Journal of Diabetes and Its Complications 22 (2008) 1 9

Suboptimal control of glycemia, blood pressure, and LDL cholesterol in

overweight adults with diabetes: the Look AHEAD Study
Alain G. Bertonia,b,4, Jeanne M. Clarkc, Patricia Feeneya, Susan Z. Yanovskid, John Bantlee,
Brenda Montgomeryf, Monika M. Saffordg, William H. Hermanh, Steven Haffneri
The Look AHEAD Research Group
a

Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest University Health Sciences
b
Department of Internal Medicine, Wake Forest University Health Sciences
c
Departments of Medicine and Epidemiology, The Johns Hopkins University
d
Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases
e
University of Minnesota
f
University of Washington
g
University of Alabama at Birmingham
h
Departments of Internal Medicine and Epidemiology, University of Michigan
i
The University of Texas Health Science Center, San Antonio
Received 24 May 2006; received in revised form 27 September 2006; accepted 9 October 2006

Abstract
Background: The characteristics associated with meeting goals for glycemia, blood pressure (BP), and low-density lipoprotein (LDL)
cholesterol for participants with diabetes were examined. Methods: Baseline information on demographics, medical history, and
anthropometry, as well as on hemoglobin A1c, BP, and LDL cholesterol levels, was measured in 5145 participants of Look AHEAD, a
multicenter randomized trial performed to determine whether long-term weight loss and increased physical fitness reduce cardiovascular
disease (CVD) in overweight and obese individuals with type 2 diabetes. Logistic regression was used to analyze these cross-sectional data to
ascertain associations between participant characteristics and attainment of risk factor goals [hemoglobin A1c b7.0%, BP b130/80 mmHg,
and LDL b100 mg/dl]. Results: The study population had a mean age of 58.7 years and a mean body mass index of 36.0 kg/m2. Of the total
number of participants, 59.5% were female, 36.8% were of ethnic/racial minority, and 87.3% were on diabetes medications. Upon
enrollment, 45.8% had hemoglobin A1cb7.0%, 51.7% had BPb130/80 mmHg, and 37.2% had LDLb100 mg/dl. All three goals were met by
only 10.1%. We found consistent evidence for differences in risk factor control by age, gender, race/ethnicity, degree of obesity, education,
income, CVD, source of medical care, and medication use. In multivariable analysis, African-American race, increasing degree of obesity,
insulin use, and nonutilization of a lipid-lowering agent were associated with not meeting all risk factor goals. Conclusion: These data
demonstrate that numerous baseline characteristics are associated with suboptimal control of these cardiovascular risk factors among
overweight and obese adults with diabetes.
D 2008 Elsevier Inc. All rights reserved.
Keywords: Hemoglobin A1c; Blood pressure; Cholesterol; Risk factor control

1. Introduction
4 Corresponding author. Public Health Sciences, Medical Center
Boulevard, Winston-Salem, NC 27157, USA. Tel.: +1 336 716 2824;
fax: +1 336 713 4300.
E-mail address: abertoni@wfubmc.edu (A.G. Bertoni).
1056-8727/08/$ see front matter D 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.jdiacomp.2006.10.003

Many diabetes complications are directly related to

vascular abnormalities, including cardiovascular disease
(CVD), peripheral vascular disease, retinopathy, nephrop-

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

athy, neuropathy, and lower extremity amputation. Some

clinical trials and epidemiologic studies suggest that adequate
control of hyperglycemia, hypertension, and hypercholesterolemia may prevent vascular complications (Collins,
Armitage, Parish, Sleigh, & Peto 2003; Haffner, 1998;
Stratton et al., 2000; UK Prospective Diabetes Study Group,
1998). The American Diabetes Association (ADA) (2005)
recommends that all adults with diabetes achieve hemoglobin
A1c b7.0%, blood pressure (BP) b130/80 mmHg, and lowdensity lipoprotein (LDL) cholesterol b100 mg/dl. However,
there is ample evidence that these goals are seldom met in the
United States (George, Tobin, Corpus, Devlin, & ONeill,
2001; Harris, Eastman, Cowie, Flegal, & Eberhardt, 1999;
Resnick, Foster, Bardsley, & Ratner, 2006; Saaddine et al.,
2002; Saydah, Fradkin, & Cowie, 2004). Few of these
studies, however, have examined the proportion of persons
with type 2 diabetes meeting all three of these risk factor
goals, which would confer the largest benefit of risk
reduction. Moreover, there has been limitedand contradictoryinformation about which patient characteristics are
associated with better control of these risk factors, although
there has been consistent evidence of poorer control,
especially of glycemia, among racial and ethnic minorities
(Kirk et al., 2005).
Our objectives were to examine the proportion achieving
ADA targets for glycemia, BP, and LDL cholesterol control,
and to determine correlates of achieving optimal control
among overweight and obese adults with type 2 diabetes
who were recruited into the Look AHEAD clinical trial.
Although a volunteer population, Look AHEAD provides a
setting to study these questions in a large diverse US cohort.

