Latent autoimmune diabetes in adults

Last updated
Latent autoimmune diabetes in adults
Other namesLADA, late-onset autoimmune diabetes of adulthood, [1] adult-onset autoimmune diabetes
Blue circle for diabetes.svg
Universal blue circle symbol for diabetes [2]
Pronunciation
Specialty Endocrinology

Slowly evolving immune-mediated diabetes, or latent autoimmune diabetes in adults (LADA), is a form of diabetes that exhibits clinical features similar to both type 1 diabetes (T1D) and type 2 diabetes (T2D), [3] [4] and is sometimes referred to as type 1.5 diabetes. [5] It is an autoimmune form of diabetes, similar to T1D, but patients with LADA often show insulin resistance, similar to T2D, and share some risk factors for the disease with T2D. [3] Studies have shown that LADA patients have certain types of antibodies against the insulin-producing cells, and that these cells stop producing insulin more slowly than in T1D patients. [3] [6] Since many people develop the disease later in life, it is often misdiagnosed as type 2 diabetes. [7]

Contents

LADA appears to share genetic risk factors with both T1D and T2D but is genetically distinct from both. [8] [9] [10] [11] [4] Within the LADA patient group, a genetic and phenotypic heterogeneity has been observed with varying degrees of insulin resistance and autoimmunity. [6] [12] With the knowledge we have today, LADA can thus be described as a hybrid form of T1D and T2D, showing phenotypic and genotypic similarities with both, as well as variation within LADA regarding the degree of autoimmunity and insulin resistance.

The concept of LADA was first introduced in 1993, [13] though The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term, instead including it under the standard definition of diabetes mellitus type 1. [14]

Symptoms

The symptoms of latent autoimmune diabetes in adults are similar to those of other forms of diabetes: polydipsia (excessive thirst and drinking), polyuria (excessive urination), and often blurred vision. [15] Compared to juvenile type 1 diabetes, the symptoms develop comparatively slowly, over a period of at least six months. [16]

Diagnosis

A fasting blood sugar level of ≥ 7.0 mmol / L (126 mg/dL) is used in the general diagnosis of diabetes. [17] 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. [3] [4] [6]

Glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulinoma-associated (IA-2) autoantibody, and zinc transporter autoantibody (ZnT8) testing should be performed in order to correctly diagnose diabetes. [18]

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 over production of insulin. [16] [19]

Autoantibodies

Destruction of Glutamate decarboxylase (pictured here) via autoantibodies is strongly linked with LADA type 1 diabetes. PDB GAD67.jpg
Destruction of Glutamate decarboxylase (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. [19]

Persons with LADA usually test positive for glutamic acid decarboxylase antibodies, whereas in type 1 diabetes these antibodies are more commonly seen in adults rather than in children. [19] [20] 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 [19] [21] [22] 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.

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. [4] Globally, it is estimated that about 8.5% of adults have some form of diabetes [17] and it is estimated that LADA accounts for about 3-12% of all adult diabetes cases. [23] Estimates from 2015 are saying that there could be as many as 10–20% of people with diabetes having LADA.

Risk factors

There is limited research on LADA and its etiology. [4] [23] As with both T1D and T2D, the risk of LADA depends on both genetic and environmental factors. [23] [17] Genetic risk factors for LADA are similar to T1D, i.e. is affected by the HLA complex, but also genetic variants associated with T2D have been identified in LADA. [23] LADA has several lifestyle risk factors in common with T2D, such as obesity, physical inactivity, smoking and consumption of sweetened beverages, all of which are linked to insulin resistance. [23]

Obesity has been shown to increase the risk of LADA in several studies, and one study showed that the risk was particularly high in combination with having diabetes in the family. [23] [24] [25] Physical activity also affects the risk of LADA, with less physical activity increasing the risk. [23] A Swedish study showed that low birth weight, in addition to increasing the risk of T2D, increases the risk of LADA. [26]

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. [23] However, results from two studies based on the same population seem to indicate that coffee consumption increases the risk of LADA. [27] [28] Other foods that have been shown to increase the risk of LADA are sweetened beverages and processed red meat [29] [30] [31] while consumption of fatty fish has been shown to have a protective effect. [32]

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. [17] There are very few studies on how to treat LADA, specifically, which is probably due to difficulties in classifying and diagnosing the disease. LADA patients often do not need insulin treatment immediately after being diagnosed because their own insulin production decreases more slowly than T1D patients, but in the long run they will need it. [3] [6] About 80% of all LADA patients initially misdiagnosed with type 2 (and who have GAD antibodies) will become insulin-dependent within 3 to 15 years (according to differing LADA sources). [33]

