糖尿病英文課件

1、2022-3-7糖尿病英文12022-3-7糖尿病英文2ldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplications2022-3-7糖尿病英文3The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabo

2、lism resulting from defects in insulin secretion, insulin action, or both2022-3-7糖尿病英文4l A metabolic condition characterised by high plasma glucose levels and chronic vascular complicationsl A vascular disease affecting small and large arteries with coexistent metabolic disturbance particularly high

3、 plasma glucose levels2022-3-7糖尿病英文5ldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplications2022-3-7糖尿病英文6lType 1 (betacell destruction, usually leading to absolute insulin deficiency) : Autoimmune: IdiopathiclType 2 (may range from predominantly insulin resistance with rela

4、tive insulin deficiency to a predominantly secretory defect with or without insulin resistance)lOther specific types Genetic defects of betacell function lGenetic defects in insulin actionlDiseases of the exocrine pancreas Endocrinopathies lDrug or chemicalinduced lInfections lUncommon forms of immu

5、nemediated diabeteslOther genetic syndromes sometimes associated with diabeteslGestational diabetes2022-3-7糖尿病英文7lPreviously known as IDDM(Insulin dependent diabetes)lKetosis prone:Usually diagnosed in younger age group( 30 yearsl1 in 1000 population as new cases each year lInsidious presentation wi

6、th symptoms of polyuria, polydipsia, lethargy, weight loss, nausea, vomiting, abdominal cramps, blurred vision and superficial infection. Often discovered at routine medicallThis presentation is the end point of the gradual loss of beta cell function in the setting of Insulin resistancelStrong (90-1

7、00%) concordance in TwinslReavans syndrome or Syndrome X Insulin resistance2022-3-7糖尿病英文14Type 2 diabetesUnderlying insulin resistance genetic and ethnicity Obesity BMI WHR inactivity / low physical fitness intrauterine & childhood factors smoking & drugsImpaired insulin secretionInsulin sec

8、retion worsens with timepost-receptorcellular mechanismsmechanismunclear-cellexhaustion2022-3-7糖尿病英文15Prandial glucoseFasting glucoseInsulin resistanceInsulin secretionPlasma glucose-cell 126 mg/dLyears2022-3-7糖尿病英文16Pancreatic -cell Insulin resistanceLiverHYPERGLYCAEMIAIslet -cell degranulationRedu

9、ced insulin contentMuscle(PKCAdipose tissueDecreased glucose transport& activity (expression) of GLUT-4Increased lipolysisElevated plasma NEFA+-Low plasmainsulinIncreased glucose outputElevatedTNF Insulin resistance and -cell dysfunctionproduce hyperglycaemia in type 2 diabetes2022-3-7糖尿病英文17 LI

10、VER a. increased glycogen hydrolysis to glucose b. increased gluconeogenesis. c. increased triacylglycerol hydrolysis and conversion of glycerol to glucose d. increased conversion of FA and protein to ketones (AcAc and BHB) e. increased protein and amino acid catabolism f. increased production of ur

11、ea2022-3-7糖尿病英文18a. serum glucose is poorly taken up by muscle (decrease GLUT activity)b. saturation of hexokinase activity, inability to retain cellular glu as glu-6-PO4c. increased LPL activity and increased FA productiond. increased b-oxidation, but TCA is overwhelmed because ATP is high alreadye

12、e. increased breakdown of muscle and serum protein into amino acidsf. increased transfer of N onto ALA / GLN and sent back to liver2022-3-7糖尿病英文19a. increased LPL and HSL send more free FA into bloodstreamb. glucose can not be taken into cell via GLUT4 for glycogen synthesisc. active HSL means TAGs

13、are not being made and stored2022-3-7糖尿病英文20Insulin Insulin Macrovascularsensitivity secretion disease 30% 50% 50% 50% 70100% 40% 70% 150% 10% 100% 100%Type 2 diabetesIGTImpaired glucose metabolismNormal glucose metabolism2022-3-7糖尿病英文21lInsulin resistancelHypertensionlDyslipidaemia( increase LDL, d

