Insulin (part 5): Sleep your diabetes off

Another main factor that excessively activates ceramides and DAG, as mentioned in the last blog, is a broken circadian rhythm. We didn't get to cover this last time, but it certainly deserves its own separate discussion. This is because we've paid so little attention to this crucial, intrinsic wiring embedded in our physiology. I've encountered many people who have done everything possible with exercise and nutrition to fight insulin resistance, yet they know nothing about how to care for their body clock. The result? To their shock, some of them are so resistant to insulin that they are on the cusp of diabetes.

I do intend to explore the circadian rhythm in depth one day, but for now, let's focus on its relationship to insulin. You might be asking: why do we need to switch between being insulin sensitive and insulin resistant within a 24-hour cycle? Why can't we simply be 'healthy' and maintain continuous insulin sensitivity? And how does breaking this cycle lead to insulin resistance?

Timing is everything. This is true for almost every facet of life, and it's certainly true for our body. We cannot be 'healthy' if we don't cycle in and out of insulin sensitivity, as that time is vital for eliminating broken, old, or misshapen cells. Remember that insulin, being anabolic, signals these cells to keep living. Generally, around sunrise, we are meant to eat and store the energy we haven't used. Similarly, around sunset, we are meant to use the stored energy and take no more in.

You might view sleep as an inactive, dormant, or insignificant state. However, in our physiology, sleep is just as important as wakefulness, if not more so. We produce melatonin when we sleep, and this hormone is naturally anti-insulin. It binds to the MT1 receptor and, to a lesser extent, the MT2 receptor on the pancreatic beta-cells, which decreases cAMP and subsequently reduces insulin production. This effectively stops insulin signaling because our body knows that the signal would be counterproductive to sleep. Recall the primary function of insulin: it inhibits pancreatic glucagon. Melatonin ensures that pancreatic glucagon continues to be produced, as our brain requires that slow and steady supply of glucose throughout the night. Glucagon stimulates the liver to provide this necessary steady glucose supply to the brain. If insulin were present, it would suppress glucagon production and push glucose into the cells. When this happens, the brain loses its primary fuel and must switch to its fallback fuel, which comes at a cost. Perhaps I should have emphasized that poor sleep may be the first sign of insulin resistance.

Many factors can cause our body clock to become disrupted. These range from stress (the notorious cortisol), pharmaceuticals, caffeine, blue light, lack of vitamin D, and overtraining, to eating at the wrong time (yes, your intermittent fasting might be causing your insulin resistance). Imagine if your body has been insulin sensitive throughout the day, as it should be, and then a rush of food comes in at night for it to process. It will have to forgo being resistant for a while longer to handle the evening's caloric load. Melatonin is put on hold. When this pattern repeats, your fat cells eventually become overfilled, much like the situation with caloric excess, which then causes increased production of ceramides and DAG over the long term. It is absolutely no surprise that human and animal studies have consistently shown that feeding outside the correct body clock window, even without caloric excess, leads to metabolic dysfunction.

There are several other ways a disrupted sleep-wake cycle can cause insulin resistance. For instance, the mitochondria produce more Reactive Oxygen Species (ROS) when the body doesn't register adequate sleep at the right time, and this directly stimulates ceramides and DAG. The immune system is another example, being closely tied to the circadian rhythm. Disrupting this internal clock leads to its overactivation, meaning increased TNF-alpha and IL-6 (markers of an overactive immune system), both of which stimulate ceramide and DAG. As you may recall, when ceramide and DAG are abundant in the cellular environment, insulin's action only lands on the serine/threonine phosphorylated IRS-1 receptors, which prevents fat or glucose uptake into the cells, defining the fundamental meaning of insulin resistance.

If you have diabetes and your doctor has told you to sleep it off, you might want to take their advice rather seriously.