I'm not so sure that insulin sensitivity is reduced for a short time though. The study below suggests that 200 mg caffeine taken twice a day (400 mg total, as you stated) in 16 healthy people can cause insulin resistance for up to 12 hours after administration.
Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.
^ can't post links yet
Baseline HOMA%S was not measured but this study recorded a 35% decline in insulin sensitivity.
Study design:
We conducted a double-blind, placebo-controlled, randomized crossover trial among healthy, nonsmoking, nonpregnant students 18 years or older. To ensure that subjects could comfortably complete the study, we required each participant to have a history of tolerance to caffeinated beverages or antifatigue caffeine tablets and no history of cardiac arrhythmia or seizures. Subjects were recruited from the student body at Dartmouth College through e-mail announcements and posters. Each subject signed an informed consent document, which was approved together with the protocol by the Institutional Review Board at Dartmouth-Hitchcock Medical Center. Consenting participants were randomized to one of two sequences: placebo followed by caffeine or caffeine followed by placebo. The randomization list was completed using a random number generator. The active agent phase of each sequence consisted of taking a 200-mg tablet of caffeine twice (total of 400 mg) daily for 7 days. The placebo phase consisted of taking an identical placebo on the same schedule. All participants made 5 visits. At the first visit (day −5), eligibility was confirmed, participants gave informed consent, and baseline caffeine intake was assessed using a questionnaire. Subjects were asked to abstain from all products containing caffeine for the subsequent 5 days. A list of caffeine-containing products was provided to aid in this effort. At visit 2 (day 0), after the 5-day washout, patients were randomized to one of the two sequences. They were given a 7-day supply of study capsules and instructed to take one capsule twice daily—one between 8:00 and 10:00 AM and one between 4:00 and 6:00 PM. They were again instructed to refrain from caffeine-containing products and were asked to return 7 days later in the morning after an overnight fast. At visit 3 (between 8:00 and 9:00 AM of day 7), participants had blood drawn for measurement of study end points and were instructed to return 5 days later while abstaining from all caffeine-containing products. At visit 4 (day 11), after the second washout period, patients were entered on another 7-day study period, conducted as in the first. This was completed at visit 5, when patients returned between 8:00 and 9:00 AM on day 18 for phlebotomy
Right, so exercise has the benefit of non-insulin mediated glucose uptake. I believe this is because exercise essentially causes Glut4 translocation which allows glucose to be shuttled where it needs to go. But isn't insulin-mediated glucose uptake still important as well?
Secondly, caffeine decreased Glut4 expression according to the study below (in rats, granted). A decrease in Glut4 is never a good thing, correct?
Acute vs chronic caffeine: Are the effects on insulin sensitivity mediated by altered insulin/AMPK signaling pathway?
Acute caffeine administration at levels relevant in humans (3-4 cups per day) decreases GLUT4 protein expression by ~30% in rat skeletal muscle. This is mediated through adenosine receptors. No affect on AMPK. Caffeine also increases phosphorylation of IRS-1 at Ser residues.
Effect in human is dependent on baseline insulin sensitivity. Caffeine restores insulin sensitivity to normal levels in the obese via reduction of plasma NEFA levels. Glucose uptake reduced by ~25% in "lean" (BMI < 25) men post light exercise (walking). Meta-analyses indicate 20-30% reduction in insulin sensitivity and glucose uptake at rest in the "lean." I don't think I've seen anything done with resistance training
Resistance training increases GLUT4 expression 60-100% post-exercise, returning to baseline ~24 hours later. Long-term trained individuals express up to ~200% GLUT4 mRNA content at baseline vs untrained or detrained while GLUT4 protein content increases 400% despite mRNA levels returning to baseline between exercise bouts.
Typed this up from old notes, I can post references when I have more time if interested
