!

OS(215!
!! ! Diabetes(in(the(Adult! Trans(B02(Exam(2!
Frances Lina Lantion-Ang, MD, FPCP, FPSEDM! 01/29/2019!
!

(
Wppeg er pHis out 13Th ●! When!there!is!insulin!resistance,!the!body!first!compensates!by!
increasing!production!of!insulin!(hyperinsulinemia!state).!Leads!
OUTLINE!
to!islet!B!failure,!leading!to!less!production!of!insulin!
I.! Introduction! VII.! Diagnosis! !
II.! Type!2!Diabetes! A.! Fasting!Blood!Sugar! IV.(UNLUCKY(THIRTEEN(
III.! Natural!History! B.! HBA1c! ●! mediating*pathways*of*hyperglycemia!
IV.! Unlucky!Thirteen! C.! Presence!of!cIpeptides!
●! ! !insulin!
V.! Associated! Metabolic! D.! Absence!of!Antibodies!
Abnormalities! E.! Subtypes! o! Treatment:!Incretins,!Ranolazine!
VI.! Profiling! VIII.! Management! ●! Incretin(effect !
A.! Demographics! A.! Healthy!Lifestyle! o! Produced!in!the!small!intestine,!up!to!level!of!ileum!
B.! Patient!Complains! B.! Pharmacologic!Therapy! o! GlucoseIdependent!release!
C.! Patient!Observations! C.! Goal!Setting! o! Stimulates!intestinal!release!of!insulin,!suppresses!glucagon!
D.! Physical!Changes! IX.! Complications! production!
A.! Acute!Complications! o! Amplifier!of!abnormal!activity!
B.! Chronic!Complications!
Italicized*notes*not*discussed*in*class.*
●! α(cell(defect ↑! !
! o! Treatment:!Incretins,!Pramlintide!
I.(INTRODUCTION( o! !
●! 6!million!Filipinos!with!diabetes!as!of!2016!
●! 2/3!diagnosed,!1/3!undiagnosed! ●! Adipose,(muscle,(liver( insulin!resistance!
●! 6th!leading!cause!of!death!in!2013! o! Insulin!sensitive!system!
!
o! Treatment:!TZDs,!Metformin!
Table(1.!Prevalence!of!Diabetes!Mellitus.!
●! Brain!
! 1998! 2003! 2008!
o! Treatment:!Incretins,!dopamine!agonists,!appetite!
FBS!>126mg/dl! 3.9! 3.4! 4.8! suppressants!
DM!by!history! I! 2.6! 4.0!
FBS!or!OGTT!or!DM! I! 4.6! 7.1! ♦! !
by!history! ♦! Notably,!bromocriptine!can!be!used!(Not!same!as!the!one!
! used!in!hyperprolactinemia\!not!available!in!Phils)!
II.(TYPE(2(DIABETES( o! Certain!cells!in!the!brain!esp.!the!hypothalamus!need!insulin!to!
●! Heterogeneous!disorder! control!appetite!!
●! Gene(polymorphisms!provide!the!predisposition! ●! Colon/Biome!
●! Environmental(factors!serve!as!precipitating!cause(s)!for! o! changes*in*flora*may*contribute*to*diabetic*state!
hyperglycemia! o! Treatment:!Probiotics,!Incretins,!Metformin!
!
o! Ability!to!degrade!chondroitin!sulfate!is!allegedly!decreased!in!
III.(NATURAL(HISTORY( DM![mentioned!by!Ma’am,!cross!checked!with!Liao!et!al.!
(2017)]!
o! Poop!transplants!possibly!in!the!future!

132 f ●! Immune(Dysregulation/Inflammation!
o! accompanies*the*endoplasmic*stress*imposed*by*increased*
insulin*demand!
prurience o! Treatment:!incretins,!antiIinflammatories,!immune!modulators!
●! Stomach/Small(intestine!
inPhll o! Treatment:!GLPI1!agonists,!Pramlintide,!AGI!
y
tem IA Much
Nutri Institute
o!
!
♦! when!giving!inhibitors,!make!sure!to!give!it!after!the!first!bite!
♦! Inhibitors!are!a!possible!treatment!option!
●! Kidney(!
o! Treatment:!SGLT2!inhibitors!(leads!to!glycosuria)!
●! Amylin( (
o! decreased*levels*lead*to*accelerated*gastric*emptying*and*
increased*glucose*absorption*in*small*intestine!
air produce ●! Vitamin(D(Deficiency(
o! affects!insulin!release!via!calcium!
aingit
w inboth
! o! immunomodulatory!effects!
Figure(1.!Natural!History!of!Type!2!DM.!IGT!=!Impaired!Glucose! o! improves!insulin!sensitivity!and!markers!of!metabolic!function!
!
Tolerance\!HGO!=!Hepatic!glucose!output!
sixes ●! Testosterone(Deficiency((
o! hypogonadal!subjects!have!a!3Ifold!higher!prevalence!of!the!
●! Predominance!of!insulin!resistance!
metabolic!syndrome!
o! Genetically!acquired!
o! Environmentally!acquired!(Lifestyle,!Obesity,!Aging)! 6thhead ♦! note:!females!with!estrogen!deficiency!will!present!as!male!
●! There!are!some!patients!who!cannot!compensate!for!the!
increased!insulin!secretion.!This!state!of!decompensation!has!
ing in!acquiring!metabolic!syndromes!
♦! testosterone!replacement!improved!insulin!sensitivity,!
cause reduced!insulin!requirements!
d death
impaired(glucose!tolerance((prediabetes)!

