Transcript insulin deficiency

Ambulatory:
Diabetes Mellitus
April 9, 2007
Subtypes


Insulin dependent (Type 1 /IDDM)
 Abrupt onset, < 30 yrs
 Autoimmune insulin deficiency due to islet cell
destruction
 Prone to ketoacidosis
Non-insulin dependent (Type 2/NIDDM)
 Gradual onset, > 30 yrs
 Obesity
 Insulin resistance
 Impaired insulin secretion (beta cell dysfunction)
Type I DM





Insulin deficiency secondary to β-cell
destruction usually by autoimmune process
Insulin and C-peptide levels low
May have islet cell autoantibodies,
Autoantibodies to insulin, or antibodies to
glutamic acid decarboxylase or tyrosine
phosphatases.
20% risk of other autoimmune diseases
Typically will present with DKA due to
absolute lack of insulin
Type II




Insulin resistance and relative insulin deficiency - β-cell
mass preserved, but decreased secretion and
response to insulin.
Strong genetic component with 100% concordance in
monozygotic twins.
Ketoacidosis is rare – though it can occur if concurrent
infection. Also there are a small group of mainly African
American patients in whom insulinopenia leads to a
tendency to DKA.
Usually hyperglycemia in Type II develops gradually
and pt may be undiagnosed for years.
Subtypes


Gestational Diabetes
 Dysfunction of glucose metabolism with
presentation in pregnancy
 Increased fetal morbidity
 Up to 63% will develop non-gestational DM in 516 years
MODY (maturity-onset diabetes of the young)
 Subset of Type 2 DM
 Family history, early age of onset (teens, 20’s)
 At least 5 subtypes
 Impairment of β-cell function
 Resistance to ketoacidosis
Subtypes

Secondary Diabetes

Pancreatic disease with resultant
insulinopenia
• Chronic pancreatitis, pancreatectomy, CF,
hemachromatosis

Drug induced
• HCTZ, steroids, estrogen, psychoactive
agents, catacholamines, pentamidine
Subtypes

Endocrinopathies
Acromegaly, pheochromocytoma,
Cushing’s, Conn’s, glucagonoma
 Insulin receptor abnormalities


Genetic syndromes

Hyperlipidemia, muscular dystrophies,
Huntington’s chorea
Diagnosis

Per the Expert Committee on the Diagnosis and
Classification of Diabetes Mellitus, 2003
Criteria
Comment

Symptoms of DM
 Casual plasma glucose
concentration ≥ 200
mg/dL OR
Casual defined as any
time of day, meal or no
meal
** 2 Fasting plasma
glucose concentrations ≥
126 mg/dL
OR
No caloric intake for at
least 8 hours
2 hour plasma glucose
concentration ≥ 200
mg/dL on OGTT
Glucose load equivalent
to 75 g of anhydrous
glucose in water
Symptoms of Diabetes

Classic

Polyuria, polydipsia, unexplained
weight LOSS
Fatigue
 Blurry vision
 Nausea, vomiting
 Infections

Screening for Diabetes


Every 3 years if age 45 or older (if results are normal)
More frequent screening if:

Pre-Diabetic
• Fasting plasma glucose concentration > 110 mg/dL or < 126 mg dL
• a.k.a. “impaired fasting glucose” or “impaired glucose tolerance”



Obese (BMI≥27)
1st degree relatives with DM
High risk ethnic group
• African-American, Hispanic-American, Native-American, Asian-American,
Pacific Islander-American

Pregnancy
• History of Gestational diabetes
• Delivery of baby weighing 9 or more pounds


HTN (>140/90)
Dyslipidemia
• HDL≤35 mg/dL, TGL≥250 mg/dL
Treatment rationale

DCCTRG


39% reduction in progression of
retinopathy for 0.9% reduction in
HbA1c
UKPDSG

HbA1c of 7% associated with
significant incidence of micro and
macrovascular disease
Treatment Rationale
Meticulous glucose control decreases
long-term microvascular complication
rates
 Aggressive insulin therapy in patients
with a recent MI was associated with
reduced mortality

Treatment of Diabetes
Mellitus

Goals set by American Diabetes
Association
Preprandial glucose values of 80 to
120 mg/dL
 Bedtime glucose values of 100 to 140
mg/dL
 Hemoglobin A1C < 7%
 2 hour post-prandial glucose values <
160 mg/dL

