ENDO CASE 2

SGD 11

Physical diagnosis
1. Abdominal pain
2. Clinical impression and differentials

General pathology
1. Diabetes mellitus
• A group of metabolic disorders sharing the common feature of hyperglycemia.
• Hyperglycemia in diabetes results from defects in insulin secretion, decreased glucose
utilization and increased glucose production.
• Chronic hyperglycemia and attendant metabolic dysregulation may be associated with
secondary damage in multiple organ systems, especially the kidneys, eyes, nerves and
blood vessels.
• Increasing number of individuals have “prediabetes’, defined as elevated blood sugar that
does not reach the criterion accepted for an outright diagnosis of diabetes but are high
risk for developing frank diabetes.
• Sedentary lifestyles and poor eating habits have contributed to the simultaneous
escalation of diabetes and obesity – the diabesity epidemic.
• Diabetes and obesity have extended to children who subsist on “junk” food and lack of
adequate exercise.

Diagnosis
• Blood glucose normal range: 70 – 120mg/dL (Robbin’s & Cotran)
• WHO Diagnostic criteria for diabetes:
1. Fasting plasma glucose : > 126 mg/dL
2. Random plasma glucose : > 200 mg/dL
3. 2-hour plasma glucose : > 200 mg/dL (OGTT) with loading dose of
75mg
4. Glycated Hemoglobin (HBA1C) : > 6.5%

* All test, except RBS test in patients with classic hyperglycemic sigs need to be repeated and
confirmed on separate day. If there is inconsistency between the tests results, the result with
greater degree of abnormality is considered.

• Impaired glucose tolerance (prediabetes) is defined as:

1) Fasting plasma glucose : 100 – 125 mg/dL (impaired fasting glucose)
2) 2-hour plasma glucose : 140 – 199 mg/dL following 75mg OGTT or
3) Glycated Hemoglobin (HBA1C) : 5.7% - 6.4%

Classification
• DM is classified on the basis of pathogenic process leading to hyperglycemia, and not
anymore according to earlier criteria such as age of onset or type of therapy.
a) DM TYPE 1 – an autoimmune disease characterized by pancreatic ß cell destruction
and absolute deficiency in insulin. Most common subtype diagnosed in patients
younger than 20 yo accounting to 5% - 10% of the cases.
b) DM TYPE 2 – is caused by combination of peripheral resistance to insulin action and
an inadequate secretory response by the pancreatic ß cells (“relative insulin
deficiency”). Approximately 90% - 95% of diabetic patients have type 2 diabetes and
majority were overweight. Previously considered “adult onset”, the prevalence of DM
type 2 in children and adolescents has been increasing due to increasing rate of
obesity.

Spectrum of glucose homeostasis and Diabetes Mellitus

 Pathophysiology of DM Type 2

Clinical pathology
1. Tests for diabetes
• A fasting plasma glucose level of
≥126 mg/dL (7.0 mmol/L) on at
least two occasions is diagnostic
of diabetes. The fasting glucose
level should be obtained after an
8-hour fast.
• Symptoms of hyperglycemia (e.g.,
polyuria, polydipsia, polyphagia,
unexplained weight loss) with a
casual plasma glucose level of 200
mg/dL (11.1 mmol/L) or higher or
hemoglobin A1c (HbA1c) of 6.5%
or higher on two different days is
sufficient to diagnose diabetes.
• If the patient has discordant results from two different tests, then the test for which
the result is above the diagnostic cut point should be repeated.
• Prediabetes designates conditions in which glucose homeostasis is abnormal, but
serum glucose levels are not high enough to be classified as diabetes. This group
includes individuals with impaired fasting glucose and impaired glucose tolerance.
They are also at increased risk for cardiovascular and cerebrovascular diseases.
• Formal oral glucose tolerance tests are not generally recommended for routine
clinical use in the diagnosis of diabetes. If used, the procedure described by the
WHO utilizing a 75-gram glucose load should be followed. For children, 1.75 grams
glucose/kg up to 75 grams is recommended. The exception is for the diagnosis of
diabetes during pregnancy.
 • Before an oral glucose tolerance test is performed, individuals should ingest at least 150
g/day of carbohydrates for the 3 days preceding the test without limitation in physical
activity, and the test should be performed after an overnight 8- to 14-hour fast. The
individual should not eat food; drink tea, coffee, or alcohol; or smoke cigarettes during the
test, and he or she should be seated.
• Venous glucose samples are preferably collected in gray-top tubes containing fluoride and
an anticoagulant.

Types of tests for diabetes

Oral glucose-tolerance test.
• This test is most commonly performed during pregnancy.
• You typically have your blood drawn once, then drink a syrupy glucose solution and have
your blood drawn at 30 to 60 minute intervals for up to three hours to see how your body
is handling the glut of sugar.
• Normal result: Depends on how many grams of glucose are in the solution, which can
vary.

Fasting blood sugar.

