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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 treatmentthe 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 insuf
27、ficient 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.However, g
28、enetic 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 featur
29、es 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 of D
30、iabetes 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.Calcium C
31、hannel 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 resi
32、stance 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 free
33、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 fasting b
34、lood 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 enough
35、 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 are a
36、lready 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 dev
37、eloping 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. Stu
38、dies 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 younger,
39、 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 3 ye
40、ars. 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 Melli
41、tusThe major components of the treatment of diabetes are:Diet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.Dietary treatment should aim at:Dietary treatment should aim at:ensuring weight controlprovidi
42、ng nutritional requirementsallowing good glycaemic control with blood glucose levels as close to normal as possiblecorrecting any associated blood lipid abnormalitiesThe following principles are recommended as dietary guidelines for The following principles are recommended as dietary guidelines for
43、people with diabetes: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. Cholesterol consumption should be restricted and limited to 300 mg or less daily.Protein intake can range between 10-15% total energ
44、y (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.Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.Excessive salt intak
45、e is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy.Physical activity promotes weight reduction and improves insulin sensitivity, thus lowering blood glucose levels.Together with dietary treatment, a programme of regular physical activity a
46、nd 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 the potential risk of hypoglycaemia and how to avoid it.There are currently four classes of oral anti-diabetic agents:i. Biguani
47、desii. Insulin Secretagogues Sulphonylureasiii. Insulin Secretagogues Non-sulphonylureasiv. -glucosidase inhibitorsv. Thiazolidinediones (TZDs)If glycaemic control is not achieved (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
48、 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-diabetic agents can be considered at the outset together with lifestyle modification.As first line therapy:Obese type 2 patients
49、, 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/obese patients. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin.If monotherapy fails, a c
50、ombination of TZDs, acarbose and metformin is recommended. If targets are still not achieved, insulin secretagogues may be addedCombination oral agents is indicated in:Newly diagnosed symptomatic patients with HbA1c 10Patients who are not reaching targets after 3 months on monotherapyIf targets have
51、 not been reached after optimal dose of combination therapy for 3 months, consider adding intermediate-acting/long-acting insulin (BIDS).Combination of insulin+ oral anti-diabetic agents (BIDS) has been shown to improve glycaemic control in those not achieving target despite maximal combination oral
52、 anti-diabetic agents.Combining insulin and the following oral anti-diabetic agents has been shown to be effective in people with type 2 diabetes:Biguanide (metformin)Insulin secretagogues (sulphonylureas)Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an approved indication)
53、-glucosidase inhibitor (acarbose)Insulin dose can be increased until target FPG is achieved.Diabetes Diabetes Management Management Algorithm Algorithm In elderly non-obese patients, short acting insulin secretagogues can be started but long acting Sulphonylureas are to be avoided. Renal function sh
54、ould be monitored.Oral anti-diabetic agent s are not recommended for diabetes in pregnancyOral anti-diabetic agents are usually not the first line therapy in diabetes diagnosed during stress, such as infections. Insulin therapy is recommended for both the aboveTargets for control are applicable for
55、all age groups. However, in patients with co-morbidities, targets are individualizedWhen indicated, start with a minimal dose of oral anti-diabetic agent, while reemphasizing diet and physical activity. An appropriate duration of time (2-16 weeks depending on agents used) between increments should b
56、e given to allow achievement of steady state blood glucose controlShort-term use:Short-term use:Acute illness, surgery, stress and emergencies Pregnancy Breast-feedingInsulin may be used as initial therapy in type 2 diabetes in marked hyperglycaemia Severe metabolic decompensation (diabetic ketoacid
57、osis, hyperosmolar nonketotic coma, lactic acidosis, severe hypertriglyceridaemia)Long-term use:Long-term use:If targets have not been reached after optimal dose of combination therapy or BIDS, consider change to multi-dose insulin therapy. When initiating this,insulin secretagogues should be stoppe
58、d and insulin sensitisers e.g. Metformin or TZDs, can be continued.The majority of patients will require more than one daily injection if good glycaemic control is to be achieved. However, a once-daily injection of an intermediate acting preparation may be effectively used in some patients.be effect
59、ively used in some patients.Twice-daily mixtures of short- and intermediate-acting insulin is a commonly used regimen. In some cases, a mixture of short- and intermediate-acting In some cases, a mixture of short- and intermediate-acting insulin may be given in insulin may be given in the morning. Fu
60、rther doses of short-acting insulin are given before lunch and the evening meal and an evening dose of intermediate-acting insulin is given at bedtime.Other regimens based on the same principles may be used.A regimen of multiple injections of short-acting insulin before the main meals, with an appro
61、priate dose of an intermediate-acting insulin given at bedtime, may be used, particularly when strict glycaemic control is mandatory.Patients should be educated to practice self-care. This allows the patient to assume responsibility and control of his / her own diabetes management. Self-care should
62、include:Blood glucose monitoringBody weight monitoringFoot-carePersonal hygieneHealthy lifestyle/diet or physical activityIdentify targets for controlStopping smokingNational Diabetes Fact Sheet 2003, DEPARTMENT OF HEALTH AND National Diabetes Fact Sheet 2003, DEPARTMENT OF HEALTH AND HUMAN SERVICES
63、 HUMAN SERVICES Centres for Disease Control and PreventionWorld Health OrganizationWorld Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of WHO. Department of Non-communicable Disease Surveillance. GenevaDepartment of Non-communicable
64、Disease Surveillance. Geneva 1999Academy of Medicine. Clinical Practice Guidelines. Management of type 2 diabetes mellitus. MOH/P/PAK/87.04(GU), 2004NHS. Diabetes - insulin initiation - University Hospitals of Leicester Diabetes - insulin initiation - University Hospitals of Leicester NHS Trust NHS Trust Working in partnership with PCTs across Leicestershire and Rutland, May 2008. Thank You
