How to properly use insulin in diabetes and the mechanism of insulin resistance

After 35 years as a primary care physician and now 5 years as a full time hospitalist, I have come to realize that at least 90% of physicians do not know how to properly prescribe insulin for diabetes. To properly dose insulin, you have to know the physiology of normal insulin release in glucose homeostasis and how that then relates to insulin dosing and then what happens in diabetes.

It starts with the liver. One of the liver’s functions is to provide a steady flow of glucose to the bloodstream for the rest of the body to use. After a meal, the liver stores excess glucose as glycogen which it then releases at a constant rate between meals to keep a steady level of glucose in the blood. If a person fasts for over two days or doesn’t eat carbohydrates, the liver’s stored glucose, glycogen, is depleted, and then the liver makes it’s own glucose out of protein through gluconeogenesis. By this mechanism, the liver keeps the body supplied with a steady stream of glucose, keeping blood glucose levels steady, even after days or even weeks of fasting. As the liver is releasing glucose, the pancreas releases insulin at a steady rate, called basal insulin secretion. Pancreatic insulin is usually released at the same constant rate between meals or during fasting. This insulin serves two functions to control glucose levels. One is enabling tissues and organs of the body to take up and utilize insulin.  The other is to actually slow down and control the release of glucose from the liver. Glucagon, the other endocrine hormone released by the pancreas, responds to low glucose levels and ingested protein and stimulates production and release of glucose from the liver.  Insulin and glucagon work against each other regarding hepatic glucose release. Insulin suppresses hepatic glucose production and release and glucagon stimulates it.  The constant release of insulin between meals enables cells of the body to take up and utilize the glucose in the blood, and it also suppresses excessive glucose production and release stimulated by glucagon.  The system stays in balance with constant basal ie fasting glucose levels.  If a person ingests a meal with glucose ie carbohydrates, the blood glucose rises and the pancreas will then release a “bolus” of insulin to cause tissues of the body including fat cells to take up the excess glucose and to suppress glucose release from the liver until glucose levels go back down to normal. Then the pancreatic insulin release goes back to the basal level.

What happens in diabetes and prediabetes?  Diabetes is caused by chronic long term excess ingestion of sugar.  So are obesity, diabetes, hypertension, heart disease, and stroke. Table sugar ie sucrose is composed of the sugars glucose and fructose. It is the fructose part that caused the problem. Fructose is metabolized by a different mechanism in the liver compared to glucose.  Fructose metabolism causes a depletion of ATP in mitochondria which leads to a physiologic response called hepatic insulin resistance. In this case the liver becomes temporarily resistant to the effects of insulin, ie suppressing hepatic glucose release. The pancreas has to overcome this hepatic resistance by secreting more insulin.  Insulin, however has another important function besides controlling blood glucose levels and that is enabling fat cells to take up nutrients for storage in the form of adipocyte triglycerides.  By this mechanism, when animals or humans ingest fructose containing foods such as fruits and berries in the fall, they are able to increase fat storage by becoming temporarily insulin resistant and raising insulin levels which increase fat storage.  Grizzly bears have been known to eat large quantities of berries in the fall to help enable themselves to increase fat stores for hibernation in the winter. Hunter/gatherer humans in their natural pre agricultural state did the same thing when they ate fruit in the fall, ie becoming temporarily insulin resistant in order to increase fat storage for the winter. The problem is when you consume large amounts of sugar, fructose over long periods of time. In this case, the liver undergoes long term permanent changes that cause a state of continuous insulin resistance with persistently high insulin levels. The liver remains resistant to insulin all the time, not just after eating fructose. Persistently elevated insulin levels cause more and more fat storage and obesity. With continued ingestion of fructose, the liver becomes progressively more and more resistant to insulin. The pancreas has to release more and more insulin until it can no longer overcome this resistance and blood glucose levels begin to rise. At that point the patient is diagnosed with diabetes, however the condition has been developing usually over the previous 20 years.