2. Methods
Look AHEAD (Action for Health in Diabetes) is a
multicenter randomized trial performed to determine, among
overweight and obese volunteers with type 2 diabetes, the
long-term effects of two study conditions: an intensive
lifestyle intervention designed to achieve and maintain
weight loss by decreased caloric intake and increased
physical activity versus a control condition (diabetes support
and education) on the combined incidence of serious CVD
events (cardiovascular death, nonfatal myocardial infarction,
and nonfatal stroke). Details regarding study design
and rationale have been published (Ryan et al., 2003).
Participants included persons with type 2 diabetes aged
4574 years with a body mass index (BMI) z25 kg/m2
(z27 kg/m2 if on insulin) who were recruited from 16 US
centers from August 2001 to April 2004. Persons with
hemoglobin A1c N11%, BP z160/100 mmHg, triglycerides
z600 mg/dl, and weight N350 lb were excluded, as
were persons with recent weight loss, recent use of weight
control medication, or past weight loss surgery. Persons
meeting these criteria were additionally screened with an
exercise stress test; those with normal results were random-

ized. Those with abnormal results were potentially eligible

for randomization after evaluation and risk stratification by
their physician.
Participant sociodemographics and medical history were
obtained by self-report and included source of medical care,
medications, and prior CVD. Prior CVD included myocardial infarction, coronary artery bypass, angioplasty/stent
procedure, peripheral vascular disease, stroke, stable angina,
and Class I/II heart failure. Staff members measured
anthropometrics, with participants wearing light clothing
without shoes. The average of two seated BPs, obtained 30 s
apart after an initial 5-min rest period using a calibrated
device (Dinamap Pro 100), was recorded. Hypertension was
defined as BP z140/90 or the use of antihypertensive
medication. Fasting blood samples were analyzed centrally.
Hemoglobin A1c was measured by a dedicated ion
exchange high-performance liquid chromatography instrument. Total serum cholesterol, high-density lipoprotein, and
triglycerides were measured enzymatically using methods
standardized to Centers for Disease Control reference. LDL
cholesterol was calculated by the Friedewald equation.
2.1. Statistical analysis
We utilized ADA recommendations to define the optimal
control of hemoglobin A1c (b7.0%), BP (b130/80 mmHg),
and LDL cholesterol (b100 mg/dl) (ADA, 2005). These were
the recommendations during the entire enrollment period. We
first examined the degree of risk factor control in the sample.
Subsequently, we compared the proportion with each
individual risk factor and with all three factors, controlled
by categories defined by demographics, degree of obesity,
comorbidity, and medication use. Statistical analyses include
simple descriptive statistics for continuous variables and
frequencies/percentages for categorical variables. Continuous BMI was collapsed into a categorical variable consistent
with frequently utilized cut points for degree of obesity.
Statistical significance tests of differences in the proportion of
participants reaching goals were performed using chi-square
analysis. When a variable included more than two categories,
we performed logistic regression by selecting a reference
category and determined which of the other categories
differed significantly. Variables that were significant in
univariate analyses (a=.05) were considered for multivariable
models. Separate bbestQ multivariable models were selected
for each outcome through the use of both forward and
backward stepwise selection algorithms applied to factors
that were significant in univariate models. As both
approaches resulted in the selection of essentially the same
variables, we present data from forward selection only.
Models were selected after testing for all interactions between
variables, and the final model contains only significant
variables. The significance of variables within the final model
was assessed by Wald test. Model goodness-of-fit was
assessed by the test of Hosmer and Lemeshow. Odds ratios
(ORs) of b1 indicate less likelihood and ORN1 indicate

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

greater likelihood to meet the goals. Analyses were

performed with SAS software (Version 9; SAS, Cary, NC).

Table 1
Baseline characteristics of the Look AHEAD clinical trial cohort (N=5145)
Characteristics

3. Results
The baseline characteristics of randomized persons are
presented in Table 1. A majority of participants were
women; 36.8% were members of ethnic/racial minority
groups. Nearly all (85.1%) were obese (BMIz30), with the
remainder being overweight. Most participants were on
diabetes medications, including 18.7% who were using
insulin; many also reported taking antihypertensives and
lipid-lowering drugs.
3.1. Univariate analyses
The mean hemoglobin A1c was 7.3%, the mean BP was
129/70 mmHg, and the mean LDL cholesterol was
112 mg/dl. Control to ADA goal levels was modest (blood
glucose, 45.8%; BP, 51.5%; LDL cholesterol, 37.2%). Only
10.1% had all three factors under optimal control. The
proportion of participants meeting each and all three goals
according to selected characteristics is presented in Table 2.
We found evidence for differential control by age, gender,
race/ethnicity, and use of medication. Participants reporting
no use of diabetes medication were more likely to meet
goals (except for LDL) than either those on oral hypoglycemic agents or those on insulin. Among those reporting
any medication use, control of hemoglobin A1c was
observed in 42.3%, control of BP was observed in 51%,
control of LDL was observed in 38.7%, and control of all
three was observed in 9.7%. Older persons more frequently
met hemoglobin A1c and LDL goals but less frequently met
BP goal than younger participants. Women less frequently
met LDL goal. African-Americans were less likely to meet
individual (and all) goals, whereas Native Americans more
frequently met BP and LDL goals compared to Whites.
Fewer of the most obese individuals reached hemoglobin
A1c, BP, and all goals compared to overweight participants.
Other variables associated with differential hemoglobin
A1c control included income and education, usual source of
care, duration of diabetes, and CVD history. BP control was
somewhat more likely among those reporting a hospital
clinic or a community health center as the usual source of
care, and among those not reporting BP or diabetes
medication use. Additional variables associated with meeting LDL goal included education, CVD, duration of
diabetes, use of antihypertensive or lipid-lowering medications, and regular aspirin use.
3.2. Multivariable analyses
The variables that remained significant for hemoglobin
A1c control are presented in Table 3. The relationship
between age and hemoglobin A1c control was modified by

