Latent autoimmune diabetes in adults

The pathophysiology of LADA is similar to that of type 1 diabetes, in that it involves autoimmune destruction of pancreatic β-cells; however, this process occurs at a slower rate than in type 1 diabetes. This results in a gradual decline in insulin production and allows for a period during which individuals are not insulin-dependent. The immune-mediated destruction of β-cells varies in rate and extent among individuals, leading to a heterogeneous clinical course. ==Symptoms and signs==

The signs and symptoms of LADA are similar to those of other types of diabetes (e.g., glucosuria, polyuria), but the onset tends to be more gradual than in other forms of diabetes. In comparison to classic type 1 diabetes, the signs and symptoms of LADA progress more gradually, as the condition results from a long-term autoimmune process that progressively destroys pancreatic β-cells. == Risk factors ==

There is limited research on LADA and its etiology. Physical activity also affects the risk of LADA, with less physical activity increasing the risk. Although smoking has been shown to increase the risk of T2D while coffee consumption has been shown to reduce the risk of T2D, the results regarding these products and LADA are unclear. Other foods that have been shown to increase the risk of LADA are sweetened beverages and processed red meat while consumption of fatty fish has been shown to have a protective effect. ==Diagnosis==

A fasting blood sugar level of ≥ 7.0 mmol / L (126 mg/dL) is used in the general diagnosis of diabetes. There are no clear guidelines for the diagnosis of LADA, but the criteria often used are that the patient should develop the disease in adulthood, not need insulin treatment for the first 6 months after diagnosis and have autoantibodies in the blood. Persons with LADA typically have low, although sometimes moderate, levels of C-peptide as the disease progresses. Those with insulin resistance or type 2 diabetes are more likely to have high levels of C-peptide due to an overproduction of insulin. Autoantibodies (pictured here) via autoantibodies is strongly linked with LADA type 1 diabetes. Glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulinoma-associated (IA-2) autoantibodies, and zinc transporter autoantibodies (ZnT8) are all associated with LADA; GADAs are commonly found in cases of diabetes mellitus type 1. The presence of islet cell complement fixing autoantibodies also aids in a differential diagnosis between LADA and type 2 diabetes. Persons with LADA often test positive for ICA, whereas type 2 diabetics only seldom do. In addition to being useful in making an early diagnosis for type 1 diabetes mellitus, GAD antibodies tests are used for differential diagnosis between LADA and type 2 diabetes and may also be used for differential diagnosis of gestational diabetes, risk prediction in immediate family members for type 1, as well as a tool to monitor prognosis of the clinical progression of type 1 diabetes. ==Management==

Diabetes is a chronic disease, i.e. it cannot be cured, but symptoms and complications can be minimized with proper treatment. Diabetes can lead to elevated blood sugar levels, which in turn can lead to damage to the heart, blood vessels, kidneys, eyes and nerves. The treatment for Type 1 diabetes/LADA is exogenous insulin to control glucose levels, prevent further destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from diabetic ketoacidosis (DKA). Although LADA may appear to initially respond to similar treatment (lifestyle and medications) as type 2 diabetes, it will not halt or slow the progression of beta cell destruction, and people with LADA will eventually become insulin-dependent. People with LADA have insulin resistance similar to long-term type 1 diabetes; some studies showed that people with LADA have less insulin resistance, compared with those with type 2 diabetes; however, others have not found a difference. A Cochrane systematic review from 2011 showed that treatment with Sulphonylurea did not improve control of glucose levels more than insulin at 3 nor 12 months of treatment. This same review actually found evidence that treatment with Sulphonylurea could lead to earlier insulin dependence, with 30% of cases requiring insulin at 2 years. When studies measured fasting C-peptide, no intervention influenced its concentration, but insulin maintained concentration better compared to Sulphonylurea. The authors also examined a study utilizing Glutamic Acid Decarboxylase formulated with aluminium hydroxide (GAD65), which showed improvements in C-peptide levels that were maintained for 5 years. Vitamin D with insulin also demonstrated steady fasting C-peptide levels in the vitamin group, with the same levels declining in the insulin-only group at a 12-month follow-up. One study examining the effects of Chinese remedies on fasting C-peptide on a 3-month follow-up did not show a difference compared to insulin alone. Still, it is important to highlight that the studies available to be included in this review presented considerable flaws in quality and design. == Genetics ==

LADA appears to share genetic risk factors with both T1D and T2D, including susceptibility loci related to HLA-associated immune function as well as loci associated with insulin resistance, but is genetically distinct from both. As a result, LADA is considered a heterogeneous and complex genetic disorder. == Comparison ==

LADA differs from both type 1 and type 2 diabetes. It has a later onset and slower progression than classic type 1 diabetes and is characterized by autoimmune-mediated β-cell destruction, while also exhibiting features of type 2 diabetes due to progressive insulin deficiency over time. Genetic testing can help distinguish LADA from monogenic forms of diabetes (e.g., MODY), which lack autoimmune markers and do not share the same genetic profile. == Prevalence ==

Since there is no regular autoantibody screening, patients with LADA are at risk of being diagnosed with type 2 diabetes, which makes it difficult to estimate the prevalence of LADA. 2015 estimates suggest that up to 10–20% of people with diabetes have LADA. ==History==

Although type 1 diabetes has been identified as an autoimmune disease since the 1970s, the concept of latent autoimmune diabetes mellitus was not noted until 1993, when it was used to describe slow-onset type 1 autoimmune diabetes occurring in adults. This followed the concept that GAD autoantibodies were a feature of type 1 diabetes and not type 2 diabetes. ==References==