Knowledge Center

Good insulin treatment can eliminate the added long-term risk associated with uncontrolled diabetes. A near-normal HbA1c level has been shown to prevent chronic complications from diabetes.

Insulin is now manufactured using genetically engineered microorganisms (bacteria and fungi).
Until 1981, all insulin was purified from beef and pork pancreas tissue.
The new engineered insulins are human insulin or modifications of the insulin molecule to speed or delay its action.

In the pancreas, insulin is made and secreted by beta cells in the islets of Langerhans, small cell groups which make up 1% of the pancreas by weight.
Other islet cells make glucagon (alpha cells), somatostatin (delta cells), or GRH (epsilon cells). These hormones oppose insulin action or raise blood sugar levels.

Some insulin pumps currently display glucose information from a continuous sensor.
New pumps will stop basal insulin infusion if the glucose sensor displays a low blood glucose level.
Research is ongoing on several systems using an insulin pump controlled by a glucose sensor. Progress is very slow.
Many hurdles are slowing progress on the artificial pancreas.
Current glucose sensors are sometimes inaccurate, especially at low glucose levels. Because sensors detect glucose in interstitial fluid, not blood, they display glucose numbers 10-15 minutes behind blood glucose levels.
The FDA has released guidelines for artificial pancreas development, and many groups are working furiously to produce a working prototype.
According to the current JDRF forecast, a successful external artificial pancreas will not be available before 2025.

Gene insertion research has successfully cured diabetes in dogs using viral vectors carrying genes for insulin and glucokinase.
These results were reported in 2012 and 2013.
Once FDA approval is obtained for human studies, beta cells may be produced from muscle cells using this technique.

The importance of a good dietitian has been repeatedly confirmed by longterm studies in diabetes treatment.
The more often you see a dietitian, the better your blood glucose control will be.
A dietitian visit every three months can kepp your Hemoglobin A1c reliably bellow 6.5% in type 2 diabetes.

Here at University Diabetes & Endocrine, we believe that nutritional counseling is as important as your visits to your doctor, if not more so.
See your dietitian at least twice a year.
Your dietitian is also a Certified Diabetes Educator, and can help with adjusting medications and insulin.

Keep a diet history for one week prior to your dietitian visit.
Our dietitians will help you learn how to eat the food you want, without having problems with your blood glucose or weight.
Food companies never stop making changes to foods that you eat. Keep abreast of what you’re made of, and stay healthy.

The Hemoglobin A1c level, or HbA1c, estimates the average blood glucose level during the past three month. Higher blood glucose levels bind more glucose to hemoglobin, the oxygen-carrying protein in the red blood cells. Once bonded to hemoglobin, glucose stays bonded until the red cell dies (lifespan of RBC = 3 months).
In persons without diabetes, the HbA1c level is 3.4%-5.7%. Levels more than 6.5% have been associated with a higher risk for chronic complications of diabetes.
Recently, a HbA1c of >6.5% has been used to make a diagnosis of diabetes.
The American Diabetes Association recommends HbA1c testing every three months, along with a foot exam, review of home blood glucose records, and adjustment of medications as needed. Blood test for kidney, liver function, and lipids are recommended every six to twelve months.

Diabetes is a Greek term meaning sluice, or spigot… referring to the increased quantities of urine excreted in this disorder.
The term Mellitus, meaning sweet, refers to the taste of the urine excreted by persons with this disorder.
Hence, Diabetes Mellitus is a term referring to the large quantities of sweet urine produced in this disorder.
Early physicians in China noted that urine from these patients attracted flies, unlike that of unaffected persons.

Hippocrates advocated the dietary therapy of diabetes, using a diet rich in fruits, grains, and vegetables.
Over two millenia, various diets for persons with diabetes were proposed; some included rancid meat, milk, bread, prunes, and starvation.

In 1869, a medical student named Paul Langerhans observed clusters, or islets, of specialized cells within the pancreas.
Islets contain three types of cells; alpha cells, which make glucagon; beta cells, producing insulin, and delta cells, which make somatostatin.

In the late 1800’s, researchers discovered that animals develop diabetes after surgical removal of the pancreas. Isolating a blood sugar-lowering factor from pancreas extract was difficult. This is because the pancreas also makes digestive enzymes which destroy proteins, like insulin, very quickly.
In 1921 Banting and Best produced an extract of bovine pancreas, which reduced blood sugar in a surgically depacreatectomized dog. They called their extract “iletin”.
In 1928, insulin was found to be a polypeptide, or small protein. Insulin is destroyed by stomach acid and intestinal enzymes, and cannot be given by mouth. Insulin skin patches, nasal sprays and inhalers are in development, but have not been as effective thus far in patients with diabetes.

