DEFINITION (Craig ME, Hattersley A, Donaghue KC. Definition, epidemiology and classification of diabetes in children and adolescents.

Pediatric Diabetes 2009: 10 (Suppl. 12): 312.) Diabetes mellitus is a group of metabolic diseases characterised by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The abnormalities in carbohydrate, fat, and protein metabolism that are found in diabetes are due to deficient action of insulin on target tissues. If ketones are present in blood or urine, treatment is urgent, because ketoacidosis can evolve rapidly. Diagnostic criteria for diabetes are based on blood glucose measurements and the presence or absence of symptoms. Three ways to diagnose diabetes are possible and each, in the absence of unequivocal hyperglycemia, must be confirmed, on a subsequent day. Diabetes in children usually presents with characteristic symptoms such as polyuria, polydipsia, blurring of vision, and weight loss, in association with glycosuria and ketonuria. In its most severe form, ketoacidosis or rarely a non-ketotic hyperosmolar state may develop and lead to stupor, coma and in absence of effective treatment, death. The diagnosis is usually confirmed quickly by measurement of a marked elevation of the blood glucose level. In this situation if ketones are present in blood or urine, treatment is urgent. Waiting another day to confirm the hyperglycemia may be dangerous in allowing ketoacidosis to evolve rapidly. In the absence of symptoms or presence of mild symptoms of diabetes, hyperglycemia detected incidentally or under conditions of acute infective, traumatic, circulatory or other stressmay be transitory and should not in itself be regarded as diagnostic of diabetes. The diagnosis of diabetes should not be based on a single plasma glucose concentration. Diagnosis may require continued observation with fasting and/or 2 hour post-prandial blood glucose levels and/or an oral glucose tolerance test (OGTT). An OGTT should not be performed if diabetes can be diagnosed using fasting, random or post-prandial criteria as excessive hyperglycemia can result. It is rarely indicated in making the diagnosis of type 1 diabetes in childhood and if doubt remains, periodic re-testing should be undertaken until the diagnosis is established.

Clasification a. Type 1 (Kaufman,FR . 2003 . Type 1 Diabetes Mellitus . journal of the American Academy of Pediatrics . Boulevard) The natural history of type 1 diabetes is shown in the Figure. Beta-cell mass is destroyed gradually over time in genetically susceptible individuals after exposure to environmental triggers that induce T-cell-mediated beta-cell injury and the production of humoral autoantibodies. The degree of beta-cell destruction can be determined by the first-phase insulin response during intravenous glucose tolerance testing. Those who have lost first-phase insulin release are at high risk to develop clinical diabetes. At the clinical onset of disease, a residual beta-cell population still survives that allows for the remission or honeymoon period after diabetes is diagnosed. If these cells could be preserved, diabetes management would become significantly less difficult over time. Preserving residual beta-cells, as well as stopping the initial autoimmune beta-cell injury, has become a focus of research interest

b. Type 2 (AMERICAN DIABETES ASSOCIATION . 2012. Diagnosis and Classification of Diabetes Mellitus. DIABETES CARE, VOLUME 35, SUPPLEMENT 1) Type 2 diabetes, or adult onset diabetes, encompasses individuals who have insulin resistance and usually have relative (rather than absolute) insulin deficiency At least initially, and often throughout their lifetime, these individuals do not need insulin treatment to survive. There are probably many different causes of this form of diabetes. Although the specific etiologies are not known, autoimmune destruction of b-cells does not occur, and patients do not have any of the other causes of diabetes listed above or below. Most patients with this form of diabetes are obese, and obesity itself causes some degree of insulin resistance. Patients who are not obese by traditional weight criteria may have an increased percentage of body fat distributed predominantly in the abdominal region. Keto acidosis seldom occurs spontaneously in this type of diabetes; when seen, it usually arises in association with the stress of another illness such as infection. This form of diabetes frequently goes undiagnosed for many years because the hyperglycemia develops gradually and at earlier stages is often not severe enough for the patient to notice any of the classic symptoms of diabetes. Nevertheless, such patients are at increased risk of developing macrovascular and microvascular complications. Whereas patients with this form of diabetes may have insulin levels that appear normal or elevated, the higher blood glucose levels in these diabetic patients would be expected to result in even higher insulin values had their b-cell function been normal. Thus, insulin secretion is defective in these patients and insufficient to compensate for insulin resistance. Insulin resistance may improve with weight reduction and/or pharmacological treatment of hyperglycemia but is seldom restored to normal. The risk of developing this form of diabetes increases with age, obesity, and lack of physical activity. It occurs more frequently in women with prior GDM and in individuals with hypertension or dyslipidemia, and its

