Significance of clinical parameters found so far regarding coffee and diabetes 7th WCPD‐2012 Pilar Riobó MD, PhD Endocrinology & Nutrition Madrid www.doctorariobo.com
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 coffeeconsumption and subsequent risk of DMEvery additional cup of coffee consumed in a day was associated with a 7% reduction in the excess risk of diabetes
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.
Certain components of coffee, such as CGAand 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 beoffset 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, placeboCGA and trigonelline reduced early glucose and insulin responses, and contribute to the putative beneficial effect of coffee
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
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 efficacyand safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7.
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 dysfunctioncross-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.
An intervention trial in coffeedrinkers to investigatethe 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 comparedKempf K et al. Influence of insulin resistance on with 0 cupsthe effect of coffee consumption on coffee/dsubclinical inflammation and lipids Am J Clin Nutr 2010;91:950-957
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 proteinlevel in a Japanese female population. Clin Chem Lab Med. 2008;46(10):1434-7.
Effect on adiponectin982 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
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 ina multi-ethnic Asian population: a cross-sectionalstudy. Nutr . 2011;10:61.
Consumption of unfiltered coffeeincreases serum levels of total & LDL cholesterolIncreases in serum lipids were greater in studies of patients with hyperlipidemiaJee SH. Am J Epidemiol 2001;153:353
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 coffeeCai L et al. The effect of coffee consumption on serum lipids: a meta-analysis ofrandomized controlled trials. Eur J Clin Nutr. 2012 ;66(8):872-7
No effect on LDL levels Phenolic acids are incorporated into LDL Ex vivo oxidation of LDL was significantly reducedEffect of coffee consumption on LDL Effect of coffee on the susceptibility of LDL to oxidative modification Natella F.. Am J Clin Nutr 2007
Coffee & Metabolic SyndromeCross sectional study, 554 adultsConsumption of coffee and green tea was assessedMetabolic syndrome was diagnosed using NCEP ATP IIIGreater coffee consumption was associated with - lower prevalence of Met-S - lower OR for high serum triglyceridesNo significant correlation was found between coffeeconsumption and either waist circumference or BMI Takami H. Journal of Epidemiology 2012
Coffee & Metabolic SyndromeThe 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 agesModerate and high (>2 cups/day) coffeeconsumption was associated with lower HDL inwomen.For men, coffee consumption was not associatedwith any of the components of the Met-S Balk L. Eur J Epidemiol.. 2009;24(4):203-9.
Blood pressure response to chronic intake of coffee and caffeine: a meta-analysisA rise of 2.04 mmHg in SBP and 0.73 mmHg in DBPWhen coffee trials and caffeine trials were analysedseparately, BP elevations appeared to be larger for caffeinethan 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, wheningested through coffee, the effect of caffeine issmaller Noordzij M J Hypertens.2005;23(5):921
Habitual coffee consumption and risk of hypertension systematic review:6 prospective studiesfollow-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
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.
Acute effects of caffeine on BP in hypertensive individualsAdministration 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
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
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
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
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 coffeeintake and cardiovascular events was observed in post–MI patients after 3.5 years follow-up Silleta MG. Circulation. 2007;116:2944-2951
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 HFAhmed 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
Coffee consumption and risk of heart failure: Systematic review and a dose-response meta-analysis Five prospective studies , including 6522 heart failure eventsModerate 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 strokea 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 ProspectiveInvestigation into Cancer and Nutrition (EPIC)–German study Am J Clin Nutr 2012 95: 901
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
Coffee and mortality2 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
Coffee and total & cause-specific mortalityHealth–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
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
What about subjects With Impaired Glucose Tolerance? The Rancho Bernardo StudyCurrent or past coffee drinkers who did not have diabetes at baseline had a 60% reduced risk of type 2 diabetes during the next 8 yearsThe 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 DM2Pimentel G. Does long-term coffee intake reduce type 2 diabetes mellitus risk? Diabetol Metab Syndr. 2009; 1: 6.
SHBGmay it account for the potential protective effect?Strong inverse association between SHBG levels and T2D risk Women’s Health Studyfollow-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
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 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: arandomized controlled trial. Nutrition Journal 2011 10:93.
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
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
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¡¡¡¡
“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 beElliot P. Joslin, 1921 important.”
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 beElliot P. Joslin, 1921 important.”
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
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 coffees 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), but this change did not correspond with changes in glucose or insulin secretionOlthof et al. Nutrition & Metabolism 2011, 8:10
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 tertile54 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 metabolism56
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