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Diabetes mellitus type 1(T1D)

MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Synonyms: T1D; Type I diabetes mellitus
SNOMED CT: Type 1 diabetes mellitus (46635009); Diabetes mellitus type 1 (46635009); T1DM - type 1 diabetes mellitus (46635009); Type I diabetes mellitus (46635009); Diabetes mellitus type I (46635009)
 
Genes (locations): HNF1A (12q24.31); IL6 (7p15.3); ITPR3 (6p21.31); PTPN22 (1p13.2)
 
HPO: HP:0100651
Monarch Initiative: MONDO:0005147
OMIM®: 222100
Orphanet: ORPHA243377

Definition

Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. [from OMIM]

Additional description

From MedlinePlus Genetics
Type 1 diabetes is a disorder characterized by abnormally high levels of blood glucose, also called blood sugar. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of glucose in the blood.

Type 1 diabetes can occur at any age, from early childhood to late adulthood. The first signs and symptoms of the disorder are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood glucose is not well controlled by insulin replacement therapy. Improper control can also cause blood glucose levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation.

Uncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood glucose can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathing rapidly; develop a fruity odor in the breath; and experience nausea, vomiting, facial flushing, stomach pain, and dryness of the mouth (xerostomia). In severe cases, diabetic ketoacidosis can lead to coma and death.

Over many years, the chronic high blood glucose associated with diabetes may cause damage to blood vessels and nerves, leading to complications affecting many organs and tissues. The retina, which is the light-sensitive tissue at the back of the eye, can be damaged (diabetic retinopathy), leading to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) may also occur and can lead to kidney failure and end-stage renal disease (ESRD). Pain, tingling, and loss of normal sensation (diabetic neuropathy) often occur, especially in the feet. Impaired circulation and absence of the normal sensations that prompt reaction to injury can result in permanent damage to the feet; in severe cases, the damage can lead to amputation. People with type 1 diabetes are also at increased risk of heart attacks, strokes, and problems with urinary and sexual function.  https://medlineplus.gov/genetics/condition/type-1-diabetes

Clinical features

From HPO
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
Autoimmunity
MedGen UID:
2136
Concept ID:
C0004368
Pathologic Function
The occurrence of an immune reaction against the organism's own cells or tissues.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Ketoacidosis
MedGen UID:
67434
Concept ID:
C0220982
Disease or Syndrome
Acidosis resulting from accumulation of ketone bodies.
Decreased level of 1,5 anhydroglucitol in serum
MedGen UID:
1635089
Concept ID:
C4703616
Finding
A decrease in the level of 1,5 anhydroglucitol in the serum. 1,5-Anhydrosorbitol is a validated marker of short-term glycemic control. This substance is derived mainly from food, is well absorbed in the intestine, and is distributed to all organs and tissues.