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unutinously in as to dirty
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! OS(215! Diabetes in Adults!
o! Not!yet!accepted! ♦! OGTT!usually!returns!to!normal!after!delivery!but!a!third!will!
●! Cow’s&Milk&(not&part&of&13)& persist!to!become!overtly!diabetic!
o! really*bad*antigen,*similar*to*virus*that*causes*Type*1*DM! o! Possible!Complications:!
●! See!Figure!of!Unlucky!13!in!the!appendix! ♦! Macrosomia!
!
♦! Sacral!agenesis!
V.(ASSOCIATED(METABOLIC(ABNORMALITIES( ♦! Septal!defect!(very!common)!–!VSD,!ASD!
●! Chronic!Hyperglycemia!(most!important!to!manage)! ♦! Kidney!or!liver!cysts!
●! Hypertension! ♦! Anencephaly!–!most!common!
●! Dyslipidemia!(apply!appropriate!target!levels!for!diabetic!patients)! ♦! Polyhydramnios!
●! Inflammation!(can!affect!the!pancreas)! ●! May*manifest*as*vaginitis*G*main*complaint*is*pruritus!
●! Hypercoagulation! *
o! Affected!by!dyslipidemia! B.(PATIENT(COMPLAINTS(
o! Reason!why!patients!are!given!antiIplatelets! ●! None/Unrelated!checkIup!
●! Endothelial!Dysfunction! ●! Gradual!weight!gain!
o! Very!important! ●! Drained!out!feeling!(“parang!nauupos!na!kandila”,”low!bat!ako”)!
o! Will!eventually!damage!the!vessels,!further!be!damaged!by! ●! Dry!skin,!lips,!throat!(notably!when!they!wake!up!in!the!morning)!
inflammation!and!lead!to!arteriosclerosis! ●! Snoring!
●! Hyperuricemia! o! Mostly!due!to!being!overweight!
!
o! Obstructive!sleep!apnea!–!cause!of!metabolic!syndrome!
VI.(PROFILING( ●! Day!time!Sleepiness!
A.(DEMOGRAPHICS(( o! Can!be!attributed!to!high!blood!sugar!
1.(Age( o! Mostly!due!to!sleep!apnea!(poor!quality!of!sleep)!
●! Testing!for!diabetes!should!be!considered!in!all!individuals!at!age! ●! Dizzy!spells!!
40(years(and(above,!particularly!in!those!with!a!BMI*(23((kg/m2! o! Due!to!high!blood!sugar!
o! If!!normal,!!should!!be!!repeated!!at!!3Iyear(intervals! o! Mistaken!for!vertigo!
●! Testing!should!be!considered!at!a!younger!age!or!be!carried!out! ●! Ear!humming!!
more!frequently!in!individuals!who!are!overweight((BMI!23! o! “Umuumbong!ang!naririnig!ko”,“may!train!sa!tenga!ko”!
kg/m2)!and!have(additional(risk(factors! o! May!manifest!with!vertigo!due!to!semilunar!canals!being!filled!
!
with!sugar!crystals!
2.(Ethnicity( ●! Changing!visual!acuity!due!to!fluctuation!of!sugar!content!leading!
●! There!are!different!prevalence!rates!among!different!ethnicities\! to!changes!in!pressure!and!shape!of!!anterior!and!posterior!
high!risk!ethnic!populations!include! chamber!of!eye!
o! African!Americans! ●! Error!of!refraction!
o! Latinos! o! Swelling!in!the!eye!may!change!shape,!and!thus!refraction!
o! Native!Americans! o! Treat!sugar!first!before!going!to!ophtha!
o! Asian!Americans! ●! Numbness,!skin!prick!sensation!
o! Pacific(Islanders! o! Can’t!feel!feet!
o! Indians! o! Patients!often!feel!“ngalay”,!“parang!may!ants”,!“parang!may!
●! Among*Filipinos,*there*is*a*high*prevalence*rate*of*DM.*According* tinutusok!ng!karayom”!
to*the*2008*NHS,*there*is*a*prevalence*rate*of*7.177.2%! ●! Cold!feet!
●! There!is!a!gradual!increase!in!the!prevalence!rate!among!the! o! Vasoconstriction!
population! o! Spasms!of!the!feet!
o! Wears!warm!socks!or!tones!down!air!conditioning!
!

3.(Family(History( ●! Itchiness!(vaginitis)!
●! Patients!with!first(degree(relatives!with!diabetes!have!a!high!risk! o! Itchiness!in!perianal!area!caused!by!sugar!
of!acquiring!diabetes!(1st!degree!–!parents!and!siblings)! o! Presents!in!males!as(anal(pruritus!
●! When!a!pregnant!woman!delivers!in!her!24th!week,!we!always! ♦! Ma’am!comment:!Possibly!due!to!aspartame!intake!
ask!for!a!family!history!of!DM! o! Due!to!crystallized!sugars!in!the!sweat!
o! Advise!patients!to!bathe!regularly!
!

