insulin
1. a protein hormone secreted by the beta cells of the pancreatic islets, serving as a hormonal signal of the fed state; it is secreted in response to elevated blood levels of glucose and amino acids and promotes efficient storage and use of these fuel molecules by controlling transport of metabolites and ions across cell membranes and regulating intracellular biosynthetic pathways. It promotes entry of glucose, fatty acids, and amino acids into cells; promotes glycogen, protein, and lipid synthesis; and inhibits gluconeogenesis, glycogen degradation, protein degradation, and lipolysis. Its secretion is also influenced by gastrointestinal hormones and by autonomic nervous activity. It is formed from a single polypeptide chain (proinsulin) that is cleaved by proteases at two points; the end pieces (A and B chains), held together by disulfide bridges, make up insulin; the connecting C peptide is also secreted but has no physiologic activity. Relative insulin deficiency is the cause of most cases of diabetes mellitus.
2. a preparation of the hormone, used in the treatment of diabetes mellitus; it may be bovine or porcine in origin or a recombinant human type, although insulin preparations of bovine origin are no longer available in the United States. Types vary in rapidity of onset, duration of action, and degree of purification (most containing some proinsulin and other antigenic components). 3. a rapid-acting, unmodified form of the hormone with an approximate time of onset of 30 minutes to 1 hour and duration of action of 6 to 8 hours, prepared from crystalline bovine or porcine insulin, or both. Administered subcutaneously, intramuscularly, intravenously, or by continuous infusion pump. Called also regular i.

Insulin. The precursor proinsulin is cleaved internally at two sides (arrows) to yield insulin and C peptide

