DiabetesDr Muries BarhamDiabetes 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 efects of diabetes mellitus include longterm damage, dysfunction and failure of various organs.Diabetes mellitus may present !ith characteristic symptoms such as thirst, polyuria, blurring of vision, and !eight loss. "n its most severe forms, #etoacidosis or a non#etotic hyperosmolar state, in absence of efective treatment, death. $ften symptoms are not severe, or may be absent, and conse%uently hyperglycaemia su&cient to cause pathological and functional changes may be present for a long time before the diagnosis is made.Diabetes The longterm efects of diabetes mellitus include progressive development of the speci'c complications of retinopathy, nephropathy that may lead to renal failure, and(or neuropathy !ith ris# of foot ulcers, amputation, )harcot *oints, and features of autonomic dysfunction, including se+ual dysfunction. ,eople !ith diabetes are at increased ris# of cardiovascular, peripheral vascular and cerebrovascular disease.Diabetes -ong.term /fects0lucose Tolerance )ategoriesAmerican Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10F! 2 - " ! (#!$$)1266080100120140160180200lasma %lucose) m%&'( (NormalDiabetes Mellitus240220Diabetes MellitusNormalIGTIFGClassifcation of Diabetes Mellitus by Etiology$)pe 1 -cell 'estruction*complete lac+ o, insulin$)pe 2 -cell ')s,unction an' insulin resistance!estational -cell ')s,unction an' insulin resistance 'urin% pre%nanc)#t"er speci,ic t)pes - !enetic 'e,ects o, -cell ,unction- ./ocrine pancreatic 'iseases- .n'ocrinopat"ies- Dru%- or c"emical-in'uce'- #t"er rare ,ormsA. Genetic defects of cell functioncharacterized by mutations in1 2.3epatocyte nuclear transcription factor (345) 6 (M$D7 2)8.0luco#inase (M$D7 8) 9.345.2 (M$D7 9)6."nsulin promoter factor.2 (",5.2: M$D7 6) ;.345.2 (M$D7 ;) T,.sensitive potassium channel A. ,roinsulin or insulin conversionB. Genetic defects in insulin action2. Type > insulin resistance 8. -eprechaunism 9. Babson.Mendenhall syndrome 6. -ipodystrophy syndromesC. Diseases of the exocrine pancreaspancreatitis, pancreatectomy, neoplasia, cystic fbrosis, hemochromatosis, fbrocalculous pancreatopathy, mutations in carboxyl ester lipaseD. EndocrinopathiesAcromegaly, Cushings syndrome, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronomaE. Drug! or chemical!inducedpentamidine, nicotinic acid, glucocorticoids, thyroid hormone, diazo+ide, Beta.adrenergic agonists, thiazides, phenytoin, >lfa.interferon, protease inhibitors, clozapine". #nfectionscongenital rubella, cytomegalovirus, co+sac#ieG. $ncommon forms of immune!mediated diabetesCstif.personC syndrome, anti.insulin receptor antibodies%. &ther genetic syndromes sometimes associated 'ith diabetesDDo!nEs syndrome, FlinefelterEs syndrome, TurnerEs syndrome, GolframEs syndrome, 5riedreichEs ata+ia, 3untingtonEs chorea, -aurence.Moon.Biedl syndrome, myotonic dystrophy, porphyria, ,rader.Gilli syndrome#(. Gestational diabetes mellitus )GDM*0lucose intolerance may develop during pregnancy. "nsulin resistance is related to the metabolic changes of late pregnancy, and the increased insulin re%uirements may lead to "0T. 0DM occurs in H6I of pregnancies in the Jnited @tates: most !omen revert to normal glucose tolerance post-partum but have a substantial ris# (9K< 7+!+< @EA60 A -> 7?5ositi4e#CA correlate 'ith declining C!peptide le4els B!increasing insulin reCuirementsA2,# G1$,AM#C AC#D DECA6&D@1A0E ) GAD*A2,# G1$,AM#C AC#D DECA6&D@1A0E ) GAD* AB AB AntiGADAntibodies 5resentinE>!F87of recent onsetDM type +.%yperglycemia5athogenesis of ,ype + Diabetes/&ne Defect$nrestrainedglucose production#mpaired glucoseclearance2o hepaticinsulin eGect2o muscleHfatinsulin eGectAbsentinsulinsecretion Glycosuria More glucose entersthe blood1ess glucose entersperipheral tissuesD.M. Type 2/pidemiology in J@ in L 2A yr of age population12. "ncidence1 2, ">>, 0>D).D.M. Type 2The combination of all those factors ultimately leads to O. cell destruction, !hich is an insidious process that may ta#e up to 2K yrs before completion: once the O. cell mass is L;.2KI of its original amount, symptoms of diabetes become manifest.1ate!