4.(Early(Cardiovascular(Deaths(
●! Delayed!wound!healing!
●! Patients!with!diabetes!may!suffer!from!heart!attacks!and!stroke! o! Patients!with!this!complaint!usually!don’t!accept!that!they!have!
●! Death!may!occur!in!males!<50y(y.o.X(females,(<55(y.o.! problems!
!
5.(Women( o! Notable!in!drivers!with!foot!wounds!
♦! Gram!negative!infection!due!to!anal!bacteria!heading!
●! Women!with!PCOS/Metabolic(reproductive!syndrome((have!an!
downwards!to!feet!during!showering!
increased!risk!of!DM!
♦! Cone!pain!radiating!from!the!central!area!of!the!foot!
o! Check!for!signs!and!symptoms!following!typical! !
hyperandrogenism! C.(PATIENT(OBSERVATIONS(
o! Would!also!present!as!insulin!resistant,!overweight! ●! Frothy!urine!
o! Present!similarly!to!Cushing’s!syndrome!(irregular!menses,! o! Early!renal!problem!
hypertensive,!central!obesity)!or!CAH!in!adults! o! Proteinuria!(just!like!cracking!an!egg)!
●! Patients!may!have!poor!obstetric!histories! o! Not!validated!in!research!
o! Check!for!miscarriages,(macrosomia,(fetal(death(in(utero,( o! Check!urinalysis,!creatinine,!CKD4!
congenital(abnormalities,(abortion! ●! Ants!around!urinal/underwear!
o! Fetal!complications:!usually!spina!bifida,!anencephaly,!etc! o! Usually!happens!after!spillage!in!urine!
●! Consider!Gestational!DM!in!highIrisk!pregnant!women!! o! In!far!flung!areas!where!you!cannot!test!the!urine,!patients!
o! Profile!of!GDM:! have!to!volunteer!to!taste!their!urine.!If!sweet,!most!probably!
♦! Glucose!intolerance!develops!during!pregnancy! have!DM!
♦! Onset!usually!in!the!2nd!or!3rd!trimester! ●! Sadness!
♦! Occurs!in!5I10%!(up!to!14%)!of!pregnancies! o! Melancholic!about!fate!of!having!diabetes!
♦! Increased!fetal!mortality!or!morbidity! o! Treat!for!possible!depressive!symptoms!
●! Metallic!taste!

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! OS(215! Diabetes in Adults!
o! High*levels*of*sugar*that*crystallize*in*the*mouth! o! 2nd!hour:!> !
o! Maraming!singaw/!Plenty!of!oral!ulcers!
●! Don’t!remove!water!
o! Be!sure!to!check!under!the!tongue!to!examine!blood!vessels! !
!
D.(PHYSICAL(CHANGES( B.(HBA1c(
●! >6.5%(!
●! Weight!change!(BMI)!I!Consider(Asia[Pacific(guidelines!
●! Not!yet!standardized(in(the(Philippines!
●! Big!tummy!
o! Need!National!Glycohemoglobin!Standardization!Program!
●! Elevated!BP!(>(130/80(mmHg) !
(NGSB)!certification!
●! Skin!changes!
o! UK!study!standards!are!currently!used!
o! Dryness!
o! Do*not*settle*in*using*thisL*may*only*be*used*in*control*of*sugar*
o! Acanthosis!–!velvety!feel!of!nape,!axilla,!pressure!areas!
when*type*2*DM*is*diagnosed*already!
o! Brown!spots!I!browning!sa!paa!
●! Random!
o! Necrobiosis(lipoidica!
o! No!need!for!fasting!
o! Reflect!sugar!control!in!the!last!3!months!
●! Adapted*from*the*Phil*UNITE*for*Diabetes*Clinical*Practice*
Guidelines*for*Diagnosis*and*Management*of*Diabetes:!
o! HbA1c*using*a*method*approved*by*the*National*
Glycohemoglobin*Standardization*Program*(NGSP)*is*
recommended*for*diagnosis*and*risk*assessment*only*by*the*
American*Diabetes*Association*as*of*2010.!
o! The*ADA*cutGoff*for*diagnosis*is*>6.5%,*and*for*patients*at*risk*
for*DM,*it*is*5.7%&to&6.4%!
o! If*it*cannot&be&confirmed*whether*the*HBA1c*assay*used*is*
NGSPGcertified*(usual*situation*in*PH),*then*the*assay*cannot&
be&used&for&diagnosis!
* &
Figure(2.!Necrobiosis!lipoidica* C.(PRESENCE(OF(C[PEPTIDE(
o! Yellow!macules!(upper!eyelid!and!around!eyes)! ●! 31Gresidue*peptide*formed*from*proinsulin&cleavage!
♦! Usually!deposits!of!lipids! ●! Stored*and*secreted*with*insulin*in*granules*within*beta7cell*
♦! Likely!due!to!hypercholesterolemia! islets!
●! Mononeuropathy:!upper!eyelid!paralysis! ●! Useful*marker*for*insulin*secretion*due*to*slower&clearance*
o! SelfIlimiting\!treat!the!blood!sugar! versus*insulin!
●! Error!of!refraction,!macular!edema,!retinopathy!–!vitreous! *

