Latent Autoimmune Diabetes In Adults
Context: Autoantibodies that are reactive to islet antigens are present at the time of diagnosis in most patients with type 1 diabetes. Additionally, approximately 10% of phenotypic type 2 diabetic patients are positive for at least one of the islet autoantibodies, and this group is often referred to as “latent autoimmune diabetes in adults (LADA).” These patients share many genetic and immunological similarities with type 1 diabetes, suggesting that LADA, like type 1 diabetes, is an autoimmune disease. However, there are differences in autoantibody clustering, T cell reactivity, and genetic susceptibility and protection between type 1 diabetes and LADA, implying important differences in the underlying disease processes. Evidence Acquisition and Synthesis: In this clinical review, we will summarize the current understanding of LADA based on the MEDLINE search of all peer-reviewed publications (original articles and reviews) on this topic between 1974 and 2009. Conclusions: In LADA, diabetes occurs earlier in the β-cell-destructive process because of the greater insulin resistance. Complexities arise also because of variable definitions of LADA and type 1 diabetes in adults. As immunomodulatory therapies that slow or halt the type 1 diabetes disease process are discovered, testing these therapies in LADA will be essential. Context: 11β-Hydroxysteroid dehydrogenase (11β-HSD) enzymes are now appreciated to be important regulators of hormone action at a tissue level. 11β-HSD1 is widely expressed and increases glucocorticoid action through its unique ability to convert inactive glucocorticoids (cortisone in man, 11-dehydrocorticosterone in rodents) to their active forms (cortisol and corticosterone, respectively). The enzyme has roles in the normal hypothalamus-pitui Continue reading >>
Prevalence Of Latent Autoimmune Diabetes In Adults In China: A Systematic Review And Meta-analysis
Abstract Studies of the prevalence of latent autoimmune diabetes in adults in China have reported inconsistent findings. We did a systematic review and meta-analysis to estimate the prevalence of latent autoimmune diabetes in adults in China. For the systematic review, we searched PubMed, Embase, China Knowledge Resource Integrated Database, and Wanfang Medicine Database to identify studies investigating the prevalence of latent autoimmune diabetes in adults in China. In our meta-analysis we included hospital-based studies that recruited patients with newly diagnosed (less than 1 year from diagnosis) type 2 diabetes or population-based studies, which assessed the prevalence of latent autoimmune diabetes in adults in China and used a radioimmunoassay to test for glutamic acid decarboxylase autoantibodies. Subgroup analyses were done by study design, sex, and types of autoantibodies. Random-effects meta-analysis was used to pool the prevalence rate with 95% CIs. Ethical approval was granted by the ethical committee of our hospital This study was registered at PROSPERO, number CRD42016040163. 12 studies with a total of 21 576 individuals were included. There were three population-based studies and nine hospital-based studies recruiting patients with newly diagnosed types 2 diabetes. The meta-analysis of 12 studies showed that the prevalence of latent autoimmune diabetes in adults in Chinese patients with type 2 diabetes was 7·4% (95% CI 6·5–8·5; 21 576 participants from 12 studies), which was similar to that in white populations (6·8%, 5·6–8·3; 28 415 participants from 15 studies). The prevalence of latent autoimmune diabetes in adults from the population-based studies was 6·7% (95% CI 5·4–8·3; 12 144 participants from three studies) and the prevalence of la Continue reading >>
Type 1.5 Diabetes: An Overview
Type 1.5 Diabetes (T1.5D) is also known as Latent Autoimmune Diabetes of Adults (LADA). LADA is considered by some experts to be a slowly progressive form of Type 1 Diabetes (T1D) while other experts in the field consider it a separate form of Diabetes. LADA or T1.5D is sometimes thought of as T1D that is diagnosed in adults over the age of 30—T1D is commonly diagnosed in children and younger adults. T1.5D is often found along with Type 2 Diabetes (T2D): up to 25% of individuals with T1.5D also have characteristics of T2D.1 This is sometimes called “double diabetes”. Individuals with T1.5D are all eventually dependent on insulin for treatment, and have a very high risk of requiring insulin within months or years (up to six years) after the initial diagnosis. This is in contrast to people with T1D—these people tend to need insulin within days or weeks of diagnosis.2 Individuals diagnosed with T2D relatively rarely require insulin treatment. Current recommendations are to treat individuals with T1.5D immediately with insulin, though this is not universally accepted (see below). The Causes of T1.5D Just as with other forms of diabetes, we don’t truly understand the underlying cause(s) of T1.5D. There are autoimmune components in Types 1, 1.5 and 2 diabetes with some overlap in the types of antibodies formed, so it is clear that as in T1D, the immune system has become “confused” and begins to act against the beta cells of the pancreas—the source of the insulin needed to control blood sugars. Both T1D and T1.5D have antibodies to glutamic acid decarboxylase or anti-GAD antibodies. As with T1D, individuals with T1.5D tend not to be obese, whereas in T2D, most individuals are overweight or obese. Genetics and Environmental Susceptibility Individuals with T1.5D Continue reading >>