• This is a common test because it's easy to perform.
• After fasting overnight, you have your blood drawn at an early morning doctor's visit and
tested to see if your blood sugar is in the normal range.
• Normal result: 70-99 milligrams per deciliter (mg/dl) or less than 5.5 mmol/L

Two-hour postprandial test.

• This blood test is done two hours after you have eaten ("prandial" means meal).
Normal result: 70-145 mg/dL (less than 7.9 mmol/L)

Random blood sugar.

• A blood sugar test is performed regardless of when you last ate a meal.
Normal result: 70-125 mg/dL (less than 7.0 mmol/L)

Hemoglobin A1C test.

• This test measures how much sugar is stuck to your red blood cells, which generally have
a lifespan of three months.
• Gauges how high your blood sugar has been in recent months.
• You don’t have to fast before having your blood drawn for an A1C test, which means that
blood can be drawn for the test at any time of the day.
• Normal result for nondiabetics: 4% to 6%
• Normal result for diabetics: 7% or lower (some groups suggest aiming for 6.5% or lower)
• If a hemoglobin A1C test result is 8% or higher, it's a sign that blood sugar is not under
control. However, making lifestyle changes can reduce your A1C.
 *Any test used to diagnose diabetes requires confirmation with a second measurement, unless there
are clear symptoms of diabetes.
Diagnosis* A1C Level
Normal below 5.7 percent
Prediabetes 5.7 to 6.4 percent
Diabetes 6.5 percent or above

2. Ketone bodies
• The ketone bodies - β-hydroxybutyric acid, acetoacetic acid, and acetone are products
of fatty acid degradation.
• β-hydroxybutyric acid and acetoacetic acid are normally present in a 1:1 ratio at
concentrations of 0.5 to 1.0 mmol/L each.
• Ketone testing - using urine or blood; important for individuals with type 1 diabetes mellitus
to detect ketosis.

Diabetic ketoacidosis (DKA)

• Serious and potentially fatal hyperglycemic condition requiring urgent treatment
• Frequently associated with nausea, vomiting, abdominal pain, electrolyte disturbances,
and severe dehydration.
• Type 2 diabetes patients who are poorly controlled, particularly in the presence of extreme
stress or severe acute illness, can also develop DKA.

Ketone testing
• May be useful in pregnancy and in determining the cause of hypoglycemic disorders.
• Ratio of β-hydroxybutyric acid to acetoacetic acid = greatly increased in DKA as a result
of the altered redox state and elevated levels of NADH in the hepatic mitochondria.
• The most commonly used strips and tablets use sodium nitroprusside; turn purple in the
presence of elevated levels of acetoacetic acid.
• Acetone is detected in the presence of glycine.
• False-negative results - old strips and with strips that have had excessive contact with air;
after ingestion of large amounts of vitamin C.
• False-positive results - observed with the use of sulfhydryl-containing medications such
as captopril (but not other ACEIs not containing the sulfhydryl group), acetylcysteine,
penicillamine, and mesna.
• β-hydroxybutyric acid - not detected by these methods; β-hydroxybutyric acid levels fall
and acetoacetic acid and acetone levels rise during the treatment of DKA, these tests are
not useful for the monitoring of therapy.
• β-hydroxybutyric acid can be measured in serum by enzymatic, electrochemical,
chromatographic, electrophoretic, and colorimetric methods.
• Reference intervals of β-hydroxybutyrate - vary among assay methods; concentrations in
healthy individuals who have fasted overnight are generally <0.5 mmol/L.
• Patients with well-documented DKA (i.e., HCO3 <17, arterial pH <7.3, plasma glucose
>250 mg/dl) generally have β-hydroxybutyrate of over 2.0 mmol/L.

Monitoring of recovery from DKA

• In hospital setting - serial measurements of serum electrolytes, including bicarbonate with
calculation of the anion gap, are used commonly
 • Serial measurement of β-hydroxybutyric acid - additional tool to monitor improvement in
DKA. This can be especially useful in patients with DKA in the presence of a concomitant
additional acid-base abnormality interfering with proper interpretation of bicarbonate
concentrations and the anion gap, such as seen in renal failure.

Pharmacology
1. Anti-hyperglycemics
A. Glucagon
1. Chemistry, mechanism, and effects—Glucagon is a protein hormone secreted by the A cells
of the endocrine pancreas. Acting through G protein-coupled receptors in heart, smooth
muscle, and liver, glucagon increases heart rate and force of contraction, increases hepatic
glycogenolysis and gluconeogenesis, and relaxes smooth muscle. The smooth muscle effect
is particularly marked in the gut.

2. Clinical uses—Glucagon is used to treat severe hypoglycemia in diabetics, but its

hyperglycemic action requires intact hepatic glycogen stores. The drug is given
intramuscularly or intravenously. In the management of severe β-blocker overdose, glucagon
may be the most effective method for stimulating the depressed heart because it increases
cardiac cAMP without requiring access to β receptors .