Internal Medicine Training Session (1); Diabetes mellitus

8/16/2019 Internal Medicine Training Session (1); Diabetes mellitus

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IInntteerrnnaall mmeeddiicciinnee ttrraaiinniinngg sseessssiioonn ((11)) DDrr.. AAhhmmeedd OOtthhmmaann

Case study (1)

Case Study

• 55 year old, obese man, routinely avoidmedical care presented to the clinic with a

fasting blood sugar of 108 mg/ml and a 2

hours post-prandial of 186 mg/ml.

DDi i aaggnnoossi i nngg DDi i aabbeet t eess Diagnosing Diabetes

Casual plasma glucose ≥ 200mg/dlAND symptoms

– Polyuria, polydipsia, unexplained weight

loss

Fasting plasma glucose of ≥ 126mg/dlAND symptoms

2 RBS or 2 FPG without symptoms

Oral Glucose Tolerance TestFasting

• Oral glucose load of 75g anhydrous glucose dissolved in water

• Plasma glucose testing at 2 hours

Oral Glucose Tolerance Test in pregnancyFasting more than 95


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• Oral glucose load of 100g glucose dissolved in water

• Plasma glucose testing at 3 hours

1 h more than 180

2 h more than 155 3 h more than140 When to screen…

•• SSccrreeeenniinngg f f oorr TT11DDMM iinnvvoollvveess tthhee mmeeaassuurreemmeenntt oof f aauuttooaannttiibbooddyy mmaarrkkeerrss ((aannttiibbooddiieess ttoo iisslleett cceellllss,,

iinnssuulliinn,, gglluuttaammiicc aacciidd ddeeccaarrbbooxxyyllaassee,, aanndd ttyyrroossiinnee

pphhoosspphhaattaassee))..

• Every 3 years for all individuals >45yo T2DM• More frequently or at a younger age if … BBMMII >>2255

-- HHyyppeerrtteennssiioonn

IInnaaccttiivvee -- HHDDLL225500

hh//oo gglluuccoossee iinnttoolleerraannccee -- PPCCOOSS

HHiigghh rriisskk eetthhnniicc ggrroouupp -- VVaassccuullaarr ddiisseeaassee


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hh//oo ggeessttaattiioonnaall DDMM --HHaavvee ddeelliivveerreedd aa bbaabbyy wweeiigghhiinngg 44kkgg

Targets for Treatment

HHbbAA11cc


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•• MMiiccrrooaallbbuummiinn mmeeaassuurreemmeenntt Nutritional Recommendation

• Provide individualized meal planningguidelines

• Carbohydrate training• Caloric balancing• Exercise

Oral Therapy

Typically reduces HbA1c by 2-3 pointsmaximum

CChhoooossiinngg aann OOrraall TThheerraappyy

•• GGlluuccoopphhaaggee ((MMeettf f oorrmmiinn)) – Increases sensitivity to endogenous insulin

– Decreases hepatic glucose production

– First line for obese patients

•• A Accaarrbboossee ((PPrreeccoossee)) – – DDeellaa y yss gglluuccoossee aabbssoorrppttiioonn

•• SSuullf f oonnyylluurreeaass – – IInnccrreeaasseess rreelleeaassee oof f eennddooggeennoouuss

iinnssuulliinn

– – FFiirrsstt lliinnee f f oorr nnoonn--oobbeessee ppaattiieennttss


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•• TThhiioozzoolliinnddiinneeddiioonneess – IInnccrreeaasseess iinnssuulliinn sseennssiittiivviittyy

Glucophage

AAddvvaannttaaggeess – – MMiinniimmaall wweeiigghhtt ggaaiinn

– – NNoo aaddddeedd rriisskk oof f hhyyppooggllyycceemmiiaa

AAddvveerrssee EEf f f f eeccttss – – GGII uuppsseett ccoommmmoonn

– – LLaaccttiicc aacciiddoossiiss ((uunnccoommmmoonn bbuutt 5500%% mmoorrttaalliittyy)) SSttaarrttiinngg DDoossee

