爱爱医资源-胡仁明－糖尿病

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

2、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 sometimes associated with diabetes lType 1 DM：inflammat

3、ion of pancreas lType 2 DM：amyloidosis of pancreas lLarge vessel ：atherosclerosis lKidney ：diffuse or nodular glomerular sclerosis lRetina：arteriolar sclerosis、 microaneurysm、exudates、new vessel formation lNerve：axon degeneration 、 myelinolysis lCarbohydrate ：anabolism ，catabolism、 utilization lLipi

4、d ： anabolism ，catabolism ， ketoplasia lprotein： anabolism ，catabolism ， glyconeogenesis 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 declined by 50% When FPG7.

5、0mmol/L， -cell insulin secretion ability When FPG10 11.0mmol/L， -C insulin secretion ability has already neared absolute deficiency NGT IGR(IFG、IGT) DM cell exhaustion Insulin resistanceInsulin resistance IG T IFG NGT DM 75gOGTT 2hPG (mmol/L) FPG (mmol/L) 7.0 6.1 FPG 7.8 11.1 IGT type1 DM type2 DM U

6、sual age of onset 40years Mode of onset acute chronic weight normal overweight or obesity or weight loss symptoms polyuria,polydipsia, similar but usually weight loss less severe presentation Acute complications often few Chronic complications Large vessel disease less then type 2 DM leading cause o

7、f death Renal disease leading cause of death 5%10% Insulin and c-peptide low or lack peak value delayed ,high or deficiency Immune marker usually + usually - Therapy insulin dependence oral antidiabetic agents are available lMacrovascular disease lMicroangiopathy Diabetic retinopathy Diabetic renal

8、disease Diabetic neuropathy lDiabetic dermatopathy lInfection lActivation of polyol （or sorbitol）pathway lFormation of non-enzyme saccharification products lChange of hemodynamics l Activation of PKC lMicroangiopathy theory lDCCT Diabetes Control and Complications Trial lUKPDS United Kingdom Prospec

9、tive Diabetes Study 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 infarction and strock .

10、 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） ，stroke by 44%， microva

11、scular complications by 37%。 lDiabetics are easy to get atherosclerosis Monckebergs sclerosis 41.5 Intimal arteriosteogenesis 29.3 lCoronary heart disease、cerebrovascular disease：24 times Risk of miocardial infarction： 10 times Risk of stroke : 3.8 times，especially in women lRisk of lower limb amput

12、ation：15times ，fatalness Morbidity rate diabetes: 20% 40% Diabetes in EU(35-54years): 30% 50% Diabetes in China: 29.2% pathogenesis aortosclerosis Arteriola resistance Hypertension associated with DN Renal hypertension caused by stenosis of renal artery lDiabetic retinopathyleading course of new cas

13、es of blindness l Pathogeny：state of illness 、course of disease、age of onset l 5 years ：eyeground disease is not common l 10 years ：50eyeground disease l 130ml/min Stage II clinically silent phase DM 25year GFR 2040 renal enlargement， with continued glomerular hypertrophy, hyperfiltration and hypert

14、rophy 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 St

15、age 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 15years lSymptoms o

16、f sense Numbness type：large medullated fibers Pain type：little medullated fibers and nonmedullated fibers Numbness-pain type lNervous symptom examination parasthesia Lower limbs pallesthetic disturbance or dissapear Tendon reflex low or dissappear Sensory staxia Paratrophy symptoms Charcot arthropat

17、hy、ischemic gangrenosis and foot ulcer lPupil disease lCardiovascular parafunction Fixed heart rate Postural hypertension Sudden cardiac death lGestrophageal ,diarrhea lNeuropathic bladder,erectile failure lAbnormal sweating Glucosuria：associated with renal threshold of sugar (only for clue) Ketonur

18、ia Blood sugar：plasma glucose，POD HBA1c：2 3 months blood sugar level Fructosamine：2 3 weeks blood sugar level OGTT：2 hour specimen Insulin and C-peptide release test FPG Random OGTT plasma glucose 2hPG mmol/L mmol/L mmol/L DM 7.0 11.1 11.1 IGR IFG 6.1FPG7.0 IGT 7.8FPG11.1 Normal 6.1 7.8 lFPG6.1mmol/

19、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 10.0 HBA1c() 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

20、0.9 TG (mmol/L) 1.5 2.2 2.2 LDL-C (mmol/L) 4.0 l26 centers、3965 patients l28patients measure HbA1c：8.12.6%， 527.5 lFPG：9.2 3.7mmol/L，55%7.8 mmol/L lDeterming rate of microalbumin in urine ： 20 Patient education Health nutrition therapy Exercise therapy Drug therapy Monitoring of blood glucose Early

