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2011 Updates in Therapeutics:

The Pharmacotherapy Preparatory Review and


Recertification Course

Endocrine and Metabolic Disorders


Brian K. Irons, PharmD, BCPS, BC-ADM
Texas Tech University Health Sciences Center
School of Pharmacy

Conflict of Interest Disclosures


Dr. Irons has no conflicts of interest to
disclose

Learning Objectives and/or


Agenda
Focus on diabetes mellitus and disorders of the
thyroid, adrenal, and pituitary glands
Diagnosis
Classification
Therapeutic agents
Treatment / Monitoring
Review treatment of polycystic ovary syndrome
and obesity
Review treatment of diabetes-related
complications 230

1
Thyroid Disorders

Hyperthyroid Disorders
Graves Disease: Toxic diffuse goiter
Pituitary adenomas
Toxic adenoma
Toxic multinodular goiter
Subacute thyroiditis
Drug--induced (amiodarone, thyroid
Drug
replacement)

247

Hypothyroid Disorders
Hashimotos Disease
Thyroid surgery / Ablative therapy

Iodine deficiency y
Secondary causes

Pituitary insufficiency (lack of TSH)

Drug
Drug--induced (amiodarone, lithium)

247-248

2
Thyroid Labs / Diagnosis
Free T4 and TSH tell most of the story
Hyperthyroid:: Low TSH, elevated free T4
Hyperthyroid
Hypothyroid:: High TSH (lack of negative
Hypothyroid
feedback), suppressed free T4
TSH may be low or normal in secondary
causes
Thyroid antibodies
Radioactive iodine uptake

248

Clinical Presentation
(Hyperthyroid)
Hyperthyroid)
Appetite increased
Weight loss
Goiter
Heat intolerance
Fine hair
Palpitations / tachycardia
Anxiety / insomnia / nervousness
Moist skin / sweating
Exophthalmos (bulging eyes)

248

Clinical Presentation
(Hypothyroid)
Hypothyroid)
Weight gain
Dry skin
Cold intolerance
Weakness / fatigue / lethargy
Bradycardia
Slow reflexes
Coarse skin / hair

248

3
Thyroid Disorder: Goals
Improve quality of life
Minimize or eliminate symptoms

Minimize long-
long-term damage
Normalize free T4 / TSH

249

Hyperthyroid Pharmacotherapy
Usual indications
Not surgical (adenomas) or ablative therapy
candidate (tx
(tx of choice in Graves disease)
Surgery / ablative therapy unsuccessful

Awaiting ablation / surgery

Deplete stored hormone

Minimize thyroiditis (reduce post-


post-treatment
hyperthyroidism)
249

Thioureas (aka Thioamides)


Propylthiouracil (PTU) and Methimazole
Inhibit iodination and synthesis of thyroid
hormones
Efficacy
Low remission rate: 40-
40-50% (1-
(1-2 years on therapy)
May take weeks for symptomatic improvement
4-6 months for maximal effect

Neither drug appears more effective than the other

Mg
Mg--Mg: methimazole is 10x more potent

249

4
Thioureas (aka Thioamides)
ADRs:
Hepatotoxicity with PTU (black box warning)

Arthralgias

Fever

Rash

Transient leukopenia

Agranulocytosis

Monthly dose titrations (symptoms / TSH


guide)
249

Beta--blockers
Beta
Primarily for symptomatic improvements
Most commonly employed: propranolol /
nadolol
Block manyy manifestations of hyperthyroidism
yp y
(tachycardia / anxiety / tremor / palpitations) -
some T4 to T3 conversion blocked
Very poor remission rates: 20-
20-30%
Significant role in thyroid storm

249-250

Iodines
Lugols Solution / SSKI
Block release ((not
not synthesis)
synthesis) of hormone / May
help in reducing size and vascularity of gland
prior to surgery
ADR: Metallic taste / hypersensitivity / oral
soreness or burning
Primary uses:
uses: Pre
Pre--surgery to shrink gland size /
post-
post-ablative tx to reduce release stored
hormone (less thyroiditis) / thyroid storm
Only used short-
short-term (1(1--2 weeks): Gland will
eventually begin to leach hormone
250

