Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool

Jacob V Stidsen; Jan E Henriksen; Michael H Olsen; Reimar W Thomsen; Jens S Nielsen; Jørgen Rungby; Sinna P Ulrichsen; Klara Berencsi; Johnny A Kahlert; Søren G Friborg; Ivan Brandslund; Aneta A Nielsen; Jens S Christiansen; Henrik T Sørensen; Thomas B Olesen; Henning Beck-Nielsen

doi:10.1002/dmrr.3005

Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool

Jacob V Stidsen, Jan E Henriksen, Michael H Olsen, Reimar W Thomsen, Jens S Nielsen, Jørgen Rungby, Sinna P Ulrichsen, Klara Berencsi, Johnny A Kahlert, Søren G Friborg, Ivan Brandslund, Aneta A Nielsen, Jens S Christiansen, Henrik T Sørensen, Thomas B Olesen, Henning Beck-Nielsen

Institut for Klinisk Medicin

15 Citationer (Scopus)

Abstract

Background: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new clinically diagnosed type 2 diabetes. Methods: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. Results: Among 5813 patients diagnosed with incident type 2 diabetes in the community clinical setting, 0.4% had rare subtypes of diabetes, 2.8% had LADA, 0.7% had secondary diabetes, 2.4% had glucocorticoid-associated diabetes, and 93.7% had WHO-defined type 2 diabetes. In the latter group, 9.7% had insulinopenic, 63.1% had classical, and 27.2% had hyperinsulinemic type 2 diabetes. Classical patients were obese (median waist 105 cm), and 20.5% had cardiovascular disease (CVD) at diagnosis, while insulinopenic patients were fairly lean (waist 92 cm) and 17.5% had CVD (P = 0.14 vs classical diabetes). Hyperinsulinemic patients were severely obese (waist 112 cm), and 25.5% had CVD (P < 0.0001 vs classical diabetes). Conclusions: Patients clinically diagnosed with type 2 diabetes are a heterogeneous group. In the future, targeted treatment based on pathophysiological characteristics rather than the current “one size fits all” approach may improve patient prognosis.

Originalsprog	Engelsk
Artikelnummer	e3005
Tidsskrift	Diabetes - Metabolism: Research and Reviews (Print Edition)
Vol/bind	34
Udgave nummer	5
Antal sider	11
ISSN	1520-7552
DOI	https://doi.org/10.1002/dmrr.3005
Status	Udgivet - jul. 2018

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10.1002/dmrr.3005

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Stidsen, J. V., Henriksen, J. E., Olsen, M. H., Thomsen, R. W., Nielsen, J. S., Rungby, J., Ulrichsen, S. P., Berencsi, K., Kahlert, J. A., Friborg, S. G., Brandslund, I., Nielsen, A. A., Christiansen, J. S., Sørensen, H. T., Olesen, T. B., & Beck-Nielsen, H. (2018). Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool. Diabetes - Metabolism: Research and Reviews (Print Edition), 34(5), [e3005]. https://doi.org/10.1002/dmrr.3005

Stidsen, JV, Henriksen, JE, Olsen, MH, Thomsen, RW, Nielsen, JS, Rungby, J, Ulrichsen, SP, Berencsi, K, Kahlert, JA, Friborg, SG, Brandslund, I, Nielsen, AA, Christiansen, JS, Sørensen, HT, Olesen, TB & Beck-Nielsen, H 2018, 'Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool', Diabetes - Metabolism: Research and Reviews (Print Edition), bind 34, nr. 5, e3005. https://doi.org/10.1002/dmrr.3005

@article{3efd2e5a32114b32a5b1d6eeb6b83969,

title = "Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool",

abstract = "Background: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new clinically diagnosed type 2 diabetes. Methods: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. Results: Among 5813 patients diagnosed with incident type 2 diabetes in the community clinical setting, 0.4% had rare subtypes of diabetes, 2.8% had LADA, 0.7% had secondary diabetes, 2.4% had glucocorticoid-associated diabetes, and 93.7% had WHO-defined type 2 diabetes. In the latter group, 9.7% had insulinopenic, 63.1% had classical, and 27.2% had hyperinsulinemic type 2 diabetes. Classical patients were obese (median waist 105 cm), and 20.5% had cardiovascular disease (CVD) at diagnosis, while insulinopenic patients were fairly lean (waist 92 cm) and 17.5% had CVD (P = 0.14 vs classical diabetes). Hyperinsulinemic patients were severely obese (waist 112 cm), and 25.5% had CVD (P < 0.0001 vs classical diabetes). Conclusions: Patients clinically diagnosed with type 2 diabetes are a heterogeneous group. In the future, targeted treatment based on pathophysiological characteristics rather than the current “one size fits all” approach may improve patient prognosis.",

