04 糖代谢紊乱

nullCarbohydrates Metabolism and Diabetes MellitusCarbohydrates Metabolism and Diabetes Mellitusnullprecipitate急冲的,猛冲的 catecholamine儿茶酚胺 omission 遗漏,疏忽 hyperglycaemia高血糖症 glycosuria糖尿 lipolysis脂解 ketonaemia酮血症 ketonuria酮尿 magnesium镁 uraemia尿毒症 hypovolaemic血容量减少 accentuate加强 interlocking联锁的 vicious恶的,恶毒的 ketone酮体 methodology方法学 subside下沉，减退 decompensation代谢失调 hyperosmolar高渗的 non-ketotic非酮体的 ketosis酮症 glucocorticoid糖皮质激素 dialysis透析 diuretic利尿剂，利尿的 nullDiabetes mellitus 糖尿病 hyperglycaemia 多糖症; 高血糖症 Insulin 胰岛素 polyuria多尿症 Polydipsia烦渴;多饮 lassitude疲倦, 疲乏, 无精神 pruritus vulvae 外阴搔痒 balanitis阴茎头炎 Fructose 果糖 galactose 半乳糖 Glycogen 动物淀粉;糖原 glycogenolysis 糖原分解 glyconeogenesis 糖异生 glycolysis 糖酵解 Lipolysis脂肪分解；脂溶解 ketogenesis生酮作用 proteolysis蛋白水解 islet cell antibodies胰岛细胞抗体 etiology病因论;病源论;原因论;病原学;病因学 cerebrospinal fluid脑脊液 ethylenediaminetetraacetic acid (EDTA) glacial acetic acid冰醋酸 hexokinase己糖激酶 thiazides 噻嗪类〔利尿药〕 Mono-saccharides fructose galactose Disaccharides PolysaccharidesMono-saccharides fructose galactose Disaccharides PolysaccharidesDigestion and Absorption Metabolism Regulation of Blood glucose null Glycogenesis(糖原生成) is the conversion of glucose to glycogen. The reverse process, the breakdown of glycogen to glucose, is termed glycogenolysis（糖原分解） The formation of glucose from non-carbohydrate sources, such as amino acid, glycerol, or lactate, is termed gluconeogenesis（糖异生） The conversation of glucose or other hexoses into lactate or pyruvate is called glycolysis（糖酵解） Oxidation of glucose to carbon dioxide and water nullnullNext slide shows the different metabolic processes which affect the blood glucose concentration. This blood glucose level is the result of a balance between input and output, synthesis and catabolism. The concentration of glucose in blood is between 3.89~6.11mmol/l nullThe actions of insulin GlyconeogenesisOther HormonesOther HormonesInsulin like growth factors, IGF Counter-regulatory Hormones Glucagon Epinephrine（肾上腺素） Growth Hormone Diabetes MellitusDiabetes MellitusIt may be defined as a syndrome characterized by hyperglycaemia due to an absolute or relative lack of insulin and/or insulin resistance. ClassificationClassificationType 1 Diabetes Type 2 Diabetes Other specific types of Diabetes Gestational diabetesnullType 1 and Type 2 DiabetesClinical noteClinical noteThe clinical symptoms of hyperglycaemia include polyuria, polydipsia, lassitude, weigh loss. These symptoms are common to both type1 and type 2 Diabetes but are more pronounced in type 1 Diabetes.Glucose metabolism and diabetes mellitusGlucose metabolism and diabetes mellitusGlucose is the carbohydrate currency of the body, all other carbohydrates being converted to glucose after digestion and absorption Insulin controls blood glucose by promoting the storage of metabolic fuel. Diabetes mellitus is characterized by hyperglycaemia, absolute or relative insulin lack and late complications.Proinsulin and C-peptideProinsulin and C-peptideProinsulin, which has relatively low biological activity, is the major storage form of insulin. Normally only small amounts of proinsulin enter the circulation. C-peptide. Proinsulin is cleaved to a 31-amino-acid connecting(C) peptide and insulin.It appears necessary to ensure the correct structure of insulin.DIAGNOSIS AND MONITORING OF DIABETES MELLITUSDIAGNOSIS AND MONITORING OF DIABETES MELLITUSBlood GlucoseBlood GlucoseRandom plasma glucose(RPG) ≧ 11.1mmol L OR Fasting plasma glucose(FPG) ≧ 7.0mmol/ /L OR Oral glucose tolerance test (OGTT) Plasma glucose(2h PG)≧11.1mmol/L Oral glucose tolerance test(OGTT)Oral glucose tolerance test(OGTT)A baseline blood sample is first taken after an overnight fast. The patient is then given 1.75g/kg of glucose orally, in about 300ml of water, to be drunk within 5 minutes. Plasma glucose levels are measured every 30 minutes for 1 hours, then every hour for 2h. Urine may also be tested for glucose at time 0, 0.5 , 1, 2 and after 3 hours. nullFPG＜7.0mmol/L and 2hPG ≥7.8mmol/L, ＜11.1mmol/L, IGT(impaired glucose tolerance, IGT) FPG≥6.1mmol/L, but ＜7.0mmol/L, 2hPG ＜ 7.8mmol/L, IFG(空腹血糖损害) FPG normal<6.1mmol/l, 0.5-1hPG between 7.0-9.0mmol/l and 2hPG ＜ 7.0mmol/L, normal. Two times FPG≥7.0mmol/L or 2hFGB≥11.1, Diabetes Plasma glucose levels following an oral glucose load in normal and diabetic subjectsPlasma glucose levels following an oral glucose load in normal and diabetic subjectsFactors Other Than Diabetes That May Influence the Oral Glucose Tolerance TestFactors Other Than Diabetes That May Influence the Oral Glucose Tolerance