DIABETES MELLITUS Farmacologia Nutrição

Apresentação em tema: "DIABETES MELLITUS Farmacologia Nutrição"— Transcrição da apresentação:

1 DIABETES MELLITUS Farmacologia Nutrição
Slide n.º 1 1

2 Classificação Etiológica da Diabetes Mellitus
Tipo 1 Destruição das células b com falta de insulina Tipo 2 Resistência à insulina com deficiência de insulina Gestacional Resistência à insulina com disfunção das células b Outros tipos Defeitos genéticos na função das células b, doenças pancreáticas exócrinas (cancer) e outros Slide n.º 2 - Etiologic Classification of Diabetes Mellitus Diabetes mellitus is best described as a group of metabolic diseases character-ized by hyperglycemia. The hyperglycemia may be the result of defects in insulin secretion or insulin sensitivity, or both. Two major forms of diabetes are recognized in the most recent classification scheme, which was developed by The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, an international group, and has been adopted by both the American Diabetes Association and the World Health Organization. Type 1 diabetes includes almost all cases that are marked by destruction of the pancreatic islet -cells. Type 2 diabetes includes those cases that result from insulin resistance accompanied by a defect in insulin secretion. Other specific forms of diabetes, which affect far fewer patients than the two major forms, include genetic defects of -cell function, genetic defects in insulin sensitivity, diseases of the exocrine pancreas, endocrinopathies, drug- or chemical-induced infections, uncommon immune-mediated conditions, and other genetic conditions. Gestational diabetes mellitus is a fourth type in this new classification system. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20: Adaptado do site da Sociedade Brasileira de Diabetes 2

3 Categorias da Tolerância à Glicose Diminuída
Glicemia 2 horas após PTGO Glicemia em Jejum Diabetes Mellitus Diabetes Mellitus 126 mg/dl 200 mg/dl Anomalia da Tolerância à Glicose Anomalia da Tolerância à Glicose 110 mg/dl 140 mg/dl Normal Normal Slide n.º 3 - Glucose Tolerance Categories Either the fasting plasma glucose (FPG) test or the 2-hour plasma glucose (PG) determination during the oral glucose tolerance test (OGTT) may be used to determine glucose tolerance status. According to the most recent diagnostic criteria established by The Expert Committee on the Diagnosis and Class-ification of Diabetes Mellitus, an FPG value 126 mg/dL (7.0 mmol/L) or a 2-hour plasma glucose value 200 mg/dL (11.1 mmol/L) are the new cutoff points for the diagnosis of diabetes. The cutoff points for the intermediate stage of hyperglycemia denoted by the terms impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have been adjusted to conform to the new diagnostic criteria for diabetes mellitus. IFG is now defined by FPG 110 mg/dL (6.1 mmol/L) and <126 mg/dL (<7.0 mmol/L), and IGT is defined by 2-hour PG measurements 140 mg/dL (7.8 mmol/L) and <200 mg/dL (<11.1 mmol/L). The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20: ATG= Anomalia da Tolerância à Glicose ou Tolerância Diminuída à Glicose (TDG) PTGO = Prova da Tolerância à Glicose Oral (75 g de glicose em 2 dl de água e ingestão em 5 min) Adaptado de Sociedade Brasileira deDiabetes 3

4 Diagnóstico da Diabetes Valores da Glicemia
Glicemia em Jejum Glicemia 2 horas após PTGO Categoria mg/dl mmol/l mg/dl mmol/l Normal <110 <6.1 <140 <7.8 AGJ >110 and <126 >6.1 and <6.9 <140 <7.8 ATG >110 and <126 >6.1 and <6.9 >140 and <200 >7.8 and <11.1 Diabetes >126 >7.0 >200 >11.1 Slide n.º 4 - Diagnosis of Diabetes: Plasma Glucose Cutoff Points The most recent criteria for the diagnosis of diabetes include new plasma glucose cutoff points. When fasting plasma glucose (FPG) values are used, diabetes mellitus is indicated by a value 126 mg/dL (7.0 mmol/L). Impaired fasting glucose (IFG) is indicated by values 110 and <126 mg/dL (6.1 and <6.9 mmol/L). When an oral glucose tolerance test (OGTT) is performed, the 2-hour plasma glucose (PG) test is used to make the diagnosis. A value 200 mg/dL (11.1 mmol/L) indicates the presence of diabetes, while impaired glucose tolerance (IGT) is indicated by values 140 and <200 mg/dL (7.8 and <11.1 mmol/L). The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20: AGJ= Anomalia da Glicemia em Jejum ou Hiperglicemia do Jejum Não Diabética ATG= Anomalia da Tolerância à Glicose ou Tolerância Diminuída à Glicose (DTG) PTGO = Prova da Tolerância à Glicose Oral (75 g de glicose em 2 dl de água e ingestão em 5 min) 4

