Transcript Diabetes - Catalyst

DIABETES
Required Medicine Clerkship Lecture
Jenny Wright, MD
Learning objectives

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

Know how to screening for and diagnose type 2
diabetes
Know how to prevent diabetes
Be familiar with the “pro and cons” of common
pharmacologic treatment of diabetes
Know the common complications of diabetes and
how to screening of them
Case
A 52 year old female with hypertension presents for a
preventative medicine visit. She has a family history of
hypertension, hyperlipidemia and type 2 diabetes. On
exam her BMI is 31 and her BP is 137/86.
Do you screen her for diabetes?
Screening
USPSTF:
 Overweight
+ adults between 40-70
 Consider earlier in patients with other risk factors
ADA:
 All
pt at age 45
 Earlier in overweight pts with additional risk factors
 Screen q 3 yrs
Type 2 Diabetes
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Non-modifiable risk factors: H/o gestational
diabetes, race (Native Americans, Hispanics, African
and Asian Americans, Pacific Islanders), family
history
Modifiable risk factors: obesity, inactivity
Disease associations: PCOS, dyslipidemia,
hypertension
Medication related side-effects: antipsychotics,
protease inhibitors, corticosteroids
Latent Autoimmune Diabetes in Adults:
LADA
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Adult onset autoimmune diabetes
Suspect in patients without classic risk factors for
type 2 diabetes
Diagnosis supported by presence of autoantibodies, most commonly glutamic acid
decarboxylase [anti-GAD]
More likely to require insulin, respond poorly to oral
medications, prone towards DKA
Case
Fasting lab results:
- total cholesterol 204, triglycerides 355 (normal is
<150), HDL 40, LDL 108
- sodium 138, potassium 4.9, creatinine 0.8, blood
sugar 106.
What diagnoses does this patient have?
Diagnosis
Test
“Impaired”
Diagnostic for DM
Fasting blood sugar*
100-125 mg/dL
≥126 mg/dL
Random blood sugar +
symptoms
≥ 200 mg/dL
Hemoglobin A1c*
5.7% - 6.4%
≥ 6.5%
2 hr 75 g OGTT*/**
140-199 mg/dL
≥ 200 mg/dL
*: Confirm by repeat testing
**: Rarely used in practice
Metabolic ‘syndrome’
3 of the 5
Waist circumference
M > 40 in, F > 35 in
Triglycerides
≥ 150 mg/dL
HDL cholesterol
M < 40, F < 50
BP
≥ 130/85
Fasting blood sugar
≥ 100
2001 National Cholesterol Education
Program/ATP III Definition
Case
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What therapy do you recommend?
Simvastatin 20 mg po q day
Fenofibrate 145 mg po q day
Metformin 500 mg po q day
Fish oil supplements
None of the above
Type 2 DM Prevention = Lifestyle modifications +/metformin
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Finnish Diabetes Prevention
Study
Intervention
Weight
loss at 2
yrs
Cumulative
incidence of
DM @ 4 yrs
Placebo
0.8 kg
23%
Lifestyle
counseling
3.5 kg
11%
N Engl J Med 2001;344:1343-1350
RRR
58%
Diabetes Prevention
Program
Intervention
Incidence of
DM/100
person-yrs
RRR
NNT
Placebo
11
Metformin
7.8
31%
14
Lifestyle
intervention
4.8
58%
7
N Engl J Med 2002;346:393-403
Clue to test…
Symptoms:
-
Polyuria, polydipsia
-
Unexplained weight loss
-
erectile dysfunction
Physical exam findings:
-
Acanthosis nigracans
Recurrent vaginal yeast
infections
-
-
Peripheral neuropathy
General Treatment Options
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Dietary counseling
Physical activity
Oral hypoglycemic agents
Insulin
Other injectables
Anti-obesity measures
Yet again - Diet and exercise are good
for you!
14.00%
12.00%
10.00%
Remission
prevalence
intensive lifestyle
intervention
standard diabetes
support and education
8.00%
6.00%
4.00%
2.00%
0.00%
Year 1 Year 2 Year 3 Year 4
JAMA 2012;308(23):2489-2496
Case
59 yo male presents for management of type 2
diabetes, hypertension and coronary artery disease.
He has a history of subarachnoid hemorrhage with
residual cognitive deficits. Initial labs reveal a
HgbA1c of 9.9%.
 What is your goal HgbA1c for this pt?
A. <6.5%
B. <7%
C. <8%
D. <8.5%
Recent Studies of Macrovascular
Outcomes

Long-standing, poorly
controlled T2DM,
aggressive A1c lowering:
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ACCORD:  all cause
death, no benefit/harm
re:CV outcomes
ADVANCE: no
benefit/harm re:CV
outcomes
VADT: no benefit/harm
re:CV outcomes,
observational f/u with
reduction in CV eents, not
in CVD or all-cuase death