frequency varies in different racial/ethnic subgroups. It is often associated with a strong genetic predisposition, more so than is the autoimmune formof type 1 diabetes. However, the genetics of this form of diabetes are complex and not clearly defined. Etiologi (Riaz,S . 2009. Diabetes mellitus . Department of Microbiology and Molecular Genetics, Punjab University, New Campus, Lahore. Pakistan. p370) The causes of diabetes are complex and only partly understood. This disease is generally considered multifactorial, involving several predisposing conditions and risk factors. In many cases genetics, habits and environment may all contribute to a persons diabetes. To complicate matters, there can be contrary risk factors for the various forms of the disease. For example, autoimmune diabetes (type 1 and latent autoimmune diabetes of adulthood, LADA) is more common in white people, but metabolic diabetes (type 2 and gestational diabetes) is more common in people of other races and ethnicities. Type 1 is usually diagnosed in children, but advancing age is a risk factor for type 2 and gestational diabetes. Insulin resistance, prediabetes and metabolic syndrome are strong risk factors for type 2 diabetes. Other diabetic risk factors and causes include: a. Genetics and family history: Certain genes are known to cause maturity-onset diabetes of the young (MODY) and Wolfram syndrome. Genes also contribute to other forms of diabetes, including types 1 and 2. b. Family medical history is also influential to varying degrees: For example, a person whose parents both have type 1 diabetes has a 10 to 25% chance of developing that disease, according to the American Diabetes Association, and someone whose parents both have type 2 diabetes has a 50% chance of developing that disease. c. Weight and body type: Overweight and obesity are leading factors in type 2 diabetes and gestational diabetes. Excess fat, especially around the abdomen (central obesity), promotes insulin resistance and metabolic syndrome. Most

people with autoimmune diabetes (type 1 and LADA) are of normal weight, and excess weight has not traditionally been considered to be related to these conditions. However, recent research indicates that obesity may hasten the development of type 1 diabetes and that the increasing rate of type 1 diabetes may be at least partly due to the rise of childhood obesity. Furthermore, patients with autoimmune diabetes who gain weight are susceptible to insulin resistance and double diabetes. d. Sex: Though men make up less than 49% of the U.S. adult population, they account for 53% of the adult cases of diabetes, according to the National Institutes of Health (NIH). The prevalence of diabetes in American men and women was similar until 1999, when a growing disparity began, according to an analysis of statistics published by the U.S. Centers for Disease Control and Prevention (CDC). Little or no research has been conducted to explain this trend. One factor may be the documented increase in recent years of low testosterone levels (male hypogonadism), which scientists have linked to insulin resistance. e. Level of physical activity: Lack of regular exercise is blamed for much of the twin global epidemics of obesity and diabetes. f. Diet: The effect of diet in the development of diabetes is controversial. Some studies have linked heavy consumption of soft drinks and other simple carbohydrates to risk of metabolic diabetes, and foods low in the glycemic index, such as whole grains, to reduced risk. Yet the ADA states that eating foods containing sugar does not cause the disease. The culprit, rather, is the weight gain due to sedentary habits and excess intake of calories, according to the ADA. Another dispute centers around whether being fed cows milk early in life might be linked to type 1 diabetes. Some researchers have noted a connection, but others have not. Further scientific research is likely on this topic. g. Other diseases: Medical conditions including high blood pressure, hyperlipidemia (unhealthy levels of cholesterol), polycystic ovarian

syndrome, asthma and sleep apnea have been linked to type 2 diabetes. Celiac disease (gluten intolerance) and other autoimmune diseases have been linked to type 1. The many conditions that may cause secondary diabetes include pancreatitis, hemochromatosis, endocrine disorders including hyperthyroiddism, Cushings disease and acromegaly, and genetic conditions including cystic fibrosis, Down syndrome and some forms of muscular dystrophy, Diabetic foot and urinary tract infection (Lipsky et al., 2004; Mokabberi and Ravakhah, 2007). h. Other chemicals: viruses, smoking and alchohol. Most of these risk factors can be described as either uncontrollable, such as genetics and age, or controllable, such as exercise and diet. Some, such as obesity, may involve genetics and lifestyle choices. People cannot alter their uncontrollable risk factors, but they can lower their risk of developing diabetes by reducing controllable risk factors through improved health habits Manifestasi