5 Diagnóstico da Diabetes Três Métodos
1. Glicemia ao acaso (em qualquer hora do dia e sem ter em conta a hora da última refeição) > 200 mg/dl em duas ocasiões separadas + sintomas (poliuria, polidipsia e perda de peso inexplicável) 2. GPJ > 126 mg/dl em duas ocasiões separadas 3. Glicemia 2 horas após PTGO > 200 mg/dl em duas ocasiões separadas Slide n.º 5 - Diagnosis of Diabetes: Three Methods The most recent diagnostic criteria for diabetes specify that the diagnosis may be made via one of three methods: (1) presence of symptoms (polyuria, polydipsia, unexplained weight loss) plus a random plasma glucose value 200 mg/dL (11.1 mmol/L); (2) a fasting plasma glucose (FPG) value 126 mg/dL (7.0 mmol/L); or (3) a 2-hour plasma glucose value 200 mg/dL (11.1 mmol/L) on the oral glucose tolerance test (OGTT). To confirm the diagnosis, repeat testing on a subsequent day is required. Any method may be used for the repeat test. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20: GPJ= Glicose Plasmática em Jejum PTGO = Prova da Tolerância à Glicose Oral (75 g de glicose em 2 dl de água e ingestão em 5 min) 5

6 Diabetes Mellitus 10 a 20 % Diabetes do Tipo 2 Magros 10 a 20%
Slide n.º 6 - Diagnosis of Diabetes: Three Methods The most recent diagnostic criteria for diabetes specify that the diagnosis may be made via one of three methods: (1) presence of symptoms (polyuria, polydipsia, unexplained weight loss) plus a random plasma glucose value 200 mg/dL (11.1 mmol/L); (2) a fasting plasma glucose (FPG) value 126 mg/dL (7.0 mmol/L); or (3) a 2-hour plasma glucose value 200 mg/dL (11.1 mmol/L) on the oral glucose tolerance test (OGTT). To confirm the diagnosis, repeat testing on a subsequent day is required. Any method may be used for the repeat test. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20: 60 a 70 % Diabetes do Tipo 2 com Peso Excessivo 6

7 Percentagem da População
Prevalência Estimada da Diabetes Adultos Homens e Mulheres (Grupos Etários) 30 Homens Mulheres 21.1 20.2 20 17.8 17.5 Percentagem da População 12.9 12.4 10 6.8 6.1 Slide n.º 7 - Estimated Prevalence of Diabetes Adult Men and Woman The 1997 prevalence of diagnosed diabetes among adults aged 20 years or older was estimated using data collected in the Third National Health and Nutrition Examination Survey (NHANES III), The most recent diagnostic criteria for diabetes (fasting plasma glucose [FPG] 126 mg/dL) was applied (see Slides 4 and 5). Prevalence rates rose with age, with a plateau after age 75 years. The highest prevalence rates (17.5% to 21.1%) were found in the 60- to 74- and 75+ -year age groups. Harris M, Flegal K, Cowie C, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. Diabetes Care. 1998;21: 1.6 1.7 20-39 40-49 50-59 60-74 75+ Idade (anos) Harris, et al. Diabetes Care. 1998;21: 7

8 DIABETES TIPO 2 Definição
Tipo de DM caracterizado por defeitos da ação (resistência à insulina) e da secreção de insulina Ambos os defeitos estão presentes na época em que a doença se manifesta clinicamente Slide n.º 8 - Estimated Prevalence of Diabetes Adult Men and Woman The 1997 prevalence of diagnosed diabetes among adults aged 20 years or older was estimated using data collected in the Third National Health and Nutrition Examination Survey (NHANES III), The most recent diagnostic criteria for diabetes (fasting plasma glucose [FPG] 126 mg/dL) was applied (see Slides 4 and 5). Prevalence rates rose with age, with a plateau after age 75 years. The highest prevalence rates (17.5% to 21.1%) were found in the 60- to 74- and 75+ -year age groups. Harris M, Flegal K, Cowie C, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. Diabetes Care. 1998;21: OMS, 1999 8

