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Jordi Salas-Salvadó
Human Nutrition Unit
Faculty of Medicine and Health Sciences of Reus
Department of Biochemistry and Biotechnology
Universitat Rovira i Virgili
Yogurt and diabetes:
Overview of the recent epidemiologic studies
Conflict of interest
regarding this presentation:
• I am member of the Executive Committee of the Spanish
Danone Institute.
• The YINI programme has paid for travel and
accommodation expenses for this presentation.
YOGURT AND DIABETES
DIABETES: THE GLOBAL BURDEN
More than 387 million people in the word have diabetes.
By 2030 is expected this will have risen to 592 million people.
• The prevalence of T2DM is increasing in parallel to
the obesity epidemics.
• 80% of the T2DM individuals are living in
developing countries.
• T2DM is a potent risk factor for cardiovascular
disease, blindness, renal failure, and lower limb
amputation, decreasing quality of life.
• T2DM is responsible of the 5 % of the total
mortality.
• In the next 10 years is expected that mortality by
diabetes will increase by 50%.
DIABETES: THE GLOBAL BURDEN
Geneticbackground
Physical inactivity
Smoking
Alcohol intake
Unhealthy diet
Overweight
DIABETES
RISK
Lifestyleriskfactors RISK FACTORS FOR DIABETES
Food groups and risk of type 2 DM
Relative risks are a comparison of extreme categories, except for processed meat (per 50 g per day increase), unprocessed red meat and
fi sh or seafood (per 100 g per day), white rice (per each serving per day), wholegrains (per three servings per day), sugar-sweetened
beverages in European cohorts (per 336 g per day), and alcohol (22 g per day for men or 24 g per day for women with abstainers).
Summary of meta-analyses of prospective cohort studies on food
and beverage intake and type 2 diabetes
Nuts (women)
Tea
Ley S et al., Lancet 2014
DHA=docosahexaenoic acid. EPA=eicosapentaenoic acid. Relative risks are a comparison of extreme categories, except for DHA/EPA
(per 250 mg per day increase) and alpha-linolenic acid (per 0.5 g per day). All nutrients and glycaemic variables were assessed from
dietary intake, except vitamin D for which blood 25-hydroxyvitamin D was used.
Summary of meta-analyses of prospective cohort studies of
nutrient intake and glycaemic variables and type 2 diabetes
Nutrients and risk of type 2 DM
TRANS, SFA ??
Ley S et al., Lancet 2014
OXIDATION
INFLAMMATION
Endothelial
dysfunction
Insulin resistance/secretion
DIABETES
Genetic
background
Low glycemic index
Fiber
MUFA / PUFA
Magnesium
Antioxidants
(-)
(-)
(-)
(-)
(-)
High glycemic index
SFA
TFA
(+)
(+)
(+)
MECHANISMS
Salas-Salvadó et al, NMCD 2011
(-)
Heme iron
(+)
DAIRY PRODUCTS
OBESITY
RISK
CARDIOVASCULAR DISEASEDIABETES
METABOLIC
SYNDROME
Minerals
Vitamins
Proteins
calcium
magnesium
potassium
phosphor
zinc
Vit. A
Vit. D
Vit. B2, B3, B6, B12
Vit. K2
Probiotic effects
“fermented foods”
OSTOPOROSIS
CH “lactose”
Fat
DAIRY PRODUCTS
Nutritional concerns:
Rich in natural trans fatty acids
Rich in saturated fatty acids
Rich in salt (ie. cheese)
Rich in added sugar (some yogurts and processed dairy foods)
Irrational beliefs that lead to a decrease in consumption:
“Humans are the unique animals that consume dairy products through the life”
DAIRY PRODUCTS
In the last years some guidelines
recommend to consume low-fat dairy
products or to limit them
DAIRY PRODUCTS
Astrup A. Yogurt and dairy product consumption to prevent cardiometabolic diseases:
epidemiologic and experimental studies. Am J Clin Nutr. 2014.
“The consumption of yogurt and other dairy products, in observational studies is associated with
a reduced risk of weight gain and obesity as well as of CVD, and these findings are, in part,
supported by randomized trials”.
Recent published evidences support
the idea that dairy products can be
beneficial (or not harmful) for
several chronic metabolic conditions
and CVD.
“four meta-analysis of prospective studies have shown a decrased risk of
diabetes in those individuals with a higher consumption of dairy
products”.
DAIRY PRODUCTS AND DIABETES
DAIRY PRODUCTS AND DIABETES
0.90 0.95 1.05 1.10
Total dairy (n=17)
(per 200g/d)
Low-fat dairy (n=13)
(per 200g/d)
High-fat dairy (n=13)
(per 200g/d)
Total milk (n=12)
(per 200g/d)
Low-fat milk (n=7)
(per 200g/d)
Cheese (n=13)
(per 10g/d)
Number
populations
Heterogenity test
I2 P-vaue
66.4 <0.001
High-fat milk (n=9)
(per 200g/d)
68.0 <0.001
51.6 0.016
57.4 0.007
71.6 0.002
84.1 <0.001
61.7 0.002
Consumption of dairy foods and diabetes incidence: a dose-response
meta-analysis of observational studies
Lieke Gijsbers et al, Am J Clin Nutr 2016
“This dose-response
meta-analysis of
observational studies
suggest a posible role
for dairy foods in the
prevention of type 2
diabetes”
22 cohort studies 579,832 individuals and 43,118 T2D cases)
RR
DAIRY PRODUCTS
Turner KM, Keogh JB, Clifton PM. Dairy consumption and insulin sensitivity:
a systematic review of short- and long-term intervention studies. Nutr
Metab Cardiovasc Dis. 2015 Jan;25(1):3-8.
Conclusions (in adults):
• 4 Showed a positive effect on insulin sensitivity as assessed by HOMA.
• 1 Showed a negative effect
• 5 Showed No effect.
As the number of weight stable intervention studies is very limited and
participant numbers small, these findings need to be confirmed by larger trials
in order to conclusively determine any relationship between dairy intake and
insulin sensitivity.
YOGURT AND HEALTH
In epidemiologic prospective studies usually
yogurt consumption
is inversely related to body weight gain, obesity,
metabolic syndrome, diabetes and cardiovascular
disease.
“ONLY YOGURT HAS BEEN ASSOCIATED TO A LOWER RISK OF DIABETES”
YOGURT AND DIABETES
17% lower risk of diabetes incidence in
those consuming 3 or more servings of
yogurt per week
41,436 men in the Health Professionals Follow-Up Study
67,138 women in the Nurses' Health Study
85,884 women in the Nurses' Health Study II
3,984,203 person-years of follow-up
15,156 incident T2D cases
HRs for a serving yogurt consumption per day and type 2 diabetes
YOGURT AND DIABETES
The Australian Diabetes Obesity and Lifestyle Study
The Whitehall II Prospective Study
EPIC-Interact Study
Women’s Health Initiative
Japan Public Health Center–based Prospective Study
Women’s Health Study
Health Professional Follow-up Study
Nurses Health Study I
Nurses Health Study II
Per 1 serving
18% lower risk
Most of the studies were conducted in apparently healthy young or
middle-aged individuals from different populations.