Newly dx’ed T2DM

UKPDS 10 yr f/u:


“legacy” effect
CV benefits of metformin
tx > insulin or sulfonylurea
ACCORD (NEJM 2008;358:2545-59)
ADVANCE (NEJM 2008;358:2560-72)
VADT (NEJM 2009;360:129-39)
UKPDS 10-yr F/U (NEJM 2008; 359:1577-89)
Putting it all together…
Ismail-Beigi F et al. Ann Intern Med 2011;154:554-559
What does hemoglobin Ac1 mean?
Hb A1c (%)
Blood glc mg/dL
6
126
7
154
8
183
9
212
10
240
11
269
12
298
Case
You are caring for a 59 year old female in the hospital,
admitted with an UGIB. You are now planning for discharge,
she has no diagnosis of diabetes but has had persistent
blood sugar elevations (fasting blood sugars 155-185, premeal blood sugars 175-215) and has been getting small
amounts of insulin since she began eating again. You tested
her hemoglobin A1c, it was 5.5%.
Do you think this patient has diabetes?
A. Yes, she likely has diabetes
B. No
C. Kind of, she is likely ‘pre-diabetic’
Accuracy of A1c
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Falsely elevated
values:
 Low
RBC turnover:
untreated iron def.
anemia
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Falsely depressed
values:
 Increased
RBC
turnover: hemolysis,
recently treated iron,
B12, folate def.
anemias,
erythropoietin
 Hemodialysis
 RBC transfusion
Pharmacotherapy
Mechanisms of action
m
u
s
c
l
e
s
Liver:
metformin
Pancreas:
sulfonylureas,
glinides
Blood stream
Metformin, TZDs
Dipeptidyl peptidase IV inhibitors
Food
eaten
Intestinal
GLP-1
release
GLP-1
active
DPP-4
DPP-4
inhibitor
GLP-1
inactive
Provided by Dr Irl Hirsch, adapted from Rothenberg P, et al. Diabetes. 2000;49(suppl 1):A39.
Oral diabetes medication

Generalities:
 Monotx
lowers HgbA1c by an absolute 1% (exception:
DDP IV inhibitors)
 Addition of a second agent lowered A1c by an
additional 1%
 Take home:
 Medication
choice is more dependent on secondary
benefits/side-effects/cost than effectiveness
 Not likely to achieve tight control without insulin for patients
with HgbA1c>9%
Bennett WL, Maruthur NM, et al. Comparative Effectiveness and Safety of
Medications for Type 2 Diabetes. Ann Intern Med 2011;154(6).
Case
62 year old male presents to establish care after his
cardiologist noted that he had a fasting blood sugar of
147, follow up HbA1c of 7.2%. He has hyperlipidemia,
ischemic cardiomyopathy (EF40%) and mild CKD, baseline
Cr 1.3.
 What medication would you start him on?
A. Exenatide/Byetta
B.
Basal insulin (e.g. insulin glargine/Lantus)
C. Metformin
D. No medication at this time, recommend TLC
Metformin
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First line therapy
Benefits include:
 CVD
risk reduction (decreased rates of MI and allcause mortality)
 Weight loss
 No risk of hypoglycemia
Metformin
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Cons:
 Lactic acidosis
 Standard
contraindications:
Creatinine ≥ 1.5 in men, ≥ 1.4 in women
 Liver dysfunction
 Unstable CHF
 Chronic hypoxia

 Hold
in the hospitalized patient
 Hold for 48 hrs after IV contrast studies
Metformin in Renal Disease
Inzucchi SE, Lipska KJ, et al. JAMA. 2014;312(24):2668-2675
Case
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Back to our patient (newly diagnosed type 2
diabetic, starting metformin monotherapy), does he
need a home glucose monitor?
A. Yes
B. No
C. If he wants one.
Home glucose monitoring
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Role in care of patients not on insulin is unclear
Medicare will cover:
 100
test strips and lancets every month if on multiple
daily insulin injections
 100 test strips and lancets every 3 months if not on
insulin
Farmer AJ et al. Meta-analysis of individual data in randomized
trials of self monitoring of blood glucose in people with non-insulin
treated type 2 DM. BMJ 2012 Feb 27:e486.
If one medication isn’t enough: ADA Position Statement, 2016
Case
82 yo female with type 2 DM and CHF presents with
daughter, concerns re: episodic confusion.
Meds include glyburide, furosemide, lisinopril.
PE: nl VS, Neuro exam, including MS exam, nl.
Labs: Cr 1.3, A1c 6.2%.
What do you recommend?
A. MRI brain
B.
Discontinue glyburide
C. Switch from glyburide to sitagliptan/Januvia
D. Decrease furosemide dose
Borrowed from MKSAP
Glycemic Targets in the Elderly
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A1c of 7.5 – 8.0% is a reasonable target in most
older adults
 American
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Geriatrics Society, 2013 guidelines
A1c of 8.0 - 8.5% appropriate for individuals with
life expectancy <10 years, frail, functional
comorbidities
 Even
higher if needed to maintain quality of life
Sulfonylureas
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Sulfonylureas
 Pros:
Cheap, convenient dosing
 Cons:
 Weight
gain (≈2 kg)
 Hypoglycemia
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Caution in the elderly and CKD
Long half-lives:
 Avoid Glyburide (Diabeta)
Drug interactions:
 Sulfonamides, gemfibrazole increase ½ life
Thiazolidinediones
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Options: Pioglitizone (Actos) and rosiglitizone (Avandia)
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Pros:
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Black box warning on rosiglitizone: increased cardiovascular risks - MI,
CHF and death
Bottom line: don’t start anyone on rosiglitizone
Preservation of beta-cell function
Possible benefits: treatment of NASH and impaired glucose tolerance
Cons:

Both increase risk of CHF, fractures, and cause weight gain
Comparative cardiovascular effects of thiazolidinediones:systematic
review and meta-analysis of observational studies. BMJ
2011;342:d1309
Case
73 yo female with poorly controlled T2DM, HgbA1c 8.7%,
h/o CVA, and osteoporosis. H/o orthostatic hypotension and
falls. On metformin, no longer on SU d/t recurrent severe
hypoglycemia. Is hesitant to change her medications d/t fear
of low blood sugars.
What oral medication would you recommend adding to her
regimen?
A. Sitagliptin/Januvia
B. Pioglitazone/Actos
C. Repaglinide/Prandin
D. Canagliflozin/Invokana
Dipeptidyl peptidase IV inhibitors
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Agents: Sitagliptin (Januvia), saxagliptin (Onglyza),
linagliptin (Tradjenta), alogliptin (Nesina)
Pros:
 Weight

neutral, no hypoglycemia
Cons:
 Expensive,
 relatively
less effective as monotherapy
 long-term safety data lacking
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Dose reduce in patient’s with renal insufficiency
New on the market…
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Sodium-glucose cotransporter 2 (SGLT2)
inhibitors
Canagliflozin (Invokana) and
Dapagliflozin/Farxiga
A1c lowering 0.5-0.7%
 No hypoglycemia,
weight loss (2-3 kg),
daily dosing
 Contraindicated in CKD
 Increased rates of
hyperkalemia and
genital candida
infections

http://www.endocrinetoday.com/pda.aspx?rid=91618
Injectable Therapies
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Insulins
Incretin based therapies
Insulin
Insulin
Onset
Peak
Duration
Rapid
(lispro/Humalog,
aspart/Novolog,
glulisine/Apidra)
5-15 min
0.5-1.5 hrs
< 5 hrs
Short
(regular/Humulin R)
30 min – 1 hr
1-5 hrs
5-7 hrs
Intermediate
(NPH/Humulin N)
3-4 hr
4-10 hrs
10-18 hrs
Long
(glargine/Lantus,
detemir/Levemir)
1-2 hrs
None
24 hrs
Insulin in Type 1 DM

Require intensive insulin therapy:
 Prandial
blood glucose: short/rapid-acting insulin
 Basal blood glucose: intermediate/long-acting insulin
 Total insulin requirement typically 0.5-1 U/kg/d,
divided 50:50 long:short acting
 Insulin pump: basal and bolus rates of a continuous
infusion of rapid-acting insulin

Without insulin will go into DKA (even if NPO)
Case
55 yr old overweight female with uncontrolled type 2 DM, recent Ac1
9.2% on metformin 1000 BID and glipizide 10 mg with dinner, presents
for follow up. You decide she needs insulin therapy.
How do you start her on insulin?
A.
Prescribe insulin glargine 5 units q HS and insulin lispro 2 units with
meals, d/c oral medications
B.
Prescribe insulin 70/30 5 units BID, d/c oral medications
C.
Prescribe insulin glargine, 10 units q HS, continue metformin,
decrease glipizide dose
D.
Start insulin lispro 2 units q AC, continue metformin, d/c glipizide
Sliding scale vs correction dose
What to call it
What we’re talking about
Basal
Long acting insulin, given to manage baseline blood
sugar
Prandial
Short acting insulin, given to manage the anticipated
increase in blood sugar due to food intake
Correction
Variable amount of insulin given to correct an elevation
in blood sugar (typically given with prandial insulin)
Sliding scale
Similar in theory to correction dose, but used at times to
imply a situation in which the only insulin given is
‘correction’
Case
She calls into clinic a few days later, she hasn’t started her
insulin because she read that it’ll lead to weight gain. “I want
to try Byetta.”
What do you think?
A.
Reassure patient that insulin will not lead to weight gain
B.
Advise patient that exenatide/Byetta will not adequate
control her blood sugar
C.
Sounds reasonable, d/c oral medications (metformin and
glipizide) and start exenatide
D.
Advise patient that she needs insulin therapy and that you
cannot use basal insulin in addition to exenatide
Incretin based injxn therapies
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Glucagon like peptide-1 agonists (ex.
exenatide/Byetta, liraglutide/Victoza):
 Mechanism:
augments glucose mediated insulin secretion
(no hypoglycemia), slows gastric emptying (n/v, weight
loss)
 SE: GI, increased risk of pancreatitis (?), $$$
 Indications: Type 2 DM, use with oral agents or basal
insulin, modest A1c lower (0.5-1%)
Question

