Coffee, Caffeine, and Risk of Type 2 Diabetes Rob M. van Dam, PhD, Joann E. Manson, MD, Walter C. Willett, MD, Frank B. Hu, MD Diabetes Care, 2006; 29,

INTRODUCTION

High coffee consumption High coffee consumption Better glucose tolerance Better glucose tolerance Substantially lower risk of type 2 diabetes Substantially lower risk of type 2 diabetes Diverse populations in Europe, the US, and Japan Diverse populations in Europe, the US, and Japan What coffee components may be responsible for the apparent beneficial effect of coffee on glucose metabolism? What coffee components may be responsible for the apparent beneficial effect of coffee on glucose metabolism?

In rats In rats Intakes of the coffee components (chlorogenic acid, quinic acid, trigonelline, and the lignan secoisolariciresinol) improved glucose metabolism Intakes of the coffee components (chlorogenic acid, quinic acid, trigonelline, and the lignan secoisolariciresinol) improved glucose metabolism In humans In humans Short-term metabolic studies: Caffeine can acutely lower insulin sensitivity Short-term metabolic studies: Caffeine can acutely lower insulin sensitivity Long-term effects of caffeine intake on glucose metabolism: unknown Long-term effects of caffeine intake on glucose metabolism: unknown

The relation between coffee consumption and type 2 diabetes The relation between coffee consumption and type 2 diabetes Drip-filtered caffeinated coffee: studied Drip-filtered caffeinated coffee: studied Data on decaffeinated coffee and various methods of coffee preparation in relation to risk of type 2 diabetes: rare Data on decaffeinated coffee and various methods of coffee preparation in relation to risk of type 2 diabetes: rare Previous studies: 5 or more cups / lower level of consumption Previous studies: 5 or more cups / lower level of consumption Current study Current study Consumption of different types of coffee and the intake of caffeine in relation to risk of type 2 diabetes in a large cohort of younger and middle-aged U.S. women Consumption of different types of coffee and the intake of caffeine in relation to risk of type 2 diabetes in a large cohort of younger and middle-aged U.S. women

RESEARCH DESIGN AND METHODS

Prospective Nurses’ Health Study II Prospective Nurses’ Health Study II 116,671 female U.S. nurses at study initiation in ,671 female U.S. nurses at study initiation in 1989 Information collection Information collection Biennial-mailed questionnaires Biennial-mailed questionnaires Response rates: ~90% for each questionnaire Response rates: ~90% for each questionnaire For the current analysis, follow-up began at the return of the 1991 questionnaire – diet: 1 st assessed For the current analysis, follow-up began at the return of the 1991 questionnaire – diet: 1 st assessed years at the start of follow-up years at the start of follow-up

Exclusion criteria Exclusion criteria Did not complete a dietary questionnaire in 1991 Did not complete a dietary questionnaire in 1991 >70 items were left blank >70 items were left blank Reported total energy intake was implausible ( 3,500 kcal/day) Reported total energy intake was implausible ( 3,500 kcal/day) History of diabetes (gestational diabetes) History of diabetes (gestational diabetes) Cancer (except nonmelanoma skin cancer) Cancer (except nonmelanoma skin cancer) Cardiovascular disease at baseline Cardiovascular disease at baseline Not provided data on physical activity in 1991 Not provided data on physical activity in 1991 Total of 88,259 U.S. women of the Nurses’ Health Study II Total of 88,259 U.S. women of the Nurses’ Health Study II

Assessment of coffee consumption Validated dietary questionnaires: 1991, 1995, and 1999 Validated dietary questionnaires: 1991, 1995, and 1999 Caffeinated and decaffeinated coffee (one cup), tea (one cup or glass), deffenent types of caffeinated soft drinks (one glass, bottle, or can), and chocolate products (bar or packet) Caffeinated and decaffeinated coffee (one cup), tea (one cup or glass), deffenent types of caffeinated soft drinks (one glass, bottle, or can), and chocolate products (bar or packet) Choose nine responses Choose nine responses Never or less than one per month, on to three per month, one per week, two to four per week, five to six per week, five to six per week, one per day, two to three per day, four to five per day, and six or more per day Never or less than one per month, on to three per month, one per week, two to four per week, five to six per week, five to six per week, one per day, two to three per day, four to five per day, and six or more per day Method of preparing coffee Method of preparing coffee Mainly filtered, mainly instant, mainly espresso or perculator, and no usual method/don’t know/don’t use Mainly filtered, mainly instant, mainly espresso or perculator, and no usual method/don’t know/don’t use

Caffeine contents Caffeine contents 137 mg/cup of coffee 137 mg/cup of coffee 47 mg/cup of tea 47 mg/cup of tea 46 mg/bottle of can of cola beverage 46 mg/bottle of can of cola beverage 7 mg/chocolate candy 7 mg/chocolate candy