5
Hypothyroid Pharmacotherapy
Drug of Choice:
Choice: Synthetic T4 ((levothyroxine
levothyroxine))
Cost / antigenicity profile / potency / ADR
profile
Initial dose: 50-
50-75 micrograms
Common maintenance dose: 1.6- 1.6-1.7 mcg/kg/day
Titrate based on T4/TSH and symptoms
6 weeks to reach steady state (usual titration
schedule)
ADRs: Hyperthyroidism / angina / MI
250

Hypothyroid Pharmacotherapy
Synthetic T3 ((liothyronine
liothyronine):
): Less
attractive alternative (higher CV ADR
p
profile))
Liotrix / Desiccated thyroid: Not used
much anymore

251

Thyroid Storm Therapy


Life-threatening thyrotoxicosis
Life-
Infection / Trauma common causes
Fever / Tachycardia / N-N-V / Dehydration /
Delirium / Tachypnea / Coma
PTU
PTU-- 300-
300-400 mg tid
Iodide treatment:
treatment: After PTU initiated
Beta-
Beta-blocker (e.g. esmolol / propranolol)
APAP (avoid NSAIDs)
Corticosteroid tx:
tx: 25-
25-100 mg prednisone or
equivalent 251

6
Pituitary Disorders
Limit treatment discussion to Acromegaly /
Hyperprolactinemia
Acromegaly pharmacotherapy often reserved
for:
Pre
Pre--surgery/irradiation (control symptoms)
Not a surgical candidate

Surgical / irradiation failure or relapse

254

Acromegaly Therapy
Cause: Growth
Growth--Hormone (GH) secreting
pituitary adenoma
Goal: Decrease IGF
IGF--1 and GH, mortality,
symptoms
y p
Dopamine Agonists (paradoxical decrease in
GH production)
Bromocriptine / cabergoline
ADRs: Nervousness / fatigue / dizziness / GI
~50% get symptom relief (10% obtain normal IGF-
IGF-
253-254 1)

255
Acromegaly Therapy
Somatostatin analog (octreotide
(octreotide))
Block GH secretion
Dosed subcutaneously three times daily initially
Can be switched to long-
long-acting formulation (once
monthly) if responsive to tx
ADR: Lot of GI / hypothyroidism / arrhythmias /
glucose abnormalities / biliary tract disorders
Good symptomatic relief (50-
(50-60% IGF
IGF--1
normalization)
GH Receptor antagonist pegvisomant
Very good IGF-
IGF-1 normalization / long-
long-term trials
needed

7
Hyperprolactinemia Therapy
Prolactinomas
Drug
Drug--induced: SSRIs, anti-
anti-psychotics
DC offending agent

Case
C where
h ddrug therapy
h may b
be b
better
than surgery
Dopamine agonists
Cabergoline More effective than bromocriptine
Bromocriptine
255

Adrenal Disorders
(Cushings Syndrome)
Hypersecretory cortisol disease
Adrenocorticotropic hormone (ACTH)
(ACTH)--
dependent
80% of cases / Excessive ACTH secretion
Most common form: Pituitary corticotroph
adenoma (Cushings disease)
Adrenocorticotropic hormone (ACTH)
(ACTH)--
independent
20% of cases / Exogenous steroid use or
excessive cortisol secretion 256

Cushings Syndrome
Clinical presentation (similar to excessive / long-
long-
term use of exogenous corticosteroids):
HTN / Osteo / Obesity / Moon face / Glucose
abnormalities etc
Treatment Options (all aimed at inhibiting
cortisol production)
Ketoconazole: Gynecomastia / GI / LFT increases
Mitotane: Ataxia / GI / Lethargy / Anorexia
Etomidate (IV): Usually reserved for acute cases

257-258

8
Hyperaldosteronism
70% cases: Bilateral adrenal hyperplasia
30% cases: Aldosterone-
Aldosterone-producing
adenoma
Dx: Elevated plasma aldosterone : renin
ratio
S/S: HTN / fatigue / HA / polydipsia

Tx: Spironolactone / Eplerenone /


Amiloride 257

Obesity

Obesity - Classification
Classification BMI
Normal 18.5-24.9
Overweight 25.0-29.9
25.0 29.9
Class I 30.0-34.9
Class II 35.0-39.9
Class III 40+

