Internal medicine training session (1)

Dr. Ahmed Othman

Case study (1)
Case Study

55 year old, obese man, routinely avoid

medical care presented to the clinic with a
fasting blood sugar of 108 mg/ml and a 2
hours post-prandial of 186 mg/ml.

Diagnosing Diabetes
Diagnosing Diabetes

Casual plasma glucose 200mg/dl

AND symptoms
Polyuria, polydipsia, unexplained weight
loss

Fasting plasma glucose of 126mg/dl

AND symptoms

2 RBS or 2 FPG without symptoms

Oral Glucose Tolerance Test
Fasting
Oral glucose load of 75g anhydrous glucose dissolved in water
Plasma glucose testing at 2 hours

Oral Glucose Tolerance Test in pregnancy

Fasting more than 95

 Oral glucose load of 100g glucose dissolved in water

Plasma glucose testing at 3 hours

1h

more than 180

2 h more than 155

3 h more than140

When to screen

Screening for T1DM involves the measurement of

autoantibody markers (antibodies to islet cells,
insulin, glutamic acid decarboxylase, and tyrosine
phosphatase).
Every 3 years for all individuals >45yo T2DM
More frequently or at a younger age if
BMI >25
- Hypertension
Inactive
- HDL<35

First degree relative with DM

>250
h/o glucose intolerance
- PCOS
High risk ethnic group
- Vascular disease

-TG

h/o gestational DM -Have delivered a baby

weighing 4kg

Targets for Treatment

HbA1c

<6.5%

(Check q 3months until stable and

<7, then q 6months)

Premeal Glucose
Peak Postprandial G
Systolic
Diastolic
LDL

90-130mg/dl
<180mg/dl
<130
<80

<100

HDL
>40

Triglycerides

<150

Annual Monitoring Tests

Dilated eye exam

Foot exam
more often if neuropathy present
Lipid profile

Microalbumin measurement

Nutritional Recommendation

Provide individualized meal planning

guidelines
Carbohydrate training
Caloric balancing
Exercise

Oral Therapy
Typically reduces HbA1c by 2-3 points
maximum

Choosing an Oral Therapy

Glucophage (Metformin)

Acarbose (Precose)

Sulfonylureas

Increases sensitivity to endogenous insulin

Decreases hepatic glucose production
First line for obese patients
Delays glucose absorption

Increases release of endogenous

insulin
F irst line for non-obese patients

Thiozolindinediones
Increases insulin sensitivity

Glucophage

Advantages
Minimal weight gain
No added risk of hypoglycemia

Adverse Effects

GI upset common
Lactic acidosis (uncommon but 50% mortality)

Starting Dose

500mg PO BID or 850mg PO QD

Increase by 500mg Q Week

Glucophage
Contraindications
Renal impairment: Creatinine > 1.5 for men
and > 1.4 for women; (caution is warranted
in elderly patients)
Cardiac or respiratory insufficiency that is
likely to cause hypoxia or reduced tissue
perfusion
CH F
History of lactic acidosis
Surgery
Severe infection that can lead to decreased

tissue perfusion
Alcohol abuse sufficient to cause acute
hepatic toxicity
Use of IV radiocontrast agents
Glucophage
Others
Cidophage 500- Retard 850

Glucophage 500- 1000

Sulfonylureas

Includes:

glipizide (Glucotrol/ minidiab 5),

glimepiride (Amaryl /Dolcy),
glyburide (Diabeta/Micronase)
- Glibenclamid (Daonil5 - Diaben 5)up to 3
- glicazid( Diamicron80 -MR30-60) antiplatles

Adverse Effects

Hypoglycemia
Weight gain

Thiozolindinediones

Includes:

rosiglitazone (Avandia)
pioglitazone (Actos / actozon 30- 45) 15:45
- Repaglinide (Diarol 0.5-1-2)

