Dietary fat intake and risk of type 2 diabetes in women1–3
Jorge Salmerón, Frank B Hu, JoAnn E Manson, Meir J Stampfer, Graham A Colditz, Eric B Rimm, and Walter C Willett

KEY WORDS
Dietary fat, polyunsaturated fat, trans fatty
acids, type 2 diabetes, risk, women

INTRODUCTION
Excess body fat resulting from an imbalance between energy
intake and physical activity is the primary risk factor for type 2
diabetes (1, 2), but a role for dietary fat has also been hypothesized. However, the long-term effects of specific types of dietary
fatty acids on insulin resistance and risk of type 2 diabetes
remain unclear (3). Beneficial effects of diets high in monounsaturated (4, 5) and polyunsaturated (6) fatty acids relative to
low-fat, high-carbohydrate diets on glucose control and insulin

See corresponding editorial on page 1001.
sensitivity have been reported, but these effects have not been
seen universally (7, 8). Short-term studies documented adverse
effects of trans fatty acid intakes on serum lipoprotein profiles(9, 10) and insulin sensitivity (11).
Epidemiologic data on dietary fats and risk of type 2 diabetes
are sparse. One cross-sectional analysis reported a positive association of saturated fatty acid intake with insulin concentrations
but an inverse association with polyunsaturated fatty acid intake(12). Two prospective studies that evaluated the incidence oftype 2 diabetes reported no association between total dietary fat(13, 14) or specific types of fatty acids and risk of diabetes (14).
However, these findings were limited by inadequate dietaryassessment, a small number of endpoints, and incomplete control
of confounding. In particular, these analyses did not adjust one
type of fatty acid for the other, which is important because theytend to be intercorrelated (15) and may have opposing effects.
We previously reported an inverse relation of vegetable fat
intake to 6-y incidence of diabetes in a large cohort of men (16),as did the Nurses’ Health Study (17, 18). In the present analysis, which is based on 14 y of follow-up in the Nurses’ HealthStudy, we examined in detail specific types of dietary fatty acids
in relation to risk of type 2 diabetes. Dietary measurements
were made repeatedly to reduce errors in dietary assessment andto account for changes in eating behaviors and food consumption
over time. In addition, we used multivariate modeling to assess
the long-term independent effects of major types of dietary fatty
acids by mutually adjusting intakes of specific types of fatty
acids for each other.

1
From the Departments of Nutrition and Epidemiology, Harvard Schoolof Public Health, Boston; the Channing Laboratory, the Division of Preventive Medicine, the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston; and the Unidad de Investigación
Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro
Social, Mexico City.
2
Supported by National Institutes of Health research grants CA40356
and DK 36798. FBH is supported by a Research Award from the American
Diabetes Association.
3
Address reprint requests to FB Hu, Department of Nutrition, Harvard
School of Public Health, 665 Huntington Avenue, Boston, MA 02115. E-mail:frank.hu@channing.harvard.edu.
Received September 26, 2000.
Accepted for publication December 7, 2000.

Am J Clin Nutr 2001;73:1019–26. Printed in USA. © 2001 American Society for Clinical Nutrition

1019

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ABSTRACT
Background: The long-term relations between specific types of
dietary fat and risk of type 2 diabetes remain unclear.
Objective: Our objective was to examine the relations between
dietary fat intakes and the risk of type 2 diabetes.
Design: We prospectively followed 84 204 women aged 34–59 ywith no diabetes, cardiovascular disease, or cancer in 1980.
Detailed dietary information was assessed at baseline and updated
in 1984, 1986, and 1990 by using validated questionnaires. Relative risks of type 2 diabetes were obtained from pooled logistic
models adjusted for nondietary and dietary covariates.
Results: During 14 y of follow-up, 2507 incident cases of type 2
diabetes were documented. Total fat intake, compared withequivalent energy intake from carbohydrates, was not associatedwith risk of type 2 diabetes; for a 5% increase in total energy
from fat, the relative risk (RR) was 0.98 (95% CI: 0.94, 1.02).
Intakes of saturated or monounsaturated fatty acids were also notsignificantly associated with the risk of diabetes. However, for a
5% increase in energy from polyunsaturated fat, the RR was 0.63
(0.53, 0.76; P < 0.0001) and for a 2% increase in energy fromtrans fatty acids the RR was 1.39 (1.15, 1.67; P = 0.0006). We
estimated that replacing 2% of energy from trans fatty acids
isoenergetically with polyunsaturated fat would lead to a 40%
lower risk (RR: 0.60; 95% CI: 0.48, 0.75).
Conclusions: These data suggest that total fat and saturated andmonounsaturated fatty acid intakes are not associated with riskof type 2 diabetes in women, but that trans fatty acids increase
and polyunsaturated fatty acids reduce risk. Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids
would likely reduce the risk of type 2 diabetes substantially.
Am J Clin Nutr 2001;73:1019-26.