Fatty Fish Consumption And Risk Of Latent Autoimmune Diabetes In Adults
It has been suggested that intake of fatty fish may protect against both type 1 and type 2 diabetes. Hypotheses rest on the high marine omega-3 fatty acid eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) and vitamin D contents, with possible beneficial effects on immune function and glucose metabolism. Our aim was to investigate, for the first time, fatty fish consumption in relation to the risk of latent autoimmune diabetes in adults (LADA). Analyses were based on data from a Swedish case–control study with incident cases of LADA (n=89) and type 2 diabetes (n=462) and randomly selected diabetes-free controls (n=1007). Diabetes classification was based on the onset of age (⩾35), glutamic acid decarboxylase autoantibodies, and C-peptide. A validated food frequency questionnaire was used to derive information on previous intake of fish, polyunsaturated long-chain omega-3 fatty acids (n-3 PUFA) and supplementation of fish oil and vitamin D. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, body mass index (BMI), family history of diabetes, physical activity, smoking, education, and consumption of alcohol, fruit, vegetables and red meat. Weekly fatty fish consumption (⩾1 vs <1 serving per week), was associated with a reduced risk of LADA but not type 2 diabetes (OR 0.51, 95% CI 0.30–0.87, and 1.01, 95% CI 0.74–1.39, respectively). Similar associations were seen for estimated intake of n-3 PUFA (⩾0.3 g per day; LADA: OR 0.60, 95% CI 0.35–1.03, type 2 diabetes: OR 1.14, 95% CI 0.79–1.58) and fish oil supplementation (LADA: OR 0.47, 95% CI 0.19–1.12, type 2 diabetes: OR 1.58, 95% CI 1.08–2.31). Our findings suggest that fatty fish consumption may reduce the risk of LADA, possibly t Continue reading >>
Prevalence Of Latent Autoimmune Diabetes Of Adults (lada) In Southern Spain
Abstract Objective: To study the prevalence of diabetes mellitus and islet autoantibodies in an adult population from Southern Spain. Research design and methods: A cross-sectional study in Southern Spain of 1226 people, age 18–65 years. Clinical data were obtained and a blood sample taken to measure autoantibodies (glutamic acid decarboxylase antibodies (GADAb), tyrosine phosphatase antibodies (IA2Ab), and insulin antibodies (IAA)). An oral glucose tolerance test (OGTT) was also given to 982 of the subjects. Results: The overall prevalence of diabetes mellitus according to the WHO 1979 criteria was 10.9% and according to the ADA 1997 criteria it was 14.7% (8.8% were unaware of their diabetes). The prevalence of impaired fasting glucose (IFG) was 12.4% and of impaired glucose tolerance (IGT) 11.5%. The prevalence of GADAb+ in the general population was 0.9% and in the diabetic population 3.7%. There were no significant differences between groups in the prevalence of IA2Ab or IAA (both were 0.8% in the general population). Of the three autoantibodies studied, only GADAb were significantly different in the diabetic population (P=0.0006). Conclusions: The prevalence of Type 2 diabetes and LADA are high in the south of Spain Continue reading >>
Eight Weeks To Latent Autoimmune Diabetes In Adults: A Case Of Rapidly Developing Latent Autoimmune Diabetes In Adults
SESSION TITLE: Critical Care 1 SESSION TYPE: Affiliate Case Report Poster INTRODUCTION: Latent Autoimmune diabetes in adult (LADA) is an uncommon type of diabetes that develops in patients older than 30 years old. It is often diagnosed in patients who are initially thought to have type 2 diabetes, but subsequently found to have circulating anti-pancreatic islet cell antibodies. Many patients progress slowly but became insulin dependent within 6 months to a year of the diagnosis. We present a case of a young woman presenting with diabetic ketoacidosis (DKA). CASE PRESENTATION: Our patient is a 32-year-old Caucasian female who presented to our hospital with a 2-week history of progressively worsening nausea, polydipsia and polyuria. Her BMI was 20. Initial laboratory workup revealed blood glucose of 407, anion gap metabolic acidosis, ketonemia and ketonuria. She was diagnosed with DKA, and treated with insulin infusion. She had history of gestational diabetes 3 years prior to presentation and a