Maturity-onset diabetes of the young MODY

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). 

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)... 

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... 

---