糖尿病英文版资料讲解

1、糖尿病英文版资料讲解Classification of diabetes(ADA-1997)Type 1 (beta-cell destruction, usually leading to absolute insulin deficiency) Autoimmune Idiopathic Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resi

2、stance) Other specific types Gestational diabetes*Other specific typesGenetic defects of beta-cell function Genetic defects in insulin action Diseases of the exocrine pancreas Endocrinopathies Drug- or chemical-induced Infections Uncommon forms of immune-mediated diabetes Other genetic syndromes som

3、etimes associated with diabetesPathogenesis Pathology Type 1 DM：inflammation of pancreasType 2 DM：amyloidosis of pancreasLarge vessel ：atherosclerosisKidney ：diffuse or nodular glomerular sclerosis Retina：arteriolar sclerosis、microaneurysm、exudates、new vessel formationNerve：axon degeneration 、myelin

4、olysisPathophysiology Abnormalities in metabolism Carbohydrate ：anabolism ，catabolism、 utilization Lipid ： anabolism ，catabolism ，ketoplasiaprotein： anabolism ，catabolism ，glyconeogenesis Insulin secretion curve :normal and diabetics Clinical PresentationNatural history of type 2 DMAfter the diagnos

5、is of type 2 diabetes:IR constantly exists Insulin secretion ability gradually declines: When FPG reachs the diagnostic criteria，insulin secretion ability has already declined by 50% When FPG，-cell insulin secretion ability When FPG，-C insulin secretion ability has already neared absolute deficiency

6、Models of the onset of two phrases of type 2 DM NGT IGR(IFG、IGT) DMcell exhaustionInsulin resistanceInsulin resistanceWHO plasma glucose guidelineIGTIFGNGTDM75gOGTT2hPG (mmol/L)FPG(mmol/L)FPGIGTComparison of type 1 and type 2 DM type1 DM type2 DMUsual age of onset 40yearsMode of onset acute chronicw

7、eight normal overweight or obesity or weight loss symptoms polyuria,polydipsia, similar but usually weight loss less severe presentation Acute complications often fewChronic complicationsLarge vessel disease less then type 2 DM leading cause of deathRenal disease leading cause of death 5%10%Insulin

8、and c-peptide low or lack peak value delayed ,high or deficiencyImmune marker usually + usually -Therapy insulin dependence oral antidiabetic agents are availableChronic complicationsMacrovascular diseaseMicroangiopathyDiabetic retinopathyDiabetic renal diseaseDiabetic neuropathyDiabetic dermatopath

9、yInfection Mechanism of complicationsActivation of polyol （or sorbitol）pathway Formation of non-enzyme saccharification products Change of hemodynamics Activation of PKCMicroangiopathy theory Hyperglycemia is the essential reason for diabetic complications DCCT Diabetes Control and Complications Tri

10、al UKPDS United Kingdom Prospective Diabetes Study UKPTS：resultsHbA1c 0 .9%，（intensive therapy vs routine therapy） Intensive therapy group: diabetis associated complications 12%，and the fatalness of microvascular complications 25%。It cannot evidently reduce the incidence of great vessel disease ,suc

11、h as miocardial infarction and strock .Most stimulating findings：Biguanides can prevent or slow the onset and/or progression of diabetic complications in overweight patients Tight control of hypertension can prevent or slow the onset and/or progression of diabetic complications by 24% （144/82mmHg vs

12、 154/87mmHg） ，stroke by 44%，microvascular complications by 37%。Epidemiology of diabetes Macrovascular diseaseDiabetics are easy to get atherosclerosis Coronary heart disease、cerebrovascular disease：24 timesRisk of miocardial infarction： 10 timesRisk of stroke : 3.8 times，especially in womenRisk of l

13、ower limb amputation：15times ，fatalness Hypertension in DMMorbidity ratediabetes: 20%40%Diabetes in EU(35-54years): 30%50%Diabetes in China: 29.2%pathogenesisaortosclerosisArteriola resistance Hypertension associated with DNRenal hypertension caused by stenosis of renal arteryDiabetic retinopathylea