The first insulins used in persons with diabetes were obtained from the human insulin molecule. Now, human insulin is made by genetically engineered bacteria or yeast, and is identical to our own insulin.
R, or Regular, insulin is a clear solution of insulin which begins to lower blood sugar about 30 after injection under the skin. Its activity peaks at 2-4 hours and is essentially gone after 6-8 hours. This insulin was the first ever used, and can be given at mealtime to control post-meal blood sugar.
The dose of R insulin required before a meal is the amount needed to control the postprandial (or after-meal) blood sugar level. Remember, a normal pre-meal blood sugar is 70-120 mg/dl. • In people without diabetes, the blood sugar can rise to 140 mg/dl after a large meal. But it rapidly returns to the 70-120 range within 4 hours.
The first long-acting insulins began appearing in the mid-1930’s. Doctors began using them once or twice per day in patients with diabetes. Now, these insulins are mainly used to control blood sugar levels overnight.
Protamine zinc insulin (PZI) was the first long-acting insulin; it acted for 48-72 hours after injection, and tended to build up in the body after months of use. This insulin was taken off the market ten years ago.
New longer-acting insulin analogs may be safer, and are in development now. See us about research projects we’re doing with these analogs now.
N insulin was introduced in 1937 as NPH (Neutral Protamine Hagedorn). It is a cloudy solution of insulin complexed with protamine, an inactive protein which is slowly degraded in the subcutaneous tissue after injection. The insulin is slowly released into the bloodstream, beginning to act in two hours and peaking at 6-8 hours after injection. Its activity persist for 24 hours.
L, or Lente insulin, is a cloudy solution of insulin in crystalline form. The crystals dissolve slowly under the skin, releasing insulin into the blood. L insulin begins acting in 2-3 hours, peaks at 6-8 hours, and persist for 18-24 hours after injection.
Human insulin is more soluble than beef and pork, and human Lente insulin never worked reliably. It has been discontinued.
The Lente series of insulins also includes Semilente, made with small crystals and acting slightly slower than R insulin, and Ultralente insulin, which consist of large crystals and last 24-30 hours. S insulin is rarely used; U insulin is used mainly to provide overnight control of blood sugar levels.
S and U insulins have been discontinued.
R insulin usually forms clusters around zinc atoms, which makes it pass more slowly into the blood after injection. It should be given 30-45 minutes before a meal to act properly on the blood sugar afterwards.
Humalog and Novolog are new insulin analogs, consisting of insulin molecules which do not aggregate. Since the analog insulin molecules do not form clusters, they pass quickly through smaller opening into the bloodstream. These insulins begin acting within 15 minutes after injection, peak at 1-2 hours, and persist for only 3-4 hours.
Unltralente insulin made with pork insulin was a very long-lasting drug, because pork insulin forms hard crystals which dissolve slowly. Human insulin on the other hand is more soluble in water, and forms loose soggy crystals which do not last nearly as long after injection.

Insulin is lifesaving treatment for persons with type I diabetes mellitus. It is also used in those patients with type II diabetes whose own insulin is inadequate for good blood sugar control. In anyone using insulin, the correct dose is the smallest dose which controls the blood sugar within normal limits.

Type I, or juvenile-onset diabetes, results from destruction of the beta (insulin-producing) cells by the body’s immune system. It appears suddenly, causing weight loss, fatigue, copious hunger, and then acidosis with shortness of breath, vomiting, and coma.
IDDM occurs most frequently in young people; peak incidence occurs at age 7-8, age 15-17, and 22-24.
Geographically, population living further north or south of the equator have higher instances of IDDM.
Studies linking IDDM to cow’s milk, dog ownership, or sugar consumption have been discounted.
The onset of IDDM may occur after an upper respiratory infection.
The virus may cause an immune response against the beta (insulin-secreting) cells in the pancreas.
Anti-beta cell antibodies then attack and injure beta cells, causing IDDM.
People who have diabetes with positive IA-2 and ICA antibody test usually lose most or all of their insulin-making cells within one year after diagnosis. Good blood sugar control seems to help preserve insulin production, but is more difficult in these persons.

