Diabetes mellitus

 A 56-year-old woman comes to your clinic for her
annual physical exam. She reports increased
urinary frequency and thirst but is otherwise feeling
generally well. She is obese, does not exercise,
and regularly eats fried foods. A random blood
glucose level is 223 ml/dL, and her hemoglobin A1c
is 9.2.

DEFINITION/ETIOLOGY
 Diabetes mellitus (DM) is defined as persistently
high fasting glucose levels
 greater than 125 on at least 2 separate occasions

 Type 1 DM
 • Onset in childhood
 • Insulin dependent from an early age
 • Not related to obesity
 • Defined as insulin deficiency
 Type 2 DM
 • Onset in adulthood
 • Directly related to obesity
 • Defined as insulin resistance

PRESENTATION
 Polyuria, polyphagia, and polydipsia are the most
common presentation.
 Type 1 diabetics are generally thinner than Type 2
diabetics. Type 2 DM is more resistant to diabetic
ketoacidosis (DKA). Both types present with
 decreased wound healing. Type 2 diabetics are
much less likely to present with polyphagia.

DIAGNOSTIC TESTS
Diabetes is defined/diagnosed as:
 Two fasting blood glucose measurements greater
than 125 mg/dL
 Single glucose level above 200 mg/dL with above
symptoms
 Increased glucose level on oral glucose tolerance
testing
 Hemoglobin A1c >6.5% is a diagnostic criterion and
is the best test to follow response to therapy over
the last several months.

TREATMENT
 Diet, Exercise, and Weight Loss
Weight loss can control as much as 25% of cases of Type 2
DM without the need for medications, since decreasing the
amount of adipose tissue helps to decrease insulin
resistance. Exercising muscle does not need insulin.

 Oral Hypoglycemic Medication
-The best initial drug therapy is with oral metformin.
-Sulfonylureas are not used as first-line therapy because
they increase insulin release from the pancreas,thereby
driving the glucose intracellularly and increasing obesity.
-The goal of therapy is HgA1c <7%.
-Metformin works by blocking gluconeogenesis.
-Thiazoladinediones (glitazones) provide no clear
benefit over the other hypoglycemic medications. They are
relatively contraindicated in CHF because they increase
fluid overload

 Metformln is contrainidicated in those with renal dysfunction
because it can accumulate and cause metabolic acidosis.
 Metformin does not cause hypoglycemia. It is the safest drug
to start in newly diagnosed diabetics.
 Nateglinide and repaglinide are stimulators of insulin release
in a similar manner to sulfonylureas, but do not contain sulfa.
They do not add any therapeutic benefit to sulfonylureas.

 Incretins (exenatide, sitagliptin, saxagliptin,
linagliptin) are part of the mechanism by which oral
glucose normally produces a rise in insulin and
decreases glucagon levels. These agents also
decrease gastric motility and help in weightloss,
decreasing Type 2 diabetes. Exenatide may cause
pancreatitis.
 Alpha glucosidase inhibitors (acarbose,
miglitol) are agents that block glucose absorption
in the bowel. They add about half a point decrease
in HgA1c.They cause flatus, diarrhea, and
abdominal pain. They can be used with renal
insufficiency.

 Pramlintide is an analog of a protein called amylin
that is secreted normally with insulin. Amylin
decreases gastric emptying, decreases glucagon
levels, and decreases appetite.
 Insulin is added if the patient is not controlled with
oral hypoglycemic agents.

 Insulin glargine gives a steady state of insulin for
the entire day. Dosing is not tested. Glargine
provides much more steady blood levels than NPH
insulin,which is dosed twice a day. Long-acting
insulin is combined with a shortacting insulin such
as lispro, aspart, or glulisine.
 Regular insulin is sometimes used as the short-
acting insulin. The goal of therapy is HgA1c <7%.

DIABETIC KETOACIDOSIS(DKA)
 Result of severe insulin deficiency.
 Although more common in those with Type 1 diabetes,
diabetic ketoacidosis
 (DKA) can definitely present in those with Type 2
diabetes.
 Precipitating factor: interrupted insulin deficiency,
infection,emotional stress, excessive alcohol ingestion.

DKA PRESENTATION
• Hyperventilation(kussmaul breathing)
• Possibly altered mental status(coma)
• Metabolic acidosis with an increased anion gap
• Hyperkalemia in blood, but decreased total body
potassium because of urinary spillage
• Serum is positive for ketones
• Nonspecific abdominal pain
• "Acetone" odor on breath
• Polydipsia, polyuria
•Dehydration
•Abdominal pain
•fatal rhythm disturbance

DIAGNOSIS
 Elevated blood glucose level glucose 300 to 800
mg/dL (rarely .1,000),
 Increase serum levels of acetoacetate
 Increase anion gap(sodium-(HCO3+Cl).
 decreased Na,
 normal or Increased serum K1 (total body K1 is
decreased),
 decreased phosphate,
 high anion gap metabolic acidosis,
 serum and urine ketones

TREATMENT
 Treat with large-volume saline and insulin
replacement. Replace potassium when the
potassium level comes down to a level approaching
normal.
 Correct the underlying cause: noncompliance with
medications, infection,pregnancy, or any serious
illness.

