胡仁明糖尿病课件

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1、胡仁明糖尿病胡仁明糖尿病Type 1 l(beta-cell destruction,usually leading to absolute insulin deficiency)Autoimmune Idiopathic lType 2(may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance)lOther specific types lGesta

2、tional diabetes*胡仁明糖尿病lGenetic defects of beta-cell function lGenetic defects in insulin action lDiseases of the exocrine pancreas lEndocrinopathies lDrug-or chemical-induced lInfections lUncommon forms of immune-mediated diabetes lOther genetic syndromes sometimes associated with diabetes胡仁明糖尿病胡仁明糖

3、尿病lType 1 DM：inflammation of pancreaslType 2 DM：amyloidosis of pancreaslLarge vessel：atherosclerosislKidney：diffuse or nodular glomerular sclerosis lRetina：arteriolar sclerosis、microaneurysm、exudates、new vessel formationlNerve：axon degeneration、myelinolysis胡仁明糖尿病胡仁明糖尿病lCarbohydrate ：anabolism，catabo

4、lism、utilization lLipid：anabolism，catabolism，ketoplasialprotein：anabolism，catabolism，glyconeogenesis胡仁明糖尿病胡仁明糖尿病胡仁明糖尿病After the diagnosis of type 2 diabetes:IR constantly exists Insulin secretion ability gradually declines:When FPG reachs the diagnostic criteria，insulin secretion ability has already

5、 declined by 50%When FPG7.0mmol/L，-cell insulin secretion ability When FPG10 11.0mmol/L，-C insulin secretion ability has already neared absolute deficiency胡仁明糖尿病NGT IGR(IFG、IGT)DM cell exhaustionInsulin resistanceInsulin resistance胡仁明糖尿病IGTIFGNGTDM75gOGTT2hPG (mmol/L)FPG(mmol/L)7.06.1FPG7.8 11.1IGT胡

6、仁明糖尿病 type1 DM type2 DMUsual age of onset 40yearsMode of onset acute chronicweight 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

7、 DM leading cause of deathRenal disease leading cause of death 5%10%Insulin and c-peptide low or lack peak value delayed ,high or deficiencyImmune marker usually +usually-Therapy insulin dependence oral antidiabetic agents are available胡仁明糖尿病lMacrovascular diseaselMicroangiopathyDiabetic retinopathy

8、Diabetic renal diseaseDiabetic neuropathylDiabetic dermatopathylInfection胡仁明糖尿病lActivation of polyol（or sorbitol）pathway lFormation of non-enzyme saccharification products lChange of hemodynamics l Activation of PKClMicroangiopathy theory 胡仁明糖尿病lDCCT Diabetes Control and Complications Trial lUKPDS U

9、nited Kingdom Prospective Diabetes Study胡仁明糖尿病lHbA1c 0.9%，（intensive therapy vs routine therapy）l Intensive therapy group:diabetis associated complications 12%，and the fatalness of microvascular complications 25%。lIt cannot evidently reduce the incidence of great vessel disease ,such as miocardial i

10、nfarction and strock.lMost stimulating findings：Biguanides can prevent or slow the onset and/or progression of diabetic complications in overweight patients lTight control of hypertension can prevent or slow the onset and/or progression of diabetic complications by 24%（144/82mmHg vs 154/87mmHg），stro

11、ke by 44%，microvascular complications by 37%。胡仁明糖尿病lDiabetics are easy to get atherosclerosis Monckebergs sclerosis 41.5Intimal arteriosteogenesis 29.3lCoronary heart disease、cerebrovascular disease：24 timesRisk of miocardial infarction：10 timesRisk of stroke:3.8 times，especially in womenlRisk of lo

12、wer limb amputation：15times，fatalness 胡仁明糖尿病Morbidity 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 artery胡仁明糖尿病lDiabetic retinopathyleading cours

13、e of new cases of blindnessl Pathogeny：state of illness、course of disease、age of onsetl 5 years ：eyeground disease is not commonl 10 years ：50eyeground diseasel 130ml/minStage II clinically silent phase DM 25year GFR 2040 renal enlargement，with continued glomerular hypertrophy,hyperfiltration and hy

