Ketosis-prone diabetes

Ketosis-prone diabetes
Ketosis-prone diabetes
Other names	KPD
Specialty	Endocrinology

Ketosis-prone diabetes (KPD) is an intermediate form of diabetes that has some characteristics of type 1 and some of type 2 diabetes. Type 1 diabetes involves autoimmune destruction of pancreatic beta cells which create insulin. This occurs earlier in a person's life, leading to patients being insulin dependent, and the lack of natural insulin makes patients prone to a condition called diabetic ketoacidosis (DKA). Type 2 diabetes is different in that it is usually caused by insulin resistance in the body in older patients leading to beta cell burnout over time, and is not prone to DKA. KPD is a condition that involves DKA like type 1, but occurs later in life and can regain beta cell function like type 2 diabetes. However, it is distinct from latent autoimmune diabetes of adults (LADA), a form of type 1 sometimes referred to as type 1.5 that does not occur with DKA.^[1] There are also distinctions to be made between KPD and LADA as patients who exhibit KPD symptoms can regain beta cell function similar to type 2 diabetics whereas LADA will not exhibit this reclamation of beta cell function.

KPD is readily diagnosable because it presents a single characteristic, ketoacidosis, which confirms it as ketosis-prone diabetes.^[2] KPD comes in four forms depending upon the presence or absence of β-cell autoantibodies (A+ or A−) and β-cell functional reserve (β+ or β−).^[3] Other styles of classification have been used for KPD, including styles incorporating BMI, but the Aβ system has been found to have the highest accuracy and predictive value of all the systems utilized.^[4] The autoantibodies used to diagnose the A+ subtypes of KPD include the autoantibodies detected in patients with type 1 diabetes, including Glutamic Acid Decarboxylase 65 (GAD65), Zinc Transporter T8 (ZnT8), Islet Antigen-2 (IA-2), and HLA class II type 1 diabetes susceptibility alleles.^[5]

^ Balasubramanyam A, Nalini R, Hampe CS, Maldonado M (May 2008). "Syndromes of ketosis-prone diabetes mellitus". Endocrine Reviews. 29 (3): 292–302. doi:10.1210/er.2007-0026. PMC 2528854. PMID 18292467. There is clearly a spectrum of clinical phenotypes among patients with islet autoantibodies who do not present with ketosis, including those termed "latent autoimmune diabetes in adults" (LADA) (30), "type 1.5 diabetes" (31,32,33), and "slowly progressing type 1 diabetes" (34). A similar spectrum exists in KPD that includes the very different phenotypes of A+β− and A+β+ KPD. A+β− KPD is synonymous with classic, early onset autoimmune type 1 diabetes; A+β+ KPD may overlap with LADA. However, there are differences between LADA, as recently defined by the Immunology of Diabetes Society, and A+β+ KPD patients; most importantly, the definition of LADA excludes patients who require insulin within the first 6 months after diagnosis, whereas the majority (90%) of A+β+ KPD patients present with DKA as the first manifestation of diabetes and therefore require insulin at the start.
^ Leslie RD, Kolb H, Schloot NC, Buzzetti R, Mauricio D, De Leiva A, et al. (October 2008). "Diabetes classification: grey zones, sound and smoke: Action LADA 1". Diabetes/Metabolism Research and Reviews. 24 (7): 511–519. doi:10.1002/dmrr.877. PMID 18615859. S2CID 205757168.
^ Nalini R, Gaur LK, Maldonado M, Hampe CS, Rodriguez L, Garza G, et al. (June 2008). "HLA class II alleles specify phenotypes of ketosis-prone diabetes". Diabetes Care. 31 (6): 1195–1200. doi:10.2337/dc07-1971. PMC 10027360. PMID 18316396.
^ Balasubramanyam A, Garza G, Rodriguez L, Hampe CS, Gaur L, Lernmark A, Maldonado MR (December 2006). "Accuracy and predictive value of classification schemes for ketosis-prone diabetes". Diabetes Care. 29 (12): 2575–2579. doi:10.2337/dc06-0749. PMID 17130187.
^ Mulukutla SN, Acevedo-Calado M, Hampe CS, Pietropaolo M, Balasubramanyam A (December 2018). "Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes". Diabetes Care. 41 (12): 2637–2640. doi:10.2337/dc18-0613. PMC 6245211. PMID 30327357.

[1] Balasubramanyam A, Nalini R, Hampe CS, Maldonado M (May 2008). "Syndromes of ketosis-prone diabetes mellitus". Endocrine Reviews. 29 (3): 292–302. doi:10.1210/er.2007-0026. PMC 2528854. PMID 18292467. There is clearly a spectrum of clinical phenotypes among patients with islet autoantibodies who do not present with ketosis, including those termed "latent autoimmune diabetes in adults" (LADA) (30), "type 1.5 diabetes" (31,32,33), and "slowly progressing type 1 diabetes" (34). A similar spectrum exists in KPD that includes the very different phenotypes of A+β− and A+β+ KPD. A+β− KPD is synonymous with classic, early onset autoimmune type 1 diabetes; A+β+ KPD may overlap with LADA. However, there are differences between LADA, as recently defined by the Immunology of Diabetes Society, and A+β+ KPD patients; most importantly, the definition of LADA excludes patients who require insulin within the first 6 months after diagnosis, whereas the majority (90%) of A+β+ KPD patients present with DKA as the first manifestation of diabetes and therefore require insulin at the start.

[2] Leslie RD, Kolb H, Schloot NC, Buzzetti R, Mauricio D, De Leiva A, et al. (October 2008). "Diabetes classification: grey zones, sound and smoke: Action LADA 1". Diabetes/Metabolism Research and Reviews. 24 (7): 511–519. doi:10.1002/dmrr.877. PMID 18615859. S2CID 205757168.

[3] Nalini R, Gaur LK, Maldonado M, Hampe CS, Rodriguez L, Garza G, et al. (June 2008). "HLA class II alleles specify phenotypes of ketosis-prone diabetes". Diabetes Care. 31 (6): 1195–1200. doi:10.2337/dc07-1971. PMC 10027360. PMID 18316396.

[4] Balasubramanyam A, Garza G, Rodriguez L, Hampe CS, Gaur L, Lernmark A, Maldonado MR (December 2006). "Accuracy and predictive value of classification schemes for ketosis-prone diabetes". Diabetes Care. 29 (12): 2575–2579. doi:10.2337/dc06-0749. PMID 17130187.

[5] Mulukutla SN, Acevedo-Calado M, Hampe CS, Pietropaolo M, Balasubramanyam A (December 2018). "Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes". Diabetes Care. 41 (12): 2637–2640. doi:10.2337/dc18-0613. PMC 6245211. PMID 30327357.

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