recent diagnosis of prediabetes which was managed with diet. She underwent a full annual physical exam eight weeks prior to presentation, and records showed a hemoglobin A1c of 6.4 at the time. She started exercising to control her A1c. At admission, further laboratory workup revealed an A1c of 10.4, C-peptide of 0.6 ng/ml (normal 0.8-3.5), Islet cell Ab IgG of 1:256, as well as GAD 65 >250 IU/ml (normal 0.0-5.0). Patient was discharged on insulin and referred to endocrinology. She was evaluated as outpatient and was started on insulin pump therapy. DISCUSSION: LADA is an uncommon type of diabetes responsible for a small fraction of patients. It is more common in populations with higher frequency of Type 1 diabetes. Patients with LADA are heterogeneous, but tend to have lower BMI. Continue reading >>
Latent Autoimmune Diabetes In Adults (lada) In Asian And European Populations
Diabetes mellitus is a chronic disorder caused by relative or absolute insulin deficiency and characterized by chronic hyperglycaemia. It is expected that by year 2025, 80% of all type 2 diabetic patients will be living in developing or low- and middle-income countries. Among Asians, there has been an overall increase in abdominal obesity; however, the risk of diabetes in these populations starts at much lower body mass index as compared to Caucasians. A significant proportion of diabetic patients with adult-onset, initially nonrequiring insulin treatment, have diabetes-associated autoantibodies in their sera. A new subclass of diabetes with the designation of latent autoimmune diabetes of adult-onset (LADA) has been proposed for this category of subjects. Studies have demonstrated that patients with autoimmune diabetes, characterized by the presence of glutamic decarboxylase autoantibodies display a different clinical phenotype from classical type 2 diabetes without glutamic decarboxylase autoantibodies. This subset of phenotypic type 2 diabetes subjects with islet autoantibodies tend to have sulphonylurea failure and need insulin treatment earlier in the disease process. Diagnosing LADA at an initial stage will be important so that insulin can be initiated earlier, facilitating improved glycemic control sooner as well as the preservation of residual beta-cell function in adult-onset autoimmune diabetes. Because of differences in dietary habits, environmental factors, and phenotypic characteristics between European and Asian populations, there may be heterogeneity in the prevalence and other characteristics of LADA in these two populations. Continue reading >>
Classifications For Diabetes In Older Adults
The risk for diabetes increases with age, making diabetes common in older adults. In fact, approximately 25% of adults over the age of 60 years have diabetes. Diabetes means that your blood glucose (sugar) level is too high. Your body’s cells need glucose for energy. When you eat, your pancreas releases the hormone insulin, which helps the glucose from food get into your cells. People with diabetes do not make enough insulin or do not use insulin well, causing glucose to build up in their blood and not reach their cells. This can lead to complications including damage to the heart, eyes, kidneys, and feet. While type 1 diabetes is usually thought of as beginning in childhood and type 2 diabetes as a beginning in adulthood, it is becoming more clear that adults—including older adults—can develop new-onset type 1 diabetes and that children can develop type 2 diabetes. The different classifications of diabetes that may occur in older people are described below. Type 2 Diabetes People with type 2 diabetes do not make or use insulin well. This is the most common type of diabetes and typically occurs in people who are overweight and inactive. Other risk factors include a family history of the disease, older age, certain ethnicities (blacks, Hispanics, American Indians and Asian-Americans), polycystic ovary syndrome, and a history of gestational diabetes (diabetes in pregnancy). Type 1 Diabetes People with type 1 diabetes make little or no insulin and need to take insulin therapy as soon as they are diagnosed. Type 1 diabetes typically begins in childhood, but also may first begin in adulthood. This form is typically caused by an autoimmune disorder, meaning that the body’s immune system mistakenly attacks cells that make insulin. In some people, type 1 diabetes may oc Continue reading >>
Diabetic Ketoacidosis As First Presentation Of Latent Autoimmune Diabetes In Adult
