Caffeine impairs glucose metabolism in type 2 diabetes.

affeine is a widely used drug despite evidence that it has deleterious con- sequences for health, including dia- betes (1). In 1967, a study reported that drinking two cups of instant coffee signif- icantly impaired glucose tolerance in a small group of men with "maturity-onset diabetes" (2). Recent studies showed that caffeine acutely decreased insulin sensi- tivity in young, nondiabetic adults (3-5). This study tested how oral caffeine affects carbohydrate metabolism in patients with type 2 diabetes, for whom decreases in insulin sensitivity might result in exagger- ated hyperglycemic responses to glucose and other carbohydrates, which would aggravate the glycemic dysregulation found in the disease. We tested the effects of caffeine on fasting glucose and insulin levels and on glucose and insulin re- sponses to a mixed-meal tolerance test (MMTT). RESEARCH DESIGN AND medications known to affect glucose me- tabolism. The subjects completed in- formed consent before testing. Caffeine and placebo treatments. Caf- feine and placebo treatments were admin- istered in identical gelatin capsules containing either 125 mg anhydrous caf- feine plus dextrose filler or dextrose alone. The total caffeine dose (375 mg) was given on a divided schedule as de- scribed below. The order of the treat- ments was counterbalanced. Procedures. Informed consent and screening data were collected at an ap- pointment before testing. The subjects also completed a 7-day diary of caffein- ated beverage consumption, recording the serving size and time of day for each caffeinated beverage. They were studied on two different mornings within a 2-week period, following overnight fast and caffeine abstinence. The subjects took prescribed diabetes medications ac- cording to their usual treatment regimen. A forearm vein was cannulated for non- traumatic blood sampling. After 30 min quiet rest, baseline fasting blood samples were drawn. The subject ingested 250 mg caffeine or placebo in two capsules with water. After a 60-min interval for caffeine absorption, a second set of fasting blood samples was drawn. Subjects then in- gested an additional 125 mg caffeine or placebo (intended to maintain drug lev- els) and consumed a commercial liquid meal (Boost) that contained 75 g carbohy- drate to begin the MMTT. Additional blood samples were drawn 1 and 2 h after the meal. The subject remained sedentary throughout the MMTT and relaxed while reading or watching television. Blood samples were centrifuged, and plasma was frozen for later assay of glucose and in- sulin. Plasma glucose levels were measured using a Beckman Glucose Analyzer II, and plasma insulin levels were measured by a double-antibody radioimmunoassay (Linco Research, St. Charles, MO). Statistical methods and calculations. The caffeine effects on fasting measures were tested by comparing the postdrug fasting levels with a repeated-measures ANCOVA, including predrug fasting lev- els as a covariate to control for within- subject variations in the initial level. To test the effects on responses to the MMTT, we calculated the incremental ar- eas under the MMTT 2-h time curves (AUC 2h ) for glucose and insulin with the trapezoidal rule, using the postdrug fast- ing value and the values 1 and 2 h after the meal. Incremental areas were compared by a repeated-measures ANOVA. Data are presented as means SE, unless other- wise specified, and P 0.05 was consid- ered statistically significant.