糖尿病英文PPT课件

,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Diabetes Mellitus,2024/9/22,1,Diabetes Mellitus,definition,types,symptoms,diagnosis,Laboratory findings,treatment,complications,2024/9/22,2,Definition-WHO (4/2000),The 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 secretion, insulin action, or both,2024/9/22,3,Definition,A metabolic condition characterised by high plasma glucose levels and chronic vascular complications,A vascular disease affecting small and large arteries with coexistent metabolic disturbance particularly high plasma glucose levels,2024/9/22,4,Diabetes Mellitus,definition,types,symptoms,diagnosis,Laboratory findings,treatment,complications,2024/9/22,5,Aetiological Classification of Disorders of Glycaemia,Type 1,(betacell destruction, usually 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 resistance),Other specific types,Genetic defects of betacell function,Genetic defects in insulin action,Diseases of the exocrine pancreas Endocrinopathies,Drug or chemicalinduced,Infections,Uncommon forms of immunemediated diabetes,Other genetic syndromes sometimes associated with diabetes,Gestational diabetes,2024/9/22,6,Type 1 diabetes,Previously known as IDDM(Insulin dependent diabetes),Ketosis prone:Usually diagnosed in younger age group( 30 years,1 in 1000 population as new cases each year,Insidious presentation with symptoms of polyuria, polydipsia, lethargy, weight loss, nausea, vomiting, abdominal cramps, blurred vision and superficial infection.,Often discovered at routine medical,This presentation is the end point of the gradual loss of beta cell function in the setting of Insulin resistance,Strong (90-100%) concordance in Twins,Reavans syndrome or Syndrome X Insulin resistance,2024/9/22,13,Type 2 diabetes,Underlying insulin resistance,genetic and ethnicity,Obesity BMI WHR,inactivity / low physical fitness,intrauterine & childhood factors,smoking & drugs,Impaired insulin secretion,Insulin secretion worsens with time,post-receptorcellular mechanisms,mechanismunclear,b,-cellexhaustion,2024/9/22,14,Type 2 diabetes,Prandial glucose,Fasting glucose,Insulin resistance,Insulin secretion,Plasma glucose,-cell,126 mg/dL,years,2024/9/22,15,Pancreatic,-cell,Insulin resistance,Liver,HYPERGLYCAEMIA,Islet,-cell degranulationReduced insulin content,Muscle,(PKC,Adipose tissue,Decreased glucose transport& activity (expression) of GLUT-4,Increased,lipolysis,Elevated,plasma NEFA,+,-,Low plasma,insulin,Increased glucose output,Elevated,TNF,Insulin resistance and,-cell dysfunction,produce hyperglycaemia in type 2 diabetes,2024/9/22,16,Tissue Responses to InsulinResistance or Failure,LIVER,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 urea,2024/9/22,17,MUSCLE,a. serum glucose is poorly taken up by muscle (decrease GLUT activity),b. saturation of hexokinase activity, inability to retain cellular glu as glu-6-PO4,c. increased LPL activity and increased FA production,d. increased b-oxidation, but TCA is overwhelmed because ATP is high alreadye,e. increased breakdown of muscle and serum protein into amino acids,f. increased transfer of N onto ALA / GLN and sent back to liver,2024/9/22,18,ADIPOSE,a. increased LPL and HSL send more free FA into bloodstream,b. glucose can not be taken into cell via GLUT4 for glycogen synthesis,c. active HSL means TAGs are not being made and stored,2024/9/22,19,Insulin resistance and insulinhypersecretion precede type 2 diabetes,Insulin Insulin Macrovascular,sensitivity secretion disease,30% 50% 50%,50% 70100% 40%,70% 150% 10%,100% 100%,Type 2 diabetes,IGT,Impaired glucose metabolism,Normal glucose metabolism,2024/9/22,20,Clinical Reavans Syndrome,Insulin resistance,Hypertension,Dyslipidaemia( increase LDL, decreased HDL),Obesity,Other factors: hyperfibrinogenemia, hyperuricaemia, propensity to microvascular diseases,“Metabolic syndrome” in most cases of type 2 