Moderate coffee consumption of 3-4 cups per day is associated with a reduced risk of type 2 diabetes, cardiovascular disease such as heart disease and stroke, and overall mortality. Higher coffee intake up to about 5 cups daily shows benefits, but intake over 5 cups may increase blood pressure levels and risk of heart failure. Certain components in coffee such as chlorogenic acid and trigonelline help reduce blood glucose levels and inflammation.

1. Significance of clinical parameters
found so far
regarding coffee and diabetes
7th WCPD‐2012
Pilar Riobó MD, PhD
Endocrinology & Nutrition
Madrid
www.doctorariobo.com

2.  Coffee consumption has been linked to poorer
health habits, such as smoking and physical
inactivity, but…
 it also has been associated with a lower risk of
type 2 diabetes mellitus in prospective studies

3. Data from 18 studies with
information on
457 922 participants showed…
...an inverse relationship between coffee
consumption and subsequent risk of DM
Every additional cup of coffee consumed
in a day was associated with a 7%
reduction in the excess risk of diabetes

4. Acute Intake of caffeine impairs glucose metabolism
caffeine stimulates the release of adrenaline, an inhibitor of insulin
activity, and increases blood pressure and serum homocysteine.

5. Certain components of coffee, such as CGA
and other phenolic compounds, magnesium,
and trigonelline, improve glucose metabolism
and reduce inflammation and endothelial
dysfunction.
In the long term, the harmful metabolic and
cardiovascular effects of caffeine would be
offset by the beneficial effects of these other
components

6. PRCT, 15 volunteers, glucose and insulin after OGTT
 12 g decaff coffee,
 1 g chlorogenic acid,
 500 mg trigonelline,
 placebo
CGA and trigonelline reduced early glucose and insulin
responses, and contribute to the putative beneficial
effect of coffee

7. Effect on weight
 Prospective study of 18417 men & 39740 women.
 Caffeine intake was assessed every 2–4 y.
Caffeine intake was associated with a smaller
weight gain over 12 y of follow-up,
differences were small (but important?)
 −0.43 kg (95% IC: −0.17, −0.69) in men
 −0.35 kg (95% IC: −0.20, −0.62) in women.
7

8. Effect on weight
PRCT to evaluate the efficacy
and safety of a green coffee
bean extract (56% CGA)
in overweight subjects added to
hypocaloric diet
Significant reductions were
observed:
body weight (−8.04 ± 2.31 kg),
BMI (−2.92 ± 0.85 kg/m2)
percent body fat (−4.44% ± 2.00%)
Vinson JA, Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy
and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7.

9.  cross-sectional survey enrolled 1514 men and 1528
women
 Compared with coffee nondrinkers, (all P<0.05)
 50% higher interleukin 6 (IL-6),
 30% higher C-reactive protein (CRP),
 12% higher serum amyloid-A (SAA),
 28% higher tumor necrosis factor (TNF-) concentrations
Moderate-to-highcoffee consumption is
associated witn increased inflammation
process
(unfiltered coffee was included)

10. Effect on inflammation & endothelial dysfunction
cross-sectional study of 730 healthy women and 663 women with type 2 diabetes from the NHS I
In women with 2DM, coffee was associated with
 lower plasma concentrations of E-selectin: a soluble vascular
adhesion molecule, overexpressed when the endothelium
encounters inflammatory stimuli, found to predict CVD)
 Lower C-reactive protein (adjusted percentage change 10.2%)
Lopez García E. Coffee consumption and markers of inflammation and endothelial
dysfunction in healthy and diabetic women. Am J Clin Nutr.2006;84(4):888-93.