What are the major causes of morbidity and
mortality in diabetes?
Longterm complications

A 54 year old male patient with type 2 diabetes
being seen in clinic for diabetes management. He is
on metformin 1000 mg po BID, last A1c 6.8%.
Diabetic Neuropathy
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
He tells you that he occasionally has his foot “go to
sleep” but otherwise hasn’t noted any concerning
pain or numbness in his feet.
How do you screen for distal symmetric
polyneuropathy?
 Options
include pinprick sensation, vibration perception
(using a 128-Hz tuning fork), monofilament testing, and
assessment of ankle reflexes, ideally do two of these
tests.
 At this time also complete a good foot exam, checking
pedal pulses and visually inspecting the foot.
Monofilament testing

Monofilament testing: with eyes closed pt indicates if
they feel the monofilament, pressure applied until it
buckles; typically tested at 5 sites (1st, 4th toe, 1st,
3rd, 5th metatarsal heads)
Now what?

If the test(s) is/are normal, what now?
 Re-screen

annually
If the test(s) is/are abnormal, what now?
 Consider
other etiologies: e.g. vitamin B12 deficiency
 In high-risk patients (e.g. h/o foot ulcer or amputation)
refer to podiatry
 In low-risk patients (e.g. unable to appreciate
monofilament at 1/5 sites, otherwise normal exam) I
recommend patient education re:foot care and
examination of feet at every visit
Question
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Which of the following are manifestations of
diabetes neuropathy?
Painful burning of the feet
Gastroparesis
Erectile dysfunction
Resting sinus tachycardia
Nephropathy


Recent labs reveal a Cr of 0.9 and a spot albumin
to creatinine ratio of 40 μg/mg (uln 30 μg/mg ).
Now what?
 Spot
albumin secretion is convenient but susceptible to
false-positive results (causes can include recent exercise,
infection, fever, significant hyperglycemia or
hypertension) therefore it should be repeated prior to
making mgmt changes based on this abnormality
Now what?

So, let’s say that he has another spot urine with
albuminuria, say 45 μg/mg creatinine. Now what?
 Start
an ACE I or ARB, work on good blood pressure
and blood sugar control

What if his repeat test is very normal, now what?
 Consider
year
going to the typical screening interval, once a
Retinopathy


Your patient tells you he saw a ophthalmologist
when he was initially diagnosed 5 years ago and
was told he was fine.
Does he need to go back?
 Yes
 Follow
up timeline will be recommended by the
ophthalmologist based on their exam findings
Macrovascular complications


His blood pressure today is 135/80, you repeat it
and get 136/78.
What is the goal blood pressure in the diabetic
patient?


JNC 8 <140/90
If his blood pressure was above goal what class of
antihypertensive would you prescribe?
Macrovascular complications


On review of the labs he brings in you see that his
lipids are: total cholesterol 198/triglycerides
246/HDL 40/LDL 102.
What do you do now?
a.
b.
c.
d.
Nothing, recheck in 1 year
Start atorvastatin
Prescribe fenofibrate
Recommend fish oil supplements
Statins

AHA/ACC Guideline, 2013: Statin therapy
recommended for diabetic patients, ages 40-75,
with LDL >70.

Recommended intensity of therapy determined by
calculated 10 year risk of ASCVD
 < 7.5% Moderate intensity statin (atorvastatin 10 mg q
day, simvastatin 20-40 mg daily)
 >7.5% High-intensity therapy (atorvastatin 80 mg daily,
rosuvastatin 20 mg daily)
Macrovascular complications

Should he take a baby aspirin daily?
 Yes
 ASA
for 1º prevention: Framingham 10 yr risk >10%,
generally >50 yo with DM and an additional risk
factor (e.g. HTN)
Immunizations

What immunizations would you recommend for this
54 year old diabetic patient?
 Annual
influenza vaccination
 Hepatitis B vaccination
 Pneumococcal vaccination
 Tdap (not specific to this patient)
Learning objectives
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


Know how to screening for and diagnose type 2
diabetes
Know how to prevent diabetes
Be familiar with the “pro and cons” of common
pharmacologic treatment of diabetes
Know the common complications of diabetes and
how to screening of them