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Elevated hemoglobin A1c

MedGen UID:
892798
Concept ID:
C4073162
Finding
Synonyms: Elevated HbA1c; Elevated hemoglobin A1C
 
HPO: HP:0040217

Definition

An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVElevated hemoglobin A1c

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.
Werner syndrome
MedGen UID:
12147
Concept ID:
C0043119
Disease or Syndrome
Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Individuals with Werner syndrome develop normally until the end of the first decade. The first sign is the lack of a growth spurt during the early teen years. Early findings (usually observed in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. Myocardial infarction and cancer are the most common causes of death; the mean age of death in individuals with Werner syndrome is 54 years.
Alstrom syndrome
MedGen UID:
78675
Concept ID:
C0268425
Disease or Syndrome
Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive bilateral sensorineural hearing impairment, acute infantile-onset cardiomyopathy and/or adolescent- or adult-onset restrictive cardiomyopathy, insulin resistance / type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), and chronic progressive kidney disease. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Sensorineural hearing loss presents in the first decade in as many as 70% of individuals and may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to T2DM in the majority by the third decade. Nearly all demonstrate hypertriglyceridemia. Other findings can include endocrine abnormalities (hypothyroidism, hypogonadotropic hypogonadism in males, and hyperandrogenism in females), urologic dysfunction / detrusor instability, progressive decrease in renal function, and hepatic disease (ranging from elevated transaminases to steatohepatitis/NAFLD). Approximately 20% of affected individuals have delay in early developmental milestones, most commonly in gross and fine motor skills. About 30% have a learning disability. Cognitive impairment (IQ <70) is very rare. Wide clinical variability is observed among affected individuals, even within the same family.
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 8
MedGen UID:
342845
Concept ID:
C1853297
Disease or Syndrome
Maturity-onset diabetes of the young type 8 (MODY8) is characterized by onset of diabetes before age 25 years, with slowly progressive pancreatic exocrine dysfunction, fatty replacement of pancreatic parenchyma (lipomatosis), and development of pancreatic cysts. Patients do not present clinical signs of chronic pancreatitis (summary by Johansson et al., 2018). For a phenotypic description and discussion of genetic heterogeneity of MODY, see 606391.
Diabetes mellitus, transient neonatal, 3
MedGen UID:
351177
Concept ID:
C1864623
Disease or Syndrome
Any transient neonatal diabetes mellitus in which the cause of the disease is a mutation in the KCNJ11 gene.
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).
Maturity-onset diabetes of the young type 14
MedGen UID:
908119
Concept ID:
C4225299
Disease or Syndrome
GCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.\n\nRCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout.\n\nHNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.\n\nThe different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.\n\nMaturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose 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.
Maturity-onset diabetes of the young type 13
MedGen UID:
897640
Concept ID:
C4225365
Disease or Syndrome
Maturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose 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.\n\nThe different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.\n\nHNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.\n\nRCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout.\n\nGCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.
Seckel syndrome 10
MedGen UID:
934614
Concept ID:
C4310647
Disease or Syndrome
Any Seckel syndrome in which the cause of the disease is a mutation in the NSMCE2 gene.
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).
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 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).
Mandibuloacral dysplasia progeroid syndrome
MedGen UID:
1741713
Concept ID:
C5436867
Disease or Syndrome
Mandibuloacral dysplasia progeroid syndrome (MDPS) is an autosomal recessive severe laminopathy-like disorder characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis, and hypertension (Elouej et al., 2020).
Microcephaly, epilepsy, and diabetes syndrome 2
MedGen UID:
1782107
Concept ID:
C5543294
Disease or Syndrome
MEDS2 is characterized by severe microcephaly and neonatal/early-onset epilepsy and diabetes (De Franco et al., 2020). For a discussion of genetic heterogeneity of microcephaly, epilepsy, and diabetes syndrome, see MEDS1 (614231).
Combined oxidative phosphorylation defect type 26
MedGen UID:
1799164
Concept ID:
C5567741
Disease or Syndrome
Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay (PNSED) is an autosomal recessive multisystemic disorder with highly variable manifestations, even within the same family. Some patients present in infancy with hypotonia and global developmental delay with poor or absent motor skill acquisition and poor growth, whereas others present as young adults with exercise intolerance and muscle weakness. All patients have signs of a peripheral neuropathy, usually demyelinating, with distal muscle weakness and atrophy and distal sensory impairment; many become wheelchair-bound. Additional features include spasticity, extensor plantar responses, contractures, cerebellar signs, seizures, short stature, and rare involvement of other organ systems, including the heart, pancreas, and kidney. Biochemical analysis may show deficiencies in mitochondrial respiratory complex enzyme activities in patient tissue, although this is not always apparent. Lactate is frequently increased, suggesting mitochondrial dysfunction (Powell et al., 2015; Argente-Escrig et al., 2022). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).

