Maturity onset diabetes of the young
Encyclopedia
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 is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes (i.e., "polygenic") and environmental factors. MODY 2 and MODY 3 are the most common forms. The severity of the different types varies considerably, but most commonly MODY acts like a very mild version of type 1 diabetes, with continued partial insulin production and normal insulin sensitivity. MODY is not type 2 diabetes in a young person, as might erroneously be inferred from the name.
without progression to diabetic ketosis or ketoacidosis
. In retrospect we can now recognize that this category covered a heterogeneous collection of disorders which included cases of dominantly inherited diabetes (the topic of this article, still called MODY today), as well as cases of what we would now call type 2 diabetes occurring in childhood or adolescence, and a few even rarer types of hyperglycemia (e.g., mitochondrial diabetes or mutant insulin). Many of these patients were treated with sulfonylurea
s with varying degrees of success.
The current usage of the term MODY dates from a case report published in 1974. This milder form of diabetes had been recognised in the pre insulin period. This was forgotton posibly because of Joslin's dictum that all young people with diabetes should be treated with insulin. With the introduction of sulphonylureas in the 1950s it was found that tolbutamide
could improve or normalize carbohydrate tolerance in some young non-obese mildly diabetic patients. The geentic basis was over looked because it was thought that diabetes was a homogeneous disease with young and old patients forming part of the same continuum. In 1973 Fajans had shown that the carbohydrate intolerance of 45 patients diagnosed under age 25 had not progressed after up to 16 years on sulphonylureas and that 43 out of 45 of these subjects had a first degree relative with diabetes. In the same year Lestradet also described a non-insulin-dependent form of childhood diabetes which was later established to be dominantly inherited. In 1974 Tattersall described three families in which diabetes, although diagnosed in adolescence, could be treated with sulphonylureas over 40 years later and was dominantly inherited. Also in 1974 Tattersall and Fajans coined the acronym MODY which was defined as 'fasting hyperglycaemia diagnosed under age 25 which could be treated without insulin for more than two years'.
By the 1990s, as the understanding of the pathophysiology of diabetes has improved, the concept and usage of "MODY" have become refined and narrower. It is now used as a synonym for dominantly inherited, monogenic defects of insulin secretion occurring at any age, and no longer includes any forms of type 2 diabetes.
There are two general types of clinical presentation.
MODY cases may make up as many as 5% of presumed type 1 and type 2 diabetes cases in a large clinic population. While the goals of diabetes management are the same no matter what type, there are two primary advantages of confirming a diagnosis of MODY.
As it occurs infrequently, many cases of MODY are initially assumed to be more common forms of diabetes: type 1 if the patient is young and not overweight, type 2 if the patient is overweight, or gestational diabetes
if the patient is pregnant. Standard diabetes treatments (insulin for type 1 and gestational diabetes, and oral hypoglycemic agents for type 2) are often initiated before the doctor suspects a more unusual form of diabetes.
The diagnosis of MODY is confirmed by specific gene
testing, now available through several commercial laboratories.
β-cells
. Several of the defects are mutation
s of transcription factor
gene
s. One form is due to mutations of the glucokinase
gene. For each form of MODY, multiple specific mutations involving different amino acid
substitutions have been discovered. In some cases, there are significant differences in the activity of the mutant gene product that contribute to variations in the clinical features of the diabetes (such as degree of insulin deficiency or age of onset).
differs between the types (from 40% to 90%).
Homozygous mutations in the other forms have not yet been described. Those mutations for which a homozygous form has not been described may be extremely rare, or may result in clinical problems not yet recognized as connected to the monogenic disorder, or may be lethal for a fetus and not result in a viable child.
Tools available for management are also those available for all forms of diabetes: blood testing, changes in diet
, physical exercise, oral hypoglycemic agents, and insulin injections. In many cases these goals can be achieved more easily with MODY than with ordinary types 1 and 2 diabetes. Some people with MODY may require insulin injections to achieve the same glycemic control that another person may attain with careful eating or an oral medication.