Conditions with this feature

Polyglandular autoimmune syndrome, type 1
MedGen UID:
39125
Concept ID:
C0085859
Disease or Syndrome
Autoimmune polyglandular syndrome type I is characterized by the presence of 2 of 3 major clinical symptoms: Addison disease, and/or hypoparathyroidism, and/or chronic mucocutaneous candidiasis (Neufeld et al., 1981). However, variable APS1 phenotypes have been observed, even among sibs. In addition, some patients may exhibit apparent isolated hypoparathyroidism, an early manifestation of APS1 with peak incidence at around age 5 years; over longterm follow-up, the development of additional features of APS1 may be observed (Cranston et al., 2022).
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
MedGen UID:
83339
Concept ID:
C0342288
Disease or Syndrome
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, endocrinopathy (most commonly insulin-dependent diabetes mellitus), and eczematous dermatitis. Most children have other autoimmune phenomena including cytopenias, autoimmune hepatitis, or nephropathy; lymphadenopathy, splenomegaly, alopecia, arthritis, and lung disease related to immune dysregulation have all been observed. Fetal presentation of IPEX includes hydrops, echogenic bowel, skin desquamation, IUGR, and fetal akinesia. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected males die within the first one to two years of life from metabolic derangements, severe malabsorption, or sepsis; a few with a milder phenotype have survived into the second or third decade of life.
Pearson syndrome
MedGen UID:
87459
Concept ID:
C0342784
Disease or Syndrome
Mitochondrial DNA (mtDNA) deletion syndromes predominantly comprise three overlapping phenotypes that are usually simplex (i.e., a single occurrence in a family), but rarely may be observed in different members of the same family or may evolve from one clinical syndrome to another in a given individual over time. The three classic phenotypes caused by mtDNA deletions are Kearns-Sayre syndrome (KSS), Pearson syndrome, and progressive external ophthalmoplegia (PEO). KSS is a progressive multisystem disorder defined by onset before age 20 years, pigmentary retinopathy, and PEO; additional features include cerebellar ataxia, impaired intellect (intellectual disability, dementia, or both), sensorineural hearing loss, ptosis, oropharyngeal and esophageal dysfunction, exercise intolerance, muscle weakness, cardiac conduction block, and endocrinopathy. Pearson syndrome is characterized by sideroblastic anemia and exocrine pancreas dysfunction and may be fatal in infancy without appropriate hematologic management. PEO is characterized by ptosis, impaired eye movements due to paralysis of the extraocular muscles (ophthalmoplegia), oropharyngeal weakness, and variably severe proximal limb weakness with exercise intolerance. Rarely, a mtDNA deletion can manifest as Leigh syndrome.
Wolcott-Rallison dysplasia
MedGen UID:
140926
Concept ID:
C0432217
Disease or Syndrome
Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis, and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, mental retardation, and cardiovascular abnormalities (summary by Delepine et al., 2000).
Type 1 diabetes mellitus 2
MedGen UID:
377588
Concept ID:
C1852092
Disease or Syndrome
Over many years, the chronic high blood glucose associated with diabetes may cause damage to blood vessels and nerves, leading to complications affecting many organs and tissues. The retina, which is the light-sensitive tissue at the back of the eye, can be damaged (diabetic retinopathy), leading to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) may also occur and can lead to kidney failure and end-stage renal disease (ESRD). Pain, tingling, and loss of normal sensation (diabetic neuropathy) often occur, especially in the feet. Impaired circulation and absence of the normal sensations that prompt reaction to injury can result in permanent damage to the feet; in severe cases, the damage can lead to amputation. People with type 1 diabetes are also at increased risk of heart attacks, strokes, and problems with urinary and sexual function.\n\nUncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood glucose can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathing rapidly; develop a fruity odor in the breath; and experience nausea, vomiting, facial flushing, stomach pain, and dryness of the mouth (xerostomia). In severe cases, diabetic ketoacidosis can lead to coma and death.\n\nType 1 diabetes can occur at any age, from early childhood to late adulthood. The first signs and symptoms of the disorder are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood glucose is not well controlled by insulin replacement therapy. Improper control can also cause blood glucose levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation.\n\nType 1 diabetes is a disorder characterized by abnormally high levels of blood glucose, also called blood sugar. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of glucose in the blood.
Immunodeficiency due to CD25 deficiency
MedGen UID:
377894
Concept ID:
C1853392
Disease or Syndrome
Immunodeficiency-41 is an autosomal recessive complex disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation (summary by Goudy et al., 2013).
Celiac disease, susceptibility to, 1
MedGen UID:
395227
Concept ID:
C1859310
Finding
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
H syndrome
MedGen UID:
400532
Concept ID:
C1864445
Disease or Syndrome