Treatment of Type 1
Diabetes Mellitus



Need insulin
Healthy people generally have insulin
production of 24-36 units per day
Type 1 DM



0.5 to 1.0 units/kg of insulin daily
Varies according to diet, exercise, stress
Various insulin preparations with various
regimens


Tailor to the patient
Attempt to mimic the healthy person’s insulin
peaks and valleys
Treatment of Type 1
Diabetes Mellitus

Rapid Acting Insulins


Short Acting Insulins


Regular
Intermediate Acting



Lispro, Aspart
NPH
Lente
Long Acting


Ultralente
Glargine
Pharmacokinetics of current insulin preparations
Insulin
Onset
Peak
Effective duration
Lispro (Humalog)
<15 min
1 hr
4-5 hr
Regular
0.5-1 hr
2-3 hr
5-8 hr
NPH, lente
2-4 hr
6-8 hr
6-16 hr
Ultralente
4 hr
Variable
18-22 hr
Glargine (Lantus)
1-2 hr
Flat, predictable
22-24 hr
NPH, isophane insulin suspension.
Compiled from Barnett and Owens (1), Lepore et al (2), and White et al (3).
Basal/Bolus regimen

Basal/Bolus regimen
 Daily insulin dose consists of a basal insulin
to inhibit hepatic glucose production and
pre-meal insulin to cover intake
• mimics natural insulin production




Typically this is achieved with Lantus QHS
and Novolog (aspart) QAC.
Patients on this regimen should either be
given a Sliding scale instructing them how to
cover their premeal accuchecks and how to
“Carb count” OR they need a standard dose
of premeal insulin which you review when
you see them in clinic based on their
readings.
15g carbs = 1 unit of insulin
Requires multiple insulin injections and
Treatment of Type 1
Diabetes Mellitus

Pancreas Transplant with or without Kidney
transplant




To help protect the transplanted kidney from
hyperglycemia
Meet certain criteria, in general, frequent,
acute metabolic complications and failure
with insulin therapy
Survival, immunosuppression
Pancreatic islet cell transplant


Similar criteria
Immunosuppression
Treatment of Type 2
Diabetes

Weight Loss, Diet, Exercise


Decrease in body weight as little as 4-7% can help
increase insulin sensitivity
United Kingdom Prospective Diabetes Study
(UKPDS)
• < 25% treated with diet and exercise alone maintain
Hgb A1C < 7% after 3 years and < 10% after 9 years
• Attributed in part to progressive loss of β-cell
secretion of insulin

Supporting evidence of dual therapy with oral
agents, i.e. one agent augmenting insulin
secretion, another improving insulin action
Treatment of Type 2
Diabetes

Insulin Secretagogues (“Beta-beaters”)



Biguanides – decrease hepatic gluconeogenesis


Metformin
Thiazolidinediones – insulin sensitizer


Sulfonylurea
Meglitinides
The “glitizones”
Alpha-glucosidase Inhibitors – decreased GI
absorption

Acarbose
Sulfonylurea




First line after diet and exercise
20-25% primary failure rate
Caution in hepatic/renal dysfunction
Mechanism of action


Promote increased pancreatic secretion
Side effects

Hypoglycemia, usually within 1st 4 months
• Increased in elderly, worsening renal function, irregular meal schedules


Weight gain
Medications

Glyburide (Micronase, Diabeta)
• Duration of action 18-24 hours
• Hypoglycemia still common


Glipizide (Glucotrol)
Glimepiride (Amaryl)
• Indicated for use with insulin
• “safe” in renal failure
Meglitinides
(rapid acting secretogogues)

Theoretically offers improved post prandial control



Mechanism of action


Similar to sulfonylureas, quicker “on-off” action
Side effects

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May benefit patients with unpredictable meal schedules or
large post prandial glucose levels
Q meal dosing
Hypoglycemia
Weight gain
Medications


Repaglinide (Prandin)
Nataglinide (Starlix)
• Ultra short acting
• Most effective agent for post-prandial control
• Hypoglycemic contraindication with insulin
Biguanides
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Weight loss due to appetite reduction
Less hypoglycemia than sulfonylurea therapy
Major effects:
 Increased hepatic insulin sensitivity
 Decreased gluconeogenesis and glycogenolysis
Side effects
 LACTIC ACIDOSIS
 GI intolerance
Mechanism of action is unclear
Medication
 Metformin (Glucophage)
• Optimal dose 2000mg/d
• BID dosing
Biguanides

