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  • Dennis Lipton, MD

Glucose and Insulin Metabolism

Updated: Jun 3, 2019

We now know that controlling your blood sugar and A1c is vitally important. Many patients get very frustrated about their stubbornly elevated A1c, insisting that they already exercise and eat right. They feel like they are somehow being betrayed by their body and body chemistry. We then talk in detail about their diet and lifestyle and how it can influence glucose and insulin and metabolism.


Glucose levels in the body are very tightly controlled. There’s only about a teaspoon of glucose in your blood stream at any one time. What happens, then, when you drink 16oz of soda or juice, or 2 slices of bread, which can contain the equivalent of 10-12 teaspoons of sugar? As the sugar is absorbed and blood levels rise, your pancreas senses this and secretes insulin into the blood stream, which acts as a key that 'unlocks' your liver, fat, and muscle cells, opening the gates’* to allow transport of

glucose into the cell, effectively removing the glucose from circulation. (Note, Type 1 diabetics are unable to make any insulin so they must inject insulin with meals). Your body is now in the ‘fed’ or ‘nutrient-rich’ state and your cells are full of glucose. Your blood glucose levels begin to drop. Then, glucagon (opposite of insulin) kicks in, and your cells release the glucose back into your bloodstream to maintain the glucose in your bloodstream, in that tight range.


Depending on what you eat, how often you eat, and some aspects of your own personal biochemistry, this process can take 2-4 hours or more. If the system works perfectly, your blood glucose level should stay in the tight range of 90-130 through this process. Your insulin level, however, goes up then down to very low levels. In the fasted state, your insulin level should be very low. Then, your cells remain very insulin sensitive, able to respond to your next meal.


Since humans spent many thousands of years as hunter-gatherers where food was relatively scarce, and physical activity was unavoidable, our bodies are very good at preserving and storing energy. Innately, the palatability and desirability of food is tied to its calorie density. In other words, our instinct is to be drawn to the most calorie-dense food source in the environment, just like other animals. (This is why processed food is loaded with fat, sugar, and salt.) This system worked very well, allowing our descendants to survive cycles of feast and famine for tens of thousands of years. This all has changed.

What’s happened in the past few thousand years, especially in the past 100 years? Food has become abundant, especially calorie-dense, highly palatable food. Physical activity has decreased. Our innate glucose and insulin metabolism, however, has not changed. The average person now ‘feeds’ 4-8 times daily. Insulin levels rise and stimulate calorie storage many more times per day than anytime in human history. Our cells are in the fed state, and before they can begin releasing their stored energy, we eat again. Some of us eat again even before insulin levels have had a chance to go down. We are storing energy for the famine that never comes.


As cells reach their capacity for glucose storage, they stop responding to the usual insulin signal to open up and take on glucose. Saturated fat also decreases the ability of the cell to respond to insulin. The 'key' no longer works. Glucose levels in the bloodstream rise more, especially after meals, prompting more insulin release. Eventually the blood glucose levels become normal, but at an increased baseline insulin level. By this time A1c has gone up, as well as other glycated proteins and advanced glycation end products (AGEs). We probably have excess stored calories in the form of body fat (liver fat, subcutaneous fat, visceral fat… topic for another post). If this process progresses, eventually the pancreas can no longer secrete enough insulin to keep glucose levels in check, blood sugar levels rise, and the person is labeled diabetic.


If I suspect this process may be occurring (and it IS occurring in 1/3 to ½ of all Americans), I will order not only an A1c, but a fasting insulin level. Your fasting insulin level should be very low (ie 2-5 uIU/ml). Getting this level down to normal or optimal is vital to your long-term health and vitality. We’ll discuss this next.


*the genetic and molecular mechanisms of glucose transport in and out of cells have been elucidated in the past 10 years and is now very well understood https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425736/)

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