DKA-SUMMARY
a. Extremely low insulin and glucagon excess cause degradation of triglycerides
into fatty acids and eventual conversion into ketoacids.
b. Occurs in patients with DM type I who do not take prescribed insulin or those who have
infections, high stress, myocardial infarction (MI), or high alcohol use
c. H/P = weakness, polyuria, polydipsia, abdominal pain, vomiting; dry mucous
membranes, decreased skin turgor, fruity odor on breath, hyperventilation
(Kussmaul respirations 5 deep, labored, regular breathing); mental status
changes develop with worsening dehydration
d. Labs =
e. Treatment =intravenous (IV) fluids, insulin, KCl; treat underlying disorder

A 57-year-old man is admitted to the intensive care
unit with altered mental status, hyperventilation, and a
markedly elevated glucose level.
Which of the following is the most accurate measure
of the severity of his condition?
a. Glucose level
b. Serum bicarbonate
c. Urine ketones
d. Blood ketones
e. pH level on blood gas

Answer: B. Hyperglycemia is not the best measure of
the severity of DKA. The glucose level can be
markedly elevated without the presence of
ketoacidosis.
Urine ketones mean very little. Although blood
ketones are important, they are not all detected. If the
serum bicarbonate is very low, the patient is at risk of
death. If the serum bicarbonate is high, it does not
matter how high the glucose level is, in terms of
severity. Serum bicarbonate level is a way of saying
"anion gap." If the bicarbonate level is low, the anion
gap is increased.

 A 19-year-old male presents to the emergency room with
altered mental status. History is remarkable for increased
urination over the past few months. On physical
examination, he is a thin, young man with labored
breathing, abdominal tenderness, and mild flank pain.
Temperature is 37.0 degrees Celsius. An arterial blood gas
shows serum pH 7.05, pCO2 17, HCO3 6, pO2 90. This
patient is most likely suffering from which of the following?
 1. Alcohol poisoning
 2. Hormone deficiency
 3. Pyelonephritis
 4. Aortic aneurysm
 5. Ruptured appendix

 PREFERRED RESPONSE ▼ 2
 DISCUSSION: The patient's presentation is consistent with
diabetic ketoacidosis (DKA). DKA is a complication of diabetes
mellitus type I, a deficiency of insulin (a hormone).
 DKA is a medical emergency that occurs in both type I and type
II diabetics, although it is more common in type I. In DKA,
insulin deficiency and glucagon excess promote hyperglycemia
and ketogenesis. Anion gap metabolic acidosis, volume
depletion, and dehydration occur. Left untreated, the condition
may progress to coma and death.
 Trachtenbarg reviews the pathophysiology and treatment of
DKA. Diagnosis is dependent upon specific clinical features,
including glucose greater than 250 mg/dL, pH less than 7.30,
and bicarbonate level less than 18 mEq/L. IV insulin and IV
fluids remain the mainstays of therapy with close monitoring of
potassium levels during the early resuscitation period.

 Incorrect Answers:
Answer 1: Alcohol (EtOH) may cause ketoacidosis
with normal glucose. levels. The presence of
increased urination for months makes DKA more
likely.
Answer 3: Pyelonephritis would present with fever
and severe flank pain. The increased urination is
more consistent with a history of diabetes, making
DKA more likely.
Answer 4: Aortic aneurysms are more common in
older men with a history of smoking. They may
present symptomatically or asymptomatically.
Answer 5: A ruptured appendix presents with
peritoneal signs on physical exam.

 An 18-year-old male with a past medical history of type
I diabetes presents to the emergency room with
polyuria, polydipsia, and dehydration. Vital signs reveal
tachycardia and hypotension. Physical exam is
significant for dry mucous membranes and decreased
skin turgor. In the waiting room he begins vomiting and
complains of intense abdominal pain. You observe him
taking rapid, deep breaths, and over the course of his
brief stay, getting more somnolent. Which of the
following abnormalities would be expected in this
patient?
 1. Hypernatremia
 2. Decreased total body potassium
 3. Hypoglycemia
 4. Absence of urinary beta-OH-butyrate
 5. Non anion-gap metabolic acidosis

 This type I diabetic is presenting with signs and symptoms of diabetic
ketoacidosis (DKA). In DKA, total body potassium stores are
generally decreased due to osmotic diuresis.
 DKA is a life-threatening emergency that may occur in either type I or
type II diabetics but is significantly more common in patients with type
I. The pathogenesis is related to insulin deficiency resulting in
hyperglycemia that leads to osmotic diuresis and hypovolemia. The
inability of the body to use the available glucose for ATP production
results in ketone formation and eventually an anion gap metabolic
acidosis. Serum potassium levels may be low, normal, or elevated,
but total body stores are generally low and require repletion. Common
precipitating factors include infection, trauma, myocardial infarction,
sepsis and, of course, inadequate insulin administration. Patients may
present with nausea, vomiting, abdominal pain, Kussmaul respirations
(rapid, deep breaths), dehydration, polydipsia, polyuria and may
eventually progress to altered mental status.

 Diagnosis requires glucose greater than 250 mg/dL, pH
less than 7.3, and bicarbonate less than 18 mEq/L.
Beta-hydroxybutyrate is a better measurement of
ketosis than serum ketones. Regarding the mechanism
of potassium dysregulation, Trachtenbarg explains that
multiple mechanisms are at work. With osmotic diuresis
due to hyperglycemia, much of the serum potassium is
lost. Further, acidosis increases serum potassium levels
and insulin administration lowers them. Thus, significant
shifts occur in the disorder. Once adequate urine output
is confirms and the potassium level is less than 5mEq/L,
potassium administration should be started due to the
usual depletion of total body stores.

 Answer 1: Patients with DKA more often present with
hyponatremia. Remember that serum sodium decreases
1.6 mEq/L for every 100 mg/dL increase in glucose.
 Answer 3: DKA requires hyperglycemia by definition.
Hypoglycemia can be a complication of treatment if
glucose is not monitored closely.
 Answer 4: Ketones, such as Beta-OH-Butyrate, are
commonly found in patients with DKA since ketogenesis
is a normal response to starvation caused by inadequate
transit of serum glucose into cells.
 Answer 5: Patients with DKA present with an anion-gap
metabolic acidosis secondary to ketoacids.

