胡仁明－糖尿病ppt课件

1、Diabetes at Fudan Diabetes at Fudan UniversityUniversityType 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 in

2、sulin resistance) Other specific types Gestational diabetes*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 somet

3、imes associated with diabeteslType 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 、myelinolysislCarbohydrate

4、 ：anabolism ，catabolism、 utilization lLipid ： anabolism ，catabolism ，ketoplasialprotein： anabolism ，catabolism ，glyconeogenesisAfter the diagnosis of type 2 diabetes:IR constantly exists Insulin secretion ability gradually declines: When FPG reachs the diagnostic criteria，insulin secretion ability h

5、as already declined by 50% When FPG7.0mmol/L，-cell insulin secretion ability When FPG10 11.0mmol/L，-C insulin secretion ability has already neared absolute deficiencyNGT IGR(IFG、IGT) DM cell exhaustionInsulin resistanceInsulin resistanceIGTIFGNGTDM75gOGTT2hPG (mmol/L)FPG(mmol/L)7.06.1FPG7.8 11.1IGT

6、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 DM l

7、eading 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 availablelMacrovascular diseaselMicroangiopathylDiabetic retinopathylDiabeti

8、c renal diseaselDiabetic neuropathylDiabetic dermatopathylInfectionlActivation of polyol or sorbitolpathway lFormation of non-enzyme saccharification products lChange of hemodynamics l Activation of PKClMicroangiopathy theory lDCCTl Diabetes Control and Complications Trial lUKPDSl United Kingdom Pro

9、spective Diabetes StudylHbA1c 0 .9%，intensive therapy vs routine therapyl 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 infarction and strock .l

10、Most 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 ，stroke by 44%，microvascula

11、r complications by 37%。lDiabetics are easy to get atherosclerosis lMonckebergs sclerosis 41.5lIntimal arteriosteogenesis 29.3lCoronary heart disease、cerebrovascular disease：24 timeslRisk of miocardial infarction： 10 timeslRisk of stroke : 3.8 times，especially in womenlRisk of lower limb amputation：1

12、5times ，fatalness 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 arterylDiabetic retinopathyleading course of new cases of blindnessl

13、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 hypertrophy expansion of the

14、 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 Stage IV Overt Nephropat

15、hy 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 of senselNumbness type：l

16、arge medullated fiberslPain type：little medullated fibers and nonmedullated fiberslNumbness-pain typelNervous symptom examinationlparasthesialLower limbs pallesthetic disturbance or dissapearlTendon reflex low or dissappear lSensory staxialParatrophy symptomslCharcot arthropathy、ischemic gangrenosis

17、 and foot ulcerlPupil diseaselCardiovascular parafunctionlFixed heart ratelPostural hypertensionlSudden cardiac deathlGestrophageal ,diarrhealNeuropathic bladder,erectile failurelAbnormal sweatingGlucosuria：associated with renal threshold of sugar (only for clue)KetonuriaBlood sugar：plasma glucose，P

18、ODHBA1c：23 months blood sugar levelFructosamine：23 weeks blood sugar levelOGTT：2 hour specimenInsulin and C-peptide release test 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 7.8lFPG6.1mmol/L is normal fasting glucose，OGTT 2hPG7.8

19、mmol/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 (mmol/L) 1.5 2.2 2.2 LDL-C (mmol/L)

20、4.0 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 Patient educationHealth nutrition therapyExercise therapyDrug therapyMonitoring of blood glucoseEarly reaction Patient therapyMedical nutrition therapyExer

21、cise therapySingle drug therapydecline of curative effect Combined drug therapySecondary failure、distinct insufficiency of insulinInsulin therapyl rational control of total calorific value lGoal ： lKeep ideal body weightlLoss weight for obese patientlAdd weight for lean patientlStandard body weightl

22、heightcm105lmale： height100 0.9lfemale： height100 0.85lBody mass indexBMI ：weightkg/height2 m2 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 we