hemorrhages,!microaneurysms! D.(ABSENCE(OF(ANTIBODIES(
o! Look*out*for*antiGTB*medications*which*cause*retinopathy:* ●! One*of*the*differences*between*Type*1*and*Type*2*Diabetes*
ethambutol,*isoniazid! Mellitus!
o! Changes!glasses!constantly! ●! Important&immunologic&markers&which*are*absent*in*T2*DM*are*
o! Don’t!forget!to!check!acute!vision!since!threatened!organ! islet*cell*autoantibodies*(ICAs),*which*include:!
●! Decreased!sensation!(feet)! o! AntiGGAD! o! ICAG512!
o! Monofilament!Test,!Vibratory!sense!(Turning!Fork)! o! AntiGinsulin! o! ZnTG*58!
o! IAG2!
●! Type*I*DM*is*more*likely*with*a*positive*antiGGAD*(glutamic*acid*
decarboxylase)*reading!
*
E.(SUBTYPES(
●! Analysis!of!the!ANDIS!Cohort!study!(2008)!(Sweden)!by!Alhqvist!
et!al.!(2018)!led!to!the!creation!of!subclassifications!of!diabetes!
based!on!six!variables!
o! Glutamic!acid!decarboxylase!antibodies!
o! Age!at!Diagnosis!
o! BMI !
o! HbA1c!
o! Homoeostatic!model!assessment!2!(HOMA2)!of!ꞵ7cell!function!
o! HOMA2!of!Insulin!Resistance!
!
Figure(3.!Monofilament!test! ●! Replication!was!done!on!3!studies,!all!mostly!Scandanavian!
●! Poor!pulses! o! this!brings!up!the!problem!of!genetic!variability!in!the!
o! Can’t!find!dorsalis!pedis!pulse! population!
●! Poor!oral!hygiene!and!dentition! ●! Subtypes!
o! Gum!examination!is!important! o! Severe!Autoimmune!Diabetes!(SAID)!
! o! Severe!InsulinIDeficient!Diabetes!(SIDD) !
VII.(DIAGNOSIS( ♦! notable!risk!of!retinopathy!
●! Diagnostic!Criteria!for!Type!2!Diabetes!Mellitus:!!! o! Severe!InsulinIResistant!Diabetes!(SIRD)!
o! Fasting!Blood!Sugar! ♦! notable!NonIAlcoholic!Fatty!Liver!Disease!(NAFLD)!
o! HbA1c! prevalence!
o! (+)!CIpeptide! o! Mild!ObesityIrelated!Diabetes!(MOD) !
o! (I)!Antibodies! ♦! “Healthy!Obese”!
!
o! Mild!AgeIRelated!Diabetes!(MARD) !
A.(FASTING(BLOOD(SUGAR( ♦! Lifestyle!or!metformin!is!fine!
●! ! ♦! Notably!the!most!prevalent!subtype!among!all!registries!
●! Fasting!is!defined!as!no!caloric!intake!for!at!least!8!hours!
●! 75g!OGTT!

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! OS(215! Diabetes in Adults!
B.(PHARMACOLOGIC(THERAPY(
!

1.(Validated(
●! “Matagal!na!sa!market”,!we!know!the!mechanism!of!action!
●! Insulin!
o! Hormone!that!lowers!blood!sugar!
o! Discovered!primarily!by!Prof.!Banting!and!Charles!Best!(a!med!
student!working!under!the!prof)!
o! Dialyzable\!crosses!placenta!so!can!be!used!for!gestational!
diabetes!
o! Watch!out!for!hypoglycemia!
●! Metformin!
o! Cheap!(₱1!!:O)!
o! Depends!on!available!insulin!in!the!body!
o! Insulin!sensitizer!
( o! Reports!show!that!abdominal!girth!of!babies!tend!to!grow!
Figure(4.!Subclassification!of!Diabetes!according!to!Alhqvist!et!al.!(2018)( bigger!
( o! Does!not!cause!hypoglycemia!(in!contrast!to!sulfonyl!urea)!
VIII.(MANAGEMENT( o! Absorbed!in!ileum!
A.(HEALTHY(LIFESTYLE( o! AntiIcancer!
1.(Nutrition((“diet”)( ●! Sulfonyl(urea!
●! Modify!calories!per!kilogram!of!body!weight!per!day!(depending! o! Insulin!secretagogue!
on!whether!patient!needs!to!gain,!lose!or!maintain!weight)! o! Direct!pancreas!to!secrete!more!insulin!
o! Also!take!note!of!patient’s!regular!meal!schedule.!Do!not! o! Overcomes!insulin!resistance!
enforce!3!meals!if!patient!is!not!used!to!it! o! May!cause!hypoglycemia!
●! Salt! o! May!lead!to!oral!hyperglycemic!failure!when!insulin!stores!
o! Do!not!restrict!patient’s!diet!to!“no!salt”.!Patients!do!not!enjoy! have!been!exhausted!
