Transcript DIABETES OVERVIEW AND UPDATE 11/11/11 Barb Bancroft, RN

DIABETES OVERVIEW AND
UPDATE
Barb Bancroft, RN, MSN, PNP
Chicago IL
Definitions—new names, new drugs, new lab tests,
new numbers, and a never-ending supply of new
patients
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(1659) Diabetes—”to siphon”
Mellitus—”sweet”
Insipidus—”tasteless”
Nurse…
• “Taste thy patient’s urine, for if it be sweet…”
---Dr. Thomas Willis
What’s in a name? The evolution…
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“Sugar diabetes”
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)
And, it’s not thaaaaaat easy
either…other types…
• Type 1A (autoimmune)
• Type 1B (idiopathic)
• LADA (latent autoimmune diabetes in
adults)—also referred to as Type 1.5
• MODY (maturity onset diabetes of the
young)
Definition
• Chronic disorder of carbohydrate, fat
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?
Definition
• Type 1—pancreatic beta cell failure due to
autoimmune disease (NO or minimal insulin)
(actually type 1A—most common)
• Type 2—insulin resistance AND pancreatic
beta cell dysfunction (50% normal insulin
secretion with dx; after 6 years w/ disease,
drops to 25%; eventually zero…)
• PLUS…diabetes is a prothrombotic,
proinflammatory, a proatherosclerotic and a
proaccelerated proaging disease! So be PROactive in DX and RX!
RISK FACTORS for DIABETES
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Who’s sitting in YOUR waiting room?
Primary care?
OB?
Geriatrics?
Pediatrics?
Who’s laying in that bed in the coronary care
unit? Stroke unit?
First question--family history?
• A family history of diabetes—for both type 1
and type 2
• Type 2—almost all cases have a parent or
grandparent; identical twin concordance rate
is 80%
• Type 1—50-90% don’t have a family history;
identical twin concordance rate is 35-50%; 5%
chance (one in twenty) if sibling has T1DM;
Type 1 diabetes--How many genes?
• In the past five years researchers have found
dozens of genes with links to diabetes
• Approximately 50 genes for type 1—about
half are genes that coordinate the HLA
system that helps the body recognize self vs.
non-self; explains why other autoimmune
diseases are associated w/ T1DM
• Celiac disease and Hashimoto’s thyroiditis
Type 1 diabetes—how many genes?
• Other genes that have been found mediate
the immune response to viruses (explains the
viral hypothesis as a possible trigger)
Type 2 diabetes--how many genes?
• Approximately 38 genes for type 2
• Believed that the known genetic links to type 2
diabetes probably account for only 6 percent of the
genetic predisposition
• What does that mean? Either some of the genes
discovered have a bigger effect than is currently
believed or that 94% of the genes are still missing
• Genes discovered affect the secretion of insulin
from the beta cells
Other risk factors for type 2 diabetes
mellitus?
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Family history of early coronary heart disease
Undesirable lipid levels
Ethnic groups
Hypertension
Weight gain
Impaired glucose tolerance—metabolic
syndrome, PCOS, gestational diabetes
Family history of early coronary
artery disease
• What’s early?
• 1st degree relative
Undesirable lipid levels
• HDL less than 40 mg/dl (1.04 mmol/L) in
men; less than 50 mg/dl (1.3 mmol) in
women
• Triglycerides greater than 150 mg/dl (1.70
mmol/L)(New AHA guidelines say 100 mg/dL)
• Think diabetes or hypothyroidism with the
above lipid profile
• Draw a FBS or HbA1C and a TSH
Reducing triglycerides
• Fish oil capsules (omega 3s) can also reduce the TG (1
gm/day lowers TG by 5-10%; statins (rosuvastatin/Crestor,
specifically) by 30%; diet changes by 20%--increased fiber,
decreased trans fats, reduce added sugars, limiting
alcohol)
• EPA (ecosapentanoic acid)
• DHA—docosahexanoic acid)
• 1000 mg/1 gram per day for established CAD
• Higher doses for high TG (platelet problems with higher
doses)
• READ THE LABEL
• Lovaza (prescription fish oil)
Hypertension—which comes first?
• Greater than 140/90 (persistent 135/80 warrants
testing for DM) increases the risk of diabetes
• 50-60% have both DM and HTN at diagnosis— “the
deadly duo”
• In a diabetic patient, a systolic pressure of 130-139
mmHg with a diastolic pressure of 85-89 mmHg,
although classified as “high normal”, warrants
PROMPT treatment
• However, lowering the BP to less than 120/70
doesn’t appear to improve outcomes
High risk ethnic groups
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Indian (from India)(#1)
Asian (#2)
Hispanic
Pacific Islanders
Native American Indians
Dark skinned individuals have a higher risk of Type 2
diabetes
• Could it have something to do with vitamin D?