Age in years [n (%)]

4555
5665
6676
MeanFS.D.
Female [n (%)]
Race/ethnicity [n (%)]
White
African-American
Hispanic
American Indian/Native American
Asian/Pacific Islander
Other/mixed
Education in years [n (%)]
b13
1316
N16
Income in US$ [n (%)]
b20,000
20,00049,999
50,00079,999
z80,000
Source of health care
Private doctors office
Hospital clinic or outpatient department
Community health center
Other kind of health care facility
No usual source of care
BMI in kg/m2 [n (%)]
b30
3034
3539
z40
MeanFS.D.
Cigarette smoker [n (%)]
Past
Current
Years since diabetes diagnosis (meanFS.D.)
History of CVD [n (%)]
Insulin use [n (%)]
Oral medication alone [n (%)]
No diabetes medication [n (%)]
Hypertension [n (%)]
On antihypertensive medication [n (%)]
On lipid-lowering medication [n (%)]
Aspirin use 5 days or more weekly [n (%)]

1620 (31.5)
2650 (51.5)
874 (17.0)
58.7F6.8
3063 (59.5)
3245
804
677
258
50
98

(63.2)
(15.7)
(13.2)
(5.0)
(1.0)
(1.9)

1024 (20.4)
1911 (38.0)
2093 (41.6)
589
1476
1212
1359

(11.4)
(28.7)
(23.6)
(26.4)

3780
635
398
290
23

(73.5)
(12.3)
(7.7)
(5.6)
(0.4)

768 (14.9)
1815 (35.3)
1411 (27.4)
1151 (22.4)
36.0F5.9
2327 (45.2)
228 (4.4)
6.8F6.5
726 (14.1)
963 (18.7)
3426 (66.6)
695 (13.5)
4149 (80.6)
3541 (68.8)
2448 (47.6)
2360 (45.9)

the duration of diabetes. Those least likely to have

hemoglobin A1c b7% were the youngest participants with
the longest duration of diabetes [those aged 4555 years
with duration of diabetes N7 years had a decreased odds
(0.33) of achieving control compared to those aged
4555 years with diabetes duration b3 years]. Those most
likely to achieve hemoglobin A1c b7.0% were those aged
5665 years with recently diagnosed diabetes. Both AfricanAmericans (OR=0.70, Pb.001) and Hispanics (OR=0.83,
P=.06) were less likely to have control of hemoglobin A1c.
Other significant correlates of poorer control included less
education and reporting a community health center as the
usual source of care.

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

Table 2
Proportion meeting ADA goals for glycemia, BP, and LDL cholesterol, by
selected participant characteristics
Characteristics

Hemoglobin
A1c

Gender
Male
46.2
Female
45.6
P
.7
Age in years
4555
41.5
5665
46.9
6676
50.5
P
b.001
Race/ethnicity
White
49.2
African-American
39.4
Hispanic
38.4
American Indian
41.5
Asian/Pacific Islander
44.0
Other/mixed
48.0
P
b.001
Education in years
b13
39.6
1316
45.5
N16
49.3
P
b.001
BMI in kg/m2
b30
50.4
3034
47.8
3539
43.1
z40
42.9
P
b.001
Years since diabetes diagnosis
b2
64.8
25
46.3
N5
33.2
P
b.001
Income in US$
b20,000
41.1
20,00049,999
43.4
50,00079,999
47.0
N80,000
47.1
P
.02
History of CVD
Not reported
46.8
Reported
40.1
P
b.001
Source of health care
Private doctors office
48.2
Hospital clinic or
41.3
outpatient department
Community health center 33.9
Other kind of health
41.7
care facility
No usual source of care
34.8
P
b.001
Diabetes treatment
Insulin
25.5
Oral medication alone
47.0
No diabetes medication
67.9
P
b.001
Lipid-lowering medication
Not reported
45.8
Reported
45.7
P
.9

BP

LDL
cholesterol

All

50.5
52.3
.2

43.3
33.0
b.001

11.5
9.1
b.01

55.4
51.4
45.2
b.001

33.1
37.4
44.2
b.001

9.1
10.2
11.6
b.001

51.7
45.8
54.9
63.2
56.0
39.8
b.001

38.9
29.3
35.6
48.1
37.5
30.2
b.001

11.6
5.1
7.9
12.2
12.5
9.4
b.001

52.4
51.8
51.3
.8

33.9
37.4
38.1
.8

8.3
9.4
11.6
b.01

59.2
55.5
48.1
44.4
b.001

35.5
40.0
34.3
37.2
.8

14.1
11.1
8.5
7.7
b.001

52.8
51.9
50.7
.4

31.5
36.8
41.4
b.001

12.3
10.6
8.3
b.001

52.1
50.3
52.1
52.2
.7

35.9
37.6
37.2
38.3
.8

8.1
10.4
10.5
10.5
.4

51.5
52.2
.7

34.7
52.3
b.001

9.8
11.7
.1

50.4
55.4

37.1
40.4

10.6
10.2

56.5
50.3

32.6
36.6

8.6
6.3

65.2
.02

39.1
.2

4.3
.1

49.4
51.4
55.3
.06

41.7
37.8
28.2
b.001

7.5
10.3
12.7
b.01

50.5
52.7
.1

23.9
51.5
b.001

5.8
14.7
b.001

Table 2 (continued)
Characteristics
BP medication
Not reported
Reported
P
Regular aspirin use
Not reported
Reported
P

