DIABETES MELLITUS

Definition
Diabetes is a disorder of metabolism the way the body uses digested food for growth and energy. Most of the food people eat is broken down into glucose, the form of sugar in the blood. Glucose is the main source of fuel for the body. After digestion, glucose passes into the bloodstream, where it is used by cells for growth and energy. For glucose to get into cells, insulin must be present. Insulin is a hormone produced by the pancreas, a large gland behind the stomach. When people eat, the pancreas automatically produces the right amount of insulin to move glucose from blood into the cells. In people with diabetes, however, the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin that is produced. Glucose builds up in the blood, overflows into the urine, and passes out of the body in the urine. Thus, the body loses its main source of fuel even though the blood contains large amounts of glucose.

Epidemiology
Various epidemiological studies indicate a trend of increase in the incidence and prevalence of type 2 diabetes in various parts of the world. WHO predicts an increase in the number of persons with diabetes are quite large in the coming years. WHO predicts rise in the number of DM in Indonesia from 8.4 million in 2000 to around 21.3 million in 2030. Similar to the WHO International Diabetes Federation (IDF) in 2009, predicts the number of persons with DM increased from 7.0 million in 2009 to 12.0 million in 2030. Although there are differences in the prevalence rate, the report showed both an increase in the number of persons with DM as much as 2-3 times by 2030. Reports of results of research in various areas in Indonesia are made in the decade of the 1980s shows the distribution of the prevalence of type 2 diabetes between 0.8% in Tanah Toraja, up 6.1% obtained in Manado. The results in the range of 1980 - 2000 showed a very sharp increase in prevalence. For example on research in Jakarta (urban areas), the prevalence of DM of 1.7% in 1982 rose to 5.7% in 1993 and rose sharply again to 12.8% in 2001.

Based on Central Bureau of Statistics Indonesia 2003, Indonesia estimated population aged over 20 years as many as 133 million inhabitants. With the prevalence of DM of 14.7% in urban areas and 7.2% in rural areas. Furthermore, based on the pattern of population growth, estimated in 2030 there will be 194 million people aged 20 years and assuming a prevalence of DM in urban (14.7%) and rural (7.2%), it is estimated there are 12 million persons with diabetes in urban areas and 8.1 million in rural areas. Report of Health Research Association in 2007 by the Ministry of Health, showed that the prevalence of DM in urban Indonesia for over 15 years of age by 5.7%. The prevalence found in Papua smallest at 1.7%, and the largest in the Province of North Maluku and West Kalimantan, which reached 11.1%. While the prevalence of impaired glucose tolerance (IGT), ranged from 4.0% in Jambi province to 21.8% in the Province of West Papua. The data above show that the number of people with diabetes in Indonesia is very large and very heavy loads to be handled by a specialist / sub spesialist or even by all the existing health workers. Given that the DM will have an impact on the quality of human resources and increasing health costs are sufficiently large, then all parties, both society and government, was supposed to participate in the response of DM, especially in prevention.

Etiology
Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as "insulin resistance." This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. Essentially, if someone is resistant to insulin, the

body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops. Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine. Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).

Classification of Diabetes Mellitus

The three main types of diabetes are type 1 diabetes type 2 diabetes gestational diabetes Other types of diabetes

Type 1 Diabetes Type 1 diabetes is an autoimmune disease. An autoimmune disease results when the bodys system for fi ghting infectionthe immune systemturns against a part of the body. In diabetes, the immune system attacks and destroys the insulinproducing beta cells in the pancreas. The pancreas then produces little or no insulin. A person who has type 1 diabetes must take insulin daily to live. At present, scientists do not know exactly what causes the bodys immune system to attack the beta cells, but they believe that autoimmune, genetic, and environmental factors, possibly viruses, are involved. Type 1 diabetes accounts for about 5 to 10 percent of diagnosed diabetes in the United States. It develops most often in children and young adults but can appear at any age.

Symptoms of type 1 diabetes usually develop over a short period, although beta cell destruction can begin years earlier. Symptoms may include increased thirst and urination, constant hunger, weight loss, blurred vision, and extreme fatigue. If not diagnosed and treated with insulin, a person with type 1 diabetes can lapse into a lifethreatening diabetic coma, also known as diabetic ketoacidosis.

Type 2 Diabetes The most common form of diabetes is type 2 diabetes. About 90 to 95 percent of people with diabetes have type 2. This form of diabetes is most often associated with older age, obesity, family history of diabetes, previous history of gestational diabetes, physical inactivity, and certain ethnicities. About 80 percent of people with type 2 diabetes are overweight. Type 2 diabetes is increasingly being diagnosed in children and adolescents, especially among African American, Mexican American, and Pacific Islander youth. When type 2 diabetes is diagnosed, the pancreas is usually producing enough insulin, but for unknown reasons the body cannot use the insulin effectively, a condition called insulin resistance. After several years, insulin production decreases. The result is the same as for type 1 diabetesglucose builds up in the blood and the body cannot make effi cient use of its main source of fuel. The symptoms of type 2 diabetes develop gradually. Their onset is not as sudden as in type 1 diabetes. Symptoms may include fatigue, frequent urination, increased thirst and hunger, weight loss, blurred vision, and slow healing of wounds or sores. Some people have no symptoms.

Gestational Diabetes Some women develop gestational diabetes late in pregnancy. Although this form of diabetes usually disappears after the birth of the baby, women who have had gestational diabetes have a 40 to 60 percent chance of developing type 2 diabetes within 5 to 10 years. Maintaining a reasonable body weight and being physically active may help prevent development of type 2 diabetes. About 3 to 8% of pregnant women in the United States develop gestational diabetes. As with type 2 diabetes, gestational diabetes occurs more often in some ethnic groups and among women with a family history of diabetes. Gestational diabetes is caused by the hormones of pregnancy or a shortage of insulin. Women

with gestational diabetes may not experience any symptoms.