When oral hypoglycemic agents are used in MODY, the sulfonylureas remain the oral medication of first resort. When compared to patients with type 2 diabetes, MODY patients are often more sensitive to sulphonylureas, such that a lower dose should be used to initiate treatment to avoid hypoglycaemia. Patients with MODY less often suffer from obesity and insulin resistance
than those with ordinary type 2 diabetes (for whom insulin sensitizers like metformin
or the thiazolidinedione
s are often preferred over the sulfonylureas).
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
forms of diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
caused by mutations in an autosomal dominant gene (sex independent, i.e. inherited from any of the parents) disrupting insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
production. MODY is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes (i.e., "polygenic") and environmental factors. MODY 2 and MODY 3 are the most common forms. The severity of the different types varies considerably, but most commonly MODY acts like a very mild version of type 1 diabetes, with continued partial insulin production and normal insulin sensitivity. MODY is not type 2 diabetes in a young person, as might erroneously be inferred from the name.
History of the concept and treatment of MODY
The term MODY dates back to 1964, when diabetes mellitus was considered to have two main forms: juvenile-onset and maturity-onset, which roughly corresponded to what we now call type 1 and type 2. MODY was originally applied to any child or young adult who had persistent, asymptomatic hyperglycemiaHyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
without progression to diabetic ketosis or ketoacidosis
Diabetic ketoacidosis
Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...
. In retrospect we can now recognize that this category covered a heterogeneous collection of disorders which included cases of dominantly inherited diabetes (the topic of this article, still called MODY today), as well as cases of what we would now call type 2 diabetes occurring in childhood or adolescence, and a few even rarer types of hyperglycemia (e.g., mitochondrial diabetes or mutant insulin). Many of these patients were treated with sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
s with varying degrees of success.
The current usage of the term MODY dates from a case report published in 1974. This milder form of diabetes had been recognised in the pre insulin period. This was forgotton posibly because of Joslin's dictum that all young people with diabetes should be treated with insulin. With the introduction of sulphonylureas in the 1950s it was found that tolbutamide
Tolbutamide
Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug sold under the brand name Orinase. This drug may be used in the management of type II diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas...
could improve or normalize carbohydrate tolerance in some young non-obese mildly diabetic patients. The geentic basis was over looked because it was thought that diabetes was a homogeneous disease with young and old patients forming part of the same continuum. In 1973 Fajans had shown that the carbohydrate intolerance of 45 patients diagnosed under age 25 had not progressed after up to 16 years on sulphonylureas and that 43 out of 45 of these subjects had a first degree relative with diabetes. In the same year Lestradet also described a non-insulin-dependent form of childhood diabetes which was later established to be dominantly inherited. In 1974 Tattersall described three families in which diabetes, although diagnosed in adolescence, could be treated with sulphonylureas over 40 years later and was dominantly inherited. Also in 1974 Tattersall and Fajans coined the acronym MODY which was defined as 'fasting hyperglycaemia diagnosed under age 25 which could be treated without insulin for more than two years'.
By the 1990s, as the understanding of the pathophysiology of diabetes has improved, the concept and usage of "MODY" have become refined and narrower. It is now used as a synonym for dominantly inherited, monogenic defects of insulin secretion occurring at any age, and no longer includes any forms of type 2 diabetes.
Signs, symptoms and differential diagnosis
Currently MODY is the final diagnosis in 1-2% people initially diagnosed with diabetes. It prevelance is 70 - 110 per million population. 50% of first degree relatives will inherit the same mutation giving them a >95% lifetime risk of developing MODY themselves. For this reason correct diagnosis of this condition is important. Typically patients present with a strong family history of diabetes (any type) and the onset of symptoms is in the second to fifth decade.There are two general types of clinical presentation.
- Some forms of MODY produce significant hyperglycemiaHyperglycemiaHyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
and the typical signs and symptoms of diabetes: increased thirst and urination (polydipsia and polyuria). - In contrast, however, many people with MODY have no signs or symptoms and are diagnosed either by accident, when a high glucose is discovered during testing for other reasons, or screening of relatives of a person discovered to have diabetes. Discovery of mild hyperglycemia during a routine glucose tolerance testGlucose tolerance testA glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...
for pregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
is particularly characteristic.