diabetes,2024/9/22,21,abdominal obesity,high blood pressure,HDL cholesterol,VLDL triglyceride,small dense LDL,hyperinsulinaemia,glucose intolerance,diabetes,hyperuricaemia,PAI-1,fibrinogen,factor VII,microalbuminuria,insulin resistance,Syndrome of insulin resistance,AKA Reavens syndrome, syndrome X,metabolic syndrome,2024/9/22,22,Type 1 diabetes,typical onset 20 years,can start at any age,gradual onset,may be no symptoms,often no weight loss,usually obese,not ketotic,detectable C-peptide,no autoimmune markers,2024/9/22,23,Diabetes in pregnancy,co-existent or newly diagnosed lifelong diabetes,type 1,type 2 (especially in South Asian women),other specific types of diabetes,gestational diabetes,2024/9/22,24,Other types of Diabetes,Genetic defects of betacell function,Chrme 20, HNF4_ (MODY1),Chrme 7, glucokinase (MODY2),Chrme 12, HNF1_ (MODY3),Chrme 13, IPF1 (MODY4),Mitochondrial DNA 3243 mutation,Genetic defects in insulin action,Type A insulin resistance,Leprechaunism,RabsonMendenhall syndrome,Lipoatrophic diabetes & Others,Diseases of the exocrine -pancreas,Fibrocalculous pancreatopathy,Pancreatitis,Trauma / pancreatectomy,Neoplasia,Cystic fibrosis,Haemochromatosis & Others,Endocrinopathies,Cushings syndrome,Acromegaly,Phaeochromocytoma,Glucagonoma,Hyperthyroidism,Somatostatinoma & Others,2024/9/22,25,Types-continued,Infections,Congenital rubella,Cytomegalovirus,Others,Uncommon forms of immunemediated diabetes,Insulin autoimmune syndrome (antibodies to insulin),Antiinsulin receptor antibodies,“Stiff Man” syndrome,Others,Drug or Chemicalinduced Diabetes,Nicotinic acid,Glucocorticoids,Thyroid hormone,Alphaadrenergic agonists,Betaadrenergic agonists,Thiazides,Dilantin,Pentamidine,Vacor,Interferonalpha therapy,Others,2024/9/22,26,Pathophysiology,Because 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 death,2024/9/22,27,Diabetes Mellitus,definition,types,symptoms,diagnosis,Laboratory findings,treatment,complications,2024/9/22,28,Symptoms of diabetes due to hyperglycaemia,Hyperglycemia,Dehydration,Excessive thirst and urination,Excessive hunger,Glycosuria,(glu spills into urine: 180mg/dl),2024/9/22,29,Symptoms of diabetes due to hyperglycaemia,plasma glucose renal threshold,about 12 mmol/L,glucose in urine,osmotic diuresis,urine volume,thirst,genital thrush,weight loss,hyperglycaemia,tiredness,2024/9/22,30,Symptoms of diabetes due to hyperglycaemia,hyperglycaemia,swelling of lensblurred vision,cerebral effectslightheadedness,malaise,mental changes,2024/9/22,31,Diabetes Mellitus,definition,types,symptoms,diagnosis,Laboratory findings,treatment,complications,2024/9/22,32,ADA diagnostic criteria (1997),Symptoms of diabetes 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 loss,or,FPG more than or equal to 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours,or,2 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 dissolved in water,2024/9/22,33,WHO diagnostic criteria,whole bloodplasma,Diabetes mellitus,(fasting), 6.1mmol/l 7.0mmol/l,2 hour post glucose load, 10.0 mmol/l 11.1mmol/l,IGT,(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%),2024/9/22,39,Laboratory findings,Glucose: FBG, 2 hr OGTT ,FBG is simple, accurate, convenient for patient,Glycohemoglobin,Creatinine,Urinalysis glucose ketone bodies,Microalbumin,Dyslipidemia,Insulin c-peptide,2024/9/22,40,Diabetes Mellitus,definition,types,symptoms,diagnosis,Laboratory findings,treatment,complications,2024/9/22,41,Treatment of Diabetes,Non Pharmacological,Exercise and Education,Diet, Low in fat, low refined sugars, high carbohydrate, high fibre, low calories if obese, spacing of meals (Healthy eating),Low cholesterol and triglyceride diet if hyperlipidemia,All Type 1 patients will require Insulin and type 2 can be on diet only, tablets or insulin treated,2024/9/22,42,Treatment of diabetes,type 1,type 2,GDM,diet, exercise & insulin,diet, exercise,metformin or sulphonylurea