1040-5488/12/8908-1165/0 VOL. 89, NO. 8, PP.

11651171
OPTOMETRY AND VISION SCIENCE
Copyright 2012 American Academy of Optometry

ORIGINAL ARTICLE

Age-Related Cataract Is Associated with Type 2

Diabetes and Statin Use
Carolyn M. Machan*, Patricia K. Hrynchak, and Elizabeth L. Irving
ABSTRACT
Purpose. Diabetes has been shown to be a risk factor for age-related (AR) cataract. As statins (HMG-CoA reductase
inhibitors) are now commonly prescribed for patients with type 2 diabetes, their impact on AR cataract prevalence should
be considered. This study determines associations between AR cataract, type 2 diabetes, and reported statin use in a large
optometric clinic population.
Methods. In all, 6397 patient files (ages 193 years) were reviewed. Overall prevalence of statin use was calculated for
patients with type 2 diabetes (n 452) and without diabetes (n 5884). Multivariable logistic regression analysis for AR
cataract was performed controlling for patient sex, smoking, high blood pressure, type 2 diabetes, and statin use.
Results. The prevalence of statin use (in patients aged 38 years) was 56% for those with type 2 diabetes and 16% for
those without diabetes. Type 2 diabetes was significantly associated with nuclear sclerosis (OR 1.62, 1.14 2.29) and
cortical cataract (OR 1.37, 1.021.83). Statin use was associated with nuclear sclerosis (OR 1.48, 1.09 2.00) and posterior
subcapsular cataract (OR 1.48, 1.072.04). The 50% probability of cataract in statin users occurred at age 51.7 and 54.9
years in patients with type 2 diabetes and without diabetes, respectively. In non-statin users, it was significantly later at age 55.1
and 57.3 years for patients with type 2 diabetes and without diabetes, respectively (p 0.001).
Conclusions. In this population, statin use was substantially higher in patients with type 2 diabetes and was associated
with AR cataracts. Further long-term study is warranted to recommend monitoring of crystalline lenses in patients with
type 2 diabetes benefiting from statins.
(Optom Vis Sci 2012;89:11651171)
Key Words: age-related cataract, type 2 diabetes, statins, epidemiology, prevalence

everal studies have identified diabetes as a risk factor for

age-related (AR) cataracts.1 6 It has been predicted that by
the year 2025, 300 million people in the world will have
diabetes,7 and a corresponding global increase in AR cataract can
be expected. Studies have shown that taking statins (HMG-CoA
reductase inhibitors) reduces cardiovascular risks in patients with
diabetes, even in those without high LDL-cholesterol.8,9 Consequently, statins are a class of pharmaceuticals commonly prescribed for patients with diabetes. Little work has been done
specifically on the wide use of statins in patients with diabetes and
their combined impact on cataract development.10 Early clinical
trials on patients without diabetes did not find significant lenticular changes with statin use of 5 years.1114 Subsequently, no
adverse side effects on the human lens were listed in current drug
compendiums, and manufacturers did not recommend monitoring of the crystalline lens. Furthermore, statin use was generally not
*OD

OD, FAAO

OD, PhD
School of Optometry, University of Waterloo, Waterloo, Ontario, Canada.

controlled for in studies on diabetes and its associations to AR

cataract. However, animal studies have clearly shown a correlation
between cataract development and chronic statin treatment, although drug dosages have been generally higher than the clinical
levels given to humans.1517 A few human population studies have
suggested a protective effect of statin use on cataract risk,18 20
hypothesizing an anti-inflammatory/antioxidant mechanism for
the effect.20 Recently, Hippilsley-Cox and Coupland21 looked at
data for 2 million patients (ages 30 84) in a prospective cohort
study involving 368 general practices in the United Kingdom. The
effects of statin type, dose, and duration of use were estimated by
Cox proportional hazard models. Refuting earlier findings, statin
use was associated with an increased risk of cataract, suggesting that
further study is warranted. The type of AR lens opacities [i.e.,
nuclear sclerosis (NS), cortical cataract (CC), and/or posterior subcapsular cataract (PSC)] involved has not been investigated for
specific association with statin use.
Type 2 diabetes accounts for 90% of all cases of diabetes in
North America.7 Most studies on the risk factors for AR cataract
have included both type 1 and type 2 diabetes. This study com-

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Age-related Cataract, Type 2 Diabetes and Statin UseMachan et al.

pared the prevalence of all clinically apparent AR lens opacities in

subgroups with type 2 diabetes and without diabetes from a large
clinic population at the University of Waterloo, School of Optometry and Vision Science. The prevalence of statin use was also
compared for these subgroups, and any associations determined
between statin use, type 2 diabetes, and AR cataract prevalence.