MODY cases may make up as many as 5% of presumed type 1 and type 2 diabetes cases in a large clinic population. While the goals of diabetes management are the same no matter what type, there are two primary advantages of confirming a diagnosis of MODY.
- Firstly, insulin may not be necessary and it may be possible to switch a person from insulin injections to oral agents without loss of glycemic control.
- Secondly, it may prompt screening of relatives and so help identify other cases in family members.
As it occurs infrequently, many cases of MODY are initially assumed to be more common forms of diabetes: type 1 if the patient is young and not overweight, type 2 if the patient is overweight, or gestational diabetes
Gestational diabetes
Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy . It is widely accepted as a disease only in the United States, there is some question whether the condition is natural during pregnancy...
if the patient is pregnant. Standard diabetes treatments (insulin for type 1 and gestational diabetes, and oral hypoglycemic agents for type 2) are often initiated before the doctor suspects a more unusual form of diabetes.
Treatment
In some forms of MODY, standard treatment is appropriate, though exceptions occur:- In MODY2, oral agents are relatively ineffective and insulin is unnecessary.
- In MODY1 and MODY3, insulin may be more effective than drugs to increase insulin sensitivity.
- SulfonylureaSulfonylureaSulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
s are effective in the KATP channel forms of neonatal-onset diabetes.
Presentation of MODY
The following characteristics suggest the possibility of a diagnosis of MODY in hyperglycemic and diabetic patients:- Mild to moderate hyperglycemia (typically 130–250 mg/dl, or 7-14 mM/L) discovered before 30 years of age. However, anyone under 50 can develop MODY.
- A first-degree relative with a similar degree of diabetes.
- Absence of positive antibodies or other autoimmunityAutoimmunityAutoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
(e.g., thyroiditisThyroiditisThyroiditis is the inflammation of the thyroid gland. The thyroid gland is located on the front of the neck below the laryngeal prominence, and makes hormones that control metabolism.-Classification:...
) in patient and family. - Persistence of a low insulin requirement (e.g., less than 0.5 u/kg/day) past the usual "honeymoonHoneymoon period (diabetes)The honeymoon period for patients with Diabetes mellitus type 1 is the period that often follows diagnosis and initiation of insulin treatment. It is often suggestive of remission, but it is important to note that the two are unrelated - it is not a cure for type 1 diabetes...
" period. - Absence of obesity (although overweight or obese people can get MODY), or other problems associated with type 2 diabetes or metabolic syndromeMetabolic syndromeMetabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
(e.g. hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, hyperlipidemiaHyperlipidemiaHyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
, polycystic ovary syndromePolycystic ovary syndromePolycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
). - Insulin resistanceInsulin resistanceInsulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
very rarely happens. - Cystic kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
disease in patient or close relatives. - Non-transient neonatal diabetes, or apparent type 1 diabetes with onset before 6 months of age.
- Liver adenoma or hepatocellular carcinoma in MODY type 3
- Renal cysts, rudimentary or bicornuate uterus, vaginal aplasia, absence of the vas deferens, epidymal cysts in MODY type 5
The diagnosis of MODY is confirmed by specific gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
testing, now available through several commercial laboratories.
Pathophysiology
The recognised forms of MODY are all due to ineffective insulin production or release by pancreaticPancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
β-cells
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
. Several of the defects are mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s of transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s. One form is due to mutations of the glucokinase
Glucokinase
Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver, pancreas, gut, and brain of humans and most other vertebrates...
gene. For each form of MODY, multiple specific mutations involving different amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
substitutions have been discovered. In some cases, there are significant differences in the activity of the mutant gene product that contribute to variations in the clinical features of the diabetes (such as degree of insulin deficiency or age of onset).
