Transcript DIABETES – It`s COMPLICATED!! Barb Bancroft, RN, MSN, PNP

DIABETES – It’s COMPLICATED!!
Barb Bancroft, RN, MSN, PNP
Chicago IL
[email protected]
Historically…the name had something to do with the kidney…
• Diabetes (Greek)— “to siphon”
• Mellitus— “sweet” or “honeyed”
• Insipidus—”tasteless”
• (1674)“Taste thy patient’s urine, for if it be sweet…”
---Dr. Thomas Willis
NURSE!...
Most diabetics lived 3-6 years after diagnosis “back in the day…”
Back porch diagnosis and dipsticks
• It took 217 years to stop tasting urine (1891)
• Urine specimens were placed on the back porch…flies, ants, or
bees…meant sugar in the urine…no critters? Diabetes insipidus
• 1953—urine tablets for testing glucose made their debut; 1964—
urine strips for testing glucose by color code became standard
practice
• So it really wasn’t thaaaat long ago that we “dipstick’d” the urine for
sugar
Today? We’re still dipsticking…
• For ketones in patients with a risk for diabetic ketoacidosis (DKA)—
type 1 (primarily)(some type 2’s are ketosis prone)
• We also dipstick for protein in the urine at every visit
• If the regular protein dipstick is negative, the urine is sent to the lab
for an albumin/creatinine ratio (microalbuminuria)
• More later on all of the above…
The evolution of a name…
• “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 and subtypes…
• Type 1A (autoimmune)
• Type 1B (idiopathic)
• LADA (10%) (latent autoimmune diabetes in adults)—more on next
slide
• MODY (1-2%) (maturity onset diabetes of the young)—monogeneic
(6 subtypes)—rare, very rare
• Gestational diabetes
• Secondary diabetes
A brief mention of LADA (Latent autoimmune diabetes in
adults)—10% of all diabetics
• Typical age of onset – adult (estimated that 50% of nonobese adult “type 2 diabetics” actually have LADA)
• Consider this diagnosis in a “skinny, type 2 diabetic that
doesn’t respond well to oral drugs”—usually
misdiagnosed as type 2
• Often there is no family history
• More likely to be Caucasian with mild insulin resistance
• Progression to insulin dependence – usually measured in
months
• Will have autoimmune antibodies to various components
of the beta cells and insulin in blood if tested
Definition of Diabetes Mellitus
• Chronic disorder of carbohydrate, LIPID* (see next slide) 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).
Let’s address the lipid issue: Should all diabetics be placed on a
statin drug? (ACA, AHA, 2015)
• YES, kind of… for sure in all diabetics (T1DM, T2DM) between
the ages of 40-75 with LDLs greater than 70 mg/dL , and for any
diabetic that has angina or hypertension, or has had an acute
coronary syndrome/stent, peripheral vascular disease, TIA, ischemic
stroke…high intensity statin (HD-atorvastatin/Lipitor or
rosuvastatin/Crestor)
• What about under the age of 40? Any cardiovascular risk factors? YES,
moderate or high intensity statin; under 40 with overt cardiovascular
disease—high-intensity statin
Just a reminder…
• Diabetes is a pro-accelerated atherosclerosis…two- to fourfold
increase in developing cardiovascular disease compared to the
general population
• All arteries (coronary, carotids, aorta, femorals, popliteals) are packing
in the fat (multi-vessel disease) faster than non-diabetic peers
• Jeez...is there any artery that doesn’t fill with fat?
Type 1A diabetes--definition.
• Type 1A—chronic autoimmune* mediated disorder characterized by
selective pancreatic beta cell destruction with severe insulin
deficiency, resulting in hyperglycemia
• *positive for antibodies to various components of the islet cells of the
pancreas
Type 2 diabetes.
• Type 2 has 8 basic defects going on…SERIOUSLY? 8???? “the Ominous
Eight” –start with the traditional 3
1. insulin resistance in peripheral tissues—muscle, liver, fat cells
2. pancreatic beta cell dysfunction—abnormal release of insulin in
response to a glucose load
3. Increased hepatic glucose production—increasing fasting blood
sugars, especially overnight (hepatic glycogenolysis-breakdown of stored glycogen to glucose)
The above three have been the traditional defects..but WAIT!!