14、ecreased HDL)lObesitylOther factors: hyperfibrinogenemia, hyperuricaemia, propensity to microvascular diseasesl“Metabolic syndrome” in most cases of type 2 diabetes2022-3-7糖尿病英文22abdominal obesityhigh blood pressureHDL cholesterol VLDL triglyceride small dense LDL hyperinsulinaemiaglucose intoleranc

15、ediabeteshyperuricaemiaPAI-1 fibrinogen factor VII microalbuminuriainsulin resistanceSyndrome of insulin resistanceAKA Reavens syndrome, syndrome Xmetabolic syndrome2022-3-7糖尿病英文23Type 1 diabetestypical onset 20 yearscan start at any agegradual onsetmay be no symptomsoften no weight lossusually obes

16、enot ketoticdetectable C-peptideno autoimmune markers2022-3-7糖尿病英文24Diabetes in pregnancyco-existent or newly diagnosed lifelong diabetes type 1 type 2 (especially in South Asian women) other specific types of diabetesgestational diabetes2022-3-7糖尿病英文25lGenetic defects of betacell functionChrme 20,

17、HNF4_ (MODY1)Chrme 7, glucokinase (MODY2)Chrme 12, HNF1_ (MODY3)Chrme 13, IPF1 (MODY4)Mitochondrial DNA 3243 mutationlGenetic defects in insulin actionType A insulin resistanceLeprechaunismRabsonMendenhall syndromeLipoatrophic diabetes & OtherslDiseases of the exocrine -pancreasFibrocalculous pa

18、ncreatopathyPancreatitisTrauma / pancreatectomyNeoplasiaCystic fibrosisHaemochromatosis & OtherslEndocrinopathiesCushings syndromeAcromegalyPhaeochromocytomaGlucagonomaHyperthyroidismSomatostatinoma & Others 2022-3-7糖尿病英文26lInfectionsCongenital rubellaCytomegalovirusOthers lUncommon forms of

19、 immunemediated diabetes Insulin autoimmune syndrome (antibodies to insulin)Antiinsulin receptor antibodies“Stiff Man” syndromeOtherslDrug or Chemicalinduced Diabetes lNicotinic acidlGlucocorticoidslThyroid hormonelAlphaadrenergic agonistslBetaadrenergic agonistslThiazideslDilantinlPentamidinelVacor

20、lInterferonalpha therapylOthers2022-3-7糖尿病英文27lBecause glucose is not getting into cells, metabolism changes Catabolism of fats and proteins instead of carbohydrates Leads to increased fatty acids and ketoacids Ketoacidosis results in lowering of pH Diabetic coma Decompensated metabolic acidosis and

21、 death2022-3-7糖尿病英文28ldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplications2022-3-7糖尿病英文29lHyperglycemia Dehydration Excessive thirst and urination Excessive hungerlGlycosuria (glu spills into urine: 180mg/dl)2022-3-7糖尿病英文30Symptoms of diabetes due to hyperglycaemiaplasma

22、glucose renal thresholdabout 12 mmol/Lglucose in urineosmotic diuresisurine volumethirstgenital thrushweight losshyperglycaemiatiredness2022-3-7糖尿病英文31Symptoms of diabetes due to hyperglycaemiahyperglycaemiaswelling of lensblurred visioncerebral effectslightheadednessmalaisemental changes2022-3-7糖尿病

23、英文32ldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplications2022-3-7糖尿病英文33lSymptoms of diabetes & a casual glucose concentration more than or equal to 200 mg/dl(11.1 mmol/l); Casual is defined as any time of day without regards to time since last meal. The classic sympt

24、oms of diabetes include polyuria, polydipsia and unexplained weight lossorlFPG more than or equal to 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hoursorl2 hour PG more than or equal to 200mg/dl(11.1 mmol/l) during an OGTT. The test should be performed as described

25、by WHO, using a glucose load containing the equivalent of 75 g glucose dissolved in water2022-3-7糖尿病英文34whole bloodplasmaDiabetes mellitus (fasting) 6.1mmol/l 7.0mmol/l2 hour post glucose load 10.0 mmol/l 11.1mmol/lIGT (fasting) 6.1mmol/l 6.7 mmol/l 7.8 mmol/l IFG (fasting) 5.6 mmol/l 6.1mmol/l&

