05 - Food Sources of Fat May Clarify The Inconsistent Role of Dietary Fat Intake For Incidence of Type 2

Food sources of fat may clarify the inconsistent role of dietary fat intake
for incidence of type 2 diabetes1–4

Ulrika Ericson, Sophie Hellstrand, Louise Brunkwall, Christina-Alexandra Schulz, Emily Sonestedt, Peter Wallström,
Bo Gullberg, Elisabet Wirfält, and Marju Orho-Melander
ABSTRACT result in high intakes of fat, SFAs, linoleic acid (LA; 18:2n–6),
Background: Dietary fats could affect glucose metabolism and and protein but lower in dietary fiber and several micronutrients.
obesity development and, thereby, may have a crucial role in the Because fat is energy dense, and fatty acids affect glucose me-
cause of type 2 diabetes (T2D). Studies indicated that replacing tabolism, fat intake may have a crucial role in the development of
saturated with unsaturated fats might be favorable, and plant foods T2D. Potential effects on gene expression, cell membrane func-
might be a better choice than animal foods. Nevertheless, epidemi- tion, lipid metabolism, and gut microbiota may also explain
ologic studies suggested that dairy foods are protective. associations with T2D (1–4). Evidence from randomized lifestyle
Objective: We hypothesized that, by examining dietary fat and its interventions indicated that reduced intakes of total and saturated
food sources classified according to fat type and fat content, some fats, in combination with increased fiber intake and physical
clarification regarding the role of dietary fat in T2D incidence could activity, prevent the development of T2D in individuals with
be provided. impaired glucose tolerance (5, 6). However, associations between
Design: A total of 26,930 individuals (61% women), aged 45–74 y, dietary fat and T2D from epidemiologic studies have been in-
from the Malmö Diet and Cancer cohort were included in the study. consistent (7), and the importance of dietary fat content and food
Dietary data were collected by using a modified diet-history method. sources of fat with regard to risk of T2D remains to be clarified.
During 14 y of follow-up, 2860 incident T2D cases were identified. The replacement of dietary intakes of SFAs with PUFAs may,
Results: Total intake of high-fat dairy products (regular-fat alterna- via various mechanisms, lead to improved insulin sensitivity (8),
tives) was inversely associated with incident T2D (HR for highest and epidemiologic studies have indicated that the replacement of
compared with lowest quintiles: 0.77; 95% CI: 0.68, 0.87; P-trend foods high in SFAs with food sources of MUFAs and PUFAs
, 0.001). Most robust inverse associations were seen for intakes of
could be favorable in the prevention of diabetes development (8).
cream and high-fat fermented milk (P-trend , 0.01) and for cheese
In addition, high blood concentrations of LA may counteract the
in women (P-trend = 0.02). High intake of low-fat dairy products
development of hyperglycemia and T2D (9). In line with those
was associated with increased risk, but this association disappeared
findings, plant sources of fat were suggested to be a better choice
when low- and high-fat dairy were mutually adjusted (P-trend =
than animal sources (10). Indeed, high intakes of red meat and
0.18). Intakes of both high-fat meat (P-trend = 0.04) and low-fat
meat products show positive associations with risk of T2D (11).
meat (P-trend , 0.001) were associated with increased risk. Finally,
we did not observe significant association between total dietary fat
Nevertheless, several epidemiologic studies indicated that high
content and T2D (P-trend = 0.24), but intakes of saturated fatty intake of dairy products may be protective (12). Effects of dif-
acids with 4–10 carbons, lauric acid (12:0), and myristic acid ferent dairy products or dairy components, including possible
(14:0) were associated with decreased risk (P-trend , 0.01).
Conclusions: Decreased T2D risk at high intake of high- but not of 1
From the Department of Clinical Sciences, Malmö, Diabetes and Cardio-
low-fat dairy products suggests that dairy fat partly could have vascular Disease, Genetic Epidemiology (UE, SH, LB, C-AS, ES, and MO-M)
contributed to previously observed protective associations between and the Department of Clinical Sciences, Malmö, Nutritional Epidemiology,
dairy intake and T2D. Meat intake was associated with increased Lund University, Lund, Sweden (PW, BG, and EW).
2
risk independently of the fat content. Am J Clin Nutr Supported by the Swedish Research Council, the Region Skåne, the
2015;101:1065–80. Skåne University Hospital, the Novo Nordic Foundation, and the Albert
Påhlsson Research Foundation.
3
Supplemental Tables 1 and 2 are available from the “Supplemental data”
Keywords: cohort study, diet, dietary fats, food intake, type 2
link in the online posting of the article and from the same link in the online
diabetes table of contents at http://ajcn.nutrition.org.
4
Address correspondence to U Ericson, Clinical Research Centre, Build-
ing 60, Floor 13, Skånes Universitetssjukhus in Malmö, Entrance 72, Jan
INTRODUCTION Waldenströms gata 35, SE-205 02 Malmö, Sweden. E-mail: ulrika.ericson@
med.lu.se.
The worldwide adaption of westernized energy-rich diets is 5
Abbreviations used: LA, linoleic acid; MDC, Malmö Diet and Cancer;
considered an important contributor to the increasing prevalence of T2D, type 2 diabetes.
obesity and type 2 diabetes (T2D).5 These diets tend to be high in Received November 12, 2014. Accepted for publication March 6, 2015.
animal foods and low in unrefined plant foods, which generally First published online April 1, 2015; doi: 10.3945/ajcn.114.103010.
Am J Clin Nutr 2015;101:1065–80. Printed in USA. Ó 2015 American Society for Nutrition 1065
Downloaded from https://academic.oup.com/ajcn/article-abstract/101/5/1065/4577562

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1066 ERICSON ET AL.
beneficial effects of yogurt, cheese, and specific fatty acids, were 2) a 168-item questionnaire for the assessment of consumption
proposed to lie behind these observations (13–15). In addition, frequencies and portion sizes of regularly eaten foods that were
intake of fatty fish (16) as well as intakes and blood concen- not covered by the menu book. Finally, 3) a 45-min interview
trations of total n–3 PUFAs (17), a-linolenic acid (18), and long- completed the dietary assessment. The MDC method has been
chain fish n–3 PUFA from foods (19) were, in some studies, described in detail elsewhere (22, 23).
inversely associated with T2D risk, whereas results from other Diet analyses were adjusted for a variable called the diet-method
studies did not indicate that fatty fish or n–3 PUFA have an version because slightly altered coding routines of dietary data
important protective role in the cause of T2D (8, 18, 20). were introduced in September 1994 to shorten the interview time
In this population-based prospective study of men and women (from 60 to 45 min). This adjustment resulted in 2 slightly different
from the MDC (Malmö Diet and Cancer) cohort, we examined if method versions (before or after September 1994) without any
dietary fat intake and, in particular, different types of fatty acids major influence on the ranking of individuals (23).
and food sources of fat classified according to fat type and fat The relative validity of the MDC method was evaluated in the
content were associated with incidence of T2D. Malmö Food study 1984–1985 by comparing the method with
18-d weighed-food records (24, 25). Pearson correlation co-
METHODS efficients, which were adjusted for total energy, between the
reference method and MDC method were, in women and men,
Study population and data collection respectively, 0.69 and 0.64 for total fat, 0.68 and 0.56 for SFA,
The MDC study is a population-based prospective cohort study in 0.66 and 0.59 for MUFA, 0.64 and 0.26 for PUFA, 0.68 and 0.23
Malmö, which is a city in the south of Sweden. Baseline examina- for LA, 0.58 and 0.22 for a-linolenic acid (18:3n–3), 0.38 and
tions were conducted between 1991 and 1996. All women born 0.24 for EPA (20:5n–3), 0.40 and 0.37 for docosapentaenoic
between 1923 and 1950 and all men born between 1923 and 1945 acid (22:5n–3), 0.27 and 0.20 for DHA (22:6n–3), 0.51 and 0.43
who were living in the city of Malmö were invited to participate (n = for low-fat meat, 0.80 and 0.40 for high-fat meat, 0.92 and 0.92
74,138). Details of the cohort and the recruitment procedures are for low-fat milk, 0.75 and 0.76 for high-fat milk, and 0.59 and
described elsewhere (21). The only exclusion criteria were mental 0.47 for cheese (24, 25).
incapacity and inadequate Swedish language skills (eligible per- The mean daily intake of foods was calculated on the basis of the
sons: n = 68,905). Participants filled out questionnaires that frequency and portion-size estimates from the questionnaire and
covered socioeconomic, lifestyle, and dietary factors, recorded menu book. Food intake was converted to energy and nutrient
meals, and underwent a diet-history interview. Anthropometric intakes by using the MDC nutrient database whereby the majority
measures were conducted by nurses. Weight was measured by of the nutrient information comes from PC-KOST2-93 from the
using a balance-beam scale with subjects wearing light clothing National Food Agency in Uppsala, Sweden. Nutrient intakes from
and no shoes. Standing height was measured by using a fixed supplements were calculated on the basis of supplement con-
stadiometer calibrated in centimeters. Waist circumference was sumption recorded in the menu book. Supplement consumption
measured midway between the lowest rib margin and iliac crest. was converted into nutrient intakes by using the MDC supplement
Body composition was estimated by using a bioelectrical imped- database (26). Dietary variables examined in this study are listed
ance analyzer (BIA 103,single-frequency analyzer; RJL Systems). and described in Supplemental Table 1. Examined nutrient in-
The percentage of body fat was calculated by using an algorithm takes were the sum from foods and supplements. Main food
provided by the manufacturer. During the screening period, 28,098 sources of fat were identified in the MDC cohort (27) and primarily
participants (40% of eligible persons) completed all baseline ex- grouped according to fat type and fat content. Some less-important
aminations. Of nonparticipants, 49% did not reply to the invitation fat sources were also examined to facilitate the interpretation of
letter, 39% answered that they were not willing to take part, 7% results regarding high-fat alternatives of the same types of foods.
died or moved before they had received an invitation, and 5% Total intake of high-fat dairy products was defined as the sum of
failed to complete all baseline examinations (21). MDC partici- portions of butter; regular-fat alternatives ($2.5% fat) of milk,
pants have been compared with participants in a mailed health yogurt, and sour milk; cream (.12% fat); and regular-fat cheese
survey in Malmö with a higher participation rate (75%) with re- (.20% fat). Portions (instead of grams) were used to analyze the
gard to subjective health, sociodemographic characteristics, and sum of dairy products with different water contents and usually
lifestyle (21). In the current study, we included 26,930 participants consumed in different weights (e.g., cheese and milk). Standard
without diabetes at baseline. We excluded 1168 participants on the portion sizes from the MDC study or National Food Agency in
basis of self-reported diabetes diagnosis, self-reported diabetes Sweden were used (28) as follows: milk and yogurt (200 g/portion),
medication, or information from medical data registries that in- cheese (20 g/portion), cream (25 g/portion), ice cream (75 g/portion),
dicated a date of diagnosis preceding the baseline examination and butter (7 g/portion). Energy-adjusted dietary intakes were
date. The ethical committee at Lund University approved the study obtained by regressing intakes on nonalcohol energy intake.
(LU 51–90), and participants gave their written informed consent. Quintiles of nutrient and food residuals were used as exposure
categories. If .20% of the individuals were zero consumers, they
constituted the lowest intake category, and the higher categories
Dietary data were defined as quartiles in consumers.
Dietary data were collected once during the baseline period.
The MDC study used an interview-based modified diet-history
method that combined 1) a 7-d menu book for the recording of Diabetes case ascertainment
intakes from meals that varied from day to day (usually lunch We identified 2860 incident cases of T2D during 377,642
and dinner meals), cold beverages, and nutrient supplements and person-years of follow-up via at least one of 7 registries (90%) or

