糖尿病英文ppt课件

1、ldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplicationsThe term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin sec

2、retion, insulin action, or bothl 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 plasma glucose levelsldefinitionltypeslsymptoms ldiagno

3、sislLaboratory findingsltreatmentlcomplicationslType 1 (betacell destruction, usually leading to absolute insulin deficiency) : Autoimmune: IdiopathiclType 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin

4、resistance)lOther specific types lGenetic defects of betacell function lGenetic defects in insulin actionlDiseases of the exocrine pancreas Endocrinopathies lDrug or chemicalinduced lInfections lUncommon forms of immunemediated diabeteslOther genetic syndromes sometimes associated with diabeteslGest

5、ational diabeteslPreviously 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 with symptoms of polyuria, polydipsia, lethargy, weight loss, nausea, vomiting, abdominal cramps, b

6、lurred 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 (90-100%) concordance in TwinslReavans syndrome or Syndrome X Insulin resistanceType 2 diabetesUnderly

7、ing insulin resistancegenetic and ethnicityObesity BMI WHR inactivity / low physical fitnessintrauterine & childhood factorssmoking & drugsImpaired insulin secretionInsulin secretion worsens with timepost-receptorcellular mechanismsmechanismunclear-cellexhaustionPrandial glucoseFasting gluco

8、seInsulin resistanceInsulin secretionPlasma glucose-cell 126 mg/dLyearsPancreatic -cell Insulin resistanceLiverHYPERGLYCAEMIAIslet -cell degranulationReduced insulin contentMuscle(PKCAdipose tissueDecreased glucose transport& activity (expression) of GLUT-4Increased lipolysisElevated plasma NEFA

9、+-Low plasmainsulinIncreased glucose outputElevatedTNFInsulin resistance and -cell dysfunctionproduce hyperglycaemia in type 2 diabetes LIVER a. increased glycogen hydrolysis to glucose b. increased gluconeogenesis. c. increased triacylglycerol hydrolysis and conversion of glycerol to glucose d. inc

10、reased conversion of FA and protein to ketones (AcAc and BHB) e. increased protein and amino acid catabolism f. increased production of ureaa. 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. incr

11、eased LPL activity and increased FA productiond. increased b-oxidation, but TCA is overwhelmed because ATP is high alreadyee. increased breakdown of muscle and serum protein into amino acidsf. increased transfer of N onto ALA / GLN and sent back to livera. increased LPL and HSL send more free FA int

12、o bloodstreamb. glucose can not be taken into cell via GLUT4 for glycogen synthesisc. active HSL means TAGs are not being made and storedInsulin Insulin Macrovascularsensitivity secretion disease 30% 50% 50% 50% 70100% 40% 70% 150% 10% 100% 100%Type 2 diabetesIGTImpaired glucose metabolismNormal glu

13、cose metabolismlInsulin resistancelHypertensionlDyslipidaemia( increase LDL, decreased HDL)lObesitylOther factors: hyperfibrinogenemia, hyperuricaemia, propensity to microvascular diseasesl“Metabolic syndrome in most cases of type 2 diabetesabdominal obesityhigh blood pressureHDL cholesterol VLDL tr

14、iglyceride small dense LDL hyperinsulinaemiaglucose intolerancediabeteshyperuricaemiaPAI-1 fibrinogen factor VII microalbuminuriainsulin resistanceSyndrome of insulin resistanceAKA Reavens syndrome, syndrome Xmetabolic syndromeType 1 diabetestypical onset 20 yearscan start at any agegradual onsetmay

15、 be no symptomsoften no weight lossusually obesenot ketoticdetectable C-peptideno autoimmune markersDiabetes in pregnancyco-existent or newly diagnosed lifelong diabetestype 1 type 2 (especially in South Asian women) other specific types of diabetesgestational diabeteslGenetic defects of betacell fu

16、nctionlChrme 20, HNF4_ (MODY1)lChrme 7, glucokinase (MODY2)lChrme 12, HNF1_ (MODY3)lChrme 13, IPF1 (MODY4)lMitochondrial DNA 3243 mutationlGenetic defects in insulin actionlType A insulin resistancelLeprechaunismlRabsonMendenhall syndromelLipoatrophic diabetes & OtherslDiseases of the exocrine -

