Study reveals type 2 diabetes diagnosis spurs cholesterol shifts, alters Ccardiovascular risk

A recent study published in the journal Scientific Reports assessed the associations between the change in total cholesterol (TC) levels after type 2 diabetes (T2D) diagnosis (relative to pre-diagnosis levels) and the risk of cardiovascular disease (CVD).

CVD is the global leading cause of mortality. T2D is a gateway disease to CVD. A study revealed higher coronary heart disease (CHD) and stroke risks in diabetes patients than in non-diabetic individuals. The global prevalence of T2D is expected to exceed 10% by 2030. Therefore, preventing CVD in people with diabetes could be of public health significance.

Hypercholesterolemia is a significant risk factor for CVD, and its adverse effects on CVD could be more evident in individuals with metabolic conditions, e.g., T2D. Diabetes patients may be more susceptible to hypercholesterolemia’s negative impact on CVD risk. Nonetheless, T2D diagnosis often results in positive lifestyle changes helping reduce hypercholesterolemia or CVD risk.

Study: Changes in total cholesterol level and cardiovascular disease risk among type 2 diabetes patients. Image Credit: crystal light / Shutterstock

About the study

In the present study, researchers explored the relationship between the change in TC levels pre- and post-T2D diagnosis with the risk of CVD. They selected participants with T2D from 2003 to 2012 from the National Health Insurance Service – Health Screening cohort in Korea. Patients were identified using relevant International Classification of Diseases, Tenth Revision (ICD-10) codes and based on the prescription history of anti-diabetes drugs.

Circulating TC levels were estimated after an eight-hour fasting period. TC levels two years before and after T2D diagnosis were classified into low (< 180 mg/dL), middle (180 to 239 mg/dL), and high (≥ 240 mg/dL). Accordingly, participants were stratified into high-low, high-middle, high-high, middle-low, middle-middle, middle-high, low-low, low-middle, and low-high groups based on the change in TC levels after T2D diagnosis from pre-diagnosis levels.

The primary outcome was the incidence of non-fatal CVD. The secondary outcome was the incidence of stroke or CHD. The team computed the cumulative probability of the incidence of CVD according to changes in TC levels. Hazard ratios of outcomes were calculated using Cox proportional hazards model. Additionally, the team performed a sub-group analysis according to the use of lipid-lowering drugs. Sensitivity analyses were restricted to those using statins.

Findings

The study included 23,821 participants; 9.9% were diagnosed with CVD. The incidence of CHD and stroke was 4.9% and 5.1%, respectively. Patients with increased TC levels after T2D diagnosis were likely to have higher use of lipid-lowering drugs, body mass index (BMI), fasting serum glucose, blood pressure, aspartate transaminase, alanine transaminase, and lower physical activity compared to those who had constant or unchanged TC levels post-T2D diagnosis.

Most participants taking lipid-lowering drugs used statins. The cumulative probability of the incidence of non-fatal CVD among T2D patients was significantly elevated in the low-middle, low-high, and middle-high groups. Conversely, it was significantly lower in middle-low, high-middle, and high-low groups. Higher and lower TC levels post-T2D diagnosis were associated with elevated and reduced CVD risk, respectively.

The risk of CVD increased in the low-middle and low-high groups but decreased in the high-middle group among participants not using lipid-lowering drugs. Among patients who used these drugs, the risk of CVD was higher in the low-middle group but lower in the high-middle and high-low groups. There was no evidence of interactions between the use of lipid-lowering drugs and the change in TC levels in the sub-group analysis.

The association of the change in TC levels was consistent for the risk of CHD or stroke but differed by the use of lipid-lowering drugs in the sub-group analysis. However, the results were not different in sensitivity analyses restricted to statin users. Additionally, the researchers conducted analyses in participants with data on high-density (HDL-C) or low-density lipoprotein cholesterol (LDL-C) and triglycerides.

There was no association between CVD risk and the changes in the triglyceride and HDL-C levels pre- and post-T2D diagnosis. However, a 10 mg/dL increase in LDL-C levels after T2D diagnosis relative to pre-diagnosis levels was associated with a higher risk of CVD and CHD, especially among those using lipid-lowering drugs.

Conclusions

Taken together, increased TC levels in T2D patients relative to pre-diagnosis levels were associated with a higher risk of CVD, whereas reduced TC levels were associated with a lower CVD risk, irrespective of the use of lipid-lowering drugs. Results were consistent for the risk of stroke and CHD. Females were likelier to exhibit no improvements in TC levels despite using lipid-lowering drugs. Therefore, the findings suggest that managing TC levels in T2D patients might be clinically significant in mitigating the risk of CVD.