胡仁明糖尿病

1、Diabetes MellitusRenming Hu M.D,PhD Department of EndocrinologyHuashan HospitalInstitute of Endocrinology and Diabetes at Fudan University,Classification of diabetes(ADA-1997),Type 1 (beta-cell destruction, usual

2、ly 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 re

3、sistance) Other specific types Gestational diabetes**,,Other specific types,Genetic defects of beta-cell function Genetic defects in insulin action Diseases of the exocrine pancreas Endocrinopathies Drug- or che

4、mical-induced Infections Uncommon forms of immune-mediated diabetes Other genetic syndromes sometimes associated with diabetes,,Pathogenesis,Pathology,Type 1 DM：inflammation of pancreasType 2 DM：amyloidosis of pancr

5、easLarge vessel ：atherosclerosisKidney ：diffuse or nodular glomerular sclerosis Retina：arteriolar sclerosis、microaneurysm、exudates、new vessel formationNerve：axon degeneration 、myelinolysis,Pathophysiology,Abnormaliti

6、es in metabolism,Carbohydrate ：anabolism? ，catabolism?、 utilization Lipid ： anabolism? ，catabolism? ，ketoplasiaprotein： anabolism? ，catabolism? ，glyconeogenesis,,Insulin secretion curve :normal and diabetics,Clini

7、cal Presentation,Natural history of type 2 DM,After the diagnosis of type 2 diabetes:IR constantly exists Insulin secretion ability gradually declines: When FPG reachs the diagnostic criteria，insulin secretion a

8、bility has already declined by 50% When FPG≥7.0mmol/L，?-cell insulin secretion ability When FPG≥10?11.0mmol/L，?-C insulin secretion ability has already neared absolute deficiency,,,Models of the onset o

9、f two phrases of type 2 DM,NGT IGR(IFG、IGT) DM,,,?cell exhaustion,Insulin resistance,Insulin resistance,WHO plasma glucose guideline,IGT,75gOGTT2hPG (mmol/L),FPG(mmol/L)7.06

10、.1,FPG,7.8 11.1,IGT,Comparison of type 1 and type 2 DM,type1 DM type2 DMUsual age of onset 40yearsMode of onset acute chroni

11、cweight normal overweight or obesity or weight loss symptoms polyuria,polydipsia, sim

12、ilar but usually weight loss less severe presentation Acute complications often fewChronic complicationsLar

13、ge vessel disease less then type 2 DM leading cause of deathRenal disease leading cause of death 5%?10%Insulin and c-peptide low or lack

14、 peak value delayed ,high or deficiencyImmune marker usually + usually -Therapy insulin dependence oral antidi

15、abetic agents are available,Chronic complications,Macrovascular diseaseMicroangiopathyDiabetic retinopathyDiabetic renal diseaseDiabetic neuropathyDiabetic dermatopathyInfection,Mechanism of complications,Activa

16、tion 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 complicat

17、ions,DCCT Diabetes Control and Complications Trial UKPDS United Kingdom Prospective Diabetes Study,UKPTS：results,HbA1c 0 .9%，（intensive therapy vs routine therapy） Intensive therapy group: diabetis associated

18、complications 12%，and the fatalness of microvascular complications 25%。It cannot evidently reduce the incidence of great vessel disease ,such as miocardial infarction and strock .Most stimulating findings：Biguanid

19、es 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

20、 24% （144/82mmHg vs 154/87mmHg） ，stroke by 44%，microvascular complications by 37%。,,,,Epidemiology of diabetes Macrovascular disease,Diabetics are easy to get atherosclerosis Monckeberg’s sclerosis 41.5％Intimal

21、arteriosteogenesis 29.3％Coronary heart disease、cerebrovascular disease：24 timesRisk of miocardial infarction： 10 timesRisk of stroke : 3.8 times，especially in womenRisk of lower limb amputation：15times ，fatalness

22、,,,,,,Hypertension in DM,,Morbidity ratediabetes: 20%?40%Diabetes in EU(35-54years): 30%?50%Diabetes in China: 29.2%pathogenesisaortosclerosisArteriola resistance Hypertension associated with DNRenal hypertensio

