Physicians' Academy for Cardiovascular Education

Three markers for the identification of individuals at high risk for statin-related diabetes

Kohli P et al., Am J Cardiol 2016


Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials)

Kohli P, Knowles JW, Sarraju A, et al.
Am J Cardiol 2016; published online ahead of print


Statin therapy has been associated with the development of type 2 DM, particularly in patients with higher blood pressures, elevated fasting plasma glucose (FPG) and higher triglyceride (TG) concentrations [1]. These parameters are also associated with insulin resistance, an independent predictor of T2DM [2,3].
It is hypothesised that the identification of insulin-resistant individuals before the initiation of statin treatment would decrease the risk of developing statin-related T2DM. Insulin resistance is increased in patients with prediabetes mellitus (PreDM), which is defined by an FPG concentration of ≥5.6 mmol/l (100 mg/dl) and <7.0 mmol/L (126 mg/dl) [4,5].
In this study, the impact of combining a diagnosis of PreDM with a measurement of either fasting TG concentration >1.7 mmol/l (>150 mg/dl) or a BMI of ≥27.0 kg/m2 on the identification of individuals on high risk of statin-associated T2DM was evaluated. 939 incident cases (8.2%) of T2DM were identified during a median follow-up of 4.9 years, in a study population pooled from patients without DM in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials.

Main results

  • The incidence of T2DM increased progressively in statin-treated patients with: normal fasting glucose (NFG) and TG ≤ 1.7 mmol/l: 2.8%, NFG and TG >1.7 mmol/l: 5.2%, PreDM and TG ≤ 1.7 mmol/l: 12.8% and PreDM and a TG >1.7 mmol/l: 22.8%.
  • In patients with PreDM, there was a substantially increased baseline risk for incident T2DM even with placebo treatment. Incident T2DM occurred in 7.6% of placebo treated patients with PreDM and TG ≤ 1.7 mmol/l, and 17.9% of placebo treated patients with PreDM and TG >1.7 mmol/l.
  • Statin treatment significantly increased the risk of T2DM in patients with PreDM compared to placebo: 22.8% of PreDM patients and TG >1.7 mmol/l developed incident T2DM, a 27% increased risk versus those on placebo.
  • HR for developing T2DM on statin treatment was significantly higher (p <0.001) in patients with either a TG concentration of >1.7 mmol/L (1.5; 95% CI: 1.2-2.0), or PreDM 4.0; 95% CI: 3.3-4.9, or both (6.7; 95% CI: 5.4-8.2), compared to those with NFG and TG ≤ 1.7 mmol/l.
  • Similar results were seen for the combination of PreDM and BMI, with HR for patients with NFG and BMI ≥ 27 kg/m2: 1.4; 95% CI: 1.1-1.9, HR for patients with PreDM and BMI <27 kg/m2: 3.5; 95% CI: 2.7-4.5, HR for patients with PreDM and BMI ≥27 kg/m2: 7.0; 95% CI: 5.6-8.6.


These data suggest that the statin-related incidence of T2DM is quite modest, but is aggravated if plasma glucose, TG concentrations and BMI increase.  The authors have created a simple 4-tier category system, based on PreDM, TG concentrations and BMI, which may be helpful in identifying individuals at high risk of developing statin-associated T2DM.
Find this article online at Am J Cardiol


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