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SALMERÓN ET AL

SUBJECTS AND METHODS
Study population

Dietary assessment
We used validated semiquantitative food-frequency questionnaires to assess the participants’ diets. Full descriptions of thefood-frequency questionnaire in its abbreviated (61 items, 1980)
and expanded (116–136 items, 1984 and on) forms, the procedures for calculating nutrient intakes, and data on reproducibility and validity in this cohort were previously reported (21–23).
A common unit or portion size for each food (eg, one egg or one
slice of bread) was specified and participants were asked how
often on average during the previous year they had consumed
that amount. The 9 responses ranged from “never or less thanonce per month” to “six or more times per day.” Detailed information about types of fat or oil used for frying, baking, and at thetable and the type of margarine usually used was collected: stickor tub in 1980 and 1984 and brand and type in 1986 and 1990.
Composition values for dietary fats and other nutrients wereobtained from the Harvard University Food Composition Database, derived from US Department of Agriculture sources (24)and supplemented with manufacturer’s information. Foodcomposition data are continuously updated to account for changes
in food processing and improved analytic methods. Values in1980 for the total trans isomer fatty acid contents of foods werebased on analyses by Enig et al (25) and Slover et al (26) andwere updated by using data from the US Department of Agriculture, food manufacturers, and analyses of commonly used margarines, shortenings, and baked products at the Harvard Schoolof Public Health (Department of Nutrition, Boston). We included
all trans isomers of 18-carbon fatty acids. The most important
determinants of trans fatty acids at baseline in the Nurses’
Health Study were margarine; beef, pork, or lamb as a main dish;cookies (biscuits); and white bread (15). All of these food items

Measurement of nondietary factors
In 1980 participants provided information on their weight andsmoking status. We updated this information every 2 y duringfollow-up. The validity of self-reported weight in this cohort waspreviously reported (r = 0.96 between self-reported and measured weight) (29). The level of physical activity in metabolic
equivalents per week was estimated based on the self-reported
duration per week of various forms of exercise, with each activity weighted by its intensity level (30) according to informationcollected via the questionnaires at baseline, 1986, and 1992. In
1982 participants provided information on the history of diabetes
in first-degree relatives.
Follow-up and ascertainment of cases
On the baseline and follow-up questionnaires that were
mailed every 2 y (from 1980 to 1994), we inquired about
whether diabetes had been newly diagnosed. When a diagnosis
of diabetes mellitus was reported on a follow-up questionnaire,participants were asked to complete a supplementary questionnaire to confirm the report and to ascertain the date of diagnosis
and details of the diagnostic tests, presenting symptoms, andmedications. After women with type 1 and gestational diabetes
only were excluded, the diagnosis of type 2 diabetes was established if one or more of the following criteria were met: 1) one
or more classic symptoms (excessive thirst, polyuria, weight
loss, and pruritus) plus a fasting plasma glucose concentration≥ 7.78 mmol/L (140 mg/dL) or a random plasma glucose concentration ≥ 11.11 mmol/L (200 mg/dL), 2) ≥ 2 elevated plasma
glucose concentrations on different occasions (fasting ≥ 7.78mmol/L, random ≥ 11.11 mmol/L, or ≥ 11.11 mmol/L after ≥ 2 hof oral-glucose-tolerance testing) in the absence of symptoms, or3) treatment with medication for hypoglycemia (insulin or oral
hypoglycemic agents). These criteria correspond to those proposed in 1979 by the National Diabetes Data Group (31) and theWorld Health Organization in 1985 (32). The high validity ofself-reported diabetes in this cohort on the supplementary questionnaire was previously documented and the diagnosis was confirmed by a review of medical records in 98% of cases (17). In
1997 the fasting plasma glucose concentration indicative oftype 2 diabetes was lowered (≥ 7.0 mmol/L, or 126 mg/dL) on
the basis of the American Diabetes Association’s recommendation (33). In the current analyses, we used the previous criterion
because at the time the follow-up was conducted, the National