TestUrine TestingUrine TestingGlucose in urine The renal glucose treshold increases with age and as a result many diabetics will not have glycosuria. Ketones in urine/plasmaSpecimen Collection and StorageSpecimen Collection and StorageDuring fasting, capillary blood glucose concentration is only about 0.1-0.28mmol/L higher than that of venous blood. After a glucose load, however, capillary blood glucose concentration are 2-4mmol/L higher. In-separated, non-hemolyzed sterile serum, the glucose concentration is generally stable as long as 8h at 25℃ and up to 72h at 4 ℃ nullPlasma removed from the cells after moderate centrifugation, contains leukocytes that also metabolize glucose,although cell-free sterile plasma has no glycolytic activity. Glycolysis can be inhibited and glucose stabilized for as long as 3d at room temperature by adding Sodium fluoride (NaF)nullIt is not necessary in routine analysis to use a fluoride-containing tube if plasma is separated from cells or glucose is measured within 60 min of blood collection.nullCerebrospinal fluid may be contaminated with bacteria or other cells and should be analyzed for glucose immediately. nullUrine samples may lose as much as 40% of their glucose after 24h at room temperature. In 24-h collection of urine, glucose may be preserved by adding 5mL of glacial acetic acid to the container before starting the collection. nullMethods for Glucose DetectionMethods for Glucose DetectionHexokinase Method for GlucoseHexokinase Method for GlucoseGlucose+ATP→Glucose-6-phosphate +ADP Glucose-6-phosphate 6-Phosphogluconate∩NADP+ Or NAD+NADPH+H+ Or NADHGlucose Oxidase Methods for GlucoseGlucose Oxidase Methods for GlucoseStandard Glucose Oxidase Photometric Method for Glucose Glucose Dehydrogenase(脱氢酶) Method for Glucose Oxidation-Reduction Method for GlucoseClinical Utility of Measuring Insulin, Proinsulin, C-Peptide, and Glucagon AssaysClinical Utility of Measuring Insulin, Proinsulin, C-Peptide, and Glucagon AssaysInsulinInsulinSpecimen Collection and Storage Measurements of insulin may be carried out on serum or plasma from a fasting patient. If analysis is performed with plasma, heparin should be used because ethylenediaminetetraacetic acid (EDTA) results in falsely elevated levels. Hemolysis is more frequent in serum and can cause falsely high insulin values. Insulin is stable in whole blood at room temperature for at least 5 h. Samples may be stored at 4°C for 7 d or at -20C for as long as 3 mo; repeated thawing and freezing should be avoided. nullUrine and cerebrospinal fluid (CSF) may be assayed for insulin content. Albumin must be added to the collection vessel to a final concentration of 0.2 to 0.5 g/dL to minimize denaturation of insulin in the specimen. These samples require an extraction step and concentration prior to analysis.null Principle 125Iodin-labeled insulin competes with insulin in a patient sample for binding to an insulin-specific antibody immobilized on the walls of a polypropylene tube. The supernatant is decanted, and the bound 125I determined in a gamma counter. Various commercial kits for insulin measurement are now available. Reference ValueReference Value2~25 IU/ml(12-150pmol/L)ProinsulinProinsulinSpecimen Collection and Storage Fasting blood samples should be collected in heparinized tubes. Plasma is stable at -70°C for at least 3 mo. nullPrinciple The blood concentrations are low. Antibody production is difficult. Most antiserum cross-react with insulin and C-peptide. The assays measure intermediate cleavage forms of proinsulin. Monoclonal antibodies to biosynthetic proinsulin. C-PeptideC-PeptideVarious RIA methods have been described for the measurement of C-peptide, and several kits are commercially available. 0.78~1.89ng/ml(0.25~0.6nmol/L)GlucagonGlucagonPrinciple A competitive RIA is available for measuring glucagon.125I-labeled glucagon competes with glucagon in patient specimen for binding to polyclonal glucagon antibody. nullSpecimen Collection and Storage Fasting blood samples should be collected in chilled EDTA tubes. Glucagon is very unstable in blood. Immerse tubes in a 2 to 8 ℃ ice-water bath. Immediately add a proteolytic inhibitor such as Trasylol. Separate plasma from cells in a refrigerated centrifuge at 4℃. Freezer at least 1 mL of plasma at -20℃ and avoid exposure to light. Thaw just before use. null70-180ng/L(20-52pmol/L)Insulin antibodiesInsulin antibodiesAssays for insulin antibodies fall into three categories: quantitative radioimmunoelectrophoresis; RIAs with separation of bound and free insulin