Background  
 Statins induced myopathy and neuropathy are more pronounced in diabetes suffering from peripheralneuropathy. Lipid lowering drugs are indispensable for cardiovascular protection in diabetes. Myopathy is principal reason for statins non adherence and discontinuation. Special caution in elderly diabetes suffering from dementia where disability is highly predicted.  
  
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Aim  
 This study aims to answer how extent of iincidence of statins undesirable effects myopathy among diabetes with complication as neuropathy aggravated it, etiology and best management alternatives to profit statins benefits overcoming its risks.   
  


Method  
 In Cohort prospective study, researchers identified patients age, sex, risk factors, cardiac status, laboratoryanalysis used patients case records to define clinical courses of statin induced myopathy. Diabetes suffered from peripheral neuropathy complication used statins for cardiovascular protection who most ofthem complained from statins induced myopathy. Evaluation &amp;therapy plan are monitored monthly with changes needed for 3 years 2016-2019 .   
 

Results  
 Incidence of myopathy among diabetes with peripheral neuropathy was=0.6777 .   
lncidence of myopathy among diabetes with no peripheral neuropathy was =0.4 .  
 Diabetes suffered from statins myopathy were 61%, among them 81% discontinued statin therapy ascouldn't tolerate myopathy ...where, those tolerated myopathy were 35%.Patients stopped statins were shifted to another statin where 68% of them experienced recurrent musclepain, and 32% tolerated other statin without recurrent muscle symptoms. 3patients are hospitalised forrhabdomyolysis management, one was sent to ICU. 1 patient with preexisting renal insufficiency began lifelong dialysis. Neuropathy pain is from statin or from diabetes complication.  
 In a study, 26% over 65 years old develop peripheral neuropathy .  
 

Discussion  
Diabetes with peripheral neuropathy have 1.69 times greater risk to develop statin associated myopathythan diabetes without neuropathy. Combination of statin and non-statin lipid lowering drug such as ezetimibe is recommended as it allowsclinicians to decrease statin doses for patients while reaching LDL-C reduction and therapeutic goals. Pharmacoeconomics benefits of cost effectiveness and clinical utility are gained. PCSK9 inhibitors also may help in this challenge that large positive targets are based on. Rechallenge of recurrent myopathy when shifted to another statin, to overcome more hydrophillic statins arerecommended as pravastatin, rosuvastatin and fluvastatin. Statin choice must be guided bypharmacogenetic patient study, which influences drug pharmacokinetics and pharmacodynamics. By evaluation of transporter function of OATP1B1 haplotypes , located on hepatocytes where statins are substrates and SLCO1B1gene codes for, myopathy status is defined.   
  
 

References  
1- Statin Neuropathy masquerading as diabetic autoimmune polyneuropathy .Tom Brooks Vaughan, MD and David S.H.Bell .ADA. Diabetes Care 2005 Aug; 28(8):2082  
.2- Peripheral neuropathy in older people. Siyum Strait , Pippa Medcalf. Geriatric medicine journal 42, November 2012. www.gmjournal.co.uk  
3- Intolerance to statins : mechanisms and management. Rafael Bitzur , MD, Hofit Cohen, MD. ADA Diabetes care 2013 Aug; 36 (suppl2) : S325 -S330. PM1D: 23882066 . Published online 2013 Jul17, doi: 10.2337/dcS13-2038.  
4- Statin toxicity mechanistic insights and clinical implications . Nathalie C.Ward , GeraldF.Watts , Robert H.Eckel. AHA journals.org . Circulation research 2019 Jan17; 124: 328 - 350.  
5- Pharmacogenomics of statins : understanding susceptibility to advere effects . Joseph P.Kitzmiller, Edward B.Mikulik, Jasmin A Luzum . PMC ncbi.nlm.nih.gov; 2016 Oct3. doi: 10.2147/PGPM-S86013 , PMID : 27757045.