11. An intervention trial in coffee
drinkers to investigate
the antiinflammatory effect
Changes were observed for:
8-isoprostane (-216%)
interleukin-18 (-8%) ,
adiponectin (+6%)
total cholesterol(+ 12%)
HDL cholesterol, (+7%)
apolipoprotein A-I (+4%)
No effects on fasting glucose,
fasting insulin, and HOMA-IR, IL-
6, leptin, LDL-C
Coffee-mediated effects were
more pronounced in
insulin-resistant individuals 8 cups compared
Kempf K et al. Influence of insulin resistance on
with 0 cups
the effect of coffee consumption on coffee/d
subclinical inflammation and lipids
Am J Clin Nutr 2010;91:950-957

12. Effect on CRP
Japanese women, (N= 459), aged 23-83 years
Clinical data included age, BMI, BP, HbA1c, serum
hsCRP) and lifestyle habits
Significantly lower levels of hsCRP were observed in
the group who drank >1 cup/day
so confirming the benefits of coffee
consumption, on serum hsCRP in Japanese
women, following similarly to other ethnic data.
Kotani K. The relationship between usual coffee consumption and serum C-reactive protein
level in a Japanese female population. Clin Chem Lab Med. 2008;46(10):1434-7.

13. Effect on adiponectin
982 diabetic and 1,058 nondiabetic women without CVD from NHS
Women with and without diabetes who drank4 cups of
coffee/day had higher adiponectin concentrations
Inverse associations of coffee consumption with
inflammatory markers, C-reactive protein, & TNF
Williams K. Coffee Consumption Is Associated With Higher Plasma Adiponectin Concentrations
in Women With or Without Type 2 Diabetes. Diabetes Care 31:504–507, 2008

14. Effect of coffee on insulin sensitivity
Singapore Prospective study-2 (SP2), 5163 participants,
Inverse association between coffee and HOMA-IR
(- 8.8% for ≥ 3 cups/day versus never; P = 0.007)
Rebelllo Coffee and tea consumption in relation to inflammation and basalglucose metabolism in
a multi-ethnic Asian population: a cross-sectionalstudy. Nutr . 2011;10:61.

15. Consumption of
unfiltered coffee
increases serum levels of
total & LDL cholesterol
Increases in serum lipids
were greater in studies
of patients with
hyperlipidemia
Jee SH. Am J Epidemiol 2001;153:353

16. Effect of coffee consumption on serum lipids
Metanalysis;12 studies , 1017 subjects
Drinking coffee for 45 days was associated with increase of
 total -C 8.1 mg/dl (95% CI: 4.5, 11.6; P<0.001)
 LDL –C 5.4 mg/dl (95% CI: 1.4, 9.5; P=0.009)
 TG 12.6 mg/dl (95% CI: 3.5, 12.6; P=0.007)
The increase was greater in trials using unfiltered coffee
Those who had hyperlipidemia were more sensitive to
the cholesterol-raising effect of coffee
Cai L et al. The effect of coffee consumption on serum lipids: a meta-analysis of
randomized controlled trials. Eur J Clin Nutr. 2012 ;66(8):872-7

17. No effect on LDL levels
Phenolic acids are incorporated into LDL
Ex vivo oxidation of LDL was significantly reduced
Effect of coffee consumption on LDL Effect of coffee on the susceptibility
of LDL to oxidative modification
Natella F.. Am J Clin Nutr 2007

18. Coffee & Metabolic Syndrome
Cross sectional study, 554 adults
Consumption of coffee and green tea was assessed
Metabolic syndrome was diagnosed using NCEP ATP III
Greater coffee consumption was associated with
- lower prevalence of Met-S
- lower OR for high serum triglycerides
No significant correlation was found between coffee
consumption and either waist circumference or BMI
Takami H. Journal of Epidemiology 2012

19. Coffee & Metabolic Syndrome
The Amsterdam Growth and Health Longitudinal Study
Observational longitudinal (1976) with 450 children
13.1 ± 0.8 y.o at baseline; 30-year follow-up
At 42 years, Met-S was measured in 344 subjects & coffee
consumption was measured at 5 ages
Moderate and high (>2 cups/day) coffee
consumption was associated with lower HDL in
women.
For men, coffee consumption was not associated
with any of the components of the Met-S
Balk L. Eur J Epidemiol.. 2009;24(4):203-9.