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. [34] 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. [35]

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. [36] 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. [36] When studies measured fasting C-peptide, no intervention influenced its concentration, but insulin maintained concentration better compared to Sulphonylurea. [36] 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. [36] 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. [36] Still, it is important to highlight that the studies available to be included in this review presented considerable flaws in quality and design. [36]

History

Although type 1 diabetes has been identified as an autoimmune disease since the 1970s, [37] 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. [38] This followed the concept that GAD autoantibodies were a feature of type 1 diabetes and not type 2 diabetes. [39]

Related Research Articles

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP), systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Type 2 diabetes</span> Type of diabetes mellitus with high blood sugar and insulin resistance

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">Sulfonylurea</span> Class of organic compounds used in medicine and agriculture

Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, a dehydrogenated derivative of urea). The side chains R1 and R2 distinguish various sulfonylureas.

Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. Along with neonatal diabetes, MODY is a form of the conditions known as monogenic diabetes. While the more common types of diabetes involve more complex combinations of causes involving multiple genes and environmental factors, each forms of MODY are caused by changes to a single gene (monogenic). GCK-MODY and HNF1A-MODY are the most common forms.

<span class="mw-page-title-main">Glutamate decarboxylase</span> Enzyme

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide. GAD uses pyridoxal-phosphate (PLP) as a cofactor. The reaction proceeds as follows:

<span class="mw-page-title-main">Type 1 diabetes</span> Form of diabetes mellitus

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks if not months.

The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.

<span class="mw-page-title-main">Diabetes management software</span>

Diabetes Management Software refers to software tools that run on personal computers and personal digital assistants to help persons with Type 1 and Type 2 diabetes manage the data associated with:

Teplizumab, sold under the brand name Tzield, is a humanized anti-CD3 monoclonal antibody that is the first approved treatment indicated to delay the onset of stage 3 type 1 diabetes (T1D) in people with stage 2 T1D.

Anti-transglutaminase antibodies (ATA) are autoantibodies against the transglutaminase protein. Detection is considered abnormal, and may indicate one of several conditions.

<span class="mw-page-title-main">HLA-DQ2</span>

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">HLA-DR4</span>

HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.

<span class="mw-page-title-main">PTPRN</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase-like N, also called "IA-2", is an enzyme that in humans is encoded by the PTPRN gene.

<span class="mw-page-title-main">Insulitis</span> Medical condition

Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas that helps regulate glucose levels, and is classified by specific targeting of immune cell infiltration in the islets of Langerhans. This immune cell infiltration can result in the destruction of insulin-producing beta cells of the islets, which plays a major role in the pathogenesis, the disease development, of type 1 and type 2 diabetes. Insulitis is present in 19% of individuals with type 1 diabetes and 28% of individuals with type 2 diabetes. It is known that genetic and environmental factors contribute to insulitis initiation, however, the exact process that causes it is unknown. Insulitis is often studied using the non-obese diabetic (NOD) mouse model of type 1 diabetes. The chemokine family of proteins may play a key role in promoting leukocytic infiltration into the pancreas prior to pancreatic beta-cell destruction.

<span class="mw-page-title-main">Autoimmune disease</span> Disorders of adaptive immune system

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.

Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications.

Ketosis-prone diabetes (KPD) is an intermediate form of diabetes that has some characteristics of type 1 and some of type 2 diabetes. Type 1 diabetes involves autoimmune destruction of pancreatic beta cells which create insulin. This occurs earlier in a person's life, leading to patients being insulin dependent, and the lack of natural insulin makes patients prone to a condition called diabetic ketoacidosis (DKA). Type 2 diabetes is different in that it is usually caused by insulin resistance in the body in older patients leading to beta cell burnout over time, and is not prone to DKA. KPD is a condition that involves DKA like type 1, but occurs later in life and can regain beta cell function like type 2 diabetes. However, it is distinct from latent autoimmune diabetes of adults (LADA), a form of type 1 sometimes referred to as type 1.5 that does not occur with DKA. There are also distinctions to be made between KPD and LADA as patients who exhibit KPD symptoms can regain beta cell function similar to type 2 diabetics whereas LADA will not exhibit this reclamation of beta cell function.

<span class="mw-page-title-main">Diabetes</span> Group of endocrine diseases characterized by high blood sugar levels

Diabetes mellitus, often known simply as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, polyuria, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths every year.