• Beta cells also have vitamin D receptors on their surface, and
people with vitamin D deficiency are at increased risk for
type 2
Age and type 2 diabetes
• 50% of all type 2 diabetics are over 60;
• 18% are 65-75;
• 40% of people over 80 have diabetes
Type 2 diabetes risk factors
• Weight gain
• 85% are overweight or obese
• (however, 2/3 of all overweight people and
1/3 of obese patients will never develop
diabetes)
What did you weigh as a kid?
The odds that a person who is a normal weight
at age 18 will develop diabetes later in life
are 1-in-5 or 1-in-6. However, if you’re very
obese at age 18, you have a 3-in-4 chance of
developing diabetes.
50% of all newly diagnosed children with
diabetes are type 2
WHY?
Let’s dispel a few “old” myths…#1
• Is a calorie just a calorie just a calorie?
• OLD ANSWER? YES, of course…cut calories?
Lose weight…
• NEW ANSWER? Not exactly…potatoes have
been found to pack on the pounds more than
the same amount of calories in walnuts…
• What kind of potatoes? FRENCH FRIES…then
chips, soda, red meat, mashed potatoes
• (N Engl J Med June 23, 2011)
Location, location, location
• Abdominal (visceral)--obesity and insulin
resistance (fat in the liver and muscle is
insulin resistant)
• It’s a new organ…it’s metabolically active
• It produces inflammatory mediators such as
TNF-α, IL-6, C-reactive protein, and
adiponectin
• Waist greater than 102 cm (40 inches) in
males and 88 cm (35 inches) in females
• Actually your waist should be ½ your height
Metabolic syndrome
• DEFINITION: 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
• Female to male ratio -- (2:1)
• Weight or body mass index is a major risk factor;
5% of normal weight; 22% overweight, and 60%
of obese individuals have the metabolic
syndrome
NCEP--ATP III guidelines for metabolic
syndrome
• Central obesity—waist size greater than 40.2 inches in
men, 34.6 inches in women
• High TG (>150 mg/dL/1.7 mmol/L or greater) or being
treated for high triglycerides
• Low HDL (less than 40 mg/dL/1.03 mmol/L in men, less
than 50 mg/dL / 1.30 mmol/L in women)—or being
treated for low HDL
• Hypertension (≥ 130/85 mm Hg) or being treated for
HTN
• Fasting glucose ≥ 100 mg/dL/ 5.5 mmol/L or being
treated for diabetes
• WHO guidelines add microalbuminuria (urinary albumin
to creatinine ratio 30-300 mg/g.
Where do you measure waist size?
• Official guidelines—locate the top of the
right iliac crest; Got it? Intersect that point
with a line dropped vertically from the
middle of the right armpit is where you place
the paper tape measure (cloth tape measures
are too easy to stretch, )
Other risk factors for Type 2
diabetes—Gestational Diabetes
• Gestational diabetes—5-9% of pregnant women in
U.S.; rates have increased 122% between 1989 and
2004
• Risk factors—obesity, advanced maternal age (over
40? 6x greater risk) FH of DM, history of GDM or
abnormal glucose metabolism,, ethnicity—Indian
and Pakistani women have a 4x greater risk; Middle
Eastern and African American women have a 2x
greater risk; Lower income—higher risk
Impaired glucose tolerance
• Baby weighing greater than 9 lbs. or a
• Small for Gestational Age (SGA) babies
• Were YOU, as a baby, exposed to intrauterine
hyperglycemia ?
Polycystic Ovary Syndrome (PCOS)
• First article published in 1922 by 2 French MDs
entitled: “The Diabetes of Bearded Ladies…”
• Metabolic syndrome is 2-3 x higher in women with
PCOS
• Type 2 diabetes is 10x higher in women with PCOS
• Liver and muscle tissues are insulin resistant; ovary is
NOT; hyperinsulinemia triggers androgen production
with hirsutism and decreased ovulation
• Metformin (Glucophage) increases insulin sensitivity,
decreases hyperinsulinemia, decreases androgens,
and improves ovulation
Abnormal beta cell function—
increased risk of type 2 DM
• “Oh, I’m so hypoglycemic…”
• ONLY if it’s a documented history of
hypoglycemia
• Documented with an oral glucose tolerance
test
• Beta cells are not functioning normally after
a glucose load, hence beta cell dysfunction
• ~30- 70% risk of developing type 2 DM
Duodenal exclusion surgery?
• Is the cure for diabetes just a scalpel away? Not so
fast…Many diabetic patients that have had gastric
by-pass surgery that bypasses the duodenum and
the upper small intestine have observed that their
diabetes disappeared within weeks of the
procedure—before any substantial weight loss.
Postprandial hyperglycemia and the return of
diabetes…
• Gut bacteria and obesity—firmacutes vs.
bacteriodetes
What does exercise do?
• Exercise has a role in fat placement
• Exercise reduces insulin resistance; one way it may
do this is to burn fat out of the muscle
• Because of this, getting enough exercise may stave
off type 2 diabetes in some cases
Back to type 2 diabetes--the perfect
storm…Type 2
• Family history– genes that control the
amount of insulin produced by the beta
cells—whether or not the insulin produced
can overcome the insulin resistance
• Abdominal obesity
• Lifestyle (Lack of physical activity and
sedentary lifestyle)
What is the best way to reduce belly fat?