There’s MORE—FIVE MORE to be exact
4) Accelerated lipolysis in the fat cells—high serum TG = small, dense LDLs
(even though the total LDL can be normal)—more later (STATINS for Core
defect #4)
5) Incretin resistance/deficiency in the small intestine—WTFudge are
incretins? HUNGRY, weight gain
6) Hyperglucagonemia (alpha cell failure)—increasing hyperglycemia
7) Increased glucose absorption by the proximal convoluted tubule of the
kidney—increasing hyperglycemia
8) Insulin resistance in the brain (reducing the feeling of satiety and
contributing to dementia of the Alzheimer’s type) – Hungry, amyloid
deposition in brain
Anything else?
• PLUS…diabetes is a pro-inflammatory, pro-thrombotic, and an
accelerated pro-aging disease! So be PRO-active in DX and RX!
• *insulin resistance is also present in overweight adult Type 1 diabetics
—but not as predominant—keep this in mind for a future discussion
on the possible benefits of glucophage/Metformin in the Type 1
diabetic
What are the risk factors for Type 1 and Type
2?
Family history is a risk factor for both Type 1 and
Type 2
• Stronger for Type 2—almost all cases have a parent or grandparent;
identical twin concordance rate is 80%--genes that regulate beta cell
function
• Type 1—50-90% don’t have a family history; identical twin
concordance rate is 35-50%
• The concept of epigenetics
Type 1 diabetes and genetic risk
• First-degree relatives (parents, children, siblings) of individuals with
type 1 diabetes have a ten-fold greater risk of developing type 1
diabetes than the rest of the population. In particular, children of
fathers with type 1 diabetes are at a greater risk of developing type 1
diabetes than children of mothers with the disease.
Higher risk of autoimmune disease in
offspring of Type 1 diabetic parents
• Higher risk of T1 diabetes in the offspring of T1 diabetic fathers
• However, there is a higher risk for other autoimmune disorders
(Crohn’s disease, rheumatoid arthritis, etc.) among offspring of type 1
diabetic mothers (0% vs. 6.2%; p=0.02, respectively, through age 20
yr).
• Dorman JS, et al. Type 1 diabetes in offspring of parents with type 1 diabetes: the
tip of an autoimmune iceberg? Pediatr Diabetes. 2000 Mar;1(1):17-22.
Does skin color have anything to do with Type
1 diabetes?
• Yes…Caucasians have a higher risk for Type 1 diabetes…appears as if
the “Founder Gene” (the original mutation) came from Scandinavia—
blonde-blue-eyed, whiter than white skin…
• That doesn’t mean that children and adults with brown or black skin
don’t get Type 1 because they DO, and the numbers are increasing;
however, Type 1 is still more common in Caucasians
• Vitamin D deficiency with the Scandinavian background
Vitamin D deficiency also plays a role with
darker skin and type 2 diabetes
• Darker skinned individuals have a higher risk of Type 2 diabetes
• The increased melanin in dark skin decreases vitamin D absorption from sun
exposure
• India and China have the most Type 2 diabetics in the world; Increased risk in
Pacific Islanders , Native American Indians, African Americans, First Nations in
Canada
• Beta cells also have vitamin D receptors on their surface, and individuals with
vitamin D deficiency have an increased risk of beta cell dysfunction
RISK FACTORS for Type 2: Hypertension
• Any person diagnosed with hypertension or being treated for
hypertension should be tested for diabetes
• Persistent HTN above 135/80 warrants testing for DM
RISK FACTOR for Type 2: Positive FH of early
cardiovascular disease
• What’s early?