Contraindications

Class III or IV CHF

Baseline ALT > 2.5x normal

Adverse Effects

Edema
Weight Gain

Alpha Glucosidase inhbitors

Work 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

Miglitol-

Voglibose- 0.2 to 0.3 mg thrice a day

25mg to 100mg thrice a day

Contraindications

an inflammatory bowel disease, such as

ulcerative 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:
Glibenclamid+met500 (glucovance)

Glyburid (Diavance 1.25-2.5-5)

Incretin concept

Insulin secretion dynamics is dependent on the

method of administration of glucose

Intravenous glucose gives a marked first and

second phase response

Oral glucose gives less marked first and second

phase insulin response, but a
prolonged and higher
insulin
concentration
Insulin secretion profiles
Iso-glycaemic profiles
What are the incretins?

GIP: Glucose-dependent insulinotrophic polypeptide

Small 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

Dipeptyl- peptidase inhibitors

Sitagliptin
Vildagliptin
Saxagliptin
Septagliptin
Allogliptin

DPP-4 Inhibitors

Sitagliptin (Januvia)
Saxagliptin (Onglyza)

Linagliptin ( Tradjenta)
Take once a day at the same time each day
Improves insulin level after a meal and lowers the
amount of glucose made by your body
Side effect
Stomach discomfort, diarrhea, sore throat, stuffy nose,
upper respiratory infection.

Comparing the Gliptins

Sitagliptin
Dosing

Vildagliptin
BD

OD
Renal Failure

Approved

Hepatic Failure

Not Approved

No info

Saxagliptin
OD
Approved

No info

Safe

With Insulin
Studies Pending

Not

Approved

Approved

On Bone

Improved BMD?

Unknown

Unknown

Infections

Slight increase

Neutral

Neutral
UTI, URI
Cardiac Impact
?reduced CV mortality

Reduced

Neutral

post ischaemic stunning

Which is the appropriate oral hypoglycaemic

to use and when?

agent

Mechanism of Action of Sitagliptin

Determinants of OAD usage
1)Body Mass Index :
BMI> 22kg/m2
2)Presence of GI symptoms:

Metformin, Gliptins

Sulpha, Gliptins, Glitazones

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

4) Aging

Meglitinides,
Gliptins(?)

5) Hepatic Dysfunction
6) Compliance
7)

Cost
Sulphas, Glitazones

Nateglinide, Saxagliptin(?)
Gliptins, Glitazones,
Metformin,

Back to our patient

During the next five years he was not compliant to his

medications despite

having laser treatment for his left eye twice. And in the
last few months
he noticed edema of his lower limbs.

Internal medicine training session (2)

Dr. Ahmed Othman
Case study (2)

A 32-year-old male with type 1 diabetes since the age

of 14 years was taken to the emergency room because of
drowsiness, fever, cough, diffuse abdominal pain, and
vomiting.
Fever and cough started 2 days ago and the patient could
not 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;

he also had dry mucous membranes, poor skin turgor, and

rales in the right lower chest. He was slightly confused

Case study (2)

Investigations:
hemoglobin 14.3 g/dl ,
white blood cell count 18,000/ l,
glucose 450 mg/dl,
creatinine 1.2 mg/dl ,

DKA Definition
Pathophysiology
Etiology

Insulin deficiency

Excess Counterregulatory hormones

Insulin missed dose

Pancreatitis
Heavy meal

Infection i.e. Pneumonia

MI
Stroke

Trauma
Emotional

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

DD of diabetic coma

DD of coma in general

Renal failure
Amonia increase in HCF
Hysterical
Lactic acidosis
Hyperosmolar non-ketotic coma
Hypoglycemia

DD of acute abdomen

DKA vs. HHS

DKA vs. HYPOGLYCEMIA
Investigations
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 <15 mEq/L

Investigations
For diagnosis

Other findings

Electrolyte serum level

Hyperkalemia (rarely Hypokalemia), Hyponatremia (rarely

Hypernatremia )

