1、Dr. Rasha SalamaPhD Public Health, Suez Canal University, Egypt Diabetes MSc, Cardiff University, United Kingdom Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. The term diabetes mellit
2、us describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.The effects of diabetes mellitus include longterm damage, dysfunction and
3、 failure of various organs.Diabetes mellitus may present with characteristic symptoms such as thirst, polyuria, blurring of vision, and weight loss. In its most severe forms, ketoacidosis or a nonketotic hyperosmolar state may develop and lead to stupor, coma and, in absence of effective treatment,
4、death. Often symptoms are not severe, or may be absent, and consequently hyperglycaemia sufficient to cause pathological and functional changes may be present for a long time before the diagnosis is made.The longterm effects of diabetes mellitus include progressive development of the specific compli
5、cations of retinopathy with potential blindness, nephropathy that may lead to renal failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints, and features of autonomic dysfunction, including sexual dysfunction. People with diabetes are at increased risk of cardiovascular, peri
6、pheral vascular and cerebrovascular disease.The development of diabetes is projected to reach pandemic proportions over the next10-20 years. International Diabetes Federation (IDF) data indicate that by the year 2025, the number of people affected will reach 333 million 90% of these people will have
7、 Type 2 diabetes.In most Western societies, the overall prevalence has reached 4-6%, and is as high as 10-12% among 60-70-year-old people.The annual health costs caused by diabetes and its complications account for around 6-12% of all health-care expenditure.Type 1 Diabetes Mellitus Type 2 Diabetes
8、MellitusGestational DiabetesOther types:vLADA (vMODY (maturity-onset diabetes of youth)vSecondary Diabetes MellitusWas previously called insulin-dependent diabetes mellitus Was previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. (IDDM) or juvenile-onset diabetes.
9、 Type 1 diabetes develops when the bodys immune system Type 1 diabetes develops when the bodys immune system destroys pancreatic beta cells, the only cells in the body destroys pancreatic beta cells, the only cells in the body that make the hormone insulin that regulates blood that make the hormone
10、insulin that regulates blood glucose. glucose. This form of diabetes usually strikes children and young This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. adults, although disease onset can occur at any age. Type 1 diabetes may account for 5
11、% to 10% of all Type 1 diabetes may account for 5% to 10% of all diagnosed cases of diabetes. diagnosed cases of diabetes. Risk factors for type 1 diabetes may include autoimmune, Risk factors for type 1 diabetes may include autoimmune, genetic, and environmental factors.genetic, and environmental f
12、actors.Was previously called non-insulin-dependent diabetes mellitus Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. (NIDDM) or adult-onset diabetes. Type 2 diabetes may account for about 90% to 95% of all Type 2 diabetes may account for about 90% to 95
13、% of all diagnosed cases of diabetes. diagnosed cases of diabetes. It usually begins as insulin resistance, a disorder in which the It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, cells do not use insulin properly. As
14、 the need for insulin rises, the pancreas gradually loses its ability to produce insulin. the pancreas gradually loses its ability to produce insulin. Type 2 diabetes is associated with older age, obesity, family Type 2 diabetes is associated with older age, obesity, family history of diabetes, hist
15、ory of gestational diabetes, impaired history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. glucose metabolism, physical inactivity, and race/ethnicity. African Americans, Hispanic/Latino Americans, American Indians, African Ameri
16、cans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Native Hawaiians or Other Pacific and some Asian Americans and Native Hawaiians or Other Pacific Islanders are at particularly high risk for type 2 diabetes. Islanders are at particularly high risk for type 2 diabetes. T
17、ype 2 diabetes is increasingly being diagnosed in children and Type 2 diabetes is increasingly being diagnosed in children and adolescents.adolescents.A form of glucose intolerance that is diagnosed in some A form of glucose intolerance that is diagnosed in some women during pregnancy. women during
18、pregnancy. Gestational diabetes occurs more frequently among Gestational diabetes occurs more frequently among African Americans, Hispanic/Latino Americans, and African Americans, Hispanic/Latino Americans, and American Indians. It is also more common among obese American Indians. It is also more co
19、mmon among obese women and women with a family history of diabetes. women and women with a family history of diabetes. During pregnancy, gestational diabetes requires treatment During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid to normalize