20. Blood pressure response to chronic intake
of coffee and caffeine: a meta-analysis
A rise of 2.04 mmHg in SBP and 0.73 mmHg in DBP
When coffee trials and caffeine trials were analysed
separately, BP elevations appeared to be larger for caffeine
than for coffee
caffeine:systolic: 4.16 mmHg ; diastolic: 2.41 mmHg
coffee: systolic: 1.22 mmHg; diastolic: 0.49 mmHg.
Although regular caffeine intake increases BP, when
ingested through coffee, the effect of caffeine is
smaller
Noordzij M J Hypertens.2005;23(5):921

21. Habitual coffee consumption and risk of hypertension
systematic review:6 prospective studies
follow-up : 6.4 to 33.0 y. Compared with the lowest
consumption ,RRs for hypertension
were 1.09 for 1–3 cups/d, 1.07 for
3–5 cups/d, and 1.08 for 5 cups/d
Habitual coffee consumption
of >3 cups/d was not
associated with an increased
risk of hypertension.
A slightly elevated risk (9%)
appeared to be associated
with consumption of 1-3
cups/d
Zhang Z. Am J Clin Nutr 2011

22. Dose-response meta-analysis of cohort study results of coffee consumption and
hypertension risk (shown by first author and year of publication).
Zhang Z et al. Am J Clin Nutr 2011;93:1212-1219
©2011 by American Society for Nutrition

23. Meta-analysis of the acute effects of caffeine on SBP and DBP
in hypertensive individuals, by time after caffeine intake.
Caffeine raises BP for ≥3 h after ingestion in hypertensives
Mesas et al. Am J Clin Nutr 2011;94:1113–26.

24. Acute effects of caffeine on BP in
hypertensive individuals
Administration of 200–300 mg caffeine produced a mean
increase of :
8.1 mm Hg in SBP and
5.7 mm Hg in DBP, and lasted 3 h
Mesas A E et al. Am J Clin Nutr 2011;94:1113-1126

25. Long-term effects of coffee consumption
on BP in hypertensive subjects
 No increase in BP was observed after coffee
(compared with a caffeine-free beverage).
 No association between habitual coffee
consumption and a higher risk of CVD.
 No evidence to justify avoidance of coffee
consumption in well-controlled hypertensives
Nonetheless, more studies are needed about
influence of coffee on the degree of BP control
and its possible variation with antihypertensive
drugs
Mesas A E et al. Am J Clin Nutr 2011;94:1113-1126

26. Coffee and CVD
 1354 subjects, Framingham Heart Study, 10 years
of follow-up
 210 deaths from CVD
 118 from CHD.
 Coffee consumption was associated with
lower risk of CHD mortality in older subjects
without hypertension.
Greenberg JA. Caffeinated coffee consumption, cardiovascular disease, and heart
valve disease in the elderly . Am J Cardiol 2008;102(11):1502

27. Coffee and risk of CVD in diabetics
 prospective cohort (NHS) study including 7,170 diabetic
women with T2D, but free of CVD
 Coffee consumption was assessed every 2 to 4/y
 658 incident cardiovascular events (434 CHD and 224 stroke)
 RRs for CVD & for all-cause mortality were:
 ≥ 4 cups/day 0.76 & 0.80
 ≥ 2 cups/day decaffeinated coffee , 0.96 & 0.76
 higher decaffeinated coffee consumption was associated
with lower HbA1c levels (more health-concerned?)
habitual coffee consumption is not associated
with increased risk for CVD or premature mortality
among diabetic women
Zhang W. Diabetologia. 2009 May ; 52(5): 810–817

28. Is coffee detrimental for persons with CVD?
 NHS: Cumulative consumption was calculated with all
available FFQs from the diagnosis of CVD to the end of the
follow-up in 2004
Coffee intake was not associated with
total or CVD mortality.
E. Lopez. Am J Clin Nutr. 2011;94(1): 218–224.