Contraindications to metformin


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
Serum creatinine >= 1.5 mg/dL in men, >=
1.4 mg/dL in women
Age > 75years
Discontinue before any radiologic contrast
studies (stop during or before) or upon
hospitalization
Hepatic dysfunction
Dehydration
Metabolic acidosis
CHF requiring treatment
Thiazolidinediones (TZD)

Mechanism of action



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Additive effect with metformin
Favorable lipid profile effects, ? atherosclerosis
Side effects




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Weight gain
Edema – caution with CHF
Hypoglycemia, especially if coupled with other diabetic medication
Liver dysfunction? – monitor LFTs
Medications



Not fully understood
Decrease insulin resistance, increase insulin sensitivity, probably at the
peripheral skeletal muscle
? Smaller effect on liver gluconeogenesis
Rosiglitizone (Avandia) - increase HDL levels
Pioglitizone (Actos) - increase HDL, decrease TG levels
Contraindicated:



Hepatic dysfunction
Age greater than 80
Advanced CHF
Thiazolidinediones (TZD)

Monotherapy or combo with
metformin, sulfonylureas, and insulin

Other effects:
• Slightly reduce BP
• Enhance fibrinolysis
• Improve endothelial function
Alpha-glucosidase Inhibitors


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Decreases digestion of complex carbohydrates in
small bowel
Slows monosaccharide absorption
Effective only with diets >40% carbohydrates
Lowers post-prandial>pre-prandial glucose
Not as efficacious as other agents (decreases A1C by
0.5% - 1%)
Side effects major limitation
 Gas, abdominal pain, diarrhea
 Minimized with slow titration
Medications
 Acarbose (Precose)
 Miglitol (Glyset)
Oral Agent Monotherapy and
Glycemic Control
Drug
Baseline
HbA1c
Decrease in HbA1c
(%)
8.7
8.1
1.8
1.9
8.7
8.1
1.8
0.9
8.4
1.8
8.9
0.74
8.8
10.3
1.5
1.6
8.2
1.5
Sulfonylurea
Glipizide XL
Glimepiride
Rapid acting
secretogogue
Repaglinide
Nateglinide
Biguanide
Metformin
Alpha-glucosidase
Inhibitor
Miglitol
Thiazolidinediones
Rosiglitazone
Pioglitazone
Miscellaeous
Glucovance
Combination Oral Therapy
Lowers A1C levels by about 2%
 No evidence that a specific
combination is any more effective in
lowering glucose levels or more
effective in preventing complications
than another
 Thus, patients with an HbA1C >9%
who are receiving monotherapy are
unlikely to reach a target of <7%




A 56-year-old woman who has had type 2 diabetes mellitus for 12 years
is evaluated because of poorly controlled diabetes. She is obese (body
mass index, 32 kg/m2). She takes glyburide, and over the past 6 months,
her hemoglobin A1C level has increased from 6.8% to 8.5%, while
measurements of her fasting plasma glucose have been greater than
200 mg/dL and postprandial measurements range from 250 to 350
mg/dL. She refuses to take insulin.
Which of following is the best therapy for this patient?
( A ) Discontinue glyburide and initiate metformin
( B ) Discontinue glyburide and initiate a thiazolidinedione
( C ) Continue glyburide and add metformin
( D ) Continue glyburide and repeat measurement of hemoglobin A1C
( E ) Continue glyburide and add acarbose

Critique (Correct Answer = C)

Type 2 diabetes mellitus is a progressive disorder, and studies have documented that
response to monotherapy is limited. Four options are available to obese patients who
have become unresponsive to sulfonylureas: 1) add metformin, 2) add a
thiazolidinedione, 3) add an α-glucosidase inhibitor, and 4) add insulin. Arguably the best
treatment could be to initiate insulin at bedtime and continue the sulfonylurea.