The histiocytosis-lymphadenopathy plus syndrome comprises features of 4 histiocytic disorders previously thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC was described as an autosomal recessive disease involving joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes (summary by Morgan et al., 2010). SHML, or familial Rosai-Dorfman disease, was described as a rare cause of lymph node enlargement in children, consisting of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal sites were involved in approximately 25% of patients, including salivary glands, orbit, eyelid, spleen, and testes. The involvement of retropharyngeal lymphoid tissue sometimes caused snoring and sleep apnea (summary by Kismet et al., 2005). H syndrome was characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss was also found in about half of patients, and many had short stature. PHID was characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome, with hepatosplenomegaly occurring in about half of patients (Cliffe et al., 2009). Bolze et al. (2012) noted that mutations in the SLC29A3 gene (612373) had been implicated in H syndrome, PHID, FHC, and SHML, and that some patients presented a combination of features from 2 or more of these syndromes, leading to the suggestion that these phenotypes should be grouped together as 'SLC29A3 disorder.' Bolze et al. (2012) suggested that the histologic features of the lesions seemed to be the most uniform phenotype in these patients. In addition, the immunophenotype of infiltrating cells in H syndrome patients was shown to be the same as that seen in patients with the familial form of Rosai-Dorfman disease, further supporting the relationship between these disorders (Avitan-Hersh et al., 2011; Colmenero et al., 2012).
Type 1 diabetes mellitus 15
MedGen UID:
401019
Concept ID:
C1866519
Disease or Syndrome
An inherited susceptibility or predisposition to developing type 1 diabetes mellitus that has material basis in mutation of the locus at chromosome 6q21.
Type 1 diabetes mellitus 20
MedGen UID:
382706
Concept ID:
C2675866
Disease or Syndrome
An inherited susceptibility or predisposition to developing type 1 diabetes mellitus in which the cause of the disease is a mutation in the HNF1A gene.
Syndromic multisystem autoimmune disease due to ITCH deficiency
MedGen UID:
461999
Concept ID:
C3150649
Disease or Syndrome
Syndromic multisystem autoimmune disease due to Itch deficiency is a rare, genetic, systemic autoimmune disease characterized by failure to thrive, global developmental delay, distinctive craniofacial dysmorphism (relative macrocephaly, dolichocephaly, frontal bossing, orbital proptosis, flattened midface with a prominent occiput, low, posteriorly rotated ears, micrognatia), hepato- and/or splenomegaly, and multisystemic autoimmune disease involving the lungs, liver, gut and/or thyroid gland.
Proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome
MedGen UID:
463309
Concept ID:
C3151959
Disease or Syndrome
Proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome is characterized by onset of proximal tubulopathy in the first year of life, followed by progressive development during childhood of skin anomalies (erythrocyanosis and abnormal pigmentation), blindness, osteoporosis, cerebellar ataxia, mitochondrial myopathy, deafness and diabetes mellitus.
Combined immunodeficiency due to LRBA deficiency
MedGen UID:
766426
Concept ID:
C3553512
Disease or Syndrome
Common variable immunodeficiency-8 with autoimmunity is an autosomal recessive disorder of immune dysregulation. Affected individuals have early childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. The presentation and phenotype are highly variable, even within families (summary by Lopez-Herrera et al., 2012 and Alangari et al., 2012). Immunologic findings are also variable and may include decreased B cells, hypogammaglobulinemia, and deficiency of CD4+ T regulatory (Treg) cells (Charbonnier et al., 2015). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome
MedGen UID:
813897
Concept ID:
C3807567
Disease or Syndrome
Lipodystrophies are rare disorders characterized by loss of body fat from various regions and predisposition to metabolic complications of insulin resistance and lipid abnormalities. FPLD7 is an autosomal dominant disorder with a highly variable phenotype. Additional features, including early-onset cataracts and later onset of spasticity of the lower limbs, have been noted in some patients (summary by Garg et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
Vasculitis due to ADA2 deficiency
MedGen UID:
854497
Concept ID:
C3887654
Disease or Syndrome
Adenosine deaminase 2 deficiency (DADA2) is a complex systemic autoinflammatory disorder in which vasculopathy/vasculitis, dysregulated immune function, and/or hematologic abnormalities may predominate. Inflammatory features include intermittent fevers, rash (often livedo racemosa/reticularis), and musculoskeletal involvement (myalgia/arthralgia, arthritis, myositis). Vasculitis, which usually begins before age ten years, may manifest as early-onset ischemic (lacunar) and/or hemorrhagic strokes, or as cutaneous or systemic polyarteritis nodosa. Hypertension and hepatosplenomegaly are often found. More severe involvement may lead to progressive central neurologic deficits (dysarthria, ataxia, cranial nerve palsies, cognitive impairment) or to ischemic injury to the kidney, intestine, and/or digits. Dysregulation of immune function can lead to immunodeficiency or autoimmunity of varying severity; lymphadenopathy may be present and some affected individuals have had lymphoproliferative disease. Hematologic disorders may begin early in life or in late adulthood, and can include lymphopenia, neutropenia, pure red cell aplasia, thrombocytopenia, or pancytopenia. Of note, both interfamilial and intrafamilial phenotypic variability (e.g., in age of onset, frequency and severity of manifestations) can be observed; also, individuals with biallelic ADA2 pathogenic variants may remain asymptomatic until adulthood or may never develop clinical manifestations of DADA2.
