A type of tumor of the pancreatic beta cells that secretes excess insulin and can result in hypoglycemia.

The presence of multiple pancreatic islet cell adenomas.

Type 2 diabetes mellitus is distinct from maturity-onset diabetes of the young (see 606391) in that it is polygenic, characterized by gene-gene and gene-environment interactions with onset in adulthood, usually at age 40 to 60 but occasionally in adolescence if a person is obese. The pedigrees are rarely multigenerational. The penetrance is variable, possibly 10 to 40% (Fajans et al., 2001). Persons with type 2 diabetes usually have an obese body habitus and manifestations of the so-called metabolic syndrome (see 605552), which is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia. Genetic Heterogeneity of Susceptibility to Type 2 Diabetes Susceptibility to T2D1 (601283) is conferred by variation in the calpain-10 gene (CAPN10; 605286) on chromosome 2q37. The T2D2 locus (601407) on chromosome 12q was found in a Finnish population. The T2D3 locus (603694) maps to chromosome 20. The T2D4 locus (608036) maps to chromosome 5q34-q35. Susceptibility to T2D5 (616087) is conferred by variation in the TBC1D4 gene (612465) on chromosome 13q22. A mutation has been observed in hepatocyte nuclear factor-4-alpha (HNF4A; 600281.0004) in a French family with NIDDM of late onset. Mutations in the NEUROD1 gene (601724) on chromosome 2q32 were found to cause type 2 diabetes mellitus in 2 families. Mutation in the GLUT2 glucose transporter was associated with NIDDM in 1 patient (138160.0001). Mutation in the MAPK8IP1 gene, which encodes the islet-brain-1 protein, was found in a family with type 2 diabetes in individuals in 4 successive generations (604641.0001). Polymorphism in the KCNJ11 gene (600937.0014) confers susceptibility. In French white families, Vionnet et al. (2000) found evidence for a susceptibility locus for type 2 diabetes on 3q27-qter. They confirmed the diabetes susceptibility locus on 1q21-q24 reported by Elbein et al. (1999) in whites and by Hanson et al. (1998) in Pima Indians. A mutation in the GPD2 gene (138430.0001) on chromosome 2q24.1, encoding mitochondrial glycerophosphate dehydrogenase, was found in a patient with type 2 diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type 2 diabetes. Triggs-Raine et al. (2002) stated that in the Oji-Cree, a gly319-to-ser change in HNF1-alpha (142410.0008) behaves as a susceptibility allele for type 2 diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type 2 diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type 2 diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type 2 diabetes in 1 family. A (single-nucleotide polymorphism) SNP in the 3-prime untranslated region of the resistin gene (605565.0001) was associated with susceptibility to diabetes and to insulin resistance-related hypertension in Chinese subjects. Susceptibility to insulin resistance has been associated with polymorphism in the TCF1 (142410.0011), PPP1R3A (600917.0001), PTPN1 (176885.0001), ENPP1 (173335.0006), IRS1 (147545.0002), and EPHX2 (132811.0001) genes. The K121Q polymorphism of ENPP1 (173335.0006) is associated with susceptibility to type 2 diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type 2 diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type 2 diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type 2 diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type 2 diabetes. Variation in the PPARG gene (601487) has been associated with risk of type 2 diabetes. A promoter polymorphism in the IL6 gene (147620) is associated with susceptibility to NIDDM. Variation in the KCNJ15 gene (602106) has been associated with T2DM in lean Asians. Variation in the SLC30A8 gene (611145) has been associated with susceptibility to T2D. Variation in the HMGA1 gene (600701.0001) is associated with an increased risk of type 2 diabetes. Mutation in the MTNR1B gene (600804) is associated with susceptibility to type 2 diabetes. Protection Against Type 2 Diabetes Mellitus Protein-truncating variants in the SLC30A8 (611145) have been associated with a reduced risk for T2D.

An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.

An increased concentration of insulin combined with a decreased concentration of glucose in the blood.

A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.

Structural abnormalities that impede fluid drainage in the eye increase ocular pressure. These abnormalities may be present at birth and usually become apparent during the first year of life. Such structural abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 3 without other associated abnormalities, it is called primary congenital glaucoma.\n\nOther individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.\n\nUsually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.\n\nIn most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.\n\nGlaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.