METHODS
Data Abstraction
The Waterloo Eye Study (WatES) database was developed from
a retrospective file review of 6397 patient visits from January 2007
to January 2008 at the University of Waterloo, School of Optometry and Vision Science. Data were abstracted for several variables
for cross-sectional analysis. Abstraction methods, data quality
analysis, study strengths and limitations, and population representation of the database have been detailed in an earlier article.22 Furthermore, overall cataract prevalence and the modeling
technique using logistic regression have been reported previously
for this data set, including a comparison between male and female
patients.23 The abstracted ocular health data in the current investigation included the presence of any clinically apparent AR cataract (NS grade I, LOCS II,2,24 any CC, any PSC, or any history
of related lens extraction [LE] and surgical dates of LE). A report of
lens opacity in either eye was accepted as a diagnosis. The systemic
health information included a diagnosis of type 1 diabetes or type
2 diabetes and any medication being taken. Patient age was electronically calculated in the database from the date of assessment
and the patients birthday, and this information was available for
all patient files.

Data Quality and Population Representation

As previously reported, the repeatability of data abstraction was
determined through interabstractor agreement rates of 425
double-entered clinic files.22 The Cohen was calculated for categorical data and the intraclass correlation coefficient for continuous data. The age and sex distributions of WatES patients with
diabetes were compared with provincial diabetes rates available in
the Ontario diabetes database.25

Outcome Assessment and Statistical Analysis

Patients with type 1 diabetes (n 61) were excluded, and the
remaining patients (n 6336) were separated into subgroups of
patients having type 2 diabetes and those not having diabetes, and
then further sorted into patients having any or no AR lens opacity.
The overall prevalence (%) of any AR cataract was determined for
patients with type 2 diabetes and without diabetes. Multivariable
logistic regression analysis, which controlled for age, was done to
determine prevalence probability functions for AR cataract in the
two subgroups.
We have previously shown a sex difference in AR cataracts in
this population, with being female being associated with an increased risk of CC.23 Smoking is known to be associated with
nuclear sclerosis.13,26 Recently, the Malay Study found that besides diabetes, the presence of high blood pressure (BP) was associated with increased odds of having cataract.27 Therefore, sex,

smoking, and high BP were controlled for, when the odds ratio
(OR) for a diagnosis of type 2 diabetes and AR cataract prevalence
was calculated through multivariable logistic regression analysis.
Associations between each cataract type (NS, CC, and PSC) and
type 2 diabetes were determined independent of whether they
occurred in a mixed-type presentation or as homogeneous opacities. There were a significant number of patients with CC or PSC
who also had NS. For this reason, an insufficient number of patients with only CC or PSC were available to consider patients with
a single type of opacity in our analysis. Instead, we chose to do a
multivariable logistic regression analysis controlling for the aforementioned variables as well as the other lens opacity types when
looking at NS, CC, and then PSC. Patients with monocular LE
were categorized by the cataract type in the other eye. Patients who
had undergone bilateral LE (n 312) were excluded, as it was not
possible to determine from the database which type of AR cataract
existed pre-surgically. For the remaining patients (n 6024), ORs
were calculated for any association between a diagnosis of type 2
diabetes and cataract subtype presence.
Finally, the prevalence of reported statin use was determined for
patients with type 2 diabetes and those without diabetes. A multivariable analysis was performed to control for age, sex, smoking,
high BP, and type 2 diabetes status, to determine any associations
(ORs) between statin use and overall AR cataract prevalence, and
then for each AR cataract subtype. Prevalence probability functions for AR cataract were determined for each of the following
groups: (1) patients with type 2 diabetes not taking statins, (2)
patients with type 2 diabetes taking statins, (3) patients without
diabetes not taking statins, and (4) patients without diabetes taking
statins. The ages at which there was a 50% probability of AR
cataracts were determined for patients in each of these groups.