14、ding course of new cases of blindness Pathogeny：state of illness 、course of disease、age of onset 5 years ：eyeground disease is not common 10 years ：50eyeground disease 130ml/minStage II clinically silent phase DM 25year GFR 2040 renal enlargement， with continued glomerular hypertrophy, hyperfiltrati

15、on and hypertrophy expansion of the mesangial matrix thickening of the glomerular basement membrane resulting in glomerulosclerosis Stage III concealed DN microalbuminuria DM510year microalbuminuria 1/5 patients with hypertension (20-200g/min retinopothy ,or30300mg/24h) GFR or =normal Stages of diab

16、etic nephropathy(2)Stage IV Overt Nephropathy DM1025year albuminuria300mg/d 6070 patients ， with hypertentio GFR(when UAER=100 and edema mg/24h , GER begin to decrease， about 1ml/min/month) retinopathy Stage V end-stage renal disease, ESRD DM1530 year albuminuria azotemic uremia GFR 15yearsSymptoms

17、of senseNumbness type：large medullated fibersPain type：little medullated fibers and nonmedullated fibersNumbness-pain typeNervous symptom examinationparasthesiaLower limbs pallesthetic disturbance or dissapearTendon reflex low or dissappear Sensory staxiaParatrophy symptomsCharcot arthropathy、ischem

18、ic gangrenosis and foot ulcerDiabetic autonomic neuropathy Pupil diseaseCardiovascular parafunctionFixed heart ratePostural hypertensionSudden cardiac deathGestrophageal ,diarrheaNeuropathic bladder,erectile failureAbnormal sweatingGlucosuria：associated with renal threshold of sugar (only for clue)K

19、etonuriaBlood sugar：plasma glucose，PODHBA1c：23 months blood sugar levelFructosamine：23 weeks blood sugar levelOGTT：2 hour specimenInsulin and C-peptide release test Laboratory tests DiagnosisCriteria for diagnosing diabetes FPG Random OGTT plasma glucose 2hPG mmol/L mmol/L mmol/LDM 7.0 11.1 11.1 IGR

20、 IGT 7.8Normal Characteristics of new diabetic diagnostic criteria ，；Impaired fasting glucose corresponding with impaired glucose tolerance (IFG)：6.1mmol/L FPG7.0 mmol/L ； FPG is the initial screening test of diabetes ，OGTT is not recommended for routine diagnostic use. The diagnoses of Gestational

21、diabetes is not changed Practical problems in diagnosisSymptoms random plasma glucose 11.1 mmol/L FPG： 7.0 mmol/L OGTT：2hPG 11.1 mmol/L Asymtomatic persons tests should be repeated the oncelatent autoimmune diabetes mellitus in adults （LADA）Adult onsetSymptoms are evidentSecretion function of cell i

22、s lowGADA positiveHLA-DQ B chain is non aspartate homozygoteManagementGoalsGood metabolism control（blood sugar、blood lipid、HBA1C etc）Relieve symptomsKeeping good physiologic state and a social lifeGood quality of livePrevent the development of acute complications of diabetes（hypoglycemia、DKA、hyperos

23、molar nonketotic syndrome、lactic acidosis）Preventing the development or delaying the progression of the chronic complications of diabetes Principle of treatmentEarly Life-longsynthesisindividualGoals of control good average badPBG(mmol/L) fasting 4.4 - 6.1 non-fasting 4.4 - 8.0 HBA1c() 7.5 BP(mmHg)

24、130/80- 140/90 BMI (Kg/m2) M 25 M27 27 F 24 F26 F26 TC (mmol/L) 1.1 1.1-0.9 0.9TG (mmol/L) 1.5 2.2 2.2 LDL-C (mmol/L) 4.0 Control actuality of DM in China26 centers、3965 patients28patients measure H2.6%，527.5FPG：9.2 3.7mmol/L，55%7.8 mmol/LDeterming rate of microalbumin in urine ：20 Diabetes Manageme

