1、Author(s):Arno Kumagai,M.D.,2009License:Unless otherwise noted,this material is made available under the terms of the Creative Commons AttributionNoncommercialShare Alike 3.0 License:creativecommons.org/licenses/by-nc-sa/3.0/We have reviewed this material in accordance with U.S.Copyright Law and hav
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9、ichigan believes can be used,shared,and adapted because it is ineligible for copyright.Content Open.Michigan has used under a Fair Use determination.DIABETES MELLITUSWinter 2009DIABETES MELLITUSDiabetes(fr.Ionian Greek):“To pass through”“Diabetes is a dreadful affliction,the melting down of flesh an
10、d limbs into urine.The patients never stop making water,and the flow is incessant,like the opening of aqueducts.Life is short,unpleasant,and painful,and thirst,unquenchable,drinking excessive,and disproportionate to the large quantity of urine,for yet more urine is passed.”Areteus of Capadocia2nd Ce
11、ntury A.D.DIABETES MELLITUSMellitus(fr.Latin)=“Sweet”or“Honey-like”Renaissance England:“The Pissing Evile”17th Cent.England.Thomas Willis:Diabetic urine contains sugar.Diabetes due to“sadnesse and longe griefe.”18th Cent.England.Matthew Dobson:Diabetic serum contains sugar.4th Cent.A.D.India:Susruta
12、 and Charaka Urine from polyuric patients tasted like honey,was sticky to the touch and attracted ants.Two types of people with this disorder:old,obese people and young,thin people who did not survive very long.“Madhumeh”=“honey disease”DIABETES:THE GROWING EPIDEMICU.S.News Magazine June 25,2019Diab
13、etes Mellitus:The Growing EpidemicCDC Diabetes Care,23:1278,2000.(All Images)CDC Study of Diabetes in the United States:1990-2019Pink 6%DMby self-report199019942019DIABETES MELLITUSBUT,Approximately 8%of the U.S.population,some 18 million individuals,have diabetes.ONE THIRD of the people who have di
14、abetes are unaware that they have the disease.Approximately 1.5 million people are diagnosed with diabetes mellitus each year in the US alone.DIABETES MELLITUSDiabetes disproportionately affects ethnic minorities in the United States.Macintosh PICTimage formatis not supported?Currently,there are no
15、nationwide prevalence data for Asian Americans.Based on regional studies,risk appears to be between 1.5-2 times higher than that for White Americans.NIDDK National Institutes of Health%in Adults 21 yoDIABETES MELLITUSAnnually,34,000 deaths are attributable to diabetes,making it the 6th leading cause
16、 of death.BUT,Diabetes is a significant contributing factor in the deaths of 320,000 Americans each year.Approximately 65%of individuals with diabetes die of cardiovascular disease(MI and stroke).DIABETES MELLITUS A.KumagaiDIABETES MELLITUS2.5x increased risk of MI 3-5x increased risk of stroke2x in
17、creased risk of congenital abnormalitiesDiabetes Mellitus A.KumagaiDIABETES MELLITUS:The Socioeconomic ImpactHEATLH CARE RESOURCES A.KumagaiDIABETES MELLITUS:The Socioeconomic ImpactHEALTH CARE RESOURCESECONOMIC BURDEN OF DIABETES$92 BILLION(direct)and$39 BILLION(indirect)annually is spent on diabet
18、es and its related problems*2019 costs(American Diabetes Association)$13,243 spent annually per capita for those with diabetes versus$2,560 for those without A.KumagaiDIABETES MELLITUS:Psychosocial IssuesM a c in to s h P IC Tim a g e fo rm a tis n o t s u p p o rte dPablo PicassoDIABETES MELLITUS:S
19、ocietal IssuesEFFECTIVE DIABETES CAREFactors such as socioeconomic status and cultural and linguistic differences may present obstacles to quality care.A.KumagaiChronic hyperglycemiaA RELATIVE or ABSOLUTE deficiency of insulin.“The Three Ps”:Polyuria,Polydipsia and Polyphagia.The development of chro
20、nic microvascular and macrovascular complications.Diabetes mellitus is a chronic disorder of carbohydrate metabolism that is characterized by:IMPORTANT!Represents 5-10%of individuals with diabetes in U.S.Absolute deficiency of endogenous insulin production and dependence on exogenous insulin for sur
21、vival.Ketosis-prone.Onset generally at young age(40-years-old)and MAY GO UNDETECTED FOR YEARS OR DECADES.High(85%)correlation with obesity in most ethnic groups.Hereditary/genetic factors very strong.IMPORTANT!Occurs only in the setting of pregnancy Affects 7%of all pregnancies in US.Higher risk:cer
22、tain ethnic groups(African Americans,Hispanic/Latino,and Native Americans),obesity,and positive family history of diabetes.There is a 30-50%risk of developing type 2 diabetes within 5-10 years.Pancreatic Damage or Destruction:chronic pancreatitis,hemachromatosis,cystic fibrosis.Endocrine Diseases:Ac
23、romegaly,Cushings Syndrome.States of extreme physiological stress:e.g.,infections,burns.Drugs:GLUCOCORTICOIDS,thiazide diuretics,niacin.Pink=important to remember Most cases seen in African Americans and Hispanic/Latinos.Almost always associated with obesity.May present with diabetic ketoacidosis.Do