17、pancreaslFibrocalculous pancreatopathylPancreatitislTrauma / pancreatectomylNeoplasialCystic fibrosislHaemochromatosis & OtherslEndocrinopathieslCushings syndromelAcromegalylPhaeochromocytomalGlucagonomalHyperthyroidismlSomatostatinoma & Others lInfectionslCongenital rubellalCytomegalovirusl

18、Others lUncommon forms of immunemediated diabetesl Insulin autoimmune syndrome (antibodies to insulin)lAntiinsulin receptor antibodiesl“Stiff Man syndromelOtherslDrug or Chemicalinduced Diabetes lNicotinic acidlGlucocorticoidslThyroid hormonelAlphaadrenergic agonistslBetaadrenergic agonistslThiazide

19、slDilantinlPentamidinelVacorlInterferonalpha therapylOtherslBecause glucose is not getting into cells, metabolism changeslCatabolism of fats and proteins instead of carbohydrateslLeads to increased fatty acids and ketoacidslKetoacidosis results in lowering of pHlDiabetic comalDecompensated metabolic

20、 acidosis and deathldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplicationslHyperglycemialDehydrationlExcessive thirst and urinationlExcessive hungerlGlycosuria (glu spills into urine: 180mg/dl)Symptoms of diabetes due to hyperglycaemiaplasma glucose renal thresholdabout 12

21、mmol/Lglucose in urineosmotic diuresisurine volumethirstgenital thrushweight losshyperglycaemiatirednessSymptoms of diabetes due to hyperglycaemiahyperglycaemiaswelling of lensblurred visioncerebral effectslightheadednessmalaisemental changesldefinitionltypeslsymptoms ldiagnosislLaboratory findingsl

22、treatmentlcomplicationslSymptoms 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 symptoms of diabetes include polyuria, polydipsia and unexplained weight losslorlF

23、PG more than or equal to 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hourslorl2 hour PG more than or equal to 200mg/dl(11.1 mmol/l) during an OGTT. The test should be performed as described by WHO, using a glucose load containing the equivalent of 75 g glucose diss

24、olved in waterwhole 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&6.1 mmol/l &6.7 mmol/l 8%)lGlucose: FBG, 2 hr OGTT ,FBG is simple, accurate, convenien

25、t for patientlGlycohemoglobinlCreatininelUrinalysis glucose ketone bodieslMicroalbuminlDyslipidemialInsulin c-peptideldefinitionltypeslsymptoms ldiagnosislLaboratory findingsltreatmentlcomplicationslNon Pharmacological lExercise and EducationlDiet, Low in fat, low refined sugars, high carbohydrate,

26、high fibre, low calories if obese, spacing of meals (Healthy eating)lLow cholesterol and triglyceride diet if hyperlipidemialAll Type 1 patients will require Insulin and type 2 can be on diet only, tablets or insulin treatedTreatment of diabetestype 1type 2GDMdiet, exercise & insulindiet, exerci

27、semetformin or sulphonylurea alonemetformin and sulphonylureametformin, sulphonylurea & thiazolidinedioneinsulindietinsulinDrugs to treat hyperglycaemiaInsulin and insulin analoguesInsulin secretagoguessulphonylureanon-sulphonylureaInsulin sensitizersbiguanidethiazolidinedioneIntestinal absorpti

28、on inhibitorsacarboseorlistatlispro insulinaspart insulininsulin glarginegliclazide, glibenclamiderepaglinide, nateglinidemetforminrosiglitazone, pioglitazonesulphonylurea agentsgliclazide, glibenclamide, glimepiridebind to receptors on islet cellsincrease insulin secretion from islet cellslong dura

29、tion of action 12-48 hours Advers effectincrease weightcan cause hypoglycaemiacan cause rashes Contraindications sulfa allergy type 1 DM, DKAl Mechanism: Binds to site on beta-cell membrane leading to insulin releaselRapid oral absorption and elimination for use in controlling post-prandial hypergly