this!diet,!not!feasible! o! In!such!cases,!exogenous!insulin!must!be!administered!
o! Better!to!choose!“no!additional!salt”! o! Once!the!pancreas!recovers,!patient!can!go!back!to!using!
o! Regulate!advice!to!patients!in!allowing!diet!soda!because!it! sulfonyl!urea!
!
has!high!salt!content!that!may!increase!blood!pressure!with! 2.(Less(Validated(
uncontrolled!consumption\!drink!plenty!of!water!to!prevent!
●! Newer!agents!
hyperosmolarity!
●! Risk!of!unstudied!long!term!effects!
●! Simple!sugars!(e.g.!soda,!candies,!juice)!
●! Rosiglitazone!–!may!cause!CHF!
o! Easily!absorbed!by!the!intestines!!
●! Pioglitazone!–!may!cause!bladder!cancer!and!CHF!
o! Limit!unless!already!in!hypoglycemic!state!
o! Substitutes!to!simple!sugars:!fresh!fruit!(3!fresh!fruits!divided! ●! DPP4!–!may!cause!CIcell!hyperplasia,!congestive!heart!failure,!
angioedema!
into!3!meals),!e.g.,!lanzones!(7!pcs!per!meal)!Pomelo!(3!
segments!per!meal)! ●! GLP1!agonists!
o! Philippines(has(very(sweet(food(culture! ●! Amylin!mimetics!
●! Protein! ●! SGPLT2!inhibitors!(Igliflozins)!
!
o! Ketogenic!diets!=!not!good! 3.(Polypharmacy(
●! Don’t!take!too!much!fiber,!they!might!get!constipated!
●! Adult!type!2!diabetics!are!polypharmacy!patients!
●! Take!note!of!patient’s!other!conditions:!
●! Many!have!DM,!HTN,!dyslipidemia,!antiIdepressants!
o! If!with!kidney!disease:!avoid!proteins!
o! AntiIdepressants!will!increase!sugar!and!can!cause!weight!
o! If!with!dyslipidemia:!avoid!fat!
gain!
●! Sorbet!good,!high!calorie!ice!cream!bad! o! Newer!antiIdepressants!have!less!diabetic!side!effects!
!
2.(Exercise( ●! Drugs!for!other!conditions!may!have!effects!on!DM!parameters,!
and!vice!versa!
●! Eat!less\!move!more!
●! Consider!the!ADME!of!statins,!metformins!and!check!function!of!
●! 150!minutes!per!week!
affected!organs!
●! Studies!supporting!healthy!lifestyle!as!a!preventive!factor!in!
o! E.g.!statins!for!dyslipidemia!affect!cholesterol!synthesis!high!
developing!frank!diabetes!from!preIdiabetic!state!(assigned!
up!in!the!biochemical!pathway!leading!to!an!increase!in!
readings,!not!discussed!in!class):!
cortisol!production!
o! Diabetes!Prevention!Program!(2002)!(USA)! ! !
♦! Treatment!of!metformin!and!modification!of!lifestyle!were! C.(GOAL(SETTING(
two!highly!effective!means!of!delaying/preventing!type!2! Table(2.!Setting!HBA1c!levels.!
diabetes! Glycosylated!Hemoglobin!Range!
o! Kuwamoto!study!(2000)!(Japan)!!
♦! Intensive!glycemic!control!(3+!insulin!injections)!can!delay! !
Most(intensive(level( Least(intensive(
the!onset!and!progression!of!the!early!stages!of!diabetic!
(aggressive(treatment),( level,(
microvascular!complications!in!Japanese!patients!with!type! Factors(
Approximately(60%(of( Approximately(0.8%(
2!diabetes! patients( of(patients(
o! Finnish!Diabetes!Prevention!Study!(2003)!(Finland)!! Less!motivated,!nonI
♦! Intensive!lifestyle!intervention!led!to!longIterm!beneficial! Highly!motivated,!
Psychological! adherent,!less!
changes!in!diet,!physical!activity,!and!reduced!diabetes!risk! adherent,!knowledgeable,!
considerations! knowledge,!weak!
o! XENDOS!study!(2004)!(Sweden)!! strong!selfIcare!capacity!
selfIcare!capacity!
♦! Compared!with!lifestyle!changes!alone,!orlistat!+!lifestyle!=! Resources!or!
greater!reduction!in!incidence!of!Type!2!DM!over!4!years!! Adequate! Inadequate!
support!system!
and!greater!weight!loss!in!obese!population! Risk!of!
! Low! High!
hypoglycemia!