Hemoglobin
A1c

BP

LDL
cholesterol

All

46.0
45.7
.8

57.8
48.8
b.001

29.2
40.7
b.001

9.5
10.4
.3

46.5
45.0
.3

51.2
51.9
.6

31.0
44.3
b.001

8.8
11.7
b.001

Goals: hemoglobin A1c, b7%; BP, 130/80 mmHg; LDL cholesterol,

100 mg/dl.
Univariate logistic regression was performed for each variable, and P values
listed on the table are derived from the overall Wald chi-square test.

The results of multivariable analyses for BP, LDL, and

control of all three risk factors are presented in Table 4. The
only variables that remained significant for BP were age,
BMI, use of antihypertensive agent, and race/ethnicity.

Table 3
Results of multivariable analysis of characteristics associated with control
of hemoglobin A1c at b7%a
Characteristic

OR (95% confidence interval)

Age of participant in years; length of diabetes diagnosis in years

(vs. 4555 years; diabetes b3 years)
Age, 4555; diabetes, 37
0.46444 (0.360.59)
Age, 4555; diabetes, N7
0.33444 (0.250.44)
Age, 5665; diabetes, b3
1.4544
Age, 5665; diabetes, 37
0.63444 (0.510.78)
Age, 5665; diabetes, N7
0.44444 (0.350.56)
Age, 6676; diabetes, b3
1.11 (0.791.57)
Age, 6676; diabetes, 37
0.87 (0.641.18)
Age, 6676; diabetes, N7
0.61444 (0.460.81)
CVD history
0.7744 (0.650.92)
Diabetes treatment (vs. insulin)
No diabetes medication
3.19444 (2.514.07)
Oral medication
1.82444 (1.532.17)
Education in years (vs. N16 years)
1316
0.90 (0.791.03)
b13
0.7744 (0.650.91)
Race/ethnicity (vs. White)
African-American
0.70444 (0.590.83)
Hispanic
0.83 (0.681.01)
American Indian
1.06 (0.771.45)
Asian/Pacific Islander
0.80 (0.441.46)
Missing
1.65 (0.505.40)
Other/mixed
1.26 (0.801.97)
Usual source of care (vs. private doctor)
Community health center
0.6644 (0.510.85)
Hospital clinic or
0.91 (0.741.11)
outpatient department
Other kind of health care
0.82 (0.631.07)
No usual source of care
0.57 (0.231.44)
a

b.001

b.001

.01

b.01

.01

Results are for variables in the final model. Variables not listed were
not entered into the final model. P values given are for the effect of the
variable on the model. ORs listed are compared to the reference category
within the variable.
444 Pb.001.
44 Pb.01.

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

Table 4
Results of multivariable analyses of characteristics associated with control of BP (b130/80) and LDL (b100 mg/dl), and simultaneous control of hemoglobin
A1c, BP, and LDL cholesterol according to ADA-recommended goalsa
BP
Characteristics

OR
(95% confidence interval)

Age in years (vs. 4555 years)

5665
0.8444
6676
0.64444 (0.530.76)
Female

Race/ethnicity (vs. White)

African-American
0.7844 (0.670.92)
American Indian
1.394 (1.051.84)
Asian/Pacific Islander
0.89 (0.51.59)
Hispanic
1.03 (0.871.23)
Missing
0.65 (0.212.07)
Other/mixed
0.594 (0.380.91)
BMI in kg/m2 (reference, N40 kg/m2)
b30
1.92444 (1.582.34)
3034
1.65444 (1.411.92)
3539
1.194 (1.021.40)
History of CVD

Duration of diabetes

Diabetes treatment (vs. insulin)

No diabetes medication

Oral medication

BP medication
0.77444 (0.680.87)
Lipid-lowering medication

Use of aspirin 5 days/week

LDL
P
b.001

.001

b.001

All

OR
(95% confidence interval)

0.76444 (0.670.87)
0.814 (0.680.98)
2.33444 (1.713.17)
1.20 (0.632.27)
1.16 (0.961.40)
0.32 (0.071.52)
0.81 (0.511.30)

1.274 (1.041.50)
1.014 (1.001.02)

1.32444 (1.151.53)
3.04444 (2.673.47)
1.27444 (1.111.42)

OR
(95% confidence interval)

b.001

0.51444 (0.360.71)
1.534 (1.02.35)
1.06 (0.442.56)
0.78 (0.571.06)
0.79 (0.16.31)
0.93 (0.461.89)

b.001

1.85444 (1.362.52)

b.001

1.384 (1.051.80)
1.10 (0.821.48)

2.05444 (1.452.89)

b.001

1.5044 (1.141.97)

2.87444 (2.333.53)

a
Results are for variables in the final model. Variables not listed were not entered into the final model. P values given are for the effect of the variable on
the model. ORs listed are compared to the reference category within the variable.
4 Pb.05.
44 Pb.01.
444 Pb.001.