260

9
Obesity Therapy
Sibutramine (Meridia)
Meridia) pulled from market 2010
Orlistat Inhibits gastric and pancreatic lipases
>> reduced fat absorption
Rx
R (Xenical
((X
Xenical):
X i ll)):) 120 mg three
h times
i daily
d il (up
( to 1 hour
h
prior to meals)
OTC (Alli
(Alli):
): 60 mg three times daily (up to 1 hour
prior to meals)
LOTS GI ADRs: flatulence, oily stool, loose stool

261

Polycystic Ovary Syndrome


(PCOS)
Androgen excess or hyperandrogenism
May be result of insulin resistance (regardless of
body mass)
Diffi l consensus on classification
Difficult l ifi i and d
diagnosis
Common signs: Hirsutism, acne, pattern
alopecia
Increased LH/FSH ratio (>2) and serum
testosterone
261-262

PCOS Therapy Goals


Improve fertility (if desired)
Normalize menses / ovulation

Minimize clinical signs

Limit progression to Type 2 DM


(mainly in those with obesity)

262

10
PCOS Therapy Options
Clomiphene citrate
Selective estrogen receptor modulator (improves
LH--FSH secretion)
LH
ADRs: Flushing
Flushing, GI discomfort,
discomfort vaginal dryness,
dryness
multiple pregnancies
Recombinant FSH or GRH (+/-
(+/- clomiphene)
clomiphene)
May result in multiple pregnancies
Metformin

263

Diabetes Mellitus

Highly Recommended References to


Review
2011 American Diabetes Association Standards
of Medical Care
Diabetes Care 2011:34(
2011:34(Suppl
Suppl 1):S11
1):S11--S61
N h D et al.l Medical
Nathan M di l management off
hyperglycemia in type 2 diabetes: a consensus
algorithm for the initiation and adjustment of
therapy
Diabetes Care 2009;32:193
2009;32:193--203

231

11
Patient Case
(Does this patient have diabetes?)
56 yo Hispanic female with complaints of
symptoms consistent with vaginal fungal
infection. Seen last month with similar
complaints.
Weight 220 lb (BMI 42 kg/m2 ), BP 148/84, ht
rate 88, temp 98.8
PMH: Gestational DM, HTN, else
unremarkable
Labs: Chem 7 glucose (fasting) 142 mg/dL, else
wnl (fasting glucose last month was 136 mg/dL)

Diabetes Classification
Type 1 Diabetes Mellitus (5
(5--10% of DM)
Pancreatic beta
beta--cell destruction / insulin required
Type 2 Diabetes Mellitus (90
(90--95% of DM)
Insulin resistance + decreased pancreatic insulin
output
Gestational diabetes
Maturity--onset diabetes of the young (MODY)
Maturity
Others (pancreatitis, drug induced, genetic
defects)
231

Screening for Diabetes


Type 1 DM
If symptomatic ((polyuria
polyuria /
polyphagia / polydipsia / weight
lloss))
High risk asymptomatic (family
history / transient hyperglycemia)

232

12
Screening for Diabetes
Gestational DM:
DM:
Previously dependent on risk (high /
average / low)
2010/2011 Recommendations by
ADA
24-
24-28 weeks of gestation
75 gram Oral Glucose Tolerance Test

232

Screening for Type 2 Diabetes


Every 3 years starting at age 45
Earlier if BMI > 25 kg/m2 and any of the below:
h/o CVD
IGT / IFG / mild increase in A1c (aka prediabetes)
prediabetes)
Polycystic ovary syndrome
Low HDL or elevated TG
Hypertension
h/o gestational DM (or delivery of large baby)
High
High--risk ethnicity
First
First--degree relative with DM
Physically inactive
232

Type 1 and 2 DM Diagnosis


(Based on glycemia
glycemia))
FastingPlasma Glucose > 126 mg/dL
mg/dL
Random Plasma Glucose > 200
mg/dL
mg/dL and symptomatic
Hemoglobin A1c > 6.5% ((new
new in
2010
2010))

232

13
Type 1 and 2 DM Diagnosis
Elevated Plasma Glucose Post
Post--OGTT
2 hours after 75 g oral glucose
ingestion
> 200 mg/dL
mg/dL
Plasma Glucose if abnormal should be
repeated on subsequent day

