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Diabetes - type 1

Highlights

Type 1 Diabetes

In type 1 diabetes, the pancreas does not produce insulin. Insulin is a hormone that is involved in regulating how the body converts sugar (glucose) into energy. People with type 1 diabetes need to take daily insulin and carefully monitor their blood glucose levels.

Type 1 diabetes is much less common than type 2 diabetes. It accounts for 5 - 10% of all diabetes cases. Type 1 diabetes can occur at any age, but it usually first develops in childhood or adolescence.

Symptoms of Diabetes

Symptoms of both type 1 and type 2 diabetes include:

In general, the symptoms of type 1 diabetes come on more abruptly and are more severe than those of type 2 diabetes.

Warning Signs of Hypoglycemia

Hypoglycemia (low blood sugar) occurs when blood sugar (glucose) levels fall below normal. All patients with diabetes should be aware of these symptoms of hypoglycemia:

It is important to quickly treat hypoglycemia and raise blood sugar levels by eating sugar, sucking on hard candy,  drinking fruit juice, or injecting the hormone glucagon. Patients who are at risk for hypoglycemia should carry some sugar product, or an emergency glucagon injection kit, in case an attack occurs. In rare and worst cases, hypoglycemia can lead to coma and death. Regular blood sugar monitoring throughout the day can help you avoid hypoglycemia. Patients should also  wear a medical alert ID bracelet or necklace that states they have diabetes and take insulin.

Patients with Type 1 Diabetes Living Longer and Healthier Lives

Rates of serious complications among people with type 1 diabetes have decreased over the past several decades. Better control of blood sugar, new treatment strategies, and improved management of co-existing conditions such as high blood pressure appear to have contributed to this positive change.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes.

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to a complete or partial lack of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism:

Pancreas
The pancreas is located behind the liver and stomach. In addition to secreting digestive enzymes, the pancreas secretes the hormones insulin and glucagon into the bloodstream. The release of insulin into the blood lowers the level of blood glucose (simple sugars from food) by enhancing glucose to enter the body cells, where it is metabolized. If blood glucose levels get too low, the pancreas secretes glucagon to stimulate the release of glucose from the liver.

In type 1 diabetes, the pancreas does not produce insulin. Onset is usually in childhood or adolescence. Type 1 diabetes is considered an autoimmune disorder that involves:

Type 2 diabetes is the most common form of diabetes, accounting for 90 - 95% of cases. In type 2 diabetes, the body does not respond properly to insulin, a condition known as insulin resistance. Over time, the pancreas may become unable to produce insulin in adequate amounts.

Gestational diabetes is a form of type 2 diabetes, usually temporary, that appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although some women go on to develop type 2 diabetes.

Gestational diabetes is not the same as the situation for women who have type 1 or type 2 diabetes before their pregnancies.

Causes

Type 1 diabetes is considered a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this process. Evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved.

Islets of Langerhans
Islets of Langerhans contain beta cells and are located within the pancreas. Beta cells produce insulin which is needed to metabolize glucose within the body.

Researchers have identified at least 18 genetic locations, labeled IDDM1 - IDDM18, which are related to type 1 diabetes. The IDDM1 region contains the HLA genes that encode proteins called major histocompatibility complex. The genes in this region affect the immune response. Other chromosomes and genes continue to be identified.

Most people who develop type 1 diabetes do not have a family history of the disease. The odds of inheriting the disease are only 10% if a first-degree relative has diabetes. Even in identical twins, one twin has only a 33% chance of having type 1 diabetes if the other twin has it. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder.

Genetic factors cannot fully explain the development of diabetes. For the past several decades, the number of new cases of type 1 diabetes has been increasing each year worldwide.

Some research suggests that viral infections may trigger the disease in genetically susceptible individuals.

Among the viruses under scrutiny are enteric viruses, which attack the intestinal tract. Coxsackie viruses are a family of enteric viruses of particular interest. Epidemics of Coxsackie virus, as well as mumps and congenital rubella, have been associated with type 1 diabetes.

Risk Factors

Type 1 diabetes is much less common than type 2 diabetes, consisting of only 5 - 10% of all cases of diabetes. Nevertheless, like type 2 diabetes, new cases of type 1 diabetes have been rising over the past few decades. While type 2 diabetes has been increasing among African-American and Hispanic adolescents, the highest rates of type 1 diabetes are found among Caucasian youth.

