Diabetics who monitor their glucose levels often find that glucose levels increase overnight despite the fact that they do not snack during the night. This morning glucose elevation is a frequent characteristic of diabetes. In order to understand why glucose levels go up overnight we need to understand normal physiology.
Glucose is the energy source for the human body. The glucose that is in the blood , enters the cell where it is burned (oxidized) to give carbon dioxide (which is excreted when we breathe), water (which is excreted by the kidneys) and energy (which is used for the heart, breathing and muscle movements). If we had no glucose we would die. Normally when we eat, the carbohydrates (starches) are broken down by the digestive enzymes into simple sugars, these sugars are then absorbed through the wall of the small intestine and enter the blood which transports the sugar to wherever it is needed to provide energy. The body needs a backup system to produce glucose whenever we are not eating but need energy such as between meals and overnight. One of the backup systems that makes glucose and releases it into the blood to be used for energy is the liver. When glucose levels go down, insulin stops being secreted by the pancreas and the low insulin level causes the liver to start making glucose and liberating it into the blood for distribution. When we eat, we no longer need the liver to continue to provide glucose. When we eat, blood glucose levels rise as the food is absorbed, the increased glucose levels stimulate the pancreas to produce insulin, the rising insulin level in turn acts as a signal to the liver to stop producing glucose because the body is now getting enough glucose from food.
In the normal state, the production of glucose by the liver is regulated by insulin levels in the blood. When blood sugar levels rise, insulin is secreted; the increased insulin level signals the pancreas to stop production of glucose. In diabetics there is always insulin deficiency so the signal to the liver to stop glucose production is blunted. In addition there is almost always a degree of insulin resistance, because the liver is resistant to the effects of insulin, it keeps on producing glucose even if glucose levels are already high and insulin levels are high. The liver manufactures glucose in an unregulated manner all night and consequently the blood glucose level which may have been normal or slightly elevated at bedtime progressively increases overnight and the fasting glucose in the morning is too high (frequently the fasting glucose is the highest glucose of the day). A high glucose in the morning is an indication that the liver is overproducing glucose at night. Often the raised morning glucose is the first sign of diabetes that we see.
Generally we regard an elevated glucose level in the morning to be a sign primarily of insulin deficiency, while elevated glucose levels after meals (post-prandial hyperglycemia) is regarded as a sign primarily of insulin resistance although we should understand that both insulin resistance and insulin deficiency co-exist. In treating the diabetic with a high morning glucose we try to decrease nighttime glucose production by the liver. One way we can do this is to give a small dose of insulin at bedtime, the extra insulin may overcome the insulin resistance of the liver and signal the liver to stop glucose production. Another way of decreasing the high fasting glucose in the morning is to give the drug metformin which works primarily by inhibiting glucose production by the liver. We usually start by using metformin and titrating the dose up from one 500 mg tablet a day to 2 tablets morning and evening. We adjust the dosage until we have sufficient decrease in liver glucose production to give a normal glucose level in the morning of 4-7. If we cannot lower morning glucose to normal levels using up to 2000 mg of metformin a day (2x500 mg tablets twice a day), there is no point in increasing the dose still further since doses of greater than 2000 mg a day actually become less effective as the dose is increased so at this point we would add a second agent with a complementary mechanism of action to work in conjunction with the metformin to lower glucose. An example of a complementary drug is a thiazolidinedione (or glitazone) such as Actos (pioglitazone) or Avandia (rosiglitazone). These drugs lower blood glucose by increasing the removal of glucose from the blood by the muscle and fat tissue. Thus we have the metformin decreasing the amount of glucose released into the blood from the liver and the glitazone increasing the amount of glucose taken out of the blood by the fat and muscle. If we still have excessive glucose production by the liver and fasting glucose levels are still higher in the morning than at bedtime, we can add a drug that increases insulin production (an insulin secretagogue) or we can add insulin to try and overcome the insulin resistance and signal the liver to stop producing glucose.
In Summary: Glucose levels in the blood may increase between bedtime and morning if the liver produces too much glucose overnight. This is a typical problem for diabetics (doctors call it "Nocturnal Hepatic Gluconeogenesis"). Treatment is directed toward decreasing liver glucose production.