insulin aspart, a rapid-acting insulin analogue in which an aspartate residue has been substituted for the usual proline at position 28 on the insulin B chain; administered by subcutaneous injection in treatment of diabetes mellitus.
buffered insulin human, insulin human buffered with phosphate; used particularly in continuous infusion pumps, but also administered subcutaneously, intramuscularly, or intravenously.
insulin detemir, a long-acting insulin analogue in which the threonine at position 30 of the B insulin chain is omitted, and a 14-carbon fatty acid chain is attached to the amino acid at position B29; administered subcutaneously in the treatment of diabetes mellitus.
extended insulin human zinc suspension, a long-acting insulin consisting of insulin human reacted with a zinc salt to produce zinc-insulin crystals. Administered subcutaneously.
extended insulin zinc suspension, a long-acting insulin with time of onset about 4 to 6 hours after injection and duration of action of 36 hours, consisting of bovine or porcine insulin modified by addition of a suitable zinc salt such that the solid phase of the suspension is predominantly crystalline. Administered subcutaneously.
insulin glargine, an insulin analogue that differs from human insulin in that the asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain; administered subcutaneously for once-daily insulin replacement therapy.
insulin glulicine, an insulin analogue having a more rapid onset and shorter duration of action than regular human insulin, administered subcutaneously at mealtimes for the control of hyperglycemia; it is used in combination with a longer-acting insulin or insulin analogue.
insulin human, a protein corresponding to insulin elaborated in the human pancreas, derived from pork insulin by enzymatic action that changes its amino acid sequence or produced synthetically by recombinant DNA techniques. The term may be used specifically to denote a preparation of regular insulin having the sequence of that in humans, or may be used generally to denote any insulin preparation with this sequence, including slow, intermediate, and fast-acting preparations.a preparation of regular insulin in which the insulin has the same sequence as that occurring in humans. Administered subcutaneously, intramuscularly, intravenously, or by continuous infusion pump.any insulin preparation with this sequence, including slow, intermediate, and fast-acting preparations.
insulin human zinc suspension, an intermediate-acting insulin consisting of a sterile suspension of insulin human in buffered water for injection with the addition of a suitable zinc salt such that the solid phase of the suspension contains a 7:3 ratio of crystalline to amorphous insulin. Administered subcutaneously.
intermediate-acting insulin, an insulin preparation whose onset of action is from 1.5 to 3.0 hours after injection and peak of action is between about 6 and 12 hours after injection. Examples include isophane insulin suspension and insulin zinc suspension.
isophane insulin human suspension, an intermediate-acting insulin consisting of insulin human reacted with zinc chloride and protamine sulfate such that the solid phase of the suspension consists of crystals composed of insulin, protamine, and zinc. Administered subcutaneously.
isophane insulin suspension, an intermediate-acting insulin with time of onset about 2 hours after injection and duration of action of 24 hours, consisting of bovine or porcine insulin reacted with zinc chloride and protamine sulfate such that the solid phase of the suspension consists of crystals composed of insulin, protamine, and zinc. Administered subcutaneously. Called also NPH i.
Lente insulin, insulin zinc suspension.
insulin lispro, a rapid-acting insulin analogue in which the lysine and proline residues at positions 28 and 29 on the insulin B chain are reversed; administered by subcutaneous injection in treatment of diabetes mellitus.
long-acting insulin, an insulin preparation whose onset of action is more than 3 hours after injection and peak of action is between 10 and 30 hours after injection. Examples include extended insulin zinc suspension and protamine zinc insulin suspension.
NPH insulin, isophane i. suspension.
prompt insulin zinc suspension, a rapid-acting insulin with an approximate time of onset of 1 hour and duration of action of 14 hours, consisting of bovine or porcine insulin modified by the addition of a suitable zinc salt to produce a suspension of amorphous insulin. Administered subcutaneously.
protamine zinc insulin suspension, a long-acting insulin with time of onset about 7 hours after injection and duration of action of 36 hours, consisting of bovine or porcine insulin reacted with zinc chloride and protamine to form a protein complex from which insulin is slowly released. It is unpredictable and is no longer used in the United States.
rapid-acting insulin, an insulin preparation whose onset of action is from 0.5 to 1.5 hours after injection and peak of action is about 2 to 4 hours after injection. Examples include insulin (def. 3) and prompt insulin zinc suspension. Called also short-acting i.
regular insulin, insulin (def. 3).
regular insulin human, insulin human (def. 2).
Semilente insulin, prompt insulin zinc suspension.
short-acting insulin, rapid-acting i.
Ultralente insulin, extended insulin zinc suspension.
insulin zinc suspension, an intermediate-acting insulin with an approximate time of onset of 2 hours and duration of action of 24 hours, consisting of a sterile suspension of insulin in buffered water for injection with the addition of a suitable zinc salt such that the solid phase of the suspension contains a 7:3 ratio of crystalline to amorphous insulin. Administered subcutaneously.
 

DIABETES
di·a·be·tes (di-be´tz) [ Gr. diabts a syphon, from dia through +bainein to go ]