Case Reports in Medicine Volume 2015 (2015), Article ID 821397, 3 pages Internal Medicine Department, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA Academic Editor: Christos D. Lionis Copyright © 2015 Omar Nadhem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 54-year-old white female with hypothyroidism presented with abdominal pain, nausea, vomiting, and diarrhea. She was found to have diabetic ketoacidosis (DKA) and admitted to our hospital for treatment. Laboratory workup revealed positive antiglutamic acid decarboxylase antibodies and subsequently she was diagnosed with latent onset autoimmune diabetes in adult (LADA). She was successfully treated with insulin with clinical and laboratory improvement. Diagnosis of LADA has been based on three criteria as given by The Immunology of Diabetes Society: (1) adult age of onset (>30 years of age); (2) presence of at least one circulating autoantibody (GADA/ICA/IAA/IA-2); and (3) initial insulin independence for the first six months. The importance of this case is the unlikely presentation of LADA. We believe that more research is needed to determine the exact proportion of LADA patients who first present with DKA, since similar cases have only been seen in case reports. Adult patients who are obese and have high blood sugar may deserve screening for LADA, especially in the presence of other autoimmune diseases. Those patients once diagnosed with LADA need extensive diabetic education including potentially serious events such as diabetic ketoacidosis. 1. Introduction Latent autoimmune diabetes in adult (LADA) is an autoimm Continue reading >>
Latent Autoimmune Diabetes In Adults
Latent autoimmune diabetes in adults (LADA) is very similar to type 1 diabetes. It is considered an autoimmune disease, meaning that your own immune system attacks and destroys insulin-producing cells in your pancreas. But LADA also shares genetic similarities to type 2 diabetes. People with LADA are usually older than 35, not obese and were able to control their diabetes initially with meal planning. However, within six months, meal planning no longer controls the diabetes and you become dependent on insulin to survive. There’s another related form of diabetes that’s called type 1.5. It’s a subset of LADA and involves people with similar experiences except that they are obese. The treatment for type 1.5 diabetes is the same as for LADA. Symptoms of LADA may occur suddenly and could include: Extreme thirst Frequent urination Drowsiness or lethargy Sugar in urine Sudden vision changes Increased appetite Sudden weight loss Fruity or sweet odor on the breath Heavy, labored breathing Stupor or unconsciousness If you experience any of these symptoms, contact your health-care provider immediately. Causes The exact causes of LADA are not known, although researchers have identified certain genes that are associated with a higher diabetes risk. Risk Factors Having a close relative with LADA increases your risk of developing the condition. Diagnosis The following tests are used for diagnosing diabetes: Fasting plasma glucose test: Measures your blood glucose after you have fasted for at least eight hours Oral glucose tolerance test: Measures your blood glucose after fasting for at least eight hours — and two hours after you drink a glucose-containing beverage. Random plasma glucose test (also called a casual plasma glucose test): Measures blood glucose without regard to w Continue reading >>
Latent Autoimmune Diabetes In Adults
Abstract Abstract: Latent autoimmune diabetes in adults (LADA) is a special form of diabetes that is clinically similar to type 2 diabetes but with positivity for pancreatic autoantibodies. The frequency of LADA patients among all patients diagnosed as type 2 varies between 6-50% in various populations. The frequency is higher in younger age groups. It is clear, however, that the frequency of autoimmune diabetes among adults is underestimated. Clinical features such as age and severity of symptoms are of no help in identifying these patients. Body mass index and C peptide levels in the general population increase with age, and these parameters are of limited use in identifying LADA patients. Determination of autoantibodies is necessary in order to correctly classify the type of diabetes. Among antibodies, GADA is the most frequently occurring autoantibody, followed by ICA. The natural course of these patients shows that C peptide will decrease with time in parallel with the curve for C peptide in classical type 1 diabetic patients. Most of the LADA patients will require insulin within three years. Our recommendation is that all patients be tested for pancreatic islet autoantibodies at diagnosis of diabetes to enable correct diagnosis and to avoid future failure of hypoglycemic agents and risk of complications due to hyperglycemia. It is still unclear whether early treatment with insulin is beneficial for the remaining beta cells. Continue reading >>
Increased Seroreactivity To Proinsulin And Homologous Mycobacterial Peptides In Latent Autoimmune Diabetes In Adults
Abstract Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity. Continue reading >>
Randomized Controlled Trial Of Insulin Versus Tablets For Latent Autoimmune Diabetes In Adults (lada) (lit)