No study has examined the association between dairy intake and risk
of diabetes in elderly individuals at high cardiovascular risk.
YOGURT AND DIABETES
PREDIMED – Participants’ characteristics
MeDiet + VOO
(n=2487)
MeDiet + Nuts
(n=2396)
Control
(n=2349)
Age, y (SD) 67 (6) 67 (6) 67 (6)
Women (%) 57 54 58
Diabetes (%) 50 47 48
Hypertension (%) 82 82 84
Current smokers (%) 14 15 14
Dyslipidemia (%) 72 73 72
BMI, kg/m2 (SD) 30 (4) 30 (4) 30 (4)
Waist circumf., cm (SD) 100 (10) 100 (10) 101 (11)
MeDiet 14-p score (SD) 8.7 (2) 8.7 (2) 8.3 (2)
Trial started October 2003, terminated July 2011
Mean follow-up for 5 years
POPULATION STUDIED
YOGURT AND DIABETES
Prospective analysis - non-diabetic PREDIMED participants at baseline.
3,454 participants (1980 ♂, 2536 ♀).
270 incident cases of diabetes (median follow-up of 4.1 years).
RESEARCH DESIGN AND METHODS
Low-fat dairy (71%)
Totaldairy(362g/d)
Total milk (63%)
Non-reduced fat dairy (29 %)
Low-fat milk (85%)
Total fermented dairy
Dairy consumption was adjusted for total energy intake using the nutrient residual method and we calculated and used the cumulative
average of dairy consumption.
Semi-skim/skim milk and skim yogurt
Whole milk, condensed milk, milkshake, whole yogurt, whipped
cream, custard, ice cream and all types of cheeses
Totaldairy(362g/d)
Total yogurt (24%)
Total cheese (11%)
Whole milk (15%)
Low-fat yogurt (70%)
Whole fat yogurt (30%)
All types of yogurt and cheese
YOGURT AND DIABETES
A validated
semiquantitative
137- item FFQ
Prospective analysis - non-diabetic PREDIMED participants at baseline.
3,454 participants (1980 ♂, 2536 ♀).
270 incident cases of diabetes (median follow-up of 4.1 years).
HRs for type 2 diabetes according to tertiles of total, low-fat and whole-fat dairy
food consumption in the PREDIMED cohort
“Total and low-fat dairy
consumption was inversely
associated to a lower risk of
diabetes”
3.454 non-diabetic participants
270 incident cases of diabetes
(median follow-up of 4.1 years).
Díaz-López et al, Eur J Nutr 2015
DAIRY AND DIABETES
aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians
(interquartile range).
Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake.
Model 1: Adjusted for age, sex and BMI.
Model 2: Additionally adjusted for dietary intervention group,
physical activity, educational level, smoking, hypertension,
dyslipidemia, and fasting glucose, HDL-cholesterol and
triglyceride levels.
Model 3: Additionally adjusted for cumulative average dietary
intakes in energy-adjusted quintiles (vegetables, legumes,
fruits, cereals, meat, fish, olive oil, nuts) and alcohol and
alcohol squared in g/day.
All models were stratified by recruitment center.
Total dairy, median (g/day): T1: 200; T2: 342; T3: 539
Low-fat dairy, median (g/day): T1: 85; T2: 256; T3: 462
Whole-fat dairy, median (g/day): T1: 0; T2: 20; T3: 97
HRs for type 2 diabetes according to tertiles of total, low-fat and whole-fat milk
food consumption in the PREDIMED cohort
“Milk was not significantly
associated to the risk of
diabetes”
3.454 non-diabetic participants
270 incident cases of diabetes
(median follow-up of 4.1 years).
Díaz-López et al, Eur J Nutr 2015
MILK AND DIABETES
aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (interquartile R
Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake.
Total milk, median (g/day): T1:109; T2: 216; T3: 400
Low-fat milk, median (g/day): T1: 32; T2: 200; T3: 370
Whole-fat milk, median (g/day): T1: 0; T2: 6; T3: 41
Model 1: Adjusted for age, sex and BMI.
Model 2: Additionally adjusted for dietary intervention group,
physical activity, educational level, smoking, hypertension,
dyslipidemia, and fasting glucose, HDL-cholesterol and
triglyceride levels.
Model 3: Additionally adjusted for cumulative average dietary
intakes in energy-adjusted quintiles (vegetables, legumes,
fruits, cereals, meat, fish, olive oil, nuts) and alcohol and
alcohol squared in g/day.
All models were stratified by recruitment center.
HRs for type 2 diabetes according to tertiles of specific yogurt consumption in
the PREDIMED cohort
“Independently of the fat
content, a higher consumption
of yogurt has associated to a
lower risk of diabetes”
3.454 non-diabetic participants
270 incident cases of diabetes
(median follow-up of 4.1 years).
Díaz-López et al, Eur J Nutr 2015
YOGURT AND DIABETES
aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (Interquartil R).
Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake.
Total yogurt, median (g/day):T1: 13; T2: 71; T3: 128
Low-fat yogurt, median (g/day): T1: 3; T2: 44; T3: 120
Whole-fat yogurt, median (g/day): T1: 0; T2: 7; T3: 45
Model 1: Adjusted for age, sex and BMI.
Model 2: Additionally adjusted for dietary intervention group,
physical activity, educational level, smoking, hypertension,
dyslipidemia, and fasting glucose, HDL-cholesterol and
triglyceride levels.
Model 3: Additionally adjusted for cumulative average dietary
intakes in energy-adjusted quintiles (vegetables, legumes,
fruits, cereals, meat, fish, olive oil, nuts) and alcohol and
alcohol squared in g/day.
All models were stratified by recruitment center.
HRs for type 2 diabetes according to tertiles of specific yogurt consumption in
the PREDIMED cohort
“Independently of the fat
content, a higher consumption
of yogurt has associated to a
lower risk of diabetes”
3.454 non-diabetic participants
270 incident cases of diabetes
(median follow-up of 4.1 years).
Díaz-López et al, Eur J Nutr 2015
YOGURT AND DIABETES
aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (interquartile
range). Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake.
Total yogurt, median (g/day): T1: 13; T2: 71; T3: 128
Low-fat yogurt, median (g/day): T1: 3; T2: 44; T3: 120
Whole-fat yogurt, median (g/day): T1: 0; T2: 7; T3: 45
An average increment of one
serving/day of the standard serving of
yogurt (125 g) was associated with a
33% lower risk of T2D.
Model 1: Adjusted for age, sex and BMI.
Model 2: Additionally adjusted for dietary intervention group,
physical activity, educational level, smoking, hypertension,
dyslipidemia, and fasting glucose, HDL-cholesterol and
triglyceride levels.
Model 3: Additionally adjusted for cumulative average dietary
intakes in energy-adjusted quintiles (vegetables, legumes,
fruits, cereals, meat, fish, olive oil, nuts) and alcohol and
alcohol squared in g/day.
All models were stratified by recruitment center.