1. any of various disorders characterized by polyuria. 2. d. mellitus.
adult-onset diabetes mellitus, type 2 d. mellitus.
alloxan diabetes, an animal model for diabetes mellitus; administration of alloxan produces selective destruction of the beta cells of the pancreas, causing hyperglycemia and ketoacidosis.
brittle diabetes, type 1 diabetes mellitus that is characterized by wide, unpredictable fluctuations of blood glucose values and is difficult to control.
bronze diabetes, bronzed diabetes, hemochromatosis.
central diabetes insipidus, diabetes insipidus due to injury of the neurohypophysial system, with a deficient quantity of vasopressin being released or produced, causing failure of renal tubular reabsorption of water. It may be inherited, acquired, or idiopathic. Called also pituitary d. insipidus.
chemical diabetes, former name for impaired glucose tolerance.
gestational diabetes, gestational diabetes mellitus, diabetes mellitus with onset or first recognition during pregnancy; it does not include diabetics who become pregnant or women who become lactosuric.
growth-onset diabetes mellitus, type 1 d. mellitus.
diabetes insi´pidus, any of several types of polyuria in which the volume of urine exceeds 3 liters per day, causing dehydration and great thirst, as well as sometimes emaciation and great hunger. The underlying cause may be hormonal (central d. insipidus) or renal (nephrogenic d. insipidus).
insulin-dependent diabetes mellitus, type 1 d. mellitus.
juvenile diabetes mellitus, juvenile-onset diabetes mellitus, type 1 d. mellitus.
ketosis-prone diabetes mellitus, type 1 d. mellitus.
ketosis-resistant diabetes mellitus, type 2 d. mellitus.
latent diabetes, former name for impaired glucose tolerance.
lipoatrophic diabetes, total lipodystrophy.
malnutrition-related diabetes mellitus, a rare type of diabetes mellitus associated with chronic malnutrition and characterized by beta-cell failure, insulinopenia, insulin resistance, and moderate to severe hyperglycemia, but without ketosis. Called also tropical or tropical pancreatic d. mellitus.
maturity-onset diabetes mellitus, type 2 d. mellitus.
maturity-onset diabetes of youth, maturity-onset diabetes of the young, an autosomal dominant variety of type 2 diabetes mellitus, classified into several types on the basis of the mutation involved, characterized by onset in late adolescence or early adulthood.
diabetes mel´litus, a chronic syndrome of impaired carbohydrate, protein, and fat metabolism owing to insufficient secretion of insulin or to target tissue insulin resistance. It occurs in two major forms: type 1 d. mellitus and type 2 d. mellitus, which differ in etiology, pathology, genetics, age of onset, and treatment.
nephrogenic diabetes insipidus, diabetes insipidus caused by failure of the renal tubules to reabsorb water in response to antidiuretic hormone, without disturbance in the renal filtration and solute excretion rates; characterized by polyuria, extreme thirst, growth retardation, and developmental delay. The condition does not respond to exogenous vasopressin. It may be inherited as an X-linked trait or be acquired as a result of drug therapy or systemic disease.
non–insulin-dependent diabetes mellitus, type 2 d. mellitus.
pituitary diabetes insipidus, central d. insipidus.
posttransplant diabetes, glucose intolerance or overt hypoglycemia that first appears after an organ transplant; some cases are steroid diabetes caused by use of steroid immunosuppressive agents.
preclinical diabetes, former name for impaired glucose tolerance.
puncture diabetes, diabetes produced in an experimental animal by puncturing the floor of the fourth ventricle in the medulla oblongata; see Bernard puncture, under puncture.
renal diabetes, see under glycosuria.
steroid diabetes, steroidogenic diabetes, glucose intolerance or overt hyperglycemia induced by glucocorticoids or estrogens; it is due in part to target tissue insulin resistance and is characterized by a relatively low incidence of microvascular sequelae.
subclinical diabetes, former name for impaired glucose tolerance.
thiazide diabetes, glucose intolerance or overt hyperglycemia induced by thiazide diuretics, which inhibit insulin secretion, possibly through thiazide-induced hypokalemia.
tropical diabetes mellitus, tropical pancreatic diabetes mellitus, malnutrition-associated d. mellitus.
Type I diabetes mellitus, type 1 d. mellitus.
type 1 diabetes mellitus, one of the two major types of diabetes mellitus, characterized by abrupt onset of symptoms, insulinopenia, and dependence on exogenous insulin to sustain life; peak age of onset is 12 years, although onset can be at any age. It is due to lack of insulin production by the beta cells of the pancreas, which may result from viral infection, autoimmune reactions, and probably genetic factors; islet cell antibodies are usually detectable at diagnosis. When it is inadequately controlled, lack of insulin causes hyperglycemia, protein wasting, and production of ketone bodies owing to increased fat metabolism, and the hyperglycemia leads to overflow glycosuria, osmotic diuresis, hyperosmolarity, dehydration, and diabetic ketoacidosis. It is accompanied by angiopathy of blood vessels, particularly the small ones (microangiopathy), which affects the retinas, kidneys, and basement membrane of arterioles throughout the body. Other symptoms include polyuria, polydipsia, polyphagia, weight loss, paresthesias, blurred vision, and irritability; if untreated, diabetic ketoacidosis progresses to nausea and vomiting, stupor, and potentially fatal hyperosmolar coma (diabetic coma). Called also insulin-dependent, juvenile, juvenile-onset, and Type I d. mellitus.

