This study used association rule mining and propensity score matching to quantify the effect of statin use on progression to diabetes in pre-diabetic patients. Association rule mining identified phenotypes associated with increased diabetes risk, including obesity, hypertension, and hyperlipidemia. Propensity score matching found statins increased diabetes risk in certain pre-diabetic phenotypes by up to 76%, but decreased risk by 41% in patients treated for hyperlipidemia and hypertension. The results suggest the effect of statins on diabetes risk in pre-diabetes depends on patient characteristics and treatment of co-morbid conditions.

1. Quantifying the Effect of Statin Use in Pre-Diabetic
Phenotypes Discovered Through Association Rule
Mining
John Schrom, MPH; Pedro Caraballo, MD; M. Regina Castro, MD; György Simon, PhD

2. + Diabetes affect >25m people in US; Pre-diabetes affects >79m.
+ Statins are used to lower cholesterol, cardiovascular mortality.
§ Among most prescribed drugs in US
§ Multi-billion dollar industry
+ Statins may increase risk of diabetes in normal populations.
+ Statins seem to have no effect in pre-diabetic populations.
+ Is this because pre-diabetes is a heterogeneous condition?
Statin Use & Pre-Diabetes: Background

3. + Association Rule Mining
+ Propensity Score Matching
+ Statin Use and Pre-Diabetic Patients
Outline

4. Association Rule Mining
Obese
Hyperlipidemia
DM
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

5. Association Rule Mining
Obese
Hyperlipidemia
DM
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
P(DM
|
Hyperlip)
=
0.8
{Hyperlip}
-­‐>
{DM}

6. Association Rule Mining
Hyperlipidemia
DM
On
Sta4n?
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Phenotype:
{Hyperlipidemia}
On
Sta4n
Not
on
Sta4n
DM
2
2
No
DM
0
1
RR:
1.51

7. Association Rule Mining
Hyperlipidemia
DM
On
Sta4n?
(Confounders)
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Are
the
staGn
and
no-­‐staGn
populaGons
really
comparable?

8. + Statistical matching technique to compensate for confounders
+ Two Steps:
§ Build a model: quantify how sick a patient is through predicting how likely they are to
receive treatment
§ Match patients based on this propensity (“sickness”) score
+ This method can adjust for the added sickness/confounding associated
with being prescribed statins.
Propensity Score Matching: Overview

9. Propensity Score Matching: Overview
Hyperlip
DM
On
Sta4n?
(Confounders)
Score
Yes
0
Yes
Yes
Yes
0.66
Yes
Yes
Yes
Yes
0.66
Yes
Yes
0
Yes
Yes
Yes
Yes
0.66
On
Sta4n
Not
on
Sta4n
DM
2
1
No
DM
0
0
RR:
1.0
Phenotype:
{Hyperlipidemia}

10. + 18,958 pre-diabetic patients from Mayo Clinic between 1999 – 2004
§ Outcome: Progression to DM within 5 years
§ Lab Values
§ Medication History
§ Diagnosis History
+ Analysis in R
§ Association Rule Mining
§ Propensity Score Matching w/in 1 percentage point caliper
Statin Use & Pre-Diabetes: Methods

11. Statin Use & Pre-Diabetes: Results
Predictor
%
Gender:
Male
49
Hypertension
31
Hyperlipidemia
37
Obese
20
IHD
10
PVD
2
ACE/ARB
13
Predictor
%
Beta
Blocker
17
Ca
Chan
Blocker
7
DiureGc
13
Fibrate
2
StaGn
18
Aspirin
29
High
SBP
21
Predictor
%
High
DBP
9
High
t-­‐chol
43
Low
HDL
23
High
LDL
63
High
BMI
27
High
TGL
30

12. Statin Use & Pre-Diabetes: Results
5-­‐year
risk
of
DM
On
StaGn
13.6%
Not
on
StaGn
9.8%

13. + Built Diagnosis + Medication Analysis Variables
§ Hypertension w/ medication
§ Hypertension w/o medication
§ Elevated BP w/ medication
§ Elevated BP w/o medication
§ Hyperlipidemia w/ (non-statin) medication
§ Hyperlipidemia w/o (non-statin) medication
Statin Use & Pre-Diabetes: Method

14. Statin Use & Pre-Diabetes: Results

15. Statin Use & Pre-Diabetes: Results
Sup
RR
Obesity,
elevated
BP
w/
meds
0.05
1.73*
Hyperlipidemia
w/o
meds,
hypertension
w/
meds
0.23
1.35*
Hyperlipidemia
w/o
meds,
elevated
BP
w/
meds
0.10
1.62*
Obesity,
Hyperlipidemia
w/o
meds,
elevated
BP
w/
meds
0.03
1.76*
Obesity,
Hypertension
w/
meds,
elevated
BP
w/
meds
0.05
1.76*
Hyperlipidemia
w/o
meds,
hypertension
w/
meds,
elevated
BP
w/
meds
0.10
1.61*

16. Statin Use & Pre-Diabetes: Results
Sup
RR
Obesity,
hyperlipidemia
w/
meds
0.19
0.59
Hyperlipidemia
w/
meds,
hypertension
w/
meds
0.02
0.59
Hyperlipidemia
w/o
meds
0.52
1.14
Elevated
BP
w/
meds
0.12
1.32
Obesity,
hyperlipidemia
w/o
meds
0.19
1.15
Obesity,
hypertension
w/
meds
0.12
1.19
Hypertension
w/
meds,
elevated
BP
w/
meds
0.11
1.31
Obesity,
hyperlipidemia
w/o
meds,
hypertension
w/
meds
0.11
1.41
Obesity,
hyperlipidemia
w/o
meds,
hypertension
w/
meds,
elevated
BP
w/
meds
0.04
1.72

17. + Unmatched: Statins increase DM risk from 13 – 41%
+ Matched:
Statin Use & Pre-Diabetes: Summary
Hyperlipidemia
Hypertension
DM
Risk
Requires
cocktail
Treated
+
Controlled
0.59
No
cocktail
Treated
+
Controlled
1.35
No
cocktail
Treated
+
Uncontrolled
1.62

18. + György Simon
+ Pedro Caraballo
+ M. Regina Castro
+ Connie Delaney
+ Stewart Speedie
+ David Pieczkiewicz
Thank You!