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The Nurses’ Health Study is a longitudinal investigation of dietand lifestyle factors in relation to incidence of chronic diseases in
121 700 US female registered nurses aged 30–55 y at enrollment.
The cohort was assembled in 1976 when the participants returneda mailed questionnaire about known and suspected risk factors
for cancer and cardiovascular disease (19). In 1980 we assessed
dietary intakes of specific types of fat and other nutrients by using
a 61-item semiquantitative food-frequency questionnaire (20).
In 1984 an expanded food-frequency questionnaire (116 fooditems) was mailed to cohort members; similar questionnaires
were used to update dietary information in 1986 and 1990.
For the present analysis, we used information from respondents(98 462 women aged 34–59 y) to the 1980 questionnaire. We
excluded participants who did not satisfy the a priori criteriaof a daily energy intake between 2092 and 14 644 kJ/d (500 and3500 kcal/d) and those who left > 10 of the 61 items on the
dietary questionnaire blank. In addition, we excluded women
who reported on the 1980 or a previous questionnaire a diagnosis
of diabetes and those who reported cancer, myocardial infarction,
angina, stroke, and coronary artery surgery because they may havemodified their diet after the diagnosis. The remaining 84 204 women
were followed for diabetes incidence during the subsequent 14 y
(1980–1994). The follow-up rates for type 2 diabetes were 98%of the total potential person-years of follow-up. The protocol ofthe study was approved by the Institutional Review Board at
Brigham and Women’s Hospital.

were assessed at baseline and updated in 1984, 1986, and 1990.
The polyunsaturated fat intakes reported in this study include
only linoleic acid, which accounted for 81% of the total polyunsaturated fatty acid intake in our cohort. Nutrient intake wascomputed by multiplying the frequency of consumption of eachfood by the nutrient content of the specified portions, taking into
account the type of fat used in preparation, including the brand,
type, and year of margarine use.
Both the original and revised questionnaires provide a reasonable measure of total and specific types of fat intakes when compared with multiple 1-wk diet records; correlation coefficientsfor total and specific types of fat assessed by dietary records andfood-frequency questionnaires ranged from 0.46 to 0.58 for theabbreviated 1980 questionnaire and from 0.48 to 0.68 for the
expanded questionnaire (27). The correlation coefficient between
calculated dietary intake of trans fatty acids and the proportionof trans fatty acids in adipose tissue was 0.51 (28).

DIETARY FAT AND DIABETES

1021

TABLE 1Baseline characteristics and risk factors for diabetes according to the intake of specific types of fat at baseline
Polyunsaturated fat
Intermediate
quintile

Highestquintile

Lowestquintiletrans Fat
Intermediate
quintile

Highestquintile

48 ± 71
24 ± 410 ± 1451.2 ± 17.9284 ± 122
14 ± 615 ± 414 ± 42 ± 0.4
2 ± 0.5
19
32
48
19

46 ± 724 ± 46 ± 1051.6 ± 18.4
257 ± 103
13 ± 516 ± 316 ± 44 ± 0.2
2 ± 0.5
18
27
45
19

45 ± 724 ± 55±848.3 ± 20.1
234 ± 9013 ± 415 ± 317 ± 37±1
3 ± 0.8
18
28
42
18

47 ± 724 ± 410 ± 1451.9 ± 24.1
313 ± 124
16 ± 613 ± 412 ± 33±2
1 ± 0.3
18
28
53
19

46 ± 724 ± 46±950.9 ± 16.7
251 ± 96
13 ± 416 ± 316 ± 34±1
2 ± 0.1
18
28
43
19

46 ± 724 ± 54±749.2 ± 16.7
216 ± 8112 ± 416 ± 318 ± 36±2
3 ± 0.5
19
30
37
17

Diabetes Data Group and World Health Organization definitions
were the standard. Also, use of a stricter definition of type 2 diabetes can minimize false-positive results and thus enhance thevalidity of the observed associations (34). Deaths were identified
from state vital records and the National Death Index or werereported by next of kin and the postal system; mortality followup was 98% complete (15).
Statistical analysis
For each participant, person-time of follow-up was counted
from the date of return of the 1980 questionnaire to the dateof diabetes diagnosis, to the time of return of the most recent
follow-up questionnaire, or to 1 June 1994, whichever came first.
Women with diabetes or cancer as indicated on a previous questionnaire were excluded from subsequent follow-up; thus, thecohort at risk included only those who remained free from diabetes or cancer at the beginning of every 2-y follow-up interval.
Women were divided into quintiles by percentage of energy
from each type of fatty acid; incidence rates were calculated by
dividing the number of events by person-time of follow-up in eachquintile. To reduce within-subject variation and best represent thelong-term diet, we used pooled logistic regression (35) to model
the cumulative average of fat intake from all available dietary
questionnaires up to the start of each 2-y follow-up interval in
relation to diabetes incidence. During the next 2 y, for example,
the fat intake from the 1980 questionnaire was related to disease
incidence during the 1980–1982 and 1982–1984 time intervals
and the average fat intake from the 1980 and 1984 questionnaires
was related to incidence during 1984–1986. Because changes indiet after development of hypercholesterolemia, hypertension,angina, myocardial infarction, coronary artery surgery, or stroke
may confound the diet-disease associations (36), we stopped
updating dietary information at the beginning of the time interval
during which individuals developed these endpoints.
In multivariate nutrient-density models (27), we simultaneously included energy intake, percentages of energy from protein
and specific fatty acids, and other potential confounding variables. The nondietary covariates included seven 2-y time periods,
age in 5-y categories, body mass index [BMI: weight (in kg)