Type II diabetes mellitus, type 2 d. mellitus.
type 2 diabetes mellitus, one of the two major types of diabetes mellitus, characterized by peak age of onset between 50 and 60 years, gradual onset with few symptoms of metabolic disturbance (glycosuria and its consequences), and no need for exogenous insulin; dietary control with or without oral hypoglycemic is usually effective. Obesity and genetic factors may also be present. Diagnosis is based on laboratory tests indicating glucose intolerance. Basal insulin secretion is maintained at normal or reduced levels, but insulin release in response to a glucose load is delayed or reduced. Defective glucose receptors on the beta cells of the pancreas may be involved. It is often accompanied by disease of various sizes of blood vessels, particularly the large ones, which leads to premature atherosclerosis with myocardial infarction or stroke syndrome. Called also adult-onset, maturity-onset, non–insulin-dependent, and Type II d. mellitus.
 

Fluorescein-labeled anti-islet autoantibodies in islet cells, characteristic of type 1 diabetes mellitus
 
 

The Diabetes Center

Introduction to Diabetes

Diabetes is a very big topic! To make the diagnosis, complications and treatment of diabetes more understandable, we have broken "diabetes" into several dozen diabetes topic pages which go into more and more detail. Our diabetes search engine will help you find specific diabetes information, or you can come back to this introduction page to see each of the diabetes topic pages listed.

Diabetes is a disorder characterized by hyperglycemia or elevated blood glucose (blood sugar). Our bodies function best at a certain level of sugar in the bloodstream. If the amount of sugar in our blood runs too high or too low, then we typically feel bad. Diabetes is the name of the condition where the blood sugar level consistently runs too high. Diabetes is the most common endocrine disorder. Sixteen million Americans have diabetes, yet many are not aware of it. African Americans, Hispanics and Native Americans have a higher rate of developing diabetes during their lifetime. Diabetes has potential long term complications that can affect the kidneys, eyes, heart, blood vessels and nerves. A number of pages on this web site are devoted to the prevention and treatment of the complications of diabetes.

Types of Diabetes

Although doctors and patients alike tend to group all patients with diabetes together, the truth is that there are two different types of diabetes which are similar in their elevated blood sugar, but different in many other ways. Throughout the remainder of these web pages we will be referring to the different types of diabetes when appropriate, but when the topic pertains to both types of diabetes we will use the general term "diabetes".

Diabetes is correctly divided into two major subgroups: Type 1 diabetes and Type 2 diabetes. This division is based upon whether the blood sugar problem is caused by insulin deficiency (Type 1) or insulin resistance (Type 2). Insulin deficiency means there is not enough insulin being made by the pancreas due to a malfunction of their insulin producing cells. Insulin resistance occurs when there is plenty of insulin made by the pancreas (it is functioning normally and making plenty of insulin) but the cells of the body are resistant to it's action which results in the blood sugar being too high.

 

This is a listing of our "topic" Diabetes pages...they will lead you to more in-depth Diabetes pages.
 

 

Symptoms of Hyperglycemia

The signs and symptoms which suggest the presence of high blood sugar and Diabetes

The basic defect in all patients with diabetes is the decreased ability of insulin to induce cells of the body to remove glucose (sugar) molecules from the blood.  Whether this decreased insulin activity is due to a decreased amount of insulin produced (e.g. Type I Diabetes), or from the insensitivity of the cells to a normal amount of insulin, the results are the same...blood glucose levels which are too high.  This is termed "hyperglycemia" which means "high glucose in the blood".

hyper = high,  glyc = glucose,  and  emia = of the blood.

Common Symptoms of Hyperglycemia

The Classic Symptoms
  • Polyphagia (frequently hungry)
  • Polyuria (frequently urinating)
  • Polydipsia (frequently thirsty)
Other Symptoms Might Include
  • Blurred vision
  • Fatigue
  • Weight loss
  • Poor wound healing (cuts, scrapes, etc.)
  • Dry mouth
  • Dry or itchy skin
  • Impotence (male)
  • Recurrent infections such as vaginal yeast infections, groin rash, or external ear infections (swimmers ear)

It is important to remember that not everyone with diabetes will have all these symptoms. In fact, many people with Type 2 diabetes may not have any of them.