26、6.1 mmol/l &6.7 mmol/l 8%)2022-3-7糖尿病英文40lGlucose: FBG, 2 hr OGTT ,FBG is simple, accurate, convenient for patientlGlycohemoglobinlCreatininelUrinalysis glucose ketone bodieslMicroalbuminlDyslipidemialInsulin c-peptide2022-3-7糖尿病英文41ldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreat

27、mentlcomplications2022-3-7糖尿病英文42lNon Pharmacological lExercise and EducationlDiet, Low in fat, low refined sugars, high carbohydrate, high fibre, low calories if obese, spacing of meals (Healthy eating)lLow cholesterol and triglyceride diet if hyperlipidemialAll Type 1 patients will require Insulin

28、 and type 2 can be on diet only, tablets or insulin treated2022-3-7糖尿病英文43Treatment of diabetestype 1type 2GDMdiet, exercise & insulindiet, exercisemetformin or sulphonylurea alonemetformin and sulphonylureametformin, sulphonylurea & thiazolidinedioneinsulindietinsulin2022-3-7糖尿病英文44Drugs to

29、 treat hyperglycaemiaInsulin and insulin analoguesInsulin secretagoguessulphonylureanon-sulphonylureaInsulin sensitizersbiguanidethiazolidinedioneIntestinal absorption inhibitorsacarboseorlistatlispro insulinaspart insulininsulin glarginegliclazide, glibenclamiderepaglinide, nateglinidemetforminrosi

30、glitazone, pioglitazone2022-3-7糖尿病英文45sulphonylurea agentsgliclazide, glibenclamide, glimepiride bind to receptors on islet cells increase insulin secretion from islet cells long duration of action 12-48 hours Advers effect increase weight can cause hypoglycaemia can cause rashes Contraindications s

31、ulfa allergy type 1 DM, DKA2022-3-7糖尿病英文46l Mechanism: Binds to site on beta-cell membrane leading to insulin release Rapid oral absorption and elimination for use in controlling post-prandial hyperglycemia. Examples: repaglinide, nateglinide Contraindications Type 1 DM, DKA Adverse effects: Hypogly

32、cemia, weight gain2022-3-7糖尿病英文47metformin lowers liver glucose output increases tissue glucose uptake acts like an insulin sensitizer mild induction of nausea possible interference with food absorption no effect on weight used alone does not cause hypoglycaemia reduces risk of myocardial infarction

33、 1/3 patients get diarrhoea, wind or abdominal pain not used in renal failure, heart failure or severe intercurrent illness2022-3-7糖尿病英文48lRenally excreted, not metabolizedlPotentially fatal lactic acidosis Contraindications: renal insufficiency (decreases drug clearance) hepatic dysfunction (decrea

34、ses lactate metabolism) tissue anoxia (increase lactate production)2022-3-7糖尿病英文49acarbose -glucosidase inhibitor blocks digestion and absorption of sugars from bowel lowers blood glucose and insulin levels after meals weak antidiabetic drug no effect on weight used alone does not cause hypoglycaemi

35、a not absorbed into body 1/2 patients get diarrhoea, wind or abdominal pain2022-3-7糖尿病英文50lUnabsorbed CHOs: Bacterial fermentation in colon results in abdominal pain, flatulence from gas Osmotic diarrhealElevated serum transaminaseslMetabolized and excreted in the GI tract Some metabolite is absorbe

36、d in GI and renally excreted lContraindicated for patients with chronic or inflammatory bowel diseaselRelatively weak antidiabetic effect, usually used adjunctively.2022-3-7糖尿病英文51 MechanismBind to PPAR-gamma receptor in peripheral tissues mainly skeletal muscle Result in expression of cell-surface

37、glucose transporters. Cautions Not recommended in NYHA Class III/IV CHF May cause fluid retention and precipitate CHF May cause mild anemia (? Dilutional effect)2022-3-7糖尿病英文52 Associated with weight gain Liver toxicity seen in older TZD (troglitazone) but not with newer agents; recommended to check