Type 1 diabetes can occur at any age but usually appears between infancy and the late 30s, most typically in childhood or adolescence. Males and females are equally at risk. Studies report the following may be risk factors for developing type 1 diabetes:

Symptoms

The process that destroys the insulin-producing beta cells can be long and invisible. At the point when insulin production bottoms out, however, type 1 diabetes usually appears suddenly and progresses quickly. Warning signs of type 1 diabetes include:

Children with type 1 diabetes may also be restless, apathetic, and have trouble functioning at school. In severe cases, diabetic coma may be the first sign of type 1 diabetes.

Complications

Type 1 diabetes increases the risk for many serious health complications. The good news is that during the past several decades, the rate of serious complications among people with diabetes has been decreasing, and more patients are living longer and healthier lives. There are two important approaches to preventing complications from type 1 diabetes:

Diabetic ketoacidosis (DKA) is a life-threatening complication caused by a complete (or almost complete) lack of insulin. In DKA, the body produces abnormally high levels of blood acids called ketones. Ketones are byproducts of fat breakdown that build up in the blood and appear in the urine. They are produced when the body burns fat instead of glucose for energy. The buildup of ketones in the body is called ketoacidosis. Extreme stages of diabetic ketoacidosis can lead to coma and death.

For some people, DKA may be the first sign that someone has diabetes. In type 1 diabetes, it usually occurs when a patient is not compliant with insulin therapy or intentionally reduces insulin doses in order to lose weight. It can also be triggered by a severe illness or infection.

Symptoms and complications include:

Life-saving treatment uses rapid replacement of fluids with a salt (saline) solution followed by low-dose insulin and potassium replacement.

Urine test for ketoacidosis
Ketoacidosis is a serious condition of glucose build-up in the blood and urine. A simple urine test can determine if high ketone levels are present.

Hyperglycemic hyperosmolar nonketonic syndrome (HHNS) is a serious complication of diabetes that involves a cycle of increasing blood sugar levels and dehydration, without ketones. HHNS usually occurs with type 2 diabetes, but it can also occur with type 1 diabetes. It is often triggered by a serious infection or another severe illness, or by medications that lower glucose tolerance or increase fluid loss (especially in people who are not drinking enough fluids).

Symptoms of HHNS include high blood sugar levels, dry mouth, extreme thirst, dry skin, and high fever. HHNS can lead to loss of consciousness, seizures, coma, and death.

Tight blood sugar (glucose) control increases the risk of low blood sugar (hypoglycemia). Hypoglycemia occurs if blood glucose levels fall below normal. It is generally defined as a blood sugar below 70 mg/dL, although this level may not necessarily cause symptoms in all patients.

Insufficient intake of food and excess exercise or alcohol intake may cause hypoglycemia. Usually the condition is manageable. Hypoglycemia can sometimes be severe or even life threatening, particularly if the patient fails to recognize the symptoms, especially while continuing to take insulin or other hypoglycemic drugs. Beta-blocking medications, which are often prescribed for high blood pressure and heart disease, can mask symptoms of hypoglycemia.

Risk Factors for Severe Hypoglycemia. Specific risk factors for severe hypoglycemia include:

Hypoglycemia unawareness. Hypoglycemia unawareness is a condition in which people become accustomed to hypoglycemic symptoms. They may no longer notice the signs of hypoglycemia until they become more severe. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Severely low blood glucose levels can cause neurologic symptoms, such as:

[For information on preventing hypoglycemia or managing an attack, see Home Management section of this report.]

People with diabetes are more likely than non-diabetics to have heart problems, and to die from cardiovascular complications, including heart attack and stroke. Diabetes affects the heart in many ways:

Atherosclerosis
Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Patients with ESRD have 13 times the risk of death compared to other patients with type 1 diabetes. If the kidneys fail, dialysis or transplantation is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color. The outlook of end-stage renal disease has greatly improved during the last four decades for patients with type 1 diabetes, and fewer people with type 1 diabetes are developing ESRD.