25、nt PlanPatient educationHealth nutrition therapyExercise therapyDrug therapyMonitoring of blood glucosePhases therapy of DMEarly reaction Patient therapyMedical nutrition therapyExercise therapySingle drug therapydecline of curative effect Combined drug therapySecondary failure、distinct insufficienc

26、y of insulinInsulin therapyPrinciples of medical nutrition theraphy rational control of total calorific value Goal ： Keep ideal body weightLoss weight for obese patientAdd weight for lean patientStandard body weightheight（cm）105male： （height100 ）female： （height100 ）Body mass index（BMI） ：weight（kg）/h

27、eight2 （m2）Adult-onset diabetes thermal energy supply per day （therm/kg standard weight ） work intension Bodily form in bed light physical middle heavy labor physical physical labor laborlean 20 25 35 40 40normal 15 20 30 35 40obesity 15 20 25 30 35 Nutrition principles of diabetics Moderate weight

28、control The distribution of total calorfic value ：carbohydrate 55 %60% fat 20%25% 1/5、 2/5、 2/5protein 15 %20% Drink limitation Avoiding diabetic foods (which contain sorbitol or frucotose)Aspartame is an acceptable calorie-free sweetenersalt10g/d，(3g/day if hypertensive)Calculation protein：0.8 fat：

29、0.6 carbohydrate：total calorific value calories of protein and fat Exercise therapyBenefitsGlycaemic controlIncrease cell sensitivity to glucose Blood lipid Weight reductionEstimation of quantity of exercise：heart rate170age (year)Drug therapySulfonylureasBiguanides-glucosidase inhibitorsTniazolidin

30、edionesMeglitinidesInsulinDry-combination therapySulfonylureas: mode of actionThe principal action of these drugs is to stimulate endogenous insulin secretion from the pancreatic -cells Not to increase synthesis of insulin Also to increase -cells sensitivity to glucose and exert some influence in di

31、minishing insulin resistance. Sulfonylureas （SU）： first choice of non-obesity T2DM General name duration of action potency merits main site of excretionTolbutamide (D860) short weak cheap renalGlyburide (micronase) long strong affirmed hypoglycemia effects in lowering blood glucose levels cheap rena

32、l Gliclazide (diamicvon) medium strong prevent and renalglipizide (minidiab) shot strong affirmed effects renalGliquidone (glurenorm ) shot week not renal(only5%)Glipizide (tonbac) long strong good compliance low incidence of hypoglycemiaTherapeutic effects of SUPrimary failure to respond to SU occu

33、rs in 20% to 25% of patientsFPG and 2hPG HbA1c 1% 2As the period of treatment progresses, effects decline： Secondary failure occurs at the rate of 10% to 15% per year After 5 years ，only half of the patients can keep ideal blood glucose control .UKPDS：first year: blood glucose ，insulin then : blood

34、glucose insulin the 6th year: returned to the state before therapy Indications and contraindications of SUIndicationsPoor control of T2DM by weight control and physical activityPoor control of T2DM by biguanides and -Combined with insulinContraindications T1DMAcute or chronic diabetic complicationsE

35、mergency Dysfunction of liver or kidneyPregnant or bleeding women Side effects of SUHypoglycemia， most common inOld patientsLong-term pharmaceuticsSymptoms of digestive tractLiver dysfunctionTetterChange of hematologyBiguanides ：first choice of obesity type 2 DM Generic name dosage merits NB phenfor

36、min 270 300mg/dl. the symptoms of hypertension are evident .Insulin therapy is availableImpaired liver and kidney function：avoid using OHALean 、 fasting and after-excitation insulin all ：insulin Drug-Combined therapyReasonable diet and poor plasma glucose control by monotherapy SU 、biguanides 、TZD a

37、nd - glucosidase inhibitors all can be used in combination with each otherSmall dosage combined with of all kinds of drugs ;enhancing effects of reduce glucaemia ;side effects of single agentsOral agents with insulinDrugs of the same class cannot be used in a combined way. Insulin therapyIndications

