Transcript MANAGEMENT OF HYPOGLYCEMIA

HYPOGLYCEMIA
UPDATE
By-Dawit Ayele
Nov,2006
OUTLINE
-Hypoglycemic disorders-in diabetics
-non diabetics
-Complications
-Diagnosis
-Management
I-Hypoglycemic disorders in Diabetes
Study –2/3 of patients admitted for hypo are diabetics
-2/3 used alcohol
Clinical context
- Hyperglycemia treatment were it not for hypo. would be
easy.
- Hypoglycemia makes diabetes mgt complex.
Due to this :-chronic complications-retinopathy,neuropathy
etc..progress despite aggressive attempts.
-plasma glucose may be <50mg/dl in ~10% of
the time.
-average 2 episodes of sxic hypoglycemia per
week & severe temporarily disabling hypoglycemia 1-2Xa
year.
-2-4%of death of such people

Risk Factors
I-Excess insulin:
1-Ill timed,wrong type & high dose
2- glucose influx
3- insulin independent glucose utilization.
4-endogenous glucose
production(alcohol,renal parenchyma dis.)
5- insulin sensitivity.(post exercise)
6- insulin clearance.(renal failure)
II-Interplay of insulin excess & compromised
glucose counterregulation
A-Absolute insulin deficiency(-ve C-Peptide)
ß-cell destruction:no in insulin in response to glucose
hence:No  in glucagon in response to glucose

B-History of severe hypglycemia or aggressive therapy per
se.(lower glucose goals,lower Hgb A1c)
Episodes of attenuated autonomic hypoglycemia
including  epinephrine activation & sxs in response to
glucose defective glucose counter regulation&
hypoglycemia unawareness
II-Non-Diabetic Hypoglycemic
Disorders
A-The Fasting(Post
absorptive)hypoglycemias
i-Drugs

Insulin,sulfonylureas
-Most common causes(in rx of diabetes)
-sometimes taken surreptitiously
-taken for criminal intent
-pharmacy/other error
Mechanisms--described
Drugs con’t
Ethanol
-Inhibits gluconeogenesis(deplets cofactor key to entry of
gluconeogenesis precursors.)
-inhibits cortisol &GH responses.
-Doesn’t inhibit glycogenolysis.
Clinical alcohol induced hypo. Typically follows 6-36 hours
post binge of moderate to heavy alcohol while the patient
eats little.
Prolonged hypoglycemia in diabetics who took alcohol is
potentially fatal.

Drugs con’t
Salicylates —in large doses(4-6gm/d)
& sulfonamides
Can cause hypoglycemia in children.
Mechanism is unknown but it may involve
increased insulin secretion from the pancreas.
· Quinine
 plasma insulin:glucagon ratio

Drugs con’t

Pentamidine:
is ß-cell toxin,especially in prolonged duration
of Rx,  dose,renal insufficiency.
*Initially can cause hypo. By causing insulin
release;later cause diabetes.
Study-Rx for PCP-7%experienced
hypoglycemia
-14%hypoglycemia followed
by diabetes.
-18%diabetes without
hypoglycemia
Drugs con’t
Non selective ßblockers:(eg.Propranolol)
cause hypoglycemia especially in insulin treated
diabetes patients by:
-  symptoms of developing hypoglycemia
- impair epinephrine mediated glucose
counterregulation. so better use selective ßblockers Atenolol/Metoprolol in diabetics on Rx.

ii-Critical Illnesses
Common in hospitalized patients 2nd to
drugs.
 -Extensive liver disease
-esp.rapid & massive destruction.egfulminant viral hepatitis,fatty liver due to
alcohol,cholangitis&biliary obstruction
&10malignant tumors( IGFIIproduction)

-Unusual in common forms of cirrhosis &
hepatitis&metastatic liver disease.
Illness con’t
Severe Cardiac Failure
-Unknown pathogenesis
-Possibly due to hepatic congestion,
hypoxia&gluconeogenetic precursor
limitation.
-inhibited gluconeogenesis(studies showed
increased blood lactate)

Illness con’t
Renal failure
-Unknown pathogenesis
-Compromised glucose counter regulation is
probable
-Studies suggest : glucose turnover

gluconeogenesis(fasting glucose
level & no increase in lactate)
usually cachectic  loss of precursor
for gluconeogenesis
in diabetic nephropathy with
exogenous insulin Rx  insulin clearance
Illness con’t
Sepsis
-relatively common cause
-glucose utilization by macrophage rich tissue

stimulated by cytokines(TNF,IL6)
-hypoglycemia develops when hepatic glucose
production decreases due to:
- hepatic responsiveness to
appropriate glucoregulatory stimuli.
-hepatic hypo perfusion(esp.in septic
shock)
Hormonal Deficiencies




 glucagon& epinephrine + insulinhypoglycemia
“
“
-insulin+hypoglycemia
Cortisol,GH or both(hypopituitarism)
no hypo in most adults;
-can occasionally cause during high glucose
utilization(exercise/pregnancy/alcohol)
Children esp.neonates would have
hypoglycemia preceded by caloric deprivation
Epinephrine secretion due to cortisol defn.might
contribute to mild hypoglycemia. such patients have no
glucagon
- Non
ß-cell tumors

Small percentage of patients developed severe hypo.

Usually large tumors of mesenchymal & epithelial cell
types ~2-4kgs located 1/3in chest&2/3retroperitoneum.

