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Type 2 diabetes mellitus(NIDDM; T2D)

MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
Synonyms: DIABETES MELLITUS, TYPE 2, PROTECTION AGAINST; KCNJ11-Related Susceptibility to Noninsulin-Dependent Diabetes Mellitus; Type II diabetes mellitus
SNOMED CT: Type 2 diabetes mellitus (44054006); Diabetes mellitus type 2 (44054006); T2DM - diabetes mellitus type 2 (44054006); Type II diabetes mellitus (44054006); Diabetes mellitus type II (44054006)
 
Genes (locations): ABCC8 (11p15.1); AKT2 (19q13.2); ENPP1 (6q23.2); GCK (7p13); GPD2 (2q24.1); HMGA1 (6p21.31); HNF1A (12q24.31); HNF1B (17q12); HNF4A (20q13.12); IGF2BP2 (3q27.2); IL6 (7p15.3); IRS1 (2q36.3); IRS2 (13q34); KCNJ11 (11p15.1); LIPC (15q21.3); MAPK8IP1 (11p11.2); MTNR1B (11q14.3); NEUROD1 (2q31.3); PAX4 (7q32.1); PDX1 (13q12.2); PPARG (3p25.2); PPP1R3A (7q31.1); PTPN1 (20q13.13); RETN (19p13.2); SLC2A2 (3q26.2); SLC30A8 (8q24.11); TCF7L2 (10q25.2-25.3); WFS1 (4p16.1)
 
HPO: HP:0005978
Monarch Initiative: MONDO:0005148
OMIM®: 125853

Definition

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 II 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 II 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 II 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 II diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type II 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 II diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type II diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type II diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type II 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 II diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type II diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type II diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type II diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type II 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 II 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. [from OMIM]

Additional description

From MedlinePlus Genetics
Type 2 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, the body stops using and making insulin properly. Insulin is a hormone produced in the pancreas that helps regulate blood sugar levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source. When blood sugar levels are high (such as after a meal), the pancreas releases insulin to move the excess glucose into cells, which reduces the amount of glucose in the blood.\n\nMost people who develop type 2 diabetes first have insulin resistance, a condition in which the body's cells use insulin less efficiently than normal. As insulin resistance develops, more and more insulin is needed to keep blood sugar levels in the normal range. To keep up with the increasing need, insulin-producing cells in the pancreas (called beta cells) make larger amounts of insulin. Over time, the beta cells become less able to respond to blood sugar changes, leading to an insulin shortage that prevents the body from reducing blood sugar levels effectively. Most people have some insulin resistance as they age, but inadequate exercise and excessive weight gain make it worse, greatly increasing the likelihood of developing type 2 diabetes.\n\nType 2 diabetes can occur at any age, but it most commonly begins in middle age or later. Signs and symptoms develop slowly over years. They include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet (diabetic neuropathy), sores that do not heal well, and weight loss. If blood sugar levels are not controlled through medication or diet, type 2 diabetes can cause long-lasting (chronic) health problems including heart disease and stroke; nerve damage; and damage to the kidneys, eyes, and other parts of the body.  https://medlineplus.gov/genetics/condition/type-2-diabetes

Clinical features

From HPO
Increased waist to hip ratio
MedGen UID:
1636491
Concept ID:
C4703554
Finding
Increased waist-to-hip ratio (WHR) is a measurement above the average for the dimensionless ratio of the circumference of the waist to that of the hips. WHR is calculated as waist measurement divided by hip measurement.
Type 2 diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
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 II 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 II 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 II 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 II diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type II 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 II diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type II diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type II diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type II 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 II diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type II diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type II diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type II diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type II 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 II 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.
Insulin resistance
MedGen UID:
43904
Concept ID:
C0021655
Pathologic Function
Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.