30、cemia.lExamples: repaglinide, nateglinidelContraindicationslType 1 DM, DKAlAdverse effects: Hypoglycemia, weight gainmetforminlowers liver glucose outputincreases tissue glucose uptakeacts like an insulin sensitizermild induction of nauseapossible interference with food absorptionno effect on weight

31、used alone does not cause hypoglycaemiareduces risk of myocardial infarction1/3 patients get diarrhoea, wind or abdominal painnot used in renal failure, heart failure or severe intercurrent illnesslRenally excreted, not metabolizedlPotentially fatal lactic acidosislContraindications:lrenal insuffici

32、ency (decreases drug clearance)lhepatic dysfunction (decreases lactate metabolism)ltissue anoxia (increase lactate production)acarbose-glucosidase inhibitorblocks digestion and absorption of sugars from bowellowers blood glucose and insulin levels after mealsweak antidiabetic drugno effect on weight

33、used alone does not cause hypoglycaemianot absorbed into body1/2 patients get diarrhoea, wind or abdominal painlUnabsorbed CHOs:lBacterial fermentation in colon results in abdominal pain, flatulence from gaslOsmotic diarrhealElevated serum transaminaseslMetabolized and excreted in the GI tractlSome

34、metabolite is absorbed in GI and renally excreted lContraindicated for patients with chronic or inflammatory bowel diseaselRelatively weak antidiabetic effect, usually used adjunctively. MechanismBind to PPAR-gamma receptor in peripheral tissues mainly skeletal muscle Result in expression of cell-su

35、rface glucose transporters. Cautions Not recommended in NYHA Class III/IV CHF May cause fluid retention and precipitate CHF May cause mild anemia (? Dilutional effect) Associated with weight gain Liver toxicity seen in older TZD (troglitazone) but not with newer agents; recommended to check LFTs q 2

36、 mo for 1st year of use. Advantages No hypoglycemia Possible improvement in vascular functionlMetabolism: hepatic conjugation by the CYP450 systemlExcretion: biliarylHepatotoxic, especially troglitazone, and contraindicated in cases of hepatic dysfunctionlCan cause edema and hypoglycemia when used i

37、n combination with other hypoglycemicsTreating hyperglycaemia in type 2 diabetesdietary changeexerciseobesemetforminnot obesesulphonylureametformin & sulphonylureaglitazone & metformin OR glitazone & sulphonylureainsulin metforminAim: HbA1c 6.5%Fasting glucose microaneurysms edemalProlif

38、erative (VEGF) New blood vessels that extend into vitreous, bleeding loss of visionlGlaucoma, intraocular pressure ocular tissue damage Non-proliferative diabetic retinopathy (NPDR) Earliest stage Microaneurisms and intraretinal “dot and blot hemorrhages Macular edema or hard exudates at/near macula

39、 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 retinal detachment. Treated with panretinal photcoagulat

40、ion.Diabetic nephropathyAffects 25% of type 1 and type 2 diabetes patientsRisk factors similar to those for retinopathyIs a progressive condition leading to renal failureCharacterised by proteinuria and high blood pressurelGlomerulosclerosis (Capillary basement membr. thickening)lMicroalbuminuria (3

41、0-300 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)lTypes of NeuropathylSensorylPain/ paresthesias in feet particularly at nightlNumbness in “stocking and

42、glove distributionlHigh risk for foot ulcerationlAutonomiclCardiovascular: resting tachycardia, painless MI, orthostasislGI: esphageal dysfunction, gastroparesis, diabetic diarrhea, constipation, fecal incontinencelGenitourinarylED, retrograde ejaculation, neurogenic bladderlOtherl“gustatory sweatin

43、g, heat intoleranceDiabetic neuropathyAffects type 1 and type 2 diabetes patients similarlyRisk factors similar to those for retinopathymay lead toloss of sensation in feetfoot ulcerationerectile dysfunctiongastroparesis and vomitingpostural hypotensionlMacrovascular ( 70% hosp/deaths)l60% of patien