HEALTH MAINTENANCE
All patients with DM should receive:
• Pneumococcal vaccine
• Yearly eye exam to check for proliferative
retinopathy, which needs laser therapy
• Statin medication if the LDL is above 100 mg/dL
• ACE inhibitors or ARBs if the blood pressure is
greater than 130/80 mm Hg
• ACEi or ARB if urine tests positive for
microalbuminuria
• Aspirin, used regularly in all diabetic patients above
the age of 30
• Foot exam for neuropathy and ulcers

COMPLICATIONS OF DIABETES
Cardiovascular Complications
 Diabetic patients are at significantly increased risk
of myocardial infarction,stroke, and CHF from
premature atherosclerotic disease.
 This is why the goal of blood pressure in these
patients (below 130/80 mmHg) is lower than in the
general population.
 diabetes is considered an equivalent of coronary
disease for treatment of LDL, and the goal is less
than 100 mg/dL when initiating treatment with
statins.

GASTROPARESIS
 After several years, DM decreases the ability of the
gut to sense the stretch of the walls of the bowel.
Stretch is the main stimulant to gastric motility.
 Gastroparesis is an immobility of the bowels that
leads to bloating, constipation,early satiety,
vomiting, and abdominal discomfort.
 Treatment is with metoclopromide and
erythromycin, which increase gastric motility.

A 53-year-old gentleman presents to your office with a
two-month history of abdominal pain. Of note, the
patient is a long-time patient of yours that you have
been treating for uncontrolled diabetes. In the office
today, his blood sugar is 322 mg/dL. Otherwise, the
patient appears non-toxic and his vital signs are
stable. Upon further questioning, the patient endorses
daily nausea, occasional vomiting, and a feeling of
post-prandial fullness. What is the most appropriate
next step in the patient's care?
1. Radioisotope gastric-emptying scan
2. Upper endoscopy
3. Treatment with metaclopromide; follow up in 3
months
4. Barium radiographic study
5. Hospital admission, nasogastric tube, no PO intake,
fluid resuscitation, and anti-emetics

 DISCUSSION: The patient is experiencing diabetic
gastroparesis. The initial work-up includes ruling out
mechanical obstruction via an upper endoscopy study.
 Diabetic gastroparesis is a pathologic state resulting in
delayed gastric emptying. It can be due to injury to the
vagus nerve leading to delayed muscular contraction of
the stomach and ultimately delayed emptying. Diagnosis
is made on the basis of a gastric emptying scan. Prior to
making the diagnosis, ruling out mechanical obstruction
with an upper endoscopy must be undertaken.

 Answer 1: Radioisotope gastric-emptying scan is the
test of choice for diagnosing diabetic gastroparesis.
Prior to this study though, it is important to rule out
any obstructing mass with an upper endoscopy.
 Answer 3: Treatment with metaclopromide is the
perferred treatment for diabetic gastroparesis. It is
important however, to confirm the diagnosis and rule
out other pathology.
 Answer 4: Barium radiographs have been used in
the diagnosis of diabetic gastroparesis. However, it
is important to rule out an obstructing mass prior to
obtaining this test.
 Answer 5: This patient does not need admission to
the hospital.

A 57-year-old female presents to her primary care physician
with complaints of nausea, vomiting, abdominal pain, and
bloating that have increased in severity over the past
several months. She reports that she occasionally vomits
after eating; the emesis contains undigested food particles.
Additionally, the patient states that she often is satiated
after only a few bites of food at meals. Her medical history
is significant for hypertension and type II diabetes mellitus
that was first diagnosed 10 years ago. Gastric emptying
scintigraphy is conducted and shows gastric retention of
80% at 2 hours and 40% at 4 hours. Which of the following
is the best first step in management of this patient's
condition. Topic Review Topic
1. Dietary modification
2. Metoclopramide
3. Erythromycin
4. Botulinum toxin injection into pylorus
5. Total parenteral nutrition

 DISCUSSION: This patient is suffering from gastroparesis/delayed
gastric emptying. The initial treatment for this condition is diet
modification to frequent, small meals that are low in fiber and fat.
 Presenting symptoms of gastroparesis include nausea, vomiting,
early satiety, postprandial fullness, as well as abdominal pain and
bloating. Management of this condition should first include:
stopping medications that exacerbate gastric stasis, improving
blood glucose control, increasing liquids in the patient's diet,
transitioning to smaller more frequent meals throughout the day,
stopping the use of tobacco and alcohol, as well as decreasing the
amount of insoluble fiber and fat in the patient's diet. If these
preliminary medication treatment options fail, pharmacologic
management can include prokinetic agents such as
metoclopramide and erythromycin.
 The diagnosis of diabetic gastroparesis is made when other
potential causes are excluded and postprandial gastroparesis is
confirmed by a gastric emptying scintigraphy study.

 Answers 2,3: Metoclopramide and erythromycin are pro-
kinetic agents that are indicated for the treatment of
gastroparesis; however, dietary modification should be
attempted first before pursuing pharmacologic treatment.
 Answer 4: A botox injection may expedite gastric emptying
and therefore alleviate some of the symptoms of
gastroparesis; however, non-pharmacologic measures
and prokinetic medications should both be attempted
before considering this management option.
 Answer 5: TPN is only required in severe cases of
gastroparesis, in which a patient is not able to obtain
sufficient nutrition; this patient's symptoms are not severe
nor frequent enough to warrant this nutritional support at
this time.

 Illustration B is a gastric emptying scintigraphy study with normal results, as
evidenced by the rapid emptying of the stomach and appearance of tracer in
the small bowel by 2 hours. Illustration C is a gastric emptying scintigraphy
study in a patient with gastroparesis; note how the tracer does not
disappear from the stomach and very little tracer appears distally in the small
intestine.
Illustration B

RETINOPATHY
 DM's effect on microvasculature is especially
apparent in the eye. In the United States, nearly
25,000 people go blind from DM each year.
 The only management for non proliferative
retinopathy is tighter control of glucose. Aspirin
does not help retinopathy.
 When neovascularization and vitreous
hemorrhages are present, it is called proliferative
retinopathy. This is treated with laser
photocoagulation,which markedly retards the
progression to blindness.