– – 550000mmgg PPOO BBIIDD oorr 885500mmgg PPOO Q Q DD

– – IInnccrreeaassee bbyy 550000mmgg Q Q WWeeeekk

Glucophage

Contraindications

– – RReennaall iimmppaaiirrmmeenntt:: CCrreeaattiinniinnee >> 11..55 f f oorr mmeenn aanndd >> 11..44 f f oorr wwoommeenn;; ((ccaauuttiioonn iiss wwaarrrraanntteedd

iinn eellddeerrllyy ppaattiieennttss))

– – CCaarrddiiaacc oorr rreessppiirraattoorryy iinnssuuf f f f iicciieennccyy tthhaatt iiss

lliikkeellyy ttoo ccaauussee hhyyppooxxiiaa oorr rreedduucceedd ttiissssuuee

ppeerrf f uussiioonn

– – CCHHFF – – HHiissttoorryy oof f llaaccttiicc aacciiddoossiiss

– – SSuurrggeerryy

– – SSeevveerree iinnf f eeccttiioonn tthhaatt ccaann lleeaadd ttoo ddeeccrreeaasseedd


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ttiissssuuee ppeerrf f uussiioonn

– – AAllccoohhooll aabbuussee ssuuf f f f iicciieenntt ttoo ccaauussee aaccuuttee

hheeppaattiicc ttooxxiicciittyy

– – UUssee oof f IIVV rraaddiiooccoonnttrraasstt aaggeennttss

Glucophage

Others

CCiiddoopphhaaggee 550000-- RReettaarrdd 885500

GGlluuccoopphhaaggee 550000-- 11000000

SSuullf f oonnyylluurreeaass

Includes: – – gglliippiizziiddee ((GGlluuccoottrrooll// mmiinniiddiiaabb 55)),,

– – gglliimmeeppiirriiddee ((AAmmaarryyll //DDoollccyy)),,

– – ggllyybbuurriiddee ((DDiiaabbeettaa//MMiiccrroonnaassee)) -- GGlliibbeennccllaammiidd ((DDaaoonniill55 -- DDiiaabbeenn 55))uupp ttoo 33

-- gglliiccaazziidd(( DDiiaammiiccrroonn8800 --MMRR3300--6600)) aannttiippllaattlleess

Adverse Effects – – HHyyppooggllyycceemmiiaa

– –WWeeiigghhtt ggaaiinn


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TThhiioozzoolliinnddiinneeddiioonneess

Includes: – – rroossiigglliittaazzoonnee ((AAvvaannddiiaa))

– – ppiioogglliittaazzoonnee ((AAccttooss // aaccttoozzoonn 3300-- 4455)) 1155::4455

-- RReeppaagglliinniiddee ((DDiiaarrooll 00..55--11--22))

Contraindications – – CCllaassss IIIIII oorr IIVV CCHHFF

– – BBaasseelliinnee AALLTT >> 22..55xx nnoorrmmaall

Adverse Effects – – EEddeemmaa

– – WWeeiigghhtt GGaaiinn

Alpha Glucosidase inhbitorsWork on the brush border of the intestine

cause carbohydrate malabsorption

Advantages:

• Selective for postprandial hyperglycaemia• No hypoglycaemic symptoms

Disadvantages:

• Abdominal Distension and flatus• Only effective in mild hyperglycaemia

Alpha Glucosidase inhbitors

• Acarbose- 25 mg to 50mg thrice a day


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• Miglitol- 25mg to 100mg thrice a day

• Voglibose- 0.2 to 0.3 mg thrice a dayContraindications

• an inflammatory bowel disease, such asulcerative colitis or Crohn's disease; or any other

disease of the stomach or intestines

• ulcers of the colon• Intestinal Obstruction• kidney disease.

Sulphonylurea + Metformin

Includes: – – GGlliibbeennccllaammiidd++mmeett550000 ((gglluuccoovvaannccee))

– – GGllyybbuurriidd ((DDiiaavvaannccee 11..2255--22..55--55))

Incretin concept

• Insulin secretion dynamics is dependent on themethod of administration of glucose


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• Intravenous glucose gives a marked first andsecond phase response

• Oral glucose gives less marked first and secondphase insulin response, but a

prolonged and higher

insulin

concentration

Insulin secretion profilesIso-glycaemic profiles

What are the incretins?