HRs (95% CI) for type 2 diabetes associated with the substitution of one serving of yogurt and low-fat
milk for one serving of other “unhealthy” alternative foods in the PREDIMED cohort
Substituted foods Yogurt (125 g) Low-fat milk (200 mL)
Dairy desserts (100g)a 0.58 (0.29-1.18) 0.71 (0.35-1.41)
Biscuits and chocolate confectionary (50g) 0.60 (0.38-0.94) 0.69 (0.47-1.03)
Whole-grain biscuits and homemade pastries (50 g) 0.55 (0.32-0.96) 0.63 (0.38-1.05)
aPetit Suisse cheese or custard or ice cream. The servings are based on energy-adjusted cumulative average food intake. Values are
given as HR (95% CI) from Cox regression models adjusted for age, sex, BMI, dietary intervention, physical activity, educational level,
smoking, hypertension, or antihypertensive use (yes/no) and dyslipidemia (yes/no), and fasting glucose, HDL-cholesterol and
triglycerides levels. All models were stratified by recruitment center.
YOGURT SUBSTITUTION AND DIABETES
Díaz-López et al, Eur J Nutr 2015
In this prospective study conducted on elderly
subjects at high cardiovascular risk, we report for the
first time that:
 a high intake of dairy products was associated with
decreased risk of T2D.
 the intake of low-fat dairy products, mainly milk and both
low-fat and non reduced-fat yogurt, were the main
contributors to this association.
 substitutions of one serving of yogurt per day for one
serving of a combination of biscuits and chocolate, or
whole-grain biscuits and homemade pastries per day was
associated with a reduced risk of T2D incidence.
YOGURT AND DIABETES
Cox regression models adjusted for intervention group, sex, age, physical activity and BMI and baseline current smoker, and hypoglycemic, hypolipidemic,
antihypertensive and insulin treatment, cumulative average consumption of vegetables, fruit, legumes, cereals, fish, red meat, alcohol, biscuits, olive oil and nuts.
Independent of the fat content,
Yogurt consumption was
inversely associated with the
incidence of MetS and its
components
Yogurt consumption and incidence of MetS or its components: PREDIMED study
1.868 participants without MetS at
baseline; 930 incident cases of
MetS (mean follow-up: 3.2 y)
P for trend=0.230
P for trend=0.004
P for trend=0.689
P for trend=0.348
P for trend=0.183
P for trend=0.048
P for trend=0.005
P for trend=0.001
P for trend<0.001
P for trend<0.001
P for trend=0.095
P for trend=0.126
P for trend=0.864
P for trend=0.011
P for trend=0.001
Central obesity
High fasting plasma glucose
High blood pressure
Low HDL-c
High triglicerides
Metabolic Syndrome P for trend=0.144
TOTAL YOGURT
Central obesity
High fasting plasma glucose
High blood pressure
Low HDL-c
High triglicerides
Metabolic Syndrome P for trend=0.003
WHOLE-FAT YOGURT
Central obesity
High fasting plasma glucose
High blood pressure
Low HDL-c
High triglicerides
Metabolic Syndrome P for trend=0.004
LOW-FAT YOGURT
0.5 1.0 2.0
HAZARD RATIO (95% CI)
Hazard ratios (95% CI) of metabolic syndrome and its components across energy-
adjusted tertiles of yogurt consumption (Tertile 3 vs Tertile 1).
↓23%
↓22%
↓27%
“Low-fat dairy products were inversely associated with MetS incidence”
“The consumption of cheese was associated with an increased risk of MetS incidence”
YOGURT AND METABOLIC SYNDROME
Babio et al, 2015
YOGURT AND DIABETES
0.90 0.95 1.05 1.10
Total dairy (n=17)
(per 200g/d)
Low-fat dairy (n=13)
(per 200g/d)
High-fat dairy (n=13)
(per 200g/d)
Total milk (n=12)
(per 200g/d)
Low-fat milk (n=7)
(per 200g/d)
Cheese (n=13)
(per 10g/d)
Number
populations
Heterogenity test
I2 P-vaue
66.4 <0.001
High-fat milk (n=9)
(per 200g/d)
68.0 <0.001
51.6 0.016
57.4 0.007
71.6 0.002
84.1 <0.001
61.7 0.002
Consumption of dairy foods and diabetes incidence: a dose-response
meta-analysis of observational studies
Lieke Gijsbers et al, Am J Clin Nutr 2016
Yogurt (n=12)
(per 10g/d)
61.7 0.002
RR
“This dose-response
meta-analysis of
observational studies
suggest a posible role for
dairy foods,
PARTICULARLY YOGURT
in the prevention of T2D
YOGURT AND DIABETES
What are the mechanisms
explaining the beneficial
metabolic effects on
diabetes prevention of dairy
products and yogurt?
DAIRY, YOGURT AND DIABETES - mechanisms
First hypothesis:
The effect of dairy products and yogurt on diabetes
prevention may be explained by their beneficial effects on
satiety, reducing adiposity.
Effects related to the Ca2+ metabolism
•An increase in intracellular Ca2+:
•Increases lipogenesis and inhibits lipolysis.
•Calcium present in dairy inhibits fatty acid absorption.
Effects related to the protein or bioactive peptides in dairy products
•Inducing satiety.
The probiotic effects of yogurt
•Inducing satiety and changing metabolic pathways implicated in lipogenesis and fat
deposition.
120,877 U.S. women and men
Free of chronic diseases and not obese
at baseline.
Relationships between changes in food and
beverage consumption and weight changes
every 4 years, according to study cohort.
Mozaffarian et al, N Engl J Med 2011
YOGUR AND OBESITY
YOGURT AND HEALTH
Second hypothesis:
The effect of dairy products and yogurt on diabetes
prevention may be explained by other mechanisms increasing
insulin sensitivity or decreasing pancreatic secretion.
Effects related to the Ca2+ metabolism
•An increase in intracellular Ca2+ favors insulin secretion and glucose uptake.
Effects related to bioactive peptides in yogurt
•Intestinal hormone activation inducing insulin secretion.
•Whey protein consumed with a CH-meal increased insulin, and the incretin hormones
glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
Beneficial effects of other components in yogurt
•Minerals (phosphor, magnesium, potassium) and vitamins (A, D, B2, B6, B12) and dairy fat.
Effects related to the fat content
Ericson U. Am J Clin Nutr 2015
Total intake of high-fat dairy products was inversely associated with
incident T2D (HR for highest compared with lowest quintiles: 0.77; CI 0.68-
0.87; P-trend<0.001).
Most robust inverse associations were seen for intakes of high-fat
fermented milk (P-trend<0.01) and for cheese in women (P-trend=0.02).
Intakes of saturated fatty acids with 4–10 carbons, lauric acid (12:0), and
myristic acid (14:0) were associated with decreased risk (P-trend<0.01).
Conclusions: Decreased T2D risk at high intake of high- but not
of low-fat dairy products suggests that dairy fat partly could
have contributed to previously observed protective associations
between dairy intake and T2D.
DAIRY PRODUCTS AND DIABETES
IS FAT FROM DAIRY UNHEALTHY AND INCREASES
THE RISK OF DIABETES?