Conditions with this feature

Bloom syndrome
MedGen UID:
2685
Concept ID:
C0005859
Disease or Syndrome
Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. Despite their very small head circumference, most affected individuals have normal intellectual ability. Women may be fertile but often have early menopause, and men tend to be infertile, with only one confirmed case of paternity. Serious medical complications that are more common than in the general population and that also appear at unusually early ages include chronic obstructive pulmonary disease, diabetes mellitus as a result of insulin resistance, and cancer of a wide variety of types and anatomic sites.
Type 2 diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
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 II 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 II 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 II 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 II diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type II 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 II diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type II diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type II diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type II 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 II diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type II diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type II diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type II diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type II 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 II 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.
Prader-Willi syndrome
MedGen UID:
46057
Concept ID:
C0032897
Disease or Syndrome
Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common (if not treated with growth hormone); characteristic facial features, strabismus, and scoliosis are often present.
Polyglandular autoimmune syndrome, type 2
MedGen UID:
39126
Concept ID:
C0085860
Disease or Syndrome
Autoimmune polyendocrine syndrome type II (APS2), or Schmidt syndrome, is characterized by the presence of autoimmune Addison disease in association with either autoimmune thyroid disease or type I diabetes mellitus, or both. Chronic candidiasis is not present. APS2 may occur at any age and in both sexes, but is most common in middle-aged females and is very rare in childhood (summary by Betterle et al., 2004). See 240300 for a phenotypic description of autoimmune polyendocrine syndrome type I (APS1).
Diabetes-deafness syndrome maternally transmitted
MedGen UID:
90979
Concept ID:
C0342289
Disease or Syndrome
Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations.
Microcephalic osteodysplastic primordial dwarfism type II
MedGen UID:
96587
Concept ID:
C0432246
Congenital Abnormality
Microcephalic osteodysplastic primordial dwarfism type II (MOPDII), the most common form of microcephalic primordial dwarfism, is characterized by extreme short stature and microcephaly along with distinctive facial features. Associated features that differentiate it from other forms of primordial dwarfism and that may necessitate treatment include: abnormal dentition, a slender bone skeletal dysplasia with hip deformity and/or scoliosis, insulin resistance / diabetes mellitus, chronic kidney disease, cardiac malformations, and global vascular disease. The latter includes neurovascular disease such as moyamoya vasculopathy and intracranial aneurysms (which can lead to strokes), coronary artery disease (which can lead to premature myocardial infarctions), and renal vascular disease. Hypertension, which is also common, can have multiple underlying causes given the complex comorbidities.
Islet cell adenomatosis
MedGen UID:
293643
Concept ID:
C1578917
Neoplastic Process
Insulinomatosis and diabetes mellitus syndrome is an autosomal dominant disorder in which affected individuals within a family present with either hyperinsulinemic hypoglycemia secondary to pancreatic neuroendocrine tumors, or a noninsulin-dependent form of diabetes mellitus. A few affected individuals show only impaired glucose tolerance. Some patients also exhibit congenital cataract and/or congenital glaucoma (Iacovazzo et al., 2018).
Familial partial lipodystrophy, Dunnigan type
MedGen UID:
354526
Concept ID:
C1720860
Disease or Syndrome
Familial partial lipodystrophy is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution beginning in late childhood or early adult life. Affected individuals gradually lose fat from the upper and lower extremities and the gluteal and truncal regions, resulting in a muscular appearance with prominent superficial veins. In some patients, adipose tissue accumulates on the face and neck, causing a double chin, fat neck, or cushingoid appearance. Metabolic abnormalities include insulin-resistant diabetes mellitus with acanthosis nigricans and hypertriglyceridemia; hirsutism and menstrual abnormalities occur infrequently. Familial partial lipodystrophy may also be referred to as lipoatrophic diabetes mellitus, but the essential feature is loss of subcutaneous fat (review by Garg, 2004). The disorder may be misdiagnosed as Cushing disease (see 219080) (Kobberling and Dunnigan, 1986; Garg, 2004). Genetic Heterogeneity of Familial Partial Lipodystrophy Familial partial lipodystrophy is a clinically and genetically heterogeneous disorder. Types 1 and 2 were originally described as clinical subtypes: type 1 (FPLD1; 608600), characterized by loss of subcutaneous fat confined to the limbs (Kobberling et al., 1975), and FPLD2, characterized by loss of subcutaneous fat from the limbs and trunk (Dunnigan et al., 1974; Kobberling and Dunnigan, 1986). No genetic basis for FPLD1 has yet been delineated. FPLD3 (604367) is caused by mutation in the PPARG gene (601487) on chromosome 3p25; FPLD4 (613877) is caused by mutation in the PLIN1 gene (170290) on chromosome 15q26; FPLD5 (615238) is caused by mutation in the CIDEC gene (612120) on chromosome 3p25; FPLD6 (615980) is caused by mutation in the LIPE gene (151750) on chromosome 19q13; and FPLD7 (606721) is caused by mutation in the CAV1 gene (601047) on chromosome 7q31.
