DIABETES OVERVIEW AND
UPDATE
Barb Bancroft, RN, MSN, PNP
BBancr9271@aol.com
www.barbbancroft.com
Historical highlights…in the old
days…
• Diabetes—”to siphon”
• Mellitus—”sweet”
• Nurse…
• “Taste thy patient’s urine, for if it be
sweet…”
---Dr. Thomas Willis
When I was in Nursing School…it was called
“sugar diabetes”…the evolution of the
name…
Juvenile Onset Diabetes Mellitus (JODM)
Adult Onset Diabetes Mellitus (AODM)
Insulin Dependent Diabetes Mellitus (IDDM)
Non-insulin Dependent Diabetes Mellitus (NIDDM)
Type I (Roman numeral used)
Type II (Roman numeral used)
Type 1 (Arabic number)
Type 2 (Arabic number)
Definition of Diabetes Mellitus
• Chronic disorder of carbohydrate, lipid, and protein
metabolism characterized in its fully expressed clinical
form by an absolute deficiency of insulin (Type 1
diabetes) or a relative insulin deficiency (Type 2
diabetes).
• Huh?
• Type 1—no insulin
• Type 2—insulin resistance
• PLUS…it’s a PROthrombotic, PROinflammatory, and
PROatherosclerotic disease! So be PRO-active in DX
and RX!
• Is this a cardiovascular disease?
Type 2 diabetes—the numbers
• 1.5 million new cases diagnosed per year in the U.S.
• Over 20 years of age: 20.8 million Americans (9.6%);
1/3 have no clue
• Over 60 years of age: 10.3 million or 20.9% of all
people
• Usual onset after 40; 70% increase in incidence under
40 in last decade
• Under 20 years of age: 176,500 or 0.22% of the
population; 1 in every 400-600 kids with Type 1
• 2 million adoloescents (1 in 6 overweight
adolescents) aged 12-19 have prediabetes
• 50% of all new cases of Pediatric diabetes are TYPE
2…not Type 1…
Who’s at risk? Who’s sitting in
YOUR waiting room?
• Genetic risk for Type 1 and for Type 2
diabetes—family history, sibling or parent
• How many genes?
Family history
• Family history of early coronary artery
disease
• What is meant by early?
Hypertension
• Greater than 140/90 increases the risk of
diabetes
• 50-60% of newly diagnosed patients also
have HTN at diagnosis
• An interesting note: A family history of
hypertension in a child with Type 1 diabetes
increases their risk of developing
nephropathy
High risk ethnic groups
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African American
Native American
Asian American
Hispanic American
Pacific Islander
Indian (from India)
Impaired glucose tolerance
• Gestational diabetes
• Baby weighing greater than 9 lbs.
• Were YOU, as a baby, exposed to
hyperglycemia en utero?
Type 2 diabetes risk factors
• Weight gain
What did you weigh as a kid?
The odds that a person who is normal weight at
age 18 will develop diabetes later in life are 1-in5 or 1-in-6. However, if a child is very obese at
age 18, they have a 3-in-4 chance of developing
diabetes. The lifetime risk of developing
diabetes, based on a body mass index at age
18, is as follows:
BMI and risk of Type 2 (T2)diabetes
• A BMI under 25 (normal BMI)—risk of T2
diabetes for women is 17%; risk of diabetes for
men is 20%
• A BMI between 25-29—risk of T2 diabetes for
women is 35%; risk of diabetes for men is 30%
• A BMI between 30-34—risk of T2 diabetes for
women is 55%; risk of diabetes for men is 57%
• A BMI greater than 35—risk of T2 diabetes for
women is 74%; risk of diabetes for men is 70%
(CDC—Diabetes Branch, May 2006)(June 2006,
ADA)
Within a single ethnic group…
• Diet (high calorie, high fat)
• Lifestyle (Lack of physical activity and
sedentary lifestyle)
• Both play a major role in obesity and
insulin resistance with DM
Abdominal obesity as a risk
factor
• Abdominal obesity and insulin resistance
• Visceral fat is an endocrine organ and is
metabolically active
• It is insulin resistant
• Produces inflammatory mediators such as TNFα and IL-6,
• Waist greater than 38 inches in females
increases the risk by 6-fold
• What should we look like?
Other conditions that increase the risk of Type 2
diabetes—PCOS and documented hypoglycemia
• Polycystic ovary syndrome
(PCOS)
• Polycystic ovary syndrome (PCOS)—5-10% of women of
reproductive age; increasing at the same rate as Type 2
DM and metabolic syndrome in U.S.