9 DIABETES TIPO 2 Definição
As razões exatas para o desenvolvimento destas anormalidades não está completamente esclarecidas É o tipo de DM mais comum (estima-se que em 2020 haverá em todo o mundo cerca de 250 milhões de diabéticos tipo 2) Slide n.º 9 - Estimated Prevalence of Diabetes Adult Men and Woman The 1997 prevalence of diagnosed diabetes among adults aged 20 years or older was estimated using data collected in the Third National Health and Nutrition Examination Survey (NHANES III), The most recent diagnostic criteria for diabetes (fasting plasma glucose [FPG] 126 mg/dL) was applied (see Slides 4 and 5). Prevalence rates rose with age, with a plateau after age 75 years. The highest prevalence rates (17.5% to 21.1%) were found in the 60- to 74- and 75+ -year age groups. Harris M, Flegal K, Cowie C, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. Diabetes Care. 1998;21: OMS, 1999 9

10 A diabetes do tipo 2 não é uma diabetes menor
A diabetes é a primeira causa de cegueira nos países industrializados Em cada dois diabéticos cegos um é do tipo 1... e o outro é do tipo 2... Slide n.º 10 - Fonte: G. Slama et al, Lancet 1992, p 244 10

11 Fisiopatologia da Diabetes do Tipo 2
Tecidos Periféricos (Músculo) Defeitos no receptor Resistência Glicose à Insulina Fígado Aumento da produção de glicose Slide n.º 11 - Plasma Insulin After Oral Glucose: Effects of Obesity and Diabetes Following a glucose challenge after overnight fasting, plasma insulin levels are dependent upon obesity as well as diabetes. Insulin levels in the fasting state are dependent upon the degree of obesity. Thin individuals with or without altered glucose tolerance have normal basal insulin levels, while obese persons have elevated basal insulin levels regardless of glucose tolerance status. After a glucose challenge, both thin and obese individuals with type 2 diabetes demonstrate reduced early insulin responses when compared with their respective control groups. However, obese individuals with type 2 diabetes have higher post-glucose insulin levels than do thin individuals with normal glucose tolerance, thus demonstrating the persistence of the effect of obesity on insulin secretion. Bagdade JD, Bierman EL, Porte D Jr. The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest. 1967;46: Pâncreas Diminuição da secreção de insulina 11 Saltiel AR, Olefsky JM. Diabetes. 1996;45:

12 Fisiopatologia da Diabetes do Tipo 2
Defeito nas células b Resistência à Insulina Periférica Hiperinsulinemia Anomalia da Tolerância à Glicose Defeito no reconhecimento da glicose Diminuição da secreção de insulina Diabetes no inicio Insuficiência das células b Obesidade Slide n.º 12 - Plasma Insulin After Oral Glucose: Effects of Obesity and Diabetes Following a glucose challenge after overnight fasting, plasma insulin levels are dependent upon obesity as well as diabetes. Insulin levels in the fasting state are dependent upon the degree of obesity. Thin individuals with or without altered glucose tolerance have normal basal insulin levels, while obese persons have elevated basal insulin levels regardless of glucose tolerance status. After a glucose challenge, both thin and obese individuals with type 2 diabetes demonstrate reduced early insulin responses when compared with their respective control groups. However, obese individuals with type 2 diabetes have higher post-glucose insulin levels than do thin individuals with normal glucose tolerance, thus demonstrating the persistence of the effect of obesity on insulin secretion. Bagdade JD, Bierman EL, Porte D Jr. The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest. 1967;46: Diabetes tardia Saltiel AR, Olefsky JM. Diabetes. 1996;45: 12

13 Desenvolvimento da Anomalia da Tolerância à Glicose
Os doentes com diabetes tipo 2 têm um fenotipo complexo com: defeitos da secreção de insulina (hiperinsulinismo não compensatório) aumento da produção hepática de glicose resistência à ação da insulina Causas possíveis deste fenotipo genéticas ambientais metabólicas (ácidos graxos livres) outras Slide n.º 13 - Cavaghan MK, et al, J Clin Invest, 106: 13

14 INSULINO-RESISTÊNCIA Definição
Insulino-resistência (ou  da sensibilidade à insulina): – dificuldade da insulina exercer a sua ação na captação da glicose a nível periférico, músculos, tecido adiposo, fígado, com  da produção hepática de glicose e células -pancreáticas contribuindo para o déficit secretor. Slide n.º 14 - 14

