One of the larger determining factors that play a role in fuel economy in these trucks is fuel atomization. The other thing seems to be turbo sizing. Timing can help too, but that's independent of the previous two things mentioned.
When you go with larger injectors, the degree of atomization begins to diminish. The larger the hole for the fuel to flow through, the less atomization for a given pressure. The only good way to offset this would be to increase pressure to increase the amount of atomization, but you'd also need to decrease duration to keep the RPM's at the same point. Then comes the wear and tear factor. More pressure will increase wear on the injector and injection pump. So, you run into a tradeoff (as with everything in life).
Turbo sizing is another important factor. If you go with a smaller turbo (say a 62/65/12), it requires less exhaust gas volume and heat to drive it to any given pressure compared to a larger turbo (say a 62/74/14). The bigger wheel/housing will decrease backpressure which is good for performance, but that means that you'll be needing more heat and exhaust volume (fuel and/or RPM) to create the same boost pressure.
Now, you can make the same HP at 0 psi and 2000 rpm as you can at 3 psi and 2000 rpm, but it's going to require more fuel to make that hp number at 0psi (because, without boost, the Volumetric Efficiency of the motor decreases significantly - thus requiring more fuel to make the same power. HP is not ONLY airflow dependent. Air to Fuel ratio plays a part in making power, too. And a slightly richer mix of fuel to air results in more power [to a certain degree - there's always a derivative], but less economy). In other words, the truck will move at the same rate of acceleration at 0 psi and 2000 rpm with a richer fuel/air mixture as it will with 3 psi and 2000 rpm with a slightly leaner fuel/air mixture. It will just get poorer fuel economy.
So, the key is to not go overboard with injector and turbo size when trying to keep fuel economy. It all needs to match for the intended use of the truck.