DIABETIC NEPHROPATHY
 Diabetes leads to microalbuminuria early in the
disease. The dipstick for urine becomes trace
positive at 300 mg of protein per 24 hours.
 Microalbuminuria means levels of albumin between
30 and 300 mg per 24 hours.
 Patients with DM should be screened annually for
microalbuminuria and started on an ACE inhibitor
or ARB when it is present.
 These agents are proven to decrease the rate of
progression of nephropathy by decreasing
intraglomerular hypertension and decreasing
damage to the kidney.

a. Intercapillary glomerulosclerosis, mesangial expansion,
and basement membrane degeneration that develops after
long-term DM
b. Slightly greater risk in DM type I than in DM type II
c. Initially presents with proteinuria; renal insufficiency later
develops with Nephrotic syndrome
d. H/P = develops after several years with DM (201); lab
abnormalities may Appear well before symptoms; symptoms
and signs of renal insufficiency
(e.g., HTN, uremia) develop as renal function deteriorates

e. Labs = hypoalbuminemia, increased creatinine
(Cr), increased blood urea nitrogen (BUN);
urinalysis shows proteinuria and microalbuminuria;
electron
microscopy shows basement membrane thickening
and Kimmelstiel-Wilson nodules in glomeruli

f. Treatment =
 control diabetes;
 angiotensin-converting enzyme inhibitor (ACE-I) or
angiotensin receptor blocker (ARB) to decrease
blood pressure,
 low-protein diet,
 infection prevention;
 dialysis may eventually be required
g. Complications = end-stage renal disease

 A 32-year-old male with type 1 diabetes presents to his
primary care physician concerned about the long-term
consequences of high blood sugar. You discuss the effects
of his condition on the major organ systems. Specifically
relating to the kidneys, which of the following is the earliest
renal abnormality seen in diabetic patients?
 1. Azotemia
 2. Potassium hypofiltration
 3. Na+/H2O retention
 4. Secondary hyperparathyroidism
 5. Glomerular hyperfiltration

 DISCUSSION: The earliest renal abnormality seen in
diabetic patients is glomerular hyperfiltration.
 Histologically, high blood glucose results in a thickening of
the glomerular basement membrane followed by
mesangial expansion (Kimmelstiel-Wilson nodules).
These changes alter the filtration unit in a manner that
increases glomerular filtration. This abnormality is the
basis of microalbuminuria screening in all diabetics. As
renal injury progresses, it is possible to quantify the level
of renal injury by the level of albuminuria. In addition to
renal damage, other diabetic vascular complications
include arteriosclerosis leading to hypertension, stroke,
and cardiovascular disease.

 A 45-year-old male with a 15-year history of diabetes
mellitus presents to his primary care provider for a
routine checkup. His doctor is concerned about his renal
function and would like to order a test to detect renal
impairment. Which of the following is the most sensitive
test for detecting renal impairment in diabetic patients?
 1. Cystatin C levels
 2. Urine microalbumin to creatinine ratio
 3. Hemoglobin A1C
 4. Urine protein dipstick
 5. Urinalysis

 DISCUSSION: The most sensitive test for detecting renal
impairment in diabetic patients is the urine microalbumin to
creatinine ratio.
 Nephropathy is a microvascular complication of diabetes
mellitus. Diabetic patients undergo thickening of the
glomerular basement membrane and mesangial expansion,
leading to increased glomerular filtration. This results in
microalbuminuria. Patients should be screened for
microalbuminuria with a urine microalbumin to creatinine
ratio in order to detect early renal dysfunction. Patients with
a urine dipstick that is positive for protein have already
progressed to macroalbuminuria.

 diabetes is a major cause of chronic kidney disease. While it
usually takes 10 years from diagnosis to develop in type 1
diabetics, type 2 diabetics may present with nephropathy at
their initial diagnosis of diabetes. Diabetics should be
screened for microalbuminuria with a spot urine
albumin/creatinine ratio. A diagnosis of diabetic nephropathy
can be made if two out of three spot urine albumin/creatinine
ratio tests are positive in a six month period.
 He states that diabetic nephropathy affects approximately 20
to 30% of diabetics. Diabetic nephropathy is associated with
increased cardiovascular mortality. Treatment modalities
known to slow the progression of diabetic nephropathy
include glycemic control, blood pressure control, and ACE
inhibitors.

 Answer 1: Cystatin C is a biomarker of kidney function that
is elevated in chronic kidney disease, but it is not the most
sensitive screening test of diabetic nephropathy.
 Answer 3: Hemoglobin A1C levels are used for detecting
the three month average plasma glucose concentration, but
it is not the most sensitive screening test of diabetic
nephropathy.
 Answer 4: Urine protein dipstick can detect
macroalbuminuria, rather than microalbuminuria, and is a
less sensitive test for detecting diabetic nephropathy.
 Answer 5: Urinalysis may be altered in patients with renal
dysfunction, but it is not the most sensitive screening test of
diabetic nephropathy.

A 62-year-old woman presents to the urgent care clinic
complaining of vision changes, headaches, and leg pain
while walking that is relieved by rest, which has been
progressing over many years. She cannot remember the
last time she visited the doctor and she takes no
medications. On physical exam, she is found to have a
blood pressure of 175/95. Her basic metabolic panel is as
follows: Na 132 K 3.8 Cl 102 HCO3 23 BUN 70 Cr 4.2 Glu
360 The patient is diagnosed with end-stage renal failure
and started on dialysis. Screening for which of the following
would have been most appropriate to detect this patient's
progressing renal failure?
1. Hematuria
2. Leukocyturia
3. Urine nitrites
4. Leukocyte esterase
5. Microalbuminuria