Background: Latent autoimmune diabetes in adults [LADA] is a type 1 diabetes that is slowly developing. This means many people are treated as having type 2 diabetes at diagnosis as they are adults who are not immediately insulin dependent. LADA can be distinguished from type 2 diabetes by antibody tests. Patients who are antibody positive have an autoimmune reaction which is similar to that of type 1 diabetes and is not found in type 2 diabetes. We would like to examine the best way of treating LADA in the early phase of the conditions, with tablets (similar to type 2 diabetes) or with insulin (similar to type 1 diabetes). Methods/Design: This is an open parallel group prospective randomised trial. Participants need to have a GAD antibody test results of 101 WHO units or more and a diagnosis of diabetes not requiring insulin at diagnosis. Participants will need to have been diagnosed within 12 months and not treated with insulin at study entry. They will be randomised to receive either insulin (NovoMix 30) or tablets (diet treated followed by metformin followed by glitazone (with or without metformin) followed by insulin). Primary outcome assessment will be for change in HbA1c and change in fasting C-peptide over 24 months. Secondary outcome measures will include Quality of life, GAD antibody levels, adverse events, inflammatory markers, insulin resistance, and markers of the metabolic syndrome. Discussion: This study seeks the best treatment for early LADA in terms of maintaining glycaemic control and maintaining natural insulin production. Study Type : Interventional (Clinical Trial) Estimated Enrollment : 200 participants Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: Randomized, Co Continue reading >>
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Latent Autoimmune Diabetes In Adults
Definition, Prevalence, β-Cell Function, and Treatment Abstract Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune β-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of β-cell function show that LADA patients with multiple islet antibodies develop β-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop β-cell failure after 5 years. Even though it may take up to 12 years until β-cell failure occurs in some patients, impairments in the β-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive β-cell failure might be a more adequate concept. In agreement with proved impaired β-cell function at diagnosis of diabetes, insulin is the treatment of choice. In 1986, Groop et al. (1) reported a subgroup of type 2 diabetic patients who, despite having islet autoantibodies, showed preserved β-cell function. The type of diabetes in these patients was referred to as latent type 1 diabetes, showing clearly different features from classic type 1 and classic type 2 diabetes. Later, Tuomi et al. (2) and Zimmet et al. (3) launched the eponym LADA (latent autoimmune diabetes in adults) for this slowly progressive form of autoimmune diabetes initially managed with diet and oral hypoglycemic agents before becoming insulin Continue reading >>
Diabetes Lada
Tweet LADA stands for Latent Autoimmune Diabetes of Adulthood. LADA is a form of type 1 diabetes that develops later into adulthood. LADA tends to develop more slowly than type 1 diabetes in childhood and, because LADA can sometimes appear similar to type 2 diabetes, doctors may mistakenly diagnose LADA as type 2 diabetes. The definition provided by Prof. David Leslie, Principle Investigator of Action LADA, is that in Europe: LADA is defined as initially non-insulin requiring diabetes diagnosed in people aged 30-50 years with antibodies to GAD - glutamic acid decarboxylase. How does LADA compare with other diabetes types? LADA is sometimes referred to as type 1.5 diabetes. This is not an official term but it does illustrate the fact that LADA is a form of type 1 diabetes that shares some characteristics with type 2 diabetes. As a form of type 1 diabetes, LADA is an autoimmune disease in which the body’s immune system attacks and kills off insulin producing cells. The reasons why LADA can often be mistaken for type 2 diabetes is it develops over a longer period of time than type 1 diabetes in children or younger adults. Whereas type 1 diabetes in children tends to develop quickly, sometimes within the space of days, LADA develops more slowly, sometimes over a period of years. The slower onset of diabetes symptoms being presented in people over 35 years may lead a GP to initially diagnose a case of LADA as type 2 diabetes. Symptoms of LADA The first symptoms of LADA include: Feeling tired all the time or regularly tired after meals Foggy headedness Experiencing hunger soon after meals As LADA develops, a person’s ability to produce insulin will gradually decrease and this may lead to symptoms such as: It is important to catch the symptoms at the earliest stage because Continue reading >>
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