医学课件：糖尿病(英文版).pptx

1、D i a b e t e s Me l l i t u s Diabetes mellitus(DM)is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production,insulin action,or both.The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperg

2、lycaemia with disturbances of carbohydrate,fat and protein metabolism resulting from defects in insulin secretion,insulin action,or both.The effects of diabetes mellitus include longterm damage,dysfunction and failure of various organs.D i a b e t e s m e l l i t u s (D M)i s a g rInsulin deficiency

3、Insulin resistanceHyperglycemiaCarbohydrateFatProteinLong-term damagesin various organsD e f i n i t i o n I n s u l i n d e f i c i e n c y I nType 1 Diabetes Mellitus Type 2 Diabetes MellitusGestational Diabetes Mellitus(GDM)Other types:vLADA(Latent Autoimmune Diabetes in Adults)vMODY(maturity-ons

4、et diabetes of youth)vSecondary Diabetes MellitusT y p e 1 D i a b e t e s Me l l i t u s T y p e sPreviously called insulin-dependent diabetes mellitus(IDDM)or juvenile-onset diabetes.Type 1 diabetes develops when the bodys immune system destroys pancreatic beta cells,the only cells in the body tha

5、t make the hormone insulin that regulates blood glucose.This form of diabetes usually strikes children and young adults,although disease onset can occur at any age.Type 1 diabetes may account for 5%to 10%of all diagnosed cases of diabetes.Risk factors for type 1 diabetes may include autoimmune,genet

6、ic,and environmental factors.P r e v i o u s l y c a l l e d i n s u l i n-d e p ePreviously called non-insulin-dependent diabetes mellitus(NIDDM)or adult-onset diabetes.Type 2 diabetes may account for about 90%to 95%of all diagnosed cases of diabetes.It usually begins as insulin resistance,a disord

7、er in which the cells do not use insulin properly.As the need for insulin rises,the pancreas gradually loses its ability to produce insulin.Type 2 diabetes is associated with older age,obesity,family history of diabetes,history of gestational diabetes,impaired glucose metabolism,physical inactivity,

8、and race/ethnicity.Type 2 diabetes is increasingly being diagnosed in children and adolescents.P r e v i o u s l y c a l l e d n o n-i n s u l i n-医学课件：糖尿病(英文版)医学课件：糖尿病(英文版)医学课件：糖尿病(英文版)A form of glucose intolerance that is diagnosed in some women during pregnancy.Gestational diabetes occurs more fr

9、equently among African Americans,Hispanic/Latino Americans,and American Indians.It is also more common among obese women and women with a family history of diabetes.During pregnancy,gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infan

10、t.After pregnancy,5%to 10%of women with gestational diabetes are found to have type 2 diabetes.Women who have had gestational diabetes have a 20%to 50%chance of developing diabetes in the next 5-10 years.A f o r m o f g l u c o s e i n t o l e r a n c e Gestational diabetes mellitus(GDM):any degree

11、of glucose intolerance with onset or first recognition during pregnancy.May go away after the baby is bornBut some women with this type of diabetes may be more likely to develop permanent diabetes after pregnancyCan cause problems for the baby including heart and lung problems and problems with the

12、babys sugarG D MG e s t a t i o n a l d i a b e t e s m e l l i tOther specific types of diabetes result from specific genetic conditions(such as maturity-onset diabetes of youth),surgery,drugs,malnutrition,infections,and other illnesses.Such types of diabetes may account for 1%to 5%of all diagnosed

13、 cases of diabetes.O t h e r s p e c i f i c t y p e s o f d i a b e tLatent Autoimmune Diabetes in Adults(LADA)is a form of autoimmune(type1diabetes)which is diagnosed in individuals who are older than the usual age of onset of type 1 diabetes.Alternate terms that have been used for LADA include La

14、te-onset Autoimmune Diabetes of Adulthood,Slow Onset Type 1 diabetes,and sometimes also Type 1.5 diabetes”.Often,patients with LADA are mistakenly thought to have type2diabetes,based on their age at the time of diagnosis.L a t e n t A u t o i m m u n e D i a b e t e s i n L A D AMODY Maturity Onset