Type II, or Adult-onset diabetes mellitus, occurs when a person has insufficient insulin to control the blood sugar.
8%-12% of the American population has AODM. About 25% of Americans have the genetic potential for developing AODM, but those who develop it usually have another risk factor along with the gene(s) for AODM.

These include obesity or weight gain, sessile lifestyle (inactivity), overeating, or taking certain medicines can precipitate AODM.
Stress, either physical or mental, can trigger or worsen diabetes.
Pregnancy can trigger AODM; about 1 in 8 pregnancies are complicated by diabetes.

Some 90% of Americans with diabetes have AODM (type II diabetes).
10% have IDDM (type I diabetes).

About 1 in 200 American school children have diabetes (almost always IDDM).
IDDM challenges young persons who must deal with teachers, principals, and fellow students regarding insulin, blood glucose monitoring, and diet/activity.
Treating IDDM in school takes courage as well as diabetes education.

“Managing diabetes is like swimming in glue.” -Anonymous(1980)
“Managing diabetes requires intelligence and capability beyond the physician” ADA (1999)
“He who knows diabetes, knows medicine.” -Sir William Osler

Diabetes is responsible for 50% of all extremity amputations in adults, for 50% of all adult renal failure, and for 65% of all blindness in the United States.
Adult-onset diabetes mellitus (type II) is 10% more common in men than in women, and two-fold more common in African-Americans than Caucasians. American Indians and Latino populations also have higher incidences of AODM than Caucasians.

The name “Diabetes was first applied by Aretaeus of Cappidocia in the year 70 A.D., to a condition characterized by “a wonderful wasting of the body into urine.”
Thomas Willis, a London physician, described the sweet taste of urine in diabetes, and added the “mellitus” meaning “honey like”.

During the second world war, the incidence of AODM in Britain and France dropped to almost zero during times of short food supplies. After the war, with food plentiful, the incidence of diabetes rose to pre-war levels.

Pathophysiology refers to the abnormalities (“Pathos”) of normal body chemistry (“physiology”) caused by disorders such as diabetes. In diabetes, abnormal body chemistry occurs because of elevated blood sugar levels.
In the human body blood sugar is usually maintained within tight limits between 70 and 105 mg/dl fasting, and < 140 after meals.
Glucose is the main energy source for cells; by breaking glucose down into water and carbon dioxide, high-energy chemicals bonds are generated inside the cells. These power the chemical reactions which make up life.
Glucose, or blood sugar, is chemically active.
Glucose molecules stick to other molecules in the body; the more glucose there is, the more of it sticks to other molecules. Adding a glucose molecule to another molecule in the body alters the shape, and sometimes the function of the second molecule.
Glucose in the blood is dissolved, surrounded by water molecules. Wherever glucose goes in the body, some 20-25 water molecules follow.
Water takes up space, and so when glucose attaches to another molecule in the body it’s like attaching a basketball to a keychain. The shape, and usefulness, of the molecule changes.
Blood glucose can attach to the walls of blood vessels. This causes the walls to thicken, decreases movement of oxygen and carbon dioxide into and out of the bloodstream.
High blood sugar thus decreases the nutrient and oxygen supply to tissues and organs in the body.
When the blood glucose level exceeds 180 mg/dl, glucose begins to spill into the urine. Water follows the glucose, increasing urine volume.
People with elevated blood glucose levels urinate frequently, and become dehydrated.
Ketones are formed from the remnants of fat molecules.
When insulin is low or absent, fat is broken down for energy.
The body cannot use ketone molecules, so they circulate in the blood, and are excreted in the urine.
Ketone molecules are acidic.
When insulin is very low or absent, fat is used for energy in large amounts, ketones build up in the blood.
This produces a condition called Diabetic Ketoacidosis (DKA). Before 1923, everyone who developed IDDM died of DKA after a terrible, wasting illness.
The liver can make fat into blood sugar.
This capability keeps your brain functioning during starvation.
Brain cells function properly only with a continuous glucose supply.
When insulin is absent, liver cells make glucose from fat. This raises blood sugar and keeps the brain supplied with glucose.
Diabetic Ketoacidosis occurs when insulin is low or absent, and ketones from fat breakdown making the blood acidic.
DKA is treated with insulin, which stops the runaway breakdown of fat by signaling the liver to stop making glucose.
A normal lean adult human produces 20-25 units of insulin per day. Inactive obese adults make 100-250 units per day. The more body a person carries, the more insulin is required to control the blood glucose.
An obese lumberjack may only produce 20-30 units of insulin per day, because exercise burns glucose without requiring insulin.
A normal human pancreas can produce up to about 300 units of insulin per day.
People with the genes for Type II diabetes (A)DM may only be able to produce up to 200 units of insulin per day.
As a person gains weight the insulin-making capacity of the pancreas may be overwhelmed. This cause AODM.
In a normal adult, beta cells make insulin under stimulation by blood glucose.
Whenever the blood glucose is over 100 mg/dl, beta cells are secreting insulin as fast as they can.
Beta cells make small amounts of insulin throughout the day. Most insulin is released after eating.
When the beta cells are making insulin rapidly, they devote ALL of their energy to insulin production. Only when resting can they repair and maintain the insulin-making enzymes, and cellular machinery.