<span class="mw-page-title-main">Autoimmune encephalitis</span> Type of encephalitis

Autoimmune encephalitis (AIE) is a type of encephalitis, and one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. The clinical manifestations include behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures.

Insulin autoimmune syndrome (IAS), a rare cause of reversible autoimmune hypoglycemia also known as Hirata's disease, was first described by Hirata in Japan in 1970.

References

  1. ↑ Williams, Wilkins & Munden 2006, p. 20.
  2. ↑ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. Archived from the original on 5 August 2007.
  3. 1 2 3 4 5 Carlsson, Sofia (2019). "Etiology and Pathogenesis of Latent Autoimmune Diabetes in Adults (LADA) Compared to Type 2 Diabetes". Frontiers in Physiology. 10: 320. doi: 10.3389/fphys.2019.00320 . ISSN   1664-042X. PMC   6444059 . PMID   30971952.
  4. 1 2 3 4 5 Mishra, Rajashree; Hodge, Kenyaita M.; Cousminer, Diana L.; Leslie, Richard D.; Grant, Struan F. A. (2018-09-01). "A Global Perspective of Latent Autoimmune Diabetes in Adults". Trends in Endocrinology & Metabolism. 29 (9): 638–650. doi:10.1016/j.tem.2018.07.001. ISSN   1043-2760. PMID   30041834. S2CID   51715011.
  5. ↑ "Latent autoimmune diabetes in adults (LADA): What is it?". Mayo Clinic . Retrieved December 26, 2022.
  6. 1 2 3 4 Buzzetti, Raffaella; Zampetti, Simona; Maddaloni, Ernesto (November 2017). "Adult-onset autoimmune diabetes: current knowledge and implications for management". Nature Reviews Endocrinology. 13 (11): 674–686. doi:10.1038/nrendo.2017.99. ISSN   1759-5037. PMID   28885622. S2CID   3339346.
  7. ↑ "Latent autoimmune diabetes in adults (LADA): What is it?". Mayo Clinic. Retrieved 2023-12-12.
  8. ↑ Andersen, Mette K.; Lundgren, Virve; Turunen, Joni A.; Forsblom, Carol; Isomaa, Bo; Groop, Per-Henrik; Groop, Leif; Tuomi, Tiinamaija (2010-09-01). "Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years". Diabetes Care. 33 (9): 2062–2064. doi: 10.2337/dc09-2188 . ISSN   0149-5992. PMC   2928363 . PMID   20805278.
  9. ↑ Andersen, Mette K.; Sterner, Maria; Forsén, Tom; Käräjämäki, Annemari; Rolandsson, Olov; Forsblom, Carol; Groop, Per-Henrik; Lahti, Kaj; Nilsson, Peter M.; Groop, Leif; Tuomi, Tiinamaija (2014-09-01). "Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes". Diabetologia. 57 (9): 1859–1868. doi: 10.1007/s00125-014-3287-8 . ISSN   1432-0428. PMID   24906951. S2CID   10477815.
  10. ↑ Cervin, Camilla; Lyssenko, Valeriya; Bakhtadze, Ekaterine; Lindholm, Eero; Nilsson, Peter; Tuomi, Tiinamaija; Cilio, Corrado M.; Groop, Leif (2008-05-01). "Genetic Similarities Between Latent Autoimmune Diabetes in Adults, Type 1 Diabetes, and Type 2 Diabetes". Diabetes. 57 (5): 1433–1437. doi: 10.2337/db07-0299 . ISSN   0012-1797. PMID   18310307.
  11. ↑ Cousminer, Diana L.; Ahlqvist, Emma; Mishra, Rajashree; Andersen, Mette K.; Chesi, Alessandra; Hawa, Mohammad I.; Davis, Asa; Hodge, Kenyaita M.; Bradfield, Jonathan P.; Zhou, Kaixin; Guy, Vanessa C. (2018-11-01). "First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes". Diabetes Care. 41 (11): 2396–2403. doi: 10.2337/dc18-1032 . ISSN   0149-5992. PMC   6196829 . PMID   30254083.
  12. ↑ Pettersen, Elin; Skorpen, Frank; Kvaløy, Kirsti; Midthjell, Kristian; Grill, Valdemar (2010-01-01). "Genetic Heterogeneity in Latent Autoimmune Diabetes Is Linked to Various Degrees of Autoimmune Activity: Results From the Nord-Trøndelag Health Study". Diabetes. 59 (1): 302–310. doi: 10.2337/db09-0923 . ISSN   0012-1797. PMC   2797937 . PMID   19833889.