Odd chain
15:00
Pentadecanoic
Odd chain
17:00
Heptadecanoic
Trans 16:1n-7
Transpalmitoleic
Even chain
14:00; 16:00
18:00
Swedish participants (Krachler 2008)
Erythrocyte membrane (-) (-) (+) palmitoleic
CHS (Mozzafarian 2010)
Circulating
(-)
Insulin resistance
EPIC-Norfolk (Patel 2010)
Erythrocyte membrane, circulating
NS (-) NS (+) palmitoleic
EPIC-Postdam (Kröger 2011)
Erythrocyte membrane
(-) (-)
NS myristic
NS palmitoleic
(+) stearic
MESA (Mozzafarian 2013)
Circulating
(-)
Insulin resistance
EPIC-Interact (Farouhi 2014)
Circulating
(-) (-) (+)
IRAS (Santoven 2014)
Circulating
(-)
Insulin sensitivity
Β-cell function
NS
CHS: Cardiovascular Health Study; MESA: Multi-Ethnic Study of Atherosclerosis
IRAS: Triethnic Multicenter Insulin Resistance Atherosclerosis Study
Circulating or erythrocyte membrane fatty acid composition and diabetes
incidence or glucose and insulin metabolism
Odd chain fatty acids
protect from diabetes
DAIRY PRODUCTS AND DIABETES
Widely distributed in many food
Endogenously
synthesized
Nurses' Health Study
Health Professionals Follow-Up Study
Astrup A.
A changing view on saturated fatty acids and dairy: from enemy to friend
Am J Clin Nutr. 2014;100(6):1407-8.
“The totality of evidence does not support that dairy SFAs increase the risk of
coronary artery disease or stroke or CVD mortality”
“In contrast, lean dairy is clearly associated with decreased risk of T2D, and this
effect is partly independent of any effect of body fat loss”
“There is no evidence left to support the existing public health advice to limit
consumption of dairy to prevent CVD and T2D”
DAIRY PRODUCTS AND DIABETES
What makes the yogurt different?
Is a marker of a healthy lifestyle?
Replace other unhealthy or healthy
foods when consumed?
Possible probiotic effects: changing
gut microbiota and body metabolism
• New active metabolites decreasing
insulin resistance.
• Insulin secretion induced by
menaquinones (Vit K2) synthetized by
the gut microbiota.
YOGURT AND HEALTH
In epidemiologic prospective studies usually yogurt consumption is
inversely related to body weight gain, obesity, metabolic syndrome,
diabetes and cardiovascular disease.
CONCLUSIONS
 A high intake of dairy products was associated with decreased risk of
T2D in several prospective studies.
 Frequent yogurt consumption was consistently associated to a lower
risk of diabetes and this association was independent of the fat
content.
 Substitutions of one serving of yogurt per day for one serving of
other “unhealthy” snacks or food alternatives per day was associated
with a reduced risk of T2D incidence.
 Several mechanisms have been suggested in order to explain these
associations, however more mechanistic studies are needed.
 Large clinical trials with an appropriate design are warranted to
definitively demonstrate that yogurt consumption protects from
diabetes.
UNANSWERED RESEARCH QUESTIONS
 If there is a cause-effect relationship between yogurt consumption
and type 2 diabetes, does dairy intake exert directs effects on insulin
sensitivity or are the effects on diabetes risk exerted through changes
in weight?
 Which components of dairy products exert the health effects?
proteins, sugars, minerals, vitamins or constituents associated with
fermentation?
 Are all the types of fat content on dairy products similar in terms of
conditioning the risk of disease?
 What is the net effect on cardiovascular disease of consuming
reduced fat dairy products with added sugar?
Baseline characteristics of the study population by tertile of total dairy intake.
Total dairy intake (g/day)a
Tertile 1 (n=1151) Tertile 2 (n=1152) Tertile 3 (n=1151) P
≤ 278 278-417 ≥ 417 valueb
Total dairy intake (g/day) 182 ± 73 343 ± 39 561 ± 119
Age (years) 66 ± 6 67 ± 6 67 ± 6 <0.001
Women, n (%) 506 (44) 744 (64) 891 (77) <0.001
BMI (kg/m2) 29.7 ± 3.5 29.89 ± 3.5 30.44 ± 3.7 <0.001
Overweight/obesity, n (%) 1080 (94) 1090 (95) 1110 (96) 0.014
Hypertension, n (%) 1039 (91) 1056 (92) 1044 (91) 0.64
Tobacco use <0.001
Never smoker, n (%) 560 (49) 754 (65) 842 (73)
Current smoker, n (%) 250 (22) 154 (13) 140 (12)
Former smoker, n (%) 341 (29) 244 (22) 169 (14)
Education level, n (%) <0.001
Primary education 789 (68) 895 (77) 932 (81)
Secondary education or academic/graduate 362 (32) 257 (22) 219 (19)
Leisure-time physical activity, (MET-min/day) 253.9 ± 232.6 222.4 ± 223.5 216.2 ± 206.1 <0.001
Medication use, n (%)
Antihypertensive agents 873 (75) 905 (78) 879 (76) 0.20
Statins or other hypolipidemic drugs 580 (50) 591 (51) 1148 (47) 0.07
Biochemistry, mg/dL
Fasting glucose 99.7 ± 15.5 97.3 ± 15.4 97.7 ± 16.8 0.002
Total cholesterol 218.7 ± 38.2 218.9 ± 37.5 222.7 ± 42.9 0.03
HDL-cholesterol 54.5 ± 14.2 56.2 ± 14.3 57.0 ± 13.8 <0.001
LDL-cholesterol 137.1 ± 33.7 137.1 ± 33.5 140.1 ± 40.4 0.10
Triglycerides 136.2 ± 78.9 129.1 ± 69.4 129.9 ± 68.6 0.049
Data are mean ± SD or number (%). aTertile cut-offs are based on energy-adjusted cumulative average dairy intake.
bP value for differences between tertiles by ANOVA.
cTotal energy-adjusted.
