Most cases (95%) of type 1 diabetes mellitus are the result of environmental factors interacting with a genetically susceptible person. This interaction leads to the development of autoimmune disease directed at the insulin-producing cells of the pancreatic islets of Langerhans. These cells are progressively destroyed, with insulin deficiency usually developing after the destruction of 90% of islet cells.
ORAL GLUCOSE TOLERANCE TEST. Blood samples are taken from a vein before and after a patient drinks a thick, sweet syrup of glucose and other sugars. In a non-diabetic, the level of glucose in the blood goes up immediately after the drink and then decreases gradually as insulin is used by the body to metabolize, or absorb, the sugar. In a diabetic, the glucose in the blood goes up and stays high after drinking the sweetened liquid. A plasma glucose level of 11.1 mmol/L (200 mg/dL) or higher at two hours after drinking the syrup and at one other point during the two-hour test period confirms the diagnosis of diabetes.
People with type 1 diabetes sometimes receive transplantation of an entire pancreas or of only the insulin-producing cells from a donor pancreas. This procedure may allow people with type 1 diabetes mellitus to maintain normal glucose levels. However, because immunosuppressant drugs must be given to prevent the body from rejecting the transplanted cells, pancreas transplantation is usually done only in people who have serious complications due to diabetes or who are receiving another transplanted organ (such as a kidney) and will require immunosuppressant drugs anyway.
The typical symptoms of diabetes mellitus are the three “polys:” polyuria, polydipsia, and polyphagia. Because of insulin deficiency, the assimilation and storage of glucose in muscle adipose tissues, and the liver is greatly diminished. This produces an accumulation of glucose in the blood and creates an increase in its osmolarity. In response to this increased osmotic pressure there is depletion of intracellular water and osmotic diuresis. The water loss creates intense thirst and increased urination. The increased appetite (polyphagia) is not as clearly understood. It may be the result of the body's effort to increase its supply of energy foods even though eating more carbohydrates in the absence of sufficient insulin does not meet the energy needs of the cells.
Of course, you’re exhausted every now and then. But ongoing fatigue is an important symptom to pay attention to; it might mean the food you’re eating for energy isn’t being broken down and used by cells as it’s supposed to. “You’re not getting the fuel your body needs,” says Dobbins. “You’re going to be tired and feel sluggish.” But in many cases of type 2 diabetes, your sugar levels can be elevated for awhile, so these diabetes symptoms could come on slowly.

Fasting glucose test This test involves giving a blood sample after you have fasted for eight hours. (18) If you have a fasting blood sugar level of less than 100 milligrams per deciliter (mg/dl), your blood sugar levels are normal. But if you have one from 100 to 125 mg/dl, you have prediabetes, and if you have 126 mg/dl on two separate occasions, you have diabetes. (17)
Watch for thirst or a very dry mouth, frequent urination, vomiting, shortness of breath, fatigue and fruity-smelling breath. You can check your urine for excess ketones with an over-the-counter ketones test kit. If you have excess ketones in your urine, consult your doctor right away or seek emergency care. This condition is more common in people with type 1 diabetes but can sometimes occur in people with type 2 diabetes.
How does type 2 diabetes progress over time? Type 2 diabetes is a progressive disease, meaning that the body’s ability to regulate blood sugar gets worse over time, despite careful management. Over time, the body’s cells become increasingly less responsive to insulin (increased insulin resistance) and beta cells in the pancreas produce less and less insulin (called beta-cell burnout). In fact, when people are diagnosed with type 2 diabetes, they usually have already lost up to 50% or more of their beta cell function. As type 2 diabetes progresses, people typically need to add one or more different types of medications. The good news is that there are many more choices available for treatments, and a number of these medications don’t cause as much hypoglycemia, hunger and/or weight gain (e.g., metformin, pioglitazone, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and better insulin). Diligent management early on can help preserve remaining beta cell function and sometimes slow progression of the disease, although the need to use more and different types of medications does not mean that you have failed.