-no single pathogenetic mechanism explains all cases
-Major cause appears to be  glucose utilization due to
tumoral secretion of IGFII(index study 25 out of 28 pts had
 IGFII)
- Other factors --glu.utilization by tumor &
sk.ms,metastatic hepatic tissue replacement,
gluconeogenesis…
Endogenous Hyperinsulinism

Pancreatic ß-cell d/o-- Insulinoma
Rare 0.4/100,000
Early1920-insulin discovered for diabetes Rx
-clinical events of insulin identified as new disease
hyperinsulinism.
1927-malignant pancreatic islet-cell tumor found in a patient
with severe hypoglycemia
tumor extracts caused marked hypo.in rats.
1929-1st cure of insulinism by tumor removal.
-Mechanism of insulin maintenance –unknown
Study-variant of insulin mRNA with translation efficiency
-**Hypoglycemia-due to hepatic glucose output rather
than glucose utilization.
B-Post prandial(reactive
hypoglycemia)

Occurs only after meals & self limited
 Occurs in children with certain rare
enzymatic defects.(fructose intolerance..)
 In some individuals who have undergone
gastric surgeryrapid passage of food from
stomach to intestinerapid in plasma
glucoseinduce extuberent
insulinhypoglycemia
Complications






1-recurrent/persistent psychosocial
morbidity(Emotional
lability,irritability,depression).
2-Fear of hypoglycemia-barrier for diabetic
control.
3-Seizure
4-permanent neurologic deficit (including
cognitive impairment)
5-Coma
6-Death
Approach to the patient

Steps: 1-Recognition & documentation
 2-Diagnosis of hypoglycemia
 3-Urgent treatment
 4-Prevention of recurrent hypoglycemia
Recognition & documentation



Draw blood before glucose administration
Convincing documentation-Whipple’s triad
Obscure cause-check additional assays
-glucose
-insulin
-C-peptide
-sulfonyluria levels
-Cortisol
-Ethanol

Note-Normal blood glucose with free symptoms
doesn’t exclude hypoglycemia
-Distinctly low plasma glucose without
history of corresponding symptoms is probably
laboratory error.
eg.abnormally high
leukocyte,erythrocyte,platelet count;delayed
separation of serum from elements
Diagnosis of Hypoglycemia

Hypoglycemia:
-non specific manifestations
-vary among individuals
-change from time to time
-Episodic
Diagnosis :can not be made solely on sn&sx
&on basis of plasma glucose
Whipple’s triad is the clinical key for
diagnosis.
Diagnosis con’t

**72-Hours supervised test
-oldest best established & probably most reliable test for
evaluation of hypoglycemia.
-Its though complicated & expensive-reserved for those w/o
reasonable diagnosis.
Approach to testing:
Purpose-provoke homeostatic response
Reasons-confirm hypoglycemia is cause of pts’sx.
-check if reversing it relieves sxs(whiple’s triad)
Diagnosis con’t
Protocol of Mayo clinic:
-Date onset of fast;continue non essential medics.
-Allow calorie free & caffeine free beverages
-Ensure patient is active during waking hrs.
-Collect blood specimens for pl.glu,insulin,C-peptide
& pro-insulin Q6hrly till Pl.Glu.<60then Q 1-2hrly
Test end points:-Pl. glu.<45mg/dl
-pt has sx or sn of hypoglycemia
-72 hrs have elapsed
-Steps after fast end:-measure plasma ß-hydroxybutyrate&
sulfonylurea concn.
-1mg of glucagon given IV& plasma
glu.measured 10,20,30minutes later
-Patient is fed.
By observing the biochemical values along with sn & sx its
usually possible to distinguish various causes!!
Diagnosis con’t

Interpretation:
- ß-hydroxybutyrate value+vigorous plasma glucose
response to IV glucagonHypoglycemia mediated by
insulin or insulin like factor
-  Plasma insulin,C-peptide,& pro insulin
valueInsulinoma& sulfonyluria induced hypo.
- Plama sulfonyluria is present only when drug administered
-  plasma insulin values& C-peptide
valuesexogenous insulin administration(Rxic
overdose/deliberate suicidal or factitious)
- Plasma concentration of ß-cell
polypeptideshypoglycemia not mediated by insulin or
insulin like factor
Urgent Treatment

1-Oral treatment prefered
-20-30gm of glucose(in form of fast acting
CHO-hard candy,glucose tab.,sweetened fruit
etc..)
-this should be followed by long acting
CHO to prevent recurrent sxs.
2-Parentral therapy
-if neuroglycopenia precludes oral feeding
the patient needs IV glucose 25gm using
50%solution followed by constant 5-10%dextrose
infusion.

If IV Rx is not practical especially in T1DM
SC or IM glucagon o.5-1mg will result in
recovery of consciousness in 10-15 min.
Prevention of recurrent hypo

D/C offending drug or dose

Treat underlying critical illness
Replace deficient hormones.eg-cortisol&GH
Surgical,radiotherapeutic or chemo of non- ß-cell
tumor.
Resect 10 pancreatic tumors-insulinoma
Auto immune hypoglycemia-often self limiting
glucosidase inhibitor for post prandial hypo due
to surgery(delays CHO digestion& glucose absn.)
Frequent feeding & avoidance of fasting.






Recommendations

For all insulin Rxed patients particulrly those
about to begin intensive insulin:
-Take detailed Hx-major episodes,frequency,how
treated
-Intensive therapy-increase risk so explain to the
patient
-Check adequacy of counterregulatory hormone.
-Education for patient-recognition & Rx hypo.
-Education for family & friends –recognition &
treatment of hypo.
-At every clinic visit ask about hypoglycemia,check
bld.glucose measuring equipment as well if
possible
REFERENCES

WILLIAMS ENDOCRINOLOGY
 UPTODATE 14.1
 HARRISON’S 16TH EDITION
 INTERNET SOURCES
THANK YOU