14、pertrophy 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)proteinuria 0.150.5g/24h GFR or=normal

15、胡仁明糖尿病Stage IV Overt Nephropathy DM1025year albuminuria300mg/d 6070 patients proteinuria0.5g/d，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 15yearslSymptoms o

16、f senseNumbness type：large medullated fibersPain type：little medullated fibers and nonmedullated fibersNumbness-pain type胡仁明糖尿病lNervous symptom examinationparasthesiaLower limbs pallesthetic disturbance or dissapearTendon reflex low or dissappear Sensory staxiaParatrophy symptomsCharcot arthropathy、

17、ischemic gangrenosis and foot ulcer胡仁明糖尿病lPupil diseaselCardiovascular parafunctionFixed heart ratePostural hypertensionSudden cardiac deathlGestrophageal,diarrhealNeuropathic bladder,erectile failurelAbnormal sweating胡仁明糖尿病Glucosuria：associated with renal threshold of sugar(only for clue)KetonuriaB

18、lood sugar：plasma glucose，PODHBA1c：2 3 months blood sugar levelFructosamine：2 3 weeks blood sugar levelOGTT：2 hour specimenInsulin and C-peptide release test胡仁明糖尿病胡仁明糖尿病 FPG Random OGTT plasma glucose 2hPG mmol/L mmol/L mmol/LDM 7.0 11.1 11.1 IGR IFG 6.1FPG7.0 IGT 7.8FPG11.1Normal 6.1 7.8胡仁明糖尿病lFPG6

19、.1mmol/L is normal fasting glucose，OGTT 2hPG7.8mmol/L is normal glucose tolerance；lImpaired fasting glucose corresponding with impaired glucose tolerance(IFG)：6.1mmol/L FPG7.0 non-fasting 4.4-8.0 10.0 10.0HBA1c()7.5 BP(mmHg)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

20、(mmol/L)1.5 2.2 2.2 LDL-C(mmol/L)4.0 胡仁明糖尿病l26 centers、3965 patientsl28patients measure HbA1c：8.12.6%，527.5lFPG：9.2 3.7mmol/L，55%7.8 mmol/LlDeterming rate of microalbumin in urine：20 胡仁明糖尿病Patient educationHealth nutrition therapyExercise therapyDrug therapyMonitoring of blood glucose胡仁明糖尿病Early rea

21、ction Patient therapyMedical nutrition therapyExercise therapySingle drug therapydecline of curative effect Combined drug therapySecondary failure、distinct insufficiency of insulinInsulin therapy胡仁明糖尿病l rational control of total calorific value lGoal：Keep ideal body weightLoss weight for obese patie

22、ntAdd weight for lean patientlStandard body weightheight（cm）105male：（height100）0.9female：（height100）0.85lBody mass index（BMI）：weight（kg）/height2（m2）胡仁明糖尿病 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

23、15 20 25 30 35胡仁明糖尿病 Moderate weight 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

24、)胡仁明糖尿病lprotein：0.8 1.2/kg standard weight lfat：0.6 1.0/kg standard weightlcarbohydrate：total calorific value calories of protein and fat 胡仁明糖尿病lBenefitsGlycaemic controlIncrease cell sensitivity to glucose Blood lipid Weight reductionlEstimation of quantity of exercise：heart rate170age(year)胡仁明糖尿病S

25、ulfonylureasBiguanides-glucosidase inhibitorsTniazolidinedionesMeglitinidesInsulinDry-combination therapy胡仁明糖尿病lThe principal action of these drugs is to stimulate endogenous insulin secretion from the pancreatic-cells lNot to increase synthesis of insulin lAlso to increase-cells sensitivity to gluc

26、ose and exert some influence in diminishing insulin resistance.胡仁明糖尿病 General name duration of action potency merits main site General name duration of action potency merits main site of of excretionexcretionTolbutamide(D860)short weak cheap renalTolbutamide(D860)short weak cheap renalGlyburide(micr