24、 not need insulin for survival.Genetic Syndromes.Example:MODY=Maturity Onset Diabetes of Youth Autosomal dominant inheritance pattern Non-insulin dependent diabetes occurs at very young age.Deletions or mutations in genes found to play role in regulating glucose metabolism.Diabetes Mellitus:DIAGNOSI
25、S-New Criteria(2019)Normal blood glucose:80-100 mg/dLDiabetes is present with either:Two fasting blood glucose values of 126 mg/dL.orA random blood glucose of 200 mg/dL+symptoms.The Oral Glucose Tolerance Test(GTT):measurement of blood glucose values in a timed manner after ingestion of a standard a
26、mount of glucose.Used clinically on a regular basis only to detect diabetes developing during pregnancy.Diabetes Mellitus:DIAGNOSISRemember:Most of the time,diabetes is Most of the time,diabetes is ASYMPTOMATIC,or its symptoms are ASYMPTOMATIC,or its symptoms are subtle and nonspecific.subtle and no
27、nspecific.Type 1 DiabetesBeta Cells:INSULINAlpha Cells:GLUCAGONIsolated islets stained for insulin(green)and caspase-3(pink).Type 1 diabetes involves selective autoimmune destruction of the insulin-secreting beta cells of the pancreatic islets.Dr.Thomas Caceci W.Moritz,Ph.D.,Univ.of ZurichType 1 Dia
28、betes:PathogenesisA T cell-mediated autoimmune process causing inflammation and destruction of the b cells of the pancreas.Associated with the presence of autoimmune antibodies,including antibodies against islet cells,insulin and the 65 kDa form of glutamic acid decarboxylase(GAD65).Autoimmune antib
29、odies play no apparent role in development of diabetes but serve as useful markers for those at high risk.Genetic factors play a role:association with specific HLA haplotypes.Concordance among identical twins:30-50%.Isolated islets stained for insulin(green)and caspase-3(pink).W.Moritz,Ph.D.,Univ.of
30、 ZurichType 2 Diabetes:PathogenesisThe pathogenesis of type 2 diabetes is slightly more complexobLiterated(Flickr)DIABETES MELLITUS:Normal Glucose MetabolismGLUCOSE SUPPLYGLUCOSE DEMANDM acintosh PICTim age form atis not supportedM a c in t o s h P IC Tim a g e f o r m a tis n o t s u p p o r t e d(
31、+)(-)INSULININSULINMacintosh PICTimage formatis not supportedBRAINInsulin-independent tissuesMacintosh PICTimage formatis not supportedDIETM acintosh P IC Tim age form atis not supportedHepatic glucose productionInsulin-dependent tissuesM acin to sh P IC Tim ag e fo rm atis n o t su p p o rted A.Kum
32、agaiType 2 Diabetes:PathophysiologyM acintosh P IC Tim age form atis not supportedM a c in t o s h P IC Tim a g e f o r m a tis n o t s u p p o r t e dIntroducing the Players in Type 2 Diabetes.M acin to sh P IC Tim ag e fo rm atis n o t su p p o rted A.KumagaiType 2 Diabetes:PathophysiologyMacintos
33、h PICTim age form atis not supportedM acintosh P IC Tim age form atis not supportedAbnormally high hepatic glucose outputM a c in t o s h P IC Tim a g e f o r m a tis n o t s u p p o r t e dINSULINAbnormal pancreatic insulin secretionM acin to sh P IC Tim ag e fo rm atis n o t su p p o rtedPeriphera
34、l insulin resistance A.KumagaiType 2 Diabetes:Development and ProgressionMacintosh PICTim age form atis not supportedM acintosh P IC Tim age form atis not supportedM a c in t o s h P IC Tim a g e f o r m a tis n o t s u p p o r t e dINSULINEventually,abnormal insulin secretion and progressive b b ce
35、ll dysfunction leads to FASTING HYPERGLYCEMIAM acin to sh P IC Tim ag e fo rm atis n o t su p p o rtedIncreasing peripheral insulin resistance leads to POSTPRANDIAL HYPERGLYCEMIAM acintosh P IC Tim age form atis not supportedINSULIN A.KumagaiPathogenesis of Type 2 Diabetes:the Molecular Levelhanall.
36、co.kr Diabetes Mellitus:Points to RememberUnderstand:The epidemiology of diabetes:the current“epidemic,”high prevalence in minority populations,effects on individuals and society.The differences between type 1 and type 2 diabetes.1.The pathogenesis of type 1 and type 2 diabetes.Additional Source Inf
37、ormationfor more information see:open.umich.edu/wiki/CitationPolicy Slide 6:U.S.News Magazine June 25,2019Slide 7:CDC Diabetes Care,23:1278,2000.(All Images)Slide 9:NIDDK National Institutes of HealthSlide 11:Arno KumagaiSlide 12:Arno KumagaiSlide 13:Arno KumagaiSlide 14:Arno KumagaiSlide 15:Pablo P
38、icassoSlide 16:Arno KumagaiSlide 26:Dr.Thomas Caceci,Image from education.vetmed.vt.edu/Curriculum/VM8054/Labs/labtoc.htm;W.Moritz,Ph.D.,Univ.of ZurichSlide 27:W.Moritz,Ph.D.,Univ.of ZurichSlide 28:CC:BY-NC-SA obLiterated,flickr/photos/obliterated/2464032152/,Flickr,creativecommons.org/licenses/by-nc-sa/2.0/deed.en Slide 29:Arno KumagaiSlide 30:Arno KumagaiSlide 31:Arno KumagaiSlide 32:Arno KumagaiSlide 33:hanall.co.kr