alone,metformin and sulphonylurea,metformin, sulphonylurea & thiazolidinedione,insulin,diet,insulin,2024/9/22,43,Drugs to treat hyperglycaemia,Insulin and insulin analogues,Insulin secretagogues,sulphonylurea,non-sulphonylurea,Insulin sensitizers,biguanide,thiazolidinedione,Intestinal absorption inhibitors,acarbose,orlistat,lispro insulin,aspart insulin,insulin glargine,gliclazide, glibenclamide,repaglinide, nateglinide,metformin,rosiglitazone, pioglitazone,2024/9/22,44,sulphonylurea agents,gliclazide, 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,sulfa allergy,type 1 DM, DKA,2024/9/22,45,Meglitinides,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: Hypoglycemia, weight gain,2024/9/22,46,metformin,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,1/3 patients get diarrhoea, wind or abdominal pain,not used in renal failure, heart failure or severe intercurrent illness,2024/9/22,47,Metformin Toxicity,Renally excreted, not metabolized,Potentially fatal lactic acidosis,Contraindications:,renal insufficiency (decreases drug clearance),hepatic dysfunction (decreases lactate metabolism),tissue anoxia (increase lactate production),2024/9/22,48,acarbose,-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 hypoglycaemia,not absorbed into body,1/2 patients get diarrhoea, wind or abdominal pain,2024/9/22,49,a,-glucosidase inhibitor toxicity,Unabsorbed CHOs:,Bacterial fermentation in colon results in abdominal pain, flatulence from gas,Osmotic diarrhea,Elevated serum transaminases,Metabolized and excreted in the GI tract,Some metabolite is absorbed in GI and renally excreted,Contraindicated for patients with chronic or inflammatory bowel disease,Relatively weak antidiabetic effect, usually used adjunctively.,2024/9/22,50,thiazolidinedione agents,rosiglitazone, pioglitazone,MechanismBind to PPAR-gamma receptor in peripheral tissues mainly skeletal muscle,Result in expression of cell-surface glucose transporters.,Cautions,Not recommended in NYHA Class III/IV CHF,May cause fluid retention and precipitate CHF,May cause mild anemia (? Dilutional effect),2024/9/22,51,thiazolidinedione agents,Associated with weight gain,Liver toxicity seen in older TZD (troglitazone) but not with newer agents; recommended to check LFTs q 2 mo for 1,st,year of use.,Advantages,No hypoglycemia,Possible improvement in vascular function,2024/9/22,52,Thiazolidinedione toxicity,Metabolism: hepatic conjugation by the CYP450 system,Excretion: biliary,Hepatotoxic, especially troglitazone, and contraindicated in cases of hepatic dysfunction,Can cause edema and hypoglycemia when used in combination with other hypoglycemics,2024/9/22,53,Treating hyperglycaemia in type 2 diabetes,dietary change,exercise,obese,metformin,not obese,sulphonylurea,metformin & sulphonylurea,glitazone & metformin OR glitazone & sulphonylurea,insulin metformin,Aim: HbA,1c,6.5%Fasting glucose microaneurysms edema,Proliferative (VEGF) New blood vessels that extend into vitreous, bleeding loss of vision,Glaucoma, intraocular pressure ocular tissue damage,2024/9/22,65,Non-proliferative diabetic retinopathy (NPDR),Earliest stage,Microaneurisms and intraretinal “dot and blot” hemorrhages,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 retinal detachment.,Treated with panretinal photcoagulation.,2024/9/22,66,Diabetic 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 pressure,2024/9/22,67,Diabetic nephropathy,Glomerulosclerosis (Capillary basement membr. thickening),Microalbuminuria (30-300 mg/24hr),Hyperfiltration (GFR),Albuminuria (300 mg/24hr),Hypertension,Nephrotic syndrome (approx 1/3 of Type 1 progress to end stage renal dis requiring dialysis),Renal failure (,GFR,Creat),2024/9/22,68,Diabetic neuropathy,Types 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, fecal incontinence,Genitourinary,ED, retrograde ejaculation, neurogenic bladder,Other,“gustatory” s