&nset ,ype + DiabetesPAbout half of patients 'ith type + diabetes are diagnosed after age +FPAutoimmune process may diGer and is slo'erP&ften mistaJen for type - diabetesKmay maJe up +.-ater becomes non.insulin dependent.4o 3-> predisposition.4o autoimmunity.$ccurs in certain ethnic groups, e.g. >frican. >mericans.5athogenesis of ,ype - Diabetes / ,'o DefectsExcessi4eglucose production#mpaired glucoseclearance%epaticinsulinresistanceMuscleHfatinsulinresistance#mpairedinsulinsecretion%yperglycemiaMore glucose entersthe blood stream1ess glucose entersperipheral tissuesGlycosuria 1oss of early!phase insulin secretion in1oss of early!phase insulin secretion intype - DMtype - DMNormal120100806040200Time )minutes(Plasma insulin )

!ml("#0 0 #0 60 $0 120T%&e 2 'iabetes"#0 0 #0 60 $0 120Time )minutes(12010080604020020 ( (lu)osePlasma insulin )

!ml(Pattern o* insulin se)retion is altere' earl% in t%&e 2 'iabetesWard WK et al. Diabetes Care 1984;7:49150220 (lu)oseM$D7M$D7 is non.insulin re%uiring form of diabetes,occurring in children and young adults,resulting from genetic defect in beta.cell function,and inherited in autosomal dominant trait(>D)M$D7 is non.insulin re%uiring form of diabetes, occurring in children and young adults, resulting from genetic defect in beta.cell function, and inherited in autosomal dominant trait(>D)M&D@MA,$6#,@&20E,D#ABE,E0&",%E MA,$6#,@&20E,D#ABE,E0&",%E @&$2G )M&D@*@&$2G )M&D@*. . )linical presentation partly similar to type 8 DMbutoccurringinyoungagegroup.mostly adolescents.>utosomaldominantinheritance:; diferent gene defects described . >ll relatively rare.)linical 5eatures,ype +2o 2o @es,ype - @es@es 2oM&D@2o 2o 2oObesityInsulin resistance AutoimmunityMODYType Mody1Mody2 Mody3Mody4Mody5Mody6Gene HNF-4 GlucokinaseHNF-1 !F-1HNF-1" Neu#oD1$O% &'T(2)linical Fea*u#es o+ He*e#o,y-ous .*a*eDia/e*es01ic#o2ascula# co1plica*ion$ #educ*ions in se#u1 *#i-lyce#ides$apolipop#o*eins31pai#ed +as*in- -lucose$ i1pai#ed -lucose *ole#ance$ dia/e*es$ no#1al p#oinsulin-*o-insulin #a*io in se#u1 3Dia/e*es$ 1ic#o2ascula# co1plica*ion$ #enal -lycosu#ia 3 Dia/e*es 3Dia/e*es0#enal cys*s and #enal dys+unc*ion$in*e#nal -eni*al 3 a/no#1ali*iesDia/e*es 3Gene*ic 4e*e#o-enei*y in MODYGlucose ,olerance CategoriesAmerican Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10F! 2 - " ! (#!$$)1266080100120140160180200lasma %lucose) m%&'( (2ormalDiabetes Mellitus240220Diabetes Mellitus2ormal#G,#"G8Type 2 Diabetes MellitusThis form of diabetes is immune.mediated in over AKI of cases and idiopathic in less than 2KI. The rate of pancreatic B cell destruction is %uite variable, being rapid in some individuals and slo! in others. Type 2 diabetes is usually associated !ith #etosis in its untreated state. "t occurs at any age but most commonly arises in children and young adults !ith a pea# incidence before school age and again at around puberty. "t is a catabolic disorder in !hich circulating insulin is virtually absent, plasma glucagon is elevated, and the pancreatic B cells fail to respond to all insulinogenic stimuli.)riteria for the Diagnosis of Diabetes Mellitus@ymptoms of diabetes plus random blood glucose concentration 22.2 mmol(- (8KK mg(d-)aor 5asting plasma glucose =.K mmol(- (28< mg(d-)bor T!o.hour plasma glucose 22.2 mmol(- (8KK mg(d-) during an oral glucose tolerance testcaBandom is de'ned as !ithout regard to time since the last meal.b5asting is de'ned as no caloric inta#e for at least ? h.cThe test should be performed using a glucose load containing the e%uivalent of =; g anhydrous glucose dissolved in !ater: not recommended for routine clinical use.Bis# 5actors for Type 8 Diabetes Mellitus5amily history of diabetes (i.e., parent or sibling !ith type 8 diabetes)$besity (BM" 8; #g(m8)3abitual physical inactivityBace(ethnicity,reviously identi'ed "50 or "0T3istory of 0DM or delivery of baby R6 #gBis# 5actors for Type 8 Diabetes Mellitus3ypertension (blood pressure 26K(AK mm3g)3D- cholesterol level L9; mg(d- (K.AK mmol(-) and(or a triglyceride level R8;K mg(d- (8.?8 mmol(-),olycystic ovary syndrome or acanthosis nigricans3istory of vascular disease