Most cells, like liver, devote a third of their energy to repair and maintenance at all times.
Liver cells rebuild themselves completely every three days.
Beta cells cannot spare any energy for repair unless the blood glucose is less than about 90-100 mg/dl.
In people who are resistant to insulin, B-cells must work harder, and longer, to make enough insulin to control the blood glucose.
These cells have less time to repair the insulin-making machinery.
If not maintained, any machinery begins to break down. Less insulin is produced, and the blood glucose becomes higher.
Eventually blood glucose levels remain high throughout the day.
The B-cells continue making insulin, but not maintaining themselves… and insulin-making capacity falls further.
The B-cells cannot occur until the blood glucose is normalized by medication or insulin.
In type II diabetes, normalizing the blood glucose permits the B-cells to heal their insulin-making capacity.
Excellent blood glucose control is the best means of producing B-cell recovery, and having a chance of using less medicine to control blood glucose.

Diet is the primary treatment for type II diabetes.
Eating a lower-calorie, lower-carbohydrate, diet helps to control the blood glucose.
Not everyone can follow a rigid diet. Other treatments are often combined with diet to control the blood glucose.
Diet therapy of diabetes helps prevent people from having risk related to poor eating, such as weight gain caused by overeating, or illnesses resulting from poor quality food, vitamin or fiber deficiencies.
Exercise is the second cornerstone of diabetes treatment.
Doctors have long noted that persons with diabetes who are physically active live longer, and have fewer complications than those who are inactive.

Exercise makes the body more sensitive to insulin.
People who exercise can eat more, lose weight more easily, and keeps their blood glucose levels within tighter limits.
People prone to AODM can prevent diabetes from occurring by staying physically active.
It has been estimated that 80% of all AODM cases can be controlled by diet and exercise alone, but most people with AODM require medications for good blood glucose control. Many factors, such as overeating, the huge number of fast food restaurants, or convenience foods, and being too busy can result in poor dietary habits.
How much exercise is required to improve insulin sensitivity.
20-30 minutes of aerobic exercise three to four times per week will reduce insulin needs 20%-30%.
A good exercise program should include DAILY activity, exercising, and to permit the personal satisfaction and well-being which occurs after a good daily workout.
Before beginning an exercise regiment, you should do a stress test to ensure your cardiovascular fitness if you are over 35 years of age, have any complications of diabetes (such as retinopathy), or have two or more risk factors associated with heart disease.

It has been estimated that 80% of all AODM cases can be controlled by diet and exercise alone, but most people with AODM require medications for good blood glucose control. Many factors, such as overeating, the huge number of fast food restaurants, or convenience foods, and being too busy can result in poor dietary habits.

People overeat because we have had a dependable food supply only for a few hundred years. Before organized farming, food was scarce, starvation was frequent, and people ate irregularly.
Food is now plentiful, and cheap. Eating must be thoughtful, or overeating can occur.
People with the genes for AODM (type II diabetes) are sometimes descended from nomadic populations which endure starvation for months at a time.
In those days, those who survived could gain weight rapidly (good appetite), and lose it more slowly (inactive). Now those characteristics can make us overweight, and resistant to insulin.
Saudi Arabia was a land of nomadic herders who wandered the dessert, and diabetes was rare.
When oil wealth produced a lifestyle of Cadillacs, Burger Kings, and corn flakes, the incidence of AODM rose to 51% in adults.
Pima indians, Mexican-Americans, and African-Americans had similar lifestyle changes and high incidence of AODM.