Other Types of Diabetes A number of other types of diabetes exist. A person may exhibit characteristics of more than one type. For example, in latent autoimmune diabetes in adults (LADA), also called type 1.5 diabetes or double diabetes, people show signs of both type 1 and type 2 diabetes. Other types of diabetes include those caused by : Genetic defects of the beta cellthe part of the pancreas that makes insulin such as maturity-onset diabetes of the young (MODY) or neonatal diabetes mellitus (NDM) Genetic defects in insulin action, resulting in the bodys inability to control blood glucose levels, as seen in leprechaunism and the Rabson-Mendenhall syndrome Diseases of the pancreas or conditions that damage the pancreas, such as pancreatitis and cystic fibrosis Excess amounts of certain hormones resulting from some medical conditionssuch as cortisol in Cushings syndromethat work against the action of insulin Medications that reduce insulin action, such as glucocorticoids, or chemicals that destroy beta cells Infections, such as congenital rubella and cytomegalovirus Rare immune-mediated disorders, such as stiff-man syndrome, an autoimmune disease of the central nervous system Genetic syndromes associated with diabetes, such as Down syndrome and Prader-Willi syndrome

Latent Autoimmune Diabetes in Adults (LADA) People who have LADA show signs of both type 1 and type 2 diabetes. Diagnosis usually occurs after age 30. Researchers estimate that as many as 10 percent of people diagnosed with type 2 diabetes have LADA. Some experts believe that LADA is a slowly developing kind of type 1 diabetes because patients have antibodies against the insulin-producing beta cells of the pancreas.

Most people with LADA still produce their own insulin when first diagnosed, like those with type 2 diabetes. In the early stages of the disease, people with LADA do not require insulin injections. Instead, they control their blood glucose levels with meal planning, physical activity, and oral diabetes medications. However, several years after diagnosis, people with LADA must take insulin to control blood glucose levels. As LADA progresses, the beta cells of the pancreas may no longer make insulin because the bodys immune system has attacked and destroyed them, as in type 1 diabetes.

Diabetes Caused by Genetic Defects of the Beta Cell Genetic defects of the beta cell cause several forms of diabetes. For example, monogenic forms of diabetes result from mutations, or changes, in a single gene. In most cases of monogenic diabetes, the gene mutation is inherited. In the remaining cases, the gene mutation develops spontaneously. Most mutations in monogenic diabetes reduce the bodys ability to produce insulin. Genetic testing can diagnose most forms of monogenic diabetes. NDM and MODY are the two main forms of monogenic diabetes. NDM is a form of diabetes that occurs in the first 6 months of life. Infants with NDM do not produce enough insulin, leading to an increase in blood glucose. NDM can be mistaken for the much more common type 1 diabetes, but type 1 diabetes usually occurs after the fi rst 6 months of life. MODY usually first occurs during adolescence or early adulthood. However, MODY sometimes remains undiagnosed until later in life. A number of different gene mutations have been shown to cause MODY, all of which limit the pancreas ability to produce insulin. This process leads to the high blood glucose levels characteristic of diabetes.

Diabetes Caused by Genetic Defects in Insulin Action A number of types of diabetes result from genetic defects in insulin action. Changes to the insulin receptor may cause mild hyperglycemiahigh blood glucoseor severe diabetes. Symptoms may include acanthosis nigricans, a skin condition characterized by darkened skin patches, and, in women, enlarged and cystic ovaries plus virilization and the development of masculine characteristics such as excess facial hair. Two syndromes in children, leprechaunism and the Rabson-

Mendenhall syndrome, cause extreme insulin resistance.

Diabetes Caused by Diseases of the Pancreas Injuries to the pancreas from trauma or disease can cause diabetes. This category includes pancreatitis, infection, and cancer of the pancreas. Cystic fibrosis and hemochromatosis can also damage the pancreas enough to cause diabetes.

Diabetes Caused by Endocrinopathies Excess amounts of certain hormones that work against the action of insulin can cause diabetes. These hormones and their related conditions include growth hormone in acromegaly, cortisol in Cushings syndrome, glucagon in glucagonoma, and epinephrine in pheochromocytoma.

Diabetes Caused by Medications or Chemicals A number of medications and chemicals can interfere with insulin secretion, leading to diabetes in people with insulin resistance. These medications and chemicals include pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, phenytoin (Dilantin), and Vacor, a rat poison.

Diabetes Caused by Infections Several infections are associated with the occurrence of diabetes, including congenital rubella, coxsackievirus B, cytomegalovirus, adenovirus, and mumps.

Rare Immune-mediated Types of Diabetes Some immune-mediated disorders are associated with diabetes. About onethird of people with stiff-man syndrome develop diabetes. In other autoimmune diseases, such as systemic lupus erythematosus, patients may have anti-insulin receptor antibodies that cause diabetes by interfering with the binding of insulin to body tissues.

Other Genetic Syndromes Sometimes Associated with Diabetes Many genetic syndromes are associated with diabetes. These conditions include Down syndrome, Klinefelters syndrome, Huntingtons chorea, porphyria, Prader-Willi syndrome, and diabetes insipidus.

