Baby I'm afraid of a lot of things but I ain't scared of loving you.
- Karen O
Diabetes scares me probably more than any other disease state. Diabetes puts patients at risk of slow healing wounds, peripheral neuropathy, increased infections, kidney failure, cardiovascular events, and is the number one cause of blindness.
My roommate has the best definition of diabetes that I've ever heard:
If you eat too much candy, your foot is going to fall off.
She has a point.
There is no way to prevent type 1 diabetes, but research into preventing type 2 diabetes is endless. Most recently there has been evidence showing that statins increase the risk of developing diabetes. An inquisitive NP at my rotation was asking me about a Huffington Post article in regards to the topic, so in the past few days I have attempted to dissect the evidence and assess the risk.
Attention was first called to incident diabetes with statin use when the JUPITER trial was published in NEJM in 2008. Despite screening for cardiovascular risk factors, an estimated half of all myocardial infarctions occur in patients that are at their target LDL goal. C-reactive protein, a marker of vascular inflammation, has been shown to be a risk factor for CV events independent of cholesterol levels. Statins have been shown to reduce C-reactive protein levels in addition to reducing LDL.
The JUPITER trial looked at patients at a LOW risk of CV events but high C-reactive protein levels: men over 50 and women over 60 who had no history of cardiovascular disease, and LDL less than 130mg/dL, and a C-reactive protein level greater than 2.0mg/L. Patients with diabetes, blood pressure above 190/100, low renal function, or use of anti-lipid therapy were excluded. 17,802 patients randomized to 20mg rosuvastatin or placebo were followed for a median of 1.9 years to the occurrence of the first event: MI, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death.
Patients taking rosuvastatin 20mg had a decreased risk of cardiovascular events; one event prevented for every 95 patients treated over two years or 31 patients treated over four years. However, the study also showed a statistically significant increase in the onset of diabetes in patients taking rosuvastatin.
The PROSPER study published in 2002 also showed a significant increase in diabetes in patients taking pravastatin.
In response, Sattar et al. conducted a meta-analysis of trials containing over 1000 patients treated with a statin for at least a year. The analysis included 13 trials and 91,140 patients. The statins used were atorvastatin, lovastatin, rosuvastatin, simvastatin, and pravastatin; where six of 13 trials utilized pravastatin.
Sattar et al. found a 9% increase in new onset diabetes in patients taking a statin, or one more new case of diabetes in a patient on a statin for every 225 patients treated for four years. Increase in diabetes was seen even without the inclusion of the JUPITER trial. The only other correlation to the development of diabetes was increasing age.
The analysis by Sattar et al. only included one trial, ASCOT-LLA, that utilized atorvastatin. The stir in the medical community lately has been over an analysis by Waters et al. published in 2011 looking at the incidence of diabetes in IDEAL, TNT, and SPARCL which all utilized atorvastatin.
I am disappointed that Waters et al. did not conduct a meta-analysis, but they found a trend to new-onset diabetes in the TNT and IDEAL trials and an increase in new-onset diabetes in SPARCL. Patients that developed diabetes were more likely at baseline to have higher fasting glucose, BMI, white blood cell count, blood pressure total cholesterol/HDL ratio, and triglycerides. 80mg of atorvastatin was more likely to worsen glycemic control than 10 or 20mg atorvastatin. Age differences, sex, and smoking were not associated with incident diabetes.
The real question is how this will change the way we treat patients. Despite a slight increase in diabetes, statins have been shown to decrease the risk of cardiovascular events and mortality. Waters tells heartwire, "Compared with their risk of a cardiovascular event, their risk of developing diabetes is paltry" and advises patients not to stop taking their statins. Dr. Blumenthal of John Hopkins Medical Institute also comments to theheart.org that this analysis will not change his use of statins. ALLHAT similarly showed an increase in diabetes in patients taking chlorthalidone, but these patients had improved mortality outcomes.
The available evidence shows that the benefit that patients receive from statins outweighs the risk of diabetes. To me, these analyses show that no medication comes without risk. Its a reminder to those that believe or believed that statins should be in our drinking water that this is a prescription medication. There is a risk of liver dysfunction, rhabdomyolysis, and now, a risk of diabetes associated with their use. Patients should be monitored accordingly.