23、n caused by stenosis of renal artery,,Diabetic retinopathy－leading course of new cases of blindness Pathogeny：state of illness 、course of disease、age of onset <5 years ：eyeground disease is not common <10

24、years ：50％eyeground disease <20 years ：80?90％eyeground disease,Diabetic Retinopathy,Classifications (China),Background retinopathyⅠ microaneurysms、dots of hemorrhagesⅡ yellow and white hard exudates , haemorrhage

25、sⅢ white soft exudates , haemorrhages spots Proliferative retinopathyⅣ new vessel formation、haemorrhage into the vitreousⅤ new vessel formation and fibrosisⅥ retinal detachment,Diabetic nephropathy,DN is the leading

26、 cause of ESRD (end-stage renal disease) Almost 40％of Type 1 DM died of uremiaIncidence of DN in type 2 DM is about 20％In EU，DN accounts for 1/3 of dialysis and kidney transplantation casesIn China, DN also acco

27、unts for quite a lot of dialyses and kidney transplantations,Stages of diabetic nephropathy(1),stage I increased kidney DM already filtration diagnosised GFR↑↑

28、 enlarged kidneys(B- ultrasonic) GFR>130ml/minStage II clinically silent phase DM 2?5year GFR ↑20?40％ r

29、enal enlargement， with continued glomerular hypertrophy, hyperfiltration and hypertrophy

30、 expansion of the mesangial matrix

31、 thickening of the glomerular basement membrane resulting in

32、 glomerulosclerosis Stage III concealed DN microalbuminuria DM5?10year microalbuminuria

33、 1/5 patients with hypertension (20-200µg/min retinopothy↑

34、 ,or30?300mg/24h) proteinuria 0.15?0.5g/24h

35、 GFR> or =normal,Stages of diabetic nephropathy(2),Stage IV Overt Nephropathy DM10?25year albuminuria>300mg/d 60?70％ p

36、atients proteinuria>0.5g/d ， with hypertentio

37、 G

38、FR↓(when UAER=100 and edema mg/24h , GER begin to decrease， about

39、1ml/min/month) retinopathy ↑↑ Stage V end-stage renal disease, ESRD DM15?30 year

40、 albuminuria azotemic→ uremia

41、 GFR< 1/3 of normal,Classification of diabetes neuropathy （1）,Peripheral neuropathy symmetric multiple peripheral neuropathy sensibility multiple neuropathy numb

42、ness type pain type numbness-pain type sensomotor multiple neuropathy acute or sub-acute motor multiple neuropathy asymmetricsingle or m

43、ultiple periphearal neuropathy member or torso mononeural cranial nerves disease radiculopathy proximal motor neuropathy autonomic neuropathy,Autonomic neuropat

44、hydiabetic myelopathy diabetic spinal ataxia spinal muscular atrophyCerebropathy Hypoglycemia cerebropathy diabetic coma cerebrovascular disease,Diabetic sensability multiple n

45、europathy,more common in femaleAverage age of onset is 58.7yearCourse of DM> 15yearsSymptoms of senseNumbness type：large medullated fibersPain type：little medullated fibers and nonmedullated fibersNumbness-pai

46、n type,,Nervous symptom examinationparasthesiaLower limbs pallesthetic disturbance or dissapearTendon reflex low or dissappear Sensory staxiaParatrophy symptomsCharcot arthropathy、ischemic gangrenosis and foot u

47、lcer,Diabetic autonomic neuropathy,Pupil diseaseCardiovascular parafunctionFixed heart ratePostural hypertensionSudden cardiac deathGestrophageal ,diarrheaNeuropathic bladder,erectile failureAbnormal sweating,Glu

48、cosuria：associated with renal threshold of sugar (only for clue)KetonuriaBlood sugar：plasma glucose，PODHBA1c：2?3 months blood sugar levelFructosamine：2?3 weeks blood sugar levelOGTT：2 hour specimenInsulin and C-p