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Duration!of!Type! ●! Insulin!deficiency!and!glucagon!excess!are!necessary!for!DKA!to!
Short! Long!
2!diabetes! develop!
Long! Life!expectancy! Short! ●! Decreased!ratio!of!insulin!to!glucagon!promotes!
Microvascular! gluconeogenesis,!glycogenolysis,!and!ketone!body!formation!in!
None! Advanced!
disease! the!liver!as!well!as!increases!substrate!delivery!from!fat!and!
Cardiovascular! muscle!to!the!liver!
None! Established!
disease! ●! Ketosis!results!from!a!marked!increase!in!the!free!fatty!acid!
CoIexisting! Multiple,!severe!or! release!from!adipocytes,!with!a!resulting!shift!toward!ketone!body!
None!
conditions! both! synthesis!in!the!liver!!
!
!
●! Important!to!set!goals! Euglycemic(Diabetic(Ketoacidosis!
o! If!you!are!young,!be!aggressive!and!aim!to!prolong!
●! SGLT2!inhibitors!(inhibits!reabsorption!of!sugar!in!kidney)!will!
o! If!old,!give!a!leeway!to!treatment,!let!them!enjoy!life!
induce!renal!problems!
o! Hypoglycemia!can!cause!death!in!senior!citizens!(heart!attack)!
o! Due!to!excessive!sugar!excretion!
●! Goals!for!regulation!of!Type!2!DM!
o! Sugar!goes!down,!endogenous!insulin!goes!down,!lipolysis!
o! Sugar!control!
isn’t!stopped!
o! Blood!pressure!control!!
o! Not!seen!if!given!exogenous!insulin,!results!in!ketoacidotic!
o! Lipid!control!
state!
o! Weight!control!
●! Can!be!caused!by!a!ketogenic!diet!
o! No!proteinuria!
o! Unhealthy!(low!carb,!high!fat!and!protein)!
o! Healthy!lifestyle!
o! Glycogen!stores!used!up!(2!weeks!max!for!stored!glycogen)!
o! Happy,!not!depressed,!no!depression!
! o! Emergency!case!when!they!arrive!at!the!hospital!
IX.(COMPLICATIONS( o!
A.(ACUTE(COMPLICATIONS(
●! Differentials!for!patients!with!decreased!sensorium!(6!I’s)!
!
o! Insulin!problems! o! !
o! Iatrogenic! ♦! Infuse!sugar!(10%!dextrose)!
o! Infection! ♦! Drip!insulin!until!lipolysis!stops!and!blood!pH!becomes!7.4!
o! Inflammatory!conditions! o! Watch!out!for!hypokalemia!(cannot!use!insulin!if!K!level!is!
o! Ischemic!conditions! below!3.5!mmol)!
o! IntoxicationI!alcohol,!street!drugs! !
! B.(CHRONIC(COMPLICATIONS(
!
Hyperosmolar(hyperglycemic(state!
1.(Microvascular(
●! previously!called!hyperosmolar!nonIketotic!coma!or!HONK!
●! Blindness!(Retinopathy)\!recent*finding:*retinopathy*may*also*be*
●! 1!of!2!serious!metabolic!derangements!that!occurs!in!patients!
caused*by*ethambutol*toxicity*(TB*drug)L*most*common*effect*in*
with!diabetes!mellitus!(DM)!and!can!be!a!lifeIthreatening!
diabetes!
emergency!
●! Foot(ulcers((can(be(neuropathic(or(ischemic,(complicated(by(
●! It!is!less!common!than!the!other!acute!complication!of!diabetes,!
infections),(Charcot(foot((from(syphilis(or(DM),(amputations!
diabetic!ketoacidosis!(DKA). !
o! Charcot!foot!I!ulcers!end!up!on!the!side,!instead!of!the!
●! Harder!to!catch!than!DKA!where!the!smell!of!acetone!is!
metatarsals!
prominent!
o! Look!at!pressure!area!of!foot!–!ball!of!metatarsal,!heel!
●! Hydrate!!
o! Must!treat!diabetes!to!remove!ulcers!
●! High!sugar,!little!ketones,!no!insulin!(due!to!obtunded!effect) o! Antibiotics!are!ineffective!
! ●! End!Stage!Renal!Disease!
o! Takes!time!before!it!happens.!Manifestations!include:!
●! Found!Type!1!DM!adults,!or!burnout!Type!2!DM!
♦! Anemia!
!
♦! Hemodialysis!
Hypoglycemia( ♦! Kidney!Transplant!I!if!younger!
●! Patients!in!PGH!come!in!with!this! ♦! If*patient*has*Internal*jugular*catheter,*you*know*they*have*
●! Taking!metformin!for!a!long!time!decreases!appetite! ESRD!
●! ! !
2.(Macrovascular(
●! Delayed(recovery(due(to(depleted(glycogen(stores(of(the(
liver! ●! Coronary!Artery!Disease!
o! Pacemaker!
●! Treat!with!glucose!
o! CABG!
●! Maintain!them!on!IV(dextrose(50%!for!1!week!
o! PCI!stents!
o! If!not!available!(like!in!Cordillera),!scoop!honey!and!put!in!
patient’s!mouth!and!rub!it!for!the!buccal!mucosa!to!absorb!it! ●! Stroke\!prevention!is!better!than!surgery!!Very!poor!prognosis!
(or!intrarectally)! once!you’ve!had!this.!
●! D50!has!delayed!recovery!so!it!won’t!work!instantaneously! ●! Peripheral!vascular!diseaseI!in!conjunction!with!ischemic!foot!I>!
o! Due!to!obtunded!effect!of!insulin,!possible!DOA!in!extreme! amputation!
!
cases!
o! Maintain!with!D10!so!that!it!will!sustain!the!glucose!in!the! 3.(Psychosocial(
mean!time! ●! Depression!
! o! Reassure!patient!if!they!aren’t!able!to:!
Diabetic(Ketoacidosis((DKA)( ♦! follow!diet,!lose!weight,!meet!goals,!etc!
●! Characterized!by:(hyperglycemia,(ketosis,(and(metabolic( ●! EMPATHY!I!BE!GRATEFUL!TO!THE!PATIENTS,!OUR!LIVING!
acidosis! TEXTBOOKS!
●! Results!from!relative!or!absolute!insulin!deficiency!combined!with! o! Knowledge,!Skills,!Attitudes,!Practices!
counterIregulatory!hormone!excess!(glucagon,!catecholamines,! o! Always!put!condition!of!patient!first!
cortisol,!&!growth!hormone)! !