Assessment of type 2 diabetes Women who reported a diagnosis of diabetes on a biennial follow-up questionnaire – supplementary questionnaire (to confirm the self- report and to distinguish between type 1, type 2, and gestational diabetes) Women who reported a diagnosis of diabetes on a biennial follow-up questionnaire – supplementary questionnaire (to confirm the self- report and to distinguish between type 1, type 2, and gestational diabetes) Diagnosis and treatment of diabetes Diagnosis and treatment of diabetes History of ketoacidosis History of ketoacidosis

Diagnostic criteria of diabetes (at least one) (through 1997) Diagnostic criteria of diabetes (at least one) (through 1997) Fasting plasma glucose ≥7.8 mmol/L [140 mg/dL], random plasma glucose ≥11.1 mmol/L [200 mg/dL], and/or plasma glucose ≥2 h after an oral glucose load ≥11.1 mmol/L plus at least on classic symptom (excessive thirst, polyuria, weight loss, or hunger) Fasting plasma glucose ≥7.8 mmol/L [140 mg/dL], random plasma glucose ≥11.1 mmol/L [200 mg/dL], and/or plasma glucose ≥2 h after an oral glucose load ≥11.1 mmol/L plus at least on classic symptom (excessive thirst, polyuria, weight loss, or hunger) No symptoms but ↑ plasma glucose contrations No symptoms but ↑ plasma glucose contrations Treatment with insulin or oral hypoglycemic medication Treatment with insulin or oral hypoglycemic medication After 1998 After 1998 Fasting plasma glucose ≥7.0 mmol/L [126 mg/dL] Fasting plasma glucose ≥7.0 mmol/L [126 mg/dL]

Assessment of medical history, anthropometry, and lifestyle Baseline questionnaires Baseline questionnaires Age, weight, and height Age, weight, and height Smoking status Smoking status Physical activity Physical activity History of diabetes in first-degree relatives History of diabetes in first-degree relatives Use of postmenopausal hormone therapy Use of postmenopausal hormone therapy Use of oral contraceptives Use of oral contraceptives Personal history of diabetes, cardiovascular diseases, and cancers Personal history of diabetes, cardiovascular diseases, and cancers Updated every 2 years (except physical activity, height, and family history) Updated every 2 years (except physical activity, height, and family history) Statistical analyses Statistical analyses

RESULTS

Pearson correlations with caffeine intake Pearson correlations with caffeine intake 0.83 for total coffee 0.83 for total coffee 0.94 for caffeinated coffee 0.94 for caffeinated coffee for decaffeinated coffee for decaffeinated coffee 0.09 for tea consumption 0.09 for tea consumption

CONCLUSSIONS

U.S. women aged years at baseline U.S. women aged years at baseline Consumption of two or more cups of coffee per day -> lower risk of type 2 diabetes during 10 years of follow-up Consumption of two or more cups of coffee per day -> lower risk of type 2 diabetes during 10 years of follow-up Inverse association between coffee consumption and risk of type 2 diabetes – independent of caffeine intake Inverse association between coffee consumption and risk of type 2 diabetes – independent of caffeine intake Prospective design and high rate of follow-up minimizes Prospective design and high rate of follow-up minimizes Recall bias Recall bias Bias due to loss of follow-up Bias due to loss of follow-up Extensive information on potential confounders Extensive information on potential confounders To examine confounding in detail To examine confounding in detail

Decaffeinated coffee consumption – lower risk of type 2 diabetes only in younger participants (aged ≤60 years) Decaffeinated coffee consumption – lower risk of type 2 diabetes only in younger participants (aged ≤60 years) Other health-related conditions Other health-related conditions Weaken the association Weaken the association Caffeine Caffeine Acutely reduced insulin sensitivity in short-term intervention study Acutely reduced insulin sensitivity in short-term intervention study Long-term effect: unclear Long-term effect: unclear Other components of coffee Other components of coffee Tolerance Tolerance

Inverse association between caffeine intake and risk of type 2 diabetes Inverse association between caffeine intake and risk of type 2 diabetes Result of confounding by coffee consumption Result of confounding by coffee consumption Coffee components other than caffeine may reduce risk of type 2 diabetes Coffee components other than caffeine may reduce risk of type 2 diabetes Decaffeinated coffee consumption – lower C-peptide concentrations in U.S. women -> beneficial effects on insulin sensitivity Decaffeinated coffee consumption – lower C-peptide concentrations in U.S. women -> beneficial effects on insulin sensitivity Coffee: strong antioxidant properties in vivo Coffee: strong antioxidant properties in vivo Chlorogenic acid: delay glucose absorption in the intestine Chlorogenic acid: delay glucose absorption in the intestine Intake of coffee components improved glucose metabolism in rats Intake of coffee components improved glucose metabolism in rats