Statins may raise the risk of new-onset type 2 diabetes by increasing insulin resistance and insulin production, a new clinical study has found.
Notably, taking high-dose atorvastatin for 10 weeks increased insulin resistance and insulin production by a median of 8% and 9%, respectively.
The study, “Statins are associated with increased insulin resistance and secretion,” was published in Arteriosclerosis, Thrombosis, and Vascular Biology.
Almost half of the adult population in the United States take statins to prevent atherosclerotic cardiovascular disease (ASCVD). Statins are generally safe, but they increase the risk of new-onset type 2 diabetes in users by 10% over five years. The risk is further increased in people with prediabetes and insulin resistance.
Although statins increase type 2 diabetes risk, the pathways involved are unclear. Past studies show that statins may increase fasting insulin and insulin resistance, but these studies measured insulin resistance and insulin secretion using indirect methods. Moreover, other studies that evaluated insulin resistance directly, measured it after treating adults with statins that are not commonly prescribed, including pravastatin, simvastatin and rosuvastatin.
Guidelines recommend atorvastatin as the first-line therapy to prevent ASCVD. While it also increases type 2 diabetes risk, it is unclear whether atorvastatin raises type 2 diabetes risk by increasing insulin resistance or reducing insulin secretion.
To investigate this, a team of scientists at Stanford University directly measured insulin resistance and insulin secretion after treating adults without ASCVD and type 2 diabetes with atorvastatin.
Eligible participants completed a lipids panel, an oral glucose tolerance test (OGTT), and tests to measure fasting insulin, insulin resistance and insulin secretion. After the tests, all participants were given 40 mg atorvastatin daily for 10 weeks and were asked to maintain their diet, weight, and physical activity levels. Participants were monitored fortnightly and, their glucose tolerance, insulin secretion and insulin resistance were remeasured on weeks eight, nine and ten, respectively.
A total of 71 participants were included in the final analysis. The median age of study participants was 61 years, 37% were women and 65% were Caucasian. Overall, the group was overweight (body mass index of 27.8) with raised total and low-density lipoprotein (LDL) cholesterol.
A total of 63.4% had abnormal glucose tolerance and 40.8% had the metabolic syndrome. Participants with abnormal glucose tolerance had higher body mass index, were more insulin resistant and had higher insulin secretion than those with normal glucose tolerance. Similarly, participants with the metabolic syndrome were more insulin resistant and had higher insulin secretion than those without the metabolic syndrome.
While atorvastatin reduced total cholesterol (37%) LDL-C (53%) and triglycerides (28%) it significantly increased insulin resistance by 8% in the cohort. Fasting insulin levels and insulin secretion were also increased by 7% and 9%, respectively. Further analysis a showed a positive link between insulin resistance and insulin secretion such that as insulin resistance increased, insulin secretion increased.
Interestingly, atorvastatin increased insulin resistance by 16% in people who were insulin-sensitive and by 1% in people who were insulin-resistant. However, it increased insulin secretion similarly in both insulin-sensitive and insulin resistant individuals, 11% vs. 9%, respectively.
Atorvastatin also increased insulin resistance in people with abnormal glucose tolerance and the metabolic syndrome, but the increase was significantly higher in people with normal glucose tolerance and without the metabolic syndrome.
“Our results show that treatment with high-dose atorvastatin for 10 weeks increases insulin resistance and insulin secretion,” the researchers wrote.
“We did not observe differences by sex, age or race/ethnicity. However, we saw proportionately greater increases in insulin resistance in those who were more insulin sensitive at baseline. This may represent a ceiling effect for some insulin resistant participants. In that vein, we have observed that those with marked insulin resistance at baseline may not get substantially more insulin resistant even with modest weight gain,” they wrote.
The short-term duration of the study did not allow the researchers to measure the effects of long-term statin therapy on insulin secretion. However, they found that in some participants, insulin secretion increased as insulin resistance increased, but in others, insulin secretion decreased despite increased insulin resistance, indicating an inability to compensate for increase in insulin resistance and a higher risk of type 2 diabetes.
“We found that short-term treatment with high-intensity atorvastatin therapy results in increases in insulin resistance accompanied by increases in insulin secretion. Over time, the risk of new-onset type 2 diabetes associated with statin therapy may increase in those individuals who become more insulin resistance but are unable to maintain compensatory increase in insulin secretion,” the researchers wrote.
The researchers caution against using this study as a basis to avoid statin therapy because modelling studies suggest that the benefits may outweigh the risk. Instead they suggest making lifestyle changes to lower the risk of type 2 diabetes.
“All individuals on statin therapy should be encouraged to mitigate the risk of diabetes though healthy lifestyle incorporating a nutrition and exercise plan,” they wrote.
Although this study provides some insight into the pathways that predispose individuals using statins to type 2 diabetes, further studies are needed to investigate the long-term effects of statins on insulin secretion.
It is well established that statins increase the risk of type 2 diabetes. But it was interesting to learn that statins may increase the risk of type 2 diabetes by increasing insulin resistance and increasing secretion. The body usually tries to compensate for insulin resistance by producing more insulin but when it can no longer produce enough compensatory insulin, type 2 diabetes results.
This study is suggesting that just by taking statins, insulin resistance and insulin production increases even in insulin-sensitive people. But the authors suggest that the benefits of taking statins (reducing CVD risk) outweigh type 2 diabetes risk. Therefore, they say that people who have a high risk of CVD (high total and LDL cholesterol) should take statins while making lifestyle changes.
In my opinion, it is better to improve the quality of your diet, increase exercise, get more sleep and lower stress. These changes will improve your lipid profile so you can avoid statins and eliminate the risk of statin-induced type 2 diabetes.
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