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral neuropathy particularly affects sensation. It is a common complication for nearly half of people who have lived with type 1 or type 2 diabetes for more than 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in unusually severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Autonomic neuropathy can cause:

Diabetic gastroparesis is a type of neuropathy that affects the digestive track. It is triggered by high blood sugar, which over time can damage the vagus nerve. The result of this damage is that the digestive system takes too long at time to move and empty food. Undigested food and the delay in stomach emptying can cause blood glucose levels to rise, and make diabetes more difficult to control. Symptoms of gastroparesis include heartburn, nausea, abdominal bloating, feeling full after eating only a small amount of food, and vomiting of undigested food several hours after a meal.

Blood sugar control is an essential component in the treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. Heart disease risk factors may increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

About 15% of patients with diabetes have serious foot problems. They are the leading cause of hospitalizations for these patients. The consequences of both poor circulation and peripheral neuropathy make this a common and serious problem for all patients with diabetes. Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Most amputations start with foot ulcers.

People with diabetes who are overweight, smokers, and have a long history of diabetes tend to be at most risk. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers.

Foot ulcers usually develop from infections, such as those resulting from blood vessel injury. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) is a degenerative condition that affects the bones and joints in the feet. It is associated with the nerve damage that occurs with neuropathy. Early changes appear similar to an infection, with the foot becoming swollen, red, and warm. Gradually, the affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Diabetes accounts for thousands of new cases of blindness annually and is the leading cause of new cases of blindness in adults ages 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma.

Retinopathy is a condition in which the retina becomes damaged. It generally occurs in one or two phases:


Diabetes mellitus - retinal conditions

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Hepatitis. Patients with diabetes are at increased risk for contracting the hepatitis B virus, which is transmitted through blood and other bodily fluids. Exposure to the virus can occur through sharing finger-stick devices or blood glucose monitors. Adults newly diagnosed with type 1 or type 2 diabetes should get hepatitis B vaccinations.

Diabetes doubles the risk for depression. Depression, in turn, may increase the risk for hyperglycemia and complications of diabetes.

Type 1 diabetes is associated with slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures.

Diabetes increases the risk for other conditions, including:

Diabetes can cause specific complications in women. Women with diabetes have an increased risk of recurrent yeast infections. In terms of sexual health, diabetes may cause decreased vaginal lubrication, which can lead to pain or discomfort during intercourse.

Women with diabetes should be aware that certain types of medication can affect their blood glucose levels. For example, birth control pills can raise blood glucose levels. Long-term use (more than 2 years) of birth control pills may increase the risk of certain health problems.

Diabetes and Pregnancy. Diabetes during pregnancy can increase the risk for birth defects. High blood sugar levels (hyperglycemia) can affect the developing fetus during the critical first 6 weeks of organ development. Women with diabetes (either type 1 or type 2) who are planning on becoming pregnant should strive to maintain good glucose control for 3 - 6 months before pregnancy.

It is also important for women to closely monitor their blood sugar levels during pregnancy. For women with type 1 diabetes, pregnancy can affect their insulin dosing needs. Insulin dosing may also need to be adjusted during and following delivery. [For more information, see “Treatment of Diabetes During Pregnancy” in Treatment of Complications section of this report.]

Diabetes and Menopause. The changes in estrogen and other hormonal levels that occur during the transition to menopause (perimenopause) can cause major fluctuations in blood glucose levels. Women with diabetes also face an increased risk of premature menopause, which can lead to higher risk of heart disease.

Lack of Blood Glucose Control. Control of blood glucose levels is generally very poor in adolescents and young adults. Adolescents with diabetes are at higher risk than adults for ketoacidosis resulting from noncompliance. Young people who do not control glucose are also at high risk for permanent damage in small vessels, such as those in the eyes.

Eating Disorders. Up to a third of young women with type 1 diabetes have eating disorders and under-use insulin to lose weight. Anorexia and bulimia pose significant health risks in any young person, but they can be especially dangerous for people with diabetes.

Diagnosis

There are three tests that can diagnose diabetes:

The fasting plasma glucose (FPG) test has been the standard test for diagnosing diabetes. It is a simple blood test taken after 8 hours of fasting.