Abstract
Title :
Statins induced myopathy among diabetes with peripheral neuropathy :incidence, etiology and
management .
Background :
Statins induced myopathy and neuropathy are more pronounced in diabetes suffering from peripheral
neuropathy. Lipid lowering drugs are indispensable for cardiovascular protection in diabetes. Myopathy is
principal reason for statins non adherence and /or discontinuation. In addition to  idiosyncratic somatic and autonomic neuropathy that may develop in diabetes treated with statins , normally more than 25% of 65 years old people complain from mononeuropathy, multiple moneuropathy and  polyneuropathy.
In addition to other statins related problems that may develop such as statins intolerance and toxicity.  Myopathy and neuropathy from DM complication and medication in order to prevention of other important complications (CV metabolic diseases) , must be managed before lead to disability . Special caution in elderly diabetes suffering from dementia where disability is highly predicted.
Aim :
This study aims to answer how extent of iincidence of statins undesirable effects myopathy among diabetes with complication as neuropathy aggravated it, etiology and best management alternatives to profit statins benefits overcoming its risks. In order to achieve best results , to avoid CV metabolic diseases in diabetes as well as prevention of all neuropathy types and to positive practice of lipid lowering drugs risk benefit rule .
Methods :
In Cohort prospective  study, researchers identified patients age, sex, risk factors, cardiac status, laboratory
analysis used patients case records to define clinical courses of statin induced myopathy. Diabetes
suffered from peripheral neuropathy complication used statins for cardiovascular protection who most of
them complained from statins induced myopathy. Evaluation and follow up of therapy plan are monitored monthly with changes needed for 3 years from 2016 till 2019 . Results are illustrates and conducted in further tests as Chisquare test, graphs and figures.
Results:
Incidence of myopathy among diabetes with peripheral neuropathy was=0.6777
Incidence of myopathy among diabetes with no peripheral neuropathy was =0.4 .
Diabetes suffered from statins myopathy were 61%, among them 81% discontinued statin therapy as
couldn't tolerate myopathy ...where, those tolerated myopathy were 35%.
Patients stopped statins were shifted to another statin where 68% of them experienced recurrent muscle
pain, and 32% tolerated other statin without recurrent muscle symptoms. 3patients are hospitalised for
rhabdomyolysis management, one was sent to ICU. 1 patient with preexisting renal insufficiency began
lifelong dialysis. Neuropathy pain is difficult to distinguish from statin or from diabetes complication.
In one study, 26% over 65 years old develop peripheral neuropathy in life(without any known risk factor).
That's third cause of those patients complaining from neuropathy.
Discussion:
Diabetes with peripheral neuropathy have OR 1.69 times greater risk to develop statin associated myopathy
than diabetes without neuropathy.
Combination of statin and non-statin lipid lipid lowering drug such as ezetimibe is recommended as it allows
clinicians to decrease statin doses for patients while reaching LDL-C reduction and therapeutic goals.
Also, PCSK9 inhibitors also may help in this challenge that large positive targets are based on.
Pharmacoeconomic benefits of cost effectiveness and clinical utility are gained in statin /ezeimibe combination "recommendation of this study that have been followed with marked improved results" . Rechallenge of recurrent myopathy when shifted to another statin, to overcome more hydrophillic statins are
recommended as pravastatin, rosuvastatin and fluvastatin. Statin choice must be guided by
pharmacogenetic patient study, which influences drug pharmacokinetics and pharmacodynamics. By
evaluation of transporter function of OATP1B1 haplotypes , located on hepatocytes where statins are
substrates and SLCO1B1gene codes for..myopathy status is defined. That is may be addressed in well designed ongoing clinical trials.
Non standard abbreviations:
PCSK9 :  Proprotein convertase subtilisin / kexin type 9
OATP1B1 : Organic-anion-transporting polypeptide B
SLCO1B1 : Solute carrier organic anion tranporter family member1 B1

References :
1- Statin Neuropathy masquerading as diabetic autoimmune polyneuropathy .Tom Brooks Vaughan, MD and David S.H.Bell .ADA. Diabetes Care 2005 Aug; 28(8):2082.
2- Peripheral neuropathy in older people. Siyum Strait , Pippa Medcalf. Geriatric medicine journal 42, November 2012. www.gmjournal.co.uk
3- Intolerance to  statins : mechanisms and management. Rafael Bitzur , MD, Hofit Cohen, MD. ADA Diabetes care 2013 Aug; 36 (suppl2) : S325 -S330. PM1D: 23882066 . Published online 2013 Jul17, doi: 10.2337/dcS13-2038.
4- Statin toxicity mechanistic insights and clinical implications . Nathalie C.Ward , GeraldF.Watts , Robert H.Eckel.  AHA journals.org . Circulation research 2019 Jan17; 124: 328 - 350.
5- Pharmacogenomics of statins : understanding susceptibility to advere effects . Joseph P.Kitzmiller, Edward B.Mikulik, Jasmin A Luzum . PMC ncbi.nlm.nih.gov; 2016 Oct3. doi: 10.2147/PGPM-S86013 , PMID : 27757045.

Statins induced myopathy among diabetes with peripheral neuropathy: incidence, etiology and management