There is no consensus about which option is most effective. Adding metformin to the
regimen provides an effective agent that complements the action of sulfonylurea. Several
studies document that fasting plasma glucose and hemoglobin A1C values decline with
this combination of sulfonylurea and metformin in patients with body mass indexes in the
range of 27 to 30 kg/m2. Maximum dosages (2000 mg) of metformin should be
administered in divided doses. A trial of this combination for 6 to 8 weeks should
determine its effectiveness. If hemoglobin A1C values do not fall to the 7.0% to 7.5%
range, the patient should be encouraged to start insulin therapy.
A thiazolidinedione and acarbose (an α-glucosidase inhibitor) are less powerful as
hypoglycemic agents than sulfonylureas and metformin, and probably would be less
effective in this patient than combination therapy. The patient’s obesity indicates that
insulin resistance is a likely factor in the progressive hyperglycemia, and a
thiazolidinedione warrants consideration; however, if it is used, greater laboratory
monitoring is required.
Oral Agent Metabolic Effects
Sulfonylurea
Rapid acting
secretogogues
Metformin
Thiazoidiniones
Insulin
Resistance
0
0
Marked
decrease
Marked decrease
Hyperinsulinemia
0
0
Marked
decrease
Marked decrease
LDL
0
0
Small
decrease
Small
decrease
HDL
0
0
0
Marked
increase
Triglycerides
0
0
Small
decrease
Moderate
decrease
LP(a)
0
0
Moderate
decrease
Moderate
decrease
Moderate
increase
Moderate
increase
Moderate
decrease
Moderate
increase
Body weight




A 52-year-old woman is found to have a fasting plasma glucose
concentration of 168 mg/dL during her annual physical examination. Her
lifestyle is sedentary. Obesity has been a problem since early adulthood,
and her weight in recent years has ranged from 90 to 103 kg (196 to 226
lb). Her blood pressure has been elevated for the past 18 years, and
while taking captopril, it is in the 160/90 to 180/100 range. The
hemoglobin A1C level is 8.4%.
After meeting with a dietitian and nurse educator, she starts a calorierestricted diet and an exercise program; 6 weeks later, she weighs 91.8
kg (202 lb) and her hemoglobin A1C is 8.6%. Other laboratory tests
include a total cholesterol of 238 mgldL and a fasting triglyceride level of
278 mgldL.
What is the best hypoglycemic agent for this patient?
( A ) Insulin
( B ) A sulfonylurea
( C ) Metformin
( D ) Acarbose
( E ) Rosiglitazone

Critique (Correct Answer = C)

Persistent hyperglycemia and hypertriglyceridemia in an obese patient make metformin
an ideal agent. The drug will facilitate weight loss and have beneficial effects on the
hypertriglyceridemia. The United Kingdom Prospective Diabetes Study indicated that
insulin and sulfonylureas equally lower plasma glucose but do not help weight loss or
prevent weight gain. The thiazinolinediones as monotherapy also increase weight as well
as possibly adversely affecting serum cholesterol levels. Although metformin as well as
insulin and sulfonylureas reduce hyperglycemia and consequently lower the risk for the
several microvascular complications, these agents do not significantly alter the risk for
myocardial infarction.
Insulin is most effective as the first choice in symptomatic patients, especially those who
are normal weight or only slightly overweight. In the setting of infection, a vascular
accident, or other medical problem, the patient with recent-onset type 2 disease benefits
from insulin as first treatment.
Sulfonylureas would also probably lower plasma glucose in this patient, but weight gain or
inability to lower weight are possible complications. In 10% to 15% of recently diagnosed
patients, sulfonylureas are ineffective as hypoglycemic agents. The exact cause of this
primary failure is unclear, although beta cells exposed to hyperglycemia for prolonged
periods will not respond to sulfonylureas.
Acarbose is reserved for patients with type 2 diabetes mellitus in whom postprandial
hyperglycemia is the major problem. In patients with elevated fasting glucose levels,
acarbose will have limited effect.
The thiazolidinediones effectively reduce fasting plasma glucose concentration. These
agents increase serum LDL-and HDL cholesterol slightly and lower triglycerides by about
10-15%.