divided by the square of the height (in m) in 11 categories], smoking status (never, past, and current smoking classified into 3 categories on the basis of the number of cigarettes smoked/d: 1–14,
15–24, and ≥ 25), alcohol consumption (g/d in 4 categories),
physical activity (metabolic equivalents/wk in 5 categories), andhistory of diabetes in a first-degree relative. We tested for significant monotonic trends across quintiles of fat intake by assigningeach participant the median value for the category and modelingthis value as a continuous variable. All P values are two-sided.
We evaluated the effects of specific types of fatty acids byexpressing them as a percentage of total energy (nutrient density)and including them in models as continuous variables. When all
types of fats, protein, and alcohol are included simultaneously,
the coefficients from these nutrient-density models can be interpreted as the effect of exchanging energy from a specific fat forthe same amount of energy from carbohydrates. We also estimated the effects of substituting one type of fat for another, using
the difference between coefficients from the same model (27).

RESULTS
During 14 y of follow-up, we documented 2507 incident casesof type 2 diabetes. As previously reported (15), intakes of specifictypes of fat at baseline tended to correlate with one another.
Intake of saturated fat correlated with intakes of monounsaturatedfat (r = 0.81) and trans fat (r = 0.30) but not with intake ofpolyunsaturated fat (r = 0.01). Intake of monounsaturated fat wascorrelated with intakes of trans fat (r = 0.55) and polyunsaturatedfat (r = 0.30). Intake of polyunsaturated fat was correlated withthat of trans fat (r = 0.58). The high correlation between monounsaturated and saturated fatty acids was due to shared sources ofthese fats (ie, dairy products and beef). As described elsewhere(15), BMI was not appreciably associated with total or specifictypes of dietary fat. Women with a higher intake of trans fat weremore likely to smoke, were less likely to engage in regular physical activity, and had lower intakes of alcohol and folate (Table 1).
Women with a higher intake of polyunsaturated fat were lesslikely to smoke, less likely to engage in regular exercise, and also
had lower intakes of alcohol and folate. Women who consumed

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Age (y)BMI (kg/m2)
Alcohol (g/d)
Cholesterol (mg·MJ1 ·d1)
Folate from diet (g/d)
Fiber (g/d)
Saturated fat (% of energy)
Monounsaturated fat (% of energy)
Polyunsaturated fat (% of energy)trans Fat (% of energy)
Family history of diabetes (%)
Current smoking (%)
Vigorous exercise ≥ 1/wk (%)
Currently receiving estrogen replacement
therapy, postmenopausal women only (%)
1–
x ± SD.

Lowestquintile

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SALMERÓN ET AL

TABLE 2
Relative risks (and 95% CIs) of type 2 diabetes according to quintiles of intake of specific types of dietary fat and fatty acids1
Variable2

Quintile
3

4

5

28.9
1.0
1.0
17.3
1.0
1.0
1.0

33.9
0.90 (0.78, 1.02)
0.87 (0.77, 1.00)
21.6
0.94 (0.82, 1.08)
0.90 (0.80, 1.06)
0.88 (0.76, 1.02)

37.2
1.07 (0.95, 1.22)
1.01 (0.88, 1.15)
25.0
1.12 (0.98, 1.28)
1.08 (0.93, 1.24)
1.00 (0.86, 1.15)

40.6
1.07 (0.94, 1.21)
0.97 (0.85, 1.10)
29.2
1.25 (1.09, 1.42)
1.17 (1.02, 1.35)
1.02 (0.88, 1.19)

46.1
1.12 (0.99, 1.27)
0.97 (0.85, 1.11)
36.4
1.36 (1.20, 1.55)
1.25 (1.08, 1.45)
0.97 (0.82, 1.15)< 0.0001< 0.0001
0.71

