wcpd 2012: pilar riobo
TRANSCRIPT
Pilar Riobó MD, PhDEndocrinology & Nutrition
Madridwww.doctorariobo.com
Significance of clinical parameters
found so far regarding coffee and
diabetes 7th WCPD‐2012
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
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 consumedin a day was associated with a 7%
reduction in the excess risk of diabetes
caffeine stimulates the release of adrenaline, an inhibitor of insulin activity, and increases blood pressure and serum homocysteine.
Acute Intake of caffeine impairs glucose metabolism
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
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
Effect on weight
7
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.
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.
Effect on weight
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)
Effect on inflammation & endothelial dysfunction
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.
cross-sectional study of 730 healthy women and 663 women with type 2 diabetes from the NHS I
Kempf K et al. Influence of insulin resistance on the effect of coffee consumption on subclinical inflammation and lipids
Am J Clin Nutr 2010;91:950-957
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
8 cups compared with 0 cups coffee/d
An intervention trial in coffee drinkers to investigatethe antiinflammatory effect
Coffee-mediated effects were more
pronounced ininsulin-resistant
individuals
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.
Effect on CRP
Effect on adiponectin
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
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
Effect of coffee on insulin sensitivity
Inverse association between coffee and HOMA-
IR
(- 8.8% for ≥ 3 cups/day versus never; P =
0.007)
Singapore Prospective study-2 (SP2), 5163 participants,
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.
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
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
Effect of coffee consumption on serum lipids
No effect on LDL levels Phenolic acids are incorporated into LDL Ex vivo oxidation of LDL was significantly
reduced
Natella F.. Am J Clin Nutr 2007
Effect of coffee consumption on LDL
Effect of coffee on the susceptibility of LDL to oxidative modification
Cross sectional study, 554 adults Consumption of coffee and green tea was assessedMetabolic 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
Coffee & Metabolic Syndrome
Observational longitudinal (1976) with 450 children 13.1 ± 0.8 y.o at baseline; 30-year follow-upAt 42 years, Met-S was measured in 344 subjects & coffee consumption was measured at 5 ages
The Amsterdam Growth and Health Longitudinal Study
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.
Coffee & Metabolic Syndrome
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
Blood pressure response to chronic intake of coffee and
caffeine: a meta-analysis
Noordzij M J Hypertens.2005;23(5):921
Habitual coffee consumption and risk of hypertension systematic review:6 prospective
studies
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
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
follow-up : 6.4 to 33.0 y.
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
Mesas et al. Am J Clin Nutr 2011;94:1113–26.
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 A E et al. Am J Clin Nutr 2011;94:1113-1126
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
Acute effects of caffeine on BP in hypertensive individuals
Mesas A E et al. Am J Clin Nutr 2011;94:1113-1126
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
Long-term effects of coffee consumption on BP in hypertensive subjects
Greenberg JA. Caffeinated coffee consumption, cardiovascular disease, and heart valve disease in the elderly . Am J Cardiol
2008;102(11):1502
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.
Coffee and CVD
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
womenZhang W. Diabetologia. 2009 May ; 52(5): 810–817
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.
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-upSilleta MG. Circulation. 2007;116:2944-2951
Coffee and Risk of heart failure
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 MenAm Heart J. 2009; 158(4): 667–672
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).
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.
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
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
Coffee consumption is
inversely associated with
the risk of bladder, breast,
buccal cavity and pharynx,
colorectum, endometrium,
esophagus, hepatocellular,
leukemia, pancreas, and
prostate cancers
Coffee and cancer risk
Coffee and 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
High coffee consumption
was not related to increased mortality and may even be
associated with lower total and cardiovascular
mortality.
2 large cohorts : NHS and HPFS followed over 2 decades.
Coffee and total & cause-specific mortality
Freedman ND. N Engl J Med. 2012;366(20):1891
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. Association of coffee drinking with total and cause-specific mortality. N Engl J Med. 2012;366:1891
Subgroup Analysis of Associations between the Consumption of 4 or More Cups of Coffee per Day
and Total Mortality.
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
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.
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
may it account for the potential protective effect?Strong inverse association between SHBG levels and T2D risk
SHBG
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.
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
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.
Adiponectin
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
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
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¡¡¡¡
Take home message
“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 important.”
Elliot P. Joslin, 1921
“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 important.”
Elliot P. Joslin, 1921
Thank you for your attention
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 diabetic and nondiabetic subjects. Diabetes Care. 2006;29(2):468.
Ix JH. Fetuin-A and incident diabetes mellitus in older persons. JAMA.2008;300(2):182–188.
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.
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), butthis change did not correspond
with changes in glucose or insulin secretion
Olthof et al. Nutrition & Metabolism 2011, 8:10
Fetuin A:
54
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 in baseline serum
was measured among 406 randomly
selected participants and all participants who developed diabetes
during 6-years
fetuin-A levels within the highest tertile had more
than two timeshigher risk of incident
diabetes (HR 2.41; 95% CI 1.28–4.53; P<0.01)
compared to subjects in the lowest tertile
JAMA. 2008 July 9; 300(2): 182–188.
Keijzers GB, De Galan BE, Tack CJ, Smits P. Caffeine can decrease insulin sensitivity in humans . Diabetes Care. 2002 25(2):364-9.
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
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