FPG levels indicate:

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the tests are normal in people who have symptoms or risk factors for diabetes. Widespread screening of patients to identify those at higher risk for diabetes type 1 is not recommended.

The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some doctors recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

OGTT levels indicate:

Patients who have the FPG and OGTT tests must not eat for at least 8 hours prior to the test.

Diagnosis of diabetes
The oral glucose tolerance test is used to diagnose diabetes. The first portion of the test involves drinking a special glucose solution. Blood is then taken several hours later to test for the level of glucose in the blood. Patients with diabetes will have higher than normal levels of glucose in their blood.

This test examines blood levels of glycosylated hemoglobin, also known as hemoglobin A1C (HbA1c). The results are given in percentages and indicate a person’s average blood glucose levels over the past 2 - 3 months. (The FPG and OGTT show a person’s glucose level for only the time of the test.) The A1C test is not affected by recent food intake so patients do not need to fast to prepare for it.

In addition to providing information on blood sugar control and diabetes treatment, the A1c test may also be used as an alternative test for diagnosing diabetes.

A1C levels indicate:

A1C tests are also used to help patients with diabetes monitor how well they are keeping their blood glucose levels under control. For patients with diabetes, A1C is measured periodically every 2 - 3 months, or at least twice a year. While finger prick self-testing provides information on blood glucose for that day, the A1C test shows how well blood sugar has been controlled over the past several months.

In general, most adult patients with diabetes should aim for A1C levels below or around 7%. Your doctor may adjust this goal depending on your individual health profile.

Goal A1C levels for children are:

Schedule for A1C Monitoring:

The American Diabetes Association recommends that results from the A1C test be used as to calculate estimated Average Glucose (eAG). EAG is a relatively new term that patients may see on lab results from their A1C tests. It converts the A1C percentages into the same mg/dL units that patients are familiar with from their daily home blood glucose tests. For example, an A1C of 7% is equal to an eAG of 154 mg/dL. The eAG terminology can help patients better interpret the results of their A1C tests, and make it easier to correlate A1C with results from home blood glucose monitoring.

Type 1 diabetes is characterized by the presence of a variety of antibodies that attack the islet cells. These antibodies are referred to as autoantibodies because they attack the body's own cells -- not a foreign invader. Blood tests for these autoantibodies can help differentiate between type 1 and type 2 diabetes.

Screening Tests for Heart Disease. All patients with diabetes should be tested for high blood pressure (hypertension) and unhealthy cholesterol and lipid levels and given an electrocardiogram. Other tests may be needed in patients with signs of heart disease.


Screening Tests for Kidney Damage. The earliest manifestation of kidney disease is microalbuminuria, in which tiny amounts of a protein called albumin are found in the urine. Microalbuminuria is also a marker for other complications involving blood vessel abnormalities, including heart attack and stroke.

The American Diabetes Association recommends that people with diabetes receive an annual urine test for albumin. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleaning the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 1 diabetes have an annual comprehensive eye exam, with dilation, to check for signs of retina disease (retinopathy). Patients at low risk may need exams only every 2 - 3 years. In addition to a comprehensive eye exam, fundus photography may be used as a screening tool. Fundus photography uses a special type of camera to take images of the back of the eye.

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including an annual comprehensive foot exam. Patients who lose sensation in their feet should have a foot exam every 3 - 6 months to check for ulcers or infections. Patients should also be screened for intermittent claudication and peripheral artery disease (PAD) using the ankle-brachial index for diagnosis.

Lifestyle Changes

Good nutrition and regular exercise can help prevent or manage medical complications of diabetes (such as heart disease and stroke), and help patients live longer and healthier lives.

There is no single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits, along with good control of blood glucose, are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Weight gain is a potential side effect of intense diabetic control with insulin. Being overweight can increase the risk for health problems. On the other hand, studies suggest that more than one-third of women with diabetes omit or underuse insulin in order to lose weight. Eating disorders are especially dangerous in patients with diabetes and can increase the risk for diabetic ketoacidosis. Ketoacidosis is a significant complication of insulin depletion and can be life threatening.