• Anovulation, irregular menses, androgen excess, insulin
resistance, increased CV risk and Type 2 DM
• Rx: Metformin and “glitazones” decrease insulin
resistance: WORD TO THE WISE: These oral drugs also
decrease the efficacy of COCs and increase ovulation—
need 2 forms of birth control unless pregnancy is the
goal
• History of hypoglycemia (documented with OGTT)
Undesirable lipid levels
• HDL less than 35 mg/dL
• Triglycerides greater than 150 mg/dL
• Think diabetes or hypothyroidism with the
above lipid profile
• Draw a FBS and a TSH
Type 1 diabetes
• Type 1 DM—primarily diagnosed in preteens or teenagers; onset prior to age 40
in the majority of patients;
• Caucasians greater than AfricanAmericans
• Finland #1 country in world with Type 1
DM
• 1 in 150 kids by the age of 15
Type 1 Diabetes
• Associated with immune response genes and
HLA-DR3 and HLA-DR4
• Autoimmune attack against specific components
of the islet beta cells of the pancreas (antiglutamic acid decarboxylase antibodies—antiGAD; anti-islet cell antibodies)
• Usually present with 3 p’s (loss—polyuria,
polydipsia, polyphagia), and weight loss
• Classic presentation is in a Caucasian, blueeyed, blonde-haired kid
Type 1 diabetes
• What triggers the autoimmune response?
• The most likely culprit is one of the
childhood viruses…
• Coxsackie B? Measles? Influenza A or B?
Other conditions associated with
Type 1 diabetes
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Autoimmune diseases are more common
Celiac disease
Thyroid disease
Pernicious anemia
Secondary diabetes
• Exocrine pancreatic disease—cystic fibrosis
• Cushing’s disease or syndrome
• Drugs—corticosteroids, L-dopa, beta-blockers,
atypical anti-psychotics (especially
Clozapine/Clozaril and Olanzapine/Zyprexa),
sympathomimetics, niacin, glucosamine, thiazide
diuretics
• Hospital critical care--stress
Hyperglycemia in the hospital
setting…
• Inpatient hyperglycemia in people with or without
diabetes is associated with an increased risk of
complications and mortality, a longer hospital stay, a
higher admission rate to the ICU, and higher
hospitalization costs
• Control is challenging…what is the best way to control
hyperglycemia in the hospital setting?
• Basal/bolus therapy is more efficient than sliding scale
which is associated with poorer glycemic control and an
increase risk of hypoglycemia
(Umpierrez GE, Palacio A, Smiley D. Sliding Scale Insulin
Use: Myth or Insanity? The Am J of Med 2007 (July): 120
(7).
Laboratory Tests
• Prediabetes…one-step away… HUH?
• 54 million Americans with prediabetes
• Asymptomatic fasting blood sugars between
100 mg/dL and 125 mg/dL
• Used to be called impaired glucose tolerance
• May have metabolic syndrome
Central obesity and the metabolic syndrome
(insulin resistance syndrome)
• What is the metabolic syndrome? (Previously
known as syndrome X)
• A clustering of risk factors that, in the aggregate,
sharply increase the risk of cardiovascular
disease and diabetes
• By the time a diagnosis of diabetes is made, 7090% of patients have metabolic syndrome,
irrespective of ethnicity or the definition used
• 1 million adolescents have metabolic syndrome
• What is the definition of metabolic syndrome?
Definition varies by group: NCEP ATP III
guidelines: Metabolic syndrome or IRS (insulin
resistance syndrome)
• Central obesity—waist size greater than 40.2 inches in
men, 34.6 inches in women
• High TG (>150 mg/dL),
• Low HDL (less than 40 mg/dL in men, less than 50
mg/dL in women)
• Hypertension (≥ 130/85 mm Hg)
• Fasting glucose ≥ 110 mg/dL (or greater than 100 mg/dL)
• Metabolic syndrome is present when any 3 of these risk
factors are present
• PCOS (polycystic ovary syndrome is a form of metabolic
syndrome/IRS)
Laboratory diagnosis
• Fasting plasma glucose—after 8 hours
without caloric intake
• A.M. specimens greater than or = to 126
mg/dL (previous was 140 mg/dL)
Or…
• Random glucose of greater than or equal
to 200 mg/dL
• Postprandial glucose excursions with
subsequent hypoglycemia—patient with
early diabetes can present with this
picture—give glucometer to take home
and measure
• Postprandial glucose excursions are also
associated with an increased risk of CV
disease…
Laboratory diagnosis
• Hemoglobin A1C—gold standard for measuring longterm glycemic control—how does it work? RBC life span
• 50% of glycosylated hemoglobin is from previous month;
25% from the month before; 25% 3-4 months ago
• Normal range is 4-6%; each percent equals 20-22 mg/dL
of plasma glucose (6% is TOO HIGH—but is considered
normal range by laboratory)
• HbA1C of 4% is the equivalent of a FPG of 80-88 mg/dL;
10% = 200-220 mg/dL
• What does the ADA recommend for HbA1C for adults?