15、Diabetes of the YoungMODY is a monogenic form of diabetes with an autosomal dominant mode of inheritance:Mutations in any one of several transcription factors or in the enzyme glucokinase lead to insufficient insulin release from pancreatic-cells,causing MODY.Different subtypes of MODY are identifie

16、d based on the mutated gene.MODY MutationMODY 1HNF-4aMODY 2GlucokinaseMODY 3HNF-1aMODY 4IPF-1MODY 5HNF-1bMODY 6NeuroD1MO D Y MO D Y Mu t a t i o n MO D Y 1 H N F-4 a MGlucokinase MODY requires no treatment,while transcription factor MODY(i.e.Hepatocyte nuclear factor-1alpha)requires low-dose sulfony

17、lurea therapy.MO D Y G l u c o k i n a s e MO D Y r e q u i r e sAcromegaly,-GHCushing syndrome,-Cortisol Thyrotoxicosis,-T3 T4Pheochromocytoma,PHA -CA,catecholamine Cancer,-lung cancerACTHChronic pancreatitis,-insulin insufficiency Drug induced hyperglycemia:Beta-blockers-Inhibit insulin secretion.

18、Corticosteroids-Cause peripheral insulin resistance and gluconeogensis.Hormones which can increase glucoseS e c o n d a r y D MH o r m o n e s w h i c h c a nType 1 DMType 1 DM-Polyuria-Polydipsia-Polyphagia-Weight loss-Weakness-Dry skin-Ketoacidosis Type 2 DM-Patients can be asymptomatic-Polyuria-P

19、olydipsia-Polyphagia-Fatigue-Weight loss-Most patients are discovered while performing urine glucose screeningC l i n i c a l P r e s e n t a t i o n T y p e 1 D MD i a g n o s i s o f D i a b e t e s Me l l i t u s1.Glucosuria1.Glucosuria To detect glucose in urine2.KetonuriaTo detect ketonbodies i

20、n urine3.Fasting blood glucose3.Fasting blood glucoseGlucose blood concentration in samples obtained after atleast 8 hours of the last meal L a b o r a t o r y T e s t s 1.G l u c o s u r i a 24.Random Blood glucose Glucose blood concentration in samples obtained at any time regardless the time of t

21、he last meal5.Glucose tolerance test5.Glucose tolerance test75 gm of glucose are given to the patient with 300 ml of water after an overnight fastBlood samples are drawn 1,2,and 3 hours after taking the glucoseThis is a more accurate test for glucose utilization if the fasting glucose is borderline

22、Plus insulin release test(IRT)and C-peptide test beta cell reserve evaluation4.R a n d o m B l o o d g l u c o s e L a b o r a t5.Glucose tolerance test(cont.)5.Glucose tolerance test(cont.)It is estimated more than 50%of beta cells were lost at the onset of diabetes.Disulfide bond5.G l u c o s e t

23、o l e r a n c e t e s t (c o nV a l u e s o f D i a g n o s i s o f D i a b e t e75 gm of glucose are given to the patient with 300 ml of water after an overnight fast(12h)-24-28wTimeGlucose(mmol/L)0h5.11h10.02h8.5One time-point exceeds normal range GDMGDM GLUCOSE TESTV a l u e s o f D i a g n o s i

24、 s o f D i a b e t e6.Glycosylated hemoglobin(HbA1C)6.Glycosylated hemoglobin(HbA1C)HbA1C is formed by condensation of glucose with free amino groups of the globin component of hemoglobinNormally it comprises 4-6%of the total hemoglobin.Increase in the glucose blood concentration increases the glyca

25、ted hemoglobin fraction.HbA1C reflects the glycemic state during the preceding 8-12 weeks.6.G l y c o s y l a t e d h e m o g l o b i n (H b7.Serum Fructosamine7.Serum FructosamineFormed by glycosylation of serum protein(mainly albumin)Since serum albumin has shorter half life than hemoglobin,serum