Dr. Erica Oberg, ND, MPH, received a BA in anthropology from the University of Colorado, her doctorate of naturopathic medicine (ND) from Bastyr University, and a masters of public health (MPH) in health services research from the University of Washington. She completed her residency at the Bastyr Center for Natural Health in ambulatory primary care and fellowship training at the Health Promotion Research Center at the University of Washington.
diabetes mel´litus a broadly applied term used to denote a complex group of syndromes that have in common a disturbance in the oxidation and utilization of glucose, which may be secondary to a malfunction of the beta cells of the pancreas, whose function is the production and release of insulin. Because insulin is involved in the metabolism of carbohydrates, proteins, and fats, diabetes is not limited to a disturbance of glucose homeostasis alone. Insulin resistance may also sometimes play a role in the etiology of diabetes. 
Home blood glucose self-monitoring is indispensable in helping patients to adjust daily insulin doses according to test results and to achieve optimal long-term control of diabetes. Insulin or other hypoglycemic agents are administered as prescribed, and their action and use explained to the patient. With help from a dietitian, a diet is planned based on the recommended amount of calories, protein, carbohydrates, and fats. The amount of carbohydrates consumed is a dietary key to managing glycemic control in diabetes. For most men, 60 to 75 carbohydrate g per meal are a reasonable intake; for most women, 45 to 60 g are appropriate. Saturated fats should be limited to less than 7% of total caloric intake, and trans-fatty acids (unsaturated fats with hydrogen added) minimized. A steady, consistent level of daily exercise is prescribed, and participation in a supervised exercise program is recommended.
Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise.[60][61] Intensive lifestyle measures may reduce the risk by over half.[24][62] The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss.[63] High levels of physical activity reduce the risk of diabetes by about 28%.[64] Evidence for the benefit of dietary changes alone, however, is limited,[65] with some evidence for a diet high in green leafy vegetables[66] and some for limiting the intake of sugary drinks.[32] In those with impaired glucose tolerance, diet and exercise either alone or in combination with metformin or acarbose may decrease the risk of developing diabetes.[24][67] Lifestyle interventions are more effective than metformin.[24] A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal.[68] While low vitamin D levels are associated with an increased risk of diabetes, correcting the levels by supplementing vitamin D3 does not improve that risk.[69]
Insulin resistance is the most common cause of type 2 diabetes, but it is possible to have type 2 and not be insulin resistant. You can have a form of type 2 where you body simply doesn’t produce enough insulin; that’s not as common. Researchers aren’t sure what exactly keeps some people from producing enough insulin, but that’s another thing they’re working hard to figure out.
FIGURE 19-1 ■. This figure shows the hyperbolic relationship of insulin resistance and beta cell function. On the y-axis is beta cell function as reflected in the first-phase insulin response during intravenous (IV) glucose infusion; on the x-axis is insulin sensitivity and its mirror image resistance. In a subject with normal glucose tolerance (NGT) and beta-cell reserve, an increase in insulin resistance results in increased insulin release and normal glucose tolerance. In an individual for whom the capacity to increase insulin release is compromised, increasing insulin resistance with partial or no beta-cell compensation results in progression from normal glucose tolerance, to impaired glucose tolerance (IGT), and finally to diabetes (T2D). Differences between these categories are small at high insulin sensitivity, which may be maintained by weight reduction, exercise, and certain drugs. At a critical degree of insulin resistance, due to obesity or other listed factors, only a further small increment in resistance requires a large increase in insulin output. Those that can increase insulin secretion to this extent retain normal glucose tolerance; those who cannot achieve this degree of insulin secretion (e.g., due to a mild defect in genes regulating insulin synthesis, insulin secretion, insulin action, or an ongoing immune destruction of beta cells) now unmask varying degrees of carbohydrate intolerance. The product of insulin sensitivity (the reciprocal of insulin resistance) and acute insulin response (a measurement beta-cell function) has been called the “disposition index.” This index remains constant in an individual with normal beta cell compensation in response to changes in insulin resistance. IGT, impaired glucose tolerance; NGT, normal glucose tolerance; T2D, type 2 diabetes.