STAT3-related early-onset multisystem autoimmune disease
MedGen UID:
863232
Concept ID:
C4014795
Disease or Syndrome
Infantile-onset multisystem autoimmune disease-1 is characterized by early childhood onset of a spectrum of autoimmune disorders affecting multiple organs. Common manifestations include insulin-dependent diabetes mellitus and autoimmune enteropathy, or celiac disease, and autoimmune hematologic disorders. Other features include short stature and nonspecific dermatitis. More variable features include hypothyroidism, autoimmune arthritis, and delayed puberty. Some patients may show recurrent infections. The disorder results from an inborn error of cytokine signaling (summary by Flanagan et al., 2014 and Milner et al., 2015). Genetic Heterogeneity of Infantile-Onset Multisystem Autoimmune Disease See also ADMIO2 (617006), caused by mutation in the ZAP70 gene (176947) on chromosome 2q12, and ADMIO3 (620430), caused by mutation in the CBLB gene (604491) on chromosome 3q13.
Polyendocrine-polyneuropathy syndrome
MedGen UID:
863698
Concept ID:
C4015261
Disease or Syndrome
A rare genetic disease with characteristics of childhood onset of multiple endocrine manifestations in combination with central and peripheral nervous system abnormalities. Reported signs and symptoms include postnatal growth retardation, moderate intellectual disability, hypogonadotropic hypogonadism, insulin-dependent diabetes mellitus, central hypothyroidism, demyelinating sensorimotor polyneuropathy, cerebellar and pyramidal signs. Progressive hearing loss and a hypoplastic pituitary gland have also been described. Brain imaging shows moderate white matter abnormalities.
Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome
MedGen UID:
863873
Concept ID:
C4015436
Disease or Syndrome
Combined cerebellar and peripheral ataxia with hearing loss and diabetes mellitus (ACPHD) is an autosomal recessive multisystem disorder including defects in glucose metabolism, diffuse neurodegeneration, multiple hormone deficiencies, severe growth retardation with possible growth hormone deficiencies, and subtle osseous changes suggesting early-onset bone dysplasia (summary by Ozon et al., 2020).
Combined oxidative phosphorylation deficiency 39
MedGen UID:
1683958
Concept ID:
C5193075
Disease or Syndrome
Combined oxidative phosphorylation deficiency-39 (COXPD39) is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. Affected individuals show global developmental delay, sometimes with regression after normal early development, axial hypotonia with limb spasticity or abnormal involuntary movements, and impaired intellectual development with poor speech. More variable features may include hypotonia, seizures, and features of Leigh syndrome (256000) on brain imaging. There are variable deficiencies of the mitochondrial respiratory chain enzyme complexes in patient tissues (summary by Glasgow et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Holoprosencephaly 12 with or without pancreatic agenesis
MedGen UID:
1684550
Concept ID:
C5193131
Disease or Syndrome
Holoprosencephaly-12 with or without pancreatic agenesis (HPE12) is a developmental disorder characterized by abnormal separation of the embryonic forebrain (HPE) resulting in dysmorphic facial features and often, but not always, impaired neurologic development. Most patients with this form of HPE also have congenital absence of the pancreas, resulting in early-onset type 1 diabetes mellitus and requiring pancreatic enzyme replacement. Other features may include hearing loss and absence of the gallbladder (summary by De Franco et al., 2019 and Kruszka et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).
Hepatitis, fulminant viral, susceptibility to
MedGen UID:
1684882
Concept ID:
C5231406
Finding
Permanent neonatal diabetes mellitus 1
MedGen UID:
1717586
Concept ID:
C5393570
Disease or Syndrome
Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype.
Diabetes mellitus, permanent neonatal 2
MedGen UID:
1713823
Concept ID:
C5394296
Disease or Syndrome
Permanent neonatal diabetes mellitus-2 (PNDM2) is characterized by onset of insulin-requiring hyperglycemia within the first months of life that requires insulin therapy throughout life. Some patients additionally have marked developmental delay, muscle weakness, and epilepsy (Gloyn et al., 2004). The triad of developmental delay, epilepsy, and neonatal diabetes is known as DEND (Shimomura et al., 2007). Proks et al. (2006) stated that heterozygous activating mutations in KCNJ11 are the most common cause of PNDM and account for 26 to 64% of cases, and that neurologic features are found in 20% of patients with KCNJ11 mutations. For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).
Diabetes mellitus, permanent neonatal 3
MedGen UID:
1717271
Concept ID:
C5394303
Disease or Syndrome