Increasing BMI was associated with a decreasing likelihood

of BP control. African-Americans were less likely
(OR=0.78) and Native Americans were more likely
(OR=1.39) to have BP control. In regard to meeting LDL
goal, aspirin use, prior history of CVD, a longer duration of
diabetes, use of BP medications, and utilization of lipidlowering medications were associated with an increased
likelihood of control. There was evidence of gender
disparity, as well as race/ethnic differences (female African-Americans were less likely; Native Americans were
more likely), in LDL control.
Increasing obesity remained a significant risk factor for
the poor control of all three risk factors in the final model.
African-Americans were half as likely as Whites to achieve
control of all three risk factors. Persons who did not report
taking any diabetes medication and those using only oral
medications were more likely to have met all three goals
than those reporting insulin use. The use of lipid-lowering
medications was associated with meeting all three goals.

4. Discussion
These data demonstrate suboptimal control of glycemia,
BP, and LDL cholesterol among type 2 diabetic subjects

recruited into Look AHEAD (20012004). It is particularly

notable that simultaneous control of these risk factors was
achieved in very few persons; given the potentially bhealthy
volunteerQ status of these trial participants, simultaneous
control of these three risk factors in the general diabetic
population may well be less than the 10.1% we observed.
We found consistent evidence for racial and ethnic differences in the control of risk factors, as well as variability by
age, gender, education, income, CVD status, degree of
obesity, and source of medical care.
These findings should be interpreted in the context of also
finding that control of risk factors in this population was
substantially better than those in several prior studies.
Among elderly diabetic participants in the Cardiovascular
Health Study (in the early 1990s), only 12% had a fasting
blood glucose b110 mg/dl, 27% had a BP b130/85 mmHg,
and 8% had an LDL level b100 mg/dl (Smith et al., 2002).
Somewhat better control was reported among diabetic
participants in the Insulin Resistance and Atherosclerosis
Study (19931998); 41% had hemoglobin A1c b7%, 32%
had a BP b130/85 mmHg, and 35% had an LDL level
b130 mg/dl (Bonds et al., 2003). These prior two studies
had somewhat different definitions of control from the
present study. A similar proportion of diabetic NHANES
participants in 19992002 (mean age=59 years, mean

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

BMI=31.8 kg/m2) achieved hemoglobin A1c b7% (49.8%)

or LDL level b100 mg/dl (36.0%), but fewer had a BP
b130/80 mmHg (39.6%) than in Look AHEAD (Resnick
et al., 2006). There are some data suggesting a secular trend
of improvement in the control of these risk factors
from national surveys spanning the 1970s up to 2000
(Imperatore et al., 2004). Another explanation is that
our participants are motivated individuals enrolled in a
clinical trial (a bhealthy volunteerQ effect). The exclusion
criteria eliminated those with the poorest control of these risk
factors. This likely biases our estimates of control higher
than that in the general diabetic population. This volunteer
bias should not affect, however, the validity of associations
between participant characteristics and control of risk factors
to recommended levels, although our approach may tend to
underestimate the magnitude of these associations.
The racial/ethnic differences observed are consistent with
prior studies (Kirk et al., 2005; Trivedi, Zaslavsky,
Schneider, & Ayanian, 2005). Of particular concern is the
finding that only 5.1% of African-Americans and 7.9% of
Hispanics achieved control of all three risk factors,
compared to a better (but still quite suboptimal) rate among
Whites (11.6%). Our analyses suggest that BlackWhite
differences in control are not related to differences in
education, income, use of diabetes medications, or source of
care. We could not explore whether differential processes of
care (such as frequency of checking hemoglobin A1c) prior
to enrollment into this study may have contributed to this
racial disparity. There have been few studies with data from
both Native American and non-Native American populations with diabetes (Kirk et al., 2005). We found evidence
for better control of LDL and BP in Native Americans than
in Whites. This finding may reflect inherent differences in
lipids between American Indians and Caucasians (Howard,
Davis, Pettitt, Knowler, & Bennett, 1983), or the impact of
Indian Health Services recent focus on the quality of
diabetes care (Wilson et al., 2005).
Obesity is known to have adverse effects on glycemia,
BP, and dyslipidemia in persons with type 2 diabetes, and
some studies have noted significant improvements in these
parameters with weight loss (Aucott et al., 2005; Maggio &
Pi-Sunyer, 2003; Norris et al., 2004). It is possible that, in
addition to the physiologic effects of obesity, the behaviors
that contributed to obesity, including poor diet and physical
activity patterns, may contribute to lack of compliance
either with lifestyle or medical therapy recommendations
(Safford, Russell, Suh, Roman, & Pogach, 2005; Wing et al.,
2001). We did not find a significant relationship between
degree of obesity and LDL control. This may reflect the
strong relationship between the use of lipid-lowering
medication and control in this sample. However, obesity
remained a significant predictor of simultaneous control of
all three factors.
The predictors of control for individual risk factors
beyond ethnicity and obesity were different for each
individual factor. For hemoglobin A1c, our findings