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FOOD SOURCES OF FAT AND INCIDENT TYPE 2 DIABETES 1067
at new screenings or examinations during follow-up (10%). The We examined baseline characteristics in cases and noncases of
mean 6 SD follow-up time was 14 6 3.9 y. Subjects contributed T2D and across intake quintiles of fat and its food sources by
person-time from date of enrollment until date of diabetes di- using the general linear model for continuous variables (adjusted
agnosis, death, migration from Sweden, or end of follow-up for age and sex) and with the chi-square test for categorical
(December 2009), whichever occurred first. During follow-up, variables. In a post hoc analysis, we used the general linear model
0.5% of subjects had migrated from Sweden. If available, we to examine intakes of nondairy foods (meat, fish, potatoes, fruit,
used information on the date of diagnosis from 2 registries vegetables, cereal products, margarine, pastry, chocolate, and
prioritized in the following order: 1) the regional Diabetes 2000 sugar-sweetened beverages) across intake quintiles of cream and
registry of Scania (29) and 2) the Swedish National Diabetes high-fat fermented milk.
Registry (30). These registries required a physician diagnosis We used Cox proportional hazards regression model to estimate
according to established diagnosis criteria (fasting plasma glu- HRs of diabetes incidence associated with quintiles of dietary
cose concentration $7.0 mmol/L or fasting whole blood con- intakes adjusted for energy intake by using the residual method. The
centration $6.1 mmol/L, measured at 2 different occasions). first quintile was used as the reference. Years of follow-up was used
Individuals with at $2 glycated hemoglobin values .6.0% with as the underlying time variable. We used covariates obtained from
the Swedish Mono-S standardization system (corresponding to baseline examinations. The basic model included adjustments for
6.9% in the US National Glycohemoglobin Standardization age (continuous), sex (when applicable), method version, season
Program and 52 mmol/mol with International Federation of (categorical), and total energy intake (continuous). Our full mul-
Clinical Chemistry and Laboratory Medicine units) (31, 32) tivariate model further included adjustments for the following
were categorized as diabetes cases in the Malmö HbA1c Reg- categorical variables: leisure-time physical activity, smoking, al-
istry. In addition, cases were identified via 4 registries from the cohol intake, and education, and, finally, BMI as a continuous
National Board of Health and Welfare in Sweden as follows: the variable. Because associations between dietary fat and T2D may
Swedish National Inpatient Registry, the Swedish Hospital- partly be mediated via BMI, we also performed analyses with an
based outpatient care, the Cause-of-death Registry, and the intermediate multivariate model without the inclusion of BMI.
Swedish Prescribed Drug Registry. Covariates were identified from the literature and indicated po-
tential confounding in the MDC cohort because of associations with
incident T2D and dietary intakes. Missing values for variables were
Other variables treated as separate categories. Analyses with additional adjustments
Information on age was obtained from the personal identi- for waist circumference or dietary change in the past were also
fication number. Age was divided into 5-y categories. BMI (in performed. Finally, additional adjustments were made for possible
kg/m2) was calculated from the direct measurement of weight dietary confounders, which previously showed associations with
and height. Leisure-time physical activity was assessed by T2D are found, in the examined foods or central in the same dietary
asking participants to estimate the number of minutes per week pattern (intake quintiles of protein, fiber, sucrose, calcium, vitamin
they spent on 17 different activities. The duration was multi- D, magnesium, meat, fruit and vegetables, sugar-sweetened bev-
plied by an activity specific intensity coefficient, and an overall erages, or high-fat dairy products). We also performed all analyses
leisure-time physical activity score was created. The score was for men and women separately. Tests for interactions between sex
divided into sex-specific quintiles. The smoking status of and nutrient and food intakes with regard to diabetes incidence were
participants was defined as current smokers (including irreg- performed [sex 3 quintile of nutrients and foods (treated as
ular smokers), ex-smokers, and never smokers. The total continuous variables)]. Tests for interactions between BMI (#25
consumption of alcohol was defined by a 4-category variable. or .25) and dietary variables were also performed.
Participants who reported zero consumption in the menu book In a sensitivity analysis, we excluded individuals with
and indicating no consumption of any type of alcohol during a reported dietary change in the past (24% of the individuals). In
the previous year were categorized as zero reporters. Other a second sensitivity analysis, we excluded individuals with
category ranges were ,15 g alcohol/d for women and ,20 g/d prevalent cardiovascular disease (coronary event or stroke) at
for men (low), 15–30 g/d for women and 20–40 g/d for men baseline (3%). All statistical tests were 2 sided, and significance
(medium), and .30 g/d for women and .40 g/d for men was assumed at P , 0.05.
(high). Participants were divided into 4 categories according to
their highest level of education (#8, 9–10, or 11–13 y or
university degree). Season was defined as the season of diet- RESULTS
data collection (winter, spring, summer, and fall). Dietary
change in the past (yes or no) was based on the question “Have Baseline characteristics
you substantially changed your eating habits because of illness At baseline, several established risk factors for T2D, as well as
or some other reasons?” potential confounders of dietary associations, differed between
cases and noncases of incident T2D (Table 1). Cases were older
and had higher BMI, a more sedentary lifestyle, lower alcohol
Statistical analysis intake, higher protein intake, and lower intakes of carbohydrates
The SPSS statistical computer package (version 20.0; IBM and dietary fiber. In addition, there were more individuals who
Corp.) was used for all statistical analyses. All food variables reported a dietary change in the past, more ever smokers, and
were log transformed (e-log) to normalize the distribution before fewer individuals with a high level of education in cases. Baseline
analysis. To handle log transformation for zero intakes, we added characteristics differed also between low and high consumers of
a very small amount (0.0001 g). several fat sources (Table 2). Subjects who reported a high total

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1068 ERICSON ET AL.
TABLE 1
Baseline characteristics for cases and noncases of incident T2D in the MDC cohort after the exclusion of individuals with
prevalent diabetes at baseline (1991–1996)1
Baseline variable n Cases (n = 2860) Noncases (n = 24,070) P2
Sex, F, % 26,930 48.5 62.7 ,0.001

Age, y 26,930 58.7 (58.5, 59.0)3 58.1 (58.0, 58.2) ,0.001
BMI, kg/m2 26,894 28.4 (28.2, 28.5) 25.4 (25.4, 25.4) ,0.001
Waist, cm 26,885 93.0 (92.6, 93.4) 84.6 (84.4, 84.7) ,0.001
Body fat, % 26,772 28.3 (28.1, 28.5) 25.3 (25.3, 25.4) ,0.001
Systolic blood pressure, mm Hg 26,892 147 (146, 147) 140 (140, 141) ,0.001
Diastolic blood pressure, mm Hg 26,890 89.1 (88.7, 89.4) 85.5 (85.4, 85.7) ,0.001
Hb A1c, % 5104 5.20 (5.16, 5.23) 4.75 (4.74, 4.77) ,0.001
Fasting blood glucose, mmol/L 5104 5.91 (5.86, 5.96) 4.88 (4.86, 4.90) ,0.001
Triglycerides, mmol/L 5110 1.74 (1.68, 1.79) 1.31 (1.29, 1.33) ,0.001
HDL cholesterol, mmol/L 5062 1.23 (1.21, 1.26) 1.38 (1.37, 1.39) ,0.001
LDL cholesterol, mmol/L 4999 4.29 (4.22, 4.37) 4.14 (4.11, 4.17) ,0.001
Fasting plasma insulin, mU/L 4931 12.9 (12.3, 13.5) 7.1 (6.89, 7.35) ,0.001
HOMA-IR 4692 2.42 (2.31, 2.53) 1.54 (1.50, 1.57) ,0.0014
Leisure-time physical activity score5 26,754 7510 (7270, 7760) 8220 (8130, 8310) ,0.001
Alcohol intake,6 g/d 25,286 11.8 (11.4, 12.3) 12.4 (12.3, 12.6) 0.02
Smoking, previous and current, % 26,920 64.8 61.6 0.001
Education .10 y, % 26,865 25.5 32.9 ,0.001
Dietary change in the past, % 26,893 27.4 21.8 ,0.001
Energy, kcal/d 26,930 2320 (2300, 2340) 2350 (2340, 2360) 0.01
Protein, E% 26,930 15.9 (15.8, 16.0) 15.4 (15.4, 15.5) ,0.001
Carbohydrates, E% 26,930 45.9 (45.7, 46.2) 46.3 (46.2, 46.4) 0.01
Fat, E% 26,930 38.3 (38.0, 38.5) 38.5 (38.4, 38.6) 0.36
Saturated fat, E% 26,930 16.3 (16.1, 16.4) 16.6 (16.5, 16.6) ,0.001
Fiber, g/1000 kcal 26,930 9.0 (8.9, 9.1) 9.1 (9.1, 9.2) 0.04
Calcium, mg/d 26,930 1170 (1150, 1180) 1150 (1140, 1160) 0.10
Dairy products, portions/d 26,930 6.3 (6.2, 6.5) 6.6 (6.6, 6.7) ,0.001
Dairy products, low-fat, portions/d 26,930 2.0 (2.0, 2.1) 1.8 (1.8, 1.8) ,0.001
Dairy products, high-fat, portions/d 26,930 4.1 (4.0, 4.3) 4.6 (4.6, 4.7) ,0.001
Margarine, g/d 26,930 31 (30, 32) 31 (30, 31) 0.10
Eggs, g/d 26,930 25 (24, 26) 23 (23, 24) ,0.001
Meat and meat products, g/d 26,930 120 (119, 122) 114 (113, 114) ,0.001
Fish, high-fat, g/d 26,930 16.6 (15.9, 17.4) 16.1 (15.8, 16.4) 0.25
Pastry and biscuits, g/d 26,930 37 (36, 39) 39 (39, 40) 0.004
Chocolate, g/d 26,930 8.0 (7.6, 8.5) 8.0 (7.8, 8.2) 0.88
1
E%, percentage of energy; Hb A1c, glycated hemoglobin; MDC, Malmö Diet and Cancer; T2D, type 2 diabetes.
2
A general linear model was used for continuous variables and adjusted for age and sex. The examination of diet was
also adjusted for the diet-method version, season, and energy intake. The chi-square test was used for categorical variables.
3
Mean; 95% CI in parentheses (all such values).
4
P value for ln-transformed values.
5
A high score indicates a high level of leisure-time physical activity.
6
In subjects who reported that they consumed alcohol during the year before baseline examinations.
dietary fat content were younger and had lower BMI, but apart inverse association between intake of SFA and T2D (P-trend =
from these variables, they were characterized by a rather un- 0.01). However, the association disappeared after adjustment for
healthy lifestyle pattern; they had a more-sedentary lifestyle intake of high-fat dairy products (P-trend = 0.61). Moreover, in
and higher alcohol intake, and there were also more ever analyses of SFAs with different chain lengths, we only observed
smokers and fewer individuals with a high level of education in significant decreased risk of T2D at high aggregated intakes of
subjects who reported a high dietary fat content. Finally, fewer short- to medium-chain SFAs with 4–10 carbons (P-trend , 0.001)
of these individuals reported a dietary change in the past. as well as at high intakes of lauric acid (12:0) (P-trend = 0.003) and
Except for the observation regarding education, a similar pat- myristic acid (14:0) (P-trend , 0.001). In contrast, high intakes of
tern was seen for individuals with a diet rich in high-fat dairy SFAs with a longer chain length, palmitic acid (16:0) (P-trend =
products. 0.10) and stearic acid (18:0) (P-trend = 0.36), were not associated
with T2D. Intakes of MUFAs and PUFAs were not significantly
Dietary content of total fat and fatty acids in relation to associated with T2D in the full multivariate analysis. Except for an
incidence of T2D interaction between n–3 PUFA intake and sex (P = 0.046), we did
We did not observe any significant associations between the not detect any significant interactions between fat intakes and sex.
dietary content of total fat and incidence of T2D (P-trend = 0.24) Men in the highest intake quintile of n–3 PUFAs tended to be at
(Table 3). In the full multivariate analysis, we observed a significant decreased risk (HR: 0.87; 95% CI: 0.74, 1.02; P = 0.08), whereas

