MODY maturity onset diabetes of the

Type 1 diabetes, formerly known as childhood , juvenile or insulin-dependent diabetes, is not exclusively a childhood problem. Adults who contract type 1 diabetes may be misdiagnosed with type 2 diabetes. A subtype of type 1 (identifiable by the presence of antibodies against /3-cells) typically develops slowly and is often confused with type 2. In addition, a small proportion of type 1 cases have the hereditary condition maturity onset diabetes of the young (MODY), which can also be confused with type 2. 

Diabetic patients under 30 years almost all need insulin the exception is the rare single-gene disorder of Maturity Onset Diabetes of the Young (MODY) due usually to mutations in the glucoki-nase gene. 

Maturity-onset diabetes of the young (MODY) is characterized by type 2 diabetes at or before adolescence. It is a genetically heterogeneous disease, for which at least five different genes have been identified. MODY3, one of the most common forms, is characterized by a mutation in the hepatocyte nuclear factor (HNF)-lo gene. MODY3 can be very sensitive to sulfonylureas (SEDA-22, 475) (9,10). 

Type-11 diabetes meilitus is defined and classified as non-insulin-dependent, although many patients receive insulin to improve their glycaemic control there is a relative deficit in insulin-secretory capacity. Maturity-onset diabetes of the young (MODY) and gestational diabetes are both variants of Type-II diabetes meilitus. There are two subgroups of Type-II normal-weight type Ila and obese-type lib. 

Type 2 Diabetes Mellitus This is the most prevalent form of diabetes and is characterized by both an insulin secretion defect and insulin resistance. Maturity-onset diabetes of the young (MODY), attributable to mutations of the glucose kinase gene (discussed earlier), may also be classified as type 2 diabetes mellitus. Obesity is a contributory factor and may predispose to insulin resistance with eventual development of type 2 diabetes mellitus. The precise mechanism by which obesity leads to insulin resistance in the target tissues is not understood. However, in several animal models (e.g., ob/ob mouse, db/db mouse) mutations have been identified that cause both obesity and diabetes mellitus. Unlike type 1 diabetes mellitus, type 2 is not an autoimmune disease. Studies with monozygotic twins have revealed a 90% concordance rate for type 2 diabetes mellitus, suggesting the involvement of genetic factors in the development of the disease. 

Maturity-onset diabetes of the young (MODY) is an autosomal dominantly inherited form of diabetes typically diagnosed before the age of 25 years that is characterised by 3-cell dysfunction. There are a number of MODY subtypes caused by mutations in different P-cell genes. The two most common subtypes in the UK are GCK-MODY due to inactivating GCK mutations and HNFIA-MODY due to inactivating mutations in a key transcription factor regulating insulin synthesis and secretion (HNFIA or hepatocyte nuclear factor 1 alpha gene name HNFIA). 

Glucokinase is less active causing decreased 3-cell glucose metabolism resulting in decreased insulin secretion and maturity-onset diabetes of the young (GCK-MODY)... 

Diabetes mellitus (DM) is characterised by hyperglycaemia due to defective insulin secretion, defective insulin action or both. The global prevalence in 2010 is 285 million cases and this is projected to be 439 million in 2030. The main types are type 1 DM (TIDM) and type 2 DM (T2DM). There is also gestational DM and other unusual types such as maturity-onset diabetes of the young (MODY). 

Monogenic diabetes or maturity-onset diabetes of the young (MODY)... 

The term maturity-onset diabetes of the young was coined in 1974 when maturity-onset diabetes described what is now T2DM. MODY is currently being replaced with the nomenclature monogenic diabetes. 

This problem concerns a small number of families with a clear pattern of dominant inheritance of an unusual form of diabetes (section 10.7) that can be classified as noninsulin dependent, as those affected secrete significant amounts of insulin (although less than normal subjects), but which develops in early childhood. It is generally referred to as maturity-onset diabetes of the young (MODY). 

Reznik Y, Dao T, Coutant R, et al (2004) Hepatocyte nuclear factor-1 alpha gene inactivation cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families. J Clin Endocrinol Metab 89 1476-1480 Russmann S, Zimmermann A, Krahenbuhl S, et al (2001) Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. Eur J Gastroenterol Hepatol 13 287-290... 

This is cliitically important because a failure to control the blood glucose level adequately can lead to diabetes melUtus. Therefore, it can be argued that glucokinase is essential to prevent the development of diabetes in normal humans. Indeed, a deficiency of glucokinase in the P-cell gives rise to one type of diabetes, known as maturity onset diabetes in the young (MODY). 

Type 1 DM idiopathic is a nonimmune form of diabetes frequently seen in minorities with intermittent insulin requirements. The prevalence of type 1 DM has been increasing over the last one hundred years. Maturity onset diabetes of youth (MODY), which has an identifiable genetic defect in the glucokinase gene, and endocrine disorders such as acromegaly and Cushing s syndrome, can be secondary causes of DM. These unusual etiologies, however, only account for 1% to 2% of the total cases of type 2 DM. See the section on other forms of diabetes mellitus later in this chapter for further discussion. 

Maturity onset diabetes of youth (MODY) is characterized by impaired insulin secretion with minimal or no insulin resistance. Patients typically exhibit mild hyperglycemia at an early age. The disease is inherited in an autosomal dominant pattern with at least three different... 

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