Type 1

Beta cell destruction, usually leads to absolute insulin deficiency Autoimmune Idiopathic

Type 2

Various cause, start from dominant insulin resistant with relative insulin deficiency until dominant defect insulin secretion with insulin resistant

Other types Diabetes

of

Genetic defect beta cell function Genetic defect in insulin action Diseases of the pancreas Diabetes caused by endocrinopathies Caused by medications or chemicals Infection Rare immune-mediated types of diabetes Other genetic syndromes associated with diabetes

Gestational Diabetes

Sign and Symptoms

- The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption. - The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein. - A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite. - Some untreated diabetes patients also complain of fatigue, nausea and vomiting. - Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas. - Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated

glucose levels can lead to lethargy and coma.

Diagnosis
The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor's office using a glucose meter. Normal fasting plasma glucose levels are less than 100 milligrams per deciliter (mg/dl). Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes. A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes. When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere. The oral glucose tolerance test Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes and in conditions of pre-diabetes, such as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose (100 grams for pregnant women). There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose. For the test to give reliable results: The person must be in good health (not have any other illnesses, not even a cold)

The person should be normally active (not lying down, for example, as an inpatient in a hospital) The person should not be taking medicines that could affect the blood glucose For three days before the test, the person should have eaten a diet high in carbohydrates (200-300 grams per day) In the morning of the test, the person should not smoke or drink coffee

The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast. People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1%-5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes. Recent studies have shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians are now understanding that impaired glucose tolerance is nor simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring. Evaluating the results of the oral glucose tolerance test 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 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl. Impaired glucose tolerance: A person is said to have impaired glucose

tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2hour glucose level is between 140 and 199 mg/dl. Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high. Gestational diabetes : A woman has gestational diabetes when she has any two of the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155 mg/dl, or a 3-hour glucose level of more than 140 mg/dl.
Not DM Randomized blood glucose Fasting blood glucose Vena plasma Capillary blood Vena plasma Capillary blood < 100 < 90 < 100 < 90 Not sure DM 100-199 90-199 100-125 90-99 DM 200 200 126 100

Hemoglobin A1c (A1c) To explain what an hemoglobin A1c is, think in simple terms. Sugar sticks, and when it's around for a long time, it's harder to get it off. In the body, sugar sticks too, particularly to proteins. The red blood cells that circulate in the body live for about three months before they die off. When sugar sticks to these cells, it gives us an idea of how much sugar is around for the preceding three months. In most labs, the normal range is 4%-5.9 %. In poorly controlled diabetes, its 8.0% or above, and in well controlled patients it's less than 7.0% (optimal is <6.5%). The benefits of measuring A1c is that is gives a more reasonable and stable view of what's happening over the course of time (three months), and the value does not bounce as much as finger stick blood sugar measurements. There is a direct correlation between A1c levels and average blood sugar levels as follows. While there are no guidelines to use A1c as a screening tool, it gives a physician a good idea that someone is diabetic if the value is elevated. Right now, it is used as a standard tool to determine blood sugar control in patients known to have diabetes.

A1c(%) 6 7 8 9 10 11 12

Mean blood sugar (mg/dl) 135 170 205 240 275 310 345

The American Diabetes Association currently recommends an A1c goal of less than 7.0%. Other Groups such as the American Association of Clinical Endocrinologists feel that an A1c of <6.5% should be the goal. Of interest, studies have shown that there is about a 10% decrease in relative risk for microvascular disease for every 1% reduction in A1c. So, if a patient starts off with an A1c of 10.7 and drops to 8.2, though there are not yet at goal, they have managed to decrease their risk of microvascular complications by about 20%. The closer to normal the A1c, the lower the absolute risk for microvascular complications. Data also suggests that the risk of macrovascular disease decreases by about 24% for every 1% reduction in A1c values. It should be mentioned here that there are a number of conditions in which an A1c value may not be accurate. For example, with significant anemia, the red blood cell count is low, and thus the A1c is altered. This may also be the case in sickle cell disease and other hemoglobinopathies.

Management of Diabetes Mellitus

Management of diabetes was originally a non-pharmacological therapy in the form of nutritional therapy and regular physical exercise. Nutritional therapy in people with diabetes can lose weight, lower blood pressure, lowering blood glucose levels, improves lipid profile, increase the sensitivity of insulin receptors, as well as improving the blood coagulation system. The goal of nutritional therapy is to achieve and maintain near normal blood glucose levels of fasting blood glucose 90-130 mg / dL, blood glucose PP <180 mg / dL, and HbA1c <7%. In addition to these goals, the

therapy also aims to achieve blood pressure <130/80 mmHg, LDL <180 mg / dL, HDL> 40 mg / dL, triglycerides <140 mg / dL, and maintain weight as normal as possible. The composition of foods for diabetics people are carbohydrates, proteins, fats, and vitamins and minerals. Carbohydrates are given no more than 55-65% of total daily energy needs. Protein is given about 10-15% of total calories per day. In patients with renal insufficiency, necessary restriction of protein intake to 40 grams per day, so given the essential amino acid supplementation. Fat is not good for diabetics especially saturated fatty acids either long chain or single chain, giving it a maximum of 10% fat of total calorie requirement per day. Calculation of ideal body weight with Brocca a modified formula is: Ideal body weight = 90% x (height in cm - 100) x 1 kg For men with a height below 160 cm and women below 150 cm, the formula is modified into: - Ideal body weight = (height in cm - 100) x 1 kg - Normal body weight: Ideal body weight + / - 10% - Underweight: <IBW - 10% - Fat :> IBW + 10%

Calculation of ideal body weight according to body mass index (BMI). BMI = weight (kg) / height (m) 2 Classification of BMI: BW is less <18.5 Normal BW 18-9.22 BW more> 23.0 The risk of 23.0-24.9 Obese I 29.9 25.0 Obese II> 30