21、reaction Patient therapy Medical nutrition therapy Exercise therapy Single drug therapy decline of curative effect Combined drug therapy Secondary failure、distinct insufficiency of insulin Insulin therapy l rational control of total calorific value lGoal ： Keep ideal body weight Loss weight for obes

22、e patient Add weight for lean patient lStandard body weight height（cm）105 male： （height100 ）0.9 female： （height100 ）0.85 lBody mass index（BMI） ：weight（kg）/height2 （m2） work intension Bodily form in bed light physical middle heavy labor physical physical labor labor lean 20 25 35 40 40 normal 15 20 3

23、0 35 40 obesity 15 20 25 30 35 Moderate weight control The distribution of total calorfic value ： carbohydrate 55 %60% fat 20%25% 1/5、 2/5、 2/5 protein 15 %20% Drink limitation Avoiding diabetic foods (which contain sorbitol or frucotose) Aspartame is an acceptable calorie-free sweetener salt10g/d，(

24、3g/day if hypertensive) lprotein：0.8 1.2/kg standard weight lfat：0.6 1.0/kg standard weight lcarbohydrate：total calorific value calories of protein and fat lBenefits Glycaemic control Increase cell sensitivity to glucose Blood lipid Weight reduction lEstimation of quantity of exercise：heart rate170a

25、ge (year) Sulfonylureas Biguanides -glucosidase inhibitors Tniazolidinediones Meglitinides Insulin Dry-combination therapy 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 sensi

26、tivity to glucose and exert some influence in diminishing insulin resistance. General name duration of action potency merits main site General name duration of action potency merits main site of of excretionexcretion TolbutamideTolbutamide (D860) short weak cheap renal (D860) short weak cheap renal

27、Glyburide (micronaseGlyburide (micronase) long strong affirmed ) long strong affirmed hypoglycemia hypoglycemia effects in lowering effects in lowering blood glucose levels blood glucose levels cheap renal cheap renal Gliclazide (diamicvonGliclazide (diamicvon) medium strong prevent and renal) mediu

28、m strong prevent and renal glipizide (minidiabglipizide (minidiab) shot strong affirmed effects renal) shot strong affirmed effects renal Gliquidone (glurenormGliquidone (glurenorm ) shot week not renal(only5%) ) shot week not renal(only5%) Glipizide (tonbacGlipizide (tonbac) long strong good compli

29、ance low ) long strong good compliance low incidence incidence of hypoglycemia of hypoglycemia lPrimary failure to respond to SU occurs in 20% to 25% of patients lFPG and 2hPG lHbA1c 1% 2 lAs the period of treatment progresses, effects decline： Secondary failure occurs at the rate of 10% to 15% per

30、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 the 6th year: returned to the state before therapy lIndications Poor control of T2DM by weight control and physical activity Poor control of T2DM

31、 by biguanides and - Combined with insulin lContraindications T1DM Acute or chronic diabetic complications Emergency Dysfunction of liver or kidney Pregnant or bleeding women lHypoglycemia， most common in Old patients Long-term pharmaceutics Symptoms of digestive tract lLiver dysfunction lTetter lCh

32、ange of hematology Generic 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 restrain oxygenic metabolism oxygenic metabolism lower energy of lower energy of oxygenic metabolism oxygenic metabolism dimethylbig

33、uanide dimethylbiguanide 1.5g/d low gastrointestinal 1.4mg/dl Acute or chronic acidosis Heart、lung disease：hypoxia、acidosis inclination Hypohepatia Severe gastroenteropathy Pregnancy l Diarrhea lAnaphylaxis lOvert macies ：common in elderly patients lLactic acidosis lInhibiting -glucosidase lDelaying

34、 the digestion of glucose l2hPG l Not stimulating the secretion of Insulin -glucosidase inhibitors: mode of action l2hPG lFPG lHbA1c about 1.When used in combination with SU,HbA1c : about2 lSerum insulin slightly declined lWeight not a few patients lWhen used as monotherapy, it do not cause hypoglyc

35、emia lWhen used in combination with other oral antidiabetic agents ,it may cause hypoglyceia If hypoglycemia happens, patient should be treated by glucose. Other kinds of sugar are ineffective lIndications Light cases using drug separately or combined IGT intervention，security lContraindications All

36、ergic reactions Severe gastroenteropathy Dysfunction of renal and liver Acute complications Emergency Pregnant and breast feeding women Insulin sensitizers; agonist at the peroxisome proliferator-activated receptor （PPAR ）;increase glucose utilization in peripheral tissues . Reducing insulin resista

37、nce，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 ,hyperglycemia Without insulin，it cannot reduce hyperglycemia Liver function should be monitored frequent

38、ly. Stop using it in case liver dysfunction is found. Incidence of edema:4 5% It may cause Hb slightly Stimulate Pancreatic insulin secretion（similar with SU）：）：specific combinition with 36KDa protein K pathway close Stimulating the first phrase secretion of insulin Action: rapid onset ，short durati