• Father, mother, brother, or sister who first developed clinical CVD at
age younger than 45-55 for males and at age younger than 55 to 60
for females
• History of an early myocardial infarction, stroke, or peripheral
vascular disease
• Xanthelasma—skin sign of underlying severe atherosclerosis—
significantly higher risk of MI/death
RISK FACTOR for Type 2: Low HDLs, high
triglycerides
• HDL < 0.9 mmol/L for males (35 mg/dL); < 1.3 mmol/L (60
mg/dL) for females )
• High triglycerides -- >1.70 mmol/L (150 mg/dL)
• If you see this lipid profile in a patient—consider either
diabetes and/or hypothyroidism
• Draw a HbA1C and a TSH
RISK FACTOR for Type 2—weight gain
• 85% are overweight or obese; however, 2/3 of all overweight people
and 1/3 of obese patients will never develop diabetes); A Nurses’
Health Study of 114,000 women found the risk of getting diabetes
was 93 times as high in obese women. A follow-up study found the
same association in men. (CDC, NIH, 2012)
FYI: A growing problem…obese kids
• The type 2 diabetes epidemic has paralleled the weight gain issue in
the U.S. and around the world
• Nearly 1 in 3 kids in the U.S. is overweight or obese
• Approximately 35% of adults in the U.S. are overweight or obese
• Type 2 diabetes in KIDS—as many as 50% of newly diagnosed
diabetes in kids is Type 2
• Adolescents with T2DM account for 45% of the new cases in the U.S.
Digression: Can certain foods pack on more
pounds for all of us?
• Is it true that a calorie is just a calorie is 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
• (N Engl J Med June 23, 2011)
Digression: Addiction to fries
• French fries light up the same areas of the brain that
nicotine, cocaine and heroin light up—the nucleus
accumbens and the ventral tegmentum
• French fries are addicting…the earlier you start, the more
addicting
By the way, chips are the
• #3 Red Meat
• #4 Soda
• #5 Mashed potatoes
nd
2
biggest offender
Location, location, location—where’s the fat?
• Visceral obesity is insulin resistant and it is metabolically active
• YOU HAVE GROWN A NEW ORGAN
• It produces inflammatory mediators via macrophages--such as TNF-α,
IL-6, C-reactive protein
• Waist less than 40 inches in males and 35 inches in
females…hmmm….doesn’t take into account your height
• Actually your waist should be ½ your height
What does exercise do?
• Improvements in tissue insulin sensitivity independent of
weight loss
• Increase glucose uptake; decreases hepatic glucose
production
• Both aerobic & resistance training
• Effect lasts 24 – 72 hours; no more than 2 consecutive days
w/out
• Sigal RJ et al. Diabetes Care 27:2518, 2004)
RISK FACTOR for TYPE 2:
Sedentary lifestyle
• Lifestyle (Lack of physical activity and sedentary lifestyle)
• As mentioned:
• Move it, move it, move it
Other risk factors…hypoglycemia and
obstructive sleep apnea
• “Oh, I’m so hypoglycemic…”
• ONLY if it’s a documented history of hypoglycemia--~30- 70% risk of
developing type 2 DM
• Documented with an oral glucose tolerance test
• Beta cells are not functioning normally after a glucose load, hence
beta cell dysfunction
Other high risk groups for Type 2 diabetes
• Girls with Polycystic ovary syndrome (PCOS)
• Non-alcoholic fatty liver disease (NAFLD)
• Acanthosis nigrans
Risk factors
• History of gestational diabetes or a baby weighing greater than 9 lbs
Sleep disorders
• OSA (obstructive sleep apnea)
• night shift work
• chronic sleep deprivation
Drugs that increase blood sugar
• Drugs—high-dose corticosteroids, L-dopa,
sympathomimetics, niacin, glucosamine, thiazide diuretics,
beta blockers,
• Antipsychotic therapy for the “spectrum of psychosis”—
clozapine and olanzapine are the biggest offenders;
risperidone with an intermediate risk
• HIV drugs—Crixivan, Kaletra, Zidovudine, ++
Whaaaaaaat?
• Children and adolescents on atypical antipsychotics have a 3fold increase for new-onset type 2 diabetes
Secondary diabetes due to disease
• Exocrine pancreatic disease—cystic fibrosis
• Cushing’s disease (pituitary tumor producing too
much ACTH) or syndrome (Prednisone, adrenal tumor)
Is it possible to prevent the weight gain and secondary
diabetes caused by certain drugs?
• Yes. Prescribe glucophage/Metformin along with
HD-Prednisone or the atypical anti-psychotics
• Risk may be reduced significantly with metformin (1000 mg
daily) at the start of therapy with the above drugs
RISK FACTOR: Age and type 2 diabetes
• The older you are, the higher the risk
• Why?