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TABLE 2
Baseline characteristics in quintiles of energy-adjusted dietary intakes of fat and food sources of fat in individuals without prevalent diabetes from the MDC cohort (1991–1996)1
on 13 February 2018
Dietary intake quintile Leisure-time physical Smoking, Dietary change
(median intake/d) Age, y BMI, kg/m2 activity score Alcohol intake,2 g/d Sex, F, % ex/current, % Education, .10 y, % in the past, %
n 26,930 26,894 26,754 25,286 26,930 26,920 26,865 26,893

Fat (E%)
Quintile 1 (31) 58.5 (58.3, 58.7)3 25.8 (25.7, 25.9) 9000 (8800, 9200) 10 (10, 11) 61.3 55.3 34.1 36.1
Quintile 5 (46) 58.1 (57.9, 58.3) 25.4 (25.3, 25.5) 7400 (7300, 7600) 15 (14, 15) 60.5 70.7 30.6 14.6
P-trend ,0.001 ,0.001 ,0.001 ,0.001 0.41 ,0.001 ,0.001 ,0.001
Dairy products, low-fat (portions)
Quintile 1 (0.1) 57.7 (57.5, 57.9) 25.3 (25.2, 25.4) 7800 (7600, 8000) 14 (13, 14) 52.8 67.7 31.2 17.7
Quintile 5 (4) 58.5 (58.3, 58.7) 26.3 (26.2, 26.4) 8600 (8400, 8700) 11 (10, 11) 64.5 60.8 31.8 32.6
P-trend ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 0.56 ,0.001
Dairy products, high-fat (portions)
Quintile 1 (0.9) 59.2 (59.0, 59.4) 26.1 (26.0, 26.2) 8200 (8100, 8400) 11 (10, 11) 51.1 61.3 24.6 34.1
Quintile 5 (8.3) 57.1 (56.9, 57.3) 25.3 (25.2, 25.4) 8000 (7800, 8200) 14 (13, 14) 68.6 65.9 34.1 16.3
P-trend ,0.001 ,0.001 0.04 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001
Margarine (g)
Quintile 1 (5) 58.1 (57.9, 58.3) 25.4 (25.3, 25.5) 8200 (8000, 8500) 13 (13, 14) 59.3 64.8 35.2 22.2
Quintile 5 (59) 58.9 (58.7, 59.1) 25.8 (25.7, 25.9) 7600 (7400, 7800) 11 (11, 11) 50.2 65.2 24.4 22.0
P-trend ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 0.70 ,0.001 0.77
Eggs (g)
Quintile 1 (4) 57.5 (57.3, 57.7) 25.4 (25.3, 25.5) 8100 (7900, 8300) 11 (11, 12) 57.9 60.7 34.4 25.1
Quintile 5 (45) 58.5 (58.3, 58.7) 26.2 (26.1, 26.3) 8100 (7900, 8300) 14 (14, 14) 65.2 65.2 32.0 23.7

P-trend ,0.001 ,0.001 0.90 ,0.001 ,0.001 ,0.001 0.01 0.11
Meat and meat products (g)
Quintile 1 (55) 58.9 (58.7, 59.1) 25.9 (24.9, 25.0) 8900 (8700, 9100) 11 (11, 11) 74.8 57.0 40.5 28.9
Quintile 5 (163) 56.7 (56.5, 56.9) 26.4 (26.2, 26.5) 7500 (7300, 7700) 15 (14, 15) 45.2 70.4 28.0 20.7
P-trend ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001
Fish, high-fat (g)
04 (0) 56.7 (56.6, 57.0) 25.8 (25.7, 25.8) 7800 (7600, 8000) 10 (10, 11) 56.9 64.9 33.2 22.3
4 (46) 59.9 (59.7, 60.1) 25.9 (25.8, 25.9) 8200 (8000, 8400) 15 (14, 15) 64.7 61.5 32.2 26.9
P-trend ,0.001 0.001 ,0.001 ,0.001 0.05 ,0.001 0.85 ,0.001
Pastry and biscuits (g)
Quintile 1 (6) 56.0 (55.8, 56.2) 25.8 (25.7, 25.9) 8100 (7900, 8300) 15 (15,16) 48.4 75.1 37.4 25.1
Quintile 5 (72) 61.4 (61.1, 61.6) 25.6 (25.5, 25.7) 8100 (7900, 8300) 10 (10, 11) 73.0 50.7 24.7 21.9
FOOD SOURCES OF FAT AND INCIDENT TYPE 2 DIABETES
P-trend ,0.001 0.01 0.48 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001

Chocolate (g)
Quintile 1 (0) 58.4 (58.2, 58.6) 25.9 (25.8, 26.0) 8000 (7800, 8200) 13 (13, 13) 52.7 68.3 29.9 27.9
Quintile 5 (16) 58.3 (58.0, 58.5) 25.6 (25.5, 25.8) 8000 (7800, 8100) 13 (12, 13) 76.6 62.8 31.9 20.5
P-trend 0.72 0.04 0.67 0.37 ,0.001 ,0.001 0.02 ,0.001
1
A general linear model was used for continuous variables and adjusted for age, sex, diet-method version, and season. The chi-square test was used for categorical variables. Quintiles for dietary intakes
were adjusted for energy by using the residual method. P-trend values were calculated across quintiles for continuous variables. In addition, P values were calculated for the comparison of percentages in highest
and lowest quintiles for categorical variables. MDC, Malmö Diet and Cancer; E%, percentage of energy.
2
In subjects who reported that they consumed alcohol during the year before baseline examinations.
3
Mean; 95% CI in parentheses (all such values).
4
Zero consumers; higher categories are quartiles in consumers.
1069
1070 ERICSON ET AL.
TABLE 3
HRs (95% CIs) of incident T2D associated with intakes of total fat and different fatty acids in the MDC cohort1
Nutrient quintile n cases/ Multivariate model Full multivariate P-interaction
(median intake) person-years Basic model2 without BMI3 model with BMI4 with sex
Fat (E%) 0.59