15 INSULINO-RESISTÊNCIA Definição
necessidade de uma insulinemia inapropriadamente elevada (hiperinsulinismo compensatório) para manutenção da homeostase metabólica. Slide n.º 15 - 15

16 DIABETES DO TIPO 2 Objetivos Terapêuticos
Parâmetro Valores Glicose em Jejum sangue total mg/dl plasma mg/dl HbA1c ótima <6% bom <7% nível de ação >8% Colesterol Total <200 mg/dl LDL-C ótimo <100 mg/dl iniciar tratamento >130 mg/dl HDL-C >45 mg/dl Triglicéridos <200 mg/dl Slide n.º 16 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: Data from American Diabetes Association. Diabetes Care. 1999;22 (suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. JAMA. 1993;209: 16

17 DIABETES DO TIPO 2 Terapêutica não Farmacológica
MODIFICAÇÕES DIETÉTICAS (a maioria são doentes com peso excessivo) Restrição calórica redução da ingestão de gorduras saturadas aumentar a ingestão de carbohidratos complexos em vez dos simples Slide n.º 17 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: 17

18 DIABETES DO TIPO 2 Terapêutica não Farmacológica
EXERCÍCIO FÍSICO como adjuvante do tratamento dietético. está associado com melhorias do controle da glicemia independentemente das alterações do peso. Slide n.º 18 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: 18

19 DIABETES DO TIPO 2 Terapêutica Farmacológica
SULFONILUREIAS e GLINIDAS (Secretagogos de Insulina) BIGUANIDAS (Anti-hiperglicemiantes) INIBIDORES DAS -GLUCOSIDASES SENSIBILIZADORES DA INSULINA (Glitazonas) Slide n.º 19 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: INSULINA 19

20 SULFONILUREIAS e GLINIDAS HIPOGLECIMIANTES (Secretagogos de Insulina)
Primeiro antidiabético oral comercializado Descoberta acidentalmente por um médico Francês (Marcel Janbon) na II Guerra Mundial, ao verificar o aparecimento de hipoglicemia quando tratava a febre tifóide com um derivado da sulfonamida. Desenvolvida posteriormente por Loubatières A 1ª Sulfonilureia disponível em 1955, na Alemanha = CARBUTAMIDA Slide n.º 20 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: 20

21 Secretagogos de Insulina: Características Básicas das Sulfonilureias e das Meglitinidas
Mecanismo de ação Aumento da secreção de insulina basal e pós prandial Dependem Do funcionamento das células  Atividade Diminuem a HbA1c de 1% a 2% Dose Uma/duas vezes ao dia (sulfonilureias); Uma a três vezes ao dia (meglitinidas) Reações adversas Aumento de peso, alergia (rara) Principal risco Hipoglicemia Slide n.º 21 - The Insulin Secretagogues: Basic Characteristics of the Sulfonylureas and the Meglitinides The insulin secretagogues, which include the sulfonylureas and the meglitinides, lower plasma glucose by augmenting insulin secretion by the pancreatic b-cells. These agents are thus effective only if functioning pancreatic b-cells are present. During treatment with the insulin secretagogues, a reduction of glycosylated hemoglobin (HbA1c) by approximately 1.0% to 2.0% may be expected. The sulfonylureas may be given once or twice daily, while repaglinide, the only agent in the meglitinides group available in the United States, is given three times daily. Weight gain is the most notable side effect; allergy occurs rarely. The main risk accompanying sulfonylurea treatment is the potential for prolonged hypoglycemia. Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:1-139. 21

22 BIGUANIDAS (Anti-hiperglicemiantes)
Primeiro antidiabético oral (utilizado desde a Idade Média = Guanidina) Nos finais da década de 50 e após as sulfunilureias são comercializadas: Fenformina Meformina Fenformina retirada do mercado em alguns países nos finais da década de 70 (Risco elevado de acidose láctica e mortalidade cardiovascular) Slide n.º 22 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: 22