suggest that the longer is the duration of diabetes,

especially among younger persons, the more difficult it is
to achieve a hemoglobin A1c level b7%. The inverse
relationship between age and the association of insulin use
with poor control has been demonstrated in other studies as
well (El Kebbi et al., 2003; Shorr et al., 2000). However, to
our knowledge, ours is the first to demonstrate a differential
deleterious effect of the duration of diabetes on glycemic
control across age groups. The influence of the duration of
diabetes on hemoglobin A1c control was strongest for the
youngest participants and lessened with age. Our study
could not explicitly examine the mechanisms underlying
this finding. A potential explanation is the possibility that
the youngest participants with a long duration of diabetes
had type 1 diabetes. Look AHEAD excluded persons aged
b25 years upon diagnosis who had never been managed
without insulin, making it unlikely that we had a significant
number of participants with type 1 diabetes. An alternate
explanation could detection bias, with older individuals
having been detected earlier in the course of their disease
since they tended to present more often for routine care and
therefore had greater opportunity for screening.
The contradictory finding that insulin users and those on
oral medication were less likely to achieve hemoglobin A1c
control may reflect confounding by indication (hemoglobin
A1c N7; thus, medications were prescribed), as well as the
reluctance of patients and providers to utilize insulin
injections until control of diabetes is poor. In addition to
the socioeconomic implications of less education, our
findings may also reflect the role of health literacy in the
control of a chronic disease such as diabetes (Dewalt,
Berkman, Sheridan, Lohr, & Pignone 2004). We did not ask
why persons in Look AHEAD utilized community health
centers, but this likely reflects fewer economic resources
being available personally or in the community.
For the control of LDL, data suggest that persons
perceived to be at higher cardiovascular risk (presence of
CVD, use of insulin, longer duration of diabetes, and use of
BP medications) were more aggressively managed
with respect to LDL. Conversely, persons not utilizing
diabetes medications may be perceived as having less
severe diabetes and being at lower CVD risk. However,
the most recent national cholesterol guideline (Third Adult
Treatment Panel) has suggested that diabetic adults be
considered to be CVD risk equivalents with respect to LDL
lowering, regardless of diabetes severity or treatment. Our
findings with respect to aspirin could also be a marker for
individuals recognized by their physicians as being at
higher risk, or may be a marker for increased patient
compliance with advice, as aspirin is available without
prescription in the United States.
This analysis benefits from several strengths, most
notably a large, diverse, nationwide sample of overweight/obese adults with diabetes. Our age and racial/
ethnic mix is consistent with NHANES 19992002 data
on adults with diabetes (62% White, mean age of 59 years)

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

(Resnick et al., 2006). There was standardized assessment

of risk factors, as well as patient-level characteristics. Our
main limitations are those inherent in a cross-sectional
analysis of randomized trial participants at baseline. As
discussed above, this may affect the generalizability of
these findings to the greater public, but should not affect
the internal validity of our findings. It is likely that the
detrimental effects of minority race/ethnicity, obesity, less
education, and female gender are also significant predictors
of control in the general diabetic population. Finally, since
we did not record the dose of medications, we cannot
address whether differences in the dosages of these
medications influenced the observed differences.
Our findings are cause for concern given the expected
relationship of these factors with future complications of
diabetes. Although achievement of triple control was rare in
all participants, African-Americans and the more obese
participants were especially unlikely to benefit from
maximal risk factor reduction. Multifaceted interventions
directed at health care providers or new models of care
(e.g., the chronic care model) have had some success in
improving the control of multiple risk factors among
patients with diabetes (Olivarius, Beck-Nielsen, Andreasen,
Horder, & Pedersen, 2001; Piatt et al., 2006). Further
attention on overcoming barriers for the achievement of
more aggressive risk factor target levels is needed.
Acknowledgement
This study was supported by the US Department of
Health and Human Services through the following
cooperative agreements from the National Institutes of
Health: DK57136, DK57149, DK56990, DK57177,
DK57171, DK57151, DK57182, DK57131, DK57002,
DK57078, DK57154, DK57178, DK57219, DK57008,
DK57135, and DK56992. The following federal agencies
have contributed support: National Institute of Diabetes and
Digestive and Kidney Diseases; National Heart, Lung, and
Blood Institute; National Institute of Nursing Research;
National Center on Minority Health and Health Disparities;
Office of Research on Womens Health; and the Centers
for Disease Control and Prevention. This research was
supported, in part, by the Intramural Research Program
of the National Institute of Diabetes and Digestive and
Kidney Diseases.
Additional support was received from The Johns
Hopkins Medical Institutions Bayview General Clinical
Research Center (M01-RR-02719); the Massachusetts
General Hospital Mallinckrodt General Clinical Research
Center (M01-RR-01066); the University of Colorado
Health Sciences Center General Clinical Research Center
(M01 RR00051) and Clinical Nutrition Research Unit (P30
DK48520); the University of Tennessee at Memphis
General Clinical Research Center (M01RR00211-40); the
University of Pittsburgh General Clinical Research Center
(M01 RR000056 44) and National Institutes of Health