29. Post-AMI patients can drink coffee?
No association between moderate coffee
intake and cardiovascular events was observed
in post–MI patients after 3.5 years follow-up
Silleta MG. Circulation. 2007;116:2944-2951

30. Coffee and Risk of heart failure
Over 9 years of follow-up,
784 men experienced a HF
event.
Compared to men who drank
≤ 1 cup of coffee per day,
RR were:
0.87 for 2 cups/day,
0.89 for 3 cups/day,
0.89 for 4 cups/day,
0.89 (for ≥ 5 cups/day
(p for trend in RR = 0.61).
This study does not support the hypothesis that high coffee
consumption is associated with increased rates of HF
Ahmed H. Coffee Consumption and Risk of Heart Failure in Men: an Analysis from the Cohort of Swedish Men
Am Heart J. 2009; 158(4): 667–672

31. Coffee consumption and risk of heart failure:
Systematic review and a dose-response meta-analysis
Five prospective studies , including 6522 heart failure events
Moderate coffee consumption is
inversely associated with risk
of heart failure,
with a J-shaped relationship
The strongest inverse
association was seen for 4
servings/day and a potentially
higher risk at higher levels of
consumption. Mostofsky E. Circ Heart Fail 2012;5(4):401-5.

32. Coffee consumption and risk of stroke
a dose-response meta-analysis of prospective studies
 11 prospective studies, with 10,003 cases of stroke and
479,689 participants
 Compared with no coffee consumption, the relative risks
of stroke were:
 0.86 (95% CI: 0.78, 0.94) for 2 cups of coffee per day,
 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day,
 0.87 (95% CI: 0.77, 0.97) for 6 cups/day,
 0.93 (95% CI: 0.79, 1.08) for 8 cups/day.
 Moderate coffee consumption may be weakly
inversely associated with risk of stroke.
Larsson SC .Am J Epidemiol 2011;174(9):993

33. Risk of AMI, Stroke or Cancer?
 Data from 40000 participants in the (EPIC)–Germany
study. Intake was assessed by FFQ
 During 8.9 y of follow-up,
 1432 cases of T2D, 394 of AMI, 310 of stroke,, 1801 of cancer.
 Neither caffeinated, nor decaff was associated with
the overall risk of chronic diseases
 (HR: 0.94; 95% CI: 0.84, 1.05, caff)(HR: 1.05; 95% CI: 0.84, 1.31, decaff)
 Lower risk of T2D associated with coffee and decaff
 (HR: 0.77; 95% CI: 0.63, 0.94; P-trend 0.009) (HR: 0.70; 95% CI:
0.46, 1.06; P-trend: 0.043)
Floegel A. Coffee consumption and risk of chronic disease in the European Prospective
Investigation into Cancer and Nutrition (EPIC)–German study Am J Clin Nutr 2012 95: 901

34. Coffee and cancer risk
Coffee consumption is
inversely associated with
the risk of
bladder, breast, buccal
cavity and
pharynx, colorectum, en
dometrium, esophagus,
hepatocellular, leukemia
, pancreas, and prostate
cancers

35. Coffee and mortality
2 large cohorts : NHS and HPFS followed over 2 decades.
High coffee
consumption was not
related to increased
mortality and may
even be associated
with lower total and
cardiovascular
mortality.
The inverse association was
mainly due to a reduced risk
for CVD mortality and was
independent of caffeine
E. Lopez Garcia. Ann Intern Med. 2008;148:904

36. Coffee and total & cause-specific mortality
Health–AARP Diet & Health Study (229,119 men & 173,141 women)
dose-dependent inverse association
between coffee drinking and total
mortality.
 Men who drank 6 or more cups of coffee per
day had a 10% lower risk of death, whereas
women had a 15% lower risk.
 Similar associations were observed for
caffeinated or decaff
 Inverse associations persisted among
diabetics
Freedman ND. N Engl J Med. 2012;366(20):1891