In Tennessee AODM affects 8%-10% of the adult population. Here our risk factors include biscuits and gravy, Krystals, cakes, and television.
Decreasing physical activity parallels the recent increase in AODM incidence in all developed countries.

Just as diet and exercise are the major treatments for diabetes, overeating and inactivity (and anything that causes them) are the major risk factors for tise disorder. Consider the following modifications to reduce your risk:

Watch television from your treadmill, or exercise bicycle.
Eat a salad first at the fast food restaurants.
Raise a garden in the summer, and sprout seeds in the winter.
Take hikes in search of edible plants in the Tennessee River Gorge.

The complications of diabetes are all associated with high blood glucose (sugar) levels.
Controlling blood glucose levels will prevent complications of diabetes.

Glucose molecules bind to the structural and functional proteins in the blood, blood vessels, filtration membranes in the kidneys, and the blood cells.
Glycohemoglobin (hemoglobin A1c is hemoglobin protein with glucose attached to one end.
The more glucose present in the blood, the more glucose adheres to other molecules in, and in, contact with the blood. Attaching glucose to proteins alters their structure, and function.
For example, glucose attaches to low-density lipoprotein (LDL) molecules, changing their shape, and causing them to be ingested by the cells which line the blood vessels. As these cells fill with LDL cholesterol, they form atherosclerotic plaques (“hardening of the arteries”). This is one way that diabetes causes heart attacks and strokes.
Risk for heart attack and stroke increases three-fold with uncontrolled diabetes. This is due to premature atherosclerosis.
Glucose also makes blood platelets more sticky, which promotes blood clotting in arteries.
In uncontrolled diabetes glucose sticks to collagen molecules, which form the arterial walls, disrupting their sheet-like structure. This causes premature aging of the skin, blood vessels, and fibrous tissues.
In the eye high blood glucose causes sugar molecules to accumulate inside the lens, which leads to cataract formation.
Uncontrolled blood glucose levels weaken the small blood vessels in the retinas; new, abnormal blood vessels grow, break, and bleed, causing retinal hemorrhages. Blood accumulates in the eyes, and causes blindness. This is retinopathy, the leading cause of blindness in adults.
In the kidney, blood is filtered through membranes called the glomerular membranes. These membranes hold electrical charges which repel blood proteins, keeping them out of the urine. Glucose can disrupt this charge barrier, allowing protein to enter the urine.

Protein in the urine is the first sign of kidney disease in diabetes. Before good diabetes control became possible, protein in the urine heralded an irreversible decline in kidney function. This caused renal failure within an average of seven years.
Excellent control of blood glucose levels, good blood pressure control, and a low-protein diet, prevents the decline of kidney function, and reduces protein in the urine.
Many people with diabetes who have kidney disease, or are at risk, take a type of blood pressure medicine called ACE inhibitor to prevent renal problems. Ask your doctor whether an ACE inhibitor might be useful for preserving your kidney function.

A low-protein diet can reduce the amount of protein in the urine, and preserve renal function in diabetes. For people with diabetes and kidney disease, a vegetarian diet is an excellent alternative.

High blood pressure occurs more frequently in persons with diabetes. People with hypertension, and diabetes, develop eye, and kidney complications more quickly if blood pressure and glucose are not controlled. Blood pressure control is very important to prevent these complications.
Blood pressure is increased by obesity, high-protein diet, smoking, alcohol use, stress, and genetic factors. Changing one’s lifestyle is sometimes sufficient to control blood pressure, but medications are often needed as well.

Your doctor may use one of many drugs to treat hypertension, or high blood pressure. Diuretics (“water pills”) are commonly used. Some diuretics, such as Dyazide (HCTZ), and beta blockers (Inderal), can increase blood sugar. Ask your doctor about the use of these drugs in diabetes.
Other anti-hypertensive drugs dilate the blood vessels. These include calcium channel blockers (Calan, Norvasc, Cardiazem, nifedipine), Apresoline, Aldomet, Hytrin, clonidine, and Tenex. In general, these drugs have little or no effect on the blood glucose level.
Protein in the diet may raise blood pressure in some persons. According to available data, animal protein is more likely to raise blood pressure than vegetable protein.
To ensure that protein is not a factor increasing blood pressure, limit animal protein to 60 grams or less per day.
Vegetables in the diet may lower blood pressure because of their potassium, magnesium, and fiber content. Green leafy vegetables are most beneficial in this regard.