38、 LFTs q 2 mo for 1st year of use. Advantages No hypoglycemia Possible improvement in vascular function2022-3-7糖尿病英文53lMetabolism: hepatic conjugation by the CYP450 systemlExcretion: biliarylHepatotoxic, especially troglitazone, and contraindicated in cases of hepatic dysfunctionlCan cause edema and

39、hypoglycemia when used in combination with other hypoglycemics2022-3-7糖尿病英文54Treating hyperglycaemia in type 2 diabetesdietary changeexerciseobesemetforminnot obesesulphonylureametformin & sulphonylureaglitazone & metformin OR glitazone & sulphonylureainsulin metforminAim: HbA1c 6.5%Fast

40、ing glucose microaneurysms edema Proliferative (VEGF) New blood vessels that extend into vitreous, bleeding loss of visionlGlaucoma, intraocular pressure ocular tissue damage 2022-3-7糖尿病英文66 Non-proliferative diabetic retinopathy (NPDR) Earliest stage Microaneurisms and intraretinal “dot and blot” h

41、emorrhages Macular edema or hard exudates at/near macula can cause visual impairment Proliferative diabetic retinopathy (PDR) Nonperfusion of retina angiogenesis growth of abnormal new vessels extending onto inner surface of retina or into vitreous cavity. Substantial risk for rupture hemorrhage or

42、retinal detachment. Treated with panretinal photcoagulation.2022-3-7糖尿病英文67Diabetic nephropathy Affects 25% of type 1 and type 2 diabetes patients Risk factors similar to those for retinopathy Is a progressive condition leading to renal failure Characterised by proteinuria and high blood pressure202

43、2-3-7糖尿病英文68lGlomerulosclerosis (Capillary basement membr. thickening)lMicroalbuminuria (30-300 mg/24hr)lHyperfiltration (GFR)lAlbuminuria (300 mg/24hr)lHypertensionlNephrotic syndrome (approx 1/3 of Type 1 progress to end stage renal dis requiring dialysis)lRenal failure ( GFR, Creat)2022-3-7糖尿病英文6

44、9lTypes of Neuropathy Sensory Pain/ paresthesias in feet particularly at night Numbness in “stocking and glove” distribution High risk for foot ulceration Autonomic Cardiovascular: resting tachycardia, painless MI, orthostasis GI: esphageal dysfunction, gastroparesis, diabetic diarrhea, constipation

45、, fecal incontinence Genitourinary ED, retrograde ejaculation, neurogenic bladder Other “gustatory” sweating, heat intolerance2022-3-7糖尿病英文70Diabetic neuropathy Affects type 1 and type 2 diabetes patients similarly Risk factors similar to those for retinopathy may lead to loss of sensation in feet f

46、oot ulceration erectile dysfunction gastroparesis and vomiting postural hypotension2022-3-7糖尿病英文71lMacrovascular ( 70% hosp/deaths) 60% of patients die of coronary disease 10% of patients die of stroke 10% suffer from fatal complications related to peripheral vascular disease2022-3-7糖尿病英文72lAnginalM

47、IlSilent infarctlCCFlECGlCardiac enzymeslTroponin IlExercise stress testlEchocardiographylAngiographylAngioplasty/CABG2022-3-7糖尿病英文73lTIAslCVAslDementialCT scanlCarotid DopplerslTreat risk factorslCarotid bypass surgery2022-3-7糖尿病英文74lIntermittent ClaudicationlCold LegslPulseless LeglFoot UlcerslGan

48、grenelDoppler StudieslDuplex ScanninglAngiographylAngioplastylTreat risk factors2022-3-7糖尿病英文75lNeuropathylPVDlCharcot ArthropathylUlcerationlMRIlAngiography2022-3-7糖尿病英文76lAcute (several days rather than hours)lCaused by Inadequate insulin Infection Stress Underdosing Food or alcohol bingelResults