RESULTSRESEARCH DESIGN AND METHODSYOGURT AND DIABETES
HRs (95% CI) for type 2 diabetes according to specific dairy food intake in the
PREDIMED cohort
Dairy intake (g/d)a
Variable Tertile 1 Tertile 2 Tertile 3 P for trend
Total cheese intake 11(6-15) 25 (22-28) 40 (35-48)
Cases/person-years, n 95/4760 81/5893 94/4491
Multivariate model 1 1.00 ref. 0.99 (0.72-1.35) 1.15 (0.85-1.55) 0.34
Multivariate model 2 1.00 ref. 1.18 (0.84-1.66) 1.31 (0.94-1.83) 0.11
Multivariate model 3 1.00 ref. 1.39 (0.97-1.99) 1.38 (0.97-1.97) 0.10
Total fermented dairy intake 39 (22-55) 100 (85-118) 167 (147-213)
Cases/person-years 127/4553 65/4834 78/4454
Multivariate model 1 1.00 ref. 0.51 (0.37-0.69) 0.68 (0.50-0.92) 0.008
Multivariate model 2 1.00 ref. 0.54 (0.38-0.76) 0.63 (0.45-0.87) 0.003
Multivariate model 3 1.00 ref. 0.59 (0.41-0.84) 0.75 (0.52-1.07) 0.049
RESULTSRESEARCH DESIGN AND METHODSCHEESE, FERMENTED DAIRY AND DIABETES
Díaz-López et al, Eur J Nutr 2015

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Yogurt May Reduce Diabetes Risk According to Epidemiological Studies

  • 1. Jordi Salas-Salvadó Human Nutrition Unit Faculty of Medicine and Health Sciences of Reus Department of Biochemistry and Biotechnology Universitat Rovira i Virgili Yogurt and diabetes: Overview of the recent epidemiologic studies
  • 2. Conflict of interest regarding this presentation: • I am member of the Executive Committee of the Spanish Danone Institute. • The YINI programme has paid for travel and accommodation expenses for this presentation. YOGURT AND DIABETES
  • 3. DIABETES: THE GLOBAL BURDEN More than 387 million people in the word have diabetes. By 2030 is expected this will have risen to 592 million people.
  • 4. • The prevalence of T2DM is increasing in parallel to the obesity epidemics. • 80% of the T2DM individuals are living in developing countries. • T2DM is a potent risk factor for cardiovascular disease, blindness, renal failure, and lower limb amputation, decreasing quality of life. • T2DM is responsible of the 5 % of the total mortality. • In the next 10 years is expected that mortality by diabetes will increase by 50%. DIABETES: THE GLOBAL BURDEN
  • 5. Geneticbackground Physical inactivity Smoking Alcohol intake Unhealthy diet Overweight DIABETES RISK Lifestyleriskfactors RISK FACTORS FOR DIABETES
  • 6. Food groups and risk of type 2 DM Relative risks are a comparison of extreme categories, except for processed meat (per 50 g per day increase), unprocessed red meat and fi sh or seafood (per 100 g per day), white rice (per each serving per day), wholegrains (per three servings per day), sugar-sweetened beverages in European cohorts (per 336 g per day), and alcohol (22 g per day for men or 24 g per day for women with abstainers). Summary of meta-analyses of prospective cohort studies on food and beverage intake and type 2 diabetes Nuts (women) Tea Ley S et al., Lancet 2014
  • 7. DHA=docosahexaenoic acid. EPA=eicosapentaenoic acid. Relative risks are a comparison of extreme categories, except for DHA/EPA (per 250 mg per day increase) and alpha-linolenic acid (per 0.5 g per day). All nutrients and glycaemic variables were assessed from dietary intake, except vitamin D for which blood 25-hydroxyvitamin D was used. Summary of meta-analyses of prospective cohort studies of nutrient intake and glycaemic variables and type 2 diabetes Nutrients and risk of type 2 DM TRANS, SFA ?? Ley S et al., Lancet 2014
  • 8. OXIDATION INFLAMMATION Endothelial dysfunction Insulin resistance/secretion DIABETES Genetic background Low glycemic index Fiber MUFA / PUFA Magnesium Antioxidants (-) (-) (-) (-) (-) High glycemic index SFA TFA (+) (+) (+) MECHANISMS Salas-Salvadó et al, NMCD 2011 (-) Heme iron (+)
  • 9. DAIRY PRODUCTS OBESITY RISK CARDIOVASCULAR DISEASEDIABETES METABOLIC SYNDROME Minerals Vitamins Proteins calcium magnesium potassium phosphor zinc Vit. A Vit. D Vit. B2, B3, B6, B12 Vit. K2 Probiotic effects “fermented foods” OSTOPOROSIS CH “lactose” Fat
  • 10. DAIRY PRODUCTS Nutritional concerns: Rich in natural trans fatty acids Rich in saturated fatty acids Rich in salt (ie. cheese) Rich in added sugar (some yogurts and processed dairy foods) Irrational beliefs that lead to a decrease in consumption: “Humans are the unique animals that consume dairy products through the life”
  • 11. DAIRY PRODUCTS In the last years some guidelines recommend to consume low-fat dairy products or to limit them
  • 12. DAIRY PRODUCTS Astrup A. Yogurt and dairy product consumption to prevent cardiometabolic diseases: epidemiologic and experimental studies. Am J Clin Nutr. 2014. “The consumption of yogurt and other dairy products, in observational studies is associated with a reduced risk of weight gain and obesity as well as of CVD, and these findings are, in part, supported by randomized trials”. Recent published evidences support the idea that dairy products can be beneficial (or not harmful) for several chronic metabolic conditions and CVD.
  • 13. “four meta-analysis of prospective studies have shown a decrased risk of diabetes in those individuals with a higher consumption of dairy products”. DAIRY PRODUCTS AND DIABETES
  • 14. DAIRY PRODUCTS AND DIABETES 0.90 0.95 1.05 1.10 Total dairy (n=17) (per 200g/d) Low-fat dairy (n=13) (per 200g/d) High-fat dairy (n=13) (per 200g/d) Total milk (n=12) (per 200g/d) Low-fat milk (n=7) (per 200g/d) Cheese (n=13) (per 10g/d) Number populations Heterogenity test I2 P-vaue 66.4 <0.001 High-fat milk (n=9) (per 200g/d) 68.0 <0.001 51.6 0.016 57.4 0.007 71.6 0.002 84.1 <0.001 61.7 0.002 Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies Lieke Gijsbers et al, Am J Clin Nutr 2016 “This dose-response meta-analysis of observational studies suggest a posible role for dairy foods in the prevention of type 2 diabetes” 22 cohort studies 579,832 individuals and 43,118 T2D cases) RR
  • 15. DAIRY PRODUCTS Turner KM, Keogh JB, Clifton PM. Dairy consumption and insulin sensitivity: a systematic review of short- and long-term intervention studies. Nutr Metab Cardiovasc Dis. 2015 Jan;25(1):3-8. Conclusions (in adults): • 4 Showed a positive effect on insulin sensitivity as assessed by HOMA. • 1 Showed a negative effect • 5 Showed No effect. As the number of weight stable intervention studies is very limited and participant numbers small, these findings need to be confirmed by larger trials in order to conclusively determine any relationship between dairy intake and insulin sensitivity.
  • 16. YOGURT AND HEALTH In epidemiologic prospective studies usually yogurt consumption is inversely related to body weight gain, obesity, metabolic syndrome, diabetes and cardiovascular disease.