ACE inhibitors are often used to treat hypertension in persons with diabetes. These agents include Capoten, Accupril, Vasotec, Altace, Zestril, and Mavik. ACE inhibitors have a beneficial effect upon kidney function in diabetes. Side effects may include a dry cough, fatigue, and sexual dysfunction particularly at high doses.

The most common oral medicines for diabetes are the sulfonylureas. Glucotrol, Glynase, Micronase, and Diabeta are all sulfonylureas. These drugs work by causing the pancreatic beta cells to make more insulin.
Oral diabetes medicines depend upon beta cells, therefore they only work in Adult onset diabetes where some insulin is produced. Persons with IDDM do not produce sufficient insulin to benefit from oral medications.
Glucotrol (glipizide) is a short-acting sulfonylurea drug used in adult onset diabetes. It is taken before meals, two or three times daily. Side effects include low blood glucose (from overdose), skin rash, and occasional nausea.
Glyburide (Glynase, Micronase, Diabeta) is a longer acting sulfonylurea drug. It is taken before meals, once or twice daily. This drug tends to build up in elderly persons, and should not be given to persons over 65 years of age.
Side effects of glyburide include low blood sugar (which may last for several days), skin rash, fatigue, and nausea.
Metformin (Glucophage) is a biguanide drug, which works by making the body more sensitive to the effects of insulin. It works only in Adult-onset diabetes. This medicine is often combined with sulfonylurea drugs like glipizide, or glyburide, to achieve greater glucose-lowering effect.
Side effects of metformin (Glucophage) include diarrhea, fatigue, and nausea. This medicine does not cause hypoglycemia (low blood sugar).
Precose is a unique medicine which is not absorbed by the body. Its effect is to slow the absorption of dietary sugars into the bloodstream. This gives the pancreas more time to make insulin before the blood sugar rises after a meal.
Precose has a tendency to cause gas and flatulence. When this side effect occurs, the dose of Precose can be reduced.
Unfortunately its effect on the blood sugar is small, and so Precose is usually given only in mild diabetes.

JAMIE MOSES APN received her advanced practice degree from Southern Adventist University, and has worked in emergency medicine, palliative care and obstetrics for ten years.
She has 25 years of personal experience with type 1 diabetes mellitus.
Her interests include advanced diabetes care and insulin pump therapy, and carbohydrates.

Actos (pioglitazone) and Avandia (rosiglitazone) are new oral medicines for adult-onset diabetes patients. They make the body more sensitive to insulin, so that any insulin made or given tends to work better.

Actos or Avandia can help many people with adult-onset diabetes avoid, or reduce, their need for insulin injections.
Either of these medications increases the number of glucose-transporting proteins in muscle cells… gradually building its effect over three or four weeks.
Rezulin, the first thiazolinediane, caused rare patients to develop liver damage, and was withdrawn from the market a few years ago. Actos and Avandia, through chemically similar to Rezulin, do not appear to cause liver damage. Nonetheless, your doctor should test blood for liver enzymes before beginning treatment with these medications.
Rezulin was the first thiazolidinedione. Actos and Avandia have been approved, and one other similar medicine may be approved in the next few years for diabetes treatment.

Prandin (repaglinide) increases insulin secretion at meals. It is given before meals, usuually three times daily. Prandin works somewhat differently from drugs like Glyburide or Glipizide, and is occasionally used with these drugs to increase their effect.
Prandin appears to be very well tolerated. Among its side effects are rare skin rash, and rare diarrhea. Low blood sugar reactions are also possible with this drug, like the sulfonylureas. Prandin may be safer for older patient than other medicines because of its short duration of action.

Starlix (nateglamide) is another medication which is given before meals…Like Prandin, it stimulates insulin secretion briefly at a meal.
Invokana is the first SGLT-2 inhibitor. It causes glucose to be lost in the urine, lowering blood sugar levels in the process.

Several types of new diabetes medicines are now in the research phase, and may be marketed in the next few years.
One family of drugs increases urinary excretion of blood sugar.
Another drug works like insulin, but can be given orally.