• GIP: Glucose-dependent insulinotrophic polypeptideSmall effect in Type 2 diabetes.

• GLP-1(glucagon-like peptide 1)augmented in the presence of hyperglycaemia.

Action less at euglycaemia and in normal subjects.

• Pituitary Adenylate Cyclase Activating Peptide(PACAP)

GLP-1 Modes of Action in Humans

Now for the bad News…………..

GLP-1 is short-acting


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Dipeptyl- peptidase inhibitors

Sitagliptin

VildagliptinSaxagliptin

Septagliptin

Allogliptin

DPP-4 Inhibitors

•• SSiittaagglliippttiinn ((JJaannuuvviiaa)) •• SSaaxxaagglliippttiinn ((OOnnggllyyzzaa)) •• LLiinnaagglliippttiinn (( TTrraadd j jeennttaa)) TTaakkee oonnccee aa ddaayy aatt tthhee ssaammee ttiimmee eeaacchh ddaayy IImmpprroovveess iinnssuulliinn lleevveell aaf f tteerr aa mmeeaall aanndd lloowweerrss tthhee

aammoouunntt oof f gglluuccoossee mmaaddee bbyy yyoouurr bbooddyy

Side effect

SSttoommaacchh ddiissccoommf f oorrtt,, ddiiaarrrrhheeaa,, ssoorree tthhrrooaatt,, ssttuuf f f f yy nnoossee,, uuppppeerr rreessppiirraattoorryy iinnf f eeccttiioonn..

Comparing the GliptinsSitagliptin Vildagliptin Saxagliptin

Dosing OD BD OD

Renal Failure Approved Not Approved Approved

Hepatic Failure No info No info

Safe

With Insulin Not Approved Approved

Studies Pending


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On Bone Improved BMD? Unknown

Unknown

Infections Slight increase NeutralNeutral

UTI, URI

Cardiac Impact RReedduucceedd Neutral

?reduced CV mortality

post ischaemic stunning

Which is the appropriate oral hypoglycaemic agentto use and when?

Mechanism of Action of Sitagliptin

Determinants of OAD usage1)Body Mass Index : Metformin, Gliptins

BMI> 22kg/m2

2)Presence of GI symptoms: Sulpha, Gliptins, Glitazones

3)Renal Dysfunction: Gliptins,Glitazones(+/-),Sulpha (variable)

4) Aging Meglitinides,

Gliptins(?)

5) Hepatic Dysfunction Nateglinide, Saxagliptin(?)

6) Compliance Gliptins, Glitazones,

7) Cost Metformin,

Sulphas, Glitazones

Back to our patient

• During the next five years he was not compliant to his


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medications despite

• having laser treatment for his left eye twice. And in thelast few months

• he noticed edema of his lower limbs.

IInntteerrnnaall mmeeddiicciinnee ttrraaiinniinngg sseessssiioonn ((22)) DDrr.. AAhhmmeedd OOtthhmmaann

Case study (2)

• A 32-year-old male with type 1 diabetes since the ageof 14 years was taken to the emergency room because ofdrowsiness, fever, cough, diffuse abdominal pain, and

vomiting.

• Fever and cough started 2 days ago and the patient couldnot eat or drink water.

• He has been treated with an intensive insulin regimen(insulin glargine 24 IU at bedtime and a rapid-acting insulin

analog before each meal )

Case study (2)

• On examination he was tachypneic.• His temperature was 39° C.• pulse rate 104 beats per minute,• respiratory rate 24 breaths per minute,• supine blood pressure 100/70 mmHg;


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• he also had dry mucous membranes, poor skin turgor, andrales in the right lower chest. He was slightly confused

Case study (2)

