胡仁明－糖尿病ppt课件

1、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 lgestational d

2、iabetes*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 diabetesltype 1 dm：inflammation

3、 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 ：anabolism ，catabolism、 utilization llipid ： anabol

4、ism ，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 has already declined by 50% when fpg7.0mmol/l， -cell

5、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 type1 dm type2 dmusual age of onset 40yearsmode of

6、 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 leading cause of deathrenal disease leading cause o

7、f 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 diseaselmicroangiopathydiabetic retinopathydiabetic renal diseasediabetic neuropathyldiabetic dermatop

8、athylinfectionlactivation of polyol （or sorbitol）pathway lformation of non-enzyme saccharification products lchange of hemodynamics l activation of pkclmicroangiopathy theory ldcct diabetes control and complications trial lukpds united kingdom prospective diabetes studylhba1c 0 .9%，（intensive therap

9、y 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 infarction and strock .lmost stimulating findings：biguanides can prevent or

10、 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%，microvascular complications by 37%。ldiabetics are easy to get

11、 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 lower limb amputation：15times ，fatalness morbidity ratediabetes: 20% 40%diab

12、etes 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 pathogeny：state of illness 、course of disease、age o

13、f 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 mesangial matrix thickening of the glomerular base

14、ment 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 nephropathy dm1025year albuminuria300mg/d 6070 patients prot

15、einuria0.5g/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 sensenumbness type：large medullated fiberspain type：little medullated fi

16、bers and nonmedullated fibersnumbness-pain typelnervous symptom examinationparasthesialower limbs pallesthetic disturbance or dissapeartendon reflex low or dissappear sensory staxiaparatrophy symptomscharcot arthropathy、ischemic gangrenosis and foot ulcerlpupil diseaselcardiovascular parafunctionfix

17、ed heart ratepostural hypertensionsudden cardiac deathlgestrophageal ,diarrhealneuropathic bladder,erectile failurelabnormal sweatingglucosuria：associated with renal threshold of sugar (only for clue)ketonuriablood sugar：plasma glucose，podhba1c：2 3 months blood sugar levelfructosamine：2 3 weeks bloo

18、d 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 2hpg7.8mmol/l is normal glucose tolerance；limpaired fasting glucose

19、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) 4.0 l26 centers、3965 patientsl28patients measure hba1c：8.12.6

20、%，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 therapyexercise therapysingle drug therapydecline of curative effect com

21、bined drug therapysecondary failure、distinct insufficiency of insulininsulin therapyl rational control of total calorific value lgoal ： keep ideal body weightloss weight for obese patientadd weight for lean patientlstandard body weightheight（cm）105male： （height100 ）0.9female： （height100 ）0.85lbody m

22、ass index（bmi） ：weight（kg）/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 moderate weight control the distribution of total calorfic value ：carbohydrate 55 %60% fat 20%25% 1/

23、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 standard weight lfat：0.6 1.0/kg standard weightlcarbohydrate：total calorific value calories

24、of protein and fat lbenefitsglycaemic controlincrease cell sensitivity to glucose blood lipid weight reductionlestimation of quantity of exercise：heart rate170age (year)sulfonylureasbiguanides-glucosidase inhibitorstniazolidinedionesmeglitinidesinsulindry-combination therapylthe principal action of

25、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 diminishing insulin resistance. general name duration of action potency merits main site general name

26、duration of action potency merits main site of of excretionexcretiontolbutamidetolbutamide (d860) short weak cheap renal (d860) short weak cheap renalglyburide (micronaseglyburide (micronase) long strong affirmed ) long strong affirmed hypoglycemia hypoglycemia effects in lowering effects in lowerin

27、g blood glucose levels blood glucose levels cheap renal cheap renal gliclazide (diamicvongliclazide (diamicvon) medium strong prevent and renal) medium strong prevent and renalglipizide (minidiabglipizide (minidiab) shot strong affirmed effects renal) shot strong affirmed effects renalgliquidone (gl

28、urenormgliquidone (glurenorm ) shot week not renal(only5%) ) shot week not renal(only5%)glipizide (tonbacglipizide (tonbac) long strong good compliance low ) long strong good compliance low incidence incidence of hypoglycemia of hypoglycemialprimary failure to respond to su occurs in 20% to 25% of p

29、atientslfpg 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 patients can keep ideal blood glucose control .ukpds：first year: blood glucose ，insulin then : blood glucose insulin th

30、e 6th year: returned to the state before therapy lindicationspoor control of t2dm by weight control and physical activitypoor control of t2dm by biguanides and -combined with insulinlcontraindications t1dmacute or chronic diabetic complicationsemergency dysfunction of liver or kidneypregnant or blee

31、ding women lhypoglycemia， most common inold patientslong-term pharmaceuticssymptoms of digestive tractlliver dysfunctionltetterlchange of hematologygeneric name generic name dosage merits nb dosage merits nb phenformin 75mg75mg/d cheap lactic acidosis /d cheap lactic acidosis （降糖灵）（降糖灵） restrain res

32、train oxygenic metabolism oxygenic metabolism lower energy of lower energy of oxygenic metabolism oxygenic metabolism dimethylbiguanide dimethylbiguanide 1.5g/d low gastrointestinal 1.4mg/dlacute or chronic acidosisheart、lung disease：hypoxia、acidosis inclinationhypohepatiasevere gastroenteropathypre

33、gnancyl diarrhealanaphylaxislovert macies ：common in elderly patientsllactic acidosislinhibiting -glucosidase ldelaying the digestion of glucosel2hpgl not stimulating the secretion of insulin-glucosidase inhibitors: mode of actionl2hpglfpglhba1c about 1.when used in combination with su,hba1c : about

