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Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus.

ABSTRACT: Type 2 diabetes mellitus (DM) is a major cardiovascular (CV) risk factor and, as such, is considered a coronary artery disease risk equivalent. Although glycemic control is associated with decreased CV events epidemiologically, many prospective clinical trials have failed to conclusively demonstrate that aggressive glycemic control improves the CV prognosis of patients with type 2 DM, especially those with long-standing DM. Many therapies for type 2 DM with widely divergent mechanisms of action are available. Some of these drugs, in addition to their glucose-lowering actions, have properties that may reduce or increase CV events. Agents that lower both insulin resistance and postprandial hyperglycemia while at the same time avoiding hypoglycemia may be beneficial for CV health. This article reviews the evidence regarding the use of these agents and appropriate glycemic control targets for improving the adverse CV prognosis associated with type 2 DM. We conducted a systematic review of English articles using MEDLINE and the Cochrane Controlled Trials Register (1970-2010) using the following search terms: cardiovascular disease, randomized trials, hypoglycemia, and insulin resistance.

SUBMITTER: O'Keefe JH

PROVIDER: S-EPMC3031437 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus.

O'Keefe James H JH Abuannadi Mohammad M Lavie Carl J CJ Bell David S H DS

Mayo Clinic proceedings 20110126 2

Type 2 diabetes mellitus (DM) is a major cardiovascular (CV) risk factor and, as such, is considered a coronary artery disease risk equivalent. Although glycemic control is associated with decreased CV events epidemiologically, many prospective clinical trials have failed to conclusively demonstrate that aggressive glycemic control improves the CV prognosis of patients with type 2 DM, especially those with long-standing DM. Many therapies for type 2 DM with widely divergent mechanisms of action ...[more]

PMID: 21270290

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Project description:BACKGROUND:Poor glycemic control is associated with increased risk of cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM); however, little is known about mechanisms specific to T1DM. In T1DM, myocardial injury can induce persistent cardiac autoimmunity. Chronic hyperglycemia causes myocardial injury, raising the possibility that hyperglycemia-induced cardiac autoimmunity could contribute to long-term CVD complications in T1DM. METHODS:We measured the prevalence and profiles of cardiac autoantibodies (AAbs) in longitudinal samples from the DCCT (Diabetes Control and Complications Trial) in participants with mean hemoglobin A1c (HbA1c) ?9.0% (n=83) and ?7.0% (n=83) during DCCT. We assessed subsequent coronary artery calcification (measured once during years 7-9 in the post-DCCT EDIC [Epidemiology of Diabetes Interventions and Complications] observational study), high-sensitivity C-reactive protein (measured during EDIC years 4-6), and CVD events (defined as nonfatal myocardial infarction, stroke, death resulting from CVD, heart failure, or coronary artery bypass graft) over a 26-year median follow-up. Cardiac AAbs were also measured in matched patients with type 2 diabetes mellitus with HbA1c ?9.0% (n=70) and ?7.0% (n=140) and, as a control for cardiac autoimmunity, patients with Chagas cardiomyopathy (n=51). RESULTS:Apart from HbA1c levels, the DCCT groups shared similar CVD risk factors at the beginning and end of DCCT. The DCCT HbA1c ?9.0% group showed markedly higher cardiac AAb levels than the HbA1c ?7.0% group during DCCT, with a progressive increase and decrease in AAb levels over time in the 2 groups, respectively ( P<0.001). In the HbA1c ?9.0% group, 46%, 22%, and 11% tested positive for ?1, ?2, and ?3 different cardiac AAb types, respectively, similar to patients with Chagas cardiomyopathy, compared with 2%, 1%, and 0% in the HbA1c ?7.0% group. Glycemic control was not associated with AAb prevalence in type 2 diabetes mellitus. Positivity for ?2 AAbs during DCCT was associated with increased risk of CVD events (4 of 6; hazard ratio, 16.1; 95% CI, 3.0-88.2) and, in multivariable analyses, with detectable coronary artery calcification (13 of 31; odds ratio, 60.1; 95% CI, 8.4-410.0). Patients with ?2 AAbs subsequently also showed elevated high-sensitivity C-reactive protein levels (6.0 mg/L versus 1.4 mg/L in patients with ?1 AAbs; P=0.003). CONCLUSIONS:Poor glycemic control is associated with cardiac autoimmunity in T1DM. Furthermore, cardiac AAb positivity is associated with an increased risk of CVD decades later, suggesting a role for autoimmune mechanisms in the development of CVD in T1DM, possibly through inflammatory pathways.

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Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus.

Publications

Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus.

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