5.3
1.0
1.0
1.0

8.7
0.88 (0.79, 0.99)
0.88 (0.78, 0.99)
0.85 (0.75, 0.96)

11.1
0.73 (0.64, 0.82)
0.71 (0.63, 0.81)
0.67 (0.59, 0.77)

13.5
0.74 (0.66, 0.84)
0.71 (0.62, 0.81)
0.65 (0.56, 0.76)

17.2
0.72 (0.64, 0.82)
0.68 (0.59, 0.78)
0.60 (0.51, 0.71)< 0.0001< 0.0001< 0.0001

10.7
1.0
1.0
1.0

12.8
1.03 (0.90, 1.18)
1.00 (0.87, 1.15)
0.97 (0.83, 1.12)

14.3
1.07 (0.94, 1.22)
1.01 (0.88, 1.15)
0.96 (0.81, 1.14)

16.0
1.21 (1.06, 1.37)
1.10 (0.96, 1.26)
1.03 (0.86, 1.24)

18.8
1.27 (1.12, 1.44)
1.11 (0.97, 1.28)
0.99 (0.80, 1.21)< 0.0001
0.05
0.98

10.9
1.0
1.0
1.0

13.1
1.08 (0.95, 1.23)
1.05 (0.92, 1.20)
1.07 (0.91, 1.25)

14.6
1.12 (0.98, 1.28)
1.05 (0.92, 1.21)
1.05 (0.88, 1.26)

16.3
1.15 (1.01, 1.31)
1.05 (0.92, 1.21)
1.02 (0.83, 1.25)

19.3
1.29 (1.14, 1.47)
1.13 (0.99, 1.39)
1.06 (0.84, 1.33)< 0.0001
0.07
0.51

2.9
1.0
1.0
1.0

3.4
0.90 (0.79, 1.01)
0.90 (0.80, 1.01)
0.86 (0.76, 0.97)

4.1
0.83 (0.73, 0.93)
0.82 (0.73, 0.93)
0.77 (0.67, 0.88)

4.8
0.84 (0.75, 0.95)
0.82 (0.72, 0.94)
0.75 (0.65, 0.86)

6.2
0.87 (0.77, 0.99)
0.85 (0.75, 0.97)
0.75 (0.65, 0.88)

0.02
0.009
0.0002

1.3
1.0
1.0
1.0

1.7
1.11 (0.97, 1.26)
1.08 (0.95, 1.23)
1.12 (0.97, 1.29)

2.0
1.16 (1.02, 1.32)
1.11 (0.98, 1.27)
1.18 (1.02, 1.37)

2.4
1.10 (0.97, 1.26)
1.04 (0.91, 1.19)
1.14 (0.97, 1.34)

2.9
1.26 (1.11, 1.43)
1.15 (1.01, 1.32)
1.31 (1.10, 1.56)

0.002
0.09
0.02

131
1.0
1.0
1.0

163
1.00 (0.87, 1.15)
1.04 (0.90, 1.20)
1.02 (0.88, 1.18)

188
1.12 (0.98, 1.28)
1.18 (1.02, 1.37)
1.16 (1.00, 1.34)

217
1.21 (1.06, 1.38)
1.29 (1.12, 1.49)
1.25 (1.08, 1.45)

273
1.32 (1.16, 150)
1.42 (1.23, 1.65)
1.36 (1.17, 1.59)< 0.0001< 0.0001< 0.0001

P for trend
0.006
0.96

1
Values are medians and were computed as a percentage of energy (except for cholesterol; mg/d) by quintile as the cumulative updated average. Age- andBMI-adjusted models included age (5-y categories) and BMI (11 categories). SFA, saturated fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid. The multivariate models included age (5-y categories), time period (7 periods), BMI (11 categories), cigarette smoking (never, past, or
current smoking of 1–14, 15–24, and ≥ 25 cigarettes/d), parental history of diabetes, alcohol consumption (4 categories), physical activity (metabolic equivalents/wk: 5 categories), percentage of energy from protein, and total energy intake. Dietary cholesterol was also included in models for total and specific fats.

both higher amounts of polyunsaturated fat and lower amounts oftrans fat tended to eat less stick margarine and use more liquid
vegetable oils, especially salad-dressing products.
In age- and BMI-adjusted analyses, higher total fat intake was
weakly related to greater risk of diabetes (Table 2). In multivariate analyses controlling for known risk factors, total fat intake
was no longer significantly associated with diabetes risk; adjustments for physical activity and alcohol intake largely accounted
for the reduction in relative risk (RR). In age- and BMI-adjusted
and multivariate analyses, vegetable fat was associated with
reduced risk of diabetes. When animal and vegetable fats wereboth included in the same model with intake of trans fatty acids
and known risk factors, animal fat was not associated with diabetes risk (Table 1).