Genetics
Some sources make a distinction between two different forms of monogenetic diabetes: MODY and neonatal diabetes. However, they have much in common, and are often studied together.Heterozygous
MODY is inherited in an autosomal dominant fashion, and most patients therefore have other members of the family with diabetes; penetrancePenetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait . In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms...
differs between the types (from 40% to 90%).
| Type | OMIM | Gene/protein | Description |
|---|---|---|---|
| MODY 1 MODY 1 MODY 1 is a form of maturity onset diabetes of the young.MODY 1 is due to a loss-of-function mutation in the gene on chromosome 20. This gene codes for HNF4-α protein also known as transcription factor 14 . HNF4α controls function of HNF1α and perhaps HNF1β as well... |
hepatocyte nuclear factor 4α | Due to a loss-of-function mutation in the HNF4α gene. 5 - 10% cases. | |
| MODY 2 MODY 2 MODY 2 is a form of maturity onset diabetes of the young.MODY 2 is due to any of several mutations in the GCK gene on chromosome 7 for glucokinase. Glucokinase serves as the glucose sensor for the beta cell. Normal glucokinase triggers insulin secretion as the glucose exceeds about 90 mg/dl... |
glucokinase Glucokinase Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver, pancreas, gut, and brain of humans and most other vertebrates... |
Due to any of several mutations in the GCK gene. 30 - 70% cases. Mild fasting hyperglycaemia throughout life. Small rise on glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... loading. |
|
| MODY 3 MODY 3 MODY 3 is a form of maturity onset diabetes of the young.MODY 3 is caused by mutations of the HNF1α gene, a homeobox gene on chromosome 12. This is the most common type of MODY in populations with European ancestry, accounting for about 70% of all cases in Europe... |
hepatocyte nuclear factor 1α | Mutations of the HNF1α HNF1A HNF1 homeobox A , also known as HNF1A, is a human gene.The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes.-Interactions:HNF1A has been shown to interact with PCAF, Src,... gene (a homeobox Homeobox A homeobox is a DNA sequence found within genes that are involved in the regulation of patterns of anatomical development in animals, fungi and plants.- Discovery :... gene). 30 - 70% cases. Tend to be responsive to sulfonylurea Sulfonylurea Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide... s. Low renal threshold for glucose. |
|
| MODY 4 MODY 4 MODY 4 is a form of maturity onset diabetes of the young.MODY 4 arises from mutations of the Pdx-1 homeobox gene on chromosome 13. Pdx-1 is a transcription factor vital to the development of the embryonic pancreas... |
insulin promoter factor-1 | Mutations of the IPF1 homeobox Homeobox A homeobox is a DNA sequence found within genes that are involved in the regulation of patterns of anatomical development in animals, fungi and plants.- Discovery :... (Pdx1) gene. < 1% cases. Associated with pancreatic agensis in homozygotes and occasionally in heterozygotes. |
|
| MODY 5 MODY 5 Renal cysts and diabetes syndrome , also known as MODY 5, is a form of maturity onset diabetes of the young.HNF1β-related MODY is one of the less common forms of MODY, with some distinctive clinical features, including atrophy of the pancreas and several forms of renal disease... |
hepatocyte nuclear factor 1β | One of the less common forms of MODY, with some distinctive clinical features, including atrophy of the pancreas and several forms of renal Kidney The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and... disease. Defect in HNF-1 beta HNF1B HNF1 homeobox B , also known as HNF1B or transcription factor 2 , is a human gene.-Further reading:... gene. 5 - 10% cases. |
|
| MODY 6 MODY 6 MODY 6 is a form of maturity onset diabetes of the young.MODY 6 arises from mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. The gene is on chromosome 2 in a region of the p arm known as IDDM7 because it includes genes affecting susceptibility to type... |
neurogenic differentiation 1 | Mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. Very rare - 5 families reported to date. | |
| MODY 7 | Kruppel-like factor 11 | KLF11 KLF11 Krueppel-like factor 11 is a protein that in humans is encoded by the KLF11 gene.... has been associated with a form of diabetes that has been characterized as "MODY7" by OMIM. |
|
| MODY 8 | Bile salt dependent lipase | CEL Bile salt dependent lipase Bile salt-dependent lipase , also known as carboxyl ester lipase is an enzyme produced by the adult pancreas and aids in the digestion of fats. Bile salt-stimulated lipase is an equivalent enzyme found within breast milk. BSDL has been found in the pancreatic secretions of all species in which it... has been associated with a form of diabetes that has been characterized as "MODY8" by OMIM. Very rare - 5 families reported to date. Associated with exocrine pancreatic dysfunction. |