(Less than 7) Clinical endocrinologists for adults? (Less
than 6.5)
Hemoglobin A1c for kids (ADA
guidelines)
• Guidelines for kids—less than 8.5 but greater than 7.5
for toddlers and preschoolers 0-6 years of age
• Less than 8 for kids 6-12
• Less than 7.5 for adolescents and young adults (13-19)
• More liberal numbers for kids and developing brains who
are more vulnerable to the effects of hypoglycemia and
who may not be able to effectively recognize or speak
about the symptoms of hypoglycemia
• The DCCT data certainly showed that tighter blood
glucose controls increase the risk of serious
hypoglycemia BUT also decrease the risk of long-term
complications
Hemoglobin A1C for older
adults
• More complex because of co-morbidities (example
aggressive control of BP + BS may increase the risk of
falls)
• How aggressive should we be?
• LIGHT mnemonic is useful
• L—life expectancy: estimate average life expectancy
based on age and health status
• I—impact of geriatric syndromes and other comorbidities
• G—goals of care and patient preferences
• H—help the patient prioritize and develop a care plan
• T—Time required to benefit from the therapeutic
intervention
Six syndromes to consider in older
patients with diabetes
• Polypharmacy—drug burden and drug-drug and
drug-disease interactions are very common
• Depression—increased prevalence and
incidence; interferes with self-management
• Cognitive impairment—screen yearly and more
often in patients having difficulty with disease
management and self-care (check TSH and
B12); is dementia more common in diabetics?
Six syndromes to consider in older
patients with diabetes
• Urinary incontinence—from glucosuria,
neurogenic bladder, stool impaction, UTI,
vaginal yeast infection
• Falls—
• Undertreated pain—may not mention or
may just blame it on normal aging; may
not describe neuropathic pain in the usual
terms of tingling, burning, but use terms
such as aching, discomfort
Basic
physiology/pathophysiology
• Insulin is a growth hormone—stores fat
and sugar and stimulates protein synthesis
after the meal
• Too much? WEIGHT GAIN; hypoglycemia
• Glucagon is a catabolic hormone
produced during the fasting state; breaks
down stored glycogen
• Too much? WEIGHT LOSS;
hyperglycemia
The fasting state
• The pancreas produces glucagon for glycogenolysis
(break down stored sugar in the liver) to maintain a
steady state of blood glucose
• Lipolysis—breaks down fat tissue and forms free fatty
acids
• Gluconeogenesis—turns proteins into sugar
• Type 1 ketoacidosis is a prolonged fasting state;
absolute deficiency of insulin; glucagon is working
overtime; weight loss; glycogenolysis and lipolysis with
hyperglycemia and fatty acid release (ketones); ketones
and glycosuria cause a significant osmotic diuresis
(significant dehydration)
Symptoms of DKA (Diabetic
Ketoacidosis)
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Dehydration
Abdominal pain
Anorexia, weight loss
Kussmaul’s respirations (acidosis)
Tachycardia
Weakness, fatigue
Fruity breath odor
hypotension
N and/or V
Confusion, decreased reflexes, coma
Treatment of DKA
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Dehydration is your first priority
GIVE FLUIDS…what kind?
Then what? Regular insulin IV
Then what? Check electrolytes and bicarb
Pathophysiology of Type 2 DM
• Early in the disease—insulin resistance is
characterized by a subnormal receptor response
to insulin (partially due to abdominal obesity)
• Abnormal beta cell response with an abnormal
release of insulin to glucose—too much released
resulting in hyperinsulinemia and hypoglycemia
in the postprandial state
• What are the consequences of
hyperinsulinemia?
Hyperinsulinemia…
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Increased TG and decreased HDLs
Sodium and water retention—HTN
Stimulate fat storage (CHO to fats)
Prothrombotic
Proinflammatory
Triggers endothelial cell dysfunction
YIKES!!
Type 2 diabetes
• Metabolic derangements aren’t usually as severe as
Type 1; as insulin resistance continues, serum glucose
levels gradually increase; with increasing glucose levels
the pancreas responds by increasing insulin output
resulting in hyperinsulinemia
• Few symptoms initially, 2 P’s (no polyphagia), weight
gain due to hyperinsulinemia
• Other symptoms—fatigue, diplopia, nocturia
• Skin infections, vaginal infections, poor wound healing,
neuropathy
• Cardiovascular complications may be the first presenting
symptoms—MI, PAD, Stroke
• “Silent” for a full decade in some individuals
Some new physiology…
• You eat a meal…and then?