Some risks of the keto diet include low blood sugar, negative medication interactions, and nutrient deficiencies. (People who should avoid the keto diet include those with kidney damage or disease, women who are pregnant or breast-feeding, and those with or at a heightened risk for heart disease due to high blood pressure, high cholesterol, or family history. (40)
Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, or by the ineffectiveness of the insulin produced. Such a deficiency results in increased concentrations of glucose in the blood, which in turn damage many of the body's systems, in particular the blood vessels and nerves.
According to the Mayo Clinic, your risk of developing type 2 diabetes increases as you age. Your risk goes up after age 45 in particular. However, the incidence of type 2 diabetes is increasing dramatically among children, adolescents, and younger adults. Likely factors include reduced exercise, decreased muscle mass, and weight gain as you age. Type 1 diabetes is usually diagnosed by the age of 30.
Considering that being overweight is a risk factor for diabetes, it sounds counterintuitive that shedding pounds could be one of the silent symptoms of diabetes. “Weight loss comes from two things,” says Dr. Cypess. “One, from the water that you lose [from urinating]. Two, you lose some calories in the urine and you don’t absorb all the calories from the sugar in your blood.” Once people learn they have diabetes and start controlling their blood sugar, they may even experience some weight gain—but “that’s a good thing,” says Dr. Cypess, because it means your blood sugar levels are more balanced.

There is currently no cure for diabetes. The condition, however, can be managed so that patients can live a relatively normal life. Treatment of diabetes focuses on two goals: keeping blood glucose within normal range and preventing the development of long-term complications. Careful monitoring of diet, exercise, and blood glucose levels are as important as the use of insulin or oral medications in preventing complications of diabetes. In 2003, the American Diabetes Association updated its Standards of Care for the management of diabetes. These standards help manage health care providers in the most recent recommendations for diagnosis and treatment of the disease.
Constant advances are being made in development of new oral medications for persons with diabetes. In 2003, a drug called Metaglip combining glipizide and metformin was approved in a dingle tablet. Along with diet and exercise, the drug was used as initial therapy for Type 2 diabetes. Another drug approved by the U.S. Food and Drug Administration (FDA) combines metformin and rosiglitazone (Avandia), a medication that increases muscle cells' sensitivity to insulin. It is marketed under the name Avandamet. So many new drugs are under development that it is best to stay in touch with a physician for the latest information; physicians can find the best drug, diet and exercise program to fit an individual patient's need.
Weight loss surgery in those who are obese is an effective measure to treat diabetes.[101] Many are able to maintain normal blood sugar levels with little or no medication following surgery[102] and long-term mortality is decreased.[103] There however is some short-term mortality risk of less than 1% from the surgery.[104] The body mass index cutoffs for when surgery is appropriate are not yet clear.[103] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[105][106]
The more common form of diabetes, Type II, occurs in approximately 3-5% of Americans under 50 years of age, and increases to 10-15% in those over 50. More than 90% of the diabetics in the United States are Type II diabetics. Sometimes called age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight and who do not exercise. It is also more common in people of Native American, Hispanic, and African-American descent. People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures also are more likely to develop Type II diabetes than those who remain in their original countries.
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Some people with type 2 diabetes are treated with insulin. Insulin is either injected with a syringe several times per day, or delivered via an insulin pump. The goal of insulin therapy is to mimic the way the pancreas would produce and distribute its own insulin, if it were able to manufacture it. Taking insulin does not mean you have done a bad job of trying to control your blood glucose—instead it simply means that your body doesn’t produce or use enough of it on its own to cover the foods you eat.
FASTING GLUCOSE TEST. Blood is drawn from a vein in the patient's arm after a period at least eight hours when the patient has not eaten, usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A plasma level of 7.8 mmol/L (200 mg/L) or greater can indicate diabetes. The fasting glucose test is usually repeated on another day to confirm the results.