1 (31) 590/76,508 1.00 1.00 1.00
2 (35) 598/75,642 1.03 (0.92, 1.16) 1.02 (0.91, 1.14) 1.00 (0.88, 1.12)
3 (38) 565/75,519 0.98 (0.87, 1.10) 0.97(0.86, 1.09) 0.95 (0.85, 1.07)
4 (41) 550/75,703 0.97 (0.86, 1.09) 0.93 (0.83, 1.05) 0.93 (0.83, 1.05)
5 (46) 557/74,269 0.99 (0.88, 1.11) 0.93 (0.82, 1.04) 0.96 (0.85, 1.08)
P-trend — 0.52 0.08 0.24
Saturated fat (E%) 0.36
1 (12) 626/76,561 1.00 1.00 1.00
2 (14) 663/75,374 1.11 (1.00, 1.24) 1.11 (0.99, 1.24) 1.07 (0.96, 1.19)
3 (16) 542/76,008 0.92 (0.82, 1.04) 0.92 (0.82, 1.03) 0.91 (0.81, 1.02)
4 (18) 534/75,327 0.94 (0.83, 1.05) 0.91 (0.81, 1.03) 0.93 (0.82, 1.04)
5 (22) 495/74,372 0.89 (0.79, 1.00) 0.85 (0.75, 0.96) 0.91 (0.81, 1.02)
P-trend — 0.002 ,0.001 0.01
Fatty acids 4:0–10:0 (E%) 0.37
1 (0.7) 731/75,372 1.00 1.00 1.00
2 (1.0) 628/76,036 0.90 (0.81, 1.00) 0.93 (0.83, 1.03) 0.92 (0.83, 1.03)
3 (1.3) 542/76,029 0.82 (0.73, 0.91) 0.86 (0.76, 0.96) 0.88 (0.78, 0.98)
4 (1.7) 493/75,646 0.76 (0.68, 0.85) 0.79 (0.71, 0.89) 0.84 (0.75, 0.95)
5 (2.6) 466/74,558 0.72 (0.64, 0.82) 0.74 (0.66, 0.83) 0.83 (0.74, 0.93)
P-trend — ,0.001 ,0.001 ,0.001
Lauric acid (12:0) (E%) 0.41
1 (0.6) 650/75,604 1.00 1.00 1.00
2 (0.8) 608/75,082 0.97 (0.86, 1.08) 0.95 (0.84, 1.06) 0.98 (0.87, 1.09)
3 (1.0) 557/75,907 0.88 (0.78, 0.98) 0.87 (0.78, 0.97) 0.92 (0.82, 1.03)
4 (1.1) 560/75,699 0.89 (0.80, 1.00) 0.88 (0.78, 0.98) 0.92 (0.82, 1.03)
5 (1.4) 485/75,349 0.80 (0.71, 0.90) 0.76 (0.67, 0.86) 0.84 (0.75, 0.95)
P-trend — ,0.001 ,0.001 0.003
Myristic acid (14:0) (E%) 0.33
1 (1.1) 701/75,680 1.00 1.00 1.00
2 (1.4) 644/75,851 0.96 (0.86, 1.07) 0.98 (0.88, 1.09) 0.98 (0.88, 1.08)
3 (1.7) 540/75,639 0.84 (0.75, 0.94) 0.86 (0.77, 0.96) 0.86 (0.76, 0.96)
4 (2.0) 501/75,649 0.79 (0.70, 0.89) 0.81 (0.72, 0.91) 0.87 (0.77, 0.98)
5 (2.7) 474/74,823 0.76 (0.68, 0.86) 0.76 (0.68, 0.86) 0.83 (0.74, 0.94)
P-trend — ,0.001 ,0.001 ,0.001
Palmitic acid (16:0) (E%) 0.92
1 (6) 614/76,720 1.00 1.00 1.00
2 (7) 619/75,884 1.05 (0.94, 1.18) 1.06 (0.95, 1.18) 1.03 (0.92, 1.15)
3 (8) 556/75,597 0.97 (0.86, 1.09) 0.96 (0.85, 1.08) 0.93 (0.82, 1.04)
4 (9) 559/75,104 1.00 (0.89, 1.12) 0.97 (0.87, 1.09) 0.97 (0.87, 1.09)
5 (10) 512/74,336 0.92 (0.82, 1.03) 0.87 (0.78, 0.98) 0.92 (0.81, 1.03)
P-trend — 0.09 0.01 0.10
Stearic acid (18:0) (E%) 0.31
1 (2.7) 593/76,505 1.00 1.00 1.00
2 (3.3) 556/76,074 0.95 (0.85, 1.07) 0.94 (0.84, 1.06) 0.93 (0.83, 1.05)
3 (3.6) 580/75,377 1.01 (0.90, 1.14) 0.99 (0.88, 1.11) 0.96 (0.86, 1.08)
4 (4.0) 564/75,284 1.00 (0.89, 1.12) 0.95 (0.85, 1.07) 0.94 (0.84, 1.06)
5 (4.5) 567/74,401 1.01 (0.90, 1.14) 0.92 (0.82, 1.04) 0.94 (0.83, 1.05)
P-trend — 0.60 0.28 0.36
MUFAs (E%) 0.75
1 (11) 545/76,597 1.00 1.00 1.00
2 (12) 561/76,057 1.04 (0.92, 1.17) 1.03 (0.91, 1.16) 0.99 (0.88, 1.12)
3 (13) 555/75,419 1.03 (0.91, 1.16) 1.01 (0.89, 1.13) 0.98 (0.87, 1.10)
4 (14) 595/75,276 1.10 (0.98, 1.23) 1.05 (0.94, 1.18) 1.03 (0.91, 1.16)
5 (16) 604/74,292 1.10 (0.98, 1.24) 1.02 (0.91, 1.15) 1.01 (0.89, 1.13)
P-trend — 0.06 0.62 0.72
PUFAs (E%) 0.62
1 (4) 496/74,893 1.00 1.00 1.00
2 (5) 570/74,850 1.13 (1.00, 1.28) 1.12 (0.99, 1.26) 1.08 (0.96, 1.22)
3 (6) 573/76,267 1.10 (0.97, 1.24) 1.09 (0.96, 1.23) 1.04 (0.92, 1.17)
(Continued)

by guest
on 13 February 2018
TABLE 3 (Continued )
Nutrient quintile n cases/ Multivariate model Full multivariate P-interaction

(median intake) person-years Basic model2 without BMI3 model with BMI4 with sex
4 (7) 600/75,952 1.14 (1.01, 1.29) 1.13 (1.00, 1.28) 1.08 (0.96, 1.22)
5 (8) 621/75,679 1.17 (1.04, 1.32) 1.13 (1.00, 1.28) 1.07 (0.95, 1.20)
P-trend — 0.02 0.07 0.37
Total n–3 PUFAs (E%) 0.046
1 (0.7) 570/75,798 1.00 1.00 1.00
2 (0.8) 533/76,093 0.92 (0.81, 1.03) 0.92 (0.82, 1.03) 0.90 (0.80, 1.02)
3 (0.9) 550/76,008 0.93 (0.82, 1.04) 0.92 (0.81, 1.03) 0.91 (0.81, 1.02)
4 (1.1) 575/75,111 0.95 (0.85, 1.07) 0.95 (0.84, 1.07) 0.93 (0.83, 1.05)
5 (1.4) 632/74,633 1.02 (0.91, 1.15) 1.03 (0.92, 1.16) 1.00 (0.89, 1.12)
P-trend — 0.47 0.43 0.80
ALA (E%) 0.84
1 (0.5) 606/75,539 1.00 1.00 1.00
2 (0.6) 548/76,483 0.89 (0.79, 1.00) 0.88 (0.78, 0.99) 0.85 (0.76, 0.95)
3 (0.7) 581/75,467 0.96 (0.85, 1.07) 0.93 (0.83, 1.04) 0.94 (0.84, 1.05)
4 (0.8) 542/75,365 0.88 (0.79, 0.99) 0.86 (0.76, 0.96) 0.85 (0.76, 0.95)
5 (1.0) 583/74,788 0.96 (0.86, 1.08) 0.92 (0.82, 1.03) 0.94 (0.83, 1.05)
P-trend — 0.49 0.12 0.31
Long-chain n–3 PUFAs (E%) 0.10
1 (0.07) 519/76,234 1.00 1.00 1.00
2 (0.12) 565/75,565 1.05 (0.93, 1.18) 1.06 (0.94, 1.19) 1.01 (0.90, 1.14)
3 (0.19) 577/75,121 1.05 (0.93, 1.18) 1.07 (0.95, 1.20) 0.99 (0.88, 1.12)
4 (0.29) 550/75,920 0.96 (0.85, 1.09) 1.01 (0.90, 1.14) 0.92 (0.81, 1.04)
5 (0.52) 649/74,802 1.12 (0.99, 1.26) 1.18 (1.05, 1.33) 1.07 (0.94, 1.20)
P-trend — 0.29 0.03 0.72
Total n–6 PUFAs (E%) 0.93
1 (3.2) 488/74,326 1.00 1.00 1.00
2 (4.0) 582/74,845 1.18 (1.05, 1.33) 1.17 (1.04, 1.32) 1.13 (1.00, 1.28)
3 (4.7) 577/75,958 1.14 (1.01, 1.28) 1.13 (1.00, 1.28) 1.07 (0.95, 1.21)
4 (5.5) 600/76,514 1.17 (1.04, 1.32) 1.16 (1.03, 1.31) 1.11 (0.98, 1.25)
5 (6.8) 613/75,998 1.18 (1.05, 1.34) 1.15 (1.02, 1.29) 1.09 (0.97, 1.23)
P-trend — 0.02 0.07 0.28
Ratio n–3:n–6 0.41
1 (0.14) 595/76,912 1.00 1.00 1.00
2 (0.17) 565/76,253 0.95 (0.84, 1.06) 0.95 (0.85, 1.07) 0.90 (0.80, 1.01)
3 (0.19) 587/75,424 1.00 (0.89, 1.12) 1.02 (0.91, 1.14) 1.00 (0.90, 1.13)
4 (0.23) 569/75,140 0.96 (0.86, 1.08) 0.99 (0.88, 1.12) 0.98 (0.87, 1.10)
5 (0.30) 544/73,913 0.91 (0.81, 1.03) 0.94 (0.84, 1.06) 0.91 (0.81, 1.03)
P-trend — 0.22 0.56 0.46
Ratio ALA:LA 0.65
1 (0.11) 631/77,233 1.00 1.00 1.00
2 (0.14) 576/76,389 0.93 (0.83, 1.04) 0.93 (0.93, 1.04) 0.91 (0.81, 1.02)
3 (0.15) 577/75,353 0.95 (0.84, 1.06) 0.94 (0.84, 1.06) 0.93 (0.83, 1.04)
4 (0.17) 595/74,562 1.02 (0.91, 1.14) 1.03 (0.92, 1.16) 1.03 (0.93, 1.16)
5 (0.21) 481/74,105 0.81 (0.72, 0.92) 0.80 (0.71, 0.91) 0.86 (0.76, 0.97)
P-trend — 0.02 0.02 0.26
1
HRs were calculated by using a Cox proportional hazards model. ALA, a-linolenic acid; E%, percentage of energy; LA, linoleic acid; MDC, Malmö
Diet and Cancer; T2D, type 2 diabetes.
2
Adjusted for age (continuous), sex (when applicable), method version (categorical), season (categorical), and total energy intake (continuous).
3
Adjusted as for the basic model and for the following categorical variables: leisure-time physical activity, smoking, alcohol intake, and education.
4
Adjusted as for the basic model and for the following categorical variables: leisure-time physical activity, smoking, alcohol intake, education, and BMI
(continuous).
the findings for women with highest intakes were rather in the incidence of T2D with higher total intake of high-fat dairy
opposite direction (HR: 1.14; 95% CI: 0.97, 1.35; P = 0.12). products (P-trend , 0.001) (Table 4), and similar protective
However, no significant trends across quintiles were seen in men or associations were seen for both fermented (P-trend = 0.01) and
women (P-trend $ 0.12). nonfermented (P-trend , 0.001) high-fat dairy products. De-
creased risk of T2D was seen with higher intakes of cream (P-
Food sources of fat and incidence of T2D trend = 0.001), butter (P-trend = 0.001), and high-fat fermented
We did not observe any significant association between total milk (P-trend = 0.007) as well as higher intake of cheese in
intake of dairy products (i.e., high fat and low fat) but a lower women (P-trend = 0.02, P-interaction with sex = 0.01).