I would attempt to make lame parallels between the JUPITER trial and the planet, but I know that I cannot do the planet justice. I think I have failed my parents. My mother builds satellites and my dad builds video servers by day, and charts the sky by night. Check out his amazing nebula photos at:
http://astrospotter.zenfolio.com/
References:
Ridker PM et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. The New England Journal of Medicine 2008;359(21):2195-207.
Shepherd J et al. Pravastatin in elderly individuals at risk of vascular disease: a randomised controlled trial. Lancet 2002;360:1623-30.
Sattar N et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735-42.
Waters DD et al. Predictors of new-onset diabetes in patients treated with atorvastatin. Journal of the American College of Cardiology 2011;57(14):1535-45.
Hughes S. More data on diabetes risk with statins. March 30, 2011; http://www.theheart.org/article/1203383.do
- Karen O
My roommate has the best definition of diabetes that I've ever heard:
If you eat too much candy, your foot is going to fall off.
She has a point.
There is no way to prevent type 1 diabetes, but research into preventing type 2 diabetes is endless. Most recently there has been evidence showing that statins increase the risk of developing diabetes. An inquisitive NP at my rotation was asking me about a Huffington Post article in regards to the topic, so in the past few days I have attempted to dissect the evidence and assess the risk.
The JUPITER trial looked at patients at a LOW risk of CV events but high C-reactive protein levels: men over 50 and women over 60 who had no history of cardiovascular disease, and LDL less than 130mg/dL, and a C-reactive protein level greater than 2.0mg/L. Patients with diabetes, blood pressure above 190/100, low renal function, or use of anti-lipid therapy were excluded. 17,802 patients randomized to 20mg rosuvastatin or placebo were followed for a median of 1.9 years to the occurrence of the first event: MI, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death.
Patients taking rosuvastatin 20mg had a decreased risk of cardiovascular events; one event prevented for every 95 patients treated over two years or 31 patients treated over four years. However, the study also showed a statistically significant increase in the onset of diabetes in patients taking rosuvastatin.
 |
| The Buttery |
In response, Sattar et al. conducted a meta-analysis of trials containing over 1000 patients treated with a statin for at least a year. The analysis included 13 trials and 91,140 patients. The statins used were atorvastatin, lovastatin, rosuvastatin, simvastatin, and pravastatin; where six of 13 trials utilized pravastatin.
Sattar et al. found a 9% increase in new onset diabetes in patients taking a statin, or one more new case of diabetes in a patient on a statin for every 225 patients treated for four years. Increase in diabetes was seen even without the inclusion of the JUPITER trial. The only other correlation to the development of diabetes was increasing age.
The analysis by Sattar et al. only included one trial, ASCOT-LLA, that utilized atorvastatin. The stir in the medical community lately has been over an analysis by Waters et al. published in 2011 looking at the incidence of diabetes in IDEAL, TNT, and SPARCL which all utilized atorvastatin.
 |
| New York |
The real question is how this will change the way we treat patients. Despite a slight increase in diabetes, statins have been shown to decrease the risk of cardiovascular events and mortality. Waters tells heartwire, "Compared with their risk of a cardiovascular event, their risk of developing diabetes is paltry" and advises patients not to stop taking their statins. Dr. Blumenthal of John Hopkins Medical Institute also comments to theheart.org that this analysis will not change his use of statins. ALLHAT similarly showed an increase in diabetes in patients taking chlorthalidone, but these patients had improved mortality outcomes.
I would attempt to make lame parallels between the JUPITER trial and the planet, but I know that I cannot do the planet justice. I think I have failed my parents. My mother builds satellites and my dad builds video servers by day, and charts the sky by night. Check out his amazing nebula photos at:
http://astrospotter.zenfolio.com/
 |
| Hyannis 2008 |
References:
Ridker PM et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. The New England Journal of Medicine 2008;359(21):2195-207.
Shepherd J et al. Pravastatin in elderly individuals at risk of vascular disease: a randomised controlled trial. Lancet 2002;360:1623-30.
Sattar N et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735-42.
Waters DD et al. Predictors of new-onset diabetes in patients treated with atorvastatin. Journal of the American College of Cardiology 2011;57(14):1535-45.
Hughes S. More data on diabetes risk with statins. March 30, 2011; http://www.theheart.org/article/1203383.do
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