  13. ↑ Vandewalle C.L.; Decraene, T.; Schuit, F.C.; De Leeuw, I.H.; Pipeleers, D.G.; F.K. Gorus (November 1993). "Insulin autoantibodies and high titre islet cell antibodies are preferentially associated with the HLA DQA1*0301-DQB1*0302 haplotype at clinical type 1 (insulin-dependent) diabetes mellitus before age 10 years, but not at onset between age 10 and 40 years". Diabetologia. 36 (11): 1155–62. doi:10.1007/bf00401060. PMID   8270130. S2CID   20735601.
  14. ↑ American Diabetes, Association (January 2007). "Diagnosis and classification of diabetes mellitus". Diabetes Care. 30 (Suppl 1): S42–7. doi: 10.2337/dc07-S042 . PMID   17192378.
  15. ↑ Flynn, Choi & Wooster 2013, p. 286.
  16. 1 2 Eisenbarth 2010, p. 316.
  17. 1 2 3 4 World Health Organization. (2016). Global Report on Diabetes. Geneva: World Health Organization.
  18. ↑ Landin-Olsson, Mona (April 2002). "Latent autoimmune diabetes in adults". Annals of the New York Academy of Sciences. 958 (1): 112–116. Bibcode:2002NYASA.958..112L. doi:10.1111/j.1749-6632.2002.tb02953.x. PMID   12021090. S2CID   6804673. Archived from the original on 2006-05-22. Retrieved 2006-05-22.
  19. 1 2 3 4 Pipi, Elena; Marietta Market; Alexandra Tsirogianni (August 15, 2014). "Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus". World Journal of Diabetes. 5 (4): 505–10. doi: 10.4239/wjd.v5.i4.505 . PMC   4127585 . PMID   25126396.
  20. ↑ Khardori, Romesh (September 30, 2016). Griffing, George T. (ed.). "Diabetes Mellitus, Type 1: A Review". eMedicine.com. Retrieved January 20, 2017.
  21. ↑ Latent Autoimmune Diabetes in Adults; David Leslie, Cristina Valerie DiabetesVoice.org; 2003
  22. ↑ Unnikrishnan AG, Singh SK, Sanjeevi CB (December 2004). "Prevalence of GAD65 antibodies in lean subjects with type 2 diabetes". Annals of the New York Academy of Sciences. 1037 (1): 118–21. Bibcode:2004NYASA1037..118U. doi:10.1196/annals.1337.018. PMID   15699503. S2CID   2179462.
  23. 1 2 3 4 5 6 7 8 Carlsson, Sofia (2019). "Environmental (Lifestyle) Risk Factors for LADA". Current Diabetes Reviews. 15 (3): 178–187. doi:10.2174/1573399814666180716150253. PMID   30009710. S2CID   51627950.
  24. ↑ Hjort, Rebecka; Ahlqvist, Emma; Carlsson, Per-Ola; Grill, Valdemar; Groop, Leif; Martinell, Mats; Rasouli, Bahareh; Rosengren, Anders; Tuomi, Tiinamaija; Åsvold, Bjørn Olav; Carlsson, Sofia (2018-06-01). "Overweight, obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study". Diabetologia. 61 (6): 1333–1343. doi:10.1007/s00125-018-4596-0. ISSN   1432-0428. PMC   6448998 . PMID   29589073.
  25. ↑ Hjort, Rebecka; Löfvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Grill, Valdemar; Groop, Leif; Sørgjerd, Elin P.; Tuomi, Tiinamaija; Åsvold, Bjørn Olav; Carlsson, Sofia (2019). "Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes". The Journal of Clinical Endocrinology & Metabolism. 104 (10): 4815–4826. doi: 10.1210/jc.2019-00183 . PMC   6735731 . PMID   31125083. S2CID   163166086.
  26. ↑ Hjort, Rebecka; Alfredsson, Lars; Carlsson, Per-Ola; Groop, Leif; Martinell, Mats; Storm, Petter; Tuomi, Tiinamaija; Carlsson, Sofia (2015-11-01). "Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case–control study". Diabetologia. 58 (11): 2525–2532. doi: 10.1007/s00125-015-3711-8 . ISSN   1432-0428. PMID   26208603.
  27. ↑ Löfvenborg, J. E.; Andersson, T.; Carlsson, P.-O.; Dorkhan, M.; Groop, L.; Martinell, M.; Rasouli, B.; Storm, P.; Tuomi, T.; Carlsson, S. (2014). "Coffee consumption and the risk of latent autoimmune diabetes in adults—results from a Swedish case–control study". Diabetic Medicine. 31 (7): 799–805. doi:10.1111/dme.12469. ISSN   1464-5491. PMID   24750356. S2CID   2394699.