• The intestine releases incretin hormones known
as GLP-1 (glucagon-like peptide 1) and GIP
(glucose-dependent insulinotropic polypeptide)
throughout the day, with an increase right after
the meal (postprandial increase)
• The incretin hormones influence the pancreas to
increase the synthesis and release of insulin and
decrease the synthesis and release of glucagon
• Drugs that affect incretin—Exenatide (Byetta);
symlin (Amlin); sitagliptin (Januvia)
And then what?
• Insulin acts on insulin receptors in the liver, skeletal
muscle tissue and adipose tissue to trigger the entry of
sugar into the cells
• (Obesity decreases the number of insulin receptors;
exercise increases the receptor sensitivity)—HENCE,
the strong recommendation to LOSE weight and
exercise!
• The liver stores extra glucose as glycogen and releases
it as necessary to keep the blood sugar levels in the
normal range throughout the day and night
• The liver does most of its work at night
• Clinical implications of giving metformin at night
(Metformin blocks the breakdown of glycogen to
glucose)—the whole dose
How do you treat it? The usual
suspects…(oral drugs)
• By decreasing the production of glucose by the liver—
Metformin (glucophage)
• By increasing insulin sensitivity in the tissues (the
glitazones—rosi- and pio-)—Avandia and Actos;
metformin (glucophage)
• By increasing insulin secretion from the pancreas and
increasing insulin receptor sensitivity (the oral
sulfonylureas)
• By giving oral drugs that reduce postprandial excursions
of glucose (repaglinide/Prandin, nateglinide/Starlix)
• By inhibiting enzymes in the intestine responsible for
breaking down incretins that potentiate insulin release
(sitagliptin/Januvia)
• By mimicking hormones (incretins) that trigger insulin
release from the pancreas (exenatide/Byetta)
Oral Drugs…the #1 bestseller
• Metformin (glucophage) does not have any direct effect
on insulin release from the pancreas—doesn’t require
insulin to work
• Primary action: DECREASE hepatic glucose production;
also, decreases glucose absorption via the GI tract, and
may increase sensitivity of insulin receptors
• Problem? GI blues, need functioning organs-kidneys and heart especially (check serum
creatinine before starting metformin)
• Se Creatinine--Cut-off is 1.4 in females and 1.5 in
males
• Other benefits: lowers BP, increases HDL, lowers
LDL
• B12 deficiency—longer the use and the higher the
dose, the greater the risk
Digression: the importance of
B12
• B12 is necessary for the healthy production of RBCs and for the
maintenance of the central and peripheral nervous system (cognitive
function in the CNS and normal PNS function)
• B12 deficiency is the one of the top 3 causes of peripheral
neuropathy in the U.S. and the #1 cause of nutritional dementia in
the U.S.
• B12 is stored in the liver for 5 years or so
• 39% of the population over 50 has a B12 deficiency
• PPIs and Metformin decrease B12
• B12 and peripheral neuropathy in the diabetic
• Supplements? How much?
• Can you overdose on B12? The one dreaded side effect is…
Oral drugs for type 2 DM…
• The “Glitazone” sisters—rosi (Avandia), pio (Actos)
• Improve muscle receptor sensitivity to insulin with
secondary effects in the liver
• May slow down the progression of the disease**
• Problem? Volume expansion, heart failure, dilutional
anemia, weight gain (peripheral, not central)
• Good news? Reduce triglycerides
• The bad news? Do these drugs increase the risk of
cardiovascular events?
• Can you use this class of drugs in the patient with
heart failure?
OLD Drugs…are these even worth using
anymore? Considered third-line therapy…
• Oral sulfonylureas—Glipizide (Glucotrol) and
glyburide (Diabeta, Micronase, Glynase) and
glimipiride (Amaryl)…
• Increase the secretion of insulin from the
pancreas and increase receptor sensitivity
• Problem? Weight gain, hypoglycemia,
increased cardiovascular risk) (highest doses
increased risk vs. metformin; may prevent heart
from recovering from brief periods of ischemia)
(Canadian Medical Association Journal January 2006)
• glimipiride (Amaryl)—safe use in elderly-decreased incidence of hypoglycemia
Drug combinations
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Glucovance (glyburide and metformin)
Avandamet (rosiglitazone and metformin)
Metaglip (glipizide and metformin)
Actosplus Met (metformin/pioglitazone)
Avandaryl (rosiglitazone/glimepiride)
Duetact
(pioglitazone HCl and glimepiride)
• Sitagliptin/metformin (Janumet)
Other drugs
• Repaglinide (Prandin)
• Nateglinide (Starlix)
• Good for elderly to prevent postprandial
excursions
• Great if your meals are sporadic
Exenatide (Byetta)—incretin
mimetic
• incretins are responsible for approx. 60% of the
post-meal insulin secretion; however, the action of
the incretins is impaired in diabetics
• Byetta is an incretin mimetic; acts at the GLP-1
receptor in the pancreas that promotes insulin
release
• Type 2 diabetics who are already receiving
metformin, a sulfonylurea, or both and do not have
optimal control
• Weight loss is a + side effect due to early satiety (1015 lbs to 40-50 lbs)
• Take less than an hour before a.m. and p.m. meals
(nausea)
Sitagliptin phosphate
(Januvia)(Merck)
• DPP-4 inhibitor…huh?
