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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
Artikelnummere3005
TidsskriftDiabetes - Metabolism: Research and Reviews (Print Edition)
Vol/bind34
Udgave nummer5
Antal sider11
ISSN1520-7552
DOI
StatusUdgivet - jul. 2018

Fingeraftryk

Medical problems
Type 2 Diabetes Mellitus
Insulin Resistance
Glucocorticoids
Insulin

Citer dette

Stidsen, Jacob V ; Henriksen, Jan E ; Olsen, Michael H ; Thomsen, Reimar W ; Nielsen, Jens S ; Rungby, Jørgen ; Ulrichsen, Sinna P ; Berencsi, Klara ; Kahlert, Johnny A ; Friborg, Søren G ; Brandslund, Ivan ; Nielsen, Aneta A ; Christiansen, Jens S ; Sørensen, Henrik T ; Olesen, Thomas B ; Beck-Nielsen, Henning. / Pathophysiology-based phenotyping in type 2 diabetes : A clinical classification tool. I: Diabetes - Metabolism: Research and Reviews (Print Edition). 2018 ; Bind 34, Nr. 5.
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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.",
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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 {\circledC} 2018 John Wiley & Sons, Ltd.",
year = "2018",
month = "7",
doi = "10.1002/dmrr.3005",
language = "English",
volume = "34",
journal = "Diabetes - Metabolism: Research and Reviews (Print Edition)",
issn = "1520-7552",
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Pathophysiology-based phenotyping in type 2 diabetes : A clinical classification tool. / Stidsen, Jacob V; Henriksen, Jan E; Olsen, Michael H; Thomsen, Reimar W; Nielsen, Jens S; Rungby, Jørgen; Ulrichsen, Sinna P; Berencsi, Klara; Kahlert, Johnny A; Friborg, Søren G; Brandslund, Ivan; Nielsen, Aneta A; Christiansen, Jens S; Sørensen, Henrik T; Olesen, Thomas B; Beck-Nielsen, Henning.

I: Diabetes - Metabolism: Research and Reviews (Print Edition), Bind 34, Nr. 5, e3005, 07.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

N1 - Copyright © 2018 John Wiley & Sons, Ltd.

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 - clinical diabetes

KW - individualized treatment

KW - insulin secretion

KW - insulin sensitivity and resistance

KW - pathophysiology

KW - treatment guidelines

KW - Prognosis

KW - Cross-Sectional Studies

KW - Biomarkers/analysis

KW - Humans

KW - Middle Aged

KW - Male

KW - Blood Glucose/analysis

KW - Monitoring, Physiologic

KW - Phenotype

KW - Diabetes Mellitus, Type 2/classification

KW - Female

KW - Hypoglycemic Agents/therapeutic use

KW - Glycated Hemoglobin A/analysis

KW - Cohort Studies

KW - Precision Medicine

U2 - 10.1002/dmrr.3005

DO - 10.1002/dmrr.3005

M3 - Journal article

VL - 34

JO - Diabetes - Metabolism: Research and Reviews (Print Edition)

JF - Diabetes - Metabolism: Research and Reviews (Print Edition)

SN - 1520-7552

IS - 5

M1 - e3005

ER -