37. Subgroup Analysis of Associations between the Consumption of 4
or More Cups of Coffee per Day and Total Mortality.
Freedman ND. Association of coffee drinking with total and cause-specific mortality. N Engl J Med. 2012;366:1891

38. What about subjects With Impaired Glucose Tolerance?
The Rancho Bernardo Study
Current or past coffee drinkers who did not have diabetes at baseline
had a 60% reduced risk of type 2 diabetes during the next 8 years
The 317 participants with impaired glucose at baseline were
similarly protected against diabetes.
Smith B. Does coffee consumption reduce the risk of type 2 diabetes in
individuals with impaired glucose? Diabetes Care. 2006 ;29(11):2385

39. Mechanisms of action of coffee and its constituents
responsible for reduce the risk of the DM2
Pimentel G. Does long-term coffee intake reduce type 2 diabetes mellitus risk? Diabetol Metab Syndr. 2009; 1: 6.

40. SHBG
may it account for the potential protective effect?
Strong inverse association between SHBG levels and T2D risk
Women’s Health Study
follow-up of 10 years (n 700)
 Coffee intake was
positively associated
with plasma SHBG.
 OR of DM2 for
women consuming 4
cups/day of coffee
was 0.47
GotoA. Coffee and Caffeine Consumption in Relation to Sex Hormone–Binding Globulin and
Risk of Type 2 Diabetes in Postmenopausal Women. Diabetes 60: 269–275, 2011

41. Effect on gastrointestinal peptides
Higher GLP-1 production after the intake
of chlorogenic acid, (the chief polyphenol
on coffee) or coffee
Johnston KL, Clifford MN, Morgan LM: Coffee acutely modifies gastrointestinal
hormone secretion and glucose tolerance: glycemic effects of chlorogenic & caffeine.
Am J Clin Nutr 2003, 78:728
McCarty MF: A chlorogenic acid-induced increase in GLP-1 production may
mediate the impact of heavy coffee consumption on diabetes risk. Med Hypotheses 2005,
64(4):848-853.

42. Fetuin A
hepatic secretory protein that binds the insulin receptor in muscle and fat
and inhibits insulin action, in vitro. In cross-sectional studies in
humans, higher fetuin-A was associated with insulin resistance
Adiponectin
8-week PRCT
Adiponectin and IL-6
levels increased for the
caffeinated coffee
group as compared
with the group
receiving no coffee.
Ix JH. Fetuin-A and incident diabetes mellitus in older persons. JAMA.2008;300(2):182–188.
Wedick et al.: Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: a
randomized controlled trial. Nutrition Journal 2011 10:93.

44. Take home message
 Coffee consumption increases insulin sensitivity
 It may actually decrease an individual’s risk for T2D
 Is associated with 20% higher adiponectin
 Lower levels of inflammatory markers and fetuin-A
 Lower levels of markers of liver damage
 Does not result in worsening of diabetic control, and it does
not increase the risk for diabetic complications
 Does not increase cancer risk: It is inversely associated
with the risk of bladder, breast, buccal cavity and pharynx,
colorectum, endometrium, esophagus, hepatocellular,
leukemia, pancreas, and prostate cancers

45. Take home message
 Coffee consumption does not cause hypertension.
 Coffee consumption causes only minor increases in BP in
individuals who do not drink coffee regularly; and this
increase disappears when coffee is consumed regularly.
 Coffee consumption does not cause CVD
 Coffee consumption does not cause MI in patients CVD;
 Coffee is safe in post AMI patients
 Moderate coffee consumption is inversely
associated with risk of heart failure, with a J-
shaped relationship
 Moderate coffee consumption may be weakly inversely
associated with risk of stroke

46. Take home message
 Coffee does not increase the risk of chronic disease
 Exists a dose-dependent inverse association between
coffee drinking and total mortality in general population,
and also in diabetics
 Coffee CC is associated with a significant reduction in risk
of fibrosis among NASH patients.
 Caffeinated coffee consumption can cause mild sleep
disturbances, but habitual coffee consumers usually
develop tolerance
 Although more research on the effect of coffee in health is
yet needed, current information suggests that….coffee
is not as bad as previously considered¡¡¡¡

47. “It is proper at the present
time to devote time not alone
to treatment but still more to
prevention of diabetes. The
results may not be so striking
or immediate, but they are
sure to come and to be
Elliot P. Joslin, 1921 important.”

