are also associated with LADA, with the strength of association varying according to the degree of autoimmunity.
Environmental triggers such as viral infections and dietary factors may also play a role, but their contribution is less well defined.
It is characterized by a pathophysiological profile that bridges features of both classic type 1 and type 2 diabetes.
The central mechanism is autoimmune destruction of pancreatic β-cells, evidenced by the presence of islet autoantibodies, but the process is slower and less intense than in childhood-onset type 1 diabetes.
Patients with LADA typically retain endogenous insulin secretion for a longer period, as reflected by measurable C-peptide levels at diagnosis.
The autoimmune response in LADA is less robust, and the genetic risk conferred by HLA alleles is lower than in classic type 1 diabetes.
Genetically, LADA exhibits a combination of risk alleles associated with both type 1 and type 2 diabetes.
Genome-wide association studies confirm that LADA is genetically more similar to type 1 diabetes, but with a greater presence of type 2 diabetes risk alleles, supporting the concept of LADA as a hybrid form of diabetes.
The molecular hallmark of LADA is the presence of islet autoantibodies, most commonly GAD, but also IA-2, ZnT8, and insulin.
The titer and number of autoantibodies correlate with the rate of β-cell destruction and the genetic risk profile: higher autoantibody titers are associated with a genetic background more similar to type 1 diabetes.
Metabolic dysfunction, particularly insulin resistance, is increasingly recognized as a contributor to the pathogenesis of LADA.
Many individuals with LADA exhibit features of metabolic syndrome, including elevated BMI, dyslipidemia, and hypertension, which are traditionally associated with type 2 diabetes.
Insulin resistance may exacerbate β-cell stress and antigen presentation, promoting further autoimmune attack and accelerating β-cell failure.
Compared with type 1 and type 2 diabetes, LADA shows high rates of dyslipidemia (~91%) and hypertension (~78%) and more diabetic kidney disease (~44%) and neuropathy (~55%), underscoring the need for aggressive risk factor management
Initial response to oral hypoglycemic agents may be seen, but insulin requirement becomes inevitable as β-cell function declines.
The diagnosis of diabetes is based on standard glycemic thresholds: fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test, HbA1c ≥6.5%, or random plasma glucose ≥200 mg/dL with classic symptoms.
C-peptide levels are typically intermediate at diagnosis but decline over time, reflecting progressive β-cell loss.
Autoantibody testing in adults with atypical features-lean adults with new-onset diabetes, or those with other autoimmune diseases.
The presence of GAD autoantibodies is the most sensitive marker, but IA-2 and ZnT8 may also be present.
Indiscriminate autoantibody testing in all adults with diabetes may lead to false positives and misclassification, and recommends restricting testing to those with clinical suspicion for autoimmune diabetes.
C-peptide measurement can be useful in assessing residual β-cell function, with lower levels indicating more advanced β-cell destruction.
Type 1.5 diabetes symptoms
Type 1.5 diabetes symptoms can be vague at first. They may include:
frequent thirst
increased urination, including at night
unexplained weight loss
blurred vision and tingling nerves
If left untreated, type 1.5 diabetes can lead to diabetic ketoacidosis, which is a condition where the body can’t utilize sugar as fuel due to the absence of insulin and starts burning fat.
This produces ketones which are toxic for the body.
Type 1.5 diabetes causes:
Type 1 diabetes is considered an autoimmune condition because it’s the result of your body destroying pancreatic beta cells.
These cells helps your body make insulin, the hormone that allows you to store glucose (sugar).
People who have type 1 diabetes need to inject insulin into their bodies to survive.
Type 2 diabetes is primarily characterized by the body resisting insulin’s effects.
Insulin resistance is caused by genetic anD environmental factors, such as a diet high in carbohydrates, inactivity, and obesity.
Type 2 diabetes can be managed with lifestyle interventions and oral medication, but many may also need insulin to keep their blood sugar under control.
Type 1.5 diabetes can be triggered by damage done to the pancreas from antibodies against insulin-producing cells.
Genetic factors may also be involved, such as a family history of autoimmune conditions.
When thepancreas becomes damaged in type 1.5 diabetes, the body destroys pancreatic beta cells, as with type 1.
If the person with type 1.5 diabetes also happens to be overweight or obese, insulin resistance might also be present.