Permanent neonatal diabetes mellitus-3 (PNDM3) is characterized by the onset of mild to severe hyperglycemia within the first months of life, and requires lifelong therapy (summary by Babenko et al., 2006). Some patients also have neurologic features, including developmental delay and epilepsy (Proks et al., 2006; Babenko et al., 2006). The triad of developmental delay, epilepsy, and neonatal diabetes is known as DEND. For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).
Diabetes mellitus, permanent neonatal 4
MedGen UID:
1711191
Concept ID:
C5394307
Disease or Syndrome
Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life (summary by Polak et al., 2008). For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).
Odontochondrodysplasia 2 with hearing loss and diabetes
MedGen UID:
1782909
Concept ID:
C5543275
Disease or Syndrome
Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability (Cauwels et al., 2005; Lekszas et al., 2020). For a discussion of genetic heterogeneity of ODCD, see ODCD1 (184260).
Congenital disorder of glycosylation, type IIw
MedGen UID:
1794196
Concept ID:
C5561986
Disease or Syndrome
Congenital disorder of glycosylation type IIw (CDG2W) is an autosomal dominant metabolic disorder characterized by liver dysfunction, coagulation deficiencies, and profound abnormalities in N-glycosylation of serum specific proteins. All reported patients carry the same mutation (602671.0017) (summary by Ng et al., 2021). For an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066).
Immunodeficiency 98 with autoinflammation, X-linked
MedGen UID:
1805285
Concept ID:
C5676883
Disease or Syndrome
X-linked immunodeficiency-98 with autoinflammation (IMD98) is characterized by onset of recurrent infections associated with lymphoproliferation and autoinflammation in the first decade of life. Mostly males are affected; carrier females may have mild symptoms. Laboratory studies show evidence of immune dysregulation, including hypogammaglobulinemia with reduced memory B cells, skewed T-cell subsets, increased levels of proinflammatory cytokines, activated T cells and monocytes, and autoimmune cytopenias, including neutropenia (Aluri et al., 2021; Fejtkova et al., 2022).
Agammaglobulinemia 10, autosomal dominant
MedGen UID:
1806624
Concept ID:
C5676900
Disease or Syndrome
Autosomal dominant agammaglobulinemia-10 (AGM10) is characterized by early-childhood onset of recurrent viral and bacterial infections affecting various organ systems, particularly the sinopulmonary system. Laboratory studies show low or absent circulating B cells and hypo- or agammaglobulinemia. Affected individuals may have adverse reactions to certain vaccinations, such as the polio vaccine. Treatment with replacement Ig is effective; hematopoietic stem cell transplantation has also been reported (summary by Le Coz et al., 2021). For a discussion of genetic heterogeneity of autosomal agammaglobulinemia, see AGM1 (601495).
Autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency
MedGen UID:
1803642
Concept ID:
C5676977
Disease or Syndrome
Autoinflammatory-pancytopenia syndrome (AIPCS) is an autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging. Laboratory studies show increased levels of proinflammatory cytokines and increased expression of interferon-stimulated genes (ISGs), consistent with a type I interferonopathy (Rodero et al., 2017). Treatment with a JAK (see 147795) inhibitor (baricitinib) may be effective (Hong et al., 2020).
Bone marrow failure and diabetes mellitus syndrome
MedGen UID:
1823991
Concept ID:
C5774218
Disease or Syndrome
Bone marrow failure and diabetes mellitus syndrome (BMFDMS) is an autosomal recessive disorder characterized by the onset of manifestations of bone marrow failure, such as anemia, thrombocytopenia, and dyserythropoiesis, in infancy or early childhood. White blood cell lineages may or may not be affected. Patients with BMFDMS also develop nonautoimmune insulin-dependent diabetes mellitus in the first or second decades, likely due to apoptosis of pancreatic beta cells. Many patients show pigmentary skin abnormalities and short stature. Bone marrow transplant is curative for the bone marrow failure, but does not have an effect on diabetes (Dos Santos et al., 2017).
Muscular dystrophy, congenital, with or without seizures
MedGen UID:
1824047
Concept ID:
C5774274
Disease or Syndrome
Congenital muscular dystrophy with or without seizures (MYOS) is an autosomal recessive disorder characterized by severe muscle hypotonia apparent from birth, as well as developmental delay. Laboratory studies show increased serum creatine kinase and muscle biopsy shows nonspecific dystrophic features. Most patients develop seizures or have abnormal epileptiform findings on EEG studies; other variable findings may include feeding difficulties, nystagmus, myopathic facies, areflexia, and brain atrophy on MRI (summary by Larson et al., 2018 and Henige et al., 2021).
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7
MedGen UID:
1841121
Concept ID:
C5830485
Disease or Syndrome
Telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-7 (PFBMFT7) is an autosomal dominant disorder characterized by variable manifestations associated with shortened telomeres. Features can include pulmonary fibrosis, emphysema, anemia, lymphopenia, liver involvement with portal hypertension and hepatopulmonary syndrome, premature graying of the hair, nail dystrophy, and predisposition to squamous cell cancers or myelodysplasia (Stanley et al., 2016). For a discussion of genetic heterogeneity of telomere-related pulmonary fibrosis and/or bone marrow failure syndromes, see PFBMFT1 (614742).