PPARG-related familial partial lipodystrophy
MedGen UID:
328393
Concept ID:
C1720861
Disease or Syndrome
Researchers have described at least six forms of familial partial lipodystrophy, which are distinguished by their genetic cause. The most common form of familial partial lipodystrophy is type 2, also called Dunnigan disease. In addition to the signs and symptoms described above, some people with this type of the disorder develop muscle weakness (myopathy), abnormalities of the heart muscle (cardiomyopathy), a form of heart disease called coronary artery disease, and problems with the electrical system that coordinates the heartbeat (the conduction system).\n\nMost people with familial partial lipodystrophy also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to inflammation of the pancreas (pancreatitis). Familial partial lipodystrophy can also cause an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and abnormal liver function. After puberty, some affected females develop multiple cysts on the ovaries, an increased amount of body hair (hirsutism), and an inability to conceive (infertility), which are likely related to hormonal changes.\n\nAbnormal storage of fat in the body can lead to health problems in adulthood. Many people with familial partial lipodystrophy develop insulin resistance, a condition in which the body's tissues cannot adequately respond to insulin, which is a hormone that normally helps to regulate blood sugar levels. Insulin resistance may worsen to become a more serious disease called diabetes mellitus. Some people with familial partial lipodystrophy develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.\n\nFamilial partial lipodystrophy is a rare condition characterized by an abnormal distribution of fatty (adipose) tissue. Adipose tissue is normally found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat as a source of energy and also provides cushioning. In people with familial partial lipodystrophy, adipose tissue is lost from the arms, legs, and hips, giving these parts of the body a very muscular appearance. The fat that cannot be stored in the limbs builds up around the face and neck, and inside the abdomen. Excess fat in these areas gives individuals an appearance described as "cushingoid," because it resembles the physical features associated with a hormonal disorder called Cushing disease. This abnormal fat distribution can begin anytime from childhood to adulthood.
Congenital generalized lipodystrophy type 2
MedGen UID:
318593
Concept ID:
C1720863
Congenital Abnormality
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Maturity-onset diabetes of the young type 4
MedGen UID:
318863
Concept ID:
C1833382
Disease or Syndrome
Monogenic diabetes caused by inactivating mutation(s) in the PDX1 gene, encoding pancreas/duodenum homeobox protein 1. Homozygous PDX1 mutations result in permanent neonatal diabetes.
Diabetes mellitus, transient neonatal, 2
MedGen UID:
372150
Concept ID:
C1835887
Disease or Syndrome
Any transient neonatal diabetes mellitus in which the cause of the disease is a mutation in the ABCC8 gene.
Maturity-onset diabetes of the young type 3
MedGen UID:
324942
Concept ID:
C1838100
Disease or Syndrome
MODY is a form of familial noninsulin-dependent diabetes mellitus (T2D; 125853) and is characterized by an early age of onset (childhood, adolescence, or young adulthood under 25 years) and autosomal dominant inheritance. For a phenotypic description and discussion of genetic heterogeneity of MODY, see 606391.
Myopathy and diabetes mellitus
MedGen UID:
333236
Concept ID:
C1839028
Disease or Syndrome
A rare, genetic, mitochondrial DNA-related mitochondrial myopathy disorder characterized by slowly progressive muscular weakness (proximal greater than distal), predominantly involving the facial muscles and scapular girdle, associated with insulin-dependent diabetes mellitus. Neurological involvement and congenital myopathy may be variably observed.
Lipase deficiency, combined
MedGen UID:
340886
Concept ID:
C1855498
Disease or Syndrome
A rare disorder caused by mutation in the LMF1 gene resulting in combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders.
Maturity-onset diabetes of the young type 7
MedGen UID:
351232
Concept ID:
C1864839
Disease or Syndrome
Any maturity-onset diabetes of the young in which the cause of the disease is a mutation in the KLF11 gene.
Myotonic dystrophy type 2
MedGen UID:
419137
Concept ID:
C2931689
Disease or Syndrome