PREFERRED RESPONSE ▼ 5
 DISCUSSION: The patient's presentation is consistent with
end-stage renal failure secondary to diabetic nephropathy.
Screening for microalbuminuria (protein) is indicated in patients
with diabetes to detect the development of diabetic
nephropathy.
Important complications of diabetes mellitus include
retinopathy, nephropathy, neuropathy, increased
atherosclerosis, and infections. Diabetic nephropathy occurs in
part due to nonenzymatic glycosylation of the glomerular
basement membrane and the afferent and efferent arterioles,
along with osmotic damage to the glomerular capillary
endothelial cells. Patients with diabetes should be screened for
the presence of small amounts of albumin in the urine
(microalbuminuria) with a spot urine collection. Note that a
urine dipstick is not sensitive enough to detect
microalbuminuria.

 incorrect Answers:
 Answer 1: Hematuria may occur in diabetic
nephropathy, but detection of microalbuminuria is
the most important screening test.
 Answer 2, 3, 4: Leukocyturia, urine nitrites, and
leukocyte esterase are seen in urinary tract
infections

A 65-year-old man with a history of diabetes mellitus type II
presents to his primary care physician for routine care. His
only medication is metformin. His vital signs are:
Temperature: 37.1 Pulse: 80 Blood Pressure: 150/95
Respiratory Rate: 16 SaO2: 99% He is found to be excreting
albumin in his urine at a rate of 150 mg per 24 hours,
compared with 50 mg per 24 hours 3 months ago. What is
the most appropriate next treatment in the care of this
patient?
1. Watchful waiting
2. Decreased protein intake
3. Lisinopril
4. Glyburide
5. Insulin

 CORRECT
 DISCUSSION: The patient's history of diabetes along with
hypertension and proteinuria are consistent with diabetic
nephropathy. Blood pressure control, usually with an ACE inhibitor
such as lisinopril, or with a beta-blocker such as atenolol, is the
most appropriate treatment to halt the progression of diabetic
nephropathy.
 The goal of treatment and prevention of diabetic nephropathy is to
lower blood pressure. Control of hypertension is usually achieved
using ACE inhibitors, which provide additional cardiovascular and
mortality reduction benefits. Beta-blockers, although they may
mask the symptoms of hypoglycemia, may be used as second line
agents. In any case, it is important to recognize that the ultimate
desired endpoint is a lower BP.

 Answer 1: The patient is a diabetic with
hypertension and requires blood pressure
medication, not observation alone.
 Answer 2: A low protein diet has not been shown to
prevent the progression of diabetic nephropathy.
See Robertson et al. (linked)
 Answer 4 and 5: Insulin and glyburide provide
glycemic control. Glycemic control is not the most
appropriate treatment for the prevention of the
progression of diabetic nephropathy.

DIABETIC NEUROPATHY
a. Neural damage and conduction defects leading to sensory,
motor, and autonomic nerve dysfunction
b. Sensory neuropathy begins in feet and progresses in
stocking-glove pattern;symptoms include paresthesias, neural
pain, and decreased vibratory and pain sensation.
c. Motor neuropathy may be distally or proximally distributed
and may be characterized by weakness or loss of coordination.
d. Autonomic neuropathy can cause postural hypotension,
impotence, incontinence,and diabetic gastroparesis (i.e.,
delayed gastric emptying).

e. Treatment =control diabetes; neural pain can be
treated with tricyclic antidepressants,
carbamazepine, or gabapentin; narcotics or tramadol
can be considered for persistent neural pain; patients
should be taught how to perform
regular foot examinations
f. Complications =Charcot joints, diabetic foot ulcers;
amputation may be needed to treat progressive
infections and deformity

 A 62-year-old female with a history of type II diabetes
presents to her primary care physician for an annual check-
up. Her long-term medications include glyburide, metoprolol,
and sertraline. She is afebrile. Blood pressure is 140/90
mmHg, pulse is 82/min, and respiratory rate is 16/min.
Fasting glucose is recorded as 160 mg/dL. Serum cholesterol
is 150 mg/dL and serum creatinine is 0.9 mg/dL. BMI is 31
kg/m^2. On physical exam, erythema is present at the fifth
metatarsal-phalangeal joint of the right foot and the patient
has decreased sensation over the affected area. Which of the
following would most likely decrease the incidence of future
neuropathy in this patient?
 1. Add atorvastatin
 2. Add hydrochlorothiazide
 3. Right-sided femoral-popliteal bypass
 4. Tight glycemic control
 5. Discontinue sertraline

 DISCUSSION: Diabetic neuropathy is a microvascular complication
of diabetes that can contribute to diabetic foot ulcers. Tight glycemic
control is critical for preventing microvascular complications of
diabetes including diabetic neuropathy and retinopathy.
 Elevated glucose levels can affect the osmotic gradient across
neurons and retinal cells through several mechanisms, leading to
cell swelling and ultimately damage. The American Diabetes
Association recommends a goal hemoglobin A1C target of < 7% to
reduce microvascular complications of diabetes in adults. The
elderly and others at risk of hypoglycemia should have a target
hemoglobin A1C of < 8%.
 Bader discusses diabetic foot ulcers: “All patients should have blood
glucose and A1C levels measured at initial presentation and then at
regular intervals. Frequent home blood glucose monitoring is
strongly encouraged. Appropriate therapeutic adjustments (e.g.,
adding or changing oral antihyperglycemic agents, initiating or
increasing insulin) must be made to optimize glycemic control.”

 Answer 1: Atorvastatin will help decrease the patient’s
serum cholesterol, which will help reduce the patient’s
risk of macrovascular diabetic complications.
 Answer 2: Hydrochlorothiazide may help decrease this
patient’s blood pressure through fluid diuresis but is
unlikely to improve glycemic control. Hydrochlorothiazide
may raise serum glucose in some individuals.
 Answer 3: Right-sided femoral popliteal bypass is not
indicated at this time, as little evidence is present to
suggest peripheral vascular disease. Furthermore, the
question stem asks about neuropathy, not the condition
of the patient's microvasculature.
 Answer 5: Sertraline is an antidepressant and is not
known to play a role in the formation of diabetic foot
ulcers.