The classic symptom of being hungry frequently stems from the fact that the diabetic can not utilize glucose well as an energy source within cells.  The glucose is circulating in the blood, but the cells can't absorb it to use it as a fuel.   The excess blood sugar molecules also "spill" into the urine, meaning that as the blood filters through the kidneys, some of the sugar comes out of the blood and is not reabsorbed.  The extra sugar which is now in the urine causes water molecules to follow (a normal physics principle) and therefore the diabetic urinates frequently (the second classic symptom of diabetes).  This obviously leads to the third classic symptom which is frequently being thirsty.  The body can sense that excess water is being lost because of the frequent urinating and the normal response is to become thirsty.

 

Diagnosing Diabetes

The two primary tests and their results which combine to make the diagnosis of diabetes

In diagnosing diabetes, physicians primarily depend upon the results of specific glucose tests.  However, test results are just part of the information that goes into the diagnosis of diabetes. Doctors also take into account your physical exam, presence or absence of symptoms, and medical history. Some people who are significantly ill will have transient problems with elevated blood sugars which will then return to normal after the illness has resolved. Also, some medications may alter your blood glucose levels (most commonly steroids and certain diuretics (water pills)).  The two main tests used to measure the presence of blood sugar problems are [1] the direct measurement of glucose levels in the blood during an overnight fast, and [2] measurement of the body's ability to appropriately handle the excess sugar presented after drinking a high glucose drink.

[1]  Fasting Blood Glucose (Blood Sugar) Level:

The "gold standard" for diagnosing diabetes is an elevated blood sugar level after an overnight fast (not eating anything after midnight). A value above 140 mg/dl on at least two occasions typically means a person has diabetes. Normal people have fasting sugar levels that generally run between 70-110 mg/dl.

[2]  The Oral Glucose Tolerance Test

An oral glucose tolerance test is one that can be performed in a doctor's office or a lab. The person being tested starts the test in a fasting state (having no food or drink except water for at least 10 hours but not greater than 16 hours). An initial blood sugar is drawn and then the person is given a "glucola" bottle with a high amount of sugar in it (75 grams of glucose), (or 100 grams for pregnant women). The person then has their blood tested again 30 minutes, 1 hour, 2 hours and 3 hours after drinking the high glucose drink.

For the test to give reliable results, you must be in good health (not have any other illnesses, not even a cold). Also, you should be normally active (for example, not lying down or confined to a bed like a patient in a hospital) and taking no medicines that could affect your blood glucose. The morning of the test, you should not smoke or drink coffee. During the test, you need to lie or sit quietly.

The oral glucose tolerance test is conducted by measuring blood glucose levels five times over a period of 3 hours.  In a person without diabetes, the glucose levels in the blood rise following drinking the glucose drink, but then then fall quickly back to normal (because insulin is produced in response to the glucose, and the insulin has a normal effect of lowing blood glucose.)  In a diabetic, glucose levels rise higher than normal after drinking the glucose drink and come down to normal levels much slower (insulin is either not produced, or it is produced but the cells of the body do not respond to it) (see details on type 1 and type 2  diabetes for more information on this topic).

As with fasting or random blood glucose tests, a markedly abnormal oral glucose tolerance test is diagnostic of diabetes.   However, blood glucose measurements during the oral glucose tolerance test can vary somewhat. For this reason, if the test shows that you have mildly elevated blood glucose levels, the doctor may run the test again to make sure the diagnosis is correct.