grant (DK 046204); and the University of Washington/VA

Puget Sound Health Care System Medical Research
Service, Department of Veterans Affairs.
The following organizations have committed to make
major contributions to Look AHEAD: Federal Express;
Health Management Resources; Johnson&Johnson, LifeScan, Inc.; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; and
Slim-Fast Foods Co.
Appendix A. Look AHEAD acknowledgements during
the baseline phase
Clinical sites
The Johns Hopkins Medical Institutions Frederick
Brancati, MD, MHS; Debi Celnik, MS, RD, LD; Jeff
Honas, MS; Jeanne Clark, MD, MPH; Jeanne Charleston,
RN; Lawrence Cheskin, MD; Kerry Stewart, EdD; Richard
Rubin, PhD; Kathy Horak, RD
Pennington Biomedical Research Center George A.
Bray, MD; Kristi Rau; Allison Strate, RN; Frank L.
Greenway, MD; Donna H. Ryan, MD; Donald Williamson,
PhD; Elizabeth Tucker; Brandi Armand, LPN; Mandy
Shipp, RD; Kim Landry; Jennifer Perault
The University of Alabama at Birmingham Cora E.
Lewis, MD, MSPH; Sheikilya Thomas, MPH; Vicki DiLillo,
PhD; Monika Safford, MD; Stephen Glasser, MD; Clara
Smith, MPH; Cathy Roche, RN; Charlotte Bragg, MS, RD,
LD; Nita Webb, MA; Staci Gilbert, MPH; Amy Dobelstein;
L. Christie Oden; Trena Johnsey
Harvard Center Massachusetts General Hospital David
M. Nathan, MD; Heather Turgeon, RN; Kristina P.
Schumann, BA; Enrico Cagliero, MD; Kathryn Hayward,
MD; Linda Delahanty, MS, RD; Barbara Steiner, EdM;
Valerie Goldman, MS, RD; Ellen Anderson, MS, RD; Laurie
Bissett, MS, RD; Alan McNamara, BS; Richard Ginsburg,
PhD; Virginia Harlan, MSW; Theresa Michel, MS
Joslin Diabetes Center Edward S. Horton, MD; Sharon
D. Jackson, MS, RD, CDE; Osama Hamdy, MD, PhD; A.
Enrique Caballero, MD; Sarah Ledbury, MEd, RD; Maureen
Malloy, BS; Ann Goebel-Fabbri, PhD; Kerry Ovalle, MS,
RCEP, CDE; Sarah Bain, BS; Elizabeth Bovaird, BSN, RN;
Lori Lambert, MS, RD
Beth Israel Deaconess Medical Center George Blackburn, MD, PhD; Christos Mantzoros, MD, DSc; Ann
McNamara, RN; Heather McCormick, RDUniversity of
Colorado Health Sciences Center James O. Hill, PhD;
Marsha Miller, MS, RD; Brent VanDorsten, PhD; Judith
Regensteiner, PhD; Robert Schwartz, MD; Richard Hamman, MD, DrPH; Michael McDermott, MD; JoAnn
Phillipp, MS; Patrick Reddin, BA; Kristin Wallace, MPH;
Paulette Cohrs, RN, BSN; April Hamilton, BS; Salma
Benchekroun, BS; Susan Green; Loretta Rome, TRS;
Lindsey Munkwitz, BSBaylor College of Medicine John P.