38、 of insulin Type 1 DMType 2 DMAcute complicationsSevere chronic complications of diabetesEmergency Severe dysfunction of liver or kidneyGestation and bleeding womenWithout tolerance OHA， curative effect of OHA ，SU invalidationDistinct leanWith diseases treated by glucocorticoidSome specific types of

39、 DM：secondary pancreas disease 、endocrinopathies、genetic diabetesObstacles to using Ins in T2DM old notion： NIDDMThe doctor uses OHA only and does not see the need to use Ins.The patient does not want to use In for fear of developing insulin dependence after useing it. Hyperinsulinism can lead AS to

40、 CVD？hypoglycemia，BW国内常用胰岛素一览表产品名 生产厂家 种属来源 包装(U/瓶)短效胰岛素 普通胰岛素(RI) 上海生物制药厂 猪 400 U/瓶 优泌林R 礼来 基因重组 400 U/瓶 诺和灵-R 诺和诺德 基因重组 400 U/瓶 Lispro 礼来 基因重组 400 U/瓶中效胰岛素 优泌林 N 礼来 基因重组 400 U/瓶 诺和灵-N 诺和诺德 基因重组 400 U/瓶 NPH 徐州生化制药厂 猪 400 U/瓶混合胰岛素 优泌林70/30 礼来 基因重组 400 U/瓶(人工合成)诺和灵-30R 诺和诺德 基因重组 400 U/瓶诺和灵-30R 诺和诺德 基

41、因重组 300 U/瓶长效胰岛素 PZI 上海生物制药厂 猪 400 U/瓶Differences between human and animal insulin Difference in pharmacodynamic ：Close action intensity Human insulin : absorption is fast ，time of onset of effect is early Difference in immunogenicity:Antigenicit of human insulin is weaker than animal insulin After

42、use human insulin, antibody titer of blood insulin is lower Synthesized insulin ：lispro（28proline29 proline ）Quick absorption, short effect time Shot-term intensive insulin therapy for T2DMIndications：monotherapy or combination therapy of oral antihyperglycemia therapy fail to achieve glucose target

43、s，overt hyperglycemia，fasting and postprandial C-peptide Method：use insulin 2 times per day： NPH/R 70/30 prebreakfast and presupper ，adjust the dosage with the monitoring results of blood sugar .use insulin 4 times per day ： RI premeal、 NPH before sleepPeriod of treatment：several weeks or monthesSho

44、t-term intensive insulin therapy for T2DM Estimation of initial dosage： 0.2 Mode of therapy RI before meals：RIRIRIO，before breakfastbefore supper before diner RI before three meals + RI before supper： RIRIRIRI RI before three meals + NPH before supper: RIRIRI/NPH RI before three meals + NPH before s

45、leep： RIRIRINPH mixed insulin（RI/NPH） before three meals（2/3before breakfast ，1/3before supper），the proportion :10R50R NPH/R 70/30before breakfast and supperSecondary failure of OHA :combination with insulin FPG oral anti-hyperglycemia agents+ NPH before sleep PPG NPH before breakfast+oral anti-hype

46、rglycemia agentsFPG PPG oral anti-hyperglycemia agents + NPH before sleep and before breakfast Insulin ： adjust per 34 days， one phrase each time up for 24U every time Before you add insulin , hypoglycemia reaction should be excluded Combination of OHA and NPH before sleepIndication ：OHA is invalid

47、or has low effect FPG not exceeding 250 300 mg/dlNon-lean LADA Still having some function of insulin secretion C-peptide：fasting0.2 mmol/Lpostload 0.4 mmol/LThe effect of supplying one injection of intermediate-acting insulin before sleep HGP ，lipolysis antagonize the somogyi effects and the dawn ph

48、enomenon caused by glucagon FPG returning to normal Helping SU to effect in daytime24hour PG ，HbA1cSupplying the deficiency of act time of former OHA The patients needs to be supplied with one injection each night and doesnt need to be hospitalized. Its easy for the patient to accept.difference of c