• Dipeptidyl-peptidase-4 is an enzyme responsible for the
inactivation of the incretin hormones GLP-1 and GIP
(glucose-dependent insulinotropic polypeptide). These
hormones are released from the intestine throughout the
day, with an increase postprandially; they potentiate
insulin synthesis and release by pancreatic beta cells
and decrease glucagon release by pancreatic alpha
cells, lowering blood sugar
• Costly…$171.90 per month vs. generic Metformin $5075/month); oral sulfonylureas are $10-40/month);
glitazones are ~$100-115/month
• Janumet (combination with metformin)
Pramlintide acetate (Symlin)
• Amylinomimetic agent for type 1 and type 2 diabetes—
synthetic analogue of the hormone amylin (released after
meals), which is deficient in patients with diabetes
• Acts by slowing gastric emptying, curbing appetite, and
suppressing postprandial plasma glucagon and hepatic
glucose output
• Adjunct therapy for patients with T2DM who use
mealtime insulin and have not maintained glycemic
control despite optimal insulin therapy with or without
oral drugs
• Improves postprandial blood glucose and promotes
weight loss
• Taken just before the meal (multiple shots w/ insulin)
Insulin
• 36% of type 2 DM use insulin today; within 5
years of diagnosis, 50% require insulin
• Weight gain can be significant– 5 to 10 kg in first
year; daytime insulin promotes weight gain;
night time insulin does not
• Insulin dose needed varies from 0.2 units to 2
units per day; no correlation with age, gender,
duration, race or HbA1c level
• Most serious side effect is HYPOGLYCEMIA
Insulins
• Rapid-acting insulins include aspart (Novolog),
glulisine (Apidra), lyspro (Humalog)
• regular insulin—Humulin R, Novolin R
• Intermediate acting—NPH; Humulin N, Novolin
N
• Long-acting insulins include detemir (Levemir),
glargine (Lantus)
• Mixtures
Mixtures
• 50% lispro protamine, 50% insulin lispro =
Humalog Mix 50/50
• 70% NPH/30% regular = Humulin 70/30;
Novolin 70/30
• 75% lispro protamine/25% lispro =
Humalog Mix 75/25
• 70% aspart protamine/30% aspart =
NovoLog Mix 70/30
RAPID-ACTING INSULINS
• Lyspro/Lispro (Humalog); Aspart (NovoLog); glulisine
(Apidra)
• quicker absorption and quicker onset of action; duration
of action is shorter, and higher peak concentrations
compared to regular insulin
• Less nocturnal episodes of hypoglycemia than regular
insulin
• Closer administration to meal times within 5-10 minutes;
even shortly after the meal if necessary
• Peak 1-2 hours; duration 3-4 hours
• Closer approximation to physiologic insulin release
• Lower peak postprandial glucose excursions
Intermediate-acting insulin
• NPH (Humulin N and Novolin N)
• Used to provide basal insulin and because they
have a peak action, they may cover the midday
meal; onset 2-4 hours, peak at 4-10 duration of
10-16 hours
• Is there a problem?
If they are still on NPH…
• Somogyi effect and NPH at dinner—peaks at 2-3
a.m. and causes nocturnal hypoglycemia
• Patient wakes up in a sweat and with
tachycardia
• Immediately checks blood sugar and it’s normal
or high, secondary to a sympathetic nervous
system response
• DON’T increase the dinner dose!!
• Change the dinner dose to a nighttime dose or
decrease the dinner dose and increase the
snack at bedtime
• Or better yet…
Switch to…
• LANTUS (insulin glargine) or LEVEMIR (insulin
detemir)—long-acting basal insulins; they don’t have a
peak; provide constant levels over 24 hours; controls
blood sugar as well as NPH given once or twice daily
with less nocturnal hypoglycemia and weight gain
• How do you switch from NPH to Lantus? Easy
• Can you mix other types of insulin with Lantus? NO
• Does Lantus “look” funny? YES, compared to NPH, it’s
clear
• Lantus stabilizes endothelial cells…HUH?