For determination of caloric needs per day used the formula: The need for basal - Men = IBW (kg) x 30 calories - Women = IBW (kg) x 25 calories Correction - Age above 40 years = -5%

- Activity mild = +10% - Medium activity = +20% - Strenuous o = +30% - Weight loss fat = -20% - Weight loss more = -10% - Weight loss skinny = +20% - Metabolic Stress = +10-30% - Pregnancy trimesters I and II = +300 calories - The third trimester Pregnancy and lactation = +500calories The results of the total calorie requirement per day is then divided into 3 major portions for breakfast (20%), lunch (30%), dinner (25%), and 2-3 servings of mild (10-15%) among a large meal. Changes in eating patterns is done in stages in accordance with the conditions and habits of the patient. Physical exercise in people with diabetes can lower HbA1c concentrations, gives a good effect on body fat, vasodilatation of blood vessels that endotheliumdependent, thereby reducing cardiovascular events. But in its implementation should be supervised physical exercise frequency, intensity, duration, and type. Frequency of physical exercise is good is 3-5 times per week with mild-moderate intensity (60-70% maximum pulse), a duration of 30-60 minutes with the type of aerobic physical exercise. Physical exercise in diabetics with uncontrolled blood sugar can lead to elevated levels of blood glucose and ketone bodies which can lead to fatal effect, so people with diabetes who perform physical exercise, blood glucose levels should have no more than 250 mg / dL.

Therapeutic targets in DM

Pharmacological treatment of people with diabetes can vary. There are three kinds of insulin sensitizing drugs anti hyperglycemic (biguanid and glitazone), insulin secretagoue (sulfonylureas and glinid), and inhibiting the absorption of glucose (alpha-glucosidase inhibitors). Biguanid class that is often used is metformin, serves to lower blood glucose by improving insulin action at the cellular level, improving insulin action on the distal insulin receptor, increasing the use of glucose by the intestinal cells, reduce hepatic glucose production, and lower absorption in the intestine after a meal glucose . Metformin have side effects lactic acidosis and digestive disturbances that are not given in diabetics with serum creatinine over 1.3 mg / dL, liver failure, heart failure, and the elderly. To avoid the side effects of digestive disorders, metformin administered with a low initial dose and concurrent with food. Achieved the highest levels in the blood after 2 hours, 2.5 hours half-life of metformin is then removed through the kidneys so it is given 2-3 times per day except in the form of extended release. Metformin does not cause hypoglycemia or weight gain such as the sulfonylurea class. Metformin can be combined with sulfonylureas or insulin. Metformin is the first choice for overweight people with dyslipidemia and insulin resistance because it can reduce insulin resistance, preventing weight gain, and improve lipid profiles. Class of Glitazone works by increasing insulin sensitivity. Glitazone an agonist Peroxisome proliferator-activated receptor (PPAR) selectively in adipose tissue, skeletal muscle, and liver so that it can stimulate protein for improved insulin sensitivity and glycemic improvement as well as affect the expression and release of mediators of insulin resistance such as TNF-alpha and leptin. Achieved the highest levels in the blood after 1-2 hours. The half-life for rosiglitazone glitazone 3-4 hours, 3-7 hours for pioglitazone. Giving glitazone can be combined with insulin or metformin secretagoue. Class of sulfonylureas can increase and maintain insulin secretion. This group is often used as initial treatment of diabetics with impaired insulin secretion. Sulfonylureas work by stimulating the pancreatic beta cells to release insulin is stored so it is not suitable for people with type 1 diabetes. Sulfonylurea have an increased risk of hypoglycemia, then the gift must be considered in patients with DM

who are elderly, with renal failure, severe liver dysfunction, or lack of food inputs. Beak long period depending on usage, chronic users have a half-life is longer than acute users. Sulfonylureas administered hour before meals and can be combined with insulin at night. Glinid group has a structure similar to sulfonylurea and works on sulfonylurea receptors, but the effect from hypoglycemia is more minimal than the sulfonylureas. The last class is the alpha-glucosidase inhibitor that works by inhibiting the enzyme alpha-glucosidase in the proximal small intestine thereby inhibiting the formation of intraluminal monosaccharides, affecting the plasma insulin response, and inhibits the increase in blood sugar regulation. Drug commonly used is acarbose. Acarbose works locally in the gastrointestinal tract and not in absorption. Acarbose does not stimulate insulin secretion thus does not cause hypoglycemia. Acarbose 2-hour half-life and is excreted through the feces. Provision of acarbose on the main meal because as a barrier competitor when carbohydrate reached the small intestine. Side effects of this class is the result of maldigestion carbohydrate, meteorismus, flatulance, and diarrhea. Acarbose can be combined with metformin, glitazone, sulfonylurea, and insulin, but the administration is in conjunction with metformin may reduce the bioavailability of metformin. In addition to anti hyperglicemic oral medication as well, diabetes can be controlled using insulin. Insulin is needed on rapid weight loss, severe hyperglycemia with ketosis, diabetic ketoacidosis, hyperglycemic hyperosmolar non ketotic, hyperglycemia with lactic acidosis, failure by a combination of maximal doses of oral medications anti hyperglicemic, severe stress (systemic infection, stroke, surgery), pregnancy with diabetes, impaired renal function or severe liver, contraindications or allergy to the drug oral anti hyperglicemic. There are four types of insulin based on its long-acting insulin that is fast, short-acting insulin, intermediate acting insulin and long acting insulin. Rapid and short-acting insulin is included in the prandial insulin so it is more useful to decrease glucose after a meal because the peak onset of action and it works fast. Medium and long-acting insulin, including the basal insulin that serves to regulate blood glucose levels daily as well as the peak onset of action is slow work. Long-acting insulin glargine and detemir is a basal insulin without a top job, this is very beneficial in controlling blood glucose levels daily because it can reduce the risk of hypoglycemia due to insulin.