  • 17. “ONLY YOGURT HAS BEEN ASSOCIATED TO A LOWER RISK OF DIABETES” YOGURT AND DIABETES 17% lower risk of diabetes incidence in those consuming 3 or more servings of yogurt per week 41,436 men in the Health Professionals Follow-Up Study 67,138 women in the Nurses' Health Study 85,884 women in the Nurses' Health Study II 3,984,203 person-years of follow-up 15,156 incident T2D cases
  • 18. HRs for a serving yogurt consumption per day and type 2 diabetes YOGURT AND DIABETES The Australian Diabetes Obesity and Lifestyle Study The Whitehall II Prospective Study EPIC-Interact Study Women’s Health Initiative Japan Public Health Center–based Prospective Study Women’s Health Study Health Professional Follow-up Study Nurses Health Study I Nurses Health Study II Per 1 serving 18% lower risk
  • 19. Most of the studies were conducted in apparently healthy young or middle-aged individuals from different populations. No study has examined the association between dairy intake and risk of diabetes in elderly individuals at high cardiovascular risk. YOGURT AND DIABETES
  • 20. PREDIMED – Participants’ characteristics MeDiet + VOO (n=2487) MeDiet + Nuts (n=2396) Control (n=2349) Age, y (SD) 67 (6) 67 (6) 67 (6) Women (%) 57 54 58 Diabetes (%) 50 47 48 Hypertension (%) 82 82 84 Current smokers (%) 14 15 14 Dyslipidemia (%) 72 73 72 BMI, kg/m2 (SD) 30 (4) 30 (4) 30 (4) Waist circumf., cm (SD) 100 (10) 100 (10) 101 (11) MeDiet 14-p score (SD) 8.7 (2) 8.7 (2) 8.3 (2) Trial started October 2003, terminated July 2011 Mean follow-up for 5 years POPULATION STUDIED
  • 21. YOGURT AND DIABETES Prospective analysis - non-diabetic PREDIMED participants at baseline. 3,454 participants (1980 ♂, 2536 ♀). 270 incident cases of diabetes (median follow-up of 4.1 years).
  • 22. RESEARCH DESIGN AND METHODS Low-fat dairy (71%) Totaldairy(362g/d) Total milk (63%) Non-reduced fat dairy (29 %) Low-fat milk (85%) Total fermented dairy Dairy consumption was adjusted for total energy intake using the nutrient residual method and we calculated and used the cumulative average of dairy consumption. Semi-skim/skim milk and skim yogurt Whole milk, condensed milk, milkshake, whole yogurt, whipped cream, custard, ice cream and all types of cheeses Totaldairy(362g/d) Total yogurt (24%) Total cheese (11%) Whole milk (15%) Low-fat yogurt (70%) Whole fat yogurt (30%) All types of yogurt and cheese YOGURT AND DIABETES A validated semiquantitative 137- item FFQ Prospective analysis - non-diabetic PREDIMED participants at baseline. 3,454 participants (1980 ♂, 2536 ♀). 270 incident cases of diabetes (median follow-up of 4.1 years).
  • 23. HRs for type 2 diabetes according to tertiles of total, low-fat and whole-fat dairy food consumption in the PREDIMED cohort “Total and low-fat dairy consumption was inversely associated to a lower risk of diabetes” 3.454 non-diabetic participants 270 incident cases of diabetes (median follow-up of 4.1 years). Díaz-López et al, Eur J Nutr 2015 DAIRY AND DIABETES aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (interquartile range). Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake. Model 1: Adjusted for age, sex and BMI. Model 2: Additionally adjusted for dietary intervention group, physical activity, educational level, smoking, hypertension, dyslipidemia, and fasting glucose, HDL-cholesterol and triglyceride levels. Model 3: Additionally adjusted for cumulative average dietary intakes in energy-adjusted quintiles (vegetables, legumes, fruits, cereals, meat, fish, olive oil, nuts) and alcohol and alcohol squared in g/day. All models were stratified by recruitment center. Total dairy, median (g/day): T1: 200; T2: 342; T3: 539 Low-fat dairy, median (g/day): T1: 85; T2: 256; T3: 462 Whole-fat dairy, median (g/day): T1: 0; T2: 20; T3: 97
  • 24. HRs for type 2 diabetes according to tertiles of total, low-fat and whole-fat milk food consumption in the PREDIMED cohort “Milk was not significantly associated to the risk of diabetes” 3.454 non-diabetic participants 270 incident cases of diabetes (median follow-up of 4.1 years). Díaz-López et al, Eur J Nutr 2015 MILK AND DIABETES aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (interquartile R Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake. Total milk, median (g/day): T1:109; T2: 216; T3: 400 Low-fat milk, median (g/day): T1: 32; T2: 200; T3: 370 Whole-fat milk, median (g/day): T1: 0; T2: 6; T3: 41 Model 1: Adjusted for age, sex and BMI. Model 2: Additionally adjusted for dietary intervention group, physical activity, educational level, smoking, hypertension, dyslipidemia, and fasting glucose, HDL-cholesterol and triglyceride levels. Model 3: Additionally adjusted for cumulative average dietary intakes in energy-adjusted quintiles (vegetables, legumes, fruits, cereals, meat, fish, olive oil, nuts) and alcohol and alcohol squared in g/day. All models were stratified by recruitment center.
  • 25. HRs for type 2 diabetes according to tertiles of specific yogurt consumption in the PREDIMED cohort “Independently of the fat content, a higher consumption of yogurt has associated to a lower risk of diabetes” 3.454 non-diabetic participants 270 incident cases of diabetes (median follow-up of 4.1 years). Díaz-López et al, Eur J Nutr 2015 YOGURT AND DIABETES aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (Interquartil R). Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake. Total yogurt, median (g/day):T1: 13; T2: 71; T3: 128 Low-fat yogurt, median (g/day): T1: 3; T2: 44; T3: 120 Whole-fat yogurt, median (g/day): T1: 0; T2: 7; T3: 45 Model 1: Adjusted for age, sex and BMI. Model 2: Additionally adjusted for dietary intervention group, physical activity, educational level, smoking, hypertension, dyslipidemia, and fasting glucose, HDL-cholesterol and triglyceride levels. Model 3: Additionally adjusted for cumulative average dietary intakes in energy-adjusted quintiles (vegetables, legumes, fruits, cereals, meat, fish, olive oil, nuts) and alcohol and alcohol squared in g/day. All models were stratified by recruitment center.
  • 26. HRs for type 2 diabetes according to tertiles of specific yogurt consumption in the PREDIMED cohort “Independently of the fat content, a higher consumption of yogurt has associated to a lower risk of diabetes” 3.454 non-diabetic participants 270 incident cases of diabetes (median follow-up of 4.1 years). Díaz-López et al, Eur J Nutr 2015 YOGURT AND DIABETES aTertile cut-offs are based on energy-adjusted cumulative average dairy food intake and values are medians (interquartile range). Cox regression models were used to assess the RR (95% CI) of diabetes according to tertiles of dairy food intake. Total yogurt, median (g/day): T1: 13; T2: 71; T3: 128 Low-fat yogurt, median (g/day): T1: 3; T2: 44; T3: 120 Whole-fat yogurt, median (g/day): T1: 0; T2: 7; T3: 45 An average increment of one serving/day of the standard serving of yogurt (125 g) was associated with a 33% lower risk of T2D. Model 1: Adjusted for age, sex and BMI. Model 2: Additionally adjusted for dietary intervention group, physical activity, educational level, smoking, hypertension, dyslipidemia, and fasting glucose, HDL-cholesterol and triglyceride levels. Model 3: Additionally adjusted for cumulative average dietary intakes in energy-adjusted quintiles (vegetables, legumes, fruits, cereals, meat, fish, olive oil, nuts) and alcohol and alcohol squared in g/day. All models were stratified by recruitment center.