• 1) Pancreas gives out
• 2) fat moves to the center—even tho’ weight is normal, belly fat
increases
• 50% of all type 2 diabetics are over 60 in the general population
• 40% of people over 80 have diabetes
Type 1A diabetes—SELF vs. Non-self
• Researchers have found dozens of genes with links to type 1 diabetes
• Approximately half of the genes coordinate the HLA system that
controls the ability of the body recognize self vs. non-self;
• This also explains why other autoimmune diseases are associated w/
T1DM
• Celiac disease, Hashimoto’s thyroiditis, pernicious anemia, and
more… (we’ll revisit this…)
Type 1 diabetes—how many genes?
• Other genes found in T1DM mediate the immune
response to viruses
• Contributes to the viral hypothesis as a possible
trigger
• How many viral infections occur in children?
Type 1A diabetes
• Type 1A DM-- onset prior to age 30 in the majority of
patients; peak onset during puberty (Curr Probl Pediatr Adolesc
Health Care 2012;42(10):269-91)
• Rate of beta cell destruction is more rapid in younger
patients (Diabetes Care, 2014;37(10);2843-63)
Type 1A Diabetes
• Associated with immune response genes and HLA-DR3 and HLA-DR4
(99% have either HLA-DR3 or DR4; 53% have both; only 3% of people
without T1A DM have both; also DQB1 (genetic background of
Northern Europeans—Sardinia, Finland, Scandinavia)
• Autoimmune attack against components of beta cells of pancreas:
GAD5 (glutamic acid decarboxylase), islet cell or ICA, IA-2 (insulinomaassociated antibody), ZnT8 (zinc transporter autoantibody)— months
to years prior to diagnosis
• Present with 3 p’s + weight loss—polyuria, polydipsia, polyphagia
(symptoms occur w/ A1C greater than 9)
• Classic presentation is in a Caucasian, blue-eyed, blonde-haired kid
named…
SVEN…
• Drinkin’ too much
• Peein’ too much
Type 1A diabetes is an autoimmune disease
• What are the proposed triggers for the autoimmune response in a
genetically susceptible individual?
• The most likely culprit is one of the childhood viruses…cross reaction?
Immune response to the virus that “cross reacts and destroys” the
beta cells of the pancreas (the beta cells have similar properties to
the virus—molecular mimicry…Coxsackie B? Measles? Influenza A or
B? enteroviruses
Too little sun—vitamin D deficiency
•
•
•
•
•
Living in Scandinavia of course…BUT we also have...
Sun-phobic and sunscreen maniac moms
The overuse and abuse of sunscreen!! Slow down with the sunscreen use!
Kids playing inside (the “thumb tribe”)—get ‘em outside
Vitamin D deficiency 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
• TH1 vs. TH2 pathway…down the wrong pathway again!
• Germphobic (mysophobic) *moms
• (*irrational fear of DIRT)
• LET THEM EAT DIRT!
Too much cow’s milk…
• Well known that kids who are breast fed have a decreased risk of
developing T1DM
• Increased risk in drinking cow’s milk early in life—is there a protein in
cow’s milk that triggers diabetes in genetically susceptible
individuals?
• Finland? No cow’s milk before age 2; U.S. before age 1
• 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
• Prevalence of biopsy-proven celiac disease in T1D in pediatric
populations around the world:
• 10.4% of T1DM kids in Denmark; Sweden--9.6%, Canada--7.7%, U.S. -4.6% in U.S.
• The younger the age at diagnosis for T1DM the greater the risk for
celiac disease (Diabetes Care 2006; 29:2452-2456)
Autoimmune hypothyroidism
• Hashimoto’s thyroiditis—autoimmune hypothyroidism—15.4% of
patients had raised anti-TPO (thyroperoxidase) and 14.4% anti-TG
(thyroglobulin). Girls had more frequently raised antibodies than
boys. Sixty two patients (9.4% boys, 61% girls) required treatment
with L-thyroxine;
• For early detection of autoimmune thyroiditis in children with T1D,
measurement of anti-TPO and TSH at T1D onset and in yearly
intervals after the age of 12 years is recommended.