Obesity causes diabetes to appear in persons who have a genetic tendency for insulin resistance. Adult-onset diabetes is strongly inherited. So if a close relative has AODM, your chance of developing diabetes increases with your body fat mass.
In families with a genetic tendency to develop diabetes more obese family members will develop AODM, while lean relatives are more often spared.
Persons with a genetic tendency toward AODM may suddenly develop very high blood glucose levels after an episode of overeating (such as a weekend in Las Vegas, browsing the casino buffets).
Often, persons with AODM are not diagnosed for a long time… sometimes not until retinopathy, kidney disease, or a heart attack occurs. Early symptoms include blurred vision, sleepiness after meals, increased urination, itching, leg cramps, yeast infections, and slow wound healing.

Diabetes is diagnosed when a fasting (AM) blood glucose level of over 116 mg/dl is persistent
Diabetes is likely if the blood glucose goes over 180 mg/dl after a meal.
The gold standard for diagnosing diabetes is the oral glucose tolerance test. In this test a sugary drink is given, and the blood sugar is measured at half-hour intervals for two hours. Diabetes is present if the blood glucose exceeds standardized limits.

Hypoglycemia occurs when the blood sugar level falls below the normal range. Most people will have symptoms (weakness, shakiness, sweating, tingling in fingers, tongue and lips) when the sugar level is less than 60 mg/dl.
The normal range of blood sugar is 70-120 mg/dl. The brain requires at least 40 mg/dl to function properly. When the sugar level falls below 40, symptoms of “neurohypoglycemia” (sleepiness, delirium, abnormal behavior, convulsions, and coma) can occur. This is very dangerous, and can eventually damage the brain.
Some people whose blood sugar has been above 150 mg/dl for weeks, or months, may have hypoglycemic symptoms when the sugar falls into normal range; these symptoms usually disappear if the sugar level remains in the normal range for a few hours.
The body reacts more to the rate of change of blood sugar than to the absolute sugar level. This means that symptoms of low blood sugar can occur when the blood sugar falls rapidly, even if the level of sugars are above the normal range! So always check the blood sugar when you have symptoms; it may just be falling fast, and not yet low.
When the blood sugar level is below 70 mg/dl, take 15 grams of simple carbohydrate (8 oz orange juice, 6 crackers, or ¼ of a typical candy bar) to bring it up to normal. Be sure to check the blood sugar in 20 minutes to confirm that it is rising; if it remains low, repeat the treatment.
Some people find it hard to resist overeating when their blood sugar is low. It is important not to overeat hypoglycemia, as the resulting high blood sugar level will be hard to treat, and taking more insulin may cause further hypoglycemia.
Most symptoms of hypoglycemia are caused by adrenalin. Adrenalin causes the liver to make sugar, which raises the blood sugar level. For 12-24 hours after a hypoglycemic episode the liver continues to make more sugar. So insulin may be required after a hypoglycemic reaction to control blood sugar levels.

Incretin hormones are secreted by cells in the intestinal lining.
These hormones act on the liver, the brain, and the pancreas during meals.
The presence of incretin hormones was suspected in the 1960’s, but the first incretins were isolated in the 1980’s.
In humans, the main incretin hormone is Glucagon-Like-Polypeptide-1 (GLP-1).
GLP-1 is secreted by cells in the small intestine at mealtimes.
GLP-1 is rapidly destroyed, circulating in the blood for only 1-2 minutes after secretion.

GLP-1 increases insulin secretion by the pancreatic beta cells.
It also decreases glucagon secretion by the pancreatic alpha cells.
More insulin and glucagon lowers the blood glucose level.
In normal people 75% of the blood sugar between meals, and at night, comes from the liver. The liver makes sugar to support the brain (brain cells need sugar to function); this is why low blood glucose levels frequently disturb one’s thinking.
At mealtimes when sugar is being absorbed from food, the liver stops making glucose. Levels of Glucagon, the hormone responsible for hepatic glucose production, fall at mealtime because GLP-1 inhibits glucagon secretion.
In humans GLP-1 also reduces appetite, and increases satiety (the “full” feeling which occurs after eating).
Medicines which mimic GLP-1 can thus reduce appetite, food consumption, and produce weight loss.

Exenatide is the first GLP-1 analog to be marketed under the BYETTA.
in 1994 exenatide was discovered in the saliva of Gila Monsters, where its function is not known, and is now biosynthesized.
In type II diabetes mellitus, Exenatide reduces blood sugar levels along with appetite and insulin resistance. Many patients who use this medication lose weight by reducing the size of their meals. Exenatide can cause bloating after excess food intake.