49、in hyperglycemia & mobilization of lipids2022-3-7糖尿病英文77lType 1 Diabetics, Severe Insulin Def.lBreakdown of fat stores Fatty AcidslOxidation Ketone Bodies ( by glucagon)lAccumul of Acetoacetic acid/ hydroxybutyric acid Plasma Hl Metabolic Ketoacidosis (Hydration vs dehydration) 2022-3-7糖尿病英文78lD

50、KA results in altered lipid metabolism increased concentrations of total lipids, cholesterol, triglycerides, and free fatty acids free fatty acids are shunted into ketone body formation due to lack of insulin; the rate of formation exceeds the capacity for their peripheral utilization and renal excr

51、etion leading to accumulation of ketoacids, and therefore metabolic acidosislWith progressive dehydration, acidosis, hyperosmolality, and diminished cerebral oxygen utilization, consciousness becomes impaired, and the patient ultimately becomes comatose2022-3-7糖尿病英文79 early manifestations are mild a

52、nd include vomiting, polyuria, and dehydration More severe cases include Kussmaul respirations, odor of acetone on the breath abdominal pain or rigidity may be present and mimic acute appendicitis or pancreatitis cerebral obtundation and coma ultimately ensue2022-3-7糖尿病英文80lLaboratory findings inclu

53、de glucosuria, ketonuria, hyperglycemia, ketonemia, and metabolic acidosis. Serum amylase may be elevated. Leukocytosis is common2022-3-7糖尿病英文81lDKA exists when there is hyperglycemia ( 300 mg/dL), ketonemia, acidosis, glucosuria, and ketonuria2022-3-7糖尿病英文82lDKA must be differentiated from acidosis

54、 and coma due to other causes: hypoglycemia, uremia, gastroenteritis with metabolic acidosis, lactic acidosis, salicylate intoxication, encephalitis2022-3-7糖尿病英文83lTreatment is divided into 3 phases treatment of ketoacidosis transition period continuing phase and guidancelGoals of treatment of DKA i

55、ntravascular volume expansion correction of deficits in fluids, electrolytes, and acid-base status initiation of insulin therapy to correct catabolism, acidosis2022-3-7糖尿病英文84lTreatment Administer insulin Rehydrate Replace electrolytes Treat acidosis with bicarbonate2022-3-7糖尿病英文85lIntravascular vol

56、ume expansion dehydration is most commonly in the order of 10% initial hydrating fluid should be isotonic saline this alone will often slightly lower the blood glucoselTreatment of electrolyte abnormalities serum K+ is often elevated, though total body K+ is depleted K+ is started early as resolutio

57、n of acidosis and the administration of insulin will cause a decrease in serum K+2022-3-7糖尿病英文86l“Maintenance” IV fluid at a rate of 2000 - 2400 cc/m2/day consists of 2/3 NS (0.66%) or NS NS is added to IVF when blood glucose is 250 mg/dL 5% Dextrose or 5% GNS is added when blood glucose is 250 mg/d

58、L2022-3-7糖尿病英文87lInsulin Therapy continuous infusion of low-dose insulin IV ( 0.1 U/kg/hr) is effective, simple, and physiologically sound goal is to slowly decrease serum glucose ( dehydration severe dehydration comalNo keto acids, lipolysis inhibited by insulin 2022-3-7糖尿病英文91lResults in blood glu

59、cose levels up tol1000mg/dL.lInsulin activity prevents buildup of ketones.lSustained hyperglycemia results in markedldehydration.lOften related to dialysis, infection, and medications.lVery high mortality rate 2022-3-7糖尿病英文92Signs & SymptomslIncreased urination and thirst, orthostaticlhypotensio

60、n, and altered mental status.lGradual onset over days. Assessment & ManagementlDifficult to distinguish from diabeticlketoacidosis in the prehospital setting.lTreatment is identical to diabeticlketoacidosis.lTreat for dehydration 2022-3-7糖尿病英文93 Thanks! 2022-3-7糖尿病英文942022-3-7糖尿病英文952022-3-7糖尿病英文96lWhat is Diabetes Mellitus?lThe difference of WHO 1985 and