Complications of type 2
diabetes
• Is diabetes a cardiovascular disease?
• Accelerated atherosclerosis--four out of five
diabetics die from complications of
cardiovascular disease and atherosclerosis
• Considered a “risk equivalent” of heart disease
• Proinflammatory, prothrombotic,
proatherosclerotic
• Endothelial dysfunction with increased
deposition of fat in the large arteries
• Coronary artery disease, cerebrovascular
disease, peripheral vascular disease—diffuse
disease; triple vessel CAD
Coronary artery disease and
angina…
• 4 out of 5 diabetics die of complications of
cardiovascular disease
• Estrogen does NOT protect the premenopausal
diabetic woman from heart disease
• If a diabetic woman under 50 years of age
presents with signs and symptoms of heart
disease, take her seriously!
Frontoparietal
stroke
• “Brain attacks”
and TIAs
• Internal carotids
• Circle of Willis
• Risk of stroke is 2.5-4x greater in diabetics
Peripheral arterial disease
• Atherosclerosis of the aorta, iliac arteries,
femoral arteries
• Intermittent claudication
• Diabetes raises the risk of amputation 14x for
men 35-44; 17x for men 45-54;
• Raises the risk for amputation 20x for women
between 35-44; 28x for women between 45-54
• 50% die within 3
years of amputation
• FOOT CARE!!
Are they on a “Statin” to improve LDL
cholesterol levels?? And to decrease
inflammation?
• If not, why not?
• LDL-levels should be reduced to 70 mg/dL
• Say yes to the “statin” sisters—lova (Mevacor), atorva
(Lipitor), prava (Pravachol), simva (Zocor), fluva
(Lescol), rosuva (Crestor)
• Statins are anti-inflammatory, anti-lipid, decrease
plaque formation, stabilize plaques, prevent plaque
rupture
• Strive for an LDL-cholesterol of 70 mg/dL; HDL greater
than 40 in men, greater than 50 in women
• Should all diabetics be on statins REGARDLESS of their
LDL level?
• YES…YES…YES…
Are they on aspirin and/or Plavix
(clopidogrel)?
• If not, why
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•
not?
Diabetes is a pro-inflammatory disease!
Diabetes is a pro-thrombotic disease
ASA for daily use as soon as diagnosed
Plavix if allergic to ASA
Plavix after a coronary event or cerebral event
Before you start the statins…
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Check liver function tests (AST)
Check CK
Consider checking the TSH in women
Caution patients to NOT drink grapefruit juice if
they are on lovastatin (Mevacor), simvastatin
(Zocor), and atorvastatin (Lipitor)
• They can drink grapefruit juice with the other
statins (Pravachol, Crestor, Lescol)
• Try not to use Lopid (to reduce TG) with the
statins
Triglycerides
• Keep triglycerides below 150 mg/dL (may need
to add fenfibrate (Tricor) or gemfibrozil (Lopid)
• Keep HDL’s above 50 mg/dL—HOW?
• May need to add NIACIN (keep eye on blood
sugars)
• FISH OIL capsules for high TG—2-4 grams/day
Combinations
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Vytorin—Zocor and Zetia (ezetimibe)
What’s Zetia?
When would you use Vytorin?
Advicor (niacin + lovastatin)
Hypertension…more pearls
• In a diabetic patient, BP control exerts a more
positive impact on CV events than BS control!
• Blood glucose control that achieves levels of
glycosylated hemoglobin of about 7% has less impact on
cardiovascular disease than does BLOOD PRESSURE
control that maintains diastolic pressure at about 85
mmHg.
• A systolic pressure of 130-139 mmHg with a diastolic
pressure of 85-89 mmHg, although classified as “high
normal”, warrants PROMPT treatment in the diabetic
patient.
• “Pre-hypertension” is 120-139 over 80-89 mg/Hg
Hypertension and the diabetic
• Which comes first, the chicken or the egg?
• Does diabetes CAUSE hypertension, or does
hypertension CAUSE diabetes?
• 60% of all newly diagnosed diabetics have
hypertension
• VIGOROUSLY treat hypertension to reduce the
cardiovascular risks and to reduce the risk of
nephropathy
• What drugs should be chosen for the treatment
of hypertension? First line therapy should be
either the…
“Prils” (ACE inhibitors)…or the ARBs
(angiotensin receptor blockers)
• Block the production of angiotensin 2
reduces blood pressure, decreases
remodeling of the heart, reduces preload
and afterload (reducing the workload of
the heart), and decreases intraglomerular
hypertension and renal disease (more
later)
• May also PREVENT Type 2 diabetes
• Reducing angiotensin is anti-inflammatory!