Saturated and monounsaturated fatty acid intakes were eachassociated with an increased risk of diabetes in age- and BMIadjusted analyses, but, in multivariate analyses including all
major types of fatty acids, these associations were greatly attenuated. In contrast, polyunsaturated fatty acid intake was inversely
associated with diabetes risk in all analyses.
Intakes of trans fatty acids was positively associated with riskof diabetes in age- and BMI-adjusted analyses. This association
was slightly attenuated after adjustment for known risk factors
but became stronger after other types of fat were controlled for.
In addition, we examined the joint effect of polyunsaturated fatty
acid and trans fatty acid intakes. The RR for the combination ofa low trans fatty acid quintile and a high polyunsaturated fatty
acid quintile compared with the opposite extreme was 0.66 (95%

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Total fatAge- and BMI-adjusted
Multivariate
Animal fat
Age- and BMI-adjusted
Multivariate
Further adjustment forvegetable and trans fats
Vegetable fat
Age- and BMI-adjusted
Multivariate
Further adjustment foranimal and trans fats
SFA
Age- and BMI-adjusted
Multivariate
Further adjustment for MUFAs,
PUFAs, and trans fats
MUFA
Age- and BMI-adjusted
Multivariate
Further adjustment for SFAs,
PUFAs, and trans fats
PUFA
Age- and BMI-adjusted
Multivariate
Further adjustment for SFAs,
MUFAs, and trans fatstrans Unsaturated fat
Age- and BMI-adjusted
Multivariate
Further adjustment for SFAs,
MUFAs, and PUFAs
Cholesterol
Age- and BMI-adjusted
Multivariate
Further adjustment for SFAs,
MUFAs, PUFAs, and trans fats1

DIETARY FAT AND DIABETESTABLE 3
Multivariate relative risk (RR) of type 2 diabetes associated withincreases in the percentage of energy from specific types of fat or fatty
acids and dietary cholesterol1
Model

RR

95% CIP

0.97(0.86, 1.10)

0.68

1.05

(0.91, 1.20)

0.52

0.63

(0.53, 0.76)< 0.0001

1.39(1.15, 1.67)

0.0006

1.12(1.05, 1.19)

0.00030.98
0.79(0.95, 1.02)(0.74, 0.84)

0.35< 0.0001

0.98(0.94, 1.02)

0.24

1

The multivariate models included age (5-y categories), time period(7 periods), BMI (11 categories), cigarette smoking (never, past, or current
smoking of 1–14, 15–24, and ≥ 25 cigarettes/d), parental history of diabetes, alcohol consumption (4 categories), physical activity (metabolic
equivalents/wk: 5 categories), percentage of energy from protein, and totalenergy intake.
2
23.9 mg/MJ = 100 mg/1000 kcal.

CI: 0.49, 0.93; P < 0.0001). Dietary cholesterol was positively
associated with diabetes risk in all analyses (Table 2).
Because polyunsaturated fat intake in these analyses included
only linoleic acid (the primary n6 fatty acid), we also examined the relation of marine n3 fatty acids (eicosapentaenoic
acid plus docosahexaenoic acid) to risk of diabetes. In a multivariate model that also included the major types of fat, the RRs
for increasing quintiles of marine n3 fatty acids were 1.0 (reference), 1.00 (95% CI: 0.88, 1.13), 0.93 (0.81, 1.06), 0.97 (0.84,1.12), and 0.80 (0.67, 0.95); the P for the trend was 0.02.
Because intakes of both n6 and marine n3 fatty acids wereinversely associated with risk of diabetes, the ratio of n6 ton3 fatty acids was not significantly related to risk of diabetes.
To examine further the relations between different dietary fats
and risk of diabetes, we also modeled the percentages of energy
from specific types of fatty acids or sources of fat (animal orvegetable) as continuous variables, adjusting one type of fat foranother and for known risk factors. In this model, a 5% increasein energy from vegetable fat was associated with a reduced riskof diabetes, whereas a similar increase in energy from animal fat
was not associated with risk. Saturated and monounsaturated
fatty acid intakes were not significantly related to diabetes risk
when compared with an equivalent amount of energy from carbohydrate (Table 3). When included in the model with othertypes of fat, a 2% increase in energy from trans fatty acids was
associated with a significantly increased risk; each increase of
23.9 mg dietary cholesterol/MJ (100 mg/1000 kcal) was associated with a 12% increased risk (Table 2).
We also estimated the effect of various isoenergetic dietary
substitutions on the risk of diabetes (Figure 1). Replacing 5% ofenergy from polyunsaturated fatty acids with the same amount ofenergy from carbohydrates was associated with a 58% greaterrisk of diabetes (RR: 1.58; 95% CI: 1.31, 1.90; P < 0.0001).
Replacing 5% of energy from saturated fatty acids with energy
from polyunsaturated fatty acids was associated with a 35% lower
risk (0.65; 0.54, 0.78; P < 0.0001). Replacing 2% of energy fromtrans fatty acids with carbohydrate was associated with a 28%
lower risk (0.72; 0.60, 0.87; P < 0.001), but replacing trans fatty
acids with polyunsaturated fatty acids was associated with a 40%
lower risk (0.60; 0.48, 0.75; P < 0.0001).
We evaluated the possibility that the associations between different types of dietary fat and diabetes risk might be modified bymajor nondietary risk factors. The observed inverse association
with polyunsaturated fatty acid intake did not appreciably differ
across categories of BMI, physical activity, alcohol consumption, or family history of diabetes. However, the positive associations with trans fatty acids and cholesterol were observed mostclearly among overweight and less physically active women(Table 4). In an analysis excluding women with either reported
hypercholesterolemia or hypertension at baseline, the association