by precipitation with PEG or a second antibody Solid-phase immobilization of insulin to test tubes or SepharoseDIABETIC KETOACIDOSISDIABETIC KETOACIDOSISThe development of diabetic ketoacidosisThe development of diabetic ketoacidosisThe development of keto-acidosis(DKA)The development of keto-acidosis(DKA)Infection Myocardial infarction Trauma Omission of insulin Precipitating factorsLaboratory InvestigationLaboratory InvestigationUrine tested for glucose and ketones Blood checked for glucose Venous blood checked for glucose and sodium, potassium, chloride, bicarbonate, urea and creatinine Arterial blood sample should be sent for blood gases. null Acetest and Ketostix methods are used to exam the concentration of ketone bodies. Gerhardt methodnullBlood glucose should be monitored hourly at the bedside until < 15mmol/L, after that it should be tested 2-hourly. In severe cases blood gases should be performed 2-hourly at least for first 4 hours. The potassium level should be checked 2-hourly at first 6 hours. The urea and electrolytes should be measured at 4-hours intervals. Effective treatment of a severe case of diabetic keto-acidosisEffective treatment of a severe case of diabetic keto-acidosisHyperosmolar Non-ketotic (HONK) ComaHyperosmolar Non-ketotic (HONK) ComaElderly, non-insulin dependent diabetics Develop slowly over days or weeks Insulin level is not so low. Blood glucose level extremely high Severe dehydrationLactic AcidosisLactic AcidosisType I lactic acidosis due to an excessive production of lactate by peripheral tissue Type II due to the impaired metabolism of lactate in the liver High anion gap High blood lactate concentration Low or absent ketones nullThe principal features of the three forms of metabolic decompensation in diabetesThe principal features of the three forms of metabolic decompensation in diabetesClinic NoteClinic NoteAlways screen for infections in the diabetic patient presenting with DKA, as this is a common precipitating factor. Blood, urine, sputum 痰 and any wound fluids should be sent for culture at the earliest opportunity and certainly before antibiotics are introduced. Diabetic ketoacidosisDiabetic ketoacidosisDiabetic ketoacidosis is arises from a number of metabolic problems caused by insulin lack. Treatment is by intravenous fluids, insulin and potassium. Only in the most severe cases of DKA should sodium bicarbonate be used. Close clinical and biochemical monitoring are required to tailor制作,适应 the management protocol草案，协议 to individual patient. Other, much less common, severe metabolic disturbances of carbohydrate metabolism are hyperosmolar non-ketotic coma and lactic acidosis.null右旋糖，葡萄糖Case history 25 A 22-year-old diabetic comes to the Accident and Emergency department. He gives a 2-day history of vomiting and abdominal pain. She is drowsy 昏昏欲睡 and her breathing is deep and rapid. There is a distinctive smell from her breath. Case history 25 A 22-year-old diabetic comes to the Accident and Emergency department. He gives a 2-day history of vomiting and abdominal pain. She is drowsy 昏昏欲睡 and her breathing is deep and rapid. There is a distinctive smell from her breath. What is the most likely diagnosis? Which bedside tests could you do to help you to confirm this diagnosis? Which laboratory tests would you request?HypoglycemiaHypoglycemiaHypoglycemia is a blood glucose concentration below the fasting level (3.33~3.89mmol/l) null Neonatal blood glucose concentrations are much lower than adult and decline shortly after birth when liver glycogen stores are depleted. Hypoglycemia in Neonate and InfantsFasting Hypoglycemia in AdultsFasting Hypoglycemia in AdultsCauses: Medications(insulin, oral hypoglycemic agents) Toxins(alcohol, Hypoglycins) Severe hepatic dysfunction Deficiency of hormones(e.g glucocorticoids, growth hormone) Insulin-producing pancreatic tumors (insulinoma) Insulin antibodies Nonpancreatic neoplasms Septicemia Chronic renal failure Reactive Postprandial（餐后的） HypoglycemiaPostprandial（餐后的） HypoglycemiaA group of disorders may produce hypoglycemia in the postprandial state. These include drugs, antibodies to insulin or insulin receptor, and in born errors.Glycogen Storage DiseaseGlycogen Storage DiseaseType I (Glucose-6-Phosphatase磷酯酶Deficiency) Type II( Acid Glucosidase葡萄糖甙酶Deficiency)nullType III (Amylo淀粉-1,6-Glucosidase葡萄糖甙酶Deficiency) Type IV (Branching Enzyme Deficiency) Type VI (Muscle Phosphorylase磷酸化酶 Deficiency) Type VII (Liver Phosphorylase or Phosphorylase Kinase Deficiency) Type VIII (Muscle Phosphofruckinase Deficiency)null