|
| MODY 9 | PAX4 PAX4 Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 gene.- Function :This gene is a member of the paired box family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain... |
||
| MODY 10 | INS Insulin Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle.... |
Mutations in the insulin gene. Usually associated with neonatal diabetes. Rare < 1% cases. | |
| Permanent neonatal diabetes mellitus Permanent neonatal diabetes mellitus A newly identified and potentially treatable form of monogenic diabetes is the neonatal diabetes caused by activating mutations of the KCNJ11 gene, which codes for the Kir6.2 subunit of the beta cell KATP channel.... |
KCNJ11 and ABCC8 ABCC8 ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.-External links:* *... |
A newly identified and potentially treatable form of monogenic diabetes is the neonatal diabetes caused by activating mutations of the ABCC8 ABCC8 ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.-External links:* *... or KCNJ11 genes which encode subunits of the KATP channel. < 1% cases. Tend to respond to sulfonylurea Sulfonylurea Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide... s. |
|
| Transient neonatal diabetes mellitus Transient neonatal diabetes mellitus Transient neonatal diabetes mellitus is a form of diabetes mellitus presenting at birth that is not permanent.Types include:It is to do with genetics and is often associated with having an added Chromosome 7 gene .... |
|
ABCC8 ABCC8 ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.-External links:* *... |
Some forms of neonatal-onset diabetes are not permanent. < 1% cases. Tend to respond to sulfonylurea Sulfonylurea Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide... s. |
Homozygous
By definition, the forms of MODY are autosomal dominant, requiring only one abnormal gene to produce the disease; the severity of the disease is moderated by the presence of a second, normal allele which presumably functions normally. However, conditions involving people carrying two abnormal alleles have been identified. Unsurprisingly, combined (homozygous) defects of these genes are both much rarer and much more severe in their effects.- MODY2: Homozygous glucokinase deficiency causes severe congenital insulin deficiency resulting in persistent neonatal diabetes mellitusNeonatal diabetes mellitusNeonatal diabetes mellitus is a monogenic form of diabetes that occurs in the first 6 months of life. It is a rare disease, occurring in only one in 100,000 to 500,000 live births. Infants with NDM do not produce enough insulin, leading to an increase in blood glucose...
. About 6 cases have been reported worldwide. All have required insulin treatment from shortly after birth. The condition does not seem to improve with age.
- MODY4: Homozygous IPF1 results in failure of the pancreas to form. Congenital absence of the pancreas, termed pancreatic agenesis, involves deficiency of both endocrine and exocrine functions of the pancreas.
Homozygous mutations in the other forms have not yet been described. Those mutations for which a homozygous form has not been described may be extremely rare, or may result in clinical problems not yet recognized as connected to the monogenic disorder, or may be lethal for a fetus and not result in a viable child.
Management
Unfortunately, chronic hyperglycemia of any cause can eventually cause blood vessel damage and the microvascular complications of diabetes. The principal treatment goals for people with MODY — keeping the blood sugars as close to normal as possible ("good glycemic control"), while minimizing other vascular risk factors — are the same for all known forms of diabetes.Tools available for management are also those available for all forms of diabetes: blood testing, changes in diet
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
, physical exercise, oral hypoglycemic agents, and insulin injections. In many cases these goals can be achieved more easily with MODY than with ordinary types 1 and 2 diabetes. Some people with MODY may require insulin injections to achieve the same glycemic control that another person may attain with careful eating or an oral medication.
When oral hypoglycemic agents are used in MODY, the sulfonylureas remain the oral medication of first resort. When compared to patients with type 2 diabetes, MODY patients are often more sensitive to sulphonylureas, such that a lower dose should be used to initiate treatment to avoid hypoglycaemia. Patients with MODY less often suffer from obesity and insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
than those with ordinary type 2 diabetes (for whom insulin sensitizers like metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
or the thiazolidinedione
Thiazolidinedione
The thiazolidinediones , also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.- Mechanism of action :...
s are often preferred over the sulfonylureas).