Myotonic dystrophy type 2 (DM2) is characterized by myotonia and muscle dysfunction (proximal and axial weakness, myalgia, and stiffness), and less commonly by posterior subcapsular cataracts, cardiac conduction defects, insulin-insensitive type 2 diabetes mellitus, and other endocrine abnormalities. While myotonia (involuntary muscle contraction with delayed relaxation) has been reported during the first decade, onset is typically in the third to fourth decade, most commonly with fluctuating or episodic muscle pain that can be debilitating and proximal and axial weakness of the neck flexors and the hip flexors. Subsequently, weakness occurs in the elbow extensors and finger flexors. Facial weakness and weakness of the ankle dorsiflexors are less common. Myotonia rarely causes severe symptoms. In a subset of individuals, calf hypertrophy in combination with brisk reflexes is notable.
Narcolepsy 7
MedGen UID:
481896
Concept ID:
C3280266
Disease or Syndrome
Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.\n\nSome people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment.\n\nAnother common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.\n\nNarcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. "Sleep attacks" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.\n\nNarcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.
Wolfram-like syndrome
MedGen UID:
481988
Concept ID:
C3280358
Disease or Syndrome
Autosomal dominant Wolfram-like syndrome is characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy. The hearing impairment, which is usually diagnosed in the first decade of life, is relatively constant and alters mainly low- and middle-frequency ranges (summary by Valero et al., 2008). Wolfram syndrome (WFS1; 222300) is an autosomal recessive allelic disorder characterized by optic atrophy, diabetes mellitus, hearing loss, and diabetes insipidus, and is caused by homozygous or compound heterozygous mutation in the WFS1 gene. An autosomal dominant syndrome involving optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy (125250), is caused by heterozygous mutation in the OPA1 gene (605290).
Thyroid hormone resistance, generalized, autosomal recessive
MedGen UID:
483749
Concept ID:
C3489796
Disease or Syndrome
A rare, autosomal recessive inherited disorder usually caused by mutations in the THRB gene. It is characterized by a defective physiological resistance to thyroid hormones, resulting in the elevation of thyroxin and triiodothyronine in the serum.
Obesity due to CEP19 deficiency
MedGen UID:
816654
Concept ID:
C3810324
Disease or Syndrome
A rare, genetic form of obesity characterized by morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidemia leading to early coronary disease, myocardial infarction and congestive heart failure. Intellectual disability and decreased sperm counts or azoospermia have also been reported.
Sideroblastic anemia 3
MedGen UID:
895975
Concept ID:
C4225155
Disease or Syndrome
Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit (summary by Liu et al., 2014). For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751).
SIN3A-related intellectual disability syndrome due to a point mutation
MedGen UID:
934771
Concept ID:
C4310804
Disease or Syndrome
Witteveen-Kolk syndrome (WITKOS) is an autosomal dominant disorder with characteristic distinctive facial features, microcephaly, short stature, and mildly impaired intellectual development with delayed cognitive and motor development and subtle anomalies on MRI-brain imaging (summary by Balasubramanian et al., 2021).
GCGR-related hyperglucagonemia
MedGen UID:
1677024
Concept ID:
C4763635
Disease or Syndrome
Mahvash disease (MVAH) is an autosomal recessive disorder caused by inactivating mutations in the glucagon receptor, leading to alpha-cell hyperplasia of the pancreas, hyperglucagonemia without glucagonoma syndrome, and occasional hypoglycemia. The disease may lead to glucagonomas and/or primitive neuroectodermal tumors (PNETs).
Abdominal obesity-metabolic syndrome 4
MedGen UID:
1704861
Concept ID:
C5231430
Disease or Syndrome
Abdominal obesity-metabolic syndrome-4 (AOMS4) is characterized by obesity, hypertension, and early-onset coronary artery disease. Most affected individuals meet the criteria for metabolic syndrome, including elevated triglyceride and low high-density lipoprotein levels, and type 2 diabetes (Esteghamat et al., 2019). For a discussion of the genetic heterogeneity of abdominal obesity-metabolic syndrome, see AOMS1 (605552).
Microcephaly, developmental delay, and brittle hair syndrome
MedGen UID:
1718781
Concept ID:
C5394425
Disease or Syndrome
Microcephaly, developmental delay, and brittle hair syndrome (MDBH) is a multisystem disorder with clinical variability. Affected individuals show cognitive and motor disabilities, as well as some degree of fine, brittle hair with microscopic shaft abnormalities. Other shared features include failure to thrive in early childhood and short stature, with some patients exhibiting feeding difficulties and hepatic steatosis (Kuo et al., 2019).
BDV SYNDROME
MedGen UID:
1785671
Concept ID:
C5543403
Disease or Syndrome
BDV syndrome (BDVS) is an autosomal recessive disorder characterized by early-onset profound obesity, hyperphagia, and moderately impaired intellectual development accompanied by infantile hypotonia and other endocrine disorders including hypogonadotropic hypogonadism, hypothyroidism, and insulin resistance (summary by Bosch et al., 2021).