WALKING…
• Ladies…the bad news…
• exercise not only reduces insulin resistance it
also jump starts weight loss…
Secondary diabetes
• Exocrine pancreatic disease—cystic fibrosis
• Cushing’s disease or syndrome
• Drugs—corticosteroids, L-dopa, sympathomimetics,
niacin, glucosamine, thiazide diuretics
• Atypical anti-psychotics--Weight gain= Clozapine
(Clozaril)(biggest offender) and #2 is Olanzapine
(Zyprexa); 10 weeks/10 pounds
• Risperidone w/ intermediate weight gain,
ziprasidone (Geodon) and aripiprazole (Abilify) with
least weight gain
Do the statin drugs increase the risk
of type 2 diabetes?
• Latest findings…yes, BUT the statins’ proven
power to prevent heart attacks and strokes
outweighs ANY potential increase in type 2
diabetes risk
• Study of postmenopausal women—6.4% not
taking statins developed type 2 DM vs. 9.9%
among statin users (over an 8 year period)
• Manson J. Harvard Medical School, 1/10/12
Type 1A diabetes
• Type 1A DM—primarily diagnosed in preteens or teenagers; onset prior to age 40 in
the majority of patients;
• Caucasians greater than darker skinned
individuals
• Finland #1 country in world with Type 1 DM
Type 1A Diabetes
• Associated with immune response genes and HLA-DR3 and
HLA-DR4 (99%; 53% with both; only 3% of people without
T1A DM have both; also DQB1 (genetic background of
Northern Europeans—Sardinia, Finland)
• Autoimmune attack against beta cells of pancreas (antiglutamic acid decarboxylase antibodies—anti-GAD; ICA {islet
cell antibodies}; IAA {Insulin autoantibodies})—months to
years
• Present with 3 p’s—polyuria, polydipsia, polyphagia, and
weight loss
• Classic presentation is in a Caucasian, blue-eyed, blondehaired kid named…
Autoimmune disease
• What triggers the autoimmune response in a
genetically susceptible individual?
• The most likely culprit is one of the childhood
viruses…cross reaction? Molecular mimicry?
• Coxsackie B? Measles? Influenza A or B?
• Or?
Triggers of Type 1 diabetes…
• Type 1 diabetes has increased by 5% per year
since the 1980s
• In addition to viruses…
• 3 other suspects..
Too little sun
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Sunphobia
Sunscreen maniac moms
SLAP A DERMATOLOGIEST TODAY!!
Kids playing inside (the “thumb tribe”)
Pushes the immune system in the wrong direction—
Abnormal regulatory T cells?
2 pathways—TH1 and TH2
Taking the TH2 pathway increases the risk of allergies and
autoimmune disease?
Too little dirt
• The hygiene hypothesis— GUT bacteria and
priming the immune system
• Germphobic (mysophobic) *moms
• LET THEM EAT DIRT!
• (*irrational fear of DIRT)
Too much cow’s milk…
• Decreased risk in babies who are breast fed
• Increased risk in drinking cow’s milk—is there a
protein that aggravates the immune system and
triggers diabetes in genetically susceptible
individuals?
• Large scale clinical trial called TRIGR, testing this
hypothesis and is scheduled for completion in 2017
Other autoimmune diseases associated
with Type 1 diabetes
• Celiac disease—(12.3% of T1DM kids in Denmark
have celiac disease; 6.4% in US have both—growth
problems, iron deficiency anemia)—younger the
age at DX for DM the greater the risk (Diabetes Care
2006; 29:2452-2456)—share HLA-DQB1 with Type 1
DM
Autoimmune disease
• Thyroid disease (Hashimoto’s
thyroiditis)—4.8% with T1DM and HT);
clinical presentation; check their TSH
• Pernicious anemia– 2.6%—antibodies to
intrinsic factor resulting in a B12
deficiency
Digression on B12 deficiency…
• B12 deficiency can cause peripheral
neuropathy which may be falsely attributed to
the neuropathy of diabetes (check B12 levels
and check MCV as B12 deficiency can also
result in a macrocytic anemia)
• Metformin can contribute to B12 deficiency
• PPIs can cause a B12 deficiency
Laboratory diagnosis
• Hemoglobin A1C—gold standard for measuring long-term
glycemic control—how does it work? RBC life span
• Glucose binds irreversibly with hemoglobin over the lifespan
of the RBC
• 50% of glycosylated hemoglobin is from previous month;
25% from the month before; 25% 3-4 months ago
• Normal range is 4-6%
• *TIGHT control in the Type 2 diabetic does NOT always lead
to the best outcomes (ADVANCE and ACCORD studies—
HbA1c’s of 7 are more feasible and provide better outcomes
Pre-diabetes
• ...one step away. HUH?