Complication
1. Diabetic Ketoacidosis Insulin is vital to patients with type 1 diabetes - they cannot live with out a source of exogenous insulin. Without insulin, patients with type 1 diabetes develop severely elevated blood sugar levels. This leads to increased urine glucose, which in turn leads to excessive loss of fluid and electrolytes in the urine. Lack of insulin also causes the inability to store fat and protein along with breakdown of existing fat and protein stores. This dysregulation, results in the process of ketosis and the release of ketones into the blood. Ketones turn the blood acidic, a condition called diabetic ketoacidosis (DKA). Symptoms of diabetic ketoacidosis include nausea, vomiting, and abdominal pain. Without prompt medical treatment, patients with diabetic ketoacidosis can rapidly go into shock, coma, and even death. Diabetic ketoacidosis can be caused by infections, stress, or trauma all which may increase insulin requirements. In addition, missing doses of insulin is also an obvious risk factor for developing diabetic ketoacidosis. Urgent treatment of diabetic ketoacidosis involves the intravenous administration of fluid, electrolytes, and insulin, usually in a hospital intensive care unit. Dehydration can be very severe, and it is not unusual to need to replace 6-7 liters of fluid when a person presents in diabetic ketoacidosis. Antibiotics are given for infections. With treatment, abnormal blood sugar levels, ketone production, acidosis, and dehydration can be reversed rapidly, and patients can recover remarkably well. 2. Hyperglicemia and hyperosmolar state In patients with type 2 diabetes, stress, infection, and medications (such as corticosteroids) can also lead to severely elevated blood sugar levels. Accompanied by dehydration, severe blood sugar elevation in patients with type 2 diabetes can lead to an increase in blood osmolality (hyperosmolar state). This condition can lead to coma (hyperosmolar coma). A hyperosmolar coma usually occurs in elderly patients with type 2 diabetes. Like diabetic ketoacidosis, a hyperosmolar coma is a medical emergency. Immediate treatment with intravenous fluid and insulin is important in reversing the hyperosmolar state. Unlike patients with type 1 diabetes, patients with

type 2 diabetes do not generally develop ketoacidosis solely on the basis of their diabetes. Since in general, type 2 diabetes occurs in an older population, concomitant medical conditions are more likely to exist, and these patients may actually be sicker overall. The complication and death rates from hyperosmolar coma is thus higher than in DKA. 3. Hypoglycemia Hypoglycemia means abnormally low blood sugar (glucose). In patients with diabetes, the most common cause of low blood sugar is excessive use of insulin or other glucose-lowering medications, to lower the blood sugar level in diabetic patients in the presence of a delayed or absent meal. When low blood sugar levels occur because of too much insulin, it is called an insulin reaction. Sometimes, low blood sugar can be the result of an insufficient caloric intake or sudden excessive physical exertion. Blood glucose is essential for the proper functioning of brain cells. Therefore, low blood sugar can lead to central nervous system symptoms such as: dizziness, confusion, weakness, and tremors. The actual level of blood sugar at which these symptoms occur varies with each person, but usually it occurs when blood sugars are less than 65 mg/dl. Untreated, severely low blood sugar levels can lead to coma, seizures, and, in the worse case scenario, irreversible brain death. At this point, the brain is suffering from a lack of sugar, and this usually occurs somewhere around levels of <40 mg/dl. The treatment of low blood sugar consists of administering a quickly absorbed glucose source. These include glucose containing drinks, such as orange juice, soft drinks (not sugar-free), or glucose tablets in doses of 15-20 grams at a time (for example, the equivalent of half a glass of juice). Even cake frosting applied inside the cheeks can work in a pinch if patient cooperation is difficult. If the individual becomes unconscious, glucagon can be given by intramuscular injection.

Glucagon causes the release of glucose from the liver (for example, it promotes gluconeogenesis). Glucagon can be lifesaving and every patient with diabetes who has a history of hypoglycemia (particularly those on insulin) should have a glucagon kit. Families and friends of those with diabetes need to be taught how to administer glucagon, since obviously the patients will not be able to do it themselves in an emergency situation. Another lifesaving device that should be mentioned is very simple; a medic alert bracelet should be worn by all patients with diabetes.

Chronic Complications
These diabetes complications are related to blood vessel diseases and are generally classified into small vessel disease, such as those involving the eyes, kidneys and nerves (microvascular disease), and large vessel disease involving the heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of the arteries (atherosclerosis) of the larger blood vessels, leading to coronary heart disease (angina or heart attack), strokes, and pain in the lower extremities because of lack of blood supply (claudication). Eye Complications The major eye complication of diabetes is called diabetic retinopathy. Diabetic retinopathy occurs in patients who have had diabetes for at least five years. Diseased small blood vessels in the back of the eye cause the leakage of protein and blood in the retina. Disease in these blood vessels also causes the formation of small aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization). Spontaneous bleeding from the new and brittle blood vessels can lead to retinal scarring and retinal detachment, thus impairing vision. To treat diabetic retinopathy a laser is used to destroy and prevent the recurrence of the development of these small aneurysms and brittle blood vessels. Approximately 50% of patients with diabetes will develop some degree of diabetic retinopathy after 10 years of diabetes, and 80% of diabetics have retinopathy after 15 years of the disease. Poor control of blood sugar and blood pressure further aggravates eye disease in diabetes. Cataracts and glaucoma are also more common among diabetics. It is also