23、ight 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)lprotein：0.8 1.2/kg sta

24、ndard weight lfat：0.6 1.0/kg standard weightlcarbohydrate：total calorific value calories of protein and fat lBenefitslGlycaemic controllIncrease cell sensitivity to glucose l Blood lipid lWeight reductionlEstimation of quantity of exercise：heart rate170age (year)SulfonylureasBiguanides-glucosidase i

25、nhibitorsTniazolidinedionesMeglitinidesInsulinDry-combination therapylThe 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 glucose and exert some influence in diminish

26、ing insulin resistance. 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 (micronase) long strong affirmed Glyburide (mi

27、cronase) 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 renalglipizide (minidiab) shot stro

28、ng 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 low incidence incide

29、nce of hypoglycemia of hypoglycemialPrimary failure to respond to SU occurs in 20% to 25% of patientslFPG and 2hPG lHbA1c 1% 2lAs the period of treatment progresses, effects decline：l Secondary failure occurs at the rate of 10% to 15% per yearl After 5 years ，only half of the patients can keep ideal

30、 blood glucose control .lUKPDS：first year: blood glucose ，insulinl then : blood glucose insulinl the 6th year: returned to the state before therapy lIndicationslPoor control of T2DM by weight control and physical activitylPoor control of T2DM by biguanides and -lCombined with insulinlContraindicatio

31、ns lT1DMlAcute or chronic diabetic complicationslEmergency lDysfunction of liver or kidneylPregnant or bleeding women lHypoglycemia， most common inlOld patientslLong-term pharmaceuticslSymptoms of digestive tractlLiver dysfunctionlTetterlChange of hematologyGeneric name dosage merits NBGeneric name

32、dosage merits NB phenformin 75mg/d cheap lactic acidosis phenformin 75mg/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 1.

33、4mg/dllAcute or chronic acidosislHeart、lung disease：hypoxia、acidosis inclinationlHypohepatialSevere gastroenteropathylPregnancyl DiarrhealAnaphylaxislOvert macies ：common in elderly patientslLactic acidosislInhibiting -glucosidase lDelaying the digestion of glucosel2hPGl Not stimulating the secretio

34、n of Insulin-glucosidase inhibitors: mode of actionl2hPGlFPGlHbA1c 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 antidiabetic agents

35、,it may cause hypoglyceialIf hypoglycemia happens, patient should be treated by glucose. Other kinds of sugar are ineffectivelIndications lLight caseslusing drug separately or combinedlIGT intervention，securitylContraindications lAllergic reactions lSevere gastroenteropathylDysfunction of renal and

36、liver lAcute complicationsl Emergency l Pregnant and breast feeding womenInsulin 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 improve

37、d 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 of ede

38、ma:4 5%It may cause Hb slightlyStimulate Pancreatic insulin secretionsimilar 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 excretion : kidney 8%，

39、fecal 92% Used as monotherapy or in combination with biguanides ，-glucosidase inhibitors Incidence of hypoglycemia is low ageweightBlood glucose level Function of liver and kidneyCharacteristic of drugcostslOlder patients：short term SU lObesity or hyperinsulinism patients：biguanides or acarbosel2hPG

40、 ：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 Reasonable diet and poor plasma glucose control by monotherap

41、y 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 a combined way. Typ

42、e 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 DM：secondary p

43、ancreas disease 、endocrinopathies、genetic diabetesl old notion old notion： NIDDM NIDDMlThe doctor uses OHA only and does not see the The doctor uses OHA only and does not see the need to use Ins.need to use Ins.lThe patient does not want to use In for fear of The patient does not want to use In for

44、fear of developing insulin dependence after useing it. developing insulin dependence after useing it. lHyperinsulinism can lead AS to CVDHyperinsulinism can lead AS to CVD？lhypoglycemiahypoglycemia，BWBW产品名 消费厂家 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/