The first of this new class of medications for type II diabetes mellitus became available in November 2006.
These drugs work by inhibiting DPP4, the enzyme which breaks downs the body’s own GLP-1. Their effects are thus similar to those of exenatide.
In clinical studies DPP4 inhibitors reduced blood glucose levels after meals, and improved satiety with a mild reduction in appetite.
Because these medications are taken orally, and do not cause low blood glucose levels, they may be safer than sulfonylurea drugs in the treatment of type II diabetes mellitus.

Amylin is a small incretin-like hormone which is produced and secreted by pancreatic beta cells. It is released along with insulin at mealtimes, and throughout the day.
Amylin inhibits glucagon effects on the liver. It also reduces appetite, and increases satiety, as does GLP-1.

Because people with type I diabetes mellitus lack beta cells, they have no insulin or amylin.
With insulin treatment in type I diabetes, blood sugars typically rise to very high levels after meals. Without amylin, the liver continues to make sugar even at mealtime.

When insulin and amylin are both given at meals hepatic glucose production is reduced, and blood sugar levels rise much less after eating.
Adding amylin also reduces mealtime insulin requirement by 10%-30%.

Amylin is unfortunately very short-lived, expensive to make, and hard to handle.
Pramlintide, the first amylin analog, is now available for use in type I diabetes. It is injected before meals, and snacks, to reduce blood glucose excursions after eating.
Pramlintide (Symlin) may cause bloating after overeating. Because it reduces mealtime insulin requirements, hypoglycemia is a potential side effect.
Unfortunately pramlintide is soluble only at a pH of 4 (insulin is pH7), so mixing the two hormones in an insulin preparation is not yet practical.
Probably the best of pramlintide effects is its ability to reduce the rapid blood glucose changes which occur in type I diabetes mellitus.
In clinical studies, many patients taking pramlintide reported improved well-being.

Type I, or autoimmune, diabetes can occur at any age. When adults develop diabetes with characteristics of type I diabetes, doctors may do a blood test for antibodies against the beta cells (insulin making cells).
Antibody test are usually done to exclude autoimmunity against the beta cells. People with diabetes, and positive islet cell antibodies, have type I diabetes, or late-onset autoimmune diabetes.
These people must be treated differently than people with type II diabetes in order to protect their insulin-producing cells from autoimmune destruction.
The antibody test include:
ICA, or islet-cell antibodies, usually positive in children or adults with type 1 diabetes.
IA-2, usually positive in type I diabetes.
GAD-65, positive in late-onset autoimmune diabetes or in type I diabetes.
Late-onset autoimmune diabetes, or LOAD, is diagnosed when GAD-65 is positive, but the other antibodies are negative.
People with LOAD can keep, or improve, their insulin-making capability for many years IF blood sugar levels are kept in excellent control.

xcellent blood glucose control has been our only means of preserving insulin production in people with type I diabetes, or late-onset autoimmune diabetes. Insulin is almost always needed for these people.
The more insulin a person makes, the easier it is to control blood glucose levels.
Some medicines like DPP4 inhibitors, and Byetta, have been shown to help restore insulin-producing cells in animals.
These medicines are employed in late-onset autoimmune diabetes based on the animal data, but no studies have been reported in humans as of yet.
Very recently, infusion of modified monoclonal antibodies have been shown to reverse type I diabetes in some people within three months after diagnosis.
These antibody treatment may be our first real means for stopping autoimmune destruction of insulin-making cells.
University Diabetes & Endocrine Consultants is one of eleven centers in the USA where the reversal of type I diabetes is now being studied.
Persons aged 8-35 years, with type I diabetes or late-onset autoimmune diabetes for less than three months, may enter this study.
Other studies have tested various vitamins, milk proteins, and medications in recent-onset type I diabetes. None of these helped control, or reverse, the autoimmune destruction of islet cells.
Insulin may slow the destruction of beta cells, but only when blood glucose levels are controlled very well.
Researchers are working with antibodies against the GAD-65 antibody, and immunizing animals against GAD protein, hoping to find other useful treatments to stop autoimmune destruction of beta cells.
Late-onset autoimmune diabetes occurs in adults of any age, any weight, and with, or without, history of diabetes.
For many years, these people were treated as if they had type I diabetes, and lost most of their insulin-making capacity within a year after diagnosis.

With the help of intensive insulin treatment, and newer medications, people with late-onset autoimmune diabetes may keep much of their insulin production for many years.
As noted, having more insulin production helps make blood glucose control much easier.

Knowledge Center

Services

Company