232

Patient Case
(Should this patient be screened?)
56 yo Hispanic female with complaints of
symptoms consistent with vaginal fungal
infection. Seen last month with similar
complaints.
Weight 220 lb (BMI 42 kg/m2 ), BP 148/84,
148/84, ht
rate 88, temp 98.8
PMH: Gestational DM DM,, HTN,
HTN, else
unremarkable
Labs: Chem 7 glucose (fasting) 142 mg/
mg/dL
dL,, else
wnl (fasting glucose last month was 136 mg/dL
mg/dL))

Patient Case
(Does this patient have diabetes?)
56 yo Hispanic female with complaints of
symptoms consistent with vaginal fungal
infection. Seen last month with similar
complaints.
Weight 220 lb (BMI 42 kg/m2 ), BP 148/84, ht
rate 88, temp 98.8
PMH: Gestational DM, HTN, else
unremarkable
Labs: Chem 7 glucose (fasting) 142 mg/dL
mg/dL,, else
wnl (fasting glucose last month was 136 mg/dL
mg/dL))

14
Goals of Therapy in DM
PREVENT ACUTE AND CHRONIC
COMPLICATIONS !
Acute:
Acute: Hypoglycemia / DKA / HHNS
Chronic:
Chronic:
Microvascular
Microvascular:: Retinopathy / Neuropathy /
Nephropathy
Macrovascular
Macrovascular:: Cardiovascular /
Cerebrovascular / Peripheral vascular disease

233

Glycemic Goals (non-


(non-pregnant adult)
Fasting Plasma Glucose: 70-70-130 mg/
mg/dL dL
A1c: < 7.0%
Obtain every 3 months if uncontrolled

Obtain every 6 months if at goal

Can be less stringent in some patients

Post--prandial (1
Post (1--2 hours after meal): < 180 mg/dL
mg/dL
Glycemic goals in gestational DM much more
aggressive
233-234

Other Goals of Therapy


Blood Pressure < 130/80 mm Hg
LDL
LDL--C < 100 mg /dL
/dL
Triglycerides < 150 mg/dL
mg/dL
HDL > 40 (men), > 50 (women)

234

15
Benefits of Good DM Control
Glycemic Control
Reduces microvascular complications

Cholesterol Control

Reduces macrovascular complications

Blood Pressure Control

Reduces both microvascular and


macrovascular complications
234

Patient Case
(Glycemic Control)
56 yo Hispanic female, one month later
Last month placed on metformin 500 mg once
daily for one week, then bid since
A1 llast month
A1c h ((at di
diagnosis):
i ) 88.6%
6%
Fasting morning BGs per patient log over this
past week:
148,152,144,198, 178, 164

No other BG readings / other times

Oral Agents For Type 2 DM


Sulfonylureas (glyburide / glipizide /
glimepiride)
glimepiride)
Meglitinides (repaglinide / nateglinide)
nateglinide)
Metformin

Thiazolidinediones (pioglitazone )

234 through 238

16
Oral Agents For Type 2 DM
Alpha
Alpha--glucosidase Inhibitors (acarbose
/ miglitol)
miglitol)
Dipeptidyl Peptidase
Peptidase--4 (DPP-
(DPP-4)
Inhibitors (sitagliptin,
sitagliptin, saxagliptin)
saxagliptin)
Colesevelam

Bromocriptine

234 through 238

Areas of Action for DM Meds

Glucosidase Inhibitors
DDP-4 Inhibitors
Incretin Mimetics
Bromocriptine

Metformin
TZDs TZDs
Metformin

Sulfonylureas
Meglitinides
DPP-4 Inhibitors
DPP-4 Inhibitors
Incretin Mimetics
Incretin Mimetics

Sulfonylureas
May affect both fasting and post-
post-prandial
glucose
Side Effect Profile
Weight gain

Hypoglycemia

Rash

HA

GI complaints

SIADH (rare)
234-235

17
Meglitinides
Better Focus on Post-
Post-prandial BG than
sulfonylureas
Repaglinide likely better than nateglinide
Side Effect Profile
Hypoglycemia (less than with sulfonylureas)
sulfonylureas)
Weight Gain
URI

