Cardio-renal-metabolic comorbidities (CRMCs) associated with type 2 diabetes (T2DM) increase patient morbidity and mortality. We evaluated the incremental contribution of various CRMCs to the risk of myocardial infarction, stroke, or cardiovascular death (MACE), heart failure (HF), and all-cause mortality (ACM) in patients with newly diagnosed T2DM. Using ICD-9 codes, T2DM patients were identified in a U.S. EMR (Humedica/Optum) database along with other CRMCs (hypertension {HTN}, hyperlipidemia {HPLD}, chronic kidney disease {CKD}) at the time of T2DM diagnosis. Patients’ records were assessed for the occurrence of MACE, HF, and ACM. Between 1 Jan 2011 and 31 Mar 2015, 180722 incident T2DM patients were identified (age {mean [SD]}: 62.4 [13.5], 52.0% male) with/without CRMCs: T2DM only (n=25114; 13.9%), T2DM+HTN (n=20863; 11.5%), T2DM+HPLD (n=13274; 7.3%) T2DM+HTN+HPLD (n=52415; 29.0%), and T2DM+HTN+HPLD+CKD (9.9%). The risk of MACE, HF and ACM increased with a greater number of CRMCs (Table), CKD being associated with the highest incremental risk for ACM. In patients with new diagnosis of T2DM, the risk of MACE, HF, and death increased incrementally with a greater number of CRMCs; with CKD being the main driver of mortality. These results may have implications for risk factor management, and potentially selection of treatment strategies among T2DM patients with various CRMCs.

Table

MACE, HF, and ACM rates in patients with incident T2DM and cardio-renal-metabolic diseases

Outcomes CRMCs at time of T2DM Diagnosis Event rate (95% CI) events/100 PY Incremental % increase in relative risk 
MACE T2DM only 5.16 (5.00, 5.32) Reference 
 T2DM + HTN + HPLD 7.04 (6.91, 7.18) 36 
 T2DM + HTN + HPLD + CKD 9.15 (8.87, 9.43) 30 
HF T2DM only 4.84 (4.69, 5.00) Reference 
 T2DM + HTN + HPLD 6.24 (6.12, 6.37) 29 
 T2DM + HTN + HPLD + CKD 8.40 (8.14, 8.66) 35 
ACM T2DM only 2.26 (2.16, 2.37) Reference 
 T2DM + HTN + HPLD 2.57 (2.50, 2.64) 14 
 T2DM + HTN + HPLD + CKD 5.19 (5.01, 5.38) 102 
ACM, all-cause mortality; CI, confidence interval; CRMCs, cardio-renal-metabolic comorbidities; CKD, chronic kidney disease; HF, heart failure; HTN, hypertension; HPLD, hyperlipidemia; MACE, myocardial infarction, stroke, or cardiovascular death; PY, patient-years; T2DM, type 2 diabetes mellitus. 
Outcomes CRMCs at time of T2DM Diagnosis Event rate (95% CI) events/100 PY Incremental % increase in relative risk 
MACE T2DM only 5.16 (5.00, 5.32) Reference 
 T2DM + HTN + HPLD 7.04 (6.91, 7.18) 36 
 T2DM + HTN + HPLD + CKD 9.15 (8.87, 9.43) 30 
HF T2DM only 4.84 (4.69, 5.00) Reference 
 T2DM + HTN + HPLD 6.24 (6.12, 6.37) 29 
 T2DM + HTN + HPLD + CKD 8.40 (8.14, 8.66) 35 
ACM T2DM only 2.26 (2.16, 2.37) Reference 
 T2DM + HTN + HPLD 2.57 (2.50, 2.64) 14 
 T2DM + HTN + HPLD + CKD 5.19 (5.01, 5.38) 102 
ACM, all-cause mortality; CI, confidence interval; CRMCs, cardio-renal-metabolic comorbidities; CKD, chronic kidney disease; HF, heart failure; HTN, hypertension; HPLD, hyperlipidemia; MACE, myocardial infarction, stroke, or cardiovascular death; PY, patient-years; T2DM, type 2 diabetes mellitus. 

Disclosure

S.V. Arnold: None. P.R. Hunt: Consultant; Self; AstraZeneca, Sanofi US. H. Chen: Employee; Self; AstraZeneca. S. MacLachlan: Consultant; Self; AstraZeneca. E. Repetto: Employee; Self; AstraZeneca. J. Vora: Other Relationship; Self; AstraZeneca. M. Kosiborod: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Amgen Inc., Sanofi, Boehringer Ingelheim GmbH, GlaxoSmithKline plc., Glytec Systems, Merck & Co., Inc., Novo Nordisk A/S, Janssen Pharmaceuticals, Inc., ZS Pharma, Inc., Intarcia Therapeutics, Inc., Novartis AG. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH.

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