 A 57-year-old with a 30-year-history of type I diabetes
presents to general medical clinic with a lesion on his foot
(Figure A). Although he was advised to wear orthotics by his
podiatrist, he decided to keep wearing his dress shoes and
reports that he observed this lesion when his sock was
stained with blood yesterday morning. His vital signs are
temperature of 37 degrees Celsius, heart rate 75/minute,
blood pressure 145/90 mmHg, respiratory rate 12/minute, and
oxygen saturation 99% on room air. Physical examination
reveals a diminished response to the monofilament test. What
is the most significant risk factor for development of this
condition?
 1. Peripheral vascular disease
 2. Female sex
 3. Duration of diabetes mellitus
 4. Smoking
 5. Neuropath

 DISCUSSION: The greatest risk factor for diabetic foot
ulcers is neuropathy. Other risk factors include peripheral
vascular disease, bone abnormalities of the foot, male
sex, smoking, long term diabetes, and a history of a
previous foot ulcer or amputation.
 Diabetic foot is caused by a combination of vascular
disease (ischemia) and neuropathy which lead to ulcers
and infections, sometimes requiring amputation.
Neuropathy is the most important risk factor because
patients do not feel pain and as a result, repetitive injuries
go unnoticed. Furthermore, neuropathy is also a barrier to
healing since patients unable to feel pain are less likely to
offload pressure on the lesion. Management of diabetic
foot ulcers requires offloading with appropriate footware,
debridement, and antibiotic therapy if osteomyelitis or
cellulitis is present. Optimal blood glucose control, and at
times, revascularization also play a role.

 A 58-year-old gentleman comes in to his primary care
physician's office complaining of "tingling in my fingers and
toes". He states that this has occurred more frequently over
the past 3-4 weeks and figured it was about time to see his
doctor. On physical examination he is noted to be obese and
denies any attempts to exercise. A random blood glucose is
found to be 223 mg/dL and his hemoglobin A1c is 9.2. What
is the most likely diagnosis?
 1. Autonomic neuropathy
 2. Compression mononeuropathy
 3. Symmetrical distal polyneuropathy
 4. Proximal neuropathy
 5. Focal neuropathy

 DISCUSSION: This individual most likely has diabetes and is
experiencing symmetrical distal polyneuropathy.
 Diabetics can often be affected by peripheral neuropathy,
which is clinically seen as numbness, paresthesias, and pain.
The symptoms of distal or peripheral neuropathy often start
bilaterally in the toes and feet and gradually rise up the
calves and into the knees - the stocking glove" pattern. It's
also common for these individuals to experience a burning
sensation, decreased deep tendon reflexes and vibration
sense along with numbness and paresthesias.

 Answer 1: Although autonomic neuropathy can be seen in
diabetics, its presentation is slightly different as it affects the nerves
of internal organs such as the bladder muscles, the cardiovascular
system, the digestive tract, and the genital organs.
 Answer 2: Compressive mononeuropathy refers to a type of
entrapment neuropathy that is caused by peripheral nerve injuries
at specific locations where a nerve is mechanically constricted in a
fibrous or fibro-osseous tunnel.
 Answer 4: Proximal neuropathy can also commonly affect type 2
diabetic patients. It predominantly affects the hips, thighs, buttocks,
or legs and typically begins on one side of the body.
 Answer 5: The head, upper body, or legs may be affected by focal
neuropathy, which appears suddenly and is usually painful. Unlike
the other forms of neuropathy, this type of neuropathy usually goes
away in a few weeks or months and leaves no lasting damage.

 A 63-year-old woman with a history of poorly-controlled
diabetes mellitus presents to your office to review labs and
her blood glucose record. Her hemoglobin A1C is 9.4%. In
addition, her blood glucose records demonstrate poor
control with numerous spikes and lows throughout the day.
Of note, it takes > 1 hr after meals for her blood glucose to
rise. She is also complaining of a decreased appetite,
nausea, reflux, and early satiety. What is the most
appropriate treatment for her current symptoms?
 1. Increasing the dose of her short acting insulin
 2. Loperamide
 3. Metoclopramide
 4. Ondansetron
 5. Gabapentin

 DISCUSSION: This patient has signs and symptoms of diabetic
gastroparesis. The appropriate therapy is a prokinetic such as
metoclopramide.
 Diabetic gastroparesis is caused by autonomic neuropathy,
which may occur with poorly controlled type 1 or type 2
diabetes mellitus. Common symptoms include nausea,
vomiting, abdominal pain, early satiety, and poor glucose
control. Diagnosis is made on the basis of a gastric emptying
scan. Treatment includes a low fiber and low residue diet as
well as prokinetic like metoclopramide. Metoclopramide is a
dopaminergic receptor antagonist, and a mixed 5-HT3 receptor
agonist/antagonist ans has both anti-emetic and prokinetic
properties. Severe case of gastroparesis may require a
jejunostomy tube.

 Answer 1: Increasing this patient's short acting glucose
would not solve her GI symptoms and may precipitate
hypoglycemic episodes due to her delayed gastric
emptying.
 Answer 2: Loperamide would decrease the activity of the
myenteric plexus likely make her GI symptoms worse.
 Answer 4: Odansetron may help this patient's nausea but
will not improve gastric emptying.
 Answer 5: Gabapentin is sometimes helpful for relief of
symptoms of peripheral neuropathy, but is not regularly
used for gastroparesis.