  28. ↑ Rasouli, B.; Ahlqvist, E.; Alfredsson, L.; Andersson, T.; Carlsson, P. -O.; Groop, L.; Löfvenborg, J. E.; Martinell, M.; Rosengren, A.; Tuomi, T.; Wolk, A. (2018-09-01). "Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study". Diabetes & Metabolism. 44 (4): 354–360. doi:10.1016/j.diabet.2018.05.002. hdl: 10138/305740 . ISSN   1262-3636. PMID   29861145. S2CID   44144330.
  29. ↑ Löfvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Dorkhan, Mozhgan; Groop, Leif; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2020-02-01). "Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes". European Journal of Nutrition. 59 (1): 127–135. doi:10.1007/s00394-019-01893-x. ISSN   1436-6215. PMC   7000500 . PMID   30656477.
  30. ↑ Löfvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Groop, Leif; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2020-05-22). "Consumption of red meat, genetic susceptibility, and risk of LADA and type 2 diabetes". European Journal of Nutrition. 60 (2): 769–779. doi: 10.1007/s00394-020-02285-2 . ISSN   1436-6215. PMC   7900036 . PMID   32444887.
  31. ↑ Löfvenborg, Josefin E.; Andersson, Tomas; Carlsson, Per-Ola; Dorkhan, Mozhgan; Groop, Leif; Martinell, Mats; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia (2016-12-01). "Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes". European Journal of Endocrinology. 175 (6): 605–614. doi: 10.1530/EJE-16-0376 . ISSN   0804-4643. PMID   27926472.
  32. ↑ Löfvenborg, J. E.; Andersson, T.; Carlsson, P.-O.; Dorkhan, M.; Groop, L.; Martinell, M.; Tuomi, T.; Wolk, A.; Carlsson, S. (October 2014). "Fatty fish consumption and risk of latent autoimmune diabetes in adults". Nutrition & Diabetes. 4 (10): e139. doi: 10.1038/nutd.2014.36 . ISSN   2044-4052. PMC   4216999 . PMID   25329601.
  33. ↑ Eisenbarth, George. "Prediction of Type I Diabetes". University of Colorado, Denver. Retrieved March 23, 2016.
  34. ↑ Castro, M. Regina. "Latent autoimmune diabetes". Mayo Clinic. Retrieved May 26, 2014.
  35. ↑ Nguyen, Than; Tara L. Muzyk (October 15, 2009). "LADA: A Little Known Type of Diabetes". Pharmacy Times. October 2009. 75 (10). Retrieved May 26, 2014.
  36. 1 2 3 4 5 6 Brophy, Sinead; Davies, Helen; Mannan, Sopna; Brunt, Huw; Williams, Rhys (2011-09-07). "Interventions for latent autoimmune diabetes (LADA) in adults". Cochrane Database of Systematic Reviews. 2011 (9): CD006165. doi:10.1002/14651858.cd006165.pub3. ISSN   1465-1858. PMC   6486159 . PMID   21901702.
  37. ↑ Bottazzo, GF; Florin-Christensen, A; Doniach, D (Nov 30, 1974). "Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies". Lancet. 2 (7892): 1279–83. doi:10.1016/s0140-6736(74)90140-8. PMID   4139522.
  38. ↑ Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR (February 1993). "Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease". Diabetes. 42 (2): 359–62. doi: 10.2337/diab.42.2.359 . PMID   8425674.
  39. ↑ Hagopian, W A; Karlsen, A E; Gottsäter, A; Landin-olsson, M; Grubin, C E; Sundkvist, G; Petersen, J S; Boel, E; Dyrberg, T; Lernmark, A (January 1993). "Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type Hagopian, W A; Karlsen, A E; Gottsäter, A; Landin-olsson, M; Grubin, C E; Sundkvist, G; Petersen, J S; Boel, E; Dyrberg, T; Lernmark, A". The Journal of Clinical Investigation. 91 (1): 368–74. doi:10.1172/JCI116195. PMC   330036 . PMID   8423232.

Sources

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.