Trans Group #40: Sarsagat, Serrano A., Serrano D., Sevilla

!

!
! OS(215! Diabetes in Adults!
REFERENCES(
2021!Trans!
Reduction!in!the!Incidence!of!Type!2!Diabetes!with!Lifestyle!Intervention!or!Metformin.!(2002).!!
New*England*Journal*of*Medicine,!346(6),!393I403.!doi:10.1056/nejmoa012512!
Ahlqvist,!E.,!Storm,!P.,!Käräjämäki,!A.,!Martinell,!M.,!Dorkhan,!M.,!Carlsson,!A.,!…!Groop,!L.!!
2018).!Novel!subgroups!of!adultIonset!diabetes!and!their!association!with!!
outcomes:!a!dataIdriven!cluster!analysis!of!six!variables.!The*Lancet*Diabetes*&*Endocrinology,!
6(5),!361I369.!doi:10.1016/s2213I8587(18)30051I2!
Liao,!T.,!Chen,!Y.,!Huang,!S.,!Tan,!L.,!Li,!C.,!Huang,!X.,!…!Zeng,!Q.!(2017).!Chondroitin!sulfate!!
elicits!systemic!pathogenesis!in!mice!by!interfering!with!gut!microbiota!homeostasis.!!
doi:10.1101/142588!
Lindstrom,!J.,!Louheranta,!A.,!Mannelin,!M.,!Rastas,!M.,!Salminen,!V.,!Eriksson,!J.,!…!!
Tuomilehto,!J.!(2003).!The!Finnish!Diabetes!Prevention!Study!(DPS):!Lifestyle!!
intervention!and!3Iyear!results!on!diet!and!physical!activity.!Diabetes*Care,!26(12),!!
3230I3236.!doi:10.2337/diacare.26.12.3230!
Murase,!Y.,!Wakasugi,!T.,!Yagi,!K.,!&!Mabuchi,!H.!(2000).!Deterioration!of!glycemic!control!after!!
longIterm!treatment!with!troglitazone!in!nonobese!type!2!diabetic!patients.!Diabetes**
Care,!23(1),!131I132.!doi:10.2337/diacare.23.1.131!
Reine,!T.!M.,!Grøndahl,!F.,!Jenssen,!T.!G.,!HadlerIOlsen,!E.,!Prydz,!K.,!&!Kolset,!S.!O.!(2013).!!
Page 6 of 7
Reduced!Sulfation!of!Chondroitin!Sulfate!but!Not!Heparan!Sulfate!in!Kidneys!of!Diabetic!db/db!Mice.!
Journal*of*Histochemistry*&*Cytochemistry,!61(8),!606I616.!doi:10.1369/0022155413494392!
Rossing,!P.!(2018).!Subclassification!of!diabetes!based!on!quantitative!traits.!Nature*Reviews**
Nephrology,!14(6),!355I356.!doi:10.1038/s41581I018I0011I9!
Schwartz,!S.!S.,!Epstein,!S.,!Corkey,!B.!E.,!Grant,!S.!F.,!Gavin,!J.!R.,!&!Aguilar,!R.!B.!(2016).!The!!
Time!Is!Right!for!a!New!Classification!System!for!Diabetes:!Rationale!and!!
Implications!of!the!βICell–Centric!Classification!Schema.!Diabetes*Care,!39(2),!!
179I186.!doi:10.2337/dc15I1585!
Torgerson,!J.!S.,!Hauptman,!J.,!Boldrin,!M.!N.,!&!Sjostrom,!L.!(2003).!XENical!in!the!Prevention!of!!
Diabetes!in!Obese!Subjects!(XENDOS)!Study:!A!randomized!study!of!orlistat!as!an!!
adjunct!to!lifestyle!changes!for!the!prevention!of!type!2!diabetes!in!obese!patients.!!
Diabetes*Care,!27(1),!155I161.!doi:10.2337/diacare.27.1.155 !
END(OF(TRANS(
!
Constantia!inter!mutanda!
!
follow!https://twitter.com/EverythingGoats!for!goats

APPENDIX(
●! Amylin!
o! 37Iamino!acid!peptide!which!is!coIsecreted!with!insulin!by!β!cells!
o! Comprises!the!amyloid!fibrils!found!in!the!islets!of!patients!with!type!2!DM!
●! Incretins!
o! Released!from!neuroendocrine!cells!of!the!GIT!
o! following!secretion!and!suppress!glucagon!secretion!
o! GLPI1!is!the!most!potent!food!ingestion!and!amplify!glucose!stimulated!insulin!incretin,!and!incretin!analogues!are!used!to!enhance!
endogenous!insulin!secretion!
(
Table(1.!Interventions!for!Pathophysiological!Alterations.!
Major(Pathophysiological(Changes(in(
Interventions(
Type(2(DM(
Sulfonylureas,!meglitidines,!GLPI1!agonists,!DPPI
Decreased!insulin!secretion!
IV!inhibitors!
Weight!loss,!exercise,!biguanides,!
Increased!insulin!resistance! thiazolidinediones,!D2!dopamine!receptor!
agonists!
Weight!loss,!exercise!biguanides,!thiazolidinones,!
Increased!hepatic!glucose!production!
bile!acid!sequestrants!
Other(Pathophysiological(Changes(in(
Interventions(
Type(2(DM(
GLPI1!agonists,!DPPIIV!inhibitors,!amylin!
Increased!glucagon!secretion!
mimetics!
Increased!appetite! GLPI1!agonists,!amylin!mimetics!
GLPI1!agonists,!DPPIIV!inhibitors,!bile!acid!
Impaired!incretin!effect!
sequestrants!
Decreased!amylin!secretion! Amylin!mimetics!
Carbohydrate!absorption! AlphaIglucosidase!inhibitors!

Figure(1.!Egregious!Eleven!(Vit!D,!Testosterone!Deficiencies!missing)!
!

Trans Group #40: Sarsagat, Serrano A., Serrano D., Sevilla

!
 Page 7 of 7
!
! OS(215! Diabetes in Adults!

!
Figure(2.!Unlucky!Thirteen!
! !
!
!

Trans Group #40: Sarsagat, Serrano A., Serrano D., Sevilla

!
1. Sources of glucose
2. Normal insulin chuhuc

Hyperglyvemia: chronic damages

Glycemia: glucose in blood
Presence of it: where is it from?
SOURCES OF GLUCOSE in blood:
• Food
• Glycogen from liver
• NOT muscle: it stores glucose
• NOT fat
• Kidneys: contributes via gluconeogenesis

Need glucose to entwer cell: by glycolysis turns into pyruvate and turn into ATP
• more ATP: will act on ATP sensitive channel, closing it (more ATPs, will close)
• Uneqal charges will depolarize and opens a votage gated channel: the Cacium channel
• Calcium enters cell and becomes a messenger that allows glucosein cell to be transported\
• INSULIN secretion happens thru glucose
• Insulin is an abnormal feature in diabetes, since it goes into the blood
• Pancrea
FOR NORMAL PHYSIO:
GLUT4: translocated to cell membrane and allows entrance of glucose into muscle cell
GLUT2: for beta cell

Tyrosine: amino acid --> if phyosphorylated: into Serine? This insulin action mech wont happen

Normal Insulin ???CHECK RECORDING: this is a PART

CHECK RECORDING for Classification of DM

1. Type 1: Autoimmune
2. Type 2: Insulin-resistance
3. Gestational DM: only in women
4. Specific types of diabetes: very heterogenous