Precautions
Concurrent use of gemfibrozil (increases repaglinide
levels) 236-237

Metformin
Initial Drug of Choice per ADA
Side Effect Profile
Common
Gastrointestinal: Cramping, Diarrhea, N/V
Severe
S (b
(but rare))
Lactic acidosis
Other
Hypoglycemia (uncommon with monotherapy)
monotherapy)
Weight Loss
Triglyceride reduction
235-236

Metformin
Precautions
High cardiovascular risk / Hypoxic state

Elderly (80+): Potential for impaired


renal function despite normal creatinine
Heart failure (h/o significant
exacerbations / unstable status)

235-236

18
Metformin
Contraindications
Increased serum creatinine
1.4+ in women, 1.5+ in men

HF ((unstable or acute HF):) Note per


p package
p g
insert caution in those with HF receiving
therapy
Significant liver dysfunction

Undergoing radiological study using IV


iodinated contrast dye (hold x 48 hr and get
235 Cr before restarting)

Thiazolidinediones (TZDs)
Side Effect Profile
Hypoglycemia (uncommon with monotherapy)
monotherapy)
Weight gain
Peripheral
p edema
HDL increase / TG decrease (pioglitazone
(pioglitazone))
Bone fracture risk (women)

Heart failure risk (both agents): Black Box Warning

MI / Cardiovascular death ((rosiglitazone


rosiglitazone))

236-237

Thiazolidinediones (TZDs)
Contraindications
Heart Failure (NYHA Class III and IV)
Liver impairment (ALT >2.5
2.5 times uln)
uln)

237

19
Glucosidase Inhibitors
Post
Post--prandialglucose focus
Side Effect Profile
LOTS of GI side effects: Flatulence,
Flatulence diarrhea,
diarrhea
cramping, pain, etc
Reason for slow titration

Increased LFTs at higher doses

237

Glucosidase Inhibitors
Precautions
Lowerdosage in patients with renal
impairment
Contraindications
Inflammatory bowel disease, ulcerative colitis,
intestinal obstruction

237

Colesevelam
Mild reductions in A1c
Side Effects
Constipation / dyspepsia / nausea / myalgia

Precautions / Contraindications
Elevated triglycerides

Bowel obstruction

Difficulty swallowing

238

20
Bromocriptine
Small reductions in A1c
Side Effects
Fatigue / dizziness / nausea / vomiting / headache
/ hypotension / syncope
Precautions/Contraindications
h/o syncopal migraines
Nursing mothers
Limits effectiveness of antipsychotics

238

GLP--1 Modulates Numerous Functions in


GLP
Humans
GLP-1: Secreted upon the
ingestion of food
Promotes satiety and
reduces appetite

Alpha cells:
Postprandial
glucagon secretion

Liver:
Glucagon reduces hepatic
Beta cells: glucose output
Enhances glucose-dependent
insulin secretion
Stomach:
Helps regulate gastric
emptying

239-240

DPP--4 Inhibitors
DPP
Side Effect Profile
GI complaints

Hypersensitivity (angioedema
(angioedema,, exfoliative skin
conditions,, anaphylaxis)
p y )
Precautions
Renal impairment (dose adjust)

History of pancreatitis

237-238

21
Injectable DM Agents

Incretin Mimetics
GLP
GLP--1 analog (in Type 2 DM)
Exenatide (Byetta) Twice daily
Liraglutide (Victoza) Once daily

Amylin analog (in Type 1 and 2 DM)


Pramlintide (Symlin) -Three times daily
pre--meals / Initially reduce insulin doses
pre
None should be mixed with insulins
239-240

Exenatide and Liraglutide


Side Effect Profile
Hypoglycemia (increased with sulfonylurea)

Weight Loss

Nausea

Vomiting

GI discomfort

Injection site discomfort

Pancreatitis risk
239

22
Exenatide and Liraglutide
Precautions
Existing gastroparesis
History of pancreatitis
Exenatide
Exenatide:: Moderate renal impairment (<50
ml/min)
Contraindications
Exenatide
Exenatide:: CrCl
CrCl<30
<30 ml/min
Liraglutide:
Liraglutide: Medullary thyroid carcinoma