Which one of the following describes the effect
of the thiazolidinediones?
 ( A ) Inducing weight loss effect
( B ) Decreasing low-density lipoprotein cholesterol
( C ) Increasing production of insulin from
pancreatic beta cells
( D ) Increasing glucose transporter expression


Critique (Correct Answer = D)

Resistance to the action of insulin is a prime cause of the hyperglycemia in most
patients with type 2 diabetes. The thiazolidinediones are a group of drugs that
improve sensitivity to insulin in several tissues by binding to PPAR-γ receptors,
leading to increased expression of glucose transporters. The agent causes
weight gain when used as monotherapy and in combination with insulin. Serum
triglyceride values fall, whereas both LDL and HDL cholesterol values increase;
the rise in LDL cholesterol in several studies is about 10% to 15%. The currently
available thiazolidinediones, rosiglitazone and proglitazone, are equally effective
in lowering glucose in patients with type 2 diabetes mellitus. Hemoglobin A1C
levels fall about 1.5% in studies of these agents. Several cases of severe liver
toxicity have been reported after troglitazone therapy, so it was removed from
the market in March of 2000. The U.S. Food and Drug Administration
recommends baseline and every 2 month monitoring of liver function tests
during the first year of therapy if this class of drugs is used. The incidence of
elevated liver enzyme levels in patients treated with proglitazone and
rosiglitazone are 0.25% and 0.2% respectively, values similar to those in
patients receiving placebos.
Insulin Therapy in Type II
DM
Newly diagnosed patients with DM2
have < 50% of normal insulin
secretion at diagnosis
 < 25% of normal insulin secretion 6
years after diagnosis

Indications for Insulin
Therapy in Type II DM

Why




More than 30% of type 2 diabetics require insulin
Progressive β-cell deterioration
Addition of a qHS basal insulin can reduce the Hgb A1C level from 8.6% to 6.9
% (Yale, Annal Int Med, 2001)
When




Persistent Fasting plasma glucose ≥ 250 mg/dL
Hgb A1C > 8% on maximum oral therapy
Hepatic or renal dysfunction that prohibits oral agents
All pregnant type II diabetics
• All oral agents are contraindicated

How


UKPDS showed combination therapy with insulin and oral agent had better
control
No recommended combinations at this time
• Metformin + sulfonylurea + insulin
• Sulfonylurea + bedtime insulin
• Lispro + glyburide

Not recommended: thiazolidinediones + insulin = HYPOGLYCEMIA




A 56-year-old overweight woman has had urinary
frequency, nocturia, and dysuria for 5 days. She also
reports increasing thirst.
On physical examination, her temperature is normal, she
appears dehydrated, and has no costovertebral angle
tenderness. Her plasma glucose concentration is 620
mg/dL. Urinalysis reveals 4+ glucose, no ketones, strongly
positive protein, and 8 to 10 leukocytes per high-power
field. Antibiotic therapy is begun for the urinary tract
infection.
Which one of the following therapies is the most
appropriate at this time?
( A ) Sulfonylurea
( B ) Diet and exercise program
( C ) Insulin
( D ) Metformin
( E ) α-Glucosidase inhibitor

Critique (Correct Answer = C)

The therapeutic goals in this patient are to alleviate symptoms and control hyperglycemia.
When a newly diagnosed patient has symptoms, evidence of a urinary tract infection and
markedly elevated plasma glucose concentration, treatment with insulin is the best
assurance that symptoms will resolve and that the infection will respond readily to
appropriate therapy. Hospitalization is usually not warranted unless ketoacidosis or
severe dehydration and hypotension are present. Some patients will respond to oral
agents, such as metformin, but that response may be slow and insufficient to alleviate
symptoms. After prolonged periods of markedly elevated glucose, the response to
sulfonylureas is blunted as the beta cells of the pancreas produce little or no insulin
because of the glucose toxicity. After 6 to 8 weeks of good glycemic control effected by
insulin, therapy may be switched to an oral agent if the patient prefers. A benefit of tight
glycemic control with intensive insulin therapy in such patients is the reversal of glucose
toxicity, with the improvement of both insulin sensitivity and insulin secretion. αGlucosidase inhibitors like acarbose, reduce postprandial hyperglycemia by delaying
glucose absorption, but do no affect glucose utilization or insulin secretion. They are less
potent agents and therefore would not be the correct agents to use to control her
hyperglycemia.
Every patient with newly diagnosed diabetes mellitus should be offered an educational
program that emphasizes the importance of diet and exercise. In symptomatic patients
with this severe a degree of hyperglycemia, diet and exercise are inadequate to achieve
the desired goals.