Glucose tolerance tests may lead to one of the following diagnoses:

Normal Response
A person is said to have a normal response when the 2-hour glucose level is less than or equal to 110 mg/dl.
Impaired Fasting Glucose
When a person has a fasting glucose equal to or greater than 110 and less than 126 mg/dl, they are said to have impaired fasting glucose. This is considered a risk factor for future diabetes, and will likely trigger another test in the future, but by itself, does not make the diagnosis of diabetes.
Impaired Glucose Tolerance
A person is said to have impaired glucose tolerance when the 2-hour glucose results from the oral glucose tolerance test are greater than or equal to 140 but less than 200 mg/dl.  This is also considered a risk factor for future diabetes. There has recently been discussion about lowering the upper value to 180 mg/dl to diagnose more mild diabetes to allow earlier intervention and hopefully prevention of diabetic complications.
Diabetes
A person has diabetes when oral glucose tolerance tests show that the blood glucose level at 2 hours is equal to or more than 200 mg/dl.  This must be confirmed by a second test (any of the three) on another day. There has recently been discussion about lowering the upper value to 180 mg/dl to diagnose more people with mild diabetes to allow earlier intervention and hopefully prevention of diabetic complications.
Gestational Diabetes
A woman has gestational diabetes when she is pregnant and has any two of the following: a fasting plasma glucose of more than 105 mg/dl, a 1-hour glucose level of more than 190 mg/dl, a 2-hour glucose level of more than 165 mg/dl, or a 3-hour glucose level of more than 145 mg/dl.

Normal Regulation of Blood Glucose

The important roles of insulin and glucagon: Diabetes and Hypoglycemia

Insulin and glucagon regulate blood sugar.The human body wants blood glucose (blood sugar) maintained in a very narrow range.  Insulin and glucagon are the hormones which make this happen.  Both insulin and glucagon are secreted from the pancreas, and thus are referred to as pancreatic endocrine hormones. The picture on the left shows the intimate relationship both insulin and glucagon have to each other. Note that the pancreas serves as the central player in this scheme.  It is the production of insulin and glucagon by the pancreas which ultimately determines if a patient has diabetes, hypoglycemia, or some other sugar problem.

Insulin and glucagon are hormones secreted by islet cells within the pancreas (more about islet cells of the pancreas). They are both secreted in response to blood sugar levels, but in opposite fashion!

Insulin is normally secreted by the beta cells (a type of islet cells) of the pancreas.  The stimulus for insulin secretion is a HIGH blood glucose...its as simple as that!  Although there is always a low level of insulin secreted by the pancreas, the amount secreted into the blood increases as the blood glucose rises.  Similarly, as blood glucose falls, the amount of insulin secreted by the pancreatic islets goes down.  As can be seen in the picture, insulin has an effect on a number of cells, including muscle, red blood cells, and fat cells (shown in the picture).  In response to insulin, these cells absorb glucose out of the blood, having the net effect of lowering the high blood glucose levels into the normal range.

Glucagon is secreted by the alpha cells of the pancreatic islets in much the same manner as insulin...except in the opposite direction.   If blood glucose is high, then no glucagon is secreted.  When blood glucose goes LOW, however, (such as between meals, and during exercise), more and more glucagon is secreted.  Like insulin, glucagon has an effect on many cells of the body, but most notably the liver.  The effect of glucagon is to make the liver release the glucose it has stored in its cells into the blood stream, with the net effect of increasing blood glucose.  Glucagon also induces the liver (and some other cells such as muscle) to make glucose out of building blocks obtained from other nutrients found in the body (e.g., protein).

Our bodies desire blood glucose to be maintained between 70 mg/dl and 110 mg/dl (mg/dl means milligrams of glucose in 100 milliliters of blood).  Below 70 is termed "hypoglycemia".   Above 110 can be normal if you have eaten within 2 to 3 hours.  That is why your doctor wants to measure your blood glucose while you are fasting...it should be between 70 and 110.  Even after you have eaten, however, your glucose should be below 180.  Above 180 is termed "hyperglycemia" (which translates to mean "too much glucose in the blood").  If you have two blood sugar measurements above 200 after drinking a sugar-water drink (glucose tolerance test), then you are diagnosed with diabetes.  We have many pages on diabetes which go into this in much more detail.