keywords = "Biomarkers/analysis, Blood Glucose/analysis, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2/classification, Female, Glycated Hemoglobin A/analysis, Humans, Hypoglycemic Agents/therapeutic use, Male, Middle Aged, Monitoring, Physiologic, Phenotype, Precision Medicine, Prognosis",

author = "Stidsen, {Jacob V} and Henriksen, {Jan E} and Olsen, {Michael H} and Thomsen, {Reimar W} and Nielsen, {Jens S} and J{\o}rgen Rungby and Ulrichsen, {Sinna P} and Klara Berencsi and Kahlert, {Johnny A} and Friborg, {S{\o}ren G} and Ivan Brandslund and Nielsen, {Aneta A} and Christiansen, {Jens S} and S{\o}rensen, {Henrik T} and Olesen, {Thomas B} and Henning Beck-Nielsen",

note = "Copyright {\textcopyright} 2018 John Wiley & Sons, Ltd.",

year = "2018",

month = jul,

doi = "10.1002/dmrr.3005",

language = "English",

volume = "34",

journal = "Diabetes/Metabolism Research and Reviews",

issn = "1520-7552",

publisher = "Wiley",

number = "5",

}

TY - JOUR

T1 - Pathophysiology-based phenotyping in type 2 diabetes

T2 - A clinical classification tool

AU - Stidsen, Jacob V

AU - Henriksen, Jan E

AU - Olsen, Michael H

AU - Thomsen, Reimar W

AU - Nielsen, Jens S

AU - Rungby, Jørgen

AU - Ulrichsen, Sinna P

AU - Berencsi, Klara

AU - Kahlert, Johnny A

AU - Friborg, Søren G

AU - Brandslund, Ivan

AU - Nielsen, Aneta A

AU - Christiansen, Jens S

AU - Sørensen, Henrik T

AU - Olesen, Thomas B

AU - Beck-Nielsen, Henning

PY - 2018/7

Y1 - 2018/7

N2 - Background: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new clinically diagnosed type 2 diabetes. Methods: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. Results: Among 5813 patients diagnosed with incident type 2 diabetes in the community clinical setting, 0.4% had rare subtypes of diabetes, 2.8% had LADA, 0.7% had secondary diabetes, 2.4% had glucocorticoid-associated diabetes, and 93.7% had WHO-defined type 2 diabetes. In the latter group, 9.7% had insulinopenic, 63.1% had classical, and 27.2% had hyperinsulinemic type 2 diabetes. Classical patients were obese (median waist 105 cm), and 20.5% had cardiovascular disease (CVD) at diagnosis, while insulinopenic patients were fairly lean (waist 92 cm) and 17.5% had CVD (P = 0.14 vs classical diabetes). Hyperinsulinemic patients were severely obese (waist 112 cm), and 25.5% had CVD (P < 0.0001 vs classical diabetes). Conclusions: Patients clinically diagnosed with type 2 diabetes are a heterogeneous group. In the future, targeted treatment based on pathophysiological characteristics rather than the current “one size fits all” approach may improve patient prognosis.

AB - Background: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new clinically diagnosed type 2 diabetes. Methods: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. Results: Among 5813 patients diagnosed with incident type 2 diabetes in the community clinical setting, 0.4% had rare subtypes of diabetes, 2.8% had LADA, 0.7% had secondary diabetes, 2.4% had glucocorticoid-associated diabetes, and 93.7% had WHO-defined type 2 diabetes. In the latter group, 9.7% had insulinopenic, 63.1% had classical, and 27.2% had hyperinsulinemic type 2 diabetes. Classical patients were obese (median waist 105 cm), and 20.5% had cardiovascular disease (CVD) at diagnosis, while insulinopenic patients were fairly lean (waist 92 cm) and 17.5% had CVD (P = 0.14 vs classical diabetes). Hyperinsulinemic patients were severely obese (waist 112 cm), and 25.5% had CVD (P < 0.0001 vs classical diabetes). Conclusions: Patients clinically diagnosed with type 2 diabetes are a heterogeneous group. In the future, targeted treatment based on pathophysiological characteristics rather than the current “one size fits all” approach may improve patient prognosis.

KW - Biomarkers/analysis

KW - Blood Glucose/analysis

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Diabetes Mellitus, Type 2/classification

KW - Female

KW - Glycated Hemoglobin A/analysis

KW - Humans

KW - Hypoglycemic Agents/therapeutic use

KW - Male

KW - Middle Aged

KW - Monitoring, Physiologic

KW - Phenotype

KW - Precision Medicine

KW - Prognosis

U2 - 10.1002/dmrr.3005

DO - 10.1002/dmrr.3005

M3 - Journal article

C2 - 29697198

SN - 1520-7552

VL - 34

JO - Diabetes/Metabolism Research and Reviews

JF - Diabetes/Metabolism Research and Reviews

IS - 5

M1 - e3005

ER -

Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool

Abstract

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