by guest
on 13 February 2018
1072 ERICSON ET AL.
TABLE 4
HRs (95% CIs) of incident T2D associated with intake of food sources of fat in the MDC cohort1
n cases/ Multivariate model Full multivariate P-interaction
Nutrient quintile (median intake/d) person-years Basic model2 without BMI3 model with BMI4 with sex
Dairy products, total (portions) 0.09

1 (3) 641/4745 1.00 1.00 1.00
2 (4) 601/4785 1.00 (0.90, 1.12) 1.04 (0.93, 1.16) 1.00 (0.89, 1.12)
3 (5) 596/4790 1.05 (0.94, 1.17) 1.10 (0.97, 1.23) 1.04 (0.93, 1.16)
4 (7) 539/4847 0.97 (0.87, 1.09) 1.03 (0.92, 1.16) 0.99 (0.88, 1.11)
5 (10) 483/4903 0.87 (0.77, 0.98) 0.90 (0.79, 1.01) 0.90 (0.80, 1.02)
P-trend — 0.03 0.13 0.14
Dairy products, low-fat (portions) 0.44
1 (0.1) 541/4845 1.00 1.00 1.00
2 (0.7) 536/4850 1.00 (0.89, 1.13) 1.04 (0.92, 1.17) 1.00 (0.89, 1.13)
3 (1.5) 494/4892 0.92 (0.92, 1.04) 0.97 (0.86, 1.10) 0.93 (0.82, 1.05)
4 (2.4) 606/4780 1.14 (1.02, 1.28) 1.19 (1.06, 1.34) 1.08 (0.96, 1.22)
5 (4.0) 683/4703 1.29 (1.15, 1.45) 1.34 (1.20, 1.51) 1.14 (1.01, 1.28)
P-trend — ,0.001 ,0.001 0.01
Dairy products, low-fat, nonfermented 0.11
(portions)
1 (0.02) 557/4829 1.00 1.00 1.00
2 (0.3) 508/4878 0.92 (0.81, 1.03) 0.94 (0.84, 1.06) 0.93 (0.82, 1.05)
3 (0.9) 500/4886 0.90 (0.79, 1.01) 0.93 (0.82, 1.05) 0.92 (0.81, 1.04)
4 (1.6) 579/4807 1.04 (0.92, 1.17) 1.07 (0.95, 1.20) 0.98 (0.87, 1.10)
5 (3.0) 716/4670 1.32 (1.18, 1.48) 1.31 (1.17, 1.46) 1.12 (1.00, 1.25)
P-trend — ,0.001 ,0.001 0.02
Dairy products, low-fat, fermented 0.78
(portions)
05 (0) 1249/10,478 1.00 1.00 1.00
1 (0.2) 398/3402 1.08 (0.96, 1.21) 1.13 (1.00, 1.26) 1.07 (0.96, 1.20)
2 (0.5) 403/3398 1.06 (0.94, 1.19) 1.13 (1.01, 1.27) 1.09 (0.98, 1.22)
3 (1.1) 385/3416 0.98 (0.87, 1.10) 1.05 (0.94, 1.18) 0.99 (0.88, 1.12)
4 (2.4) 425/3376 1.06 (0.94, 1.18) 1.15 (1.03, 1.29) 1.06 (0.95, 1.18)
P-trend — 0.56 0.02 0.42
Dairy products, high-fat (portions) 0.15
1 (0.9) 739/4657 1.00 1.00 1.00
2 (2.3) 611/4775 0.86 (0.77, 0.95) 0.88 (0.79, 0.98) 0.88 (0.79, 0.98)
3 (3.3) 552/4834 0.82 (0.74, 0.92) 0.86 (0.77, 0.96) 0.89 (0.79, 0.99)
4 (5.0) 514/4872 0.78 (0.70, 0.88) 0.82 (0.73, 0.92) 0.89 (0.79, 1.00)
5 (8.3) 444/4942 0.69 (0.61, 0.77) 0.69 (0.62, 0.78) 0.77 (0.68, 0.87)
P-trend — ,0.001 ,0.001 ,0.001
Dairy products, high-fat, nonfermented 0.60
(portions)
1 (0.1) 716/4670 1.00 1.00 1.00
2 (0.4) 622/4764 0.91 (0.82, 1.02) 0.95 (0.85, 1.06) 0.99 (0.89, 1.10)
3 (0.9) 528/4858 0.78 (0.69, 0.87) 0.82 (0.73, 0.91) 0.88 (0.78, 0.98)
4 (2.4) 534/4852 0.78 (0.70, 0.88) 0.80 (0.72, 0.90) 0.88 (0.79, 0.99)
5 (5.8) 460/4926 0.71 (0.63, 0.79) 0.70 (0.62, 0.79) 0.80 (0.71, 0.90)
P-trend — ,0.001 ,0.001 ,0.001
Dairy products, high-fat, fermented 0.01
(portions)
1 (0.3) 709/4677 1.00 1.00 1.00
2 (1.1) 634/4752 0.92 (0.82, 1.02) 0.94 (0.85, 1.05) 0.98 (0.88, 1.09)
3 (1.7) 535/4851 0.78 (0.70, 0.88) 0.82 (0.74, 0.92) 0.85 (0.76, 0.95)
4 (2.4) 516/4870 0.78 (0.70, 0.88) 0.85 (0.75, 0.95) 0.88 (0.79, 0.99)
5 (3.6) 466/4920 0.76 (0.68, 0.86) 0.83 (074, 0.94) 0.89 (0.79, 1.01)
P-trend — ,0.001 ,0.001 0.01
Milk, total (g) 0.23
1 (71) 570/4816 1.00 1.00 1.00
2 (221) 513/4873 0.91 (0.81, 1.02) 0.93 (0.83, 1.05) 0.92 (0.82, 1.04)
3 (331) 535/4851 0.96 (0.86, 1.08) 0.99 (0.88, 1.12) 0.95 (0.84, 1.07)
4 (450) 586/4800 1.10 (0.98, 1.24) 1.12 (1.00, 1.26) 1.07 (0.95, 1.20)
5 (633) 656/4730 1.29 (1.15, 1.44) 1.27 (1.14, 1.43) 1.09 (0.98, 1.23)
P-trend — ,0.001 ,0.001 0.02
(Continued)

by guest
on 13 February 2018

Milk, low-fat (g) 0.28

05 (0) 666/5911 1.00 1.00 1.00
1 (57) 479/4609 0.96 (0.86, 1.08) 1.01 (0.90, 1.14) 0.99 (0.88, 1.12)
2 (182) 463/4625 0.94 (0.84, 1.06) 1.00 (0.88, 1.12) 0.93 (0.83, 1.05)
3 (322) 570/4519 1.14 (1.01, 1.27) 1.20 (1.07, 1.34) 1.10 (0.98, 1.23)
4 (546) 682/4406 1.34 (1.20, 1.49) 1.37 (1.24, 1.54) 1.15 (1.04, 1.29)
P-trend — ,0.001 ,0.001 0.003
Milk, low-fat, nonfermented (g) 0.12
05 (0) 833/7702 1.00 1.00 1.00
1 (43) 440/4158 0.98 (0.87, 1.10) 1.03 (0.92, 1.16) 1.00 (0.90, 1.13)
2 (157) 448/4151 1.03 (0.92, 1.16) 1.08 (0.96, 1.22) 1.02 (0.91, 1.14)
3 (289) 497/4102 1.13 (1.01, 1.26) 1.17 (1.04, 1.30) 1.05 (0.94, 1.18)
4 (503) 642/3957 1.48 (1.33, 1.64) 1.46 (1.32, 1.62) 1.21 (1.09, 1.34)
P-trend — ,0.001 ,0.001 0.001
Milk, low-fat, fermented (g) 0.46
05(0) 1938/16,011 1.00 1.00 1.00
1 (29) 224/2021 1.04 (0.90, 1.20) 1.08 (0.94, 1.25) 1.04 (0.90, 1.20)
2 (71) 239/2006 1.06 (0.93, 1.22) 1.12 (0.98, 1.28) 1.04 (0.91, 1.20)
3 (140) 216/2030 0.93 (0.81, 1.08) 1.00 (0.87, 1.15) 0.96 (0.83, 1.11)
4 (250) 243/2002 0.94 (0.82, 1.08) 1.02 (0.89, 1.17) 1.04 (0.91, 1.19)
P-trend — 0.38 0.48 0.73
Milk, high-fat (g) 0.83
1 (6) 647/4739 1.00 1.00 1.00
2 (29) 627/4759 1.01 (0.90, 1.12) 1.01 (0.90, 1.13) 1.00 (0.90, 1.12)
3 (68) 568/4818 0.93 (0.83, 1.04) 0.93 (0.83, 1.04) 0.93 (0.84, 1.05)
4 (161) 513/4873 0.83 (0.74, 0.94) 0.84 (0.75, 0.95) 0.89 (0.79, 1.00)
5 (330) 505/4881 0.86 (0.76, 0.96) 0.84 (0.75, 0.94) 0.91 (0.81, 1.03)
P-trend — ,0.001 ,0.001 0.02
Milk, high-fat, nonfermented (g) 0.40
1 (3) 601/4785 1.00 1.00 1.00
2 (16) 577/4809 0.98 (0.86, 1.08) 0.98 (0.87, 1.10) 0.95 (0.84, 1.06)
3 (33) 595/4791 1.03 (0.92, 1.16) 1.04 (0.93, 1.17) 1.04 (0.93, 1.17)
4 (63) 555/4831 0.98 (0.87, 1.10) 0.97 (0.86, 1.09) 0.98 (0.87, 1.10)
5 (271) 532/4854 0.94 (0.83, 1.06) 0.89 (0.79, 1.00) 0.94 (0.84, 1.06)
P-trend — 0.40 0.09 0.52
Milk, high-fat, fermented (g) 0.77
05(0) 1812/13,917 1.00 1.00 1.00
1 (25) 287/2513 0.94 (0.83, 1.07) 0.97 (0.86, 1.10) 0.99 (0.87, 1.13)
2 (61) 283/2517 0.92 (0.81, 1.04) 0.95 (0.84, 1.08) 0.97 (0.86, 1.10)
3 (107) 270/2531 0.87 (0.79, 0.99) 0.91 (0.80, 1.03) 0.94 (0.83, 1.07)
4 (179) 208/2592 0.69 (0.59, 0.79) 0.73 (0.63, 0.84) 0.80 (0.69, 0.92)
P-trend — ,0.001 ,0.001 0.007
Milk, nonfermented (g) 0.15
1 (24) 509/4877 1.00 1.00 1.00
2 (119) 532/4854 1.05 (0.93, 1.19) 1.06 (0.94, 1.20) 1.05 (0.93, 1.19)
3 (244) 540/4846 1.07 (0.95, 1.21) 1.08 (0.95, 1.22) 1.05 (0.92, 1.18)
4 (357) 579/4807 1.19 (1.05, 1.34) 1.16 (1.03, 1.31) 1.07 (0.95, 1.21)
5 (515) 700/4686 1.55 (1.38, 1.74) 1.47 (1.31, 1.65) 1.24 (1.10, 1.39)
P-trend — ,0.001 ,0.001 0.001
Milk, fermented (g) 0.40
05 (0) 1132/8292 1.00 1.00 1.00
2 (36) 469/3907 0.97 (0.87, 1.08) 1.03 (0.92, 1.14) 1.04 (0.94, 1.16)
3 (75) 440/3937 0.89 (0.80, 1.00) 0.95 (0.85, 1.06) 0.93 (0.83, 1.04)
4 (143) 431/3946 0.86 (0.77, 0.96) 0.94 (0.84, 1.05) 0.97 (0.86, 1.08)
5 (250) 388/3988 0.77 (0.68, 0.86) 0.85 (0.76, 0.96) 0.91 (0.81, 1.02)
P-trend — ,0.001 0.01 0.08
Cheese (g) 0.01
1 (11) 666/4720 1.00 1.00 1.00
2 (27) 589/4797 0.89 (0.80, 0.99) 0.93 (0.83, 1.04) 0.94 (0.84, 1.05)
3 (40) 571/4851 0.89 (0.79, 0.99) 0.94 (0.84, 1.06) 0.92 (0.82, 1.03)
(Continued)