) A 55-year-old male with a medical history significant for
type II diabetes mellitus, hypertension, and benign prostatic
hypertrophy (BPH) presents to your office with worsening
urinary retention. He was started on tamsulosin for his BPH
one year ago, and had immediate improvement of his urinary
symptoms. However, his urinary symptoms returned and
began to worsen after he was started on several new
medications at an annual checkup three months ago. The
medications started at that time included hydrochlorothiazide
for his hypertension, and a combination of amytriptyline and
gabapentin for severe diabetic neuropathy. What is the likely
culprit of this patient's worsening urinary retention? Topic
Review Topic
1. Hydrochlorothiazide
2. Amitriptyline
3. Gabapentin
4. Tachyphylaxis of tamsulosin
5. Progression of his BPH

 DISCUSSION: The anticholinergic effects of the tricyclic (TCA)
amitriptyline is the most likely cause of this patient's worsening
urinary retention issues.
 For medical treatment of diabetic neuropathic pain, first line
therapy is generally a TCA, such as amitryptyline (see
illustration A for an algorithm in treating diabetic neuropathic
pain). If these are contraindicated or do not work alone for the
patient, anticonvulsants and/or serotonin-norepinephrine
reuptake inhibitors (SNRIs) can be used.
 As Lindsay et al. note, tricyclics should not generally be used
in patients over the age of 60 years. They are also relatively
contraindicated in patients with urinary retention issues/BPH
(due to anticholingeric effects), glaucoma, impaired liver
function, thyroid disease, and certain cardiac conditions (e.g.
arrythmias and orthostatic hypertension).

 Incorrect answers:
 Answer 1: The major side effects of
hydrochlorothiazide are hypokalemia,
hyponatremia, hyperglycemia, and hyperlipidemia.
 Answer 3: The major side effects of gabapentin are
somnolence, dizziness and ataxia.
 Answer 4: There is no evidence of tachyphylaxis to
tamsulosin.
 Answer 5: Although progression of BPH would
worsen urinary retention issues, it would not cause
these problems in a short period of time.

) A 52-year-old man comes to your clinic for his annual
physical exam. He is overweight (BMI=31) and is
currently on captopril for hypertension. He reports
increased urinary frequency and thirst but is otherwise
feeling generally well. He does not exercise and
describes his diet as consisting mainly of fast or frozen
food. Which of the following values would be sufficient
to diagnosis this patient with diabetes? Topic Review
Topic
1. Random blood glucose of 185 mg/dL
2. 2 separate fasting glucoses of 130 and 120 mg/dL
3. 2 hour postprandial glucose (glucose tolerance test)
of 180 mg/dL
4. Hemoglobin A1c (HbA1c) of 6.8%
5. The presence of diabetic symptoms only

 DISCUSSION: This patient most likely has type II diabetes
mellitus (DM) as a rseult of his high BMI, unhealthy
lifestyle, and increased urinary frequency and thirst. DM
can be diagnosed by a single hemoglobin A1c (HbA1C) of
>6.5%.
 Type 2 diabetes results from insulin insensitivity in
peripheral organs, which results in an increased insulin
requirement. Eventually, the pancreas cannot produce
enough insulin. The condition has a gradual onset and is
typically seen in older individuals, athough it is
increasingly found in children with obesity. The HbA1c
correlates with the mean glucose from the previous 8-12
weeks (approximate lifespan of a red blood cell). The
currently recommended goal for management is < 7%.

 Answer 1: DM is diagnosed with a random blood glucose of
at > 200mg/dL AND diabetic symptoms.
 Answer 2: DM is diagnosed with 2 separate fasting glucoses
>126 mg/dL.
 Answer 3: DM is diagnosed with a 2 hour postprandial
glucose (glucose tolerance test) > 200 mg/dL.
 Answer 5: DM diagnosis requires evidence of high glucose
in some form, not simply diabetic symptoms.

HYPEROSMOLAR HYPERGLYCEMIC STATE
(HHS)/HYPEROSMOLAR NONKETOTIC
COMA(HONK)
A. Extremely high glucose with profound dehydration
b. Occurs in patients with DM type II with lengthy
infections, stress, or illness; insulin production is
sufficient to prevent DKA by suppressing lipolysis and
ketogenesis

HHS/HONK SYMPTOMS:
 polyuria,
 polydipsia,
 dehydration,
 mental status changes(convulsion,coma)
 seizures and
 stroke can occur in severe cases

HHS/ HONK DIAGNOSIS& TREATMENT
 glucose >800 mg/dL (frequently .1,000), no acidosis
and extremely high serum osmolality.
 A high BUN(prerenal azotemia) and mild metabolic
acidosis(bicarbonate~20mEq/L) is also seen
without ketosis.
Treatment
 IV fluids,
 insulin,
 correction of electrolyte abnormalities;
 treat underlying disorder

An 81-year-old man with a long history of type II
diabetes presents with altered mental status. He is
accompanied with his wife who reports that he has
become confused over the past twelve hours and has
been complaining of thirst. She also notes that he has
hardly been urinating. Initial assessment in the ER
reveals blood pressure of 90/62 and heart rate of 124
but no fever. The patient is lethargic but has no other
pertinent findings on his physical examination. Initial
labs reveal a serum glucose of 720 mg/dL. What
would be an additional cardinal feature of this clinical
syndrome?
1. Ketosis
2. Severe non-anion gap metabolic acidosis
3. Severe anion gap metabolic acidosis
4. Serum osmolarity > 320 mOsm/L
5. Mortality rate < 1%

 This type II diabetic presents with signs and symptoms of
hyperglycemic hyperosmolar nonketotic coma. A feature of this
condition is serum osmolarity > 320 mOsm/L.
 Several different names have been used to describe this state
including hyperosmolar hyperglycemic nonketotic syndrome
(HHNS), hyperosmolar nonketotic coma (HHNC), and
hyperosmolar nonacidotic diabetes. The clinical syndrome refers
to a state of severe hyperglycemia, hyperosmolarity, and
dehydration, most commonly affecting an elderly type II diabetic.
In contrast, type I diabetics commonly present with diabetic
ketoacidosis. Nevertheless, pathogenesis is similar. In HHNS,
low insulin levels cause hyperglycemia resulting in osmotic
diuresis which leads to dehydration. However, ketogenesis is
minimal because a small amount of endogenous insulin is
present, thus preventing significant acidosis. Diagnostic criteria
include hyperglycemia with serum glucose greater than 600
mg/dL and hyperosmolarity with serum osmolarity > 320
mOsm/L, along with no acidosis. Treatment includes fluid and
electrolyte replacement and insulin.