RESULTS
As previously reported, Cohen statistic values were high for
abstraction repeatability of patient sex and the presence of NS, CC,
PSC, and LE, as was the intra-class coefficient value for patient
age.23 The Kappa value for the presence of diabetes was high at
0.99 with 1% disagreement rate between abstractors. The Kappa
value was somewhat lower for overall medications ( 0.84);
however, when considered on its own, the interabstractor agreement for statin use was high at 0.95, with a disagreement rate
of 1%.
Table 1 details patient characteristics for this study. There were
61(1%) patients with type 1 diabetes who were not included in
the remaining analysis. The mean age for the type 2 diabetes subgroup was approximately 14 years older than that for the patients
without diabetes. Patients without diabetes had a slightly higher
proportion of female patients compared with male patients. However, there were fewer female patients compared with male patients
with type 2 diabetes.
The Canadian Diabetes Association used algorithms applied to
health care administrative data from 1995 to 1999 to create the
Ontario Diabetes Database (ODD).25 Fig. 1 compares the age
distribution of WatES patients with diabetes (type 1 and type 2
diabetes) with the 1999 ODD numbers using their age groupings.
The overall rate of diabetes in people 19 years of age was 10.5%
for the WatES database in 2007 and 6.2% for the ODD in 1999.

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Age-related Cataract, Type 2 Diabetes and Statin UseMachan et al.

1167

TABLE 1.
Characteristics of the patients with type 2 diabetes and without diabetes, and a subset of those 38 years of age for
each group
Type 2 Diabetes

Mean age SD (yr)

Females
Smoking
High blood pressure
Statin use
AR cataracts
Bilateral lens extraction
Nuclear sclerosis
Cortical cataract
Posterior subcapsular cataract

Without Diabetes

All
n 452

38 years
n 438

All
n 5884

38 years
n 3135

64.3 12.4
194 (42.9)
33 (7.3)
270 (59.7)
248 (54.9)
348 (77.0)
57 (12.6)
282 (62.4)
104 (23.0)
44 (9.7)

65.3 11.1
183 (41.8)
30 (6.8)
268 (61.2)
246 (56.2)
348 (79.5)
57 (13.0)
282 (64.4)
104 (23.7)
44 (10.0)

40.8 25.4
3236 (55.0)
273 (4.6)
894 (15.2)
490 (8.3)
1885 (32.0)
256 (4.4)
1546 (26.3)
525 (8.9)
194 (3.3)

61.8 13.2
1755 (56.0)
196 (6.3)
880 (28.1)
486 (15.5)
1874 (59.8)
255 (8.1)
1543 (49.2)
519 (16.6)
192 (6.1)

Presented as the number of patients (%), unless otherwise specified.

FIGURE 1.
Prevalence of diabetes (%) as a function of age group for males (M) and
females (F), in the WatES 2007 and the ODD 1999.

For both databases, women in the 20- to 34-year age-group had a

slightly higher prevalence of diabetes than men, but a lower prevalence in all remaining age-groups. WatES has a lower proportion
of patients with diabetes who are 64 years of age, and a slightly
higher proportion of patients with diabetes in the 35- to 64-year
age range.
The relatively older WatES type 2 diabetes subgroup had 77.0%
of its patients with some clinically apparent AR cataract, whereas
the proportionately younger no diabetes subgroup only had 32%.
Fig. 2 shows the prevalence of AR cataract in the subgroups in
yearly age-groups. Prevalence probability functions determined
with logistic regression are also shown, and, as expected, AR cataracts occurred significantly earlier in patients with type 2 diabetes
compared with those without diabetes. For this population, a diagnosis of type 2 diabetes was associated with increased odds of
having AR cataracts (OR 1.86, 95% CI: 1.34 2.59) across the
life span when controlling for age, being female, smoking, and high
BP. After multivariable analysis, a diagnosis of type 2 diabetes in
this study group was associated with increased odds of having NS