20、maternal blood glucose levels to avoid complications in the infant. complications in the infant. After pregnancy, 5% to 10% of women with gestational After pregnancy, 5% to 10% of women with gestational diabetes are found to have type 2 diabetes. diabetes are found to have type 2 diabetes. Women who
21、 have had gestational diabetes have a 20% to Women who have had gestational diabetes have a 20% to 50% chance of developing diabetes in the next 5-10 years.50% chance of developing diabetes in the next 5-10 years.Other specific types of diabetes result from Other specific types of diabetes result fr
22、om specific genetic conditions (such as maturity-specific genetic conditions (such as maturity-onset diabetes of youth), surgery, drugs, onset diabetes of youth), surgery, drugs, malnutrition, infections, and other illnesses. malnutrition, infections, and other illnesses. Such types of diabetes may
23、account for 1% to Such types of diabetes may account for 1% to 5% of all diagnosed cases of diabetes. 5% of all diagnosed cases of diabetes. Latent Autoimmune Diabetes in Adults (LADA) is a form of autoimmuneautoimmune (type1 diabetestype1 diabetes) which is diagnosed in individuals who are older th
24、an the usual age of onset of type 1 diabetes. Alternate terms that have been used for LADA include Late-onset Autoimmune Diabetes of Adulthood, Slow Onset Type 1 diabetes, and sometimes also Type 1.5 Often, patients with LADA are mistakenly thought to have type2 diabetestype2 diabetes, based on thei
25、r age at the time of diagnosis. About 80% of adults apparently with recently diagnosed Type 2 diabetes but with GAD auto-antibodies (i.e. LADA) progress to insulin requirement within 6 years.The potential value of identifying this group at high risk of progression to insulin dependence includes: the
26、 avoidance of using metformin treatment the early introduction of insulin therapyMODY Maturity Onset Diabetes of the YoungMODY is a monogenic form of diabetes with an autosomal dominant mode of inheritance: Mutations in any one of several transcription factors or in the enzyme glucokinase lead to in
27、sufficient insulin release from pancreatic -cells, causing MODY. Different subtypes of MODY are identified based on the mutated gene.Originally, diagnosis of MODY was based on presence of non-ketotic hyperglycemia in adolescents or young adults in conjunction with a family history of diabetes.Howeve
28、r, genetic testing has shown that MODY can occur at any age and that a family history of diabetes is not always obvious.Within MODY, the different subtypes can essentially be divided into 2 distinct groups: glucokinase MODY and transcription factor MODY, distinguished by characteristic phenotypic fe
29、atures and pattern on oral glucose tolerance testing. Glucokinase MODY requires no treatment, while transcription factor MODY (i.e. Hepatocyte nuclear factor -1alpha) requires low-dose sulfonylurea therapy and PNDM (caused by Kir6.2 mutation) requires high-dose sulfonylurea therapy.Secondary causes
30、of Diabetes mellitus include: Acromegaly, Cushing syndrome, Thyrotoxicosis, PheochromocytomaChronic pancreatitis, CancerDrug induced hyperglycemia:Atypical Antipsychotics - Alter receptor binding characteristics, leading to increased insulin resistance.Beta-blockers - Inhibit insulin secretion.Calci
31、um Channel Blockers - Inhibits secretion of insulin by interfering with cytosolic calcium release.Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium channels.Naicin - They cause increased insulin
32、resistance due to increased free fatty acid mobilization.Phenothiazines - Inhibit insulin secretion.Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause increased insulin resistance due to increased f
33、ree fatty acid mobilization.Prediabetes is a term used to distinguish people who are at increased risk of developing diabetes. People with prediabetes have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Some people may have both IFG and IGT. IFG is a condition in which the fasti
34、ng blood sugar level is elevated (100 to 125 milligrams per decilitre or mg/dL) after an overnight fast but is not high enough to be classified as diabetes. IGT is a condition in which the blood sugar level is elevated (140 to 199 mg/dL after a 2-hour oral glucose tolerance test), but is not high en
35、ough to be classified as diabetes. Progression to diabetes among those with prediabetes is not inevitable. Studies suggest that weight loss and increased physical activity among people with prediabetes prevent or delay diabetes and may return blood glucose levels to normal. People with prediabetes a
36、re already at increased risk for other adverse health outcomes such as heart disease and stroke. Research studies have found that lifestyle changes can prevent or delay the onset of type 2 diabetes among high-risk adults. These studies included people with IGT and other high-risk characteristics for
37、 developing diabetes.Lifestyle interventions included diet and moderate-intensity physical activity (such as walking for 2 1/2 hours each week). In the Diabetes Prevention Program, a large prevention study of people at high risk for diabetes, the development of diabetes was reduced 58% over 3 years.