Jump up ^ Picot, J; Jones, J; Colquitt, JL; Gospodarevskaya, E; Loveman, E; Baxter, L; Clegg, AJ (September 2009). "The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation". Health Technology Assessment. Winchester, England. 13 (41): iii–iv, 1–190, 215–357. doi:10.3310/hta13410. PMID 19726018.

Jump up ^ Cheng J, Zhang W, Zhang X, Han F, Li X, He X, Li Q, Chen J (May 2014). "Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis". JAMA Internal Medicine. 174 (5): 773–85. doi:10.1001/jamainternmed.2014.348. PMID 24687000.
The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[123]

Can type 2 diabetes be prevented? It is possible to reduce the risk of developing type 2 diabetes, although the underlying risk of type 2 diabetes depends strongly on genetic factors. But there was less type 2 diabetes around some years ago when people had a more active life and didn’t eat a modern Western diet. So it is fair to say that risk of getting type 2 diabetes is based on a genetic predisposition that is aggravated by lifestyle. Type 2 diabetes is associated with obesity, as well as a variety of environmental factors. To lower the risk of developing type 2 diabetes (as well as other diseases), it is highly recommended to exercise often, eat healthily, and maintain a healthy weight. 
Although some people with this type of diabetes are thin, the majority of people (90%) are overweight. Losing weight, even 2 kg to 5 kg (5 lbs to 10 lbs) can help lower blood glucose levels. For many people, following a healthy diet and an exercise program may be all that is needed to help control glucose levels. For others, healthy eating and exercise alone aren't enough to lower blood glucose levels.
All children with type 1 diabetes mellitus require insulin therapy. Most require 2 or more injections of insulin daily, with doses adjusted on the basis of self-monitoring of blood glucose levels. Insulin replacement is accomplished by giving a basal insulin and a preprandial (premeal) insulin. The basal insulin is either long-acting (glargine or detemir) or intermediate-acting (NPH). The preprandial insulin is either rapid-acting (lispro, aspart, or glulisine) or short-acting (regular).
DM affects at least 16 million U.S. residents, ranks seventh as a cause of death in the United States, and costs the national economy over $100 billion yearly. The striking increase in the prevalence of DM in the U.S. during recent years has been linked to a rise in the prevalence of obesity. About 95% of those with DM have Type 2, in which the pancreatic beta cells retain some insulin-producing potential, and the rest have Type 1, in which exogenous insulin is required for long-term survival. In Type 1 DM, which typically causes symptoms before age 25, an autoimmune process is responsible for beta cell destruction. Type 2 DM is characterized by insulin resistance in peripheral tissues as well as a defect in insulin secretion by beta cells. Insulin regulates carbohydrate metabolism by mediating the rapid transport of glucose and amino acids from the circulation into muscle and other tissue cells, by promoting the storage of glucose in liver cells as glycogen, and by inhibiting gluconeogenesis. The normal stimulus for the release of insulin from the pancreas is a rise in the concentration of glucose in circulating blood, which typically occurs within a few minutes after a meal. When such a rise elicits an appropriate insulin response, so that the blood level of glucose falls again as it is taken into cells, glucose tolerance is said to be normal. The central fact in DM is an impairment of glucose tolerance of such a degree as to threaten or impair health. Long recognized as an independent risk factor for cardiovascular disease, DM is often associated with other risk factors, including disorders of lipid metabolism (elevation of very-low-density lipoprotein cholesterol and triglycerides and depression of high-density lipoprotein cholesterol), obesity, hypertension, and impairment of renal function. Sustained elevation of serum glucose and triglycerides aggravates the biochemical defect inherent in DM by impairing insulin secretion, insulin-mediated glucose uptake by cells, and hepatic regulation of glucose output. Long-term consequences of the diabetic state include macrovascular complications (premature or accelerated atherosclerosis with resulting coronary, cerebral, and peripheral vascular insufficiency) and microvascular complications (retinopathy, nephropathy, and neuropathy). It is estimated that half those with DM already have some complications when the diagnosis is made. The American Diabetes Association (ADA) recommends screening for DM for people with risk factors such as obesity, age 45 years or