(OR 1.84, 1.322.56), CC (OR 1.38, 1.04 1.82), and PSC

(OR 1.52, 1.04 2.19) compared with patients with no diabetes.
The mean age of patients taking statins was 68.5 years (11.1).
Statin use increased with age such that 0.4% of WatES patients
39 years of age, 9.2% of patients between 39 and 59 years, and
30.5% of patients 60 years were taking statins. In patients 38
years, statin use was reported in 56% of patients with type 2 diabetes, but only 16% of patients without diabetes. Table 2 shows
the result of multivariable regression analysis that included statin
use. After controlling for age, sex, smoking, high BP, and type 2
diabetes, statin use was significantly associated with AR cataract
(OR 1.57, 1.152.13), NS (OR 1.48, 1.09 2.00), and PSC
(OR 1.48, 1.072.04), but not CC (OR 1.02, 0.80 1.30).
PSC was no longer significantly associated with type 2 diabetes
when statin use was considered. CC was still associated with being
female (OR 1.59, 1.30 1.94), and in this analysis, with high BP
(OR 1.24, 1.00 1.53). NS was associated with smoking (OR
1.62, 1.08 2.42).
Table 3 shows the prevalence of cataract in patients (30 years),
sorted by a diagnosis of type 2 diabetes and statin use, in 10-year
intervals. The prevalence of cataract increased at a faster rate in
patients with diabetes who used statins. Similar prevalence levels
were seen in patients with diabetes who did not use statins and in
patients without diabetes who did use statins. The prevalence of
cataract increased at the slowest rate in patients without diabetes
who did not use statins. Fig. 3 demonstrates the result of logistic
regression for each of the four groups. The probability of AR
cataract in patients who used statins reached 50% at age 51.7 years
for patients with type 2 diabetes and at age 54.9 years for patients
without diabetes. In patients who did not use statins, it was later at
55.1 and 57.3 years for patients with type 2 diabetes and without
diabetes, respectively.

DISCUSSION
In WatES patients 38 years of age, reported statin use was
almost 3.5 times higher in patients with type 2 diabetes than in
those without diabetes. Statin use was significantly associated with
AR cataract such that the probability of cataract for patients with

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Age-related Cataract, Type 2 Diabetes and Statin UseMachan et al.

FIGURE 2.
The prevalence of AR cataract in WatES patients with type 2 diabetes (n 452) and patients that do not have diabetes (n 5884) over the entire life
span in yearly age-groups. The probability function of AR cataract using logistic regression has been included with 95% confidence intervals.

TABLE 2.
Odds ratio (95% CI) for AR cataracts and cataract subtypes: NS, CC, and PSC, in WatES patients using multivariable
logistic regression analysis
Age

Female

Smoking

High BP

Type 2 diabetes

Statin use

1.22
(1.201.23)

1.01
(0.821.24)

1.52
(1.032.24)

1.21
(0.951.55)

1.60
(1.132.27)

1.57
(1.152.13)

NS

1.21
(1.191.23)

0.97
(0.791.19)

1.62
(1.082.42)

1.21
(0.951.55)

1.62
(1.142.29)

1.48
(1.092.00)

CC

1.08
(1.071.10)

1.59
(1.301.94)

0.99
(0.631.55)

1.24
(1.001.53)

1.37
(1.021.83)

1.02
(0.801.30)

PSC

1.06
(1.051.08)

0.93
(0.711.23)

1.06
(0.571.98)

0.95
(0.701.28)

1.33
(0.901.96)

1.48
(1.072.04)

AR cataract

Note: Patients with type 1 diabetes were excluded.

type 2 diabetes who did not use statins was similar to patients
without diabetes who did use statins. Furthermore, a clinically
meaningful difference (5.6 years) was found for the age of 50%
probability of AR cataract between WatES patients without diabetes who did not use statins and those with type 2 diabetes who did
take statins. Specifically, statin use was associated with NS and
PSC types of AR cataracts.
The bio-plausibility of these results lies in the fact that the crystalline lens membrane requires high cholesterol for proper epithelial cell development and lens transparency.28 Increased cataract
formation has been seen in both animals and humans with hereditary cholesterol deficiency,28,29 and the risk exists that statins can
inhibit cholesterol biosynthesis in the human lens.
Another important finding was that PSC, long associated with
diabetes, was no longer significantly associated with type 2 diabetes
when statin use was considered. This can be the result of statin use
being directly associated with PSC in people with diabetes rather
than diabetes itself. But it may also be the result of too few patients

with type 2 diabetes who are not using statins to reach statistical
significance. Also, only a few studies have found diabetes to be a
risk factor for NS.4,6,30 However, most studies looked at much
higher grades of NS than WatES, resulting in weak associations
between diabetes and NS. It is possible that NS at these levels tends
to occur at fairly advanced ages where the prevalence of severe
diabetes diminishes because of increased mortality.31
It is likely that some of the associations found in this study, but
not in previous investigations, reflect the potential additional years
of statin use compared with earlier studies. Statins are intended for
long-term use and Neutel et al.,32 in their report on statin use in
Canada, found that approximately 75% of users continue to take
statins for at least 2 years once they have started. Cenedella28 suggests that the long-term impact of statin use requires study periods
of between10 to 20 years.
This study had several strengths. More than 6000 patient visits
contributed to the information in the WatES database providing
significant statistical power throughout analyses. Age-related cata-

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Age-related Cataract, Type 2 Diabetes and Statin UseMachan et al.