44、ts die of coronary diseasel10% of patients die of strokel10% suffer from fatal complications related to peripheral vascular diseaselAnginalMIlSilent infarctlCCFlECGlCardiac enzymeslTroponin IlExercise stress testlEchocardiographylAngiographylAngioplasty/CABGlTIAslCVAslDementialCT scanlCarotid Dopple

45、rslTreat risk factorslCarotid bypass surgerylIntermittent ClaudicationlCold LegslPulseless LeglFoot UlcerslGangrenelDoppler StudieslDuplex ScanninglAngiographylAngioplastylTreat risk factorslNeuropathylPVDlCharcot ArthropathylUlcerationlMRIlAngiographylAcute (several days rather than hours)lCaused b

46、y lInadequate insulinlInfection lStresslUnderdosinglFood or alcohol bingelResults in hyperglycemia & mobilization of lipidslType 1 Diabetics, Severe Insulin Def.lBreakdown of fat stores Fatty AcidslOxidation Ketone Bodies ( by glucagon)lAccumul of Acetoacetic acid/ hydroxybutyric acid Plasma Hl

47、Metabolic Ketoacidosis l (Hydration vs dehydration) lDKA results in altered lipid metabolismlincreased concentrations of total lipids, cholesterol, triglycerides, and free fatty acidslfree fatty acids are shunted into ketone body formation due to lack of insulin; the rate of formation exceeds the ca

48、pacity for their peripheral utilization and renal excretion 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 c

49、omatose early manifestations are mild and 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 ensuelL

50、aboratory findings include glucosuria, ketonuria, hyperglycemia, ketonemia, and metabolic acidosis. Serum amylase may be elevated. Leukocytosis is commonlDKA exists when there is hyperglycemia ( 300 mg/dL), ketonemia, acidosis, glucosuria, and ketonurialDKA must be differentiated from acidosis and c

51、oma due to other causes:lhypoglycemia, uremia, gastroenteritis with metabolic acidosis, lactic acidosis, salicylate intoxication, encephalitislTreatment is divided into 3 phasesltreatment of ketoacidosisltransition periodlcontinuing phase and guidancelGoals of treatment of DKAlintravascular volume e

52、xpansionlcorrection of deficits in fluids, electrolytes, and acid-base statuslinitiation of insulin therapy to correct catabolism, acidosislTreatmentlAdminister insulinlRehydratelReplace electrolyteslTreat acidosis with bicarbonatelIntravascular volume expansionldehydration is most commonly in the o

53、rder of 10%linitial hydrating fluid should be isotonic salinelthis alone will often slightly lower the blood glucoselTreatment of electrolyte abnormalitieslserum K+ is often elevated, though total body K+ is depletedlK+ is started early as resolution of acidosis and the administration of insulin wil

54、l cause a decrease in serum K+l“Maintenance IV fluid at a rate of 2000 - 2400 cc/m2/day consists of 2/3 NS (0.66%) or NSlNS is added to IVF when blood glucose is 250 mg/dLl5% Dextrose or 5% GNS is added when blood glucose is 250 mg/dLlInsulin Therapylcontinuous infusion of low-dose insulin IV ( 0.1

55、U/kg/hr) is effective, simple, and physiologically soundlgoal is to slowly decrease serum glucose ( dehydration severe dehydration comalNo keto acids, lipolysis inhibited by insulin lResults in blood glucose levels up tol1000mg/dL.lInsulin activity prevents buildup of ketones.lSustained hyperglycemi

56、a results in markedldehydration.lOften related to dialysis, infection, and medications.lVery high mortality rate Signs & SymptomsIncreased urination and thirst, orthostatichypotension, and altered mental status.Gradual onset over days. Assessment & ManagementDifficult to distinguish from dia

57、beticketoacidosis in the prehospital setting.Treatment is identical to diabeticketoacidosis.Treat for dehydration Thanks! lWhat is Diabetes Mellitus?lThe difference of WHO 1985 and ADA 1997 about classification of diabetes.lThe difference between type 1 diabetes and type 2 diabetes.lWhat are macrovascu