Incorrect Answers:
Answer 1: Ketosis is a laboratory finding in DKA not
HHNS.
Answers 2 and 3: Typically, HHNS presents without
metabolic acidosis. In a minority of cases, it may
present with a mild gap lactic acidosis. However, this
is not a cardinal symptom. In contrast, in DKA, there
is usually a profound anion gap metabolic acidosis
from ketone production.
Answer 5: Mortality rate is 5-10% in DKA but 10-20%
in HHNS. Thus, mortality rate < 1% is not a feature of
either of these illnesses.

 A 61-year-old female with congestive heart failure and
type 2 diabetes is brought to the emergency room by her
husband because of an altered mental status. He states
he normally helps her be compliant with her medications,
but he had been away for several days. On physical
exam, her temperature is 37.2 C, BP 85/55, and HR 130.
Serum glucose is 500 mg/dL. Which of the following is the
first step in the management of this patient? Topic Review
Topic
 1. IV ½ NS
 2. IV NS
 3. IV D5W
 4. Subcutaneous insulin injection
 5. IV insulin

 DISCUSSION: The patient in this vignette is most likely
suffering from non-ketotic hyperosmolar syndrome
(NKHS). The first step in the management of this
condition is the administration of IV NS.
 NKHS is a complication of type 2 diabetes. The
concentration of insulin required to prevent ketoacidosis
is lower than the concentration required to adequately
control glucose levels. Thus, the blood glucose may be
very high, but ketoacidosis will be absent (unlike in type
1 DM). NKHS is seen most commonly in older patients
with concurrent cardiac and renal pathology. This
conditon presents with symptoms and signs of shock.
There is a high mortality with NKHS, approximately 50%.

PRESENTATION
 faintness,
 weakness,
 diaphoresis, and
 palpitations because of responsive excess
secretion of epinephrine (attempt to mobilize
glycogen);
 headache,
 confusion,
 mental status changes, and
 decreased consciousness because of inadequate
supply of glucose to the brain

 A 74-year-old male is brought to the emergency
department by his son during an episode of dizziness,
diaphoresis, and nervousness. The patient's past medical
history includes diabetes mellitus type 2, hypertension,
and end-stage renal disease (ESRD) for which the patient
is on dialysis. Medications include glyburide and
valsartan. Serum glucose is 33 mg/dL, and subsequent
testing shows elevated serum sulfonylurea levels.
Symptoms improve upon intravenous administration of
50% dextrose but blood glucose remains below 80 mg/dL
for 24 hours. Which of the following tests is NOT indicated
in the work-up of this patient's hypoglycemia? Topic
Review Topic
 1. Serum proinsulin level
 2. Urine 5-hydroxyindolacetic acid (5-HIAA) level
 3. Serum insulin-like growth factor II (IGF-II) level
 4. Serum C-peptide level
 5. Serum insulin level

 DISCUSSION: The patient presents with dizziness,
diaphoresis, and nervousness and a blood sugar of 33 mg/dL
consistent with symptomatic hypoglycemia.
 Hypoglycemia is associated with multiple differential diagnoses.
In this patient with chronic kidney disease, the use of glyburide,
a sulfonylurea cleared by the kidneys, is the agent most likely
to be responsible for the patient's hypoglycemic episode.
Serum insulin, pro-insulin, c-peptide, and IGF-II levels can help
elucidate alternative diagnoses. Urine 5-HIAA levels are
elevated in carcinoid syndrome and do not contribute to the
work-up of hypoglycemia.
 Havas discusses hypoglycemia in the management of type I
diabetes. Fatigue, mental slowing, confusion, irritability,
weakness, pallor and twitching are all symptoms that may
indicate hypoglycemia. Monitoring blood glucose frequently,
maintaining a prudent diet and regular exercise can help
minimize the risk of significant hypoglycemia.

 Answers 1 and 4: Serum C-peptide levels and
proinsulin levels are decreased in the setting of
exogenous insulin use.
 Answer 3: Elevated IGF-II levels can be found in
the setting of acromegaly, a potential underlying
cause of hypoglycemia.
 Answer 5: Serum insulin levels help measure if the
body's response to hypoglycemia is appropriate.
When blood glucose levels are below 60 mg/dL,
serum insulin should be almost entirely suppresed.

 A 52-year-old woman comes to your clinic for her
annual physical exam. She is obese, does not
exercise, and regularly eats fried foods. A random
blood glucose is 249 mg/dL. Her hemoglobin A1C is
9.5. Which of the following treatments would be
weight neutral or cause weight loss in this patient?
Topic Review Topic
 1. Glargine
 2. Glyburide
 3. Pioglitazone
 4. Metformin
 5. Glipizide

 4
 DISCUSSION: The patient in this vignette most likely has
type II diabetes. Of the given treatments, only metformin is
weight neutral in the majority of cases (i.e. it does not
cause significant weight gain/loss).
 Metformin is a first-line treatment for type II DM in most
patients. Although the exact mechanism is unknown, it
appears to decrease gluconeogenesis and increase insulin
sensitivity. There is no risk of hypoglycemia or weight gain
(though some patients even lose weight). The most high
yield side effect involves lactic acidosis, particularly in
patients with renal insufficiency.

 incorrect Answers:
 Answer 1: Glargine, a long-acting insulin, can
cause weight gain.
 Answer 2: Glyburide, a second generation
sulfonylurea, can cause weight gain.
 Answer 3: Pioglitazone, a thiazolidinedione, can
cause weight gain.
 Answer 5: Glipizide, a second generation
sulfonylurea, can cause weight gain.

Diabetes mellitus

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