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Type 1 diabetes mellitus 12(T1D12)

MedGen UID:
318618
Concept ID:
C1832392
Disease or Syndrome
Synonyms: Diabetes mellitus, insulin-dependent, 12; T1D12
 
Gene (location): CTLA4 (2q33.2)
 
Monarch Initiative: MONDO:0011068
OMIM®: 601388

Definition

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.

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.

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. [from MedlinePlus Genetics]

Professional guidelines

PubMed

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
Reynolds AN, Akerman AP, Mann J
PLoS Med 2020 Mar;17(3):e1003053. Epub 2020 Mar 6 doi: 10.1371/journal.pmed.1003053. PMID: 32142510Free PMC Article
Alexopoulos AS, Blair R, Peters AL
JAMA 2019 May 14;321(18):1811-1819. doi: 10.1001/jama.2019.4981. PMID: 31087027Free PMC Article

Recent clinical studies

Etiology

Park J, Ntelis S, Yunasan E, Downton KD, Yip TC, Munir KM, Haq N
J Clin Endocrinol Metab 2023 Dec 21;109(1):279-292. doi: 10.1210/clinem/dgad471. PMID: 37561012
Simmons KM, Sims EK
J Clin Endocrinol Metab 2023 Nov 17;108(12):3067-3079. doi: 10.1210/clinem/dgad328. PMID: 37290044
Patil SP
Prim Care 2022 Jun;49(2):225-237. Epub 2022 Apr 22 doi: 10.1016/j.pop.2021.11.003. PMID: 35595479
Sharif K, Watad A, Coplan L, Amital H, Shoenfeld Y, Afek A
Expert Rev Clin Immunol 2018 Dec;14(12):1081-1088. Epub 2018 Oct 24 doi: 10.1080/1744666X.2018.1538787. PMID: 30336709
Maraschin Jde F
Adv Exp Med Biol 2012;771:12-9. doi: 10.1007/978-1-4614-5441-0_2. PMID: 23393666

Diagnosis

Imagawa A, Hanafusa T
J Clin Endocrinol Metab 2023 Nov 17;108(12):e1473-e1478. doi: 10.1210/clinem/dgad329. PMID: 37309685
Simmons KM, Sims EK
J Clin Endocrinol Metab 2023 Nov 17;108(12):3067-3079. doi: 10.1210/clinem/dgad328. PMID: 37290044
Ben-Skowronek I
Genes (Basel) 2021 Feb 24;12(3) doi: 10.3390/genes12030323. PMID: 33668198Free PMC Article
de Groot P, Nikolic T, Pellegrini S, Sordi V, Imangaliyev S, Rampanelli E, Hanssen N, Attaye I, Bakker G, Duinkerken G, Joosten A, Prodan A, Levin E, Levels H, Potter van Loon B, van Bon A, Brouwer C, van Dam S, Simsek S, van Raalte D, Stam F, Gerdes V, Hoogma R, Diekman M, Gerding M, Rustemeijer C, de Bakker B, Hoekstra J, Zwinderman A, Bergman J, Holleman F, Piemonti L, De Vos W, Roep B, Nieuwdorp M
Gut 2021 Jan;70(1):92-105. Epub 2020 Oct 26 doi: 10.1136/gutjnl-2020-322630. PMID: 33106354Free PMC Article
Kietsiriroje N, Pearson S, Campbell M, Ariëns RAS, Ajjan RA
Diabetes Obes Metab 2019 Dec;21(12):2609-2618. Epub 2019 Aug 19 doi: 10.1111/dom.13848. PMID: 31373146

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
Abraham MB, de Bock M, Smith GJ, Dart J, Fairchild JM, King BR, Ambler GR, Cameron FJ, McAuley SA, Keech AC, Jenkins A, Davis EA, O'Neal DN, Jones TW; Australian Juvenile Diabetes Research Fund Closed-Loop Research group
JAMA Pediatr 2021 Dec 1;175(12):1227-1235. doi: 10.1001/jamapediatrics.2021.3965. PMID: 34633418Free PMC Article
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
Taylor SI, Blau JE, Rother KI, Beitelshees AL
Lancet Diabetes Endocrinol 2019 Dec;7(12):949-958. Epub 2019 Oct 1 doi: 10.1016/S2213-8587(19)30154-8. PMID: 31585721Free PMC Article
Ovalle F, Grimes T, Xu G, Patel AJ, Grayson TB, Thielen LA, Li P, Shalev A
Nat Med 2018 Aug;24(8):1108-1112. Epub 2018 Jul 9 doi: 10.1038/s41591-018-0089-4. PMID: 29988125Free PMC Article