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1074 ERICSON ET AL.

4 (53) 532/4854 0.86 (0.77, 0.96) 0.94 (0.83, 1.05) 0.93 (0.83, 1.05)
5 (82) 502/4884 0.87 (0.77, 0.98) 0.96 (0.85, 1.07) 0.92 (0.81, 1.04)
P-trend — 0.01 0.50 0.21
Cream (g) 0.28
1 (0.3) 671/4715 1.00 1.00 1.00
2 (5) 623/4763 0.95 (0.85, 1.06) 0.99 (0.88, 1.10) 1.01 (0.90, 1.13)
3 (11) 590/4796 0.91 (0.82, 1.02) 0.96 (0.86, 1.07) 1.00 (0.89, 1.12)
4 (18) 501/4885 0.76 (0.68, 0.86) 0.81 (0.72, 0.91) 0.88 (0.78, 0.99)
5 (32) 475/4911 0.71 (0.63, 0.80) 0.75 (0.67, 0.85) 0.85 (0.76, 0.96)
P-trend — ,0.001 ,0.001 0.001
Ice cream (g) 0.27
1 (0) 632/4754 1.00 1.00 1.00
2 (3) 539/4847 0.86 (0.76, 0.96) 0.89 (0.79, 1.00) 0.89 (0.79, 1.00)
3 (6) 575/4811 0.94 (0.84, 1.05) 0.97 (0.86, 1.08) 0.93 (0.83, 1.04)
4 (13) 530/4856 0.86 (0.77, 0.96) 0.91 (0.81, 1.02) 0.87 (0.77, 0.98)
5 (29) 584/4802 0.94 (0.84, 1.05) 1.00 (0.89, 1.12) 0.93 (0.83, 1.04)
P-trend — 0.33 0.93 0.20
Butter/butter blends (g)
1 (0) 1781/13,548 1.00 1.00 1.00 0.60
2 (3) 281/2619 0.83 (0.73, 0.94) 0.88 (0.77, 1.00) 0.89 (0.78, 1.01)
3 (16) 290/2610 0.87 (0.77, 0.99) 0.90 (0.79, 1.02) 0.94 (0.83, 1.06)
4 (28) 255/2646 0.76 (0.67, 0.87) 0.77 (0.67, 0.88) 0.83 (0.73, 0.95)
5 (33) 253/2647 0.72 (0.72, 0.93) 0.79 (0.69, 0.91) 0.86 (0.75, 0.98)
P-trend — ,0.001 ,0.001 0.001
Margarine total (g)
1 (5) 541/4845 1.00 1.00 1.00 0.28
2 (13) 499/4887 0.95 (0.84, 1.07) 0.97 (0.86, 1.10) 0.94 (0.83, 1.07)
3 (25) 578/4808 1.07 (0.95, 1.21) 1.10 (0.97, 1.23) 1.04 (0.93, 1.18)
4 (38) 601/4785 1.08 (0.96, 1.22) 1.08 (0.96, 1.21) 1.03 (0.91, 1.15)
5 (59) 641/4745 1.09 (0.97, 1.22) 1.04 (0.93, 1.17) 0.99 (0.88, 1.11)
P-trend — 0.03 0.19 0.69
Margarine, low-fat (g) 0.16
05(0) 1102/9962 1.00 1.00 1.00
1 (8) 382/3584 1.05 (0.93, 1.18) 1.09 (0.96, 1.23) 1.01 (0.89, 1.14)
2 (19) 421/3546 1.09 (0.97, 1.22) 1.12 (1.00, 1.26) 1.08 (0.96, 1.21)
3 (30) 440/3527 1.07 (0.96, 1.20) 1.08 (0.96, 1.20) 1.02 (0.92, 1.14)
4 (52) 515/3451 1.13 (1.02, 1.26) 1.09 (0.98, 1.21) 1.02 (0.91, 1.13)
P-trend — 0.02 0.06 0.55
Margarine, high-fat (g) 0.42
1 (3) 617/4769 1.00 1.00 1.00
2 (6) 565/4821 0.92 (0.82, 1.03) 0.92 (0.82, 1.03) 0.91 (0.81, 1.02)
3 (8) 557/4829 0.91 (0.81, 1.02) 0.90 (0.80, 1.01) 0.88 (0.78, 0.98)
4 (12) 543/4843 0.91 (0.81, 1.02) 0.92 (0.82, 1.03) 0.94 (0.84, 1.06)
5 (26) 578/4808 0.95 (0.85, 1.06) 0.94 (0.84, 1.05) 0.97 (0.86, 1.08)
P-trend — 0.36 0.32 0.77
Oils and dressing (g) 0.38
1 (0) 566/4820 1.00 1.00 1.00
2 (1) 632/4754 1.16 (1.03, 1.30) 1.21 (1.08, 1.35) 1.16 (1.04, 1.31)
3 (4) 560/4826 1.04 (0.92, 1.17) 1.11 (0.98, 1.25) 1.06 (0.94, 1.20)
4 (7) 561/4825 1.04 (0.93, 1.18) 1.13 (1.00, 1.27) 1.09 (0.97, 1.22)
5 (14) 541/4845 1.04 (0.92, 1.17) 1.14 (1.01, 1.28) 1.09 (0.96, 1.23)
P-trend — 1.00 0.17 0.49
Eggs (g) 0.89
1 (4) 528/4858 1.00 1.00 1.00
2 (12) 565/4821 1.08 (0.96, 1.21) 1.08 (0.96, 1.21) 1.07 (0.95, 1.20)
3 (19) 538/4848 1.02 (0.90, 1.15) 1.02 (0.90, 1.15) 0.99 (0.88, 1.12)
4 (28) 592/4794 1.16 (1.03, 1.30) 1.16 (1.03, 1.31) 1.10 (0.98, 1.24)
5 (45) 637/4749 1.27 (1.13, 1.42) 1.27 (1.13, 1.42) 1.14 (1.02, 1.28)
P-trend — ,0.001 ,0.001 0.03
(Continued)