27、onase)long strong affirmed Glyburide(micronase)long strong affirmed hypoglycemia hypoglycemia effects in lowering effects in lowering blood glucose levels blood glucose levels cheap renal cheap renal Gliclazide(diamicvon)medium strong prevent and renalGliclazide(diamicvon)medium strong prevent and r

28、enalglipizide(minidiab)shot strong affirmed effects renalglipizide(minidiab)shot strong affirmed effects renalGliquidone(glurenorm)shot week not renal(only5%)Gliquidone(glurenorm)shot week not renal(only5%)Glipizide(tonbac)long strong good compliance low Glipizide(tonbac)long strong good compliance

29、low incidence incidence of hypoglycemia of hypoglycemia胡仁明糖尿病lPrimary failure to respond to SU occurs in 20%to 25%of patientslFPG and 2hPG lHbA1c 1%2lAs 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 patient

30、s can keep ideal blood glucose control.UKPDS：first year:blood glucose ，insulin then:blood glucose insulin the 6th year:returned to the state before therapy 胡仁明糖尿病lIndicationsPoor control of T2DM by weight control and physical activityPoor control of T2DM by biguanides and-Combined with insulinlContr

31、aindications T1DMAcute or chronic diabetic complicationsEmergency Dysfunction of liver or kidneyPregnant or bleeding women 胡仁明糖尿病lHypoglycemia，most common inOld patientsLong-term pharmaceuticsSymptoms of digestive tractlLiver dysfunctionlTetterlChange of hematology胡仁明糖尿病Generic name dosage merits NB

32、Generic name dosage merits NB phenformin 75mg75mg/d cheap lactic acidosis/d cheap lactic acidosis（降糖灵）（降糖灵）restrain restrain oxygenic metabolism oxygenic metabolism lower energy of lower energy of oxygenic metabolism oxygenic metabolism dimethylbiguanide 1.5g/d low gastrointestinal dimethylbiguanide

33、 1.4mg/dlAcute or chronic acidosisHeart、lung disease：hypoxia、acidosis inclinationHypohepatiaSevere gastroenteropathyPregnancy胡仁明糖尿病l DiarrhealAnaphylaxislOvert macies：common in elderly patientslLactic acidosis胡仁明糖尿病lInhibiting-glucosidase lDelaying the digestion of glucosel2hPGl Not stimulating the

34、secretion of Insulin-glucosidase inhibitors:mode of action胡仁明糖尿病l2hPGlFPGlHbA1c about 1.When used in combination with SU,HbA1c:about2lSerum insulin slightly declined lWeight not a few patients lWhen used as monotherapy,it do not cause hypoglycemia lWhen used in combination with other oral antidiabet

35、ic agents,it may cause hypoglyceiaIf hypoglycemia happens,patient should be treated by glucose.Other kinds of sugar are ineffective胡仁明糖尿病lIndications Light casesusing drug separately or combinedIGT intervention，securitylContraindications Allergic reactions Severe gastroenteropathyDysfunction of rena

36、l and liver Acute complications Emergency Pregnant and breast feeding women胡仁明糖尿病Insulin sensitizers;agonist at the peroxisome proliferator-activated receptor （PPAR）;increase glucose utilization in peripheral tissues.Reducing insulin resistance，hyperglycemia and hyperlipaemia and hypertension can be

37、 improved at varies degrees For T2DM:used as monotherapy or in combination with SU,insulin.When used in combination with SU or insulin,hyperglycemia Without insulin，it cannot reduce hyperglycemiaLiver function should be monitored frequently.Stop using it in case liver dysfunction is found.Incidence

38、of edema:4 5%It may cause Hb slightly胡仁明糖尿病Stimulate Pancreatic insulin secretion（similar with SU）：）：specific combinition with 36KDa protein K pathway closeStimulating the first phrase secretion of insulin Action:rapid onset，short duration，suppressing postload hyperglycemia quickly Sites of excretio

39、n:kidney 8%，fecal 92%Used as monotherapy or in combination with biguanides ，-glucosidase inhibitors Incidence of hypoglycemia is low 胡仁明糖尿病ageweightBlood glucose level Function of liver and kidneyCharacteristic of drugcosts胡仁明糖尿病lOlder patients：short term SU lObesity or hyperinsulinism patients：bigu