older, family history of DM, or history of gestational diabetes. If screening yields normal results, it should be repeated every 3 years. The diagnosis of DM depends on measurement of plasma glucose concentration. The diagnosis is confirmed when any two measurements of plasma glucose performed on different days yield levels at or above established thresholds: in the fasting state, 126 mg/dL (7 mmol/L); 2 hours postprandially (after a 75-g oral glucose load) or at random, 200 mg/dL (11.1 mmol/L). A fasting plasma glucose of 100-125 mg/dL (5.5-6.9 mmol/L) or a 2-hour postprandial glucose of 140-199 mg/dL (7.8-11 mmol/L) is defined as impaired glucose tolerance. People with impaired glucose tolerance are at higher risk of developing DM within 10 years. For such people, lifestyle modification such as weight reduction and exercise may prevent or postpone the onset of frank DM. Current recommendations for the management of DM emphasize education and individualization of therapy. Controlled studies have shown that rigorous maintenance of plasma glucose levels as near to normal as possible at all times substantially reduces the incidence and severity of long-term complications, particularly microvascular complications. Such control involves limitation of dietary carbohydrate and saturated fat; monitoring of blood glucose, including self-testing by the patient and periodic determination of glycosylated hemoglobin; and administration of insulin (particularly in Type 1 DM), drugs that stimulate endogenous insulin production (in Type 2 DM), or both. The ADA recommends inclusion of healthful carbohydrate-containing foods such as whole grains, fruits, vegetables, and low-fat milk in a diabetic diet. Restriction of dietary fat to less than 10% of total calories is recommended for people with diabetes, as for the general population. Further restriction may be appropriate for those with heart disease or elevated cholesterol or triglyceride levels. The ADA advises that high-protein, low-carbohydrate diets have no particular merit in long-term weight control or in maintenance of a normal plasma glucose level in DM. Pharmaceutical agents developed during the 1990s improve control of DM by enhancing responsiveness of cells to insulin, counteracting insulin resistance, and reducing postprandial carbohydrate absorption. Tailor-made insulin analogues produced by recombinant DNA technology (for example, lispro, aspart, and glargine insulins) have broadened the range of pharmacologic properties and treatment options available. Their use improves both short-term and long-term control of plasma glucose and is associated with fewer episodes of hypoglycemia. SEE ALSO insulin resistance

Insulin is a hormone produced by the beta cells within the pancreas in response to the intake of food. The role of insulin is to lower blood sugar (glucose) levels by allowing cells in the muscle, liver and fat to take up sugar from the bloodstream that has been absorbed from food, and store it away as energy. In type 1 diabetes (previously called insulin-dependent diabetes mellitus), the insulin-producing cells are destroyed and the body is not able to produce insulin naturally. This means that sugar is not stored away but is constantly released from energy stores giving rise to high sugar levels in the blood. This in turn causes dehydration and thirst (because the high glucose ‘spills over’ into the urine and pulls water out of the body at the same time). To exacerbate the problem, because the body is not making insulin it ‘thinks’ that it is starving so does everything it can to release even more stores of energy into the bloodstream. So, if left untreated, patients become increasingly unwell, lose weight, and develop a condition called diabetic ketoacidosis, which is due to the excessive release of acidic energy stores and causes severe changes to how energy is used and stored in the body.
As of 2016, 422 million people have diabetes worldwide,[101] up from an estimated 382 million people in 2013[17] and from 108 million in 1980.[101] Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.5% among adults, nearly double the rate of 4.7% in 1980.[101] Type 2 makes up about 90% of the cases.[16][18] Some data indicate rates are roughly equal in women and men,[18] but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.[102][103]
Type 2 diabetes is one of the major degenerative diseases in the Western world today. It happens when your body can’t use insulin properly, or can’t make enough insulin. Insulin is a hormone the assists the body’s cells in utilizing glucose. It also helps the body store extra sugar in fat, liver, and muscle cells. If you don’t have insulin, your body can’t use the sugar in the bloodstream.