Prognosis

Thomson I, Anderson N, Bath L, Kiff S, Patterson C, Philip S, Waugh N, Wild SH; Scottish Study Group for the Care of Diabetes in the Young and the Scottish Diabetes Research Network Epidemiology Group
Diabet Med 2023 Aug;40(8):e15069. Epub 2023 Feb 25 doi: 10.1111/dme.15069. PMID: 36786040
Kara I, Temiz F, Doganer A, Sagıroglu S, Yıldız MG, Bilal N, Orhan I
Eur Arch Otorhinolaryngol 2023 Jan;280(1):269-275. Epub 2022 Jul 13 doi: 10.1007/s00405-022-07543-z. PMID: 35829805
Gregory GA, Robinson TIG, Linklater SE, Wang F, Colagiuri S, de Beaufort C, Donaghue KC; International Diabetes Federation Diabetes Atlas Type 1 Diabetes in Adults Special Interest Group, Magliano DJ, Maniam J, Orchard TJ, Rai P, Ogle GD
Lancet Diabetes Endocrinol 2022 Oct;10(10):741-760. Epub 2022 Sep 13 doi: 10.1016/S2213-8587(22)00218-2. PMID: 36113507
Cohen A, Mok E, Simard M, Dubé M, Larocque I, Plante C, Legault L, Huot C, Wafa S, Rahme E, Nakhla M
Can J Diabetes 2022 Mar;46(2):189-195. Epub 2021 Aug 21 doi: 10.1016/j.jcjd.2021.08.006. PMID: 35101343
Pedersen-Bjergaard U, Thorsteinsson B
Curr Diab Rep 2017 Oct 28;17(12):131. doi: 10.1007/s11892-017-0965-1. PMID: 29080929

Clinical prediction guides

Joglekar MV, Kaur S, Pociot F, Hardikar AA
Lancet Diabetes Endocrinol 2024 Jul;12(7):483-492. Epub 2024 May 23 doi: 10.1016/S2213-8587(24)00103-7. PMID: 38797187
Simmons KM, Sims EK
J Clin Endocrinol Metab 2023 Nov 17;108(12):3067-3079. doi: 10.1210/clinem/dgad328. PMID: 37290044
Redondo MJ, Oram RA, Steck AK
Curr Diab Rep 2017 Oct 28;17(12):129. doi: 10.1007/s11892-017-0961-5. PMID: 29080981
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
Stene LC, Gale EA
Diabetologia 2013 Sep;56(9):1888-97. Epub 2013 May 10 doi: 10.1007/s00125-013-2929-6. PMID: 23657800

Recent systematic reviews

Chiavaroli L, Lee D, Ahmed A, Cheung A, Khan TA, Blanco S, Mejia, Mirrahimi A, Jenkins DJA, Livesey G, Wolever TMS, Rahelić D, Kahleová H, Salas-Salvadó J, Kendall CWC, Sievenpiper JL
BMJ 2021 Aug 4;374:n1651. doi: 10.1136/bmj.n1651. PMID: 34348965Free 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
Reynolds AN, Akerman AP, Mann J
PLoS Med 2020 Mar;17(3):e1003053. Epub 2020 Mar 6 doi: 10.1371/journal.pmed.1003053. PMID: 32142510Free PMC Article
Quirk H, Blake H, Tennyson R, Randell TL, Glazebrook C
Diabet Med 2014 Oct;31(10):1163-73. doi: 10.1111/dme.12531. PMID: 24965376Free PMC Article
Roy T, Lloyd CE
J Affect Disord 2012 Oct;142 Suppl:S8-21. doi: 10.1016/S0165-0327(12)70004-6. PMID: 23062861

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