40、anides or acarbosel2hPG ：glucosidaselConcentration of plasma glucose：270 300mg/dl.the symptoms of hypertension are evident.Insulin therapy is availablelImpaired liver and kidney function：avoid using OHAlLean、fasting and after-excitation insulin all ：insulin 胡仁明糖尿病Reasonable diet and poor plasma gluc

41、ose control by monotherapy SU、biguanides、TZD and-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

42、 a combined way.胡仁明糖尿病胡仁明糖尿病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 spe

43、cific types of DM：secondary pancreas disease、endocrinopathies、genetic diabetes胡仁明糖尿病l old notionold notion：NIDDMNIDDMFThe doctor uses OHA only and does not see The doctor uses OHA only and does not see the need to use Ins.the need to use Ins.FThe patient does not want to use In for fear The patient

44、does not want to use In for fear of developing insulin dependence after useing of developing insulin dependence after useing it.it.lHyperinsulinism can lead AS to CVDHyperinsulinism can lead AS to CVD？lhypoglycemiahypoglycemia，BWBW胡仁明糖尿病产品名 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

45、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 基因重组 300 U/瓶长效胰岛素 PZI 上海生物制药厂 猪 400 U/瓶胡仁明糖尿病lDifference in pharmacodynamic：Close action intens

46、ity Human insulin :absorption is fast，time of onset of effect is early lDifference in immunogenicity:Antigenicit of human insulin is weaker than animal insulin After use human insulin,antibody titer of blood insulin is lower lSynthesized insulin：lispro（28proline29 proline）Quick absorption,short effe

47、ct time 胡仁明糖尿病lIndications：monotherapy or combination therapy of oral antihyperglycemia therapy fail to achieve glucose targets，overt hyperglycemia，fasting and postprandial C-peptide lMethod：use insulin 2 times per day：NPH/R 70/30 prebreakfast and presupper，adjust the dosage with the monitoring resu

48、lts of blood sugar .use insulin 4 times per day：RI premeal、NPH before sleeplPeriod of treatment：several weeks or monthes胡仁明糖尿病l Estimation of initial dosage：0.2 0.4U/Kg weight per daylMode of therapyF RI before meals：RIRIRIO，before breakfastbefore supper before dinerF RI before three meals+RI before

49、 supper：RIRIRIRIF RI before three meals+NPH before supper:RIRIRI/NPHF RI before three meals+NPH before sleep：RIRIRINPHF mixed insulin（RI/NPH）before three meals（2/3before breakfast，1/3before supper），），the proportion :10R50RF NPH/R 70/30before breakfast and supper胡仁明糖尿病FPG oral anti-hyperglycemia agen

50、ts+NPH before sleep PPG NPH before breakfast+oral anti-hyperglycemia 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 胡仁明糖尿病lIndic

51、ation：OHA is invalid 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/L胡仁明糖尿病l HGP ，lipolysis l antagonize the somogyi effects and the dawn phenomenon caused by glucagon lFPG returning to norma

52、l lHelping SU to effect in daytimel24hour PG，HbA1clSupplying the deficiency of act time of former OHA lThe patients needs to be supplied with one injection each night and doesnt need to be hospitalized.Its easy for the patient to accept.胡仁明糖尿病Complementary therapyOHA are basic therapy，combination wi

53、th insulin NPH before sleep,FPG:daytime postprandial hyperglycemia can be improved evidently NPH perbreakfast with OHA for postprandial hyperglycemia (often used)Substitution therapyStop using OHA;substituted by insulinMixed insulin before breakfast and supperThree injections perday R，R，R+NFour inje

54、ctions perday R，R，R，R or R，R，R，N 胡仁明糖尿病lhypoglycemialocal reactionlAnaphylaxissystemic reactioninsulin drug resistance lLipid dystrophia：atrophy and fleshy 胡仁明糖尿病lInject position abdomen wall the upper armthighbuttockslInject depth hypodermatic,not muscle lPreservation cold storage,not freeze 胡仁明糖尿病