Aerobic exercise has significant and particular benefits for people with type 1 diabetes. It increases sensitivity to insulin, lowers blood pressure, improves cholesterol levels, and decreases body fat. Because glucose levels swing dramatically during workouts, people with type 1 diabetes need to take certain precautions:

Avoid resistance or high impact exercises. They can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet. Because patients with diabetes may have silent heart disease, they should always check with their doctors before undertaking vigorous exercise.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. The US Food and Drug Administration (FDA) and Federal Trade Commission (FTC) warn patients with diabetes not to be duped by bogus and unproven remedies.

Treatment

Insulin is essential for control of blood glucose levels in type 1 diabetes. Good blood glucose control is the best way to prevent major complications in type 1 diabetes, including those that affect the kidneys, eyes, nerve pathways, and blood vessels. Intensive insulin treatment in early diabetes may even help preserve any residual insulin secretion for at least 2 years.

There are, however, some significant problems with intensive insulin therapy:

A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. Pancreas transplantation may eventually be considered for patients who cannot control glucose levels without frequent episodes of severe hypoglycemia.

The goal of intensive insulin therapy is to keep blood glucose levels as close to normal as possible.

Normal

Goal

Blood glucose levels before meals

Less than 100 mg/dL

70 - 130 mg/dL for adults

100 - 180 mg/dL for children under age 6

90 - 180 mg/dL for children 6 - 12 years old

90 - 130 mg/dL for children 13 - 19 years old

Bedtime blood glucose levels

Less than 120 mg/dL

Less than 180 mg/dL for adults

110 - 200 mg/dL for children under age 6

100 - 186 mg/dL for children 6 - 12 years old

90 - 150 mg/dL for children 13 - 19 years old

Glycosylated hemoglobin (A1C) levels

Less than 5.7%

Less than or around 7% for adults

Less than 8.5% for children under age 6

Less than 8% for children 6 – 12 years old

Less than 7.5% for children 13 – 19 years old

Major source: Standards of Medical Care In Diabetes -- 2013, American Diabetes Association.

Standard insulin therapy usually consists of one or two daily insulin injections, one daily blood sugar test, and visits to the health care team every 3 months. For strictly controlling blood glucose, however, intensive management is required. The regimen is complicated although newer insulin forms may make it easier.

There are two components to insulin administration:

In achieving insulin control the patient must also take other steps:

Because of the higher risk for hypoglycemia in children, doctors recommend that intensive insulin treatment be used very cautiously in children under 13 and not at all in very young children.

Insulin cannot be taken orally because the body's digestive juices destroy it. Injections of insulin under the skin ensure that it is absorbed slowly by the body for a long-lasting effect. The timing and frequency of insulin injections depend upon a number of factors:

Fast-Acting Insulin. Insulin lispro (Humalog) and insulin aspart (Novo Rapid, Novolog) lower blood sugar very quickly, usually within 5 minutes after injection. Insulin peaks in about 4 hours and continues to work for about 4 more hours. This rapid action reduces the risk for hypoglycemic events after eating (postprandial hypoglycemia). Optimal timing for administering this insulin is about 15 minutes before a meal, but it can also be taken immediately after a meal (but within 30 minutes). Fast-acting insulins may be especially useful for meals with high carbohydrates.

Regular Insulin. Regular insulin begins to act 30 minutes after injection, reaches its peak at 2 - 4 hours, and lasts about 6 hours. Regular insulin may be administered before a meal and may be better for high-fat meals.

Intermediate Insulin. NPH (Neutral Protamine Hagedorn) insulin has been the standard intermediate form. It works within 2 - 4 hours, peaks 4 - 12 hours later, and lasts up to 18 hours. Lente (insulin zinc) is another intermediate insulin that peaks 4 - 12 hours and lasts up to 18 hours.

Long-Acting (Ultralente) Insulin. Long-acting insulins, such as insulin glargine (Lantus), are released slowly. Long-acting insulin peaks at 10 hours and lasts up to 20 hours. Researchers are studying new types of long-acting insulins including one called degludec that requires injections only three times a week.

Combinations. Regimens generally include combinations of short and longer-acting insulins to help match the natural cycle. For example, one approach in patients who are intensively controlling their glucose levels uses 3 injections of insulin, which includes a mixture of regular insulin and NPH at dinner. Another approach uses 4 injections, including a separate short-acting form at dinner and NPH at bedtime, which may pose a lower risk for nighttime hypoglycemia than the 3-injection regimen.