48. Thank you for your attention
“It is proper at the present
time to devote time not alone
to treatment but still more to
prevention of diabetes. The
results may not be so striking
or immediate, but they are
sure to come and to be
Elliot P. Joslin, 1921 important.”

51. Fetuin-A
 a biomarker for inflammation and liver
function, is a glycoprotein secreted by the
hepatocytes with effects on insulin signaling via
inhibition of the insulin receptor tyrosine kinase
in both liver and skeletal tissue .
 Higher fetuin-A levels have been associated with
insulin resistance and a higher risk of T2DM
 Mori K. Association of serum fetuin-A with insulin resistance in type 2

52. In cross-sectional studies, coffee
consumption has been associated with:
 higher adiponectin concentrations,
 Williams CJ. Coffee consumption is associated with higher plasma adiponectin
concentrations in women with or without type 2 diabetes: a prospective cohort
study. Diabetes Care. 2008;31(3):504–507.
 lower concentrations of inflammatory
markers
 Kempf K. Effects of coffee consumption on subclinical inflammation and other risk
factors for type 2 diabetes: a clinical trial. Am J Clin Nutr. pp. 950–957.
 and lower levels of markers of liver
damage.
 Homan DJ. Coffee: good, bad, or just fun? A critical review of coffee's effects on liver
enzymes. Nutr Rev. 2006;64(1):43–46.

53. Plasma concentrations of total GLP-
1, intact GLP-1 (B) and GIP (C) before
and throughout an OGTT, following
ingestion of chlorogenic
acid, decaffeinated coffee, trigonelline
and placebo in 15 healthy overweight
men
Decaffeinated coffee slightly
increased total
GLP-1 concentration 30
minutes after ingestion (before
the OGTT) relative to placebo
(2.7 pmol/L, p = 0.03), but
this change did not correspond
with changes in glucose or
insulin secretion
Olthof et al. Nutrition & Metabolism 2011, 8:10

54. Fetuin A:
hepatic secretory protein that binds the insulin receptor in muscle and fat
and inhibits insulin action, in vitro.
In cross-sectional studies in humans, higher fetuin-A was associated with
insulin resistance
case-cohort study, fetuin-A levels within the
fetuin-A in baseline serum highest tertile had more
was measured than two times
among 406 randomly higher risk of incident
selected participants and diabetes (HR 2.41; 95% CI
all participants who 1.28–4.53; P<0.01)
developed diabetes compared to subjects in
during 6-years the lowest tertile
54
JAMA. 2008 July 9; 300(2): 182–188.

55. Keijzers GB, De Galan BE, Tack CJ, Smits P.
Caffeine can decrease insulin sensitivity in humans .
Diabetes Care. 2002 25(2):364-9.

56. Caffeine metabolism
 takes place in the liver
 removal of the methyl 1 and 7 groups in a
reaction catalyzed by cytochrome P450, enabling
the formation of three methylxanthine groups:
 paraxantine (84%) increases lypolisis,
 theobromine (12%) stimulates blood vessels
dilatation and increases the urine volume
 theophylline (4%) controls the glucose metabolism
56

57. Coffee consumption and CRP levels in postmenopausal
overweight/obese women:
importance of hormone replacement therapy use
 Plasma CRP was positively associated with BMI and
negatively associated with coffee consumption.
 Coffee consumption appears to attenuate the association
between BMI and CRP, but only in women not using HRT
European Journal of Clinical Nutrition (2009), 1–6