38、 Studies have shown that medications have been successful in preventing diabetes in some population groups. In the Diabetes Prevention Program, people treated with the drug metformin reduced their risk of developing diabetes by 31% over 3 years. Treatment with metformin was most effective among youn
39、ger, heavier people (those 25-40 years of age who were 50 to 80 pounds overweight) and less effective among older people and people who were not as overweight. Similarly, in the STOP-NIDDM Trial, treatment of people with IGT with the drug acarbose reduced the risk of developing diabetes by 25% over
40、3 years. Other medication studies are ongoing. In addition to preventing progression from IGT to diabetes, both lifestyle changes and medication have also been shown to increase the probability of reverting from IGT to normal glucose tolerance. Management of Management of Diabetes MellitusDiabetes M
41、ellitusThe major components of the treatment of diabetes are:Diet and ExerciseDiet and ExerciseAOral hypoglycaemic Oral hypoglycaemic therapytherapyBInsulin TherapyInsulin TherapyCDiet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to en
42、suring appropriate nutrition.Dietary treatment should aim at:Dietary treatment should aim at: ensuring weight control providing nutritional requirements allowing good glycaemic control with blood glucose levels as close to normal as possible correcting any associated blood lipid abnormalitiesThe fol
43、lowing principles are recommended as dietary guidelines The following principles are recommended as dietary guidelines for people with diabetes:for people with diabetes:Dietary fat should provide 25-35% of total intake of calories but saturated fat intake should not exceed 10% of total energy. Chole
44、sterol consumption should be restricted and limited to 300 mg or less daily.Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable body weight). Requirements increase for children and during pregnancy. Protein should be derived from both animal and vegetable sources.Carbohydra
45、tes provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.Excessive salt intake is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy.Physical activity promotes weight reduction and improves insu
46、lin sensitivity, thus lowering blood glucose levels.Together with dietary treatment, a programme of regular physical activity and exercise should be considered for each person. Such a programme must be tailored to the individuals health status and fitness. People should, however, be educated about t
47、he potential risk of hypoglycaemia and how to avoid it.There are currently four classes of oral anti-diabetic agents:i. Biguanidesii. Insulin Secretagogues Sulphonylureasiii. Insulin Secretagogues Non-sulphonylureasiv. -glucosidase inhibitorsv. Thiazolidinediones (TZDs)If glycaemic control is not ac
48、hieved (HbA1c 6.5% and/or; FPG 7.0 mmol/L or; RPG 11.0mmol/L) with lifestyle modification within 1 3 months, ORAL ANTI-DIABETIC AGENT should be initiated.In the presence of marked hyperglycaemia in newly diagnosed symptomatic type 2 diabetes (HbA1c 8%, FPG 11.1 mmol/L, or RPG 14 mmol/L), oral anti-d
49、iabetic agents can be considered at the outset together with lifestyle modification.As first line therapy:Obese type 2 patients, consider use of metformin, acarbose or TZD.Non-obese type 2 patients, consider the use of metformin or insulin secretagoguesMetformin is the drug of choice in overweight/o
50、bese patients. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin.If monotherapy fails, a combination of TZDs, acarbose and metformin is recommended. If targets are still not achieved, insulin secretagogues may be addedCombination oral agents is indicated in:Newly