FIGURE 1. Estimated changes in risk of type 2 diabetes associated with isoenergetic substitutions of 2% of energy. Associations were adjusted forthe same covariates as in Table 2. trans, trans fatty acids; PUFA, polyunsaturated fatty acids; SFA, saturated fatty acids; Carbo, carbohydrates; MUFA,
monounsaturated fatty acids. The arrows indicate substitution of the second fat listed for the first fat listed. Bars represent 95% CIs.

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Model 1
Saturated fat (5% increasein energy)
Monounsaturated fat(5% increase in energy)
Polyunsaturated fat(5% increase in energy)trans Unsaturated fat(2% increase in energy)
Cholesterol (23.9-mg/MJ increase)2Model 2
Animal fat (5% increase in energy)
Vegetable fat (5% increase in energy)
Model 3
Total fat (5% increase in energy)

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TABLE 4
Relative risks (RR) of type 2 diabetes associated with increases in the percentage of energy from specific types of dietary fatty acids and dietarycholesterol according to major risk factors1

Risk factor

trans Unsaturated fat(2% increase in energy)
RR
95% CIP

Cholesterol(23.9-mg/MJ increase)2
RR
95% CI
P

0.75
0.51
0.68

(0.43, 1.31)(0.35, 0.74)(0.52, 0.88)

0.31
0.0004
0.004

0.76
1.28
1.31

(0.44, 1.32)(0.89, 1.86)(1.00, 1.72)

0.33
0.18
0.05

1.04
1.01
1.15

(0.84, 1.28)(0.89, 1.56)(1.07, 1.25)

0.74
0.91
0.00050.58
0.69(0.44, 0.76)(0.53, 0.89)

0.0001
0.005

1.82
1.05

(1.39, 2.38)(0.88, 1.37)

0.0001
0.71

1.16
1.08

(1.03, 1.26)(0.99, 1.18)

0.0006
0.07

0.77
0.43
0.52

(0.58, 1.02)(0.29, 0.64)(0.31, 0.87)

0.07
0.0001
0.01

1.11
1.60
1.61

(0.83, 1.48)(1.10, 2.34)(0.94, 2.74)

0.43
0.01
0.08

1.08
1.15
1.17

(0.98, 1.19)(1.02, 1.30)(1.01, 1.35)

0.12
0.02
0.04

0.62
0.64

(0.45, 0.85)(0.51, 0.81)

0.003
0.00021.51
1.35(1.10, 2.06)(1.07, 1.70)

0.01
0.01

1.13
1.12

(1.02, 1.24)(1.03, 1.20)

0.02
0.006

1
The multivariate models included age (5-y categories), time period (7 periods), BMI (11 categories), cigarette smoking (never, past, or current smoking of 1–14, 15–24, and ≥ 25 cigarettes/d), parental history of diabetes, alcohol consumption (4 categories), physical activity (metabolic equivalents/wk: 5
categories), percentage of energy from protein, and total energy intake. Intakes of specific types of fat and cholesterol were entered into the model simultaneously so that the effects of fats were compared with those of an equivalent amount of energy from carbohydrates. METS, metabolic equivalents.
2
23.9 mg/MJ = 100 mg/1000 kcal.

with intakes of polyunsaturated fatty acids (for 5% of energy:
0.64; 0.50, 0.82) and trans fatty acids (for 2% of energy: 1.37;
1.08, 1.74) were similar to those in the overall population.