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

Foreyt, PhD; Rebecca S. Reeves, DrPH, RD; Henry Pownall,

PhD; Peter Jones, MD; Ashok Balasubramanyam, MD;
Molly Gee, MEd, RD
University of California at Los Angeles School of
Medicine Mohammed F. Saad, MD; Ken C. Chiu, MD;
Siran Ghazarian, MD; Kati Szamos, RD; Magpuri Perpetua,
RD; Michelle Chan, BS; Medhat Botrous
The University of Tennessee Health Science Center
Karen C. Johnson, MD, MPH; Abbas E. Kitabchi, PhD,
MD; Helen Lambeth, RN, BSN; Leeann Carmichael, RN;
Lynne Lichtermann, RN, BSN
University of Minnesota Robert W. Jeffery, PhD; Carolyn
Thorson, CCRP; John P. Bantle, MD; J. Bruce Redmon,
MD; Richard S. Crow, MD; Jeanne Carls, MEd; Carolyne
Campbell; La Donna James; T. Ockenden, RN; Kerrin
Brelje, MPH, RD; M. Patricia Snyder, MA, RD; Amy
Keranen, MS; Cara Walcheck, BS, RD; Emily Finch, MA;
Birgitta I. Rice, MS, RPh, CHES; Vicki A. Maddy, BS, RD;
Tricia Skarphol, BS
St. Lukes Roosevelt Hospital Center Xavier Pi-Sunyer,
MD; Jennifer Patricio, MS; Jennifer Mayer, MS; Stanley
Heshka, PhD; Carmen Pal, MD; Mary Anne Holowaty, MS,
CN; Diane Hirsch, RNC, MS, CDE
University of Pennsylvania Thomas A. Wadden, PhD;
Barbara J. Maschak-Carey, MSN, CDE; Gary D. Foster,
PhD; Robert I. Berkowitz, MD; Stanley Schwartz, MD;
Shiriki K. Kumanyika, PhD, RD, MPH; Monica Mullen,
MS, RD; Louise Hesson, MSN; Patricia Lipschutz,
MSN; Anthony Fabricatore, PhD; Canice Crerand, PhD;
Robert Kuehnel, PhD; Ray Carvajal, MS; Renee Davenport;
Helen Chomentowski
University of Pittsburgh David E. Kelley, MD; Jacqueline Wesche-Thobaben, RN, BSN, CDE; Lewis Kuller, MD,
DrPH; Andrea Kriska, PhD; Daniel Edmundowicz, MD;
Mary L. Klem, PhD, MLIS; Janet Bonk, RN, MPH; Jennifer
Rush, MPH; Rebecca Danchenko, BS; Barb Elnyczky, MA;
Karen Vujevich, RN-BC, MSN, CRNP; Janet Krulia, RN,
BSN,CDE; Donna Wolf, MS; Juliet Mancino, MS, RD,
CDE, LDN; Pat Harper, MS, RD, LDN; Anne Mathews,
MS, RD, LDNBrown University Rena R. Wing, PhD;
Vincent Pera, MD; John Jakicic, PhD; Deborah Tate, PhD;
Amy Gorin, PhD; Renee Bright, MS; Pamela Coward, MS,
RD; Natalie Robinson, MS, RD; Tammy Monk, MS; Kara
Gallagher, PhD; Anna Bertorelli, MBA, RD; Maureen Daly,
RN; Tatum Charron, BS; Rob Nicholson, PhD; Erin
Patterson, BS; Julie Currin, MD; Linda Foss, MPH;
Deborah Robles; Barbara Bancroft, RN, MS; Jennifer
Gauvin, BS; Deborah Maier, MS; Caitlin Egan, MS;
Suzanne Phelan, PhD; Hollie Raynor, PhD, RD; Don
Kieffer, PhD; Douglas Raynor, PhD; Lauren Lessard, BS;
Kimberley Chula-Maguire, MS; Erica Ferguson, BS, RD;
Richard Carey, BS; Jane Tavares, BS; Heather Chenot, MS;
JP Massaro, BS
The University of Texas Health Science Center at San
Antonio Steve Haffner, MD; Maria Montez, RN, MSHP,
CDE; Connie Mobley, PhD, RD; Carlos Lorenzo, MD

University of Washington/VA Puget Sound Health

Care System Steven E. Kahn, MB, ChB; Brenda
Montgomery, MS, RN, CDE; Robert H. Knopp, MD;
Edward W. Lipkin, MD, PhD; Matthew L. Maciejewski,
PhD; Dace L. Trence, MD; Roque M. Murillo, BS; S. Terry
Barrett, BS
Southwestern American Indian Center, Phoenix, AZ, and
Shiprock, NM William C. Knowler, MD, DrPH; Paula
Bolin, RN, MC; Tina Killean, BS; Carol Percy, RN; Rita
Donaldson, BSN; Bernadette Todacheenie, EdD; Justin
Glass, MD; Sarah Michaels, MD; Jonathan Krakoff, MD;
Jeffrey Curtis, MD, MPH; Peter H. Bennett, MB, FRCP;
Tina Morgan; Ruby Johnson; Cathy Manus; Janelia Smiley;
Sandra Sangster; Shandiin Begay, MPH; Minnie Roanhorse;
Didas Fallis, RN; Nancy Scurlock, MSN, ANP; Leigh
Shovestull, RD
Coordinating center
Wake Forest University School of Medicine Mark A.
Espeland, PhD; Judy Bahnson, BA; Lynne Wagenknecht,
DrPH; David Reboussin, PhD; W. Jack Rejeski, PhD;
Wei Lang, PhD; Alain Bertoni, MD, MPH; Mara Vitolins,
DrPH; Gary Miller, PhD; Paul Ribisl, PhD; Kathy Dotson,
BA; Amelia Hodges, BA; Patricia Hogan, MS; Kathy Lane,
BS; Carrie Combs, BS; Christian Speas, BS; Delia S. West,
PhD; William Herman, MD, MPH
Central resources centers
DXA Reading Center, University of California at
San Francisco Michael Nevitt, PhD; Ann Schwartz, PhD;
John Shepherd, PhD; Jason Maeda, MPH; Cynthia Hayashi;
Michaela Rahorst; Lisa Palermo, MS, MA
Central Laboratory, Northwest Lipid Research Laboratories Santica M. Marcovina, PhD, ScD; Greg Strylewicz, MS
ECG Reading Center, EPICARE, Wake Forest University
School of Medicine Ronald J. Prineas, MD, PhD; Zhu-Ming
Zhang, MD; Charles Campbell, AAS, BS; Sharon Hall
Diet Assessment Center, University of South Carolina,
Arnold School of Public Health, Center for Research in
Nutrition and Health Disparities Elizabeth J. Mayer-Davis,
PhD; Cecilia Farach, DrPH
Federal sponsors
National Institute of Diabetes and Digestive and Kidney
Diseases Barbara Harrison, MS; Susan Z. Yanovski, MD;
Van S. Hubbard, MD PhD
National Heart, Lung, and Blood Institute Lawton S.
Cooper, MD, MPH; Eva Obarzanek, PhD, MPH, RD;
Denise Simons-Morton, MD, PhD
Centers for Disease Control and Prevention David F.
Williamson, PhD; Edward W. Gregg, PhD

A.G. Bertoni et al. / Journal of Diabetes and Its Complications 22 (2008) 1 9

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