• Investigations:• hemoglobin 14.3 g/dl ,• white blood cell count 18,000/ μ l,• glucose 450 mg/dl,•

creatinine 1.2 mg/dl ,

DKA Definition

Pathophysiology

Etiology

• Insulin deficiency Insulin missed dose Pancreatitis Heavy meal

• Excess Counterregulatory hormones

• Infection i.e. Pneumonia• MI• Stroke• Trauma• Emotional


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• Pregnancy• Iatrogenic

Clinical manifestations

• Special notes• Abdominal pain It is more common in children than in adults It is multifactorial

dehydration of muscle tissue

Delayed gastric emptying Ileus from electrolyte disturbances Metabolic acidosis;

It sometimes mimicks acute abdomen It is classically periumbilical

Differential Diagnosis

• DD of acidotic breathing – Renal failure – Amonia increase in HCF – Hysterical

• DD of diabetic coma

– Lactic acidosis – Hyperosmolar non-ketotic coma – Hypoglycemia

• DD of coma in general


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• DD of acute abdomen

DKA vs. HHS

DKA vs. HYPOGLYCEMIAInvestigations

For diagnosis

Triad for diagnosis

• RBS Hyperglycemia > 250 mg/dl• Ketonemia and ketonuria

• Blood gas metabolic acidosis – pH < 7.35, anion gap (Na + K) – (Cl + Bicarb) > 10, and Bicarbonate


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For Monitoring

•• RRBBSS –

Every 1 hour till RBS reaches 200 mg/dL or less, then

every 6 hours

•• UUrriinnee kkeettoonneess – Every 8h

• BBlloooodd ggaass after fluid replacement• EElleeccttrroollyyttee sseerruumm lleevveell every 4 hours till correctionTreatment of DKA

• Treatment of predisposing factors• Initial hospital management

– Care of comatosed patients – Fluid and electrolytes replacement – Insulin replacement and glucose administration when

needed

– Treatment of complications

• Once resolved – Convert to home insulin regimen

– Prevent recurrenceFluids and Electrolytes

• Fluid replacement – Restores perfusion of the tissues


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– Average fluid deficit 3-6 liters• Initial resuscitation with saline

– 1 L of normal saline over the first ½ hour then – 1 L of normal saline over ½ hour then – ½ L of normal saline over 1 hour then – ½ L of normal saline over 2 hours

– Then the rate will depend on clinical judge(BP, CVP, basal lung crepitation)

Fluids and Electrolytes

•• KK++ lleevveell ((cchheecckk aatt 00,,22,,66,,1100,,2244 hhr r )).. – If Hyperkalemia (> 5.5 meqlL)

• initially present•

No treatment as it resolves quickly with insulin drip – If normal level (3.5-5.5 meqlL)

• Add 20-30 meql for each Liter of infused fluid

– If Hypokalemia (


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• If corrected Na is Low use NS, rate depends on severity ofvolume depletion

Insulin Therapy

• Initial dose – IV bolus of 0.1-0.2 units/kg (~ 10 units) regular insulin – Infusion insulin at 0.1 units/kg/hr (max 8 units/hr).

• Maintenance dose (Check BG Q1hour, goal is 50-80 mg/dl/hr ) –

If falling too rapidly, decrease the rate – If falling too slowly increase the rate by 50-100%

• Continue IV insulin until urine is free ofketones and RBS reaches 250-300 mg/dl

Insulin Therapy

•• WWhheenn RRBBSS rreeaacchheess 225500--330000 mmgg//ddll –

Decrease the rate of insulin infusion to 0.05-0.1 IU/kg/hr(goal is to keep RBS in this range until the gap closes(normal gap 7-8 mEq/l)

– then start home maintenance SC insulin underumbrella of infused insulin for 2 hours, then

continue on SC insulin only .

Glucose Administration

• Supplemental glucose – Hypoglycemia occurs


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• Insulin has restored glucose uptake• Suppressed glucagon

–

Prevents rapid decline in plasma osmolality

• Rapid decrease in insulin could lead to cerebral edema

• Glucose decreases before ketone levels decrease• Start glucose when plasma glucose < 300

mg/dl

Insulin-Glucose Infusion for DKA

Complications of DKA

Causes of Cerebral EdemaMechanism:

• The brain adapts by producing intracellular osmoles (idiogenic osmoles) whichstabilize the brain cells from shrinking while the DKA was developing.