DKA
HONC
Glucose
300-600
600-1200
Sodium
125-135
135-145
Potassium
Nml to increased
Nml
Magnesium
Nml
Nml
Phosphate
Decreased
Nml
CRE
Nml to slight increased
Mod increased
Ketones
++++++
-----
HCO3
<15 meq/l
Nml to slightly decreased
Ph
6.8-7.3
>7.3
Anion Gap
Increased
Nml to increased
Initial Visit
History
 Physical – don’t forget eye exam and
foot exam (monofilament)
 Labs



Fasting Chem 7, Hgb A1C (not
diagnostic!!!), fasting lipids, LFTs, UA
with urine microalbumin, TSH
ECG
Prevent, Monitor, Manage
and Educate








Diet, exercise, weight control
Smoking cessation
Blood pressure (strict BP goals)
Lipids (remember DM = CAD equivalent)
Renal function
Annual eye exam
Podiatric/orthopedic exam
Pneumovax, influenza vaccine
Prevent, Monitor, Manage
and Educate


Weekly, monthly follow up
Diabetic education!!!







Medication administration
Blood glucose monitoring
Lifestyle changes
HgbA1C q 3-6 months along with any other
labs
Support groups
Websites (www.diabetes.org)
Your encouragement, support
Diabetic Complications


Coronary Artery Disease
Acute Complications



DKA, HONK
Hyperglycemia, Hypoglycemia
Long Term Complications



CAD
Peripheral Vascular Disease
Diabetic Retinopathy
• Nonproliferative, proliferative


Diabetic Nephropathy
Diabetic Neuropathy
•
•
•
•

Peripheral Sensory
Cardiovascular Autonomic
Gastrointestinal Autonomic
Erectile dysfunction
Diabetic Foot
• Dr. Attinger
Cardiovascular Disease






BP goal < 130/80
Lipids: LDL < 100, TG < 150, HDL > 40/50
Statins for DM patients > 40 to achieve LDL reduction of
30% regardless of baseline (Heart Protection Study)
Aspirin for primary or secondary prevention
Smoking cessation
Cardiac stress testing





any symptoms – typical or atypical
abnormal EKG
h/o peripheral vascular disease
Sedentary lifestyle, age > 35 and plans to exercise
> 2 risk factors (dyslipidemia, HTN, smoking, FH,
micro/macroalbuminuria)
Peripheral vascular
disease/Foot care





Examine feet at
every visit
Check pedal pulses
Check skin and
nails
Vibrations sense,
monofilament exam
Recommend
podiatry
Retinopathy



Optimal glycemic and BP control can
substantially reduce the risk and
progression of DM retinopathy
Annual screening for most
Laser therapy can reduce the risk of vision
loss in patients with high risk characteristics
(disc neovascularization or vitreous
hemorrhage with any retinal
neovascularization)
Retinopathy

Background
retinopathy





Vision normal
Microaneurysms
Hemorrhages
Exudates
May see a
macular star
Pre-proliferative
Retinopathy



Cotton-wool spots
Venous dilatation
Large deep
hemorrhages
Diabetic maculopathy


Retinopathy in
macula
Causes reduced
visual accuity and
blindness and
requires urgent
laser therapy
Proliferative retinopathy



Retinal
neovascularization
Vitreous
hemorrhage
Fibrosis and retinal
detachment
A 41-year-old man with type 1 diabetes mellitus has a funduscopic examination
during a routine office visit. The findings are seen on the funduscopic photograph.
What does the funduscopic photograph on the left show?
( A ) Diabetic background retinopathy
( B ) Diabetic proliferative retinopathy
( C ) Diabetic macular degeneration
( D ) Papilledema
Nephropathy
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25-30% of patients with diabetes develop nephropathy
Can be prevented or delayed with tight glycemic and BP
control
All pts need screening UA
 If UA shows proteinuria then needs 24 hour urine
protein
 If UA negative check for microalbuminuria (30-299
mg/24hr) annually
• Spot albumin:Cr ratio vs. 24hr albumin measurement
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Albuminuria is associated with a 4-8 fold increased
cardiovascular risk
If albuminuria present pt should be started on ACE
inhibitor/ARB and glycemic control should be tightened.
Neuropathies
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Peripheral sensory neuropathy
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Symmetrical distal dysasthesias and pain
Initially loose vibration sense
Tx with tricyclics and gabapentin
Autonomic neuropathy
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Presents with orthostatic hypotension,
absent normal variation of heart rate with
breathing
Tachycardia and sudden death
Treat orthostatic hypotension with
Fludrocortisone and Midodrine
Neuropathies II