Insulin Pens. Insulin pens, which contain cartridges of insulin, have been available for some time. Until recently, they were fairly complicated and difficult to use. Newer, prefilled pens (Humulin Pen, Humalog) are disposable and allow the patient to dial in the correct amount.

An insulin pump can improve blood glucose control and quality of life with fewer hypoglycemic episodes than multiple injections. The pumps correct for the “dawn phenomenon” (sudden rise of blood glucose in the morning) and allow quick reductions for specific situations, such as exercise. Many different brands are available.

The typical pump is about the size of a beeper and has a digital display. Some are worn externally and are programmed to deliver insulin through a catheter in the skin or the abdomen. They generally use rapid-acting insulin, the most predictable type. They work by administering a small amount of insulin continuously (the basal rate) and a higher dose (a bolus dose) when food is eaten.

Although learning to use the pump can be complicated at first, most patients find over time that the devices are fairly easy to use. Adults, adolescents, and school children use insulin pumps and even very young children (ages 2 - 7 years) are able to successfully use them.

Insulin pump
The catheter at the end of the insulin pump is inserted through a needle into the abdominal fat of a person with diabetes. Dosage instructions are entered into the pump's small computer, and the appropriate amount of insulin is then injected into the body in a calculated, controlled manner.

To achieve good blood sugar control, patients and parents of children must undergo some training. The patient and doctor must determine the amount of insulin used -- it is not automatically calculated. This requires an initial learning period, including understanding insulin needs over the course of the day and in different situations and knowledge of carbohydrate counting. Frequent blood testing is very important, particularly during the training period.

Insulin pumps are more expensive than insulin shots and occasionally have some complications, such as blockage in the device or skin irritation at the infusion site. Despite early concerns, pumps do not appear to increase the risk of ketoacidosis.

Pramlintide (Symlin) is an injectable drug that is used to help control postprandial hyperglycemia, the sudden increase in blood sugar after a meal. Pramlintide is injected before meals and can help lower blood sugar levels in the 3 hours after meals. Pramlintide is used in addition to insulin for patients who take insulin regularly but still need better blood sugar control. Pramlintide and insulin are the only two drugs approved for treatment of type 1 diabetes.

Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Side effects may include nausea, vomiting, abdominal pain, headache, fatigue, and dizziness. Patients with type 1 diabetes have an increased risk of severe low blood sugar (hypoglycemia) that may occur within 3 hours following a pramlintide injection. This drug should not be used if patients have trouble knowing when their blood sugar is low or have slow stomach emptying (gastroparesis).

Treatment of Complications

All patients with diabetes and high blood pressure should adopt lifestyle changes. These include weight reduction (when needed), following the Dietary Approaches to Stop Hypertension (DASH) diet, smoking cessation, limiting alcohol intake, and limiting salt intake to no more than 1,500 mg of sodium per day.

High Blood Pressure Control. In general, people with diabetes should strive for blood pressure levels of less than 140/80 mm Hg (systolic/diastolic). For some people, especially younger patients, a systolic blood pressure goal of less than 130 mm Hg may be appropriate.

Patients with diabetes and high blood pressure need an individualized approach to drug treatment, based on their particular health profile. Dozens of anti-hypertensive drugs are available. The most beneficial fall into the following categories

Nearly all patients who have diabetes and high blood pressure should take an ACE inhibitor (or ARB) as part of their regimen for treating their hypertension. These drugs help prevent kidney damage.

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances, including low HDL (“good”) cholesterol and high triglycerides.

Adult patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Children should be treated for LDL cholesterol above 160 mg/dL, or above 130 mg/dL if they have other cardiovascular risk factors.

Lifestyle changes for cholesterol management in patients with diabetes focus on:

For medications, statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor, generic), lovastatin (Mevacor,, generic), pravastatin (Pravachol, generic), simvastatin (Zocor, Simcor, Vytorin, and generics), fluvastatin (Lescol, generic), rosuvastatin (Crestor), and pitavastatin (Livalo).