39、on， 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 weight Blood glucose level Function of liver and kidney Characteristic of drug costs lOlder pati

40、ents：short term SU lObesity or hyperinsulinism patients：biguanides or acarbose l2hPG ：glucosidase lConcentration of plasma glucose：270 300mg/dl. the symptoms of hypertension are evident .Insulin therapy is available lImpaired liver and kidney function：avoid using OHA lLean 、 fasting and after-excita

41、tion 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 other Small dosage combined with of all kinds of drugs ;enhancing effects of reduce glucaemia ;side effects of single ag

42、ents Oral agents with insulin Drugs of the same class cannot be used in a combined way. Type 1 DM Type 2 DM Acute complications Severe chronic complications of diabetes Emergency Severe dysfunction of liver or kidney Gestation and bleeding women Without tolerance OHA， curative effect of OHA ，SU inva

43、lidation Distinct lean With diseases treated by glucocorticoid Some specific types of DM：secondary pancreas disease 、endocrinopathies、genetic diabetes l old notionold notion： NIDDMNIDDM FThe doctor uses OHA only and does not see The doctor uses OHA only and does not see the need to use Ins.the need

44、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. lHyperinsulinismHyperinsulinism can lead AS to CVD can lead AS to CVD？ lhypoglycemiahypoglycemia，

45、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 (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 P

46、ZI 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 After use human insulin, antibody titer of blood insulin is lowe

47、r 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 postprandial C-peptide lMethod：use insulin 2 times per day： NPH/

48、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 sleep lPeriod of treatment：several weeks or monthes l Estimation of initial dosage： 0.2 0.4U/Kg weight per day lMode of therapy F RI before meals：RIR

49、IRIO，before breakfastbefore supper before diner F RI before three meals + RI before supper： RIRIRIRI F RI before three meals + NPH before supper: RIRIRI/NPH F RI before three meals + NPH before sleep： RIRIRINPH F mixed insulin（RI/NPH） before three meals（2/3before breakfast ，1/3before supper），），the p

50、roportion :10R50R F NPH/R 70/30before breakfast and supper FPG oral anti-hyperglycemia agents+ NPH before sleep PPG NPH before breakfast+oral anti-hyperglycemia agents FPG PPG oral anti-hyperglycemia agents + NPH before sleep and before breakfast Insulin ： adjust per 34 days ， one phrase each time u

51、p 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/dl Non-lean LADA Still having some function of insulin secretion C-peptide： fasting0.2 mmol/L postload 0.4 mmol/L l HGP ，lipolysis l anta

52、gonize the somogyi effects and the dawn phenomenon caused by glucagon lFPG returning to normal lHelping SU to effect in daytime l24hour PG ，HbA1c lSupplying 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. I

53、ts easy for the patient to accept. Complementary therapy OHA 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 therapy Stop using OHA;subst

54、ituted by insulin Mixed insulin before breakfast and supper Three injections perday R，R，R+N Four injections perday R，R，R，R or R，R，R，N lhypoglycemia local reaction lAnaphylaxissystemic reaction insulin drug resistance lLipid dystrophia ：atrophy and fleshy lInject position abdomen wall the upper armth

55、ighbuttocks lInject depth hypodermatic ,not muscle lPreservation cold storage, not freeze lNeed to increase the quantity of insulin： Hyperpyrexia Hyperthyrea Pachyacria Ketoacidosis Severe infection or trauma Serious surgery Pregnant woman ，especially in metaphase or anaphase of pregnancy Adolescent

56、 children l need to cut down the quantity of insulin ： Metabolize and excretion of insulin in kidney ： hypohepatia 、kidney dysfunction、thyroid insufficiency Diseases which can lead to hypoglycemia：hypadrenia、 diarrhea 、gastroanesthesia 、intestinal obstruction、 vomit 、absorption of food Elderly patie

57、nts (easy to get hypoglycemia) lCombined drugs（ glucemia ） Agents which increase plasma glucose：glucocorticoid、ACTH、 glucagon、estradiol、oral prophylactic、thyroxin、adrenalin 、 thiazide diuretic 、dilantin Carbohydrate metabolism abnormality、PG ：felodipine、可乐定、 二氮嗪、GH、heparin、-blocker 、大麻、morphin、 nico

58、ltin、 -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 lowering glucemi

59、a ：OHA、 assimilation steroid androgenic hormones、 monoamine oxidase inhibitor 、NSAID Lower 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) FPG HBA1c：2 3 months blood sugar level Fructosamine：2 3 weeks blood sugar

60、level OGTT：2 hour specimen lOne of the acute metabolic complications of diabetes lCan be initial symptoms of diabetes lOne of the important emergency of internal medicine lNeed rapid ,reasonable treatment lFull-scale examination of specialty knowledge of internist or general practitioner lNeed docto