The ADA recommends using patient age as one consideration in the establishment of glycemic goals, with different targets for preprandial, bedtime/overnight, and hemoglobin A1c (HbA1c) levels in patients aged 0-6, 6-12, and 13-19 years. [4] Benefits of tight glycemic control include not only continued reductions in the rates of microvascular complications but also significant differences in cardiovascular events and overall mortality.
Excess glucose in the blood can damage small blood vessels in the nerves causing a tingling sensation or pain in the fingers, toes and limbs. Nerves that lie outside of the central nervous system may also be damaged, which is referred to as peripheral neuropathy. If nerves of the gastrointestinal tract are affected, this may cause vomiting, constipation and diarrhea.
All children with type 1 diabetes mellitus require insulin therapy. Most require 2 or more injections of insulin daily, with doses adjusted on the basis of self-monitoring of blood glucose levels. Insulin replacement is accomplished by giving a basal insulin and a preprandial (premeal) insulin. The basal insulin is either long-acting (glargine or detemir) or intermediate-acting (NPH). The preprandial insulin is either rapid-acting (lispro, aspart, or glulisine) or short-acting (regular).

Janis McWilliams, RN, MSN, CDE, BC-ADM, responds: Yes, in type 1 diabetes in particular, the onset of symptoms like frequent urination and extreme thirst can be very sudden. In type 2 diabetes, the symptoms tend to come about more gradually, and sometimes there are no signs at all. People who have symptoms should contact their health care provider immediately for an accurate diagnosis. Keep in mind that these symptoms could signal other problems, too.
Studies in type 1 patients have shown that in intensively treated patients, diabetic eye disease decreased by 76%, kidney disease decreased by 54%, and nerve disease decreased by 60%. More recently the EDIC trial has shown that type 1 diabetes is also associated with increased heart disease, similar to type 2 diabetes. However, the price for aggressive blood sugar control is a two to three fold increase in the incidence of abnormally low blood sugar levels (caused by the diabetes medications). For this reason, tight control of diabetes to achieve glucose levels between 70 to120 mg/dl is not recommended for children under 13 years of age, patients with severe recurrent hypoglycemia, patients unaware of their hypoglycemia, and patients with far advanced diabetes complications. To achieve optimal glucose control without an undue risk of abnormally lowering blood sugar levels, patients with type 1 diabetes must monitor their blood glucose at least four times a day and administer insulin at least three times per day. In patients with type 2 diabetes, aggressive blood sugar control has similar beneficial effects on the eyes, kidneys, nerves and blood vessels.
The beta cells may be another place where gene-environment interactions come into play, as suggested by the previously mentioned studies that link beta cell genes with type 2. "Only a fraction of people with insulin resistance go on to develop type 2 diabetes," says Shulman. If beta cells can produce enough insulin to overcome insulin resistance, a factor that may be genetically predetermined, then a person can stay free of diabetes. But if the beta cells don't have good genes propping them up, then diabetes is the more likely outcome in a person with substantial insulin resistance.
The term brittle diabetes has been used to refer to people who have dramatic recurrent swings in blood glucose levels, often for no apparent reason. However, this term is no longer used. People with type 1 diabetes may have more frequent swings in blood glucose levels because insulin production is completely absent. Infection, delayed movement of food through the stomach, and other hormonal disorders may also contribute to blood glucose swings. In all people who have difficulty controlling blood glucose, doctors look for other disorders that might be causing the problem and also give people additional education on how to monitor diabetes and take their drugs.
Type 1 Diabetes: About 5 to 10 percent of those with diabetes have type 1 diabetes. It's an autoimmune disease, meaning the body's own immune system mistakenly attacks and destroys the insulin-producing cells in the pancreas. Patients with type 1 diabetes have very little or no insulin, and must take insulin everyday. Although the condition can appear at any age, typically it's diagnosed in children and young adults, which is why it was previously called juvenile diabetes.
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