239

Insulin Kinetics 240-241


Type Drug Name Onset Peak Duration
Rapid-
Rapid- Aspart 5-15 minutes
Acting (Novolog) (10--20)
(10
1-2 hours 4-6 hours
Lispro 5-15 minutes
(Humalog) (15--30)
(15
Glulisine
5-15 minutes 1-2 hours 4-6 hours
(Apidra
Apidra))
Short-
Short- Regular
0.5-
0.5-1 hour 1-5 hours 6-10 hours
Acting
Intermed-
Intermed- NPH 1-2 hours 4-8 hours 10-
10-20 hours
Acting

Intermed Detemir 6-8 hours


2-4 hours
To Long (Levemir) 3-4h (0.2
(0.2--0.4) 5.7-
5.7-23.2 hrs
Acting
Long
Long-- Glargine Not significant
1-2 hours ~24 hours
Acting (Lantus) (Flat)

A1c Efficacy of DM Meds


Intervention Reduction in A1c Expected
Diet / Exercise 1.0-
1.0-2.0
Metformin 1.0-
1.0-2.0
Sulfonylurea 1.0-
1.0-2.0
TZD 0.5-
0.5-1.4
GLP--1 Mimetic
GLP 0.5-
0.5-1.0
Glucosidase Inhibitor 0.5-
0.5-0.8
DPP--4 Inhibitor
DPP 0.5-
0.5-0.8
Meglitinide 0.5-
0.5-1.5
Insulin 1.5--3.5
1.5
Diabetes Care 2009;32:193

23
Treating Type 1 DM

Natural Insulin Secretion

75
Breakfast Lunch Dinner
n (U/mL))

50
Plasma
Insulin

25

8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time

Treating Type 1 DM

Basal / Bolus Insulin Regimens (mimic nature)


Basal to prevent ketosis and control fasting
BG
Detemir / Glargine / (NPH)

Bolus to control post-


post-prandial glucose
excursions
Glulisine / Aspart / Lispro / (Regular)

241

24
Treating Type 1 DM

Initial treatment often weight-


weight-based estimate
e.g 0.6 units / kg / day = total daily insulin
needs
B l is
Basal i 50% off totall daily
d il insulin
i li needsd
Bolus is 50% of total daily insulin needs split
three ways and given prior to each meal

241

Assessing Therapy and Dosage


Adjustment
Know your goal fasting and post-
post-prandial
BGs
Identify where in the day problems occur

Determine which insulin(s) can affect


problem areas
Adjust medication (or behavior)

242

Type 1 DM Case
42 yo WF with Type 1 DM x 22 years: A1c last
week = 7.6%
Current insulin regimen
Detemir 60 units once daily at bedtime
Lispro:: 6 units before breakfast, 5 before lunch, 8
Lispro
before dinner (very consistent diet/dosing)
Fasting am BGs: 162, 155, 168, 140, 166
Post--prandials
Post prandials:: 172, 176, 154, 166, 170, 142, 133
No bouts of daytime or nocturnal hypoglycemia
Patient Case 3 page 242

25
Treating Type 2 DM

ADA Stepwise Algorithm


(Tier 1: Well-
Well-validated Core Tx)
Step 1

Lifestyle and Metformin


Step 2

ADD Sulfonylurea ADD Basal Insulin

Step 3
Lifestyle and Metformin and
Intensive Insulin Therapy
242
Diabetes Care 2009;32:193

ADA Stepwise Algorithm


(Tier 2: Less Well-
Well-validated Core Tx)
Lifestyle and Metformin

ADD Pioglitazone ADD GLP-1 Agonist

Metformin Metformin
Sulfon + Pioglit Basal Insulin

Metformin and Intensive Insulin Therapy


242
Diabetes Care 2009;32:193

26
Assessing Therapy and Dosage
Adjustment

Know your goal fasting and post-


post-prandial
BGs
Identify where in the day problems occur

Determine which medication(s) can affect


problem areas
Adjust medication (or behavior)

Patient Case
(Glycemic Control)
56 yo Hispanic female, one month later
Last month placed on metformin 500 mg
once daily for one week, then bid since
A1c last month (at diagnosis): 8.6%

