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Development and validation of optimal phenomapping methods to estimate long-term atherosclerotic cardiovascular disease risk in patients with type 2 diabetes

Diabetologia, 2021-07, Vol.64 (7), p.1583-1594 [Peer Reviewed Journal]

The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021 ;The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021. ;ISSN: 0012-186X ;EISSN: 1432-0428 ;DOI: 10.1007/s00125-021-05426-2 ;PMID: 33715025

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Title:
Development and validation of optimal phenomapping methods to estimate long-term atherosclerotic cardiovascular disease risk in patients with type 2 diabetes
Author: Segar, Matthew W. ; Patel, Kershaw V. ; Vaduganathan, Muthiah ; Caughey, Melissa C. ; Jaeger, Byron C. ; Basit, Mujeeb ; Willett, Duwayne ; Butler, Javed ; Sengupta, Partho P. ; Wang, Thomas J. ; McGuire, Darren K. ; Pandey, Ambarish
Subjects: Aged ; Angina ; Angioplasty ; Arteriosclerosis ; Atherosclerosis - diagnosis ; Atherosclerosis - epidemiology ; Atherosclerosis - etiology ; Bayesian analysis ; Biological Variation, Population ; Cardiometabolic Risk Factors ; Cardiovascular diseases ; Cardiovascular Diseases - diagnosis ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - etiology ; Cardiovascular system ; Cluster Analysis ; Cohort Studies ; Demography ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - therapy ; Diabetic Angiopathies - diagnosis ; Diabetic Angiopathies - epidemiology ; Diabetic Angiopathies - etiology ; Epidemiology ; Female ; Follow-Up Studies ; Heart attacks ; Human Physiology ; Humans ; Internal Medicine ; Male ; Mathematical models ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Myocardial infarction ; Patients ; Phenotype ; Principal components analysis ; Prognosis ; Risk Assessment - methods ; Risk Factors ; Statistics as Topic - methods ; Treatment Outcome ; United States - epidemiology
Is Part Of: Diabetologia, 2021-07, Vol.64 (7), p.1583-1594
Description: Aims/hypothesis Type 2 diabetes is a heterogeneous disease process with variable trajectories of CVD risk. We aimed to evaluate four phenomapping strategies and their ability to stratify CVD risk in individuals with type 2 diabetes and to identify subgroups who may benefit from specific therapies. Methods Participants with type 2 diabetes and free of baseline CVD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial were included in this study ( N = 6466). Clustering using Gaussian mixture models, latent class analysis, finite mixture models (FMMs) and principal component analysis was compared. Clustering variables included demographics, medical and social history, laboratory values and diabetes complications. The interaction between the phenogroup and intensive glycaemic, combination lipid and intensive BP therapy for the risk of the primary outcome (composite of fatal myocardial infarction, non-fatal myocardial infarction or unstable angina) was evaluated using adjusted Cox models. The phenomapping strategies were independently assessed in an external validation cohort (Look Action for Health in Diabetes [Look AHEAD] trial: n = 4211; and Bypass Angioplasty Revascularisation Investigation 2 Diabetes [BARI 2D] trial: n = 1495). Results Over 9.1 years of follow-up, 789 (12.2%) participants had a primary outcome event. FMM phenomapping with three phenogroups was the best-performing clustering strategy in both the derivation and validation cohorts as determined by Bayesian information criterion, Dunn index and improvement in model discrimination. Phenogroup 1 ( n = 663, 10.3%) had the highest burden of comorbidities and diabetes complications, phenogroup 2 ( n = 2388, 36.9%) had an intermediate comorbidity burden and lowest diabetes complications, and phenogroup 3 ( n = 3415, 52.8%) had the fewest comorbidities and intermediate burden of diabetes complications. Significant interactions were observed between phenogroups and treatment interventions including intensive glycaemic control ( p -interaction = 0.042) and combination lipid therapy ( p -interaction < 0.001) in the ACCORD, intensive lifestyle intervention ( p -interaction = 0.002) in the Look AHEAD and early coronary revascularisation ( p -interaction = 0.003) in the BARI 2D trial cohorts for the risk of the primary composite outcome. Favourable reduction in the risk of the primary composite outcome with these interventions was noted in low-risk participants of phenogroup 3 but not in other phenogroups. Compared with phenogroup 3, phenogroup 1 participants were more likely to have severe/symptomatic hypoglycaemic events and medication non-adherence on follow-up in the ACCORD and Look AHEAD trial cohorts. Conclusions/interpretation Clustering using FMMs was the optimal phenomapping strategy to identify replicable subgroups of patients with type 2 diabetes with distinct clinical characteristics, CVD risk and response to therapies. Graphical abstract
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
Language: English
Identifier: ISSN: 0012-186X
EISSN: 1432-0428
DOI: 10.1007/s00125-021-05426-2
PMID: 33715025
Source: MEDLINE
ProQuest Central

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Development and validation of optimal phenomapping methods to estimate long-term atherosclerotic cardiovascular disease risk in patients with type 2 diabetes

The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021 ;The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021. ;ISSN: 0012-186X ;EISSN: 1432-0428 ;DOI: 10.1007/s00125-021-05426-2 ;PMID: 33715025

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