“Prils”—The ACE inhibitors
(Brazilian pit viper)
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Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moxepril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
HUH?…..
“Sartans”--ARBs
• Angiotensin receptor blockers (bypass ACE) and work by
blocking the tissue receptors
• Who are they? The “Sartan Sisters”…
•
losartan—Cozaar
•
valsartan—Diovan
•
candesartan—Atacand
•
irbesartan—Avapro
•
telmisartan—Micardis
•
olmesartan—Benicar
• Less side effects—may substitute if cough is unbearable
Most diabetics need more than 1
drug to treat hypertension
•
•
•
•
ACE inhibitor
ARB
Diuretic
Calcium channel blockers
Dietary changes to reduce blood
pressure—the DASH diet
• Increase potassium containing foods
(4700 mg/day)
• Decrease sodium containing foods (stop
eating out of the box or can; decrease
processed foods)—less than 2400 mg/day
• Increase low-fat calcium containing
foods—greater than 1200 mg/day
Can dietary changes lower
cholesterol and protect the heart?
• The Mediterranean diet with nuts, fiber,
fish, vegetables, fresh fruits, olive oil, and
vino, lots of vino
• Lowers the markers of inflammation
(Environmental Nutrition, July 2004;27(7)
And don’t forget…exercise boosts tissue
sensitivity to circulating insulin
Is there such a thing as a “diabetic
diet”?
• Low calorie (PORTION CONTROL)
• Low-fat (especially trans and saturated
fats)
• Low protein (especially ANIMAL protein)
• High fiber (20-35 grams per day)
• Carbohydrates—what type?
• Glycemic index of foods??
The Cardiologist’s diet?
• “If it tastes good, spit
it out!”
What about the Atkin’s diet to lose
weight?
• The Atkin’s diet is PRO-inflammatory
• Saturated and trans fats
• Nephrotoxic
Know how to estimate portion
size…
• One teaspoon of peanut butter is the size
of your thumb’s first joint
Portion control…
• Roll the dice…cheese portion
• Think baseball or tennis ball size for a portion of
fruit or pasta
• Think deck of cards or palm of your hand (sans
fingers) for a portion of meat, fish, or chicken
• Dove soap bar or mouse for the size of a baked
potato
Should a diabetic drink to lower
cholesterol ?
• Only if BS and TG are under control
• Discuss with health care professional
• Alcohol has a cholesterol lowering effect and an
anti-inflammatory effect
• 1-7 drinks per week has an anti-inflammatory
effect
• What constitutes “1 drink”?
Diabetic peripheral neuropathic
pain (DPNP)
• Monofilament screening for sensory loss at
every office visit
• Longest nerves first
• Small fiber loss resulting in the loss of pain, light
touch, and temperature sensation
• Large fiber loss —loss of vibration and
proprioception
• Stocking-glove distribution
Diabetic peripheral neuropathy—”Now
where did I put that sewing needle?”
• Tingling, numbness, or burning pain— “ I
feel like I’m walking on hot coals.”
• Stabbing pain– “I feel like I’m walking on
shards of glass.”
Treating diabetic peripheral
neuropathic pain
• Analgesics (NSAIDS)—neuropathy has an
inflammatory component; however, most
patients are already on aspirin—mixing ASA and
an NSAID increases the risk for gastric bleeding
• Antidepressants—duloxetine (Cymbalta)** is
FDA approved for treating both depression and
diabetic peripheral neuropathy; amitryptiline
(Elavil) may be used in small doses @ night for
neuropathy (remember that escalating the dose
of Elavil escalates the anti-cholinergic side
effects)
Treating diabetic peripheral
neuropathic pain
• Anticonvulsants—gabapentin (Neurontin),
pregabalin (Lyrica), and carbamazepine
(Tegretal),
• Antiarrhythmics (oral lidocaine)
• Acupuncture
• TENS
• Magnet therapy for just feet (but not with an insulin
PUMP)
• Α-Lipoic Acid—600 mg daily; has been shown to reduce
symptoms in some patients with DN; available as a
nonprescription dietary supplement and thus is not
regulated; use a reputable company for all dietary
supplements
(Ziegler D et al. Oral treatment with alpha lipoic acid
improves symtpomatic diabetic polyneuropathy: The
SYDNEY 2 trial. Diabetes Care 2006 Nov; 29:2365-70.