• Asymptomatic fasting blood sugars between
(5.5/100mg/dl)/6.1 (110) to 7.0 mmol
• Used to be called impaired glucose tolerance
• May have metabolic syndrome
The Geriatric Patient and blood glucose
control
• Blood sugars? (may want to keep the HbA1C
in the 7-8 range)—hypoglycemia can break a
hip
• Blood pressure? Hypotension can break a hip
• Consider co-morbidities before aggressively
treating
• Polypharmacy
• Life expectancy?
Life expectancy?
• Consider co-morbidities before aggressively
treating—8 years needed benefit of glycemic
control in reducing microvascular
complications
• 2-3 years for benefit from BP and lipid control
for reducing macrovascular complications
What about kids?
• 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
INSULIN and GLUCAGON
• Insulin is a growth hormone—stores fat and sugar and
stimulates protein synthesis after the meal
• Produced by the beta cells of the pancreas
• Too much insulin? WEIGHT GAIN
• Glucagon is a catabolic hormone produced during the fasting
state; breaks down stored glycogen
• Produced by the alpha cells of the pancreas
• Too much? WEIGHT LOSS
Right after a meal (The postprandial state)
• The pancreatic beta cells produce insulin
• Insulin triggers glucose to enter cells and to be
stored as glycogen in the liver and muscle
(glycogenesis)
• Lipogenesis—insulin transports lipids into
adipocytes
• Protein synthesis—transports amino acids into
muscle
• GROWTH
Postprandial state
• The meal
CHO, lipids,
proteins
pancreas
Blood vessel
Insulin*
Incretins
Amylin*
GLP-1—
GI tract
Muscle, fat, liver cell insulin
receptors
Stores sugar as glycogen
Stores lipids in fat tissue
Stores protein and glucose
in muscle tissue
Receptor sensitivity/exercise
During the fasting state
• Between meals and overnight primarily
• The pancreatic alpha cells produce glucagon
• Glucagon triggers glycogenolysis (breaks
down stored glucose 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
Ketoacidosis (DKA) in Type 1 diabetes
• Type 1 ketoacidosis is a prolonged fasting state
with an absolute deficiency of insulin;
• Glucagon is working overtime—glycogenolysis;
lipolysis; and gluconeogenesis
• All contribute to hyperglycemia and osmotic
diuresis
• fatty acid release (ketones in the urine—osmotic
diuresis)--ketoacidosis
• A young girl presenting with alternating
hypoglycemia and DKA – consider an eating
disorder
A quick primer on Diabetic Ketoacidosis
(DKA)
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Dehydration (usually 7-10%)
Abdominal pain
Anorexia, weight loss
Kussmaul’s respirations (acidosis)(hyperventilation
with slow, deep sighing breathing)
Tachycardia
Weakness, fatigue
Fruity breath odor
hypotension
N or V
Confusion, decreased reflexes, coma
A quick primer on Ketoacidosis
• Dehydration is your biggest concern initially (10-20 mL/kg for
1-2 hours)
• GIVE FLUIDS…what kind? NS or RL)
• Then what? Regular insulin IV (0.1 U kg/hr)
• Then what? Check electrolytes and pH
• ICU
• Should bicarb be given?
Pathophysiology of Type 2 DM
• Early in the disease—as the body becomes resistant
to insulin, the beta cells in the pancreas must pump
out more hormone to compensate; people with
beta cells that can’t keep up with insulin resistance
can’t move the glucose into the muscle, fat and liver
cells
• Insulin resistance is characterized by a rise in
postprandial blood sugars
• Hyperinsulinemia results.
• What are the consequences of hyperinsulinemia?
Hyperinsulinemia results in…
• Increased triglycerides and decreased HDLs
• Triggers release of angiotensin 2 → aldosterone
• Vasoconstriction and sodium and water retention—
hypertension
• Stimulate fat storage (CHO to fats)
• Prothrombotic (increased AT2)
• Proinflammatory (increased AT2)
• Triggers endothelial cell dysfunction-fancy way of
saying, deposits LDL cholesterol and triglycerides
into the arterial walls
• YIKES!!
Type 2 diabetes
• Metabolic derangements aren’t usually as severe as
Type 1
• Few symptoms initially, 2 P’s (no polyphagia),
weight gain due to hyperinsulinemia
• Other symptoms—fatigue, diplopia, nocturia
(nocturnal diarrhea)
• Skin infections, vaginal yeast infections, poor
wound healing (BS >180 mg/dL or 9 mmol/l),
neuropathy
• “Silent” for a full decade in some individuals
Oral Drugs—the #1 oral drug
• 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 (nighttime dosing/give with food),
need functioning organs--kidneys and heart
especially (check serum creatinine before starting
metformin)
• Se Creatinine--Cut-off is 1.4 (50-90 mmol/L) in
females and 1.5 (70-120 mmol/L) in males;
Metformin (Glucophage)
• Other benefits: lowers BP, increases HDL,
lowers LDL; has been shown to be safe during
PG (? Use for gestational diabetes?)(N Engl J
Med May 8, 2008)
• B12 deficiency
• Metformin and gestational diabetes
• Metformin and breast cancer reduction
(54%)—Diabetes Care December 2010
• Metformin and slowing the aging process
Oral drugs for type 2 DM…
• 2nd tier: The “Glitazone” sister— pioglitazone (Actos)
(troglitazone/Rezulin and rosiglitazone/Avandia are
history)—black box warning for bladder cancer with
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; reduce fatty liver
OLD Drugs…are these even worth using anymore?