Fasting morning BGs per patient log over


this past week:
148,152,144,198, 178, 164

No other BG readings / other times

Insulin Patient Case


32 year old female with Type 2 DM receiving
metformin 1000 mg twice daily, insulin glargine
72 units q hs,
hs, and insulin glulisine (10 units
before breakfast
breakfast, 15 before lunch,
lunch and 22 before
dinner)
A1c = 8.2%

All post-
post-prandial BGs < 180 mg/dl but fasting
BGs consistently elevated over the last 3 weeks

27
Treatment of Diabetes
Complications

Hypoglycemia
Treatment depends on degree of hypoglycemia
Plasma glucose < 70 mg/dl (+/-
(+/- symptoms)
Mild--moderate low BGs: 15-
Mild 15-20 gm oral glucose
or equivalent
i l
Severe (cognitive impairment, requires help):
1 mg IM glucagon

IV Dextrose

243

Diabetic Ketoacidosis
Significantly elevated BG / ketoacidosis /
dehydration
Signs/symptoms: Thirst, abdominal pain, mental
status changes,
changes fruity breath,
breath tachycardia,
tachycardia low Na
/ high K, ketones in urine/serum
Most common causes: infection/acute illness or
inappropriate/inadequate insulin therapy

243-244

28
DKA--Treatment (see ADA statement)
DKA
Find and fix underlying cause (if known)
NOT about normalizing blood glucose
Fluid Replacement (IV Na% depends on serum
Na)
IV insulin: 0.1 unit/kg bolus, 0.1 unit/kg/hr
drip (double drip rate if minimal response)
Hold if baseline serum K < 3.3 meq
meq/L
/L until
corrected
Potassium supplementation: Depends on
baseline K
244 Diabetes Care 2009;32:1335-43

DKA Treatment Goals


Serum glucose < 200 mg/dL
mg/dL and at least 2
of the following:
pH > 7.3
Serum bicarbonate >15 meq/L
meq/L
Anion gap < 12 mEq
mEq/L
/L
Convert IV drip to subcutaneous insulin

244

Screening for DM Microvascular


Complications
Type 2 DM: At diagnosis
Type 1 DM: At 5 years post-
post-diagnosis
Screen yearly thereafter

244-245

29
Diabetic Nephropathy
Urine albumin / creatinine
(mg/g or mcg/mg)
Normal < 30
Microalbuminuria 30-
30-300
Macroalbuminuria > 300
(Proteinuria / overt
nephropathy)
244

Treatment DM Nephropathy
Type 1 DM / HTN / any degree of
nephropathy : ACE
ACE--Inhibitor
Type 2 DM / HTN / microalbuminuria:

ACE--Inhibitor or ARB
ACE
Type 2 DM / HTN / proteinuria / serum
Cr > 1.5: Angiotensin Receptor Blocker

244

Diabetic Neuropathies
Neuropathic Pain
TCAs (smaller doses than in depression)
Desipramine / Nortriptyline /
Amitriptyline
Anticonvulsants

Gabapentin / Lamotrigine / Pregabalin

May be better tolerated than TCAs

SSRIs / SSNRI

Duloxetine
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Diabetic Neuropathies
Gastroparesis
Often symptomatic post-
post-prandially (N/ V)
Non
Non--pharmacologic treatments:
Smaller,
Smaller more frequent meals
Homogenize food

Pharmacologic treatments:

Metoclopramide ac (risk for tardive


dyskinesia)
Erythromycin ac
245

Cardiovascular Disease Prevention


Blood pressure control:
control: Regimen ideally
contains an ACE-
ACE-Inhibitor or ARB (goal <
130/80)
Cholesterol control:
control: Statin therapy regardless of
baseline LDL-
LDL-C (goal < 100 mg/dL)
In established heart disease patients (LDL < 70 is
option)
> 40 years old with other CVD risk factors

If LDL-
LDL-C still not below 100 mg/dL despite statin
therapy, 30-
30-40% reduction is alternative
246

Cardiovascular Disease Prevention


Aspirin Therapy (75-
(75-162 mg daily)
Secondary prevention: All unless contraindicated
Primary prevention
2010 ADA Changes
Ch n s
10-
10-year risk for cardiovascular event is > 10%
Will include most men > 50 and women > 60
with at least one other CVD risk factor
Clopidogrel is alternative in ASA
allergy/intolerance
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Questions ???

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