These drugs are very effective for lowering LDL cholesterol levels. However, they may increase blood glucose levels in some patients, especially when taken in high doses. Still, statin drugs are considered generally safe and the best first choice for managing high cholesterol. If one statin drug does not work, the doctor may recommend switching to a different statin.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms.

Occasionally, patients do not respond to statins and need a different type of medication such as a fibrate (gemfibrozil, fenofibrate, or fenofibric acid) or niacin drug. This is especially true for patients who have very low HDL levels or severe triglyceride imbalances. Combination therapy of a statin with a fibrate or niacin drug is not recommended due to increased risk for rhabdomolysis and other serious side effects.

Aspirin for Heart Disease Prevention. For patients with diabetes who have additional heart disease risk factors, taking a daily aspirin can reduce the risk for blood clotting and may help protect against heart attacks. (There is not enough evidence to indicate that aspirin prevention is helpful for patients at lower risk.) The recommended dose is 75 - 162 mg/day. Aspirin as primary prevention is recommended for men who are older than age 50 or women who are older than age 60 who have at least one additional heart risk factor. These risk factor include a family history of heart disease, high blood pressure, smoking, unhealthy cholesterol levels, or excessive urine levels of the protein albumin. Talk to your doctor, particularly if you are at risk for aspirin side effects such as gastrointestinal bleeding and ulcers.

Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser or photocoagulation eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients. Drug therapy with anti-vascular endothelial growth factor (VEGF ) is also recommended for treatment of diabetic macular edema.

About a third of foot ulcers will heal within 20 weeks with good wound care treatments. Some treatments are as follows:

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

The only FDA-approved drugs for treating neuropathy are pregabalin (Lyrica) and duloxetine (Cymbalta). Other drugs and treatments are used on an off-label basis.

The American Academy of Neurology’s (AAN) guidelines for treating painful diabetic neuropathy recommend:

Non-Drug Treatments. Percutaneous electrical nerve stimulation (PENS) may help some patients. PENS uses electrodes attached to precisely placed acupuncture-type needles to deliver electrical current to peripheral sensory nerves. Doctors also recommend lifestyle measures, such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy (diabetic gastroparesis). Patients need to watch their nutrition if the problem is severe.

Erectile dysfunction is also associated with neuropathy. Studies indicate that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis), and avanafil (Stendra) are safe and effective, at least in the short term, for many patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms. Patients who take nitrate medications for heart disease cannot use PDE-5 drugs.

Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease and for slowing the progression of the disease.

ACE inhibitors are the best class of blood pressure medications for delaying kidney disease and slowing disease progression in patients with diabetes. Angiotensin-receptor blockers (ARBs) are also very helpful.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally need higher amounts of protein.

Anemia.Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually need injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. However, these drugs -- darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) -- can increase the risk of blood clots, stroke, heart attack, and heart failure in patients with end-stage kidney disease when they are given at higher than recommended doses.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Some recommendations for preventing pregnancy complications include:

Home Management

Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to carefully monitor blood glucose levels. In general, patients with type 1 diabetes need to take readings four or more times a day. Patients should aim for the following measurements:

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Finger-Prick Test. A typical blood sugar test includes the following:

Home monitors are less accurate than laboratory monitors and many do not meet the standards of the American Diabetes Association. However, they are usually accurate enough to indicate when blood sugar is too low.

Blood test
To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some simple procedures may improve accuracy:

Continuous glucose monitoring systems (CGMs) use a needle-like sensor inserted under the skin of the abdomen to monitor glucose levels every 5 minutes. Depending on the system, CMGs measure glucose levels for 3- 7 days and sound an alarm if glucose levels are too high or low. These devices are used in addition to traditional fingerstick test kits and glucose meters but do not replace them.

Urine tests are useful for detecting the presence of ketones. These tests should always be performed during illness or stressful situations, when diabetes is likely to go out of control. The patient should also undergo yearly urine tests for microalbuminuria (small amounts of protein in the urine), a risk factor for future kidney disease. Tests for sugar in the urine are no longer used to diagnose diabetes or monitor therapy.

The following tips may help avoid hypoglycemia or prepare for attacks.