DISCUSSION
In this large prospective study of women, we found no association between total fat intake and risk of type 2 diabetes after controlling for known risk factors. However, polyunsaturated fatty
acid intake was associated with a substantial reduction in risk,
and trans fatty acids and dietary cholesterol were associated withincreased risk. We estimated that replacing 5% of energy fromsaturated fatty acid with energy from polyunsaturated fatty acidwas associated with a 35% lower risk and that replacing 2% ofenergy from trans fatty acids with polyunsaturated fatty acid was
associated with a 40% lower risk. Because the average intake oftrans fatty acids from partially hydrogenated vegetable oils is
3% of energy in the United States (37, 38), our data suggest thatthe incidence of type 2 diabetes could be reduced by ≥ 40% ifthese oils were consumed in their original, unhydrogenated form.
Epidemiologic data on dietary fat and risk of diabetes aresparse and most of these studies are limited by incomplete control of potential confounding variables. Cross-sectional analyses
have reported positive associations with saturated and monounsaturated fatty acids (12, 39) and an inverse association withpolyunsaturated fatty acid intake (12). Two previous prospective
studies, a 12-y follow-up study of 1462 women in Sweden (13)and a 25-y follow-up of 841 men in the Zutphen Study (14),found no significant associations between total dietary fat or specific types of fat and risk of diabetes. However, these studies were
small and did not adjust simultaneously for other types of fats.
Our results regarding the lack of association with total fat andthe inverse association with vegetable fat intake are also consistent
with recently reported findings in a large prospective study of men(16). These findings are also consistent with earlier analyses in the

Nurses’ Health Study involving shorter follow-up periods (17, 18),
but in the present study none of the specific types of fatty acids
were significantly associated with risk of diabetes. However, ourprevious analyses with shorter follow-up periods did not include
the mutual adjustment of one type of fatty acid for other types.
Because some food sources of polyunsaturated fat, such as margarines, are also important sources of trans fatty acids, and because
they have opposing effects, simultaneous control for the major typeof fat appears to be essential to assess their independent effects.
The importance of this multivariate modeling approach was previously documented for coronary heart disease (15, 40). The relativerisk associated with polyunsaturated fatty acid intake adjusted for
known risk factors was similar to that obtained in the age- andBMI-adjusted analysis, suggesting that confounding by lifestylevariables was only minor. However, intakes of other fats had more
important confounding effects; adjustment for them strengthened
the inverse association for polyunsaturated fatty acid intake and thepositive association for trans fatty acids.
Imprecise dietary measurement and residual confounding are
possible alternative explanations for some of the observed associations. However, errors in dietary assessment measures might
have accounted for a lack of association but not the reverse (41).
Notably, although simultaneous adjustments for other specifictypes of fat strengthened our findings, qualitatively similar associations were seen in analyses adjusted for age and BMI only. The
repeated dietary measurements made in this study were advantageous because they allowed for fewer measurement errors and forchanges in behavioral dietary patterns and food composition overtime to be assessed (15, 40). On the basis of baseline dietary datafrom 1980 only, the associations with polyunsaturated (5% ofenergy) and trans (2% of energy) fatty acids were much weaker.
The inverse association with polyunsaturated fatty acid intake
in the present analysis is consistent with the findings of a 6-y
metabolic study in 102 diabetic patients that compared isoenergetic diets with different amount of linoleic acid [1.3 compared

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BMI (kg/m2)< 25 (n = 267)
25–30 (n = 665)
> 30 (n = 1213)
Physical activity level (METS/wk)
1st and 2nd quintile (n = 1237)
3rd to 5th quintile (n = 1234)
Alcohol consumption
Nondrinker (n = 1054)
0.1–5.00 mg/d (n = 634)
> 5.0 mg/d (n = 315)
Family history of diabetes
Yes (n = 920)
No (n = 1574)

Polyunsaturated fat(5% increase in energy)
RR
95% CIPDIETARY FAT AND DIABETES

risk of type 2 diabetes in women but that dietary trans fatty acids
increase and dietary polyunsaturated fatty acids reduce the risk.
Thus, substitution of nonhydrogenated polyunsaturated fatty
acids for trans fatty acids in the diet is likely to reduce the riskof type 2 diabetes substantially.
We are indebted to the participants in the Nurses’ Health Study for theircontinuing outstanding level of cooperation, to Simin Liu for advice, and to
Al Wing, Karen Corsano, Laura Sampson, and Debbie Flynn for theirunfailing help.

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