important to note that since the lens of the eye lets water through, if blood sugar concentrations vary a lot, the lens of the eye will shrink and swell with fluid accordingly. As a result, blurry vision is very common in poorly controlled diabetes. Patients are usually discouraged from getting a new eyeglass prescription until their blood sugar is controlled. This allows for a more accurate assessment of what kind of glasses prescription is required. Kidney damage Kidney damage from diabetes is called diabetic nephropathy. The onset of kidney disease and its progression is extremely variable. Initially, diseased small blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the kidneys lose their ability to cleanse and filter blood. The accumulation of toxic waste products in the blood leads to the need for dialysis. Dialysis involves using a machine that serves the function of the kidney by filtering and cleaning the blood. In patients who do not want to undergo chronic dialysis, kidney transplantation can be considered. The progression of nephropathy in patients can be significantly slowed by controlling high blood pressure, and by aggressively treating high blood sugar levels. Angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) used in treating high blood pressure may also benefit kidney disease in diabetic patients.

Nerve damage Nerve damage from diabetes is called diabetic neuropathy and is also caused

by disease of small blood vessels. In essence, the blood flow to the nerves is limited, leaving the nerves without blood flow, and they get damaged or die as a result (a term known as ischemia). Symptoms of diabetic nerve damage include numbness, burning, and aching of the feet and lower extremities. When the nerve disease causes a complete loss of sensation in the feet, patients may not be aware of injuries to the feet, and fail to properly protect them. Shoes or other protection should be worn as much as possible. Seemingly minor skin injuries should be attended to promptly to avoid serious infections. Because of poor blood circulation, diabetic foot injuries may not

heal. Sometimes, minor foot injuries can lead to serious infection, ulcers, and even gangrene, necessitating surgical amputation of toes, feet, and other infected parts. Diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction (ED, impotence). Erectile dysfunction can also be caused by poor blood flow to the penis from diabetic blood vessel disease. Diabetic neuropathy can also affect nerves to the stomach and intestines, causing nausea, weight loss, diarrhea, and other symptoms of gastroparesis (delayed emptying of food contents from the stomach into the intestines, due to ineffective contraction of the stomach muscles).

Prevention for DM type 2

Primary Prevention

Aim from primary prevention : Primary prevention efforts are aimed at groups who have risk factors, those who have not been affected by diabetes, but has the potential to get DM and glucose intolerance groups Risk factor for DM that cant be modified : Ethnic Family history with DM Age. risk of developing glucose intolerance increases with increasing age. age> 45 years should be screening for DM a history of having a baby with birth weight > 4000 gr or a history of suffered from gestational diabetes mellitus (DMG) A history of having a baby with low birth weight, < 2,5 kg. Baby with low birth weight have higher risk compare with baby with normal birth weight. Risk factor that can be modified : Overweight (BMI > 23 kg/m2) Lack of physical activity

Hypertension (>140/90 mmHg) Dyslipidemia (HDL < 35 mg/dL and trigliserid > 250 mg/dL) Unhealthy diet. Diet with high glucose dan low fibers will increase risk to suffer prediabetes / glucose intolerance and type II DM

Other risk factors associated with diabetes : patients with polycystic ovary syndrome (PCOS) or other clinical conditions associated with insulin resistance patients with metabolic syndrome have a history of impaired glucose tolerance (IGT) or impaired fasting blood glucose (IFBG) before. have a history of cardiovascular disease such as stroke, coronary heart disease or PAD (Peripheral Arterial Disease) Glucose Intolerance glucose intolerance is a condition that precedes the onset of diabetes. the incidence of glucose intolerance reported continues to increase This term was first introduced in 2002 by the Department of Health and Human Services (DHHS) and the American Diabetes Associated (ADA). Previously the term to describe the state of glucose intolerance is the impaired glucose tolerance (IGT) and impaired fasting blood glucose (IFBG) glucose intolerance have a greater risk for the onset of cardiovascular disorders a half times higher than normal people glucose intolerance diagnosis is made by TTGO account after fasting 8 hours. established diagnosis of glucose intolerance when blood glucose test results show that there is one of the following: fasting blood glucose between 100 125 mg/dl blood glucose 2 hours after some liquid glucose between 140 199 mg/dl in patients with glucose intolerance, anamnesis and physical examination considered aimed to look for risk factors that can be modified Primary Prevention Materials Material consists of primary prevention counseling and management actions aimed at community groups who have a high risk and glucose intolerance. Counseling addressed to: A. group of people with high risk and glucose intolerance

Outreach materials include: 1. Weight counseling program. In someone with diabetes risk and have overweight, weight loss is the main way to reduce the risk of type 2 diabetes or glucose intolerance. Several studies have shown weight loss 50-10% can prevent or slow the emergence of type 2 diabetes. 2. A healthy diet It is recommended given to every person who has a risk. The amount of calorie intake is intended to achieve the ideal body weight. Complex carbohydrates are a choice and given divided and balanced so it does not cause high blood glucose peaks after meals. Contain less saturated fat and high in soluble fiber.

3. Physical exercise Regular physical exercise can improve blood glucose control, maintain or lose weight, and can increase HDL cholesterol levels. Physical exercise is recommended: Exercise for at least 150 minutes / week with moderate aerobic exercise (up to 50-70% maximum heart rate), or 0 minutes / week with heavy aerobic exercise (heart rate reached> 70% maximum). Exercise Physical activity was divided into 3-4 times / week. 4. Stop smoking Smoking is one of the risk to get cardiovascular disease. Although snoking is not correlate directly with glucose intolerance, but smoking can make complication cardiovascular heavier from glucose intolerance and DM type II. B. Health policy planning in order to understand the socio-economic impact of this disease and the importance of providing adequate facilities in primary prevention efforts Management aimed to: - Groups of glucose intolerance - Risk group (obesity, hypertension, dyslipidemia, etc) 1. Management of glucose intolerance Glucose intolerance is often associated with metabolic syndrome,

characterized by central obesity, dyslipidemia (high triglycerides or low HDL cholesterol) and hypertension.

