Lynne A. Wolfe, MS, PNP, BC
Blood Sugar Regulation
Glucose is the major carbohydrate used as fuel in our body to supply energy. It can easily be measured because some circulates in our blood stream, and can be easily checked with finger sticks. Average blood sugar levels are 100 mg/dl (70-120 mg/dl) or 5 mmol/L. The risk of developing Diabetes is increased when FASTING blood sugars stay consistently > 125mg/dl or 7 mmol/L. The risk of developing a Hypoglycemic Coma occurs when blood sugars are consistently < 45 mg/dl or 2.5 mmol/L. Under normal circumstances glucose is the preferred fuel of brain cells, and also muscle cells in early exercise.
Blood glucose levels are regulated by several hormones ~ Insulin, Glucagon, Epinephrine, Cortisol, and Growth hormone. Insulin promotes Glycogen synthesis, fat storage in the form of Triglycerides, and cellular uptake of blood glucose. Too much Insulin can lead to hypoglycemia (low blood glucose). Insulin acts in two phases. The first phase is secretion within 10 minutes of eating. The second phase is secretion about 2 hours after eating. Glucagon, Epinephrine, Cortisol, and Growth hormone all cause Glycogen breakdown and stimulate conversion of Amino acids to glucose. Persistent elevations of these hormones can lead to hyperglycemia (high blood sugar.) Glucagon breaks down Liver Glycogen stores to release glucose into the blood stream and it prevents the normal storage of extra glucose into Glycogen and Triglycerides. Glucagon has no effect on Muscle Glycogen. Epinephrine is very important during times of stress, including acute illnesses/infections, trauma etc. It causes increased glucose levels in the blood stream to ensure adequate glucose reaches brain cells. It stimulates the breakdown of muscle glycogen to raise blood glucose.
The FED State
When we are healthy and eating regular meals our body uses what it needs for energy immediately, then stores energy for later use. Stored energy comes from conversion of glucose into Glycogen and Triglycerides. Glycogen stores are in the Liver and Muscle. Glycogen can supply up to 1900 kcal. That will only last about 16 hours in an adult. Fats are stored in Adipose tissue. Depending on how much Adipose tissue we have, it can supply up 130,000 kcal. Glycogen stores and Fat stores increase with age. Proteins are also stored to be later broken down into their Amino acids, which can be converted into glucose if needed.
The FASTED State
Defined as no food intake for 6-12 hours, depending on your age. After 12 hours of no food intake, it is called a Prolonged Fast or Starvation. At the end of 6-12 hours 80% of glucose from food, will have been absorbed by tissues. The brain uses 50% of that glucose. After 12 hours, the body will get up to 75% of its energy from the breakdown of Glycogen stores. More glucose gets released from fat and muscle breakdown. Early in Fasting periods, free fatty acids and ketones begin to circulate in the blood. These can be used for energy by many tissues, including brain cells.
Blood sugars consistently < 45 mg/dl or 2.5 mmol/L defines hypoglycemia. Symptoms include: feeling hungry, sweating, trembling, and fast heart rate. These symptoms reflect the action of Epinephrine, as it tries to ensure that brain cells get adequate blood glucose. Remember, that under normal circumstances glucose is the preferred fuel of brain cells. If the action of Epinephrine and Glucagon cannot maintain a normal glucose supply to the brain cells we see confusion, loss of consciousness, and coma. Most Emergency Protocols, therefore require IV glucose be given if blood sugars are < 60 mg/dl to avoid the risk of severe hypoglycemia that can lead to coma or death.
Hyperglycemia defined as blood sugars consistently > 125mg/dl or 7 mmol/L. It is only valid after a 6-12 hour fast, of a healthy child. Because of the normal stimulation of both Glucagon and Epinephrine, during periods of stress (which include fever, acute illnesses like a GI infection or cold, trauma), a slightly higher than normal blood glucose is considered normal and protective to the brain and other tissues.
Prevention/Treatment of Hypoglycemia in Fatty Acid Oxidation Disorders
The normal body response to prevent severe hypoglycemia, is the release of fats that are broken down into ketones. In Fatty Acid Oxidation disorders the ability of the body to make ketones is limited NOT eliminated. The risk of developing severe hypoglycemia, and not having enough Glycogen stores is increased in infants and young children, in periods of Fasting longer than 6 hours, during acute illnesses especially those with fever, and only in certain Fatty Acid Oxidation disorders. MCAD and hypoglycemic VLCAD are the two Fatty Acid Oxidation disorders really at risk for severe hypoglycemia. Most children with SCAD will not experience severe hypoglycemia and the Carnitine Uptake disorders are also not usually associated with hypoglycemia. Also, once a child has been diagnosed and is under treatment for their FOD, they are less likely to develop severe hypoglycemia ~ especially if they are drinking Cornstarch at bedtime.
Nonetheless, since severe hypoglycemia can be life threatening, most Metabolic Specialists do set up Emergency Protocols for the recognition and prevention of a severe hypoglycemia. The precautions usually include: 1) preventing periods of fasting > 6 hours (infants usually 4 hours), 2) adjusting the Carbohydrate Sources in the Diet during periods of increased stress or illness, and, 3) use of Raw Cornstarch shakes.
During periods of “Low” stress, Carbohydrates in the diet should include complex carbohydrates with fiber, such as High fiber cereals, Whole grain breads, Brown rice, Bulgar wheat, Vegetables, Legumes, Apples, Oranges, Apricots, and low fat Dairy products. During periods of “high” stress, Carbohydrates in the diet should include more simple sugars and foods that breakdown easily into glucose, such as Sports drinks, Soft drinks, White rice, low fiber breads and cereals, Crackers, cooked potatoes, Fruit juices, Fruit Roll-ups, Jello, Jams, Jelly, and Bananas.
The use of Raw Cornstarch was first introduced in the 1980s as a therapy for Glycogen Storage diseases. It was given because it is a complex carbohydrate, high in fiber that takes 6-8 hours to fully breakdown. It therefore, could be given at bedtime, to prevent drops in blood sugar during the overnight fast. It could also be given 4 times a day during periods of illness to prevent severe hypoglycemia. Because of that Research we know several important things. First, Argo brand cornstarch appears to have the highest amount of Amylose, gets metabolized the slowest, and therefore has the longest action. We also know that Cornstarch shakes must be mixed in cool or room temperature fluids – cooking breaks the starch down and therefore stops the benefit of giving it. We know that compared to other starches, such as, Potato, Rice, Arrowroot, and Tapioca – Cornstarch has no flavor, although it does change the consistency of fluids which can be an issue for some children. Cornstarch has the best absorption of all the other starches as well. Additionally, Cornstarch has altered absorption when mixed in high sugar drinks, especially those high in Vitamin C, such as Orange juice or Lemonade. So it is recommended that Cornstarch be mixed in Sugar-free liquids. The one limitation to the use of Cornstarch, is that the enzyme, Amylase, is required to break it down. Normally Amylase function does not begin until after 8 months of age, sometimes as late as 2 years of age. That is one reason we usually recommend Infants get fed every 4 hours around the clock – we can’t use Cornstarch to prevent hypoglycemia during the overnight fast in them.
Glucagon should not be used to treat hypoglycemia in children with FODs, since their Glycogen stores are usually significantly depleted in the face of limited ketones as a secondary source of energy.