The state of persistent insulin resistance with persistently elevated insulin is a condition called metabolic syndrome. Metabolic syndrome is associated with obesity, hypertension, diabetes , coronary artery disease, and cancer.  A physician named George Campbell, in South Africa, had clinics in the “bush” where he treated native Africans eating their natural diet devoid of much sugar as well as in the city of Durban where he treated the native Africans who had moved there and had adopted the “western diet” which included sugar. He noted that the Africans living in their natural environment, eating their natural foods, were free of all the chronic diseases of western society ie obesity, diabetes, hypertension, vascular disease, and cancer. He then observed the transition from being thin and healthy to being obese, diabetic, and with vascular disease after moving to the city and adopting western diets. He observed that the main dietary change that correlated with this change was ingestion of sugar. He took meticulous dietary histories and calculated that it took ingestion of over 70 lb of sugar per year for 20 years to develop the spectrum of obesity, diabetes, hypertension, and vascular disease.  Other explorers and physicians observed these same changes in other societies that made the “dietary transition,” including the Inuit living in the arctic, and Native Americans.  This same change has been observed in the general US population over the past 150 years. In the early 1800’s the average sugar consumption was less than 10 lb per person per year.  By 1850 with the availability of cheaper sugar from sugar beets rather than more expensive cane sugar, consumption began to increase.  By 1900 sugar consumption had increased to 70 lb per person per year.  Sugar consumption continued to increase until it peaked in 1995 at 150 lb per person per year.  During the 1800’s, the incidence of diabetes was extremely low, less than one case per 30,000.  The incidence of diabetes has steadily climbed along with the increase in sugar consumption.  After the obesity and diabetes epidemics of the past 20 years, the incidence is now one in 8.  Again please read Gary Taubes’ The Case Against Sugar for more on this.

Now to the use of insulin in treating diabetes:

As above, the cause of diabetes is chronic excess sugar consumption causing permanent injury to the liver with permanent insulin resistance. Sugar causes diabetes, and once someone becomes diabetic, continued sugar consumption causes causes the diabetes to worsen. Initially most diabetics are treated with diet, and usually a medication called metformin which helps reduce insulin resistance. If the patient continues to consume sugar, the diabetes worsens and other medications are started to help control glucose levels.  Then when this doesn’t work, insulin is started.  The initial form of insulin prescribed is what is called “basal” insulin.  This works along with the basal insulin secreted by the pancreas described above to control the glucose that is released by the liver.  In diabetes, the basal pancreatic insulin secretion is not enough to control fasting glucose levels ie the glucose that is being released by the liver.  In some cases, this basal insulin has to be supplemented by a “basal” or long acting insulin.  The main basal, long acting, insulin preparations that are prescribed include NPH insulin which lasts for 12 hours and has to be taken twice a day, and the newer, synthetic, 24 hour basal types of insulin, Lantus and Levemir.  These long acting, basal, types of insulin stay at a constant level in the blood and ONLY work on glucose released by the liver.  They have nothing to do with glucose that comes from ingested glucose ie carbohydrates.  Since they work on the glucose that is continuously released by the liver, not food, the only blood glucose “sugar” level that indicates whether a patient is on the correct dose of basal insulin is the first fasting, morning glucose before anything has been eaten.  That shows how the basal insulin worked on the hepatic glucose overnight without the effect of any food ingested.  The dose of basal insulin should be adjusted up and down, usually by one or two units at a time, until the fasting blood glucose is in the 100-140 range.  Once that range is achieved the patient usually continues on that dose.  If blood glucose levels rise or fall during the day, this is due to glucose, ie carbohydrate consumed.  Basal insulins only work on basal liver glucose that is released into the blood, they can do nothing for ingested dietary glucose.
As described above, when a normal, non diabetic patient ingests glucose, the pancreas releases a bolus of insulin to clear that dietary increase in glucose and bring blood glucose levels to normal.  Then the normal basal insulin secretion resumes to act on glucose being released by the liver.  If a diabetic patient on basal insulin with well controlled fasting glucose levels then eats carbohydrates ie glucose, the basal insulin, Lantus can’t do anything about this. In this case the patient has to take a quick acting type of insulin such as “regular” or R insulins, which works for about 4 hours, or one on the newer very quick acting insulins such as Humalog or Novolog that only act for about one hour. So, some patients on insulin use the basal, long acting insulin, Lantus or Levmir to control fasting glucose and then if they eat carbohydrates, they usually need to take a quick acting insulin like Novolog or Humalog to control the rises in insulin from consuming carbohydrates.  Through my years of treating many diabetic patients, I worked out a formula to calculate the usual amounts of quick acting insulin needed to control blood glucose after eating carbohydrates, mainly starches and fruit.  To know how much quick acting insulin is required to “cover” the glucose rise from ingesting starches or fruit you basically observe how many 15 gram portions of starch or fruit are eaten with each meal.  This can be found in diabetic food charts, but basically a fifteen gram starch portion would be one piece of bread, a half cup of starchy vegetables such as peas and beans, rice, noodles, mashed potatoes, half a baked potato, half cup of corn, grits, cereal, a medium apple, medium orange, half a banana, etc.  Each 15 gram portion of starch or fruit would require quick acting insulin at a dose of 1/10 the dose of basal insulin the patient is taking.  So if a patient is on 40 units of Lantus or Levemir he or she would need to take 4 units of quick acting insulin ie 1/10th of the basal insulin dose, for each 15 gm portion of starch or fruit eaten.  Some diabetic patients who choose to eat starches don’t take quick acting insulin to cover carbohydrates consumed and instead check their blood sugars 3 or 4 times a day and use a sliding scale to pull down blood glucose levels that have risen as a result of consuming starches and fruit.