34、2lserum 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 ,it may cause hypoglyceiaif hypoglycemia happens, patient should be treated by glucose. other kinds of sugar are ineffect

35、ivelindications light casesusing drug separately or combinedigt intervention，securitylcontraindications allergic reactions severe gastroenteropathydysfunction of renal and liver acute complications emergency pregnant and breast feeding womeninsulin sensitizers; agonist at the peroxisome proliferator

36、-activated receptor （ppar ）;increase glucose utilization in peripheral tissues .reducing insulin resistance，hyperglycemia and hyperlipaemia and hypertension can be improved at varies degrees for t2dm:used as monotherapy or in combination with su,insulin.when used in combination with su or insulin ,h

37、yperglycemia without insulin，it cannot reduce hyperglycemialiver function should be monitored frequently. stop using it in case liver dysfunction is found.incidence of edema:4 5%it may cause hb slightlystimulate pancreatic insulin secretion（similar with su）：）：specific combinition with 36kda protein

38、k pathway closestimulating the first phrase secretion of insulin action: rapid onset ，short duration，suppressing postload hyperglycemia quickly sites of excretion : kidney 8%，fecal 92% used as monotherapy or in combination with biguanides ，-glucosidase inhibitors incidence of hypoglycemia is low age

39、weightblood glucose level function of liver and kidneycharacteristic of drugcostslolder patients：short term su lobesity or hyperinsulinism patients：biguanides or acarbosel2hpg ：glucosidaselconcentration of plasma glucose：270 300mg/dl. the symptoms of hypertension are evident .insulin therapy is avai

40、lablelimpaired liver and kidney function：avoid using ohallean 、 fasting and after-excitation insulin all ：insulin reasonable diet and poor plasma glucose control by monotherapy su 、biguanides 、tzd and - glucosidase inhibitors all can be used in combination with each othersmall dosage combined with o

41、f 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. type 1 dmtype 2 dmacute complicationssevere chronic complications of diabetesemergency severe dysfunction of liver or kidneygest

42、ation and bleeding womenwithout tolerance oha， curative effect of oha ，su invalidationdistinct leanwith diseases treated by glucocorticoidsome specific types of dm：secondary pancreas disease 、endocrinopathies、genetic diabetesl old notionold notion： niddmniddmfthe doctor uses oha only and does not se

43、e 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 does not want to use in for fear of developing insulin dependence after useing of developing insulin dependence after useing it. it. lhyperinsulinismhyperinsu

44、linism can lead as to cvd can lead as to cvd？lhypoglycemiahypoglycemia，bwbw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

45、(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 ：close action intensity human insulin : absorption is fast ，time of onset of effect is early ldifference in immunogenicity:antigenicit of human insulin is weaker than animal insulin afte

46、r use human insulin, antibody titer of blood insulin is lower lsynthesized insulin ：lispro（28proline29 proline ）quick absorption, short effect time lindications：monotherapy or combination therapy of oral antihyperglycemia therapy fail to achieve glucose targets，overt hyperglycemia，fasting and postpr

47、andial 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 times per day ： ri premeal、 nph before sleeplperiod of treatment：several weeks or monthesl estimation of initial dosage： 0.2 0.4u/

48、kg weight per daylmode of therapyf ri before meals：riririo，before breakfastbefore supper before dinerf ri before three meals + ri before 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 me

49、als（2/3before breakfast ，1/3before supper），），the proportion :10r50rf nph/r 70/30before breakfast and supperfpg oral anti-hyperglycemia agents+ nph before sleep ppg nph before breakfast+oral anti-hyperglycemia agentsfpg ppg oral anti-hyperglycemia agents + nph before sleep and before breakfast insuli

50、n ： adjust per 34 days ， one phrase each time up for 24u every time before you add insulin , hypoglycemia reaction should be excluded lindication ：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/l

51、postload 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 daytimel24hour pg ，hba1clsupplying the deficiency of act time of former oha lthe patients needs to be supplied with one injection each nig

52、ht 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 : daytime postprandial hyperglycemia can be improved evidently nph perbreakfast with oha for postprandial hyperglycemia (often used)subs

53、titution 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 lhypoglycemialocal reactionlanaphylaxissystemic reactioninsulin drug resistance llipid dystrophia ：atrophy and fleshy linject positio

54、n abdomen wall the upper armthighbuttockslinject depth hypodermatic ,not muscle lpreservation cold storage, not freeze lneed to increase the quantity of insulin：hyperpyrexiahyperthyreapachyacria ketoacidosis severe infection or trauma serious surgerypregnant woman ，especially in metaphase or anaphas

55、e of pregnancy adolescent childrenl 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、diarrhea 、gastroanesthesia 、intestinal obstruction、vomit 、absorption of

56、 food elderly patients (easy to get hypoglycemia)lcombined drugs（ glucemia ）agents which increase plasma glucose：glucocorticoid、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、

57、morphin、 nicoltin、-blocker(普萘洛尔可阻止肾上腺素升高血糖的反应)lcombination drug therapy（help lower plasma glucose ）slow degradation of insulin chloroquine 、 quinidine 、 quinin insulin combine globulin competely，dissociated insulin anticoagulative agents、 salicylate 、sulfanilamide 、anti-tumor agents can help lowerin

58、g 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glucosuria：associated with renal threshold of glucose(only for clue)fpghba1c：2 3 months blood sugar levelfructosamine：2 3 weeks blood suga

59、r levelogtt：2 hour specimen lone of the acute metabolic complications of diabetes lcan be initial symptoms 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 docto

60、rs and nurses to take concerted action lketosisldkalhypoglycaemic keto-acidotic comalacetoacetic 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 tractlox