  • 27. HRs (95% CI) for type 2 diabetes associated with the substitution of one serving of yogurt and low-fat milk for one serving of other “unhealthy” alternative foods in the PREDIMED cohort Substituted foods Yogurt (125 g) Low-fat milk (200 mL) Dairy desserts (100g)a 0.58 (0.29-1.18) 0.71 (0.35-1.41) Biscuits and chocolate confectionary (50g) 0.60 (0.38-0.94) 0.69 (0.47-1.03) Whole-grain biscuits and homemade pastries (50 g) 0.55 (0.32-0.96) 0.63 (0.38-1.05) aPetit Suisse cheese or custard or ice cream. The servings are based on energy-adjusted cumulative average food intake. Values are given as HR (95% CI) from Cox regression models adjusted for age, sex, BMI, dietary intervention, physical activity, educational level, smoking, hypertension, or antihypertensive use (yes/no) and dyslipidemia (yes/no), and fasting glucose, HDL-cholesterol and triglycerides levels. All models were stratified by recruitment center. YOGURT SUBSTITUTION AND DIABETES Díaz-López et al, Eur J Nutr 2015
  • 28. In this prospective study conducted on elderly subjects at high cardiovascular risk, we report for the first time that:  a high intake of dairy products was associated with decreased risk of T2D.  the intake of low-fat dairy products, mainly milk and both low-fat and non reduced-fat yogurt, were the main contributors to this association.  substitutions of one serving of yogurt per day for one serving of a combination of biscuits and chocolate, or whole-grain biscuits and homemade pastries per day was associated with a reduced risk of T2D incidence. YOGURT AND DIABETES
  • 29. Cox regression models adjusted for intervention group, sex, age, physical activity and BMI and baseline current smoker, and hypoglycemic, hypolipidemic, antihypertensive and insulin treatment, cumulative average consumption of vegetables, fruit, legumes, cereals, fish, red meat, alcohol, biscuits, olive oil and nuts. Independent of the fat content, Yogurt consumption was inversely associated with the incidence of MetS and its components Yogurt consumption and incidence of MetS or its components: PREDIMED study 1.868 participants without MetS at baseline; 930 incident cases of MetS (mean follow-up: 3.2 y) P for trend=0.230 P for trend=0.004 P for trend=0.689 P for trend=0.348 P for trend=0.183 P for trend=0.048 P for trend=0.005 P for trend=0.001 P for trend<0.001 P for trend<0.001 P for trend=0.095 P for trend=0.126 P for trend=0.864 P for trend=0.011 P for trend=0.001 Central obesity High fasting plasma glucose High blood pressure Low HDL-c High triglicerides Metabolic Syndrome P for trend=0.144 TOTAL YOGURT Central obesity High fasting plasma glucose High blood pressure Low HDL-c High triglicerides Metabolic Syndrome P for trend=0.003 WHOLE-FAT YOGURT Central obesity High fasting plasma glucose High blood pressure Low HDL-c High triglicerides Metabolic Syndrome P for trend=0.004 LOW-FAT YOGURT 0.5 1.0 2.0 HAZARD RATIO (95% CI) Hazard ratios (95% CI) of metabolic syndrome and its components across energy- adjusted tertiles of yogurt consumption (Tertile 3 vs Tertile 1). ↓23% ↓22% ↓27% “Low-fat dairy products were inversely associated with MetS incidence” “The consumption of cheese was associated with an increased risk of MetS incidence” YOGURT AND METABOLIC SYNDROME Babio et al, 2015
  • 30. YOGURT AND DIABETES 0.90 0.95 1.05 1.10 Total dairy (n=17) (per 200g/d) Low-fat dairy (n=13) (per 200g/d) High-fat dairy (n=13) (per 200g/d) Total milk (n=12) (per 200g/d) Low-fat milk (n=7) (per 200g/d) Cheese (n=13) (per 10g/d) Number populations Heterogenity test I2 P-vaue 66.4 <0.001 High-fat milk (n=9) (per 200g/d) 68.0 <0.001 51.6 0.016 57.4 0.007 71.6 0.002 84.1 <0.001 61.7 0.002 Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies Lieke Gijsbers et al, Am J Clin Nutr 2016 Yogurt (n=12) (per 10g/d) 61.7 0.002 RR “This dose-response meta-analysis of observational studies suggest a posible role for dairy foods, PARTICULARLY YOGURT in the prevention of T2D
  • 31. YOGURT AND DIABETES What are the mechanisms explaining the beneficial metabolic effects on diabetes prevention of dairy products and yogurt?
  • 32. DAIRY, YOGURT AND DIABETES - mechanisms First hypothesis: The effect of dairy products and yogurt on diabetes prevention may be explained by their beneficial effects on satiety, reducing adiposity. Effects related to the Ca2+ metabolism •An increase in intracellular Ca2+: •Increases lipogenesis and inhibits lipolysis. •Calcium present in dairy inhibits fatty acid absorption. Effects related to the protein or bioactive peptides in dairy products •Inducing satiety. The probiotic effects of yogurt •Inducing satiety and changing metabolic pathways implicated in lipogenesis and fat deposition.
  • 33. 120,877 U.S. women and men Free of chronic diseases and not obese at baseline. Relationships between changes in food and beverage consumption and weight changes every 4 years, according to study cohort. Mozaffarian et al, N Engl J Med 2011 YOGUR AND OBESITY
  • 34. YOGURT AND HEALTH Second hypothesis: The effect of dairy products and yogurt on diabetes prevention may be explained by other mechanisms increasing insulin sensitivity or decreasing pancreatic secretion. Effects related to the Ca2+ metabolism •An increase in intracellular Ca2+ favors insulin secretion and glucose uptake. Effects related to bioactive peptides in yogurt •Intestinal hormone activation inducing insulin secretion. •Whey protein consumed with a CH-meal increased insulin, and the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Beneficial effects of other components in yogurt •Minerals (phosphor, magnesium, potassium) and vitamins (A, D, B2, B6, B12) and dairy fat. Effects related to the fat content
  • 35. Ericson U. Am J Clin Nutr 2015 Total intake of high-fat dairy products was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.77; CI 0.68- 0.87; P-trend<0.001). Most robust inverse associations were seen for intakes of high-fat fermented milk (P-trend<0.01) and for cheese in women (P-trend=0.02). Intakes of saturated fatty acids with 4–10 carbons, lauric acid (12:0), and myristic acid (14:0) were associated with decreased risk (P-trend<0.01). Conclusions: Decreased T2D risk at high intake of high- but not of low-fat dairy products suggests that dairy fat partly could have contributed to previously observed protective associations between dairy intake and T2D. DAIRY PRODUCTS AND DIABETES IS FAT FROM DAIRY UNHEALTHY AND INCREASES THE RISK OF DIABETES?