23 BIGUANIDAS (Anti-hiperglicemiantes)
Características Básicas da Metformina Mecanismo de ação Diminui a produção hepática de glicose Depende Da presença de insulina Atividade Diminui a HbA1c de 1 % a 2% Dose Uma a três vezes ao dia Reações adversas Diarreia, náuseas Principal risco Acidose Láctica Slide n.º 23 - The Biguanides: Basic Characteristics of Metformin Metformin, the sole available representative of the biguanide class in the United States, decreases hepatic glucose production. This agent works only in the presence of insulin, which may be of endogenous or exogenous origin. It reduces the plasma level of glycosylated hemoglobin (HbA1c) by 1.0% to 2.0%. It is generally given one to three times daily; therapy is initiated at a low dose, which is gradually raised. Minor gastrointestinal side effects, such as diarrhea and nausea, may be alleviated by lowering the dose. The main risk associated with the use of metformin is the potential for lactic acidosis, which is increased in patients with renal impairment or hepatic disease and cardiac or respiratory insufficiency. Bell P, Hadden D. Metformin. Endocrinol Metab Clin. 1997;26: ; De Fronzo R, Goodman AM, and The Multicenter Metformin Study Group. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333: ; Bailey D, Turner R. Metformin. N Engl J Med. 1996;334: ; Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:1-139. SBD 23

24 Efeitos da Metformina Reduz a glicemia em jejum ( 70mg/dl) e a HbA1c ( 1,5%) Reduz o peso corporal e o hiperinsulinismo Induz  de LDL e TG e  de HDL A nível periférico induz um  da sensibilidade à insulina O principal efeito é a supressão da produção hepática da glicose basal, induzindo uma  da glicemia do jejum inibindo a glicogenólise e a neoglicogênese Slide n.º 24 - 24

25 INIBIDORES DAS -GLICOSIDASES
Os Hidratos de Carbono sofrem, no trato gastrintestinal, a digestão enzimática pelas -glicosidases desdobrando-os em monossacaridos para que assim possam ser absorvidos São inibidores competitivos reversíveis da digestão dos polissacarídeos Acarbose Slide n.º 25 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: 25

26 SENSIBILIZADORES DA INSULINA Tiazolidinedionas (TZDs) (Glitazonas)
Mecanismo de ação está diretamente relacionado com o “receptor gama activado de proliferação dos peroxisomas” (Peroxisomal Proliferator Activator Receptor  = PPAR) no tecido adiposo e músculo esquelético. Aumenta a sensibilidade da insulina nos tecidos periféricos São: Troglitazona= Retirada em 2000 por toxicidade hepática Rosiglitazona Pioglitazona Slide n.º 26 - TYPE 2 DIABETES Metabolic Targets Because diabetes mellitus affects many organ systems, treatment is assessed by the measurement of blood glucose, glycosylated hemoglobin (HbA1c), and plasma lipid levels. Optimal metabolic control is indicated by a fasting blood glucose concentration between 80 and 120 mg/dL and a postprandial (2 h) blood glucose concentration <180 mg/dL. The American Diabetes Association goal and action point for HbA1c is based on evidence from the Diabetes Control and Complications Trial and recently confirmed by the United Kingdom Prospective Diabetes Study. Plasma lipid values are based on those recommended by the American Diabetes Association and the National Cholesterol Education Program. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1999;22(suppl 1):S32-S41; The National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the NCEP expert panel on the detection, evaluation, and treatment of high blood cholesterol. JAMA. 1993;209: 26

27 Redução dos níveis de TG e  HDL
EFEITOS DOS SENSIBILIZADORES DA INSULINA Tiazolidinedionas (TZDs) (Glitazonas)  da utilização periférica da glicose (insulino mediada) em cerca de % (80% a nível muscular ) Redução da glicemia em jejum e pós-prandial e insulinemia do jejum (redução da produção hepática de glicose) Redução dos níveis de TG e  HDL Slide n.º 27 - 27

28 Fármacos Anti-diabéticos: Mecanismos de Ação
Aumentar o Aumentar a Atrasar a Fornecimento de Ação da Absorção dos Insulina Insulina Hidrat. Carbono Sulfonilureias Biguanidas Inibidores das -Glucosidases Meglitinidas Tiazolidinedionas Insulinas Slide n.º 28 - Antihyperglycemic Agents: Mechanisms of Action The six classes of therapeutic agents used in the management of type 2 diabetes mellitus may be divided into three groups by their basic mechanism of action. Some agents augment insulin supply (sulfonylureas, meglitinides, and insulins); others enhance the action of insulin on the liver and/or peripheral tissues (biguanides, thiazolidinediones); others delay carbohydrate absorption (-glucosidase inhibitors). 28