Professional guidelines

PubMed

Blonde L, Umpierrez GE, Reddy SS, McGill JB, Berga SL, Bush M, Chandrasekaran S, DeFronzo RA, Einhorn D, Galindo RJ, Gardner TW, Garg R, Garvey WT, Hirsch IB, Hurley DL, Izuora K, Kosiborod M, Olson D, Patel SB, Pop-Busui R, Sadhu AR, Samson SL, Stec C, Tamborlane WV Jr, Tuttle KR, Twining C, Vella A, Vellanki P, Weber SL
Endocr Pract 2022 Oct;28(10):923-1049. Epub 2022 Aug 11 doi: 10.1016/j.eprac.2022.08.002. PMID: 35963508Free PMC Article
Yapanis M, James S, Craig ME, O'Neal D, Ekinci EI
J Clin Endocrinol Metab 2022 May 17;107(6):e2221-e2236. doi: 10.1210/clinem/dgac034. PMID: 35094087Free PMC Article
Winkley K, Upsher R, Stahl D, Pollard D, Kasera A, Brennan A, Heller S, Ismail K
Health Technol Assess 2020 Jun;24(28):1-232. doi: 10.3310/hta24280. PMID: 32568666Free PMC Article

Curated

UK NICE Guideline NG238, Cardiovascular disease: risk assessment and reduction, including lipid modification, 2023

UK NICE Guideline NG18, Diabetes (type 1 and type 2) in children and young people: diagnosis and management, 2023

UK NICE Guidance, Clinical Guideline CG181, Cardiovascular disease: risk assessment and reduction, including lipid modification, 2023

UK NICE Guideline NG17, Type 1 diabetes in adults: diagnosis and management, 2022

UK NICE Guideline NG3, Diabetes in pregnancy: management from preconception to the postnatal period