45、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lDifference in pharmacodynamic ：lClose action intensity lHuman insulin : absorption is fas

46、t ，time of onset of effect is early lDifference in immunogenicity:lAntigenicit of human insulin is weaker than animal insulin l After use human insulin, antibody titer of blood insulin is lower lSynthesized insulin ：lispro28proline29 proline lQuick absorption, short effect time lIndications：monother

47、apy 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 results of blood sugar .use insulin 4

48、 times per day ： RI premeal、 NPH before sleeplPeriod of treatment：several weeks or monthesl Estimation of initial dosage： 0.2 0.4U/Kg weight per daylMode of therapyl RI before meals：RIRIRIO，before breakfastbefore supper before dinerl RI before three meals + RI before supper： RIRIRIRIl RI before thre

49、e meals + NPH before supper: RIRIRI/NPHl RI before three meals + NPH before sleep： RIRIRINPHl mixed insulinRI/NPH before three meals2/3before breakfast ，1/3before supper，the proportion :10R50Rl NPH/R 70/30before breakfast and supperFPG oral anti-hyperglycemia agents+ NPH before sleep PPG NPH before

50、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 lIndication ：lOHA is invalid or has low e

51、ffect lFPG not exceeding 250 300 mg/dllNon-lean l LADA lStill having some function of insulin secretion lC-peptide：lfasting0.2 mmol/Llpostload 0.4 mmol/Ll HGP ，lipolysis l antagonize the somogyi effects and the dawn phenomenon caused by glucagon lFPG returning to normal lHelping SU to effect in dayt

52、imel24hour 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.Complementary therapyOHA are basic therapy，combination with insulin NPH before sleep ,FPG :

53、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 injections perday R，R，R，R or R，R，R，N

54、 lhypoglycemiallocal reactionlAnaphylaxissystemic reactionlinsulin drug resistance lLipid dystrophia ：atrophy and fleshy lInject positionl abdomen wall the upper armthighbuttockslInject depthl hypodermatic ,not muscle lPreservationl cold storage, not freeze lNeed to increase the quantity of insulin：

55、lHyperpyrexialHyperthyrealPachyacria lKetoacidosis lSevere infection or trauma lSerious surgerylPregnant woman ，especially in metaphase or anaphase of pregnancy lAdolescent childrenl need to cut down the quantity of insulin ：lMetabolize and excretion of insulin in kidney ：hypohepatia 、kidney dysfunc

56、tion、thyroid insufficiencylDiseases which can lead to hypoglycemia：hypadrenia、diarrhea 、gastroanesthesia 、intestinal obstruction、vomit 、absorption of food lElderly patients (easy to get hypoglycemia)lCombined drugs glucemia lAgents which increase plasma glucose：glucocorticoid、ACTH、glucagon、estradiol

57、、oral prophylactic、thyroxin、adrenalin 、thiazide diuretic 、dilantinlCarbohydrate 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响)lCombination drug therapyhelp lower plasma glucose lSlow degradation of insulin l chloroquine 、 quinidin

58、e 、 quinin lInsulin combine globulin competely，dissociated insulin l anticoagulative agents、 salicylate 、sulfanilamide 、anti-tumor agents can help lowering glucemia ：OHA、assimilation steroid androgenic hormones、 monoamine oxidase inhibitor 、NSAIDlLower glucemia l ACEI、溴隐停、氯贝特、酮康唑、lithium 、甲苯咪唑、theop

59、hylline、alcohol、奥曲肽Glucosuria：associated with renal threshold of glucose(only for clue)FPGHBA1c：23 months blood sugar levelFructosamine：23 weeks blood sugar levelOGTT：2 hour specimen Diabetic KetoacidosisDKAlOne of the acute metabolic complications of diabetes lCan be initial symptoms of diabeteslOn

60、e 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 KetosisDKAHypoglycaemic keto-acidotic comalAcetoacetic acid is the first product：s