Professional guidelines

PubMed

Munir KM, Davis SN
Expert Opin Pharmacother 2015;16(15):2331-41. Epub 2015 Sep 4 doi: 10.1517/14656566.2015.1084502. PMID: 26340427
Shaefer C, Reid T, Vlajnic A, Zhou R, DiGenio A
Endocr Pract 2015 Dec;21(12):1323-32. Epub 2015 Aug 26 doi: 10.4158/EP14498.OR. PMID: 26307902
Dutton GR, Phillips JM, Kukkamalla M, Cherrington AL, Safford MM
Diabetes Educ 2015 Jun;41(3):361-8. Epub 2015 Mar 4 doi: 10.1177/0145721715575356. PMID: 25740817Free PMC Article

Recent clinical studies

Etiology

Sun B, Ge X, Li X, Zhang J, Zhao Z, Liu X, Zhou Y, Xu J, Zhao H, Sun J
Arterioscler Thromb Vasc Biol 2022 Apr;42(4):504-513. Epub 2022 Mar 3 doi: 10.1161/ATVBAHA.121.317190. PMID: 35236109
Nwokedi U, Zia M, Xu J, Sadhu AR, Baio FE, Kash BS, Sherman V, Tariq N
Surg Endosc 2022 Sep;36(9):6915-6923. Epub 2022 Jan 24 doi: 10.1007/s00464-022-09030-2. PMID: 35075523
Diaz R, DeJesus J
Curr Diab Rep 2022 Jan 6;21(12):68. doi: 10.1007/s11892-021-01434-z. PMID: 34997363Free PMC Article
Noguchi-Shinohara M, Yuki-Nozaki S, Abe C, Mori A, Horimoto M, Yokogawa M, Ishida N, Suga Y, Ishizaki J, Ishimiya M, Nakamura H, Komai K, Nakamura H, Shibata M, Ohara T, Hata J, Ninomiya T, Yamada M; Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) study group
J Alzheimers Dis 2022;85(1):235-247. doi: 10.3233/JAD-215153. PMID: 34806607
Cunningham A, McAna J, Silverio A, Mills G, LaNoue M
Popul Health Manag 2021 Aug;24(4):478-481. Epub 2020 Nov 23 doi: 10.1089/pop.2020.0169. PMID: 33226887

Diagnosis

Guan Y, Yuan L, Yuan L
Neurocase 2023 Jun;29(3):90-91. Epub 2024 Feb 17 doi: 10.1080/13554794.2024.2317788. PMID: 38367007
Sun B, Ge X, Li X, Zhang J, Zhao Z, Liu X, Zhou Y, Xu J, Zhao H, Sun J
Arterioscler Thromb Vasc Biol 2022 Apr;42(4):504-513. Epub 2022 Mar 3 doi: 10.1161/ATVBAHA.121.317190. PMID: 35236109
Chen T, Li S, Eisenberg ML
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Gao Y, Jiang L, Wang H, Yu C, Wang W, Liu S, Gao C, Tong X, Wang J, Jin Y, Wu J
PLoS One 2016;11(8):e0160223. Epub 2016 Aug 3 doi: 10.1371/journal.pone.0160223. PMID: 27486868Free PMC Article
Roberts RO, Knopman DS, Cha RH, Mielke MM, Pankratz VS, Boeve BF, Kantarci K, Geda YE, Jack CR Jr, Petersen RC, Lowe VJ
J Nucl Med 2014 May;55(5):759-64. Epub 2014 Mar 20 doi: 10.2967/jnumed.113.132647. PMID: 24652830Free PMC Article