UK NICE Guideline NG19, Diabetic foot problems: prevention and management, 2019

Recent clinical studies

Etiology

Lu X, Zhao C
Adv Exp Med Biol 2020;1228:107-121. doi: 10.1007/978-981-15-1792-1_7. PMID: 32342453
Streisand R, Monaghan M
Curr Diab Rep 2014;14(9):520. doi: 10.1007/s11892-014-0520-2. PMID: 25009119Free PMC Article
Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ
Endocrinol Metab Clin North Am 2010 Sep;39(3):481-97. doi: 10.1016/j.ecl.2010.05.011. PMID: 20723815Free PMC Article
Bluestone JA, Herold K, Eisenbarth G
Nature 2010 Apr 29;464(7293):1293-300. doi: 10.1038/nature08933. PMID: 20432533Free PMC Article
Gillespie KM
CMAJ 2006 Jul 18;175(2):165-70. doi: 10.1503/cmaj.060244. PMID: 16847277Free PMC Article

Diagnosis

Haak T, Gölz S, Fritsche A, Füchtenbusch M, Siegmund T, Schnellbächer E, Klein HH, Uebel T, Droßel D
Exp Clin Endocrinol Diabetes 2019 Dec;127(S 01):S27-S38. Epub 2019 Dec 20 doi: 10.1055/a-0984-5696. PMID: 31860925
De Beaufort C, Besançon S, Balde N
Med Sante Trop 2018 Nov 1;28(4):359-362. doi: 10.1684/mst.2018.0834. PMID: 30799818
Li W, Huang E, Gao S
J Alzheimers Dis 2017;57(1):29-36. doi: 10.3233/JAD-161250. PMID: 28222533
Streisand R, Monaghan M
Curr Diab Rep 2014;14(9):520. doi: 10.1007/s11892-014-0520-2. PMID: 25009119Free PMC Article
Bluestone JA, Herold K, Eisenbarth G
Nature 2010 Apr 29;464(7293):1293-300. doi: 10.1038/nature08933. PMID: 20432533Free PMC Article

Therapy

Battelino T, Alexander CM, Amiel SA, Arreaza-Rubin G, Beck RW, Bergenstal RM, Buckingham BA, Carroll J, Ceriello A, Chow E, Choudhary P, Close K, Danne T, Dutta S, Gabbay R, Garg S, Heverly J, Hirsch IB, Kader T, Kenney J, Kovatchev B, Laffel L, Maahs D, Mathieu C, Mauricio D, Nimri R, Nishimura R, Scharf M, Del Prato S, Renard E, Rosenstock J, Saboo B, Ueki K, Umpierrez GE, Weinzimer SA, Phillip M
Lancet Diabetes Endocrinol 2023 Jan;11(1):42-57. Epub 2022 Dec 6 doi: 10.1016/S2213-8587(22)00319-9. PMID: 36493795
Dejgaard TF, von Scholten BJ, Christiansen E, Kreiner FF, Bardtrum L, von Herrath M, Mathieu C, Madsbad S; ADJUNCT ONE and ADJUNCT TWO Investigators
Diabetes Obes Metab 2021 Dec;23(12):2752-2762. Epub 2021 Sep 28 doi: 10.1111/dom.14532. PMID: 34463425Free PMC Article
Blair HA
Drugs 2021 Jun;81(9):1115-1120. doi: 10.1007/s40265-021-01531-z. PMID: 34047955
van der Feltz-Cornelis C, Allen SF, Holt RIG, Roberts R, Nouwen A, Sartorius N
Brain Behav 2021 Feb;11(2):e01981. Epub 2020 Dec 4 doi: 10.1002/brb3.1981. PMID: 33274609Free PMC Article
Diabetes Care 1987 Jan-Feb;10(1):1-19. doi: 10.2337/diacare.10.1.1. PMID: 2882967

Prognosis

Gottesman BL, Yu J, Tanaka C, Longhurst CA, Kim JJ
JAMA Pediatr 2022 Apr 1;176(4):414-415. doi: 10.1001/jamapediatrics.2021.5801. PMID: 35072727Free PMC Article
Lin X, Xu Y, Pan X, Xu J, Ding Y, Sun X, Song X, Ren Y, Shan PF
Sci Rep 2020 Sep 8;10(1):14790. doi: 10.1038/s41598-020-71908-9. PMID: 32901098Free PMC Article
Patterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G, Ogle GD
Diabetes Res Clin Pract 2019 Nov;157:107842. Epub 2019 Sep 10 doi: 10.1016/j.diabres.2019.107842. PMID: 31518658
Rawshani A, Rawshani A, Franzén S, Eliasson B, Svensson AM, Miftaraj M, McGuire DK, Sattar N, Rosengren A, Gudbjörnsdottir S
N Engl J Med 2017 Apr 13;376(15):1407-1418. doi: 10.1056/NEJMoa1608664. PMID: 28402770
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group
Diabetes Care 2016 May;39(5):686-93. Epub 2016 Feb 9 doi: 10.2337/dc15-1990. PMID: 26861924Free PMC Article