• Pernicious anemia– 2.6%—antibodies to intrinsic factor resulting in a
B12 deficiency (may present with peripheral neuropathy in addition
to anemia)
Digression on B12 deficiency and diabetes…
4 possible causes in patients with DM
1) pernicious anemia (autoimmune) in type 1 diabetes
2) metformin in type 2 diabetes (22%)
3) use of PPIs in either type 1 or type 2 diabetes
4) over age 55
• B12 deficiency can cause peripheral neuropathy which may be falsely
attributed to the neuropathy of diabetes (check B12 levels or the
methyl malonic acid test (MMA) and check MCV as B12 deficiency can
also result in a macrocytic anemia)
Metformin is a fabulous drug tho’…
• Don’t hesitate to prescribe it just because of the possibility of a B12
deficiency
• Just add B12 to their regimen
• Pill
• Lozenges
• Nasal gel
• Injection
• The 4 S’s
A1C and the diagnosis of diabetes
• 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 (glycated/glycosylated hemoglobin) – over 2 to 3 months
• the A1C test is a weighted average—the glucose level of the
preceding 30 days contributes more to the test result than glucose
levels 60—120 days earlier. So, clinically significant changes in glucose
can be seen in the A1C without waiting 120 days for red blood cell
turnover.
• Normal range is 4-5.6%; Diagnosis of diabetes with level greater than
6.5% (ADA, WHO)
• “Pre-diabetes”—A1C range of 5.7 -- 6.4%
A1C and glycemic control
• Perform the A1C test at 1- 2x per year in patients who are meeting
treatment goals (and have stable glycemic control) – no need to OVER
test
• Perform the A1C test quarterly in patients whose therapy has
changed or who are not meeting glycemic goals
Goals—A1C
• A management plan to achieve normal or near-normal glycemia with
specific A1C goals
• American College of Clinical Endocrinologists—≤ 6.5%
• American Diabetic Association--≤ 7%
• Why can’t we all just get along? 
• Goals should be individualized, of course; less stringent treatment
goals may be appropriate for patients with a history of severe
hypoglycemia, patients with limited life expectancies, elderly adults,
and individuals with co-morbid conditions
Notes on HbA1C levels for T1DM
• For teenagers? Tighter control for young adults (19 and over) reduces
the risk of long-term complications considerably – A1C 5-6.5
For kids?
• Kids under 6 years? <8.5% but >7.5%
• Kids 6-12 years?
< 8%
• Kids 13-19?
< 7.5% but < 7% is better if it can be achieved
without excessive hypoglycemia
• REMEMBER: the higher the A1C, the greater the complications of
diabetes (ADA 2014)
Type 2 diabetes
• However, TIGHT control in the Type 2 diabetic does NOT always lead
to the best outcomes (ADVANCE and ACCORD studies)—A1C of ~7 are
more feasible and provide better outcomes
What about the geriatric patient?
• Each patient case is individualized
• Quality of life is the biggest concern
• We usually think of long-term complications of treating diabetes, but
in the elderly there can be some significant short-term complications
The geriatric diabetic patient
• Consider co-morbidities before aggressively treating—8 years of
glycemic control is needed to reduce microvascular complications
(retinopathy, nephropathy)
• 2-3 years for benefit from BP and lipid control for reducing
macrovascular complications
The Geriatric patient
• Blood sugar -- A1C in the 8-9% range is reasonable in older patients
unable to live independently; if it’s less than 7%, geriatric patients
have a significant risk of functional decline & death (regardless of
treatment) (Yau, J Am Geri Soc 2012 July;60:1215)
The Geriatric patient
• Don’t keep the A1C is too high-- hyperglycemia can lead to polyuria,
incontinence, bed-wetting with skin excoriation, decubitus ulcers,
dehydration, weight loss, visual changes (diplopia)
• Too low? hypoglycemia can break a hip
Hypoglycemia
• Less than 70 mg/dL (3.88 mmol/L)
• Hypoglycemia—may not be able to self manage due to impaired
cognitive and motor function;
• NEVER LEAVE THE HYPOGLYCEMIC PATIENT ALONE
• IMPORTANT CAVEAT: the signs and symptoms consistent with
hypoglycemia can often be confused with intoxication or withdrawal
from drugs or alcohol.
• If the patient has S & S consistent w/ hypoglycemia, particularly
altered mental status, agitation, combativeness, and diaphoresis,
measure their finger-stick blood glucose levels immediately.
Hypoglycemia—lots of causes
1) too much insulin or oral hypoglycemic meds (except metformin