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Muscle-related symptoms
Elevated hepato-cellular enzymes
Cancer
New diabetes
Hemorrhagic stroke
Fatigue
Neuro-psychiatric effects and insomnia
Proteinuria / hematuria
Erectile dysfunction
Alopecia
STATIN-INDUCED DIABETES
1. Clinical Evidence :
a. Major Statin Trial
b. Meta-analysis
2. Predictor of New Onset Diabetes (NOD)
3. Low-Dose vs High-Dose Statin Therapy
4. Types of Statin
5. Mechanism o9f Diabetogenic Effect of
Statin
STATIN-INDUCED DIABETES
1. Clinical Evidence :
a. Major Statin Trial
b. Meta-analysis
2. Predictor of New Onset Diabetes (NOD)
3. Low-Dose vs High-Dose Statin Therapy
4. Types of Statin
5. Mechanism o9f Diabetogenic Effect of
Statin
Statins and New-Onset Diabetes
Proportion of patients with
new-onset diabetes (%)
Study Statins Placebo RR, statin vs 95% CI
placebo
WOSCOPS (N=5974) 1.9% 2.8% 0.69 0.49-0.96
HPS (N=14,543) 4.6% 4.0% 1.14 0.98-1.33
ASCOT (N=7773) 3.9% 3.5% 1.14 0.90-1.43
LIPID (N=7937) 4.3% 4.6% 0.95 0.77-1.16
CORONA (N=3534) 5.6% 5.0% 1.13 0.86-1.49
JUPITER (N=17,802) 3.0% 2.4% 1.25 1.05-1.49
Combined all above (N=57,593) 3.8% 3.5% 1.06 0.93-1.22 (P=0.38)
Combined all above except 4.0% 3.5% 1.13 1.03-1.23 (P=0.008)
WOSCOPS (N=51,619)
Adapted from Baigent C et al. Cholesterol Treatment Trialists (CTT) Collaborators. Lancet 2005;
366:1267-78
Effect of Statins on CV Event Rates
Related to 1 mmol/l LDL Reduction
Paul M Ridker, et al
In the JUPITER primary prevention trial, the
cardiovascular and mortality benefits of statin
therapy exceed the diabetes hazard, including
in participants at high risk of developing
diabetes.
Diabetes Care
October 2009; vol. 32: no.10: 1924-1929
RESULTS
In the meta-analysis of the hypothesis-testing trials, we
observed a small increase in diabetes risk
(RR 1.13 [95% CI 1.031.23])
Meta-analysis of clinical trials evaluating the effects of
statins on diabetes risk
Statins and risk of incident diabetes:
a collaborative meta-analysis of randomised
statin trials
Conclusions
Risk of diabetes was increased after statins,
but outcomes were favorable.
Kang-Ling Wang, et al. - J Am Coll Cardiol. 2012;60(14):1231-1238
Kaplan-Meier Curves for Outcomes Among
Statin and Control Groups
1. Clinical Evidence :
a. Major Statin Trial
b. Meta-analysis
2. Predictor of New Onset Diabetes (NOD)
3. Low-Dose vs High-Dose Statin Therapy
4. Types of Statin
5. Mechanism o9f Diabetogenic Effect of
Statin
PREDICTORS OF DIABETES
1. IFG
2. Metabolic Syndrome
3. Elevated Hba1c
4. Elevated Triglyseride serum
5. Elevated BMI (overweight and
obese).
6. Hypertension
J Am Coll Cardiol. 2011;57(14):1535-1545
After 1 year:
15% reduction in major vascular events
1. Clinical Evidence :
a. Major Statin Trial
b. Meta-analysis
2. Predictor of New Onset Diabetes (NOD)
3. Low-Dose vs High-Dose Statin Therapy
4. Types of Statin
5. Mechanism o9f Diabetogenic Effect of
Statin
TYPE OF STATIN
Primary & Secondary Prevention of CVD
Pravastatin vs Simvastatin, Atorvastatin & Rosuvastatin
(increased risk of incident of Diabetes).
Pravastatin vs Fluvastatin & Lovastatin (no significant risk of
incident of Diabetes)
Pitavasta n 4 & 20 mg 40 % dose of Atorvasta n :
15-25 % increased on HDL-C
Favourable effect on glucose control (decrease HOMA score
& Hba1c)
no large trials have been performed
STATIN-INDUCED DIABETES
1. Clinical Evidence :
a. Major Statin Trial
b. Meta-analysis
2. Predictor of New Onset Diabetes (NOD)
3. Low-Dose vs High-Dose Statin Therapy
4. Types of Statin
5. Mechanism of Diabetogenic Effect of
Statin
ANTIOXIDANTS & REDOX SIGNALING Volume 20, Number 8, 2014. Differential Metabolic Actions of Specific Statins:
Clinical and Therapeutic Considerations
Possible Mechanism of
Diabetogenic Effect of STATIN
Chan DC & JPang J & Gerald F. Watts P. Pathogenesis and Management of the Diabetogenic
Effect of Statins: a Role for Adiponectin and Coenzyme Q10?Curr Atheroscler Rep (2015) 17:472
Pathophysiology
SUMMARY
1. Statin ---> minor increase on Incident of New
Onset Diabetes (0.3 0. %)
2. Incident increase with higher dose of Statin
3. Predictors of Diabetes were IFG, Metabolic
Syndrome, elevated Hba1c, elevated TG,
elevated BMI. Hypertension
4. Although New onset of diabetes is one of the
side-effect of statin, but benefit of the statin
in CVD is bigger than this effect
THANK YOU
High-Dose Statins May Increase
Diabetes Risk
but,
Mipomersen
Inhibits protein synthesis of apoB
Reduces LDL ~30%
Injected weekly
No outcomes trials
PCSK9 inhibitors
Reduce LDL 50-60 %,
Injected q 2 weeks
No outcomes trials
Biochemical Effects of Statins
Acetate
Acetyl-CoA
Acetoacetyl-CoA
HMG-CoA Co-enzyme Q10
Statins Protein
Mevalonate prenylation
MVK
Mevalonate-5-P Geranylgeranyl-PP
Mevalonate-5-PP
Geranyl-PP Farnesyl-PP Squalene
Isopentyl-PP
Dolichols Squalene-2,3-epoxide
Sec-tRNA
N-linked glycosylation Lanosterol
7-Dehydrocholesterol *3
Lanosterol Cholestadien-3-ol
DHCR7
DHCR24
Cholesterol Desmosterol *2
How effective are statins for people
with diabetes?
Most people with diabetes
'have poor cholesterol control'