Professional guidelines

PubMed

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.; Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.
Genet Med 2013 Aug;15(8):612-7. Epub 2013 Mar 14 doi: 10.1038/gim.2013.9. PMID: 23492873
Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, Stalenhoef AF; Endocrine society.
J Clin Endocrinol Metab 2012 Sep;97(9):2969-89. doi: 10.1210/jc.2011-3213. PMID: 22962670Free PMC Article

Recent clinical studies

Etiology

Gao F, Li C, Wang Y, Lu J, Lu W, Zhou J, Yin J, Ma X
BMC Endocr Disord 2022 Oct 22;22(1):256. doi: 10.1186/s12902-022-01176-3. PMID: 36273168Free PMC Article
Huang T, Nazir B, Altaf R, Zang B, Zafar H, Paiva-Santos AC, Niaz N, Imran M, Duan Y, Abbas M, Ilyas U
Front Endocrinol (Lausanne) 2022;13:985857. Epub 2022 Aug 16 doi: 10.3389/fendo.2022.985857. PMID: 36051390Free PMC Article
Yen FS, Wei JC, Liu JS, Hsu CC, Hwu CM
J Diabetes Investig 2022 Nov;13(11):1905-1913. Epub 2022 Jul 1 doi: 10.1111/jdi.13873. PMID: 35726692Free PMC Article
Asgari S, Masrouri S, Hosseinpour-Niazi S, Moslehi N, Azizi F, Hadaegh F
J Diabetes Investig 2022 Oct;13(10):1711-1722. Epub 2022 Jun 20 doi: 10.1111/jdi.13839. PMID: 35588067Free PMC Article
Qiu Y, Yi Q, Li S, Sun W, Ren Z, Shen Y, Wu Y, Wang Z, Xia W, Song P
J Diabetes Investig 2022 Aug;13(8):1426-1437. Epub 2022 May 5 doi: 10.1111/jdi.13805. PMID: 35426487Free PMC Article

Diagnosis

Kersten CJBA, Knottnerus ILH, Heijmans E, Haalboom M, Zandbergen AAM, den Hertog HM
J Stroke Cerebrovasc Dis 2022 Sep;31(9):106648. Epub 2022 Jul 18 doi: 10.1016/j.jstrokecerebrovasdis.2022.106648. PMID: 35863262
Yen FS, Wei JC, Liu JS, Hsu CC, Hwu CM
J Diabetes Investig 2022 Nov;13(11):1905-1913. Epub 2022 Jul 1 doi: 10.1111/jdi.13873. PMID: 35726692Free PMC Article
Markus MRP, Ittermann T, Schipf S, Bahls M, Nauck M, Völzke H, Santos RD, Peters A, Zeller T, Felix SB, Vasan RS, Thorand B, Steinhagen-Thiessen E, Dörr M
Cardiovasc Diabetol 2021 Aug 18;20(1):168. doi: 10.1186/s12933-021-01363-x. PMID: 34407812Free PMC Article
Tang J, Wu T, Hu X, Gao L
Int J Nurs Pract 2021 Dec;27(6):e12987. Epub 2021 Jun 8 doi: 10.1111/ijn.12987. PMID: 34101931
Huang SF, Yu YL, Cui YF, Lou YM, Liao MQ, Wang CY, Xu S, Chen HE, Gao XP, Dai SH, Peng XL, Zhao D, Wang L, Ping Z, Zeng FF
J Diabetes Investig 2021 Sep;12(9):1560-1568. Epub 2021 Mar 4 doi: 10.1111/jdi.13521. PMID: 33544958Free PMC Article

Therapy

Gao F, Li C, Wang Y, Lu J, Lu W, Zhou J, Yin J, Ma X
BMC Endocr Disord 2022 Oct 22;22(1):256. doi: 10.1186/s12902-022-01176-3. PMID: 36273168Free PMC Article
Liang B, Gu N
Int J Med Sci 2022;19(7):1118-1121. Epub 2022 Jun 21 doi: 10.7150/ijms.72772. PMID: 35919809Free PMC Article
Yen FS, Wei JC, Liu JS, Hsu CC, Hwu CM
J Diabetes Investig 2022 Nov;13(11):1905-1913. Epub 2022 Jul 1 doi: 10.1111/jdi.13873. PMID: 35726692Free PMC Article
Zhang X, Wang H, Xie C, Hu Z, Zhang Y, Peng S, He Y, Kang J, Gao H, Yuan H, Liu Y, Fan G
J Chromatogr B Analyt Technol Biomed Life Sci 2022 Apr 1;1194:123189. Epub 2022 Feb 24 doi: 10.1016/j.jchromb.2022.123189. PMID: 35219959
Jeon B, Luyster FS, Sereika SM, DiNardo MM, Callan JA, Chasens ER
J Clin Sleep Med 2022 Apr 1;18(4):1103-1111. doi: 10.5664/jcsm.9812. PMID: 34879902Free PMC Article