  • 36. Odd chain 15:00 Pentadecanoic Odd chain 17:00 Heptadecanoic Trans 16:1n-7 Transpalmitoleic Even chain 14:00; 16:00 18:00 Swedish participants (Krachler 2008) Erythrocyte membrane (-) (-) (+) palmitoleic CHS (Mozzafarian 2010) Circulating (-) Insulin resistance EPIC-Norfolk (Patel 2010) Erythrocyte membrane, circulating NS (-) NS (+) palmitoleic EPIC-Postdam (Kröger 2011) Erythrocyte membrane (-) (-) NS myristic NS palmitoleic (+) stearic MESA (Mozzafarian 2013) Circulating (-) Insulin resistance EPIC-Interact (Farouhi 2014) Circulating (-) (-) (+) IRAS (Santoven 2014) Circulating (-) Insulin sensitivity Β-cell function NS CHS: Cardiovascular Health Study; MESA: Multi-Ethnic Study of Atherosclerosis IRAS: Triethnic Multicenter Insulin Resistance Atherosclerosis Study Circulating or erythrocyte membrane fatty acid composition and diabetes incidence or glucose and insulin metabolism Odd chain fatty acids protect from diabetes DAIRY PRODUCTS AND DIABETES Widely distributed in many food Endogenously synthesized Nurses' Health Study Health Professionals Follow-Up Study
  • 37. Astrup A. A changing view on saturated fatty acids and dairy: from enemy to friend Am J Clin Nutr. 2014;100(6):1407-8. “The totality of evidence does not support that dairy SFAs increase the risk of coronary artery disease or stroke or CVD mortality” “In contrast, lean dairy is clearly associated with decreased risk of T2D, and this effect is partly independent of any effect of body fat loss” “There is no evidence left to support the existing public health advice to limit consumption of dairy to prevent CVD and T2D” DAIRY PRODUCTS AND DIABETES
  • 38. What makes the yogurt different? Is a marker of a healthy lifestyle? Replace other unhealthy or healthy foods when consumed? Possible probiotic effects: changing gut microbiota and body metabolism • New active metabolites decreasing insulin resistance. • Insulin secretion induced by menaquinones (Vit K2) synthetized by the gut microbiota. YOGURT AND HEALTH In epidemiologic prospective studies usually yogurt consumption is inversely related to body weight gain, obesity, metabolic syndrome, diabetes and cardiovascular disease.
  • 39. CONCLUSIONS  A high intake of dairy products was associated with decreased risk of T2D in several prospective studies.  Frequent yogurt consumption was consistently associated to a lower risk of diabetes and this association was independent of the fat content.  Substitutions of one serving of yogurt per day for one serving of other “unhealthy” snacks or food alternatives per day was associated with a reduced risk of T2D incidence.  Several mechanisms have been suggested in order to explain these associations, however more mechanistic studies are needed.  Large clinical trials with an appropriate design are warranted to definitively demonstrate that yogurt consumption protects from diabetes.
  • 40. UNANSWERED RESEARCH QUESTIONS  If there is a cause-effect relationship between yogurt consumption and type 2 diabetes, does dairy intake exert directs effects on insulin sensitivity or are the effects on diabetes risk exerted through changes in weight?  Which components of dairy products exert the health effects? proteins, sugars, minerals, vitamins or constituents associated with fermentation?  Are all the types of fat content on dairy products similar in terms of conditioning the risk of disease?  What is the net effect on cardiovascular disease of consuming reduced fat dairy products with added sugar?
  • 41.
  • 42.
  • 43. Baseline characteristics of the study population by tertile of total dairy intake. Total dairy intake (g/day)a Tertile 1 (n=1151) Tertile 2 (n=1152) Tertile 3 (n=1151) P ≤ 278 278-417 ≥ 417 valueb Total dairy intake (g/day) 182 ± 73 343 ± 39 561 ± 119 Age (years) 66 ± 6 67 ± 6 67 ± 6 <0.001 Women, n (%) 506 (44) 744 (64) 891 (77) <0.001 BMI (kg/m2) 29.7 ± 3.5 29.89 ± 3.5 30.44 ± 3.7 <0.001 Overweight/obesity, n (%) 1080 (94) 1090 (95) 1110 (96) 0.014 Hypertension, n (%) 1039 (91) 1056 (92) 1044 (91) 0.64 Tobacco use <0.001 Never smoker, n (%) 560 (49) 754 (65) 842 (73) Current smoker, n (%) 250 (22) 154 (13) 140 (12) Former smoker, n (%) 341 (29) 244 (22) 169 (14) Education level, n (%) <0.001 Primary education 789 (68) 895 (77) 932 (81) Secondary education or academic/graduate 362 (32) 257 (22) 219 (19) Leisure-time physical activity, (MET-min/day) 253.9 ± 232.6 222.4 ± 223.5 216.2 ± 206.1 <0.001 Medication use, n (%) Antihypertensive agents 873 (75) 905 (78) 879 (76) 0.20 Statins or other hypolipidemic drugs 580 (50) 591 (51) 1148 (47) 0.07 Biochemistry, mg/dL Fasting glucose 99.7 ± 15.5 97.3 ± 15.4 97.7 ± 16.8 0.002 Total cholesterol 218.7 ± 38.2 218.9 ± 37.5 222.7 ± 42.9 0.03 HDL-cholesterol 54.5 ± 14.2 56.2 ± 14.3 57.0 ± 13.8 <0.001 LDL-cholesterol 137.1 ± 33.7 137.1 ± 33.5 140.1 ± 40.4 0.10 Triglycerides 136.2 ± 78.9 129.1 ± 69.4 129.9 ± 68.6 0.049 Data are mean ± SD or number (%). aTertile cut-offs are based on energy-adjusted cumulative average dairy intake. bP value for differences between tertiles by ANOVA. cTotal energy-adjusted. RESULTSRESEARCH DESIGN AND METHODSYOGURT AND DIABETES
  • 44. HRs (95% CI) for type 2 diabetes according to specific dairy food intake in the PREDIMED cohort Dairy intake (g/d)a Variable Tertile 1 Tertile 2 Tertile 3 P for trend Total cheese intake 11(6-15) 25 (22-28) 40 (35-48) Cases/person-years, n 95/4760 81/5893 94/4491 Multivariate model 1 1.00 ref. 0.99 (0.72-1.35) 1.15 (0.85-1.55) 0.34 Multivariate model 2 1.00 ref. 1.18 (0.84-1.66) 1.31 (0.94-1.83) 0.11 Multivariate model 3 1.00 ref. 1.39 (0.97-1.99) 1.38 (0.97-1.97) 0.10 Total fermented dairy intake 39 (22-55) 100 (85-118) 167 (147-213) Cases/person-years 127/4553 65/4834 78/4454 Multivariate model 1 1.00 ref. 0.51 (0.37-0.69) 0.68 (0.50-0.92) 0.008 Multivariate model 2 1.00 ref. 0.54 (0.38-0.76) 0.63 (0.45-0.87) 0.003 Multivariate model 3 1.00 ref. 0.59 (0.41-0.84) 0.75 (0.52-1.07) 0.049 RESULTSRESEARCH DESIGN AND METHODSCHEESE, FERMENTED DAIRY AND DIABETES Díaz-López et al, Eur J Nutr 2015