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LADA (Latent Autoimmune Diabetes in Adults) Definition & prevalence
LADA is the common term describing patients with a type 2 diabetic phenotype combined with islet antibodies & slowly progressive β-cell failure. If it is defined as a type 2 diabetic phenotype combined with islet antibodies, the prevalence of LADA (Latent Autoimmune Diabetes in Adults) is a approximately 10% among incident case subjects of diabetes aged between 40–75 years. A like prevalence is found among non-insulin-requiring cases older than 35 yrs at diagnosis with phenotypic type 2 diabetes. In reality, a similar frequency of LADA (∼10%) was found among type 2 diabetic patients of all ages in the U.K. Among type 2 diabetic patients younger than 35 years of age at diagnosis, the frequency of LADA is much higher (∼25%). Although LADA patients by definition are not insulin requiring at & during the first time after diagnosis of diabetes, within 6 years, β-cell function is severely impaired, leading to insulin dependency in most LADA patients. Nevertheless, β-cell failure, defined as not measurable fasting C-peptide, may take up to 12 years until it occurs in patients with islet antibodies. It is important to clarify that obesity does not exclude LADA. Obese type 2–like diabetic patients with islet antibodies show progressive β-cell failure. In agreement, Juneja et al. found that only islet antibodies (islet cell antibodies [ICAs] or GAD antibodies [GADAs]) defined “LADA” (≈ type 1 1/2 diabetes); not BMI, age, or clinical presentation. High concentrations of islet antibodies predict future β-cell failure, whereas a low number of islet antibodies, particularly lack of ICAs, is associated with lack of progression to β-cell failure. Although LADA is considered to be confined to adulthood, Lohmann et al. recently introduced the term “LADY-like” (latent autoimmune diabetes in the young) based on two children diagnosed with islet antibodies without insulin dependency, who later showed slowly progressive β-cell failure. A similar observation in a Turkish case gave birth to another eponym: LADC (latent autoimmune diabetes in children). The rising prevalence of obesity among children indicates that assessment for islet antibodies will be increasingly important. Without determination of islet antibodies, it is not possible to separate type 1 diabetes from type 2 diabetes among obese children. Slowly progressive autoimmune diabetes is a growing problem in children.
To distinguish LADA (Latent Autoimmune Diabetes in Adults) from classic type 1 diabetes, HLA studies may be of value. Although it has been suggested that LADA deviates from classic type 1 diabetes, others have found classic type 1 diabetes risk HLA genotypes in LADA. Indeed, low frequencies of type 1 diabetes protective HLA genotypes, particularly HLA DQA1-DQB1*0102(3)-*0602(3)/X, are associated with LADA. It has been claimed that there might be a co-segregation between type 1 & type 2 diabetes in the context of LADA . An assumption that LADA may be a feature of a general autoimmune tendency has support from an increased frequency of serological markers of thyroid & adrenal disease in type 2 diabetic patients with GADAs. Antibodies associated with celiac disease are also found more often in LADA patients than in type 2 diabetic patients. However, these antibodies are also more frequent than expected in classic type 1 diabetic patient & thereby cannot be used to separate LADA from classic type 1 diabetes.
Most recently, the eponym ADA (autoimmune diabetes in adults) has been suggested to replace the term LADA for diabetic patients with islet antibodies without a need for insulin treatment for at least the first 6 months after diagnosis. ADA is meant to distinguish slowly progressive autoimmune diabetes from the classic rapid onset autoimmune type 1 diabetes.
Definition of MODY (Maturity onset diabetes of the young)
MODY refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene (sex independent, i.e. inherited from any of the parents) disrupting insulin production. MODY (Maturity onset diabetes of the young) is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (especially type 1 & type 2), which involve more complex combinations of causes involving multiple genes (i.e., "polygenic") & environmental factors. MODY 2 & MODY 3 are the most common forms. MODY is a rare autosomal dominant form of type 2 DM affecting young people with a positive family history. MODY should not be confused with latent autoimmune diabetes of adults (LADA) — a form of type 1 DM, with slower progression to insulin dependence in later life
Types of MODY (Maturity onset diabetes of the young)
MODY 1 - Due to a loss-of-function mutation in the HNF4α gene. 5%–10% cases.
MODY 2 - Due to any of several mutations in the GCK gene. 30%–70% cases. Mild fasting hyperglycaemia throughout life. Small rise on glucose loading.
MODY 3 - Mutations of the HNF1α gene (a homeobox gene). 30%–70% cases. Tend to be responsive to sulfonylureas. Low renal threshold for glucose.
MODY 4 - Mutations of the IPF1 homeobox (Pdx1) gene. < 1% cases. Associated with pancreatic agensis in homozygotes and occasionally in heterozygotes.
MODY 5 - One of the less common forms of MODY, with some distinctive clinical features, including atrophy of the pancreas and several forms of renal disease. Defect in HNF-1 beta gene. 5%–10% cases.
MODY 6 - Mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. Very rare: 5 families reported to date.
MODY 7 - KLF11 has been associated with a form of diabetes that has been characterized as MODY 7 by OMIM.
MODY 8 - CEL has been associated with a form of diabetes that has been characterized as MODY 8 by OMIM.It is very rare with five families reported to date. It is associated with exocrine pancreatic dysfunction.
MODY 9 - Pax4 is a transcription factor. MODY 9 is a very rare medical condition.
MODY 10 - Mutations in the insulin gene. Usually associated with neonatal diabetes. Rare < 1% cases.
MODY 11 - Mutated B-lymphocyte tyrosin kinase, which is also present in pancreatic islet cells. Very rare.
Definition of diabetes insipidus
A condition characterised by frequent & heavy urination, excessive thirst & an overall feeling of weakness. This condition may be caused by a defect in the pituitary gl& or in the kidney. In diabetes insipidus, blood glucose levels are normal.
Definition of diabetes mellitus
a condition characterised by hyperglycemia resulting from the body's inability to use blood glucose for energy. In Type 1 diabetes, the pancreas no longer makes insulin & therefore blood glucose cannot enter the cells to be used for energy. In Type 2 diabetes, either the pancreas does not make enough insulin or the body is unable to use insulin correctly.
Definition of diabetic diarrhea
Symptoms in diabetes - loose stools, fecal incontinence, or both that result from an overgrowth of bacteria in the small intestine & diabetic neuropathy in the intestines. This nerve damage can also result in constipation.
Definition of diabetic ketoacidosis
Symptoms in diabetes - an emergency condition in which extremely high blood glucose levels, along with a severe lack of insulin, result in the breakdown of body fat for energy & an accumulation of ketones in the blood & urine. Signs of DKA are nausea & vomiting, stomach pain, fruity breath odor & rapid breathing. Untreated DKA can lead to coma & death.
Definition of diabetic mastopathy
Symptoms in diabetes - a rare fibrous breast condition occurring in women, & sometimes men, with long-st&ing diabetes. The lumps are not malignant & can be surgically removed, although they often recur.
Definition of diabetic myelopathy
Symptoms in diabetes - damage to the spinal cord found in some people with diabetes.
Definition of diabetic retinopathy
Symptoms in diabetes - diabetic eye disease; damage to the small blood vessels in the retina. Loss of vision may result.
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