Most people with glucose intolerance can be improved by lifestyle changes, losing weight, eating a healthy diet and adequate physical exercise and regular Diabetes Prevention Program study showed that lifestyle changes more effectively to prevent the emergence of type 2 diabetes compared with the use of drugs.

Weight loss of 5-10% accompanied by regular physical exercise can reduce the risk of type 2 diabetes by 58%. While the use of drugs (such as metformin, tiazolidindion, acarbose) is only able to reduce their risk by 31% and the use of various drugs for the treatment of glucose intolerance is still a controversy

When accompanied by obesity, hypertension, and dyslipidemia, carried weight control, blood pressure and lipid profiles in order to reach the target set.

2. Management of various risk factors a. obesity b. hypertension c. dyslipidemia Secondary Prevention Secondary prevention is an attempt to prevent or inhibit the onset of complications in patients who already suffer from DM. Done by providing adequate treatment and early detection measures since the early management of disease complications of DM. In secondary prevention outreach programs play an important role to improve patient compliance in carrying out the program and in towards healthy behaviors. For secondary prevention is aimed primarily at new patient. Extension made since the first meeting and the need to always be repeated at every opportunity and the next meeting. One of the most common complications of DM is cardiovascular disease, which is the leading cause of death in persons with diabetes. In addition to the treatment of high blood glucose levels, weight control, blood pressure, lipid profile in blood and antiplatelet administration can reduce the risk of cardiovascular disorders in people with diabetes. Tertiary Prevention Tertiary prevention is aimed at groups of people with diabetes who have experienced complications in an effort to prevent further disability.

Efforts to rehabilitate the patient as early as possible, before permanent disability. As an example of low-dose aspirin (80-325 mg / day) can be given routinely for persons with diabetes who already have microangiopathic complications.

In tertiary prevention efforts remain to be done on the patient and family counseling. Materials including rehabilitation counseling can be done to achieve optimal quality of life.

Tertiary prevention requires a holistic and integrated health service interrelated disciplines, particularly at a referral hospital. A good collaboration between experts in various disciplines (heart and kidney, eye, orthopedic surgery, vascular surgery, radiology, medical rehabilitation, nutrition, pediatric, etc.) is indispensable in the success of tertiary prevention.

Others Problems
I. Diabetes with Infection The presence of infection in patients is very influential on the control of blood glucose. Infection can worsen blood glucose control, and high blood glucose levels increase the ease or worsen the infection. Infection is the case, among others: - Urinary tract infections - Respiratory tract infections: pneumonia, pulmonary tuberculosis - Skin infections: furuncles, abscesses - Infection of the oral cavity: infection of the teeth and gums - Ear infections: otitis external malignant - UTI is an infection that often occurs and is more difficult to control. May result in pyelonephritis and septicemia. Germs are often leading causes were: Escherichia coli and Klebsiella. Fungal infections candida species can cause cystitis and renal abscess. Vaginal pruritus is a manifestation that often occurs due to vaginal yeast infections. - Pneumonia in diabetes is usually caused by streptococcus, stafilococcus, and gramnegative bacterial rods. Fungal infection of the respiratory by aspergilossis, and mucormycosis are also common.

- People with diabetes are more vulnerable to suffer pulmonary tuberculosis. Chest Xray examination, showed at 70% people with diabetes have lower lung lesions and cavitation. People with diabetes is also often accompanied by tuberculosis drugs resistance. - The skin on the lower extremities is a frequent site of infection. Staphylococcus is the main cause of the infection. Usually infected foot ulcers involves many microorganisms, which often involved is staphylococcus, streptococcus, gramnegative rods and anaerobic bacteria. - The incidence of periodontitis is increased in persons with diabetes and often lead to tooth loss. Maintaining good oral hygiene is essential to prevent complications of the oral cavity. - There are people with diabetes, malignant otitis externa is often not detected as a cause of infection. The principles of treatment of diabetic foot ulcers can be seen in Table 9 Metabolic control: a state of metabolic control as possible such as control of blood glucose, lipids and so on Vascular control: improvement of vascular supply (with surgery or angioplasty), usually takes on the state of ischemic ulcers Infection control: an aggressive treatment of infections, if visible clinical signs of infection (an indication of colonization of the growth of organisms on the swab is not an infection, if there are no clinical signs) Wound control: the disposal of infected and necrotic tissue on a regular basis Pressure control: reducing the pressure. Repeated pressure can cause ulcers, so it should be avoided. It is very important to do on neuropathic ulcers, and required removal of callus and put on shoes that fit that serves to reduce the pressure Education control: A good advices

II. Diabetes with Diabetic Nephropathy

- Around 20 - 40% of persons with diabetes will have diabetic nephropathy - Acquisition of persistent albuminuria in the range of 30 -229 mg/24 h (micro albuminuria) is an early sign of diabetic nephropathy - Patients who are accompanied with micro albuminuria and turned into a macro albuminuria (> 300 mg/24 hours), in the end often progress to end-stage chronic renal failure. Classification of albuminuria can be seen in Table 10. Diagnosis - The diagnosis of diabetic nephropathy is suspected when obtained albumin levels> 30 mg in the urine 24 hours on 2 of 3 times the examination within a period of 3-6 months, without other causes of albuminuria. Table 10. Classification of albuminuria Category Urine 24 hours Urine within a Randomized urine (g/mg creatinine) <30 30 299 >= 300