by guest
on 13 February 2018

Meat and meat products, total (g) 0.80

1 (55) 394/4992 1.00 1.00 1.00
2 (84) 522/4864 1.28 (1.12, 1.46) 1.24 (1.09, 1.41) 1.13 (1.00, 1.29)
3 (102) 581/4805 1.41 (1.24, 1.60) 1.36 (1.19, 1.54) 1.20 (1.06, 1.37)
4 (123) 499/4787 1.44 (1.27, 1.64) 1.36 (1.19, 1.55) 1.15 (1.01, 1.31)
5 (163) 764/4622 1.82 (1.61, 2.06) 1.68 (1.48, 1.91) 1.36 (1.20, 1.55)
P-trend — ,0.001 ,0.001 ,0.001
Meat and meat products, low-fat (g)
1 (9) 504/4926 1.00 1.00 1.00 0.56
2 (24) 553/4892 1.06 (0.94, 1.19) 1.06 (0.94, 1.20) 1.05 (0.93, 1.19)
3 (35) 573/4810 1.15 (1.02, 1.29) 1.16 (1.03, 1.31) 1.14 (1.01, 1.29)
4 (49) 592/4784 1.20 (1.06, 1.35) 1.21 (1.08, 1.37) 1.17 (1.04, 1.32)
5 (75) 658/4658 1.34 (1.19, 1.50) 1.34 (1.19, 1.51) 1.25 (1.11, 1.41)
P-trend — ,0.001 ,0.001 ,0.001
Meat, red, low-fat, nonprocessed (g) 0.46
1 (1) 509/4877 1.00 1.00 1.00
2 (15) 545/4841 1.08 (0.96, 1.22) 1.09 (0.99, 1.22) 1.11 (0.99, 1.26)
3 (24) 542/4844 1.08 (0.96, 1.22) 1.08 (0.96, 1.22) 1.07 (0.95, 1.21)
4 (36) 602/4784 1.18 (1.05, 1.33) 1.19 (1.06, 1.34) 1.17 (1.04, 1.32)
5 (57) 662/4724 1.30 (1.16, 1.46) 1.28 (1.15, 1.46) 1.24 (1.10, 1.39)
P-trend — ,0.001 ,0.001 ,0.001
Meat products, low-fat, processed (g) 0.69
05(0) 628/5628 1.00 1.00 1.00
1 (3) 582/4586 1.17 (1.04, 1.31) 1.20 (1.07, 1.34) 1.16 (1.04, 1.30)
2 (8) 520/4649 1.05 (0.94, 1.18) 1.07 (0.96, 1.21) 1.07 (0.95, 1.20)
3 (14) 542/4627 1.10 (0.98, 1.23) 1.12 (1.00, 1.26) 1.09 (0.97, 1.22)
4 (27) 588/4580 1.20 (1.08, 1.35) 1.23 (1.10, 1.37) 1.16 (1.04, 1.30)
P-trend — 0.01 0.01 0.06
Meat and meat products, high-fat (g)
1 (16) 444/5032 1.00 1.00 1.00 0.17
2 (36) 531/4913 1.15 (1.01, 1.30) 1.10 (0.97, 1.25) 1.04 (0.92, 1.18)
3 (51) 566/4851 1.21 (1.07, 1.37) 1.13 (1.00, 1.28) 1.06 (0.94, 1.20)
4 (68) 655/4676 1.42 (1.25, 1.60) 1.30 (1.15, 1.47) 1.17 (1.04, 1.32)
5 (93) 664/4598 1.44 (1.28, 1.63) 1.27 (1.12, 1.44) 1.09 (0.97, 1.24)
P-trend — ,0.001 ,0.001 0.04
Meat, red, high-fat, nonprocessed (g) 0.51
1 (4) 504/4882 1.00 1.00 1.00
2 (16) 527/4859 1.02 (0.90, 1.15) 1.00 (0.88, 1.13) 0.96 (0.85, 1.08)
3 (25) 587/4799 1.14 (1.01, 1.28) 1.10 (0.97, 1.24) 1.04 (0.93, 1.18)
4 (36) 610/4776 1.17 (1.04, 1.32) 1.12 (0.99, 1.26) 1.04 (0.92, 1.17)
5 (55) 632/4754 1.22 (1.08, 1.37) 1.13 (1.00, 1.27) 1.01 (0.90, 1.14)
P-trend — ,0.001 0.01 0.48
Meat products, high-fat, processed (g) 0.97
1 (2) 433/4953 1.00 1.00 1.00
2 (16) 552/4834 1.20 (1.05, 1.36) 1.16 (1.02, 1.32) 1.12 (0.99, 1.28)
3 (29) 578/4808 1.26 (1.11, 1.42) 1.20 (1.16, 1.36) 1.18 (1.04, 1.33)
4 (38) 667/4719 1.47 (1.30, 1.66) 1.37 (1.21, 1.55) 1.29 (1.14, 1.46)
5 (50) 630/4756 1.43 (1.26, 1.62) 1.29 (1.14, 1.46) 1.15 (1.01, 1.30)
P-trend — ,0.001 ,0.001 0.01
Poultry (g) 0.33
1 (0) 114/9498 1.00 1.00 1.00
2 (1) 412/3667 1.03 (0.92, 1.16) 1.04 (0.93, 1.17) 1.02 (0.91, 1.14)
3 (13) 396/3684 0.99 (0.88, 1.11) 1.02 (0.91, 1.14) 1.00 (0.90, 1.13)
4 (22) 458/3622 1.11 (1.00, 1.24) 1.15 (1.03, 1.28) 1.10 (0.99, 1.23)
5 (36) 480/3599 1.12 (1.00, 1.24) 1.14 (1.03, 1.28) 1.06 (0.96, 1.18)
P-trend — 0.02 0.004 0.11
Fish and shellfish, low-fat (g) 0.46
1 (0) 620/4766 1.00 1.00 1.00
2 (9) 579/4807 0.94 (0.84, 1.05) 0.98 (0.87, 1.10) 0.95 (0.85, 1.07)
3 (21) 551/4835 0.90 (0.81, 1.02) 0.95 (0.84, 1.06) 0.95 (0.84, 1.06)
(Continued)

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1076 ERICSON ET AL.

4 (33) 553/4833 0.89 (0.80, 1.00) 0.94 (0.84, 1.06) 0.95 (0.85, 1.06)
5 (55) 557/4829 0.90 (0.80, 1.00) 0.98 (0.87, 1.10) 0.97 (0.86, 1.09)
P-trend — 0.04 0.52 0.60
Fish, high-fat (g) 0.67
05 (0) 691/5978 1.00 1.00 1.00
1 (3) 549/4516 1.01 (0.90, 1.14) 1.05 (0.93, 1.17) 1.07 (0.95, 1.20)
2 (9) 534/4531 0.98 (0.87, 1.10) 1.03 (0.92, 1.15) 1.02 (0.91, 1.14)
3 (23) 507/4559 0.90 (0.80, 1.02) 0.96 (0.86, 1.08) 0.93 (0.82, 1.04)
4 (46) 579/4486 1.04 (0.93, 1.16) 1.11 (0.99, 1.25) 1.05 (0.94, 1.18)
P-trend — 0.78 0.31 0.86
Pastry and biscuits (g) 0.70
1 (6) 660/4726 1.00 1.00 1.00
2 (20) 573/4813 0.87 (0.77, 0.97) 0.90 (0.80, 1.00) 0.92 (0.82, 1.03)
3 (33) 542/4844 0.81 (0.72, 0.91) 0.84 (0.75, 0.94) 0.87 (0.78, 0.98)
4 (48) 554/4832 0.83 (0.74, 0.93) 0.86 (0.77, 0.97) 0.90 (0.80, 1.01)
5 (72) 531/4855 0.80 (0.71, 0.90) 0.82 (0.72, 0.92) 0.89 (0.79, 1.01)
P-trend — ,0.001 0.001 0.06
Chocolate (g) 0.08
1 (0) 656/4730 1.00 1.00 1.00
2 (2) 564/4822 0.83 (0.74, 0.93) 0.87 (0.78, 0.97) 0.88 (0.79, 0.99)
3 (4) 561/4825 0.86 (0.76, 0.96) 0.91 (0.81, 1.02) 0.94 (0.84, 1.06)
4 (8) 542/4844 0.86 (0.77, 0.97) 0.92 (0.82, 1.03) 0.93 (0.83, 1.05)
5 (16) 537/4849 0.90 (0.80, 1.01) 0.94 (0.84, 1.06) 1.01 (0.90, 1.14)
P-trend — 0.14 0.54 0.66
1
HRs were calculated by using a Cox proportional hazards model. MDC, Malmö Diet and Cancer; T2D, type 2 diabetes.
2
Adjusted for age (continuous), sex (when applicable), method version (categorical), season (categorical), and total energy intake (continuous).
3
Adjusted as for the basic model and for the following categorical variables: leisure-time physical activity, smoking, alcohol intake, and education.
4
Adjusted as for the basic model and for the following categorical variables: leisure-time physical activity, smoking, alcohol intake, education, and BMI
(continuous).
5
Zero consumers; higher categories are quartiles in consumers.
Although high intake of total low-fat dairy products was asso- sugar-sweetened beverages) did not substantially affect any of
ciated with increased risk (P-trend = 0.01), this association was our observed associations. Except for the interaction between
NS when intakes of low- and high-fat dairy products were cheese intake and sex [also reflected in the interaction between
mutually adjusted (P-trend = 0.18), whereas the protective as- intake of high-fat fermented dairy products and sex (P = 0.01)],
sociation with high-fat dairy products remained significant we did not observe any significant interactions between any
(P-trend = 0.003). Furthermore, the association with low-fat other examined food intakes and sex.
dairy products also disappeared after adjustment for protein
intake (P-trend = 0.37); similar observations were made for low- Statistical models without BMI
fat nonfermented milk. Results regarding high-fat dairy products
Overall, statistical models without BMI did not substantially
remained unchanged. High intakes of meats, both low-fat (P-
change our observations. However, inverse associations be-
trend , 0.001) and high-fat (P-trend = 0.04) meat and meat
tween several of the high-fat dairy foods and T2D were
products, were associated with increased risk of T2D. In-
somewhat stronger before adjustment for BMI (i.e., for cream,
creased risk seemed mainly driven by intakes of low-fat
high-fat fermented milk, and butter). In addition, individuals in
nonprocessed red meat (P-trend , 0.001) and high-fat pro-
the highest quintile of high-fat nonfermented milk tended to be
cessed meat products (P-trend = 0.01). Finally and similarly to
at decreased risk before adjustment for BMI (HR: 0.89; CI:
what has previously been reported after analyses with shorter
0.79, 1.00). Moreover, high-fat nonprocessed red meat was
follow-up time in the MDC cohort (33), high egg intake was
significantly associated with increased risk of T2D only before
associated with increased risk. All observed associations re-
adjustment for BMI (P-trend = 0.01). The inclusion of waist
mained virtually unchanged after additional adjustments for
circumference in our statistical models did not substantially
dietary change in the past.
affect any results.
A post hoc analysis indicated that intakes of several nondairy
foods tended to differ significantly across intake quintiles
of cream and high-fat fermented milk; decreased intakes of Sensitivity analysis
both sugar-sweetened beverages and fiber-rich bread and cereals In an analysis excluding individuals who reported less-stable
were, for example, seen across quintiles (Supplemental Table food habits (24% of participants), we did not observe an inverse
2). However, adjustment for dietary intakes (fiber, sucrose, association between total intake of SFAs and T2D (P-trend = 0.69
calcium, vitamin D, magnesium, meat, fruit and vegetables, or in the full multivariate model including BMI). However,

