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To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1058 non-diabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank ≥4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 μg/ml, respectively, in diabetic women, P=0.004; 15.0 vs. 13.2 μg/ml in nondiabetic women, P=0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein and tumor necrosis factor-α receptor II. Adjustment for adiponectin did not weaken these associations, nor did adjustment for inflammatory markers attenuate the association between coffee consumption and adiponectin. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations.
We studied 982 women with type 2 diabetes and 1058 non-diabetic women from the Nurses' Health Study with measures of plasma adiponectin concentration and data on usual coffee consumption who were free of coronary heart disease, myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and stroke at blood draw in 1990. Disease status was confirmed as previously reported(1).
Data on exposures, outcomes, and covariates were collected from questionnaires, as previously reported(1-4). Food intake in NHS has been assessed using a semi-quantitative food frequency questionnaire (SFFQ)(4), the validity and reliability of which has been previously described(5-7), with high correlations between responses to the SFFQ and four 1-week dietary records for coffee (r=0.78), tea (r=0.94), and caffeinated sodas (r=0.85)(5). We also assessed the total intake of caffeine(8). Averages of coffee, tea, and caffeine intake from the 1984, 1986, and 1990 SFFQs were calculated to account for long-term dietary exposure and reduce within-person variability. Blood samples were taken in 1989 or 1990, and adiponectin was assayed(2,9).
Comparisons of descriptive measures were conducted using ANOVA for continuous variables and appropriate X2 tests for categorical variables across groups of caffeine-containing coffee consumption. Associations between beverage consumption and plasma adiponectin concentrations were evaluated using simple linear regression models for crude analysis and multiple linear regression with logarithmic transformation of hormone values to achieve normal distribution. We adjusted for potential confounders in multivariate analyses. Tests for interaction were conducted using linear regression with multiplicative interaction terms. Analyses were conducted using the SAS (Version 9.1 for UNIX, SAS Institute, Cary, NC). P values are two-sided.
Both diabetic and healthy women who drank coffee on a daily basis had significantly higher total energy and caffeine intake and were more likely to be current smokers and less likely to be hypertensive or use thiazide diuretics. Diabetic women in the highest coffee consumption group also had a significantly lower BMI, higher alcohol intake, and were more likely to report a family history of diabetes, while non-diabetic women in the highest coffee group had significantly higher weekly physical activity and were more likely to be employed full-time. (Table 1)
Diabetic women who consumed four or more cups of caffeine-containing coffee per day had significantly higher adiponectin concentrations than those who drank lower amounts, even after full adjustment (Table 1). Non-diabetic women in the same group had higher adiponectin concentrations as well, with significant differences among coffee groups after adjustment. Also presented are analyses by quartile of caffeine intake, which were very similar to results for caffeine-containing coffee. We found no evidence of interaction by age, obesity, alcohol consumption, or smoking status on the association of caffeine-containing coffee with adiponectin. Additional adjustment for the dietary factors of glycemic load, dietary fiber intake, and Mediterranean diet pattern adherence did not significantly change the results.
No association between consumption of decaffeinated coffee and adiponectin was found in either group. Intake of two or more cups of tea per day tended to be associated with higher adiponectin concentrations among diabetic women, and the association remained marginal after adjusting for lifestyle and medical history covariates (P=0.07). (Data not shown).
We confirm previously reported inverse associations of coffee consumption with inflammatory markers(4) among diabetic women, specifically C-reactive protein (P=0.001) and tumor necrosis factor-α receptor II (P=0.03). Adjustment for adiponectin did not weaken these associations, nor did adjustment for inflammatory markers attenuate the association between coffee consumption and adiponectin (P<0.05 for all).
Regular consumption of coffee may have beneficial effects, including decreased insulin resistance, decreased incidence of type 2 diabetes, and lower levels for markers of inflammation but the exact underlying mechanisms are not completely understood (4, 8, 10-17). Our study suggests that favorable metabolic effects of caffeine-containing coffee may partly operate through associations with serum adiponectin concentrations. We found that habitual consumption of 4 or more cups of caffeine-containing coffee per day was associated with ~20% higher serum adiponectin concentrations as compared with women who drank less than 4 cups of coffee daily, indicating that increased adiponectin may play a role in the beneficial effects of coffee on insulin sensitivity. Our data are consistent with several previous prospective studies demonstrating a decreased risk of type 2 diabetes with higher coffee consumption, with observed benefits starting at three to six cups per day(8,12,15). Our data extend recent findings that coffee consumption is associated with lower levels of E-selectin and C-reactive protein among women with diabetes(4), and suggest that coffee and/or caffeine may have unique effects on inflammatory processes, insulin sensitivity, and metabolism. Decaffeinated coffee and tea consumption was not associated with adiponectin but only a small number of women consumed ≥4 cups of decaffeinated coffee per day.
In addition to genetic factors, several modifiable lifestyle factors, diet(2,18) and increased physical activity(19), may at least partially determine circulating levels of the endogenous insulin sensitizer adiponectin(20-23). However, unlike high levels of physical activity and eating a healthy diet, which commonly cluster with an overall healthy lifestyle, coffee consumption has been linked to poorer health habits, such as cigarette smoking and physical inactivity(24).
Phenolic compounds found in coffee, may slow intestinal glucose absorption postprandially and improve GLP-1 secretion and glucose metabolism(25,26), and coffee may have antioxidant activities(27). Mechanistic studies and interventional studies are necessary to determine whether the association between coffee and adiponectin is causal and what bioactive components might underlie this relationship.
This work was funded by grants HL65582, HL60712, HL34594, DK58785, and DK58845 from the NIH. F.B.H. is a recipient of the American Heart Association Established Investigator Award. C.S.M. is supported by a discretionary grant from BIDMC, a grant-in-aid by Tanita Corporation, and is a recipient of the Bessel Award by the Alexander von Humboldt Foundation.