26、fructosamine reflects the glycemic state in the preceding 2 weeksNormal is 1.5-2.4 mmol/L when serum albumin is 5 g/dL.7.S e r u m F r u c t o s a m i n e L a b o r a t o r8.Autoantibodies Insulin autoantibody(IAA):more frequently detected in very young child diabetes Islet cell antibody(ICA):more f

27、requently detected in juvenile diabetes Glutamic acid decarboxylase(GADA):appears relatively lateL a b o r a t o r y T e s t s 8.A u t o a n t i b o dPrediabetes is a term used to distinguish people who are at increased risk of developing diabetes.People with prediabetes have impaired fasting glucos

28、e(IFG)or impaired glucose tolerance(IGT).Some people may have both IFG and IGT.IFG is a condition in which the fasting blood sugar level is elevated(6.1-6.9mmol/L)after an overnight fast but is not high enough to be classified as diabetes.IGT is a condition in which the blood sugar level is elevated

29、(7.8-11.1mmol/L)after a 2-hour oral glucose tolerance test,but is not high enough to be classified as diabetes.P r e d i a b e t e s i s a t e r m u s e d t o D i a g n o s t i c C r i t e r i aCharacteristicsType 1Type 2%of diabetic pop5-10%90%Age of onsetUsually 40+some obese childrenPancreatic fu

30、nctionUsually noneInsulin is low,normal or high PathogenesisAutoimmune processAuto-antibodies positive(GADA+)Defect in insulin secretion,tissue resistance to insulinAuto-antibodies negativeFamily historyGenerally not strongStrongObesityUncommonCommonHistory of ketoacidosisOften presentRare except in

31、 stress Clinical presentationmoderate to severe symptoms:3Ps,fatigue,wt loss and ketoacidosisMild symptoms:Polyuria and fatigue.Diagnosed on routine physical examinationTreatmentInsulin,DietExerciseDiet,ExerciseOral antidiabetics,Insulin C h a r a c t e r i s t i c s T y p e 1 T y p e 2%Management o

32、f Diabetes MellitusMa n a g e m e n t o f D i a b e t e s Me l l i t uThe major components of the treatment of diabetes are:Diet,Exercise,and Self careA Oral hypoglycaemic therapyB Insulin TherapyCT h e m a j o r c o m p o n e n t s o f t h e t rG l y c e m i c g o a l sDiet is a basic part of manag

33、ement in every case.Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.Dietary treatment should aim at:ensuring weight controlproviding nutritional requirementsallowing good glycaemic control with blood glucose levels as close to normal as possiblecorr

34、ecting any associated blood lipid abnormalitiesD i e t i s a b a s i c p a r t o f m a n a g eThe following principles are recommended as dietary guidelines for people with diabetes:Dietary fat should provide 25-35%of total intake of calories but saturated fat intake should not exceed 10%of total en

35、ergy.Cholesterol consumption should be restricted and limited to 300 mg or less daily.Protein intake can range between 10-15%total energy(0.8-1 g/kg of desirable body weight).Requirements increase for children and during pregnancy.Protein should be derived from both animal and vegetable sources.Carb

36、ohydrates provide 50-60%of total caloric content of the diet.Carbohydrates should be complex and high in fibre.Excessive salt intake is to be avoided.It should be particularly restricted in people with hypertension and those with nephropathy.T h e f o l l o w i n g p r i n c i p l e s a r e rPhysica

37、l activity promotes weight reduction and improves insulin sensitivity,thus lowering blood glucose levels.Together with dietary treatment,a programme of regular physical activity and exercise should be considered for each person.Such a programme must be tailored to the individuals health status and f

38、itness.People should,however,be educated about the potential risk of hypoglycaemia and how to avoid it.P h y s i c a l a c t i v i t y p r o m o t e s w e iPatients should be educated to practice self-care.This allows the patient to assume responsibility and control of his/her own diabetes managemen

39、t.Self-care should include:Blood glucose monitoringBody weight monitoringFoot-carePersonal hygieneHealthy lifestyle/diet or physical activityIdentify targets for controlStopping smokingP a t i e n t s s h o u l d b e e d u c a t e d t oThere are currently six classes of oral anti-diabetic agents:i.B

