MODY

Genetic defects of insulin secretion Maturity-onset diabetes of the young

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent or maturity-onset type diabetes in children and young adults inherited in an autosomal-dominant pattern. MODY, which may account for 15% of all cases of diabetes in industrialized countries, is a heterogeneous group of disorders. MODY is caused by mutations of genes expressed in the -cell. Mutations in six genes have been described. Mild asymptomatic hyperglycemia in non-obese children, adolescents, and young adults who have a family history of diabetes in successive generations is the most common clinical presentation. The diagnosis should be considered whenever three or more consec- utive generations are affected by diabetes in an auto- somal-dominant fashion. Pancreatic auto-antibodies are typically absent. The diagnosis is usually made on clinical grounds. Confirmation of the diagnosis and identification of the specific t ype of MODY require molecular genetic testing. Some patients have mild fasting hyperglycemia, whereas others have varying degrees of glucose intol- erance for several years before developing persistent fasting hyperglycemia. Because mild hyperglycemia may not cause classic symptoms, diagnosis may be delayed until adulthood. In some cases, progression to overt symptomatic hyperglycemia requiring therapy with an oral hypoglycemic agent or insulin may be rapid. Most cases of MODY do not require insulin but do require careful monitoring to ensure good glycemic control to avoid complications. Exercise and nutri- tion to maintain normal weight and insulin sensitiv- ity should be emphasized; pharmacological treatment, when necessary, is tailored to the patients specific type of diabetes and level of hyperglycemia.

Treatment of MODY
Most cases of MODY do not require insulin but do require careful monitoring to insure good glycemic control to avoid complications. Exercise and nutrition to maintain normal weight and insulin sensitivity should be emphasized; pharmacologic treatment, when necessary, is tailored to the patients specific type of diabetes and level of hyperglycemia.

Kematangan-onset diabetes kaum muda (Mody) merupakan suatu bentuk 'kematangan-onset' diabetes non-insulin-dependent atau ketik anak-anak dan dewasa muda diwariskan dalam pola autosomal dominan. Mody, yang dapat menjelaskan 1-5% dari semua kasus diabetes di negaranegara industri-ized, adalah sekelompok heterogen gangguan. MODY disebabkan oleh mutasi gen diekspresikan dalam sel -. Mutasi pada gen enam telah dijelaskan. Hiperglikemia tanpa gejala ringan pada non-obesitas anak, remaja, dan dewasa muda yang memiliki riwayat keluarga diabetes pada generasi selanjutnya adalah presentasi klinis yang paling umum. Diagnosis harus dipertimbangkan ketika tiga atau lebih consec-utive generasi yang terkena diabetes dalam mode auto-Somal-dominan. Pankreas auto-antibodi yang biasanya absen. Diagnosis biasanya dibuat atas dasar klinis. Konfirmasi diagnosis dan identifikasi jenis tertentu MODY membutuhkan pengujian genetika molekuler. Beberapa pasien memiliki hiperglikemia puasa ringan, sedangkan yang lain memiliki berbagai tingkat glukosa intol-erance selama beberapa tahun sebelum mengembangkan hiperglikemia puasa persisten. Karena hiperglikemia ringan mungkin tidak menyebabkan gejala klasik, diagnosis mungkin tertunda hingga dewasa. Dalam beberapa kasus, perkembangan terapi hiperglikemia yang jelas gejala yang membutuhkan dengan agen hipoglikemik oral atau insulin mungkin cepat. Sebagian besar kasus Mody tidak memerlukan insulin tetapi memerlukan pemantauan yang cermat untuk memastikan kontrol glikemik yang baik untuk menghindari komplikasi. Latihan dan gizi untuk menjaga berat badan normal dan sensitivitas insulin harus ditekankan, pengobatan farmakologis, bila perlu, disesuaikan dengan jenis tertentu pasien diabetes dan tingkat hiperglikemia.

Karakteristik

Karakteristik Pola diturunkan Onset Pedigree Klinis Sindrom Metabolik

MODY Monogenik, autosomal dominan Anak-anak dan remaja (<25 tahun) biasanya multigenerasi tidak obesitas Tidak ada

Diabetes tipe 2 Polygenik dan lingkungan Dewasa (40-60 tahun) Jarang multigenerasi Obesitas Biasanya muncul

The liver-enriched transcription factors HNF-1a, HNF-1b, and HNF-4a were first discovered in studies designed to identify the proteins responsible for the tissue-specific regulation of gene expression in the liv- er.18 They are also found in other tissues and organs, including the pancreatic islets, the kidneys, and gen- ital tissues. HNF-1a and HNF-1b are members of a family of transcription factors. 18 HNF-4a is an orphan nuclear receptor.19 HNF-1a, HNF-1b, and HNF-4a constitute part of a network of transcription factors that function together to control gene expression dur- ing embryonic development and during adulthood in tissues in which they are coexpressed. In pancreatic beta cells, these transcription factors regulate the ex- pression of the insulin gene as well as the expression of genes encoding proteins involved in glucose transport and metabolism 20 and mitochondrial metabolism21 all of which are linked to insulin secretion. In the liver, these proteins regulate lipoprotein biosynthesis.22 The expression of HNF-1a is regulated at least in part by HNF-4a.21