55、lNeed to increase the quantity of insulin：HyperpyrexiaHyperthyreaPachyacria Ketoacidosis Severe infection or trauma Serious surgeryPregnant woman，especially in metaphase or anaphase of pregnancy Adolescent children胡仁明糖尿病l need to cut down the quantity of insulin ：Metabolize and excretion of insulin

56、in kidney ：hypohepatia、kidney dysfunction、thyroid insufficiencyDiseases which can lead to hypoglycemia：hypadrenia、diarrhea、gastroanesthesia、intestinal obstruction、vomit、absorption of food Elderly patients(easy to get hypoglycemia)胡仁明糖尿病lCombined drugs（glucemia ）Agents which increase plasma glucose：g

57、lucocorticoid、ACTH、glucagon、estradiol、oral prophylactic、thyroxin、adrenalin、thiazide diuretic、dilantinCarbohydrate 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)胡仁明糖尿病lCombination drug therapy（help lower plasma glucose）Slow degradatio

58、n of insulin chloroquine、quinidine、quinin Insulin combine globulin competely，dissociated insulin anticoagulative 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

59、、lithium、甲苯咪唑、theophylline、alcohol、奥曲肽胡仁明糖尿病Glucosuria：associated with renal threshold of glucose(only for clue)FPGHBA1c：2 3 months blood sugar levelFructosamine：2 3 weeks blood sugar levelOGTT：2 hour specimen 胡仁明糖尿病胡仁明糖尿病lOne of the acute metabolic complications of diabetes lCan be initial symptoms

60、 of diabeteslOne of the important emergency of internal medicine lNeed rapid,reasonable treatment lFull-scale examination of specialty knowledge of internist or general practitioner lNeed doctors and nurses to take concerted action 胡仁明糖尿病lKetosislDKAlHypoglycaemic keto-acidotic coma胡仁明糖尿病lAcetoaceti

61、c acid is the first product：strong organic acid;can reacted with ketone powder strongly lDimethylketone：least quantity、neutral、no renal reabsorption threshold;can be excreted from respiratory tractloxybutyric acid：strong organic acid，biggest quantity（70）胡仁明糖尿病glucagon Abnormalities in carbohydrate m

62、etabolismlipolysisAcidosis Abnormal nervous system Circulation faliure携氧系统异常携氧系统异常Electrolyte disturbanceAcetone body Plasma glucose Severe dehydration 胡仁明糖尿病lInterrupted drug therapy lImproper dietlFatiguelinfectionlTrauma operationpregnancy、deliverydrinkingmiocardial infarction else胡仁明糖尿病lIntensiv

63、e thirsty,diuresis lExtremely tired、nausea、vomitinglVaried degrees of disorder of consciousness lCirculation failure lPresentations of precipitating factors胡仁明糖尿病l Abdominal pain lHypothermy and abnormal “normal body temperature”lNumber of leucocyte胡仁明糖尿病lUrine testsglucosuriaketourinelBlood testsBl

64、ood sugarBlood ketoneCO2CPelectrolyte胡仁明糖尿病lAcetoacetic acid acetone body powder rose purple When ketosis fades away，-hydroxy-butyric acid turn to acetoacetic acid，the color test of the latter with acetone body power is evidently better than the former In case of lack of oxygen，more acetoacetic acid

65、 turns to -hydroxy-butyric 胡仁明糖尿病lCorrecting acute metabolic turbulencelPreventing and curing complicationslReducing the case fatality rate胡仁明糖尿病lRestoration of circulating plasma volume lRebuild ERPF lHelping insulin to exert its effect lReducing blood sugar lRemoving blood ketonelReducing the conc

66、entration of insulin counterregulatory hormone胡仁明糖尿病lWhy：blood sugar 14mmol/L is the cutoff valuelHow：double vein channels lReference index:-age-vital signs-function of heart and kidney-shock or not-urine quantity per hour -CVP胡仁明糖尿病lInsulin in small dosage is a simple、efficient、safe therapy(0.1u/kg/h)NS 250ml+RI 25U/iv,15 drops/min Blood sugar 5 6mmol/L/hringnition？：RI 20U/ivlroutePresistent venous inflow(other approach)intermittent intervenous injection Intermittent intramuscular injection 胡仁明