Investigation for the cause such as

Urine Analysis, AMI panel and ECG, Chest x-ray

Normal = 285-295 milli-osmoles per kilogram (mOsmol/kg)

[Glucose] and [BUN] are measured in mg/dL

Hyperosmolarity

Investigations

For Monitoring

RB S

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

every 6 hours

Urine ketones

Every 8h
Blood gas after fluid replacement
Electrolyte serum level every 4 hours till correction

Treatment 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 recurrence

Fluids and Electrolytes

Fluid replacement

Restores perfusion of the tissues

Average fluid deficit 3-6 liters

Initial resuscitation with saline

1 L of normal saline over the first hour then

1 L of normal saline over hour then
L of normal saline over 1 hour then
L of normal saline over 2 hours
Then the rate will depend on clinical judge
(BP, CVP, basal lung crepitation)

Fluids and Electrolytes

K+ level (check at 0,2,6,10,24 hr).

If Hyperkalemia

initially present
No treatment as it resolves quickly with insulin drip

If normal level

(> 5.5 meqlL)

(3.5-5.5 meqlL)

Add 20-30 meql for each Liter of infused fluid

If Hypokalemia (<3.5 meqlL)

Add 40 meq for each Liter of infused fluid

Fluids and Electrolytes

Na level:

Calculate the corrected Sodium (for each 100 mg/dL

glucose above 100, add 1.6 meq/l to Na level)

If corrected Na is High or Normal use Half NS (250-1000

ml/hr)

If corrected Na is Low use NS, rate depends on severity of

volume 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 of

ketones and RBS reaches 250-300 mg/dl

Insulin Therapy

When RBS reaches 250-300 mg/dl

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 under

umbrella of infused insulin for 2 hours, then
continue on SC insulin only .

Glucose Administration

Supplemental glucose

Hypoglycemia occurs

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 Edema
Mechanism:

The brain adapts by producing intracellular osmoles (idiogenic osmoles) which

stabilize the brain cells from shrinking while the DKA was developing.
When the hyperosmolarity is rapidly corrected, the extracellular fluids is corrected
faster than brain cells

The brain becomes more hypertonic than the extracellular fluids

water flows into the cells cerebral edema

Causes of Cerebral Edema

The 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

Cerebral Edema Presentations include:

Deterioration of level of consciousness.

 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

 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 azotemia
secondary to dehydration.

Serum amylase is often raised even in the

absence of pancreatitis

Case study (3)

A 82-year-old male patient was taken to the emergency
room in the afternoon for loss of consciousness in the
previous hour.

The patient had hypertension, chronic ischemic heart

disease, 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 glucose
level is raised

Risk factors

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

type

influx of exogenous glucose

insulin-independent glucose utilization
sensitivity to insulin
endogenous glucose production
insulin clearance
Clinical features
MILD HYPOGLYCEMIA
- mainly adrenergic or cholinergic symptoms

Pallor

 Diaphoresis
Tachycardia
Palpitations
Hunger
Paresthesias
Clinical features
MODERATE HYPOGLYCEMIA (<40 mg/dL)
- mainly neuroglycopenic symptoms

Inability to concentrate
Confusion
Slurred speech
Irrational behaviour
Slower reaction time
Blurred vision
Somnolence
Extreme fatigue
Clinical features
SEVERE HYPOGLYCEMIA (<20 mg/dL )

Associated with severe impairment of

neurologic function

Completely disoriented behavior

LOC
Coma
Seizures
Treatment

MILD HYPOGLYCEMIA

 Oral carbohydrates (at least 15gm)

Sources include

Three glucose tablets (5g each)

2 cups of fruit juice
to cup regular soda
1 cup of milk

If patient is unable to take orally give IV dextrose

Treatment
MODERATE TO SEVERE HYPOGLYCEMIA

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 possible
Prevention

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

QUESTIONS