Family and friends should be aware of the symptoms and be prepared:

Emergency treatment

Patients with type 1 diabetes should always wear a medical alert ID bracelet or necklace that states that they have diabetes and take insulin.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:


Transplantation Procedures

Researchers are investigating islet-cell transplantation as a way to help patients to come off insulin or reduce their use of it. Most research in recent years has focused on an islet-transplantation procedure called the Edmonton protocol.

This procedure has been used only in clinical trials, but it has helped some patients with severe type 1 diabetes to become free of insulin injections. However, many of these insulin-independent patients needed to resume insulin injections within 2 years. Researchers are continuing to work on refining the Edmonton protocol so that its benefits can be more sustainable and long lasting.

A major obstacle for the islet cell transplantation is the need for two or more donor pancreases to supply sufficient islet cells. Unfortunately, there are not enough pancreases available to make this procedure feasible for even 1% of patients. Researchers are looking for alternative approaches, including the use of umbilical cord cells, embryonic or adult stem cells, bone marrow transplantation, and other types of cellular therapies. These studies are still in very early stages, but researchers predict that there will be major advances in these fields in the coming years.

Most pancreas transplants use a cadaver pancreas from a deceased donor. There are three main types of cadaver pancreas transplants:

A fourth option, which is much less commonly performed, is for the patient to receive a partial pancreas from a living donor (typically a relative). This type of transplant may be performed at the same time as a living donor kidney transplant. Sometimes islet cells from the pancreas may be transplanted.

Survival rates are best for simultaneous pancreas-kidney transplants and are worst for pancreas-alone transplants.

Organ transplantation can have significant surgical and postsurgical complications. In addition, to prevent organ rejection, patients need to take immunosuppressive drugs on a lifelong basis following a transplant. Doctors generally recommend transplants in cases of end-stage kidney failure or when diabetes poses more of a threat to the patient's life than the transplant itself.

Pancreas and kidneys
Uncontrolled diabetes causes damage to many tissues of the body, including the kidneys. Kidney damage caused by diabetes most often involves thickening and hardening of the internal kidney structures. Strict blood glucose control may delay the progression of diabetic kidney disease.

Resources

References

Alemzadeh R and Ali O. Diabetes mellitus. In: Kliegman RM, ed. Nelson Textbook of Pediatrics. 19th ed. Saunders; 2011:chap 583.

American Diabetes Association. Standards of medical care in diabetes -- 2013. Diabetes Care. 2013 Jan;36 Suppl 1:S11-66.

Birkeland KI, Home PD, Wendisch U, Ratner RE, Johansen T, Endahl LA, et al. Insulin Degludec in Type 1 Diabetes: A randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine. Diabetes Care. 2011 Mar;34(3):661-5. Epub 2011 Jan 26.

Camilleri M. Clinical practice. Diabetic gastroparesis. N Engl J Med. 2007 Feb 22;356(8):820-9.

Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011 Dec 23;60(50):1709-11.

DCCT/EDIC Research Group, de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011 Dec 22;365(25):2366-76. Epub 2011 Nov 12.

de Kort H, de Koning EJ, Rabelink TJ, Bruijn JA, Bajema IM. Islet transplantation in type 1 diabetes. BMJ. 2011 Jan 21;342:d217. doi: 10.1136/bmj.d217.

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group, Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007 May 3;356(18):1842-52.

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group, Nathan DM, Zinman B, Cleary PA, Backlund JY, Genuth S, et al. Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005). Arch Intern Med. 2009 Jul 27;169(14):1307-16.

Fiorina P, Secchi A. Pancreatic islet cell transplant for treatment of diabetes. Endocrinol Metab Clin North Am. 2007 Dec;36(4):999-1013; ix.

Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Tamborlane WV, Beck RW, Bode BW, Buckingham B, Chase HP, et al. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008 Oct 2;359(14):1464-76. Epub 2008 Sep 8.

Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12):e132-73.

Pickup JC. Insulin-pump therapy for type 1 diabetes mellitus. N Engl J Med. 2012 Apr 26;366(17):1616-24.

Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010 Jun 22;121(24):2694-701. Epub 2010 May 27.

Retnakaran R, Zinman B. Type 1 diabetes, hyperglycaemia, and the heart. Lancet. 2008 May 24;371(9626):1790-9.

Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30.

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76.



Review Date: 6/25/2013
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
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