49、omplementary therapy and subtitution therapy of insulinComplementary therapyOHA are basic therapy，combination with insulin NPH before sleep ,FPG : daytime postprandial hyperglycemia can be improved evidently NPH perbreakfast with OHA for postprandial hyperglycemia (often used)Substitution therapySto

50、p using OHA;substituted by insulinMixed insulin before breakfast and supperThree injections perday R，R，R+NFour injections perday R，R，R，R or R，R，R，N Side effects of insulinhypoglycemialocal reactionAnaphylaxissystemic reactioninsulin drug resistance Lipid dystrophia ：atrophy and fleshy Artificial fac

51、tors in influencing curative effect of insulin Inject position abdomen wall the upper armthighbuttocksInject depth hypodermatic ,not muscle Preservation cold storage, not freeze NB (1)Need to increase the quantity of insulin：HyperpyrexiaHyperthyreaPachyacria Ketoacidosis Severe infection or trauma S

52、erious surgeryPregnant woman ，especially in metaphase or anaphase of pregnancy Adolescent childrenNB (2) need to cut down the quantity of insulin ：Metabolize and excretion of insulin in kidney ：hypohepatia 、kidney dysfunction、thyroid insufficiencyDiseases which can lead to hypoglycemia：hypadrenia、di

53、arrhea 、gastroanesthesia 、intestinal obstruction、vomit 、absorption of food Elderly patients (easy to get hypoglycemia)NB (3)Combined drugs（ glucemia ）Agents which increase plasma glucose：glucocorticoid、ACTH、glucagon、estradiol、oral prophylactic、thyroxin、adrenalin 、thiazide diuretic 、dilantinCarbohydr

54、ate metabolism abnormality、PG ：felodipine、可乐定、二氮嗪、GH、heparin、-blocker 、大麻、morphin、 nicoltin、-blocker(普萘洛尔可阻止肾上腺素升高血糖的反应)NB (4)Combination drug therapy（help lower plasma glucose ）Slow degradation of insulin chloroquine 、 quinidine 、 quinin Insulin combine globulin competely，dissociated insulin antico

55、agulative agents、 salicylate 、sulfanilamide 、anti-tumor agents can help lowering glucemia ：OHA、assimilation steroid androgenic hormones、 monoamine oxidase inhibitor 、NSAIDLower glucemia ACEI、溴隐停、氯贝特、酮康唑、lithium 、甲苯咪唑、theophylline、alcohol、奥曲肽 Monitor of DM Glucosuria：associated with renal threshold o

56、f glucose(only for clue)FPGHBA1c：23 months blood sugar levelFructosamine：23 weeks blood sugar levelOGTT：2 hour specimen Diabetic Ketoacidosis（DKA）summarize(1)One of the acute metabolic complications of diabetes Can be initial symptoms of diabetesOne of the important emergency of internal medicine Ne

57、ed rapid ,reasonable treatment Full-scale examination of specialty knowledge of internist or general practitioner Need doctors and nurses to take concerted action Summarize (2)KetosisDKAHypoglycaemic keto-acidotic coma Composition and characteristics of ketone bodyAcetoacetic acid is the first produ

58、ct：strong organic acid ;can reacted with ketone powder strongly Dimethylketone ： least quantity 、neutral、no renal reabsorption threshold ;can be excreted from respiratory tractoxybutyric acid ：strong organic acid ，biggest quantity（70） Pathophysiology glucagon Abnormalities in carbohydrate metabolism

59、lipolysisAcidosis Abnormal nervous system Circulation faliure携氧系统异常Electrolyte disturbanceAcetone body Plasma glucose Severe dehydration Inducement of DKA (1)Interrupted drug therapy Improper dietFatigueinfectionTrauma operationpregnancy、deliverydrinkingmiocardial infarction elseClinical presentatio

60、ns of DKA Intensive thirsty, diuresis Extremely tired、nausea 、vomitingVaried degrees of disorder of consciousness Circulation failure Presentations of precipitating factorsSpecial presentations of DKA Abdominal pain Hypothermy and abnormal “ normal body temperature” Number of leucocyte Laboratory te