GI autonomic neuropathies

Gastroparesis
• Nausea, vomiting, bloating and GERD

Diarrhea
• Especially nocturnal diarrhea

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Treatment: Metoclopramide (Reglan)
Erectile dysfunction
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> 50% of men with DM have erectile
dysfunction
Typically unable to achieve both
nocturnal and morning erections
(distinguishes arousal problem from
vascular problem)
Treatment: Sildenafil, but avoid in pts
with cardiovascular disease or on
Neuropathies III

Mononeuropathies
Can develop wrist drop (radial nerve),
foot drop (sciatic nerve) or CN III palsy
 Probably related to damage to
microvascular supply to nerve


Diabetic Amyotrophy

Pain, atrophy and fasciculations of the
limb girdle muscles.
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A 70-year-old woman has developed weakness and numbness of her legs and
arms during the past 8 months. The symptoms began with tingling in her feet.
Later, severe weakness gradually developed. For 2 years, she has been taking
oral hypoglycemic agents to treat diabetes.
On physical examination, the patient has a pulse rate of 70/min and a blood
pressure of 120/85 mm Hg. She cannot rise from her chair without pushing off
with her arms. She has moderately severe weakness (3/5) of the thigh and
lower leg muscles. There is little movement remaining in her feet and toes (1/5).
Her hands are also very weak (2/5). She has no deep tendon reflexes in her
lower extremities. Vibration sensation and position sense are slightly reduced at
the toes and malleoli. Pinprick and touch sensations are normal. Her toes do not
move in response to plantar stimulation. Fasting plasma glucose level is 95
mg/dL; the 2-hour postprandial plasma glucose level is 125 mg/dL. HgbA1C is
5.6%.
Which of the following is the most likely diagnosis?
( A ) Spinal cord tumor
( B ) Polymyositis
( C ) Hemispheric stroke
( D ) Chronic inflammatory demyelinating polyneuropathy
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Critique (Correct Answer = D)
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This woman has chronic inflammatory demyelinating polyneuropathy predominantly
affecting motor fibers, causing significant limb paralysis. The combination of greater distal
than proximal muscle weakness, areflexia, and distal loss of vibration sense is
characteristic of a peripheral polyneuropathy that affects mostly myelinated fibers. A
muscle disease such as polymyositis would cause greater proximal than distal weakness.
A spinal cord lesion would not be symmetric, and sensory loss would not be limited to
vibration. A hemispheric stroke would produce unilateral signs and symptoms. The
differential diagnosis is between a demyelinating polyneuropathy and a diabetic peripheral
polyneuropathy.
Diabetic peripheral polyneuropathy is most often a rather mild disorder that causes some
decreased sensation in the toes and feet and a loss of ankle reflexes. More severe
polyneuropathies do occur, especially in long-standing diabetes, especially if diabetic
control is poor. This woman had very mild diabetes that is well controlled. A rapidly
progressive, severe, paralyzing polyneuropathy explained by diabetes would be extremely
rare in her circumstances. Chronic inflammatory demyelinating polyneuropathy is a
relatively common polyneuropathy presumed to be of an autoimmune basis in which
proximal and distal weakness and areflexia are common. Usually sensory loss is limited
to vibration and position sense, sensory functions mediated by large myelinated fibers
within peripheral nerves. Some have thought of this disorder as a kind of chronic GuillainBarré syndrome. The history and physical examination presented are typical of chronic
inflammatory demyelinating polyneuropathy. Electrophysiologic studies will document
widespread decrease in motor and sensory nerve conduction velocities indicative of a
demyelinating polyneuropathy.
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Summary
• GLYCEMIC CONTOL (GOALS)
• Pre-prandial glucose: 80-120
• 2 hour post prandial glucose: <160
• Pre-bed glucose: 100-140
• HbA1c <6.5 - 7%
• REVIEW REGIMEN
• Insulin vs. oral hypoglycemics
• MONITORING
• HbA1c
• Urine microalbumin
• Lipid profile LDL < 100, TG<150, HDL>50
• CLINICAL EXAM
• Fundoscopy
• Foot exam
• Cardiac and peripheral pulses
• BP <130/80
• EDUCATION
• Smoking
• Diet
• Exercise
• Consider Aspirin unless contraindication