Clinical prediction guides

Kaiafa G, Veneti S, Polychronopoulos G, Pilalas D, Daios S, Kanellos I, Didangelos T, Pagoni S, Savopoulos C
Postgrad Med J 2021 Jun;97(1148):380-383. Epub 2020 Sep 10 doi: 10.1136/postgradmedj-2020-138756. PMID: 32913038Free PMC Article
Feig DS, Donovan LE, Corcoy R, Murphy KE, Amiel SA, Hunt KF, Asztalos E, Barrett JFR, Sanchez JJ, de Leiva A, Hod M, Jovanovic L, Keely E, McManus R, Hutton EK, Meek CL, Stewart ZA, Wysocki T, O'Brien R, Ruedy K, Kollman C, Tomlinson G, Murphy HR; CONCEPTT Collaborative Group
Lancet 2017 Nov 25;390(10110):2347-2359. Epub 2017 Sep 15 doi: 10.1016/S0140-6736(17)32400-5. PMID: 28923465Free PMC Article
Buzzetti R, Prudente S, Copetti M, Dauriz M, Zampetti S, Garofolo M, Penno G, Trischitta V
Nutr Metab Cardiovasc Dis 2017 Feb;27(2):99-114. Epub 2016 Aug 26 doi: 10.1016/j.numecd.2016.08.005. PMID: 28063875
Zhang L, Eisenbarth GS
J Diabetes 2011 Mar;3(1):48-57. doi: 10.1111/j.1753-0407.2010.00102.x. PMID: 21073664
Hill J
Nurs Times 2005 Apr 19-25;101(16):28-30. PMID: 15871371

Recent systematic reviews

Rahmati M, Keshvari M, Mirnasuri S, Yon DK, Lee SW, Il Shin J, Smith L
J Med Virol 2022 Nov;94(11):5112-5127. Epub 2022 Jul 22 doi: 10.1002/jmv.27996. PMID: 35831242Free PMC Article
Kelkar A, Kelkar J, Mehta H, Amoaku W
Indian J Ophthalmol 2018 Oct;66(10):1401-1410. doi: 10.4103/ijo.IJO_1158_17. PMID: 30249823Free PMC Article
Turton JL, Raab R, Rooney KB
PLoS One 2018;13(3):e0194987. Epub 2018 Mar 29 doi: 10.1371/journal.pone.0194987. PMID: 29596460Free PMC Article
Li W, Huang E, Gao S
J Alzheimers Dis 2017;57(1):29-36. doi: 10.3233/JAD-161250. PMID: 28222533
van Netten JJ, Price PE, Lavery LA, Monteiro-Soares M, Rasmussen A, Jubiz Y, Bus SA; International Working Group on the Diabetic Foot
Diabetes Metab Res Rev 2016 Jan;32 Suppl 1:84-98. doi: 10.1002/dmrr.2701. PMID: 26340966

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2023
      UK NICE Guideline NG238, Cardiovascular disease: risk assessment and reduction, including lipid modification, 2023
    • NICE, 2023
      UK NICE Guideline NG18, Diabetes (type 1 and type 2) in children and young people: diagnosis and management, 2023
    • NICE, 2023
      UK NICE Guidance, Clinical Guideline CG181, Cardiovascular disease: risk assessment and reduction, including lipid modification, 2023
    • NICE, 2022
      UK NICE Guideline NG17, Type 1 diabetes in adults: diagnosis and management, 2022
    • NICE, 2020
      UK NICE Guideline NG3, Diabetes in pregnancy: management from preconception to the postnatal period
    • NICE, 2019
      UK NICE Guideline NG19, Diabetic foot problems: prevention and management, 2019

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