There is also a formula to calculate how much quick acting insulin is needed for sliding scale doses to correct elevated blood glucose levels.  It is as follows:  Take the usual total insulin used ie long and quick acting, divide this into 1500.  That is how many blood sugar points will be lowered by each unit of quick acting, sliding scale insulin.

Now if a diabetic patient is on a low carbohydrate diet and not consuming starches or fruit, he or she wouldn’t need to take any quick acting insulin at all during the day, only the daily dose of basal insulin.

Low Carbohydrate diet to control and reverse diabetes:

Please see my blog about this but basically, as above, diabetes is caused initially by long term ingestion of excess sugar.  The excess sugar consumption causes permanent changes in the liver that leads to permanent insulin resistance, metabolic syndrome, and diabetes.  Once someone has diabetes, further consumption of sugar causes the diabetes to progress and worsen eventually to the point of requiring administration of insulin.  Also, once a person has diabetes caused by chronic sugar consumption, then consuming carbohydrates as well as sugar will cause the obesity, metabolic syndrome, and diabetes to worsen.  So once someone has diabetes or metabolic syndrome, it is imperative to stop consumption of sugar to prevent progression.  If that person can also decrease consumption of carbohydrates and follow a low carbohydrate, ketogenic diet, he or she can not only stop the progression of the diabetes and metabolic syndrome, but actually reverse it.  Twenty years ago, when I had my heart attack, I was diabetic and weighed 250 lb.  My triglycerides were 600 and my HDL was 25.  After going on a low carb ketogenic diet, I lost 80 lb.  My fasting glucose is now normal off all medication and my triglycerides are 90 with HDL of 60. My AlC is 5.5.  I have reversed my diabetes and metabolic syndrome as long as I say on the diet.  There are now ongoing trials of low carbohydrate, ketogenic diets to control and reverse diabetes. The most notable is the Virta health project done in conjunction with the University of Indiana.  In this study, as well as in several others, most diabetics are either off all medications or on drastically reduced doses after 6 months.

How to adjust and get off basal, ie Lantus, Levemir insulin:

As above, most diabetics make adjustments in the Lantus or Levemir doses either by increasing of lowering the dose by about 2 units at a time until the morning fasting glucose level is in the 100 to 140 range.  If a person with diabetes on basal insulin goes on a low carbohydrate, ketogenic diet, he or she will lose weight.  As the weight comes down, the insulin resistance actually improves and the requirement for basal insulin goes down.  What will happen is the morning fasting glucose will begin to drop.  When it goes below 80 or 90, I usually tell patients to cut the basal insulin dose by 5 units.  Then the glucose may rise for a few days.  Then as the patient continues the diet, and the insulin requirement goes down, the morning glucose usually eventually drops to 80 or 90 again, and the patient can cut another 5 units off the insulin dose.  This can be repeated until he or she is eventually on a lower dose of basal insulin or, hopefully off completely.

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