40、iguanidesii.Insulin Secretagogues Sulphonylureas and Glinidesiii.-glucosidase inhibitorsiv.Thiazolidinediones(TZDs)v.DPP4(dipeptidyl peptidase 4)inhibitorsvi.SGLT(sodium-glucose cotransporter-2)inhibitorsT h e r e a r e c u r r e n t l y s i x c l a s s eO r a l H y p o g l y c a e m i c Me d i c a

41、t i o n sInsulinresistancePancreasMuscle and fatLiverMetforminThiazolidinedionesGLP-1 agonistsDPP-4 inhibitorsSulfonylureasMeglitinidesGLP-1 agonistsDPP-4 inhibitorsThiazolidinedionesMetforminAlpha-glucosidase inhibitorsGLP-1 agonistsGutKidneySGLT-2 inhibitorsAbbreviations:DPP-4,dipeptidyl peptidase

42、-4;GLP-1,glucagon-like peptide-1;T2DM,type 2 diabetes mellitus.Ma j o r T h e r a p e u t i c T a r g e t s i n T41Pharmacological effectStimulate the pancreatic secretion of insulin4 1 B 1.S u l f o n y l u r e a s P h a r m a c o l o gSulfonylureas bind to and close ATP-sensitive K+(KATP)channels

43、on the cell membrane of pancreatic beta cells,which depolarizes the cell by preventing potassium from exiting.This depolarization opens voltage-gated Ca2+channels.The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane,and therefore increased secretion

44、of(pro)insulin.S u l f o n y l u r e a s b i n d t o a n d c l o s43ClassificationFirst generationFirst generatione.g.tolbutamide,chlorpropamide,and acetohexamideLower potency,more potential for drug interactions and side effects Second/Third generationSecond/Third generatione.g.glimepiride,glipizid

45、e,and glyburidehigher potency,less potential for drug interactions and side effectsAll sulfonylurea drugs are equally effective in reducing the blood glucose when given in equipotent doses.4 3 B 1.S u l f o n y l u r e a s (C o n t d)C l aMajor Pharmacokinetic Properties of SulfonylureasEqv.Dose(mg)

46、Duration(h)Active metabolitesFirst GenerationFirst Generation Tolbutamide1000-150012-24Yes(p-OH derivative)Chlorpropamide250-37524-60Yes(2-OH and 3OH groups)Tolazamide250-37512-24No(4-COOH derivative)Second Second generationgeneration Glipizide1010-24No(cleavage of pyrazine ring)Glyburide(glibenclam

47、ide)Third generationThird generation516-24Some(trans+cis 4-OH groups)Glimepiride1-224Yes(-OH on CH3 of R group)Ma j o r P h a r m a c o k i n e t i c P r o p e r t iAdverse effectsHypoglycemiaWeight gain HbA1c:1.5 1.7%reduction.FPG:50 70 mg/dL reduction.PPG:92 mg/dL reduction.EfficacyB 1.S u l f o n

48、 y l u r e a s (C o n t d)A d v e rPharmacological effectStimulation of the pancreatic secretion of insulinStimulation of the pancreatic secretion of insulinShould be given before meal or with the first bite of each meal.If you skip a meal dont take the dose!Repaglinide NateglinideShort-acting Secre

49、togoguesB 2.G l i n i d e s P h a r m a c o l o g i c a l e fThey bind to an ATP-dependent K+(KATP)channel on the cell membrane of pancreatic beta cells in a similar manner to sulfonylureas but have a weaker binding affinity and faster dissociation from the SUR1 binding site.GlinidesT h e y b i n d

50、t o a n A T P-d e p e n d e n t 48Incidence of hypoglycemia is very low about 0.3%Adverse effectDrug Interactions Inducers or inhibitors of CYP3A4 affect the action of repaglinide Nateglinide is an inhibitor of CYP2C94 8 I n c i d e n c e o f h y p o g l y c e m i a i sPharmacological effectReduces