• HORMONES that anatgonize. Insulin

1. Growth Hormon: excess, acromegaly
2. Cortisol, Cushings
3. Somatostatin. Increase due to tumor, Somatostatinoma
4. Glucagon, Tumor of alpha cells: glucagonoma
• diseases that are endocrine in nature that produce against insulin
• DRUG: if used in excess can lead to diabetes: cotisol (steroids), Beta-agonists (can induce some
insulin resistance)
• VIRUSES: HIV
• UNCOMMON: those that lead to autoimmune, genetic disorders hehe

HOW TO DIAGNOSE DIABETES

• very labs heavy: need to monitor glucose in blood

5110
• Criteria !!! MEMORIZE !!!
◦ Puro OR
◦ FBG: muultiply by 18 (7): cut off for fasting blood glucose
◦ 7 or 126: cut off, based on development of retinopathy complication
◦ Memorize vaues!!
 ◦ Yellow: impaired fasting glucose (middle) and impaired glucose tolerance (dulo) = PRE-
DIABETIC
◦ Not normal but not diabetic: being prediabetic is 25% will become diabetic

CLASSIC SYMPTOMS OF DM
1. Polyuria: kidney filters glucose when osmolality increasess; glucose absorbs water, so when
glucose gets excreted
2. Polydypsia: especially during night (alternating 1 and 2); you drink a lot since a lot of water loss
3. Weight Loss despite good appetite: glucose is not used properly
Glucosuria: a lot in the urine, so genital areas get infected
Prone to periodontisits
Delayed wound healing
Nerve complications: burning pain and numbness of feet
Decreased vision: catarac, swelling of lens due to glucose in lens (glucose is converted to sugar
alcohol in lens (Sorbitol)

RISK FACTORS
[patterned after how to interview/take hx]
Clinical Hx:
All asians at risk
In the U: 9 lbs of baby weighing (8lbs is for Filipinos)!! Take note of context, if for Filipinos or
American*
Comorbids: PAD, peripheral artery disease, Coronary Artery disease
Onl;y philippines" schizo (drugs made them insulin resistant) and TB(low immune system that made
them prone to TB)

PCOS

PE: Overweight = Pre-Obese

waist circumference: lowest intercostal cartilage and ASIS midpoint
Waist: hip ratio (hip: "pinakamatambok sa pwet")
Pre-Obesity: BMI >23 <25 in AP region; Obese: >25
Waistline

PE: Acanthosis Nigricans: elevated, course hyperpigmentation

• Important manifestations of insulin resistance

TRIGLYCERIDES:
• glycolysis: glucose will evernytually get converted into gtriglycerides: hypertrigylcerid

PATHOGENESIS & NATURAL HISTORY

In 2008, in American
• if diabetic the ??goes fdown: UKPDS; lost at least 50% beta cell mass when diagnosed as
diabetic
◦ Lower insulin, higher sugar
◦ C-peptide lowers,
2 DIFFERENT DIABETIC PHENOTYPES
1. Lean phenotype: destruction of beta cells, progressively deteriorates: progressive beta-cell and
type 2 diabetes

2 hormones released from the gut:

1. L-cells in ileum: proglucagon
2. K-cell in jejenum: ProGIP
Higher glucose intake: higher GIP and GLP-1
• if gastric emptying is inhibited, faster to feel full/longer
• Iibit glucaagon secretion: insulin action will be enhanced
• beta cell survival
• Food intake in brain (GLP-1 reaches brain)
In contrast, GIP: opposite of everything except effects on beta cell
Lots of GLP 1: enchances, then glucose control

1960s: experiemtns with rats, administering glucose via IV adn GI tract, same degree
• INCRETIN EFFECT decreased
◦ - increase in insulin secretion due to the contribution of your GLP 1
◦ In diabetic: smaller or mas mababa
◦ DPP-4 !!!!!!!: enzymes that break down your GLP-1, glucagon will go up if not enough GLP-1

SETACEUOS SEXTET
High glcagon

HYPERGLUCOGANEMIA: ??? Check recording

If sugar is elevated: urine will have urine --> GLUCOSURIA

• glucose shgould be reabsorbed by SGLT2 + SGLT1 in distal convuluted tube
• GLUT2 in beta cell is different from GLUT2 in kidneys
◦ Filtered glucose is returned to the blood
◦ In diabetes: SGLT2 and GLUT2 is overly expressed: HIGHER BLOOD SUGAR

BRAIN: neurotransmitters stop you from eating when youre full

• lower magnitude of inhibitory response and longer before it takes action (duration doubled): more
intake adn then more glucose in blood!!
• dopamine is low in hypothalamus in the mornin in diabetic:

EGREGIOUELEVEN!! BETA CELL PAR IN PROBLEM

UNLUCKY 13
In adult: 10-3pm to get sunlight

TYPE 1: presejnce of islet antibodies

5 CLUSTERS OF DIABETES

ALL OF THEM HAVE 1 THING IN COMMON: SUGAR IS HIGH

Ned to bring it down to: Harrisons pic:
In clinical practice:

COMPLICATIONS: can reduce quantity and quality of life

1. Acute: days-hours
A. DKA, HHS, Hypoglycemia
2. Chronic: weeks-months
A. Microvascular
a. Retinopathy, Nephropathy, neuropathy
b. Dialysis, cut off foot: quanlity of life will be poor
B. Macrovascular
a. CVA, CAD, PAD
 b. Die at once: quantity of life

MANAGEMENT
• not just look at sugar: lipids, BP, weight, cholesterol
A: control blood A1c
B: BP
C: cholesterol + cigarette smoking avoidance
D: Diet and wieght management
E: Exercise