49、eptide release test,Laboratory tests,Diagnosis,Criteria for diagnosing diabetes,FPG Random OGTT plasma glucose 2hPG

50、 mmol/L mmol/L mmol/LDM ≥7.0 ≥11.1 ≥11.1 IGR IFG 6.1≤FPG<7.0 IGT

51、 7.8≤FPG<11.1Normal <6.1 <7.8,Characteristics of new diabetic diagnostic criteria,FPG<6.1mmol/L is normal fasting

52、 glucose，OGTT 2hPG<7.8mmol/L is normal glucose tolerance；Impaired fasting glucose corresponding with impaired glucose tolerance (IFG)：6.1mmol/L ≤FPG<7.0 mmol/L ；The cutoff value of FPG decline from 7.8mmol/L to

53、 7.0mol/L.the cutoff values of OGTT2hrPG and random plasma glucose level are still 11.1mmol/L； FPG is the initial screening test of diabetes ，OGTT is not recommended for routine diagnostic use. The diagnoses of G

54、estational diabetes is not changed,Practical problems in diagnosis,Symptoms ＋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 once,latent aut

55、oimmune diabetes mellitus in adults （LADA）,Adult onsetSymptoms are evidentSecretion function of ?cell is lowGADA positiveHLA-DQ B chain is non aspartate homozygote,Management,Goals,Good metabolism control（blood su

56、gar、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、hyperosmolar nonketotic syndr

57、ome、lactic acidosis）Preventing the development or delaying the progression of the chronic complications of diabetes,Principle of treatment,Early Life-longsynthesisindividual,Goals of control,good avera

58、ge badPBG(mmol/L) fasting 4.4 - 6.1 ?7.0 >7.0 non-fasting 4.4 - 8.0 ?10.0 >10.0HB

59、A1c(％) 7.5 BP(mmHg) 130/80- 140/90 BMI (Kg/m2) M 1.1 1.1-0.9 4.0,Control actuality of DM in Chi

60、na,26 centers、3965 patients28％patients measure HbA1c：8.1?2.6%，52％>7.5％FPG：9.2 ? 3.7mmol/L，55%>7.8 mmol/LDeterming rate of microalbumin in urine ：20％,Diabetes Management Plan,Patient educationHealth nutrition t

61、herapyExercise therapyDrug therapyMonitoring of blood glucose,Phases therapy of DM,Early reaction Patient therapyMedical nutrition therapyExercise therapySingle drug therapydecline of curative effect Combined

62、drug therapySecondary failure、distinct insufficiency of insulinInsulin therapy,Principles of medical nutrition theraphy,rational control of total calorific value Goal ： Keep ideal body weightLoss weight for obese

63、 patientAdd weight for lean patientStandard body weight＝height（cm）－105male： （height－100 ）×0.9female： （height－100 ）×0.85Body mass index（BMI） ：weight（kg）/height2 （m2）,Adult-onset diabetes thermal energy su

64、pply per day （therm/kg standard weight ）,work intension Bodily form in bed light physical middle heavy labor physical physical

65、 labor laborlean 20 ? 25 35 40 >40normal 15 ? 20 30 35 40obesity 15

66、 20 ? 25 30 35,,Nutrition principles of diabetics,Moderate weight control The distribution of total calorfic value ：carbohydrate 55 %?60% fat 20%?25% 1/5、

67、 2/5、 2/5protein 15 %?20% Drink limitation Avoiding ‘diabetic’ foods (which contain sorbitol or frucotose)Aspartame is an acceptable calorie-free sweetenersalt<10g/d，(<3g/day if hypertensive

68、),,,,,Calculation,protein：0.8 ?1.2/kg standard weight fat：0.6 ?1.0/kg standard weightcarbohydrate：total calorific value －calories of protein and fat,Exercise therapy,BenefitsGlycaemic controlIncrease βcell sensitivit

69、y to glucose Blood lipid Weight reductionEstimation of quantity of exercise：heart rate<170－age (year),,Drug therapy,SulfonylureasBiguanidesα-glucosidase inhibitorsTniazolidinedionesMeglitinidesInsulinDry-c