(mg/24hours) Normal Microalbuminuria Macroalbuminuria <30 30 229 >= 300

certain time <20 20 199 >= 200

Filtering In type 2 diabetes mellitus at the time of initial diagnosis. If microalbuminuria is negative, re-evaluation carried out every year. Method of Inspection - The ratio of albumin / creatinine in urine during - Levels of albumin in the urine 24 hours - Micral test for microalbuminuria

- Dipstick / tablet reagent for macroalbuminuria - Urine in a certain time (4 hours or overnight urine) Management - Control of blood glucose - Control your blood pressure - Dietary protein 0.8 g / kg / day. If a decline in kidney function gets worse, given dietary protein from 0.6 to 0.8 g / kg / day - Treatment with angiotensin II receptor, ACE inhibitors, or a combination of both - If there are contraindications to ACE or angiotensin receptor blockers, calcium antagonists non dihidropirin can be administered. - If serum creatinine> 2.0 mg / dL should be involved nephrologys expert. - Ideally if creatinine clearance <15 mL / min is an indication of replacement therapy (dialysis, transplantation). III. Diabetes with Erectile Dysfunction (ED) - Prevalence of erectile dysfunction in people with type 2 diabetes over 10 years is quite high and is due to the autonomy neuropathy, angiopathy and psychological problems. - Erectile dysfunction is a source of anxiety with diabetes, but rarely delivered to the doctor therefore needs to be asked at the time of consultation. - Management of erectile dysfunction in diabetes may refer to the Management of Erectile Dysfunction (Continuing Medical Education Material, IDI, 1999). Erectile dysfunction can be diagnosed using a simple instrument which IIEF5 questionnaire (International Index of Erectile Function 5). - Efforts main treatment is to improve control of blood glucose as normal person and improve other erectile dysfunction risk factors such as dyslipidemia, smoking, obesity and hypertension.

- Need identified a variety of patients consumed drugs that affect the onset of erectile dysfunction. - First-line treatment is psychosexual therapy and oral medications such as sildenafil and vardenafil. IV. Diabetes in Pregnancy / Gestational Diabetes Mellitus - Diabetes mellitus gestational (DMG) is a disorder of carbohydrate tolerance (IGT, GDPT, DM) which was first known to occur or when the pregnancy is ongoing. - Assessment of the risk needs to be done since DMG's first visit to check her pregnancy. - DMG risk factors include: obesity, a history of never having DMG, glucosuria, a family history of diabetes, recurrent abortion, a history of having a baby with congenital defects or birth to a baby weighing> 4000 grams, and a history of preeclampsia. In patients with risk DMG should be done immediately clear examination of blood glucose. When we got the result when blood glucose 200 mg / dL or fasting blood glucose 126 mg / dL in accordance with the limits for the diagnosis of diabetes, it is necessary to check at any other time for confirmation. Pregnant patients with IGT and GDPT managed as a DMG. - Diagnosis based on examination results TTGO done with a 75 gram glucose load after fasting 8-14 hours. Later examination of fasting blood glucose, 1 hour and 2 hours after the load. - DMG enforced if found to be the results of fasting blood glucose 95 mg / dL, 1 hour after the load <180 mg / dL and 2 hours after load 155 mg / dL. Where can only be done 1 time checks of blood glucose 2 hours after loading, if the obtained results of blood glucose 155 mg / dL, it can be diagnosed as a DMG. - Test results TTGO can be used to predict the occurrence of DM in the mother later - Management of DMG should be implemented in an integrated manner by a specialist in internal medicine, obstetrics gynecology specialists, dieticians and pediatricians. - The goal is to reduce morbidity management dna maternal mortality, perinatal

morbidity and mortality. This can only be achieved if the state of normoglycaemia can be maintained during pregnancy until delivery, - Target normoglycaemia DMG is a fasting blood glucose 95 mg / dL and 2 hours after eating 120 mg / dL. If the target blood glucose levels are not achieved by setting eating and physical exercise, directly administered insulin. V. Diabetes with Fasting Worship - People with diabetes is controlled with meal arrangements alone would not have difficulty to fast. During fasting, to be seen a change in schedule, the amount and composition of food intake. - Elderly diabetic people have a tendency to dehydration when fasting, therefore it is recommended to drink enough. - Need to increase patient awareness of symptoms of hypoglycemia. To avoid the occurrence of hypoglycemia during the day, approached the recommended schedule of meal times imsak / subuh, reduce physical activity during the day and when physical activity is recommended in the afternoon. - People with diabetes are quite restrained with OHO single dose, is also not difficult to fast. OHO given when fasting. Beware of the occurrence of hypoglycemia in patients receiving maximal doses of OHO. - For those who are controlled by OHO divided doses, dosing of drugs administered in such a way that dose before buka is greater than the dose in sahur. - For people with type 2 diabetes mellitus who use insulin, used intermediate-acting insulin is given when breaking it. - It takes a higher vigilance against the occurrence of hypoglycemia in diabetic insulin users. Need more stringent monitoring with adjustment of dose and schedule of insulin injections. When symptoms of hypoglycemia, fasting is stopped. - For patients who need to use multiple doses of insulin is recommended for not fasting in Ramadan. VI. Perioperative Management of Diabetes

- Operation, especially with general anesthesia is a stress factor triggering the occurrence of acute complications of diabetes. Therefore any elective surgery in people with diabetes should be prepared as optimal as possible (target fasting blood glucose levels <150 mg / dL) - Preparation of elective surgery and non-elective can be seen in the guidelines insulin therapy in the hospital.