OK, so let's talk about the last topic I want to discuss this morning. And it has to do with poor sleep and how most of us, I think, are aware when we don't get a good night's sleep, we don't feel cognitively on game. Our mood is affected. We feel lethargic. We don't have as much energy. But I'm not sure that most people realize the profound effect that even mild sleep restriction has on our metabolic health and glucose regulation. And this is extremely relevant because about 1/3 of people in the United States do not meet the recommendations, which is 7 to 9 hours of sleep per night for sleep. And again, this is very relevant for jet lag. I mean, there's a lot of— relevance here for poor sleep. So mild sleep restriction— this is 1 to 3 fewer hours of sleep per night.

So I mean, 1 is not a lot. Doing that 3 nights in a row can increase fasting insulin levels. It can lead to higher insulin concentrations, elevated fasting glucagon levels, and also it decreases insulin sensitivity. Again, this is just— getting 1 hour less of sleep a night for 3 nights. I mean, how many of us have probably even done that at this conference? I mean, it's very easy and very applicable. And it's having a profound effect on metabolism. Sleep debt is the cumulative effect of sleep restriction. So this is when you're having multiple days of the sleep restriction. So in this case, it was 4— sorry, 3 days of 4 hours less sleep per night. That led to 40% slower glucose clearance, 30% decrease in glucose effectiveness. So this is independent of insulin, similar to diabetes.

And 30% lower insulin response. So this is really indicating early diabetes. And these are in healthy people. This is healthy people after just 3 nights of having 4 hours less sleep a night. Very profound effect on metabolism. There's been large meta-analyses done on longitudinal studies looking at type 2 diabetes risk and sleep duration. And it's been identified that the optimal range of sleep for the lowest type 2 diabetes risk is 7 to 9 hours of sleep a night. So going below 7 hours or above 9 hours were both associated with increased risk for type 2 diabetes. So the 7-hour threshold, getting less than 7 hours of sleep a night, was associated with increases in fasting insulin, increases in glucose levels.

HOMA-IR was elevated, higher HbA1c, and then also visceral fat was increased as well. So again, getting less than 7 hours of sleep a night, which a lot of people do routinely. And speaking of the elevated HbA1c, I think this is really important. Most of you probably realize this, but when you are constantly having elevations in blood glucose levels, this leads to advanced glycation end products, or AGEs, as they're called. And it's certainly a huge problem in people with type 2 diabetes because they are constantly having glucose dysregulation and their elevated blood glucose levels. But generally speaking, when you have the HbA1c high, you are talking about glucose reacting with lipids and proteins through the Maillard reaction, including collagen.

And this is all inside of our blood vessels, our arteries, our myocardium surrounding our heart. When you have those advanced glycation end products forming, it stiffens that collagen. HbA1c levels turn over after about, what, 120 days? Your collagen has been there forever. So what happens is you have those advanced glycation end products. If it's in your blood vessels, it stiffens the blood vessels, and this leads to hypertension, plays a big role in hypertension. When it's happening in the arteries and in the myocardium, this decreases cardiovascular compliance, and it really plays a role in the stiffening of your heart with age. And so these advanced glycation end products increase the risk of cardiovascular disease, heart attacks, and hypertension.

So having these elevations in your blood glucose levels and subsequently the HbA1c biomarker, which reflects that, is so much more than just type 2 diabetes risk. It's cardiovascular health. And it's really a cumulative effect that plays a role as we age. There are a variety of mechanisms that have been identified for how short sleep and mild sleep restriction can cause dysfunctional metabolism. So we're going to talk about decreased insulin signaling in adipocytes. We're going to talk about lower beta cell sensitivity to glucose. We're going to talk about impaired glucose absorption in muscle and liver, and then changes in satiety hormones. So there's been some studies looking at sleep restriction. This is about 4 hours of sleep a night for 4 days.

It decreased insulin signaling in adipocytes by 30%. So I mean, your adipocytes are one of the major sinks, aside from muscle, for glucose disposal, storing it as fat for energy. But a 30% reduction in cellular insulin signaling in adipocytes is I mean, you're talking about— these are in healthy people. This is like a healthy person immediately becoming obese or immediately becoming type 2 diabetic after just 4 days of sleep restriction. So it's very profound in terms of metabolic health. Sleep loss, so mild sleep loss even, it does promote an obesogenic profile. And so a lot of work has been done out of Eve Van Cauter's lab. And she's looked a lot at these hunger hormones, satiety hormones. So after 2 days of 4 hours less sleep, leptin levels go down.

So people are not feeling satiated by their food because leptin regulates satiation. And their ghrelin levels increase. So it's a double whammy. Ghrelin is the hunger hormone. It tells you you're hungry. And so they're getting this continual hunger. So global hunger ratings go up, global appetite goes up. So people are not satiated by their food and they're hungry throughout their day. And again, Eve Van Cauter's work has shown that people eat more, and they're consuming foods and have cravings for processed foods, highly refined sugars, salty foods, processed fats, and fatty foods. So they're eating up to 45% more of those processed unhealthy foods. And their hunger ratings are 24% higher. So they're eating even more than they would if they were getting a good night's sleep.