by guest
on 13 February 2018
although decreased risks of T2D at high intakes of SFAs with 4– intake of dairy products and showed inverse associations with
10 carbons, lauric acid, and myristic acid were no longer sig- T2D (15). Similar observations were made in other studies (36,
nificant, tendencies of protective associations were still seen, 37). Also, it was recently concluded, in a meta-analysis, that
especially in women (P-trend = 0.09, 0.06, and 0.06, re- total dairy intake was inversely associated with risk of T2D (12).
spectively). As concerns specific food sources of fat, the con- However, in contrast to our findings, the meta-analysis showed
sumption of cream and high-fat fermented milk remained protective associations with low-fat dairy. Only one of the in-
significantly and inversely associated with T2D (P-trend = 0.01), cluded studies reported an inverse association with high-fat
whereas inverse associations with butter became nonsignificant. dairy products (38), and high-fat dairy was inversely associated
Observed associations with intakes of different types of meat with the metabolic syndrome in another study (39). Still, all
and meat products remained virtually unchanged. Moreover, an studies could not distinguish between low- and high-fat dairy
increased incidence of T2D was now seen in individuals in the (13), studies included different dairy foods (40, 41), and clas-
highest compared with lowest quintiles of n–6 PUFA intake sifications of low- compared with high-fat products differed.
(HR: 1.17; 95% CI: 1.02, 1.35), and in line with this result, we Finally, dairy intake in Sweden is relatively high compared with
observed decreased risk in the highest quintile of the ratio between that in other populations. Dairy is the most important fat source
intakes of n–3 and n–6 PUFAs (HR: 0.86; 95% CI: 0.75, 0.99), but in the MDC cohort and contributes, on average, 30% of total fat
no significant trends were seen across quintiles (P-trend = 0.10 and intake and 35% of SFA intake in Sweden (27, 42); corre-
0.16, respectively). sponding figures in the United States are 12% and 24% (43),
After the exclusion of individuals who reported less-stable whereas meat contributes less to fat intake in Sweden (42, 44).
food habits and additional adjustment for protein intake to the full In line with previous findings, in the MDC cohort after a shorter
multivariate model, a significant trend of increased risk across follow-up and in other cohorts (33, 45), we observed higher risk
intake quintiles of n–6 PUFAs was seen (P-trend = 0.046) as well of T2D for individuals with high-meat diets. Because our ob-
as a tendency of decreased risk with a higher ratio between servations were independent of the fat content of the meat,
intakes of n–3 and n–6 PUFAs (P-trend = 0.07). Finally, after compounds such as nitrite, heterocyclic amines, and iron may
adjustment for protein, we also observed an inverse association explain our findings.
between long-chain n–3 PUFAs and T2D (P-trend = 0.04) in Dietary SFAs with shorter chain lengths (4:0–10:0) that in-
men. dicated protective associations with T2D in this study were
The results remained virtually unchanged in analysis that mainly found in dairy products. Dairy products are also better
excluded individuals with prevalent cardiovascular disease at sources of lauric acid (12:0) and myristic acid (14:0) than are
baseline. Finally, our observations were similar in normal-weight other important food sources of fat in Sweden (46). In contrast,
and overweight individuals. palmitic acid (16:0) and stearic acid (18:0), which are abundant
in both dairy foods and meat, fish, and eggs, showed null as-
sociations with T2D (46). The importance of dairy fats in the
DISCUSSION development of T2D is not well understood. Fatty acids reflected
Our main findings were that, in contrast to low-fat dairy in blood and tissue concentrations such as odd-chained SFAs
products, high intake of high-fat dairy products was associated pentadecanoic acid (15:0) and heptadecanoic acid (17:0) (15, 36,
with decreased incidence of T2D, whereas the consumption of 37), which are also present in fish, and trans palmitoleic acid
both low- and high-fat meats was associated with increased (trans-16:1n–7), which is a biomarker of dairy fat, showed in-
incidence. Intakes of palmitic and stearic acids did not show verse associations with T2D (47). Likewise, conjugated LA may
significant associations, whereas SFAs with shorter chain lengths have beneficial effects in metabolic disease, but studies have
were inversely associated with T2D. Although associations with been inconclusive and even suggested adverse effects (48). A
dairy intakes were weaker after the exclusion of individuals with study in mice indicated that butyrate (4:0) may prevent diet-
potentially unstable dietary habits, high intakes of cream and induced insulin resistance (49). Although SFAs with shorter
high-fat fermented milk, together with cheese in women, were chains may also promote insulin resistance via mechanisms that
still associated with significantly decreased risk of T2D. In lead to inflammatory processes (8), some experimental studies
a sensitivity analysis, we also observed increased risk at high n–6 indicated that SFAs with $16 carbons were more prone to cause
PUFA intake. insulin resistance (50, 51). In addition, biomarkers of dairy fat
SFAs 12–16 are known to have adverse effects on LDL- and a food pattern characterized by dairy fat have indicated
cholesterol concentrations, and even though there is evidence cross-sectional protective associations with hyperinsulinemia
that shows that these SFAs can have beneficial effects on HDL (52, 53). Future studies need to distinguish whether any SFAs
cholesterol, triglycerides, or apolipoprotein A-I (34), a system- with chain lengths from 4 to 14 carbons may account for any
atic review indicated similar improvements by unsaturated fats diabetes protective properties or if these properties can be re-
(7), and SFAs do not seem to change the ratio between total ferred to other dairy fats or food-specific characteristics.
cholesterol and HDL cholesterol (34). Nevertheless, findings Health effects of dairy are most likely the result of a complex
from observational studies provided a more balanced picture interplay between many components. For instance, SFAs in
of the role of SFAs in the development of obesity and car- cheese may be less detrimental for serum cholesterol than SFAs
diometabolic diseases, and researchers recognized the value of in butter (54). Besides, fermented dairy may affect the gut
examining food sources of fat and specific SFAs separately microbiota composition, which was shown to be altered in in-
(14, 35). In a recent report from the European Prospective In- dividuals with T2D (4), and high intake has been associated with
vestigation into Cancer and Nutrition-InterAct, odd-chained lower risk of T2D (13). However, we observed inverse associ-
SFAs in plasma phospholipids were positively correlated with ations with high-fat dairy products regardless of fermentation.

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1078 ERICSON ET AL.
Although sucrose, calcium, vitamin D, and magnesium in dairy was associated with unhealthy lifestyle characteristics, and other
may affect insulin secretion, insulin sensitivity, and risk of T2D studies also showed that high-fat dairy is more common in in-
(55, 56), adjustment for those intakes did not change our findings. dividuals with a lower socioeconomic status (66). Besides, meat
Also, whey proteins showed favorable effects on glucose me- intake was associated with higher rather than lower risk, as would
tabolism (57), but they are not likely to explain differing asso- have been expected on the basis of a similar potential for reverse
ciations with high- compared with low-fat dairy. causation. The relatively low validity for some PUFA intakes
Our observation of increased risk at high n–6 PUFA intake in was a limitation (25). A lower relative validity in men may have
sensitivity analysis needs cautious interpretation. Some reports explained that the association with cheese intake was restricted
suggested that diets with a high ratio between n–3 and n–6 to women and that associations with intakes of specific SFAs
PUFAs may prevent insulin resistance and T2D (58), which were more robust in women. Moreover, an analysis of some
supports our findings, but other reports were inconclusive (18, plant sources of fat, such as nuts and seeds, was not meaningful
59). High n–6 PUFAs may also improve insulin sensitivity (60), because of low intakes. Finally, we could not exclude the oc-
and blood concentration of LA has been inversely associated currence of residual confounding.
with T2D (7). In conclusion, our results indicate that analyses of food sources
Even if fat intake may promote a positive energy balance, and of fat may partially clarify the inconsistent role of dietary fat for
there has been probable evidence for a positive association with risk of T2D. We observed a decreased incidence of T2D at high
body weight from randomized controlled trials, the magnitude of intake of high-fat dairy products but not of low-fat dairy products.
this association is most likely modest (7), and results from long- Meat intake was associated with increased risk independently of
term prospective studies have been less convincing (61). Fur- fat content. Although intake of palmitic acid, which is the most-
thermore, there has been evidence that linked high-fat dairy abundant SFA in both dairy and meat, was not significantly
intake to satiety (62). Nevertheless, BMI adjustments are crucial associated with T2D, intakes of SFAs with 4–14 carbons, which
to minimize confounding by differing food preferences in lean are more abundant in dairy than in meat, showed inverse asso-
and obese individuals. Besides, misreporting may be of special ciations with T2D. Our study indicates a protective role of fat
concern in obese individuals (63). We observed inverse associ- from dairy and suggests that dairy fat may also have contributed
ations between high-fat dairy intake and T2D regardless of BMI to previously observed protective associations between dairy
adjustment, and our findings were similar in normal-weight and intake and T2D.
overweight persons. Because adjustment for waist circumference
Of 28,098 participants in the MDC cohort, 1758 incident diabetes cases and
had an even smaller influence on our results, it is possible that 1758 controls are included in the European Prospective Investigation into
overweight in general (independently of fat distribution) is a more Cancer and Nutrition InterAct Consortium for the study of genetic factors
important confounder because of potentially stronger links to and gene-lifestyle interactions in regard to incident diabetes. As a large cohort
food choices and dietary reporting. study, the MDC represents a different study design than the case-control study
A loss of power may have partly explained the weakened design of the European Prospective Investigation into Cancer and Nutrition
associations between high-fat dairy products and T2D and that InterAct. Dietary data used within the European Prospective Investigation into
associations with specific SFAs became nonsignificant when Cancer and Nutrition InterAct are harmonized between several study centers,
and many details in the MDC dietary data used in the current study were lack-
participants who reported unstable food habits were excluded
ing in these harmonized data. That is, a different study design, different study
(almost one-fourth of subjects were excluded). Inverse associ- size, extensive information on confounding variables, the possibility to ex-
ations with cream and high-fat fermented milk remained sig- clude individuals with reported dietary change, and uniform dietary data
nificant. Because dietary change was more common in subjects of high relative validity ensured the uniqueness of the current study compared
who developed T2D and inversely related to high-fat dairy intake, with the pooled analyses that may be performed within the European Prospec-
we also treated the variable as a confounder [i.e., a potential tive Investigation into Cancer and Nutrition InterAct.
marker of unhealthy dietary habits earlier in life because health The authors’ responsibilities were as follows—UE: designed the research,
reasons were the major cause of dietary change (64)]. This ad- performed the statistical analysis, wrote the manuscript, and had primary
responsibility for the final content of the manuscript; BG: gave statistical
justment did not significantly affect any results.
advice; and all authors: contributed to the interpretation of results and re-
This study had several strengths. It was a large study with vision of the manuscript and read and approved the final version of the
a long follow-up time. Because it was a population-based pro- manuscript. None of the funders had any role in the study design, data
spective study, selection bias and reverse causation were minor collection and analysis, interpretation of data, decision to publish, or prep-
issues. A main objective of the MDC study was to examine fat aration of the manuscript. None of the authors reported a conflict of interest
intake (65), and the relative validity for dietary intakes of im- related to the study.
portance to this study (e.g., total milk correlation coefficient was
0.8) has been well documented (24, 25). The intake range was
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05 - Food Sources of Fat May Clarify The Inconsistent Role of Dietary Fat Intake For Incidence of Type 2

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Food sources of fat may clarify the inconsistent role of dietary fat intake

for incidence of type 2 diabetes1–4

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Sex, F, % 26,930 48.5 62.7 ,0.001

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n 26,930 26,894 26,754 25,286 26,930 26,920 26,865 26,893

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P-trend ,0.001 0.01 0.48 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001

Fat (E%) 0.59

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Nutrient quintile n cases/ Multivariate model Full multivariate P-interaction

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Dairy products, total (portions) 0.09

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n cases/ Multivariate model Full multivariate P-interaction

Milk, low-fat (g) 0.28

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n cases/ Multivariate model Full multivariate P-interaction

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n cases/ Multivariate model Full multivariate P-interaction

Meat and meat products, total (g) 0.80

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n cases/ Multivariate model Full multivariate P-interaction

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