Autonomic neuropathy
• Evaluated and followed by a cardiologist
• Orthostatic hypotension
• Resting tachycardia is an important sign of
the LOSS of vagal input
• Silent ischemia and congestive heart
failure
Autonomic neuropathy
• Gastroparesis (wide swings in blood sugar with
slowed digestion interfering with the timing of
insulin), early satiety, chronic N & vomiting of
food digested hours before
• Metoclopramide (Reglan), erythromycin,
cisapride (special use)
• Tegaserod (Zelnorm)
Erectile dysfunction
• Atherosclerosis and neuropathy are the 2
major causes
• The Pfizer riser (and relatives—Levitra
and Cialis) are effective treatments in 50%
of the cases
• Injections, implants, and suction devices
• VED not TED
Autonomic neuropathy
• Impaired bladder emptying with
hydroureter, hydronephrosis, chronic
infection
• Urecholine, DuVoid
The healthy kidney…
•
Afferent arteriole
(vasodilated via
(prostaglandins)
• Blood entering
glomerulus
PG
filter
• Glomerulus→filter
• Efferent arteriole
(vasoconstricted via
(angiotensin 2)
• Blood exiting
glomerulus
AT2
Toilet
The Diabetic
Kidney…hyperglycemia
•
Afferent arteriole
(  vasodilation by
(  prostaglandins)
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
(  vasoconstriction via
(  angiotensin 2)
• Blood exiting
glomerulus
microalbuminuria
Clinical significance of microalbuminuria
• Microalbuminuria ≥ 20μg/min or A/C ratio ≥
30 mg/g
• “window” to the health of the vascular
system
• Assume that vascular disease is already
present when microalbuminuria is present
Diabetic
nephropathy…PREVENTION!!
•
•
•
•
Treat high blood pressure!
Reduce the animal protein in the diet!
Reduce serum glucose!
SAY YES to the ACE inhibitors or ARBs—
the PRILS or SARTANS (something to
inhibit Angie and Al (Angiotensin and
Aldosterone)
• If they are NOT on a PRIL or
SARTAN…the question is:
Diabetic Retinopathy
• Non-proliferative—macular edema, microaneurysms,
small intraretinal hemorrhages, exudates
• Blot hemorrhages, cotton-wool exudates
• Proliferative stage with neovascular growth; scar
tissue and retinal detachment
• Control blood sugars!
• SEE the EYE GUY once a year!
And lastly…TREAT the
DEPRESSION!
• Depression and compliance
• Before discharge, evaluate for depression
Bibliography
• Insulin glulisine (Apidra): A New Rapid-Acting Insulin.
The Medical Letter 2006; 48(1233).
• Sitagliptin (Januvia) for Type 2 Diabetes. The Medical
Letter 2007; 49(1251).
• Sitagliptin/Metformin (Janumet) for Type 2 Diabetes. The
Medical Letter 2007; (49)1262).
• Expanding the Therapeutic Options for Type 2 Diabetes
Mellitus. Clinical News 2006 (December supplement).
• Umpierrez GE, Palacio A, Smiley D. Sliding Scale Insulin
Use: Myth or Insanity? The American Journal of
Medicine 2007; 120 (7).
Bibliography
• Bloomgarden ZT, Comi RJ, Kendall DM. New therapies
to achieve glycemic control and weight loss in T2DM.
Patient Care 2006 (February): 46-53.
• Nissen SE and Wolski K. Effect of rosiglitazone on the
risk of myocardial infarction and death from
cardiovascular causes. N Engl J Med 2007 Jun 14;
356:2457-71.
• Psaty BM and Furber CD. Rosiglitazone and
cardiovascular risk. N Engl J Med 2007 Jun 14;
356:2522-4.
• Shah AA, Durso SC. Applying clinical practice guidelines
in caring for older adults with diabetes. Patient Care
2007 (February): 18-25.
• Is Avandia a flawed drug or was the big new study
flawed? Prescriber’s Letter 2007 (July).
Bibliography
• Brown AF, Mangione CM, Saliba D, et al.
Guidelines for improving the care of the older
person with diabetes mellitus. J Am Geriatr
Soc.2003; 51(suppl 5):S265-S280)
• Dargie HJ, Hildebraindt PR, Riegger GA, et al. A
randomized placebo-controlled trial assessing
the effects of rosiglitazone on echocardiographic
function and cardiac status in type 2 diabetic
patients with NYHA Functional Class I or II Heart
Failure. J Am Coll Cardiol. 2007;49(16):16961704.
ADA Contacts
• Diabetes.org
• Diabetes.org/research
• To locate an ADA/NCQA Recognized provider of
diabetes care in your area Call 1-800-342-2383.
• Just for kids…diabetes.org/youthzone
• ADA fundraising events—America’s Walk for
Diabetes annual national walk event; call 1-888342-2383.