• When the hyperosmolarity is rapidly corrected, the extracellular fluids is correctedfaster than brain cells

– The brain becomes more hypertonic than the extracellular fluids water flows into the cells cerebral edema

Causes of Cerebral EdemaThe many factors have been implicated:

Rapid and/or sharp decline in serum osmolality with treatment. High initial corrected serum Na concentration. High initial serum glucose concentration.

Failure of serum Na to raise as serum glucose falls during treatment.

Presentations of Cerebral Edema

CCeerreebbrraall EEddeemmaa PPrreesseennttaattiioonnss iinncclluuddee::

Deterioration of level of consciousness.


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Headache and blurring of vision Vomiting

Convulsion.Treatment of Cerebral Edema

• Reduce IV fluids• Raise foot of Bed• IV Mannitol• Elective Ventilation• Dialysis if associated with fluid overload or renal failure.• Use of IV dexamethasone is not recommended.

Prevention of DKA

• Never omit insulin – Cut long acting in half

• Prevent dehydration and hypoglycemia• Monitor blood sugars frequently• Monitor for ketosis• Provide supplemental fast acting insulin• Treat underlying triggers• Maintain contact with medical team

Pitfalls in DKA

• Plasma glucose is usually high but not always


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– DKA can be present with RBS < 300 due to• Impaired gluconeogenesis

– Liver disease – Acute alcohol ingestion – Prolonged fasting – Insulin-independent glucose is high (pregnancy)

• Chronic poor control but taking insulin

• Ketone in urine may be –ve in DKA, but always +ve in blood – Due to measurement of acetoacetic acid in urine not,

betahydroxybuteric acid

– Acetone in blood should be done in this case

Pitfalls in DKA

• High WBC may be present without infection• Infection may be present without fever• High Creatinine may be present without true renal function: it

may cross react with ketone bodies.

• Blood urea may be elevated with prerenal azotemiasecondary to dehydration.

• Serum amylase is often raised even in theabsence of pancreatitis

Case study (3) A 82-year-old male patient was taken to the emergencyroom in the afternoon for loss of consciousness in theprevious hour.


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The patient had hypertension, chronic ischemic heartdisease, and mild diabetes treated with glibenclamide daily.

On examination the patient had coma (Glasgow scale 5)

and right hemiplegia.

Whipples triad

• Symptoms consistent with hypoglycemia• Low plasma glucose concentration

• Relief of those symptoms after the plasma glucoselevel is raised

Risk factors

insulin doses are excessive, ill-timed, or of the wrongtype

influx of exogenous glucose insulin-independent glucose utilization sensitivity to insulin endogenous glucose production insulin clearance

Clinical features

MMIILLDD HHYYPPOOGGLLYYCCEEMMIIAA

- mainly adrenergic or cholinergic symptoms

Pallor


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Diaphoresis Tachycardia

Palpitations Hunger Paresthesias

Clinical features

MMOODDEERRAATTEE HHYYPPOOGGLLYYCCEEMMIIAA ((


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Oral carbohydrates (at least 15gm) Sources include

•

Three glucose tablets (5g each)

• 2 ½ cups of fruit juice• ½ to ¾ cup regular soda• 1 cup of milk

If patient is unable to take orally give IV dextrose

Treatment

MMOODDEERRAATTEE TTOO SSEEVVEERREE HHYYPPOOGGLLYYCCEEMMIIAA

Dextrose - 50mL of 50% dextrose IV bolus followed by 10%dextrose

Glucagon – 1mg IM or SC can be given Effective in treating hypoglycemia only if sufficient liver

glycogen present

These measures raise blood glucose only transiently Patient is urged to eat as soon as possiblePrevention

Patient education Knowing signs and symptoms of hypoglycemia Take meals on a regular schedule Carry a source of carbohydrate Self monitoring of blood glucose Take regular insulin at least 30 min before eating


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QUESTIONS

Internal Medicine Training Session (1); Diabetes mellitus

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Transcript of Internal Medicine Training Session (1); Diabetes mellitus