Prognosis

Adegoke O, Bello BT, Olorunfemi G, Odeniyi IA
Ann Afr Med 2022 Oct-Dec;21(4):348-354. doi: 10.4103/aam.aam_78_21. PMID: 36412333
Qiu H, Yang H, Yang Z, Yao Q, Duan S, Qin J, Zhu J
Front Endocrinol (Lausanne) 2022;13:963246. Epub 2022 Oct 13 doi: 10.3389/fendo.2022.963246. PMID: 36313781Free PMC Article
Liang B, Gu N
Int J Med Sci 2022;19(7):1118-1121. Epub 2022 Jun 21 doi: 10.7150/ijms.72772. PMID: 35919809Free PMC Article
Yen FS, Wei JC, Liu JS, Hsu CC, Hwu CM
J Diabetes Investig 2022 Nov;13(11):1905-1913. Epub 2022 Jul 1 doi: 10.1111/jdi.13873. PMID: 35726692Free PMC Article
Asgari S, Masrouri S, Hosseinpour-Niazi S, Moslehi N, Azizi F, Hadaegh F
J Diabetes Investig 2022 Oct;13(10):1711-1722. Epub 2022 Jun 20 doi: 10.1111/jdi.13839. PMID: 35588067Free PMC Article

Clinical prediction guides

Adegoke O, Bello BT, Olorunfemi G, Odeniyi IA
Ann Afr Med 2022 Oct-Dec;21(4):348-354. doi: 10.4103/aam.aam_78_21. PMID: 36412333
Qiu H, Yang H, Yang Z, Yao Q, Duan S, Qin J, Zhu J
Front Endocrinol (Lausanne) 2022;13:963246. Epub 2022 Oct 13 doi: 10.3389/fendo.2022.963246. PMID: 36313781Free PMC Article
Jeon B, Luyster FS, Sereika SM, DiNardo MM, Callan JA, Chasens ER
J Clin Sleep Med 2022 Apr 1;18(4):1103-1111. doi: 10.5664/jcsm.9812. PMID: 34879902Free PMC Article
Jürgens M, Schou M, Hasbak P, Kjær A, Wolsk E, Zerahn B, Wiberg M, Brandt-Jacobsen NH, Gæde P, Rossing P, Faber J, Inzucchi SE, Gustafsson F, Kistorp C
J Am Heart Assoc 2021 Aug 3;10(15):e020418. Epub 2021 Jul 19 doi: 10.1161/JAHA.120.020418. PMID: 34278803Free PMC Article
Ma Y, Xiong J, Zhang X, Qiu T, Pang H, Li X, Zhu J, Wang J, Pan C, Yang X, Chu X, Yang B, Wang C, Zhang J
J Diabetes Investig 2021 Jun;12(6):950-962. Epub 2020 Dec 4 doi: 10.1111/jdi.13443. PMID: 33068491Free PMC Article

Recent systematic reviews

Dahal PK, Rawal LB, Mahumud RA, Paudel G, Sugishita T, Vandelanotte C
Int J Environ Res Public Health 2022 Aug 30;19(17) doi: 10.3390/ijerph191710799. PMID: 36078539Free PMC Article
Azmiardi A, Murti B, Febrinasari RP, Tamtomo DG
J Prev Med Public Health 2022 Jan;55(1):37-48. Epub 2022 Jan 10 doi: 10.3961/jpmph.21.490. PMID: 35135047Free PMC Article
Piera-Mardemootoo C, Lambert P, Faillie JL
Therapie 2021 Nov-Dec;76(6):647-656. Epub 2018 Feb 21 doi: 10.1016/j.therap.2018.01.006. PMID: 29605144
Pulipati VP, Ravi V, Pulipati P
Eur J Prev Cardiol 2020 Dec;27(18):1922-1930. Epub 2020 Feb 23 doi: 10.1177/2047487320903638. PMID: 32089007
García-Molina L, Lewis-Mikhael AM, Riquelme-Gallego B, Cano-Ibáñez N, Oliveras-López MJ, Bueno-Cavanillas A
Eur J Nutr 2020 Jun;59(4):1313-1328. Epub 2019 Nov 28 doi: 10.1007/s00394-019-02147-6. PMID: 31781857

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