1169

TABLE 3.
Raw data for age-groups 30 years (n 3985): number of patients in each of the four subgroups, number in each
subgroup that have AR cataract, and the percentage of the total number in each age-group that have AR cataract
Age-group

Type 2 diabetes (N 447)

Statin use
N
N with AR cataract
% with AR cataract
No statin use
N
N with AR cataract
% with AR cataract
No diabetes (N 3538)
Statin use
N
N with AR cataract
% with AR cataract
No statin use
N
N with AR cataract
% with AR cataract

3039

4049

5059

6069

7079

4
1
25.0

17
5
29.4

49
32
65.3

77
72
93.5

76
75
98.7

7
0
0.0

25
3
12.0

50
28
56.0

51
41
80.4

4
0
0.0

24
4
16.7

64
36
56.3

141
123
87.2

164
161
98.2

451
8
1.8

692
76
11.0

618
214
34.6

598
486
81.3

476
468
98.3

49
49
100

80

25
25
100
17
17
100

93
92
98.9
213
213
100

FIGURE 3.
Comparison of the probability of AR cataract using logistic regression analysis in four patient groups: having type 2 diabetes and using statins, type 2
diabetes and not using statins, no diabetes and using statins, and no diabetes and not using statins. The age of 50% probability of AR cataract is indicated
by a dash line for each of the four groups.

racts, type 2 diabetes, and statin use were found to be prevalent

conditions in this population, especially after 38 years of age, making them appropriate factors for cross-sectional analysis. The study
benefited from using the criterion of any clinically apparent AR
cataract, as opposed to the more commonly chosen advanced levels
of lens opacity. Thus, yearly prevalence levels for overall AR cataract approached 100% by the late 70s. Also, the WatES database

included data for all yearly age-groups so that a probability of AR

cataract function for the entire human age range could be generated through logistic regression analysis.
Study limitations include the fact that cross-sectional studies
cannot determine causation. Because WatES is a clinic population,
the results may not be generalizable to the entire population. For
example, patients with diabetes are encouraged to get routine eye

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Age-related Cataract, Type 2 Diabetes and Statin UseMachan et al.

assessments because of their increased risk of ocular disease, and

therefore, we could expect a clinical eye care population to have a
somewhat higher percentage of patients with diabetes than the
general population.26 Selection bias in clinic-based population
studies can occur, as patients with symptoms from maturing cataracts are more likely to seek out vision care than those without.31
Our inclusion of pre-symptomatic levels of cataract should help
offset this bias. Limitations in available file information did not
allow for analysis of type, dosage, or duration of statin use or
patient blood cholesterol levels and their relationships to lens opacity. However, the strong association found between statin use and
AR cataract in this study indicates a need for additional study to
investigate these more specific aspects of statin use. Given the high
cost of LE to the health care system, further work on the impact of
statin use on cataract surgery rates is also recommended.
Regardless of the outcome of further study, the benefits of statin
use in people with type 2 diabetes are anticipated to continue to
outweigh any associated increased risk of AR cataract. However,
given the known financial and functional burdens, both in terms of
surgical costs and visual impairment when surgery is inaccessible or
pending,26,3336 it is important to identify and minimize factors
that accelerate cataract development. Information provided here
can serve public health efforts to educate people on the risks of
treatments associated with type 2 diabetes. It also supports current
efforts to curtail type 2 diabetes prevalence trends. Finally, results
from further investigation into these associations may encourage
the development of alternative medications for lowering cholesterol that are not associated with an increased risk of cataract
development.37

ACKNOWLEDGMENTS
We thank Linda Lillakas of the University of Waterloo, School of Optometry
and Vision Science for help with the preparation of the manuscript. This work
was supported by NSERC (Canada) and CRC (Canada) to ELI and presented
in part at the American Academy of Optometry, Boston MA, October 1215,
2011.
Received: February 8, 2012; accepted May 10, 2012.

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Optometry and Vision Science, Vol. 89, No. 8, August 2012

Elizabeth L. Irving
School of Optometry
University of Waterloo
200 University Ave W.
Waterloo, Ontario
Canada N2L3G1
e-mail:elirving@uwaterloo.ca