Therapy

Alkhatib EH, Grundman JB, Adamusiak AM, Bellin MD, Brooks JP, Buckley KS, Janssen EM, Kitcharoensakkul M, McNerney KP, Pfeifer TL, Polk BI, Marks BE
Front Endocrinol (Lausanne) 2023;14:1226231. Epub 2023 Oct 20 doi: 10.3389/fendo.2023.1226231. PMID: 37929017Free PMC Article
Nwokedi U, Zia M, Xu J, Sadhu AR, Baio FE, Kash BS, Sherman V, Tariq N
Surg Endosc 2022 Sep;36(9):6915-6923. Epub 2022 Jan 24 doi: 10.1007/s00464-022-09030-2. PMID: 35075523
Chen T, Li S, Eisenberg ML
J Sex Med 2021 Jun;18(6):1104-1109. Epub 2021 Jun 6 doi: 10.1016/j.jsxm.2021.03.077. PMID: 34103256Free PMC Article
Domek N, Dux K, Pinzur M, Weaver F, Rogers T
J Foot Ankle Surg 2016 Sep-Oct;55(5):939-43. Epub 2016 Jun 20 doi: 10.1053/j.jfas.2016.04.009. PMID: 27338653
Engoren M, Schwann TA, Habib RH
Asian Cardiovasc Thorac Ann 2014 Sep;22(7):800-6. Epub 2013 Dec 6 doi: 10.1177/0218492313515895. PMID: 24887924

Prognosis

Galvin JE, Tolea MI, Chrisphonte S
PLoS One 2020;15(7):e0235534. Epub 2020 Jul 1 doi: 10.1371/journal.pone.0235534. PMID: 32609745Free PMC Article
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Health Psychol 2019 Jul;38(7):577-585. Epub 2019 Apr 11 doi: 10.1037/hea0000719. PMID: 30973748
Wang H, Cheng Y, Chen S, Li X, Zhu Z, Zhang W
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Gao Y, Jiang L, Wang H, Yu C, Wang W, Liu S, Gao C, Tong X, Wang J, Jin Y, Wu J
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Clinical prediction guides

Nwokedi U, Zia M, Xu J, Sadhu AR, Baio FE, Kash BS, Sherman V, Tariq N
Surg Endosc 2022 Sep;36(9):6915-6923. Epub 2022 Jan 24 doi: 10.1007/s00464-022-09030-2. PMID: 35075523
Noguchi-Shinohara M, Yuki-Nozaki S, Abe C, Mori A, Horimoto M, Yokogawa M, Ishida N, Suga Y, Ishizaki J, Ishimiya M, Nakamura H, Komai K, Nakamura H, Shibata M, Ohara T, Hata J, Ninomiya T, Yamada M; Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) study group
J Alzheimers Dis 2022;85(1):235-247. doi: 10.3233/JAD-215153. PMID: 34806607
Galvin JE, Tolea MI, Chrisphonte S
PLoS One 2020;15(7):e0235534. Epub 2020 Jul 1 doi: 10.1371/journal.pone.0235534. PMID: 32609745Free PMC Article
Wang H, Cheng Y, Chen S, Li X, Zhu Z, Zhang W
J Stroke Cerebrovasc Dis 2019 Feb;28(2):470-476. Epub 2018 Nov 8 doi: 10.1016/j.jstrokecerebrovasdis.2018.10.026. PMID: 30415918
Domek N, Dux K, Pinzur M, Weaver F, Rogers T
J Foot Ankle Surg 2016 Sep-Oct;55(5):939-43. Epub 2016 Jun 20 doi: 10.1053/j.jfas.2016.04.009. PMID: 27338653

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