Considered third-line therapy…cheap drugs
• Oral sulfonylureas—Glipizide (Glucotrol) and
glyburide (Diabeta, Micronase, Glynase) (used for
gestational diabetes)and glimipiride (Amaryl)…
• Increase the secretion of insulin from the pancreas
and increase receptor sensitivity
• Problem? Weight gain, hypoglycemia, increased
cardiovascular risk
• glimipiride (Amaryl)—safe use in elderly--decreased
incidence of hypoglycemia
• Increased risk of cardiovascular events (highest doses
increased risk vs. metformin; may prevent heart from
recovering from brief periods of ischemia) (Canadian Medical
Association Journal January 2006)
Oral drugs before a meal
• Repaglinide (Prandin)*
• Nateglinide (Starlix)
• Good for elderly to prevent postprandial
excursions
• Great if your meals are sporadic
• Prandin* (better than Starlix)
The “gliptins”
• Weight neutral
• Sitagliptan (Januvia) inhibits enzymes in the
intestine responsible for breaking down
incretins; incretins potentiate insulin release
• Saxagliptin (Onglyza)
• Newest: linagliptin (Tradjenta)
• Januvia + simvastatin in one pill
Better…drug combinations
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Actosplus Met (metformin/pioglitazone)
Metaglip (glipizide and metformin)
Glucovance (glyburide and metformin)
Duetact (pioglitazone HCl and glimepiride)
Janumet (sitagliptan and metformin)
Kombiglyze (onglyza + metformin)
Incretin mimetics (April 28, 2005)—
• Exenatide (Byetta)—isolated from saliva of a Gila Monster
• (incretins are responsible for approx. 60% of the post-meal
insulin secretion, but the action of the incretins is impaired
in diabetics)
• Type 2 diabetics who are already receiving metformin, a
sulfonylurea, or both and do not have optimal control
• Acts at the GLP-1 receptor, promoting insulin release
• Weight loss is a + side effect (due to slowing of gastric
emptying and “feeling full”)
• 2nd generation—liraglutide (Victoza)
Insulin
• The discovery of insulin…
• Frederick Banting and his assistant, Charles Best
experimented on diabetic dogs over the summer
of 1921, and finally, dog number 92, a collie,
hopped off the table after an injection and
wagged her tail—this was the breakthrough
• In the spring of 1922, Elizabeth Hughes,
daughter of Justice Charles Evans Hughes
traveled to Toronto to receive insulin; she was
52 pounds when she arrived
• By the time she died in 1981, at age 74, she
had received 42,000 insulin shots
Eli J. Lilly and Company (Indianapolis)
• Won the right to mass produce insulin
• First partnership negotiated among academia,
individual physicians and the pharmaceutical
industry
• Chicago played a major role—slaughterhouses
began sending trainloads of frozen porcine (pig)
and bovine (cow) pancreas to Lilly’s plant in Indy.
• By 1932 insulin’s price had fallen by 90 percent
Insulin
• The pancreas will eventually give out and the oral
agents will no longer work; over the course of 15
years, the proportion of patients using oral agents
alone declines from 65% to 25%, with a
corresponding increase in those using insulin
• BUT new studies show that insulin should be
started EARLIER in Type 2 DM…better glucose
control than w/ oral meds
Insulins
• Old “down –on-the-farm” insulins
• Anything with the last name “ine”—bovine, porcine
• Rapid-acting insulins include aspart (Novolog), glulisine
(Apidra), lyspro (Humalog),
• Regular insulin—Novolin R and Humulin -R
• Intermediate acting insulin—neutral protamine Hagedorn
(NPH)—Humulin N, Novolin N
• Long-acting insulins include detemir (Levemir), glargine
(Lantus)
NPH continues to have some
usefulness
• Used to provide basal insulin and because it has a
peak action, they may cover the midday meal;
onset 4-6 hours, peak at 8-14, duration of 16-20
hours
• Human NPH with shorter onset (2-4 hours), peak in
4-10, and duration is 10-16
• SOMOGYI effect at 2-3 a.m.—nocturnal
hypoglycemia with rebound SNS response and
subsequent hyperglycemia
• DAWN phenomenon—early morning rise in BS
• Still used but if possible switch to…
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 and Levemir stabilize endothelial
cells…HUH? Reduce atherosclerosis risk
Complications of type 2 diabetes
• Accelerated atherosclerosis--four out of five diabetics
die from complications of cardiovascular disease and
atherosclerosis
• Coronary artery disease, cerebrovascular disease,
peripheral vascular disease—diffuse disease; triple
vessel CAD
• 10x greater risk of CHF in females with diabetes and
a 6x greater risk of CHF in males with diabetes
• Risk of stroke is 2.5-4x greater in diabetics
Protect your heart! Floss your teeth!
• “Floss only the teeth
you want to keep…”
Dental care and diabetes
• 1 to 2 periodontal treatments per year
decreased diabetes costs by 11-12%
• Univ of Michigan School of Public Health
• January 8, 2009, Science Daily
• Neuropathy and dry mouth
• Increased risk of yeast infections
Peripheral arterial disease
• Atherosclerosis of the aorta, iliac arteries, femoral
arteries
• Intermittent claudication
• Risk of amputation is 15-40 x higher in the diabetic
• A diabetic foot ulcer precedes amputation 85% of
the time
• Let’s hear it for WOCNs!
• FOOT CARE!!
Wound care: What do they do with all of
that circumcised foreskin?
• Apligraf
• Regranex (PDGF)
• How about honey for wounds??
Are they on aspirin and/or Plavix
(clopidogrel)?
• Diabetes is a pro-inflammatory disease!
• Diabetes is a pro-thrombotic disease
• ASA is not for men under 50 and women under 60 UNLESS…
other risk factors (smoking, HTN, high LDL) are present
• Plavix if allergic to ASA
• Plavix after a coronary event or cerebral event
• Plavix with a stent
• Diabetes Care , June 2010
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), pitavastatin (Livalo)
• Statins are anti-inflammatory, anti-lipid, decrease
plaque formation, stabilize plaques and prevent plaque
rupture
• HDL greater than 40 mg/dL in men, greater than 50 in
women
• Statins may also slow the progression of chronic renal
disease (Fried)
Statin drugs
• Should all diabetics be on statins REGARDLESS of their
LDL level?
• YES…YES…YES…their anti-inflammatory effects are
even more beneficial; and even if their LDL level is
normal, their LDLs tend to be small and dense
(Pattern B—think BBs floating around in the arteries);
statins may change the size of LDLs to large and
LOOSE (Pattern A)!
• Small dense LDLs are even more damaging to artery
walls
• The reason their LDLs are small and dense is because
their triglycerides are too high--PAY ATTENTION to
TG!!
• Fibric acid derivatives (fenofibrate) lower TG and
increase particle size; extended release niacin also
increases particle size
FYI
• Particle size and particle number can be
determined by the NMR (nuclear magnetic
resonance) LipoProfile—cost ~ $100 to $120,
slightly higher than a lipid profile
• Many insurance companies cover the cost of
NMR, including Medicare
• Goal for particle number is less than 1000
nmil/L and goal for LDL size is 20.6 nm or
greater
What’s not to love about the statins? Yeah,
yeah…side effects
• Myalgias **(other causes in elderly patients…)
• Myositis; rhabdomyolysis (rare)
• About 1/20 patients experiences muscle pain
or weakness
• Reduce the dose, don’t stop the drug
• Change to Crestor? Give the statin every other
day?
• Check the creatine kinase if muscle aches and
pains are severe
Hypertension and the diabetic
• 50-60% 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? (Usually 2 are needed) First line
therapy should be either the…
Prils
•
•
•
•
•
•
•
•
•
Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moxepril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
• DO NOT USE DURING
PREGNANCY!!
or
ARBs
•
•
•
•
•
•
•
•
losartan—Cozaar
valsartan—Diovan
candesartan—Atacand
irbesartan—Avapro
telmisartan—Micardis
olmesartan—Benicar
Eprosartan—Tevetan
Azilsartan--Edarbi
Side effects of the ACE inhibitors…
• Hypotension
• Hyperkalemia (excreting sodium and water and
retaining potassium)
• Hypoglycemia
• Cough (gender difference)
• Angioedema (“Does my voice sound funny to you?”)
What should the 2nd anti-hypertensive
drug be?
• Thiazide diuretic? (may increase BS)
• Beta-blocker if they have tachycardia, angina
or previous MI (may mask symptoms of
hypoglycemia)
• Calcium Channel blocker—verapamil or
diltiazem for renoprotection
• Amlodipine (Norvasc)—another calcium
channel blocker
Diabetic nephropathy…PREVENTION!!
• Treat high blood pressure!
• Reduce the animal protein in the diet! Especially
if they have any evidence of renal involvement—
the amino acids valine and lysine from animal
meat increase intraglomerular hypertension and
accelerate kidney damage
• Reduce serum glucose!
• SAY YES to the ACE inhibitors or ARBs—the PRILS
or SARTANS (something to inhibit Angie and Al
(Angiotensin and Aldosterone)
The healthy kidney…
•
Afferent arteriole
(vasodilated via
(prostaglandins)
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
(vasoconstricted via
(angiotensin 2)
• Blood exiting
glomerulus
PG
filter
AT2
Toilet
The Diabetic Kidney…insulin resistance,
hyperglycemia, hypertension, animal protein
•
Afferent arteriole
(  vasodilation by
(  prostaglandins)
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
(  vasoconstriction via
(  angiotensin 2)
• Blood exiting
glomerulus
**CVD and microalbuminuria
Microalbuminuria**
Digression on the diabetic diet…
• Diabetic Diet—circa 1917
• “Forty-eight hours after admission to the hospital the
patient is kept on ordinary diet to determine the
severity of his diabetes. Then he is starved, and no food
allowed save whiskey and black coffee. Whiskey is
given in the coffee: one ounce of whiskey every two
hours, from 7 a.m. until 7 p.m. This furnishes roughly
about 800 calories. The whiskey is not an essential part
of the treatment: it merely furnishes a few calories and
keeps the patient more comfortable while he is being
starved.” (Starvation Treatment for Diabetes—1917)
Other diets
•
•
•
•
Exchange diet
Counting carb diet
Glycemic index diet
Mediterranean diet
The Cardiologist’s diet?
• “If it tastes good, spit it out!”
• Say NO to the Old Country Buffet Diet…
In addition to reducing animal protein, 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 to protect the
kidneys)
• High fiber (20-35 grams per day)
• Carbohydrates—what type? Count those carbs!
• One visit to a nutritionist can save $13,872 per person
over a 4 year period; savings in hospital charges…one
visit makes a HUGE difference
What about the Atkin’s diet to lose weight?
NOOOOOOOO
• The Atkin’s diet is PRO-inflammatory
• Saturated and trans fats
• Increases intraglomerular hypertension
Know how to estimate portion size…
• One teaspoon of peanut butter is the size of your
thumb’s first joint
• 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
Burning calories to lose weight…
• Besides the obvious activities for burning
calories—walking, biking, hiking, swimming…
• The “little” things mean a lot too…
When you’re just about ready to take a bite..
• It takes 2 hours and one minute for a 130-pound
person to walk off the calories in a McDonald’s BIG
MAC;
• 3 hours and 26 minutes to walk off a Burger King
Double Whopper, with cheese
Burn more calories than you take in…
• Stand up when talking on the phone…burn an
extra 15 calories
• Chewing gum…burn an extra 11 calories
• Tighten your rear-end when walking through a
doorframe…15 extra calories per squeeze
• FIDGET
Burning calories
• Kiss your honey every a.m. burns 6-12 calories
depending on the intensity of the kiss
Burning calories…
• A wild ride in the hay burns 125 to 300 calories
depending on how wild that ride happens to be!
• New partner or “same old same old”…??
Helpful hints for burning calories..
• Passionate kiss three times a day…
+
• Mad, passionate love twice a week…
=
• 32,000 calories per year, the equivalent of a 9pound weight loss
OR...
• Banging your head against the steps for one hour
burns 150 calories…this is a suggested alternative
when a wild ride in the hay isn’t an option.
Diabetic peripheral neuropathy (DPN)—
FOOT CARE
• 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 later—loss of vibration and
proprioception
• Stocking-glove distribution
Diabetic peripheral neuropathy— “Now
where did I put that sewing needle?”
•
•
•
•
•
•
•
Tingling or burning
Walking on hot coals
Walking on shards of glass—lancinating/shooting pains
Treatment—analgesics, antidepressants
Amitriptyline/Elavil,
(duloxetine/Cymbalta),
anticonvulsants (pregabalin/Lyrica) or
(gabapentin/Neurontin)
• Opioids as necessary
• Acupuncture, TENS, magnets (but not with an insulin
PUMP)
Metanx as a therapeutic option
• Prescription only medical food, regulated by the
FDA
• Contains active forms of folate, vitamin B6, and
vitamin B12
• Nutritional support for improvement in
symptoms and sensations for DPN
(Said G. Diabetic Neuropathy—A Review. Nature Clinical Practice
Neurology 6/26/07; Casellini C and Vinik A. Clinical
Manifestations and Treatment Options for Diabetic
Neuropathies. Endocrine Practice 11/19/07)
Autonomic neuropathy
• Evaluated and followed by a cardiologist
• Orthostatic hypotension (also common w/ aging)
• Resting tachycardia is an important sign of the LOSS
of vagal input
• Silent ischemia and congestive heart failure
• Need a beta-blocker (atenolol {Tenormin)
• metoprolol {Lopressor, Toprol XL}),
bisoprolol/Monocor/Zebeta
• Metoprolol or carvedilol (Lopressor or Coreg) with
CHF
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, Maxeran),
erythromycin, cisapride (special use),
domperidone (Motilium)(Canada only)
• Gastric pacer
Erectile dysfunction
• Atherosclerosis and neuropathy are the 2
major causes
• ED is an accurate indicator of CVD
• 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
Diabetic Retinopathy—number 1 cause of
blindness in U.S.
• SEE the EYE GUY once a year!
And lastly…TREAT the DEPRESSION!
• Pick a pill any pill
• Happy patients are
compliant patients
• SSRIs improve selfesteem
• Diabetes is a 24/7
job
Thank you.
• Barb Bancroft, RN, MSN, PNP
• www.barbbancroft.com
• [email protected]
Bibliography
• Bloomgarden ZT, Comi RJ, Kendall DM. New therapies to achieve
glycemic control and weight loss in T2DM. Patient Care 2006
(February): 46-53.
• Fogel N, Zimmerman D. Management of Diabetic Ketoacidosis in
the ED. Clinical Pediatric Emergency Medicine 2009; 10(4).
• Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the
progression of renal disease: a meta-analysis. Kidney Int
2001;59:260-9.
• Gebel E. The other diabetes. Diabetes Forecast 2010 May:46-48.
• Gondeck K. LDL particle number and size. ADVANCE for NPs and
PAs. January 2012
• Nestler JF. Metformin for the treatment of polycystic ovary
syndrome. N Engl J Med 2008 Jan 3; 358:47-54
• 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.
Bibliography
• Psaty BM and Furber CD. Rosiglitazone and cardiovascular
risk. N Engl J Med 2007 Jun 14; 356:2522-4.
• Ribowsky J. Gestational Diabetes. ADVANCE for NPs & PAs;
November 2010; 31-48.
• 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
• 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).
• Gavi S, Hensley J. Diagnosis and management of type 2
diabetes in adults: A review of the ICSI guideline. Geriatrics
(2009);64(6):12-17.
• Gebel E. Why Me? Diabetes Forecast 2010 (October); 44-50.
Bibliography
• Sernyak MJ, Leslie DL, Alarcon RD et al. Association of
diabetes mellitus with the use of atypical neuroleptics in the
treatment of schizophrenia. Am J Psychiatr 2002;159:561-6.
• Szerszen A, Seminara DP, Castellanos MR. Glucose control in
the hospitalized elderly—a concern not just for patients with
diabetes. Geriatrics (2009); 64(6):18-20.
• Umpierrez GE, Palacio A, Smiley D. Sliding Scale Insulin Use:
Myth or Insanity? The American Journal of Medicine 2007;
120 (7).
• Umpierrez GE, Isaacs SD, Bazargan N, et al. Hyperglycemia: an
independent marker of in-hospital mortality in patients with
undiagnosed hyperglycemia. J of Clin Endoc and Metabol
(2002); 87(3):978-82.
• Vasconcelos A. Could surgery spell the end of diabetes? New
Scientist, Sept 2007
LADA (Latent autoimmune diabetes in
adults)—10% of all diabetics
• Typical age of onset – adult
• Progression to insulin dependence – months to years
• Presence of autoantibodies—yes
• Insulin dependence – within 6 years
• Insulin resistance – some
The presence of autoantibodies distinguishes this type
from type 2 and no need for insulin within the first six
months distinguishes it from type 1.
Consider this diagnosis in a “skinny, type 2 diabetic that
doesn’t respond well to oral drugs”—usually
misdiagnosed
MODY—1 to 5% of all diabetics
• Maturity-onset diabetes of the young
• Monogenic (single gene abnormality)—the pancreas
cannot make enough insulin and/ or a defect in insulin
secretion; autosomal dominant
• Usually diagnosed before age 25
• 6 different subtypes—some don’t require insulin and
can be treated with oral medications
• doesn’t progress to ketoacidosis; persistent
hyperglycemia; continued partial insulin secretion with
no insulin resistance; mild to moderate hyperglycemia
with a range of 130 – 250 (7 -14 mmol); absence of ++
antibodies or other autoimmune diseases
Intrauterine hyperglycemia and future
risk of Type 2 DM or prediabetes
1) offspring of women with diet-treated gestational
DM (21% of offspring develop T2DM or
prediabetes )
2) offspring of genetically predisposed women with
a normal OGTT (12% develop T2DM or
prediabetes)
3) Offspring of women with T1DM (11% develop T2
DM or prediabetes)
4) Offspring of women from the normal population
(4% develop T2DM or prediabetes)
(Diabetes Care 2008 Feb 01: 31(2):340-6)
Estimated average glucose—a calculated
conversion of A1c
• eAG = 28.7 x A1c – 46.7
• A1c (%)
eAG (mg/dL)
5.5
97
6
126 (7 mmol)
7
154
8
183
9
212 (11 mmol)
10
240
11
269
12
298
eAG is a running average over the past 3 months of all glucose fluctuations;
used to help patients correlate their numbers with A1c.
Symlin (Pramlinitide)
• Amylinomimetic agent for type 1 and type 2 diabetes—
synthetic analogue of the hormone amylin, 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 T1DM and T2DM who use
mealtime insulin and have not maintained glycemic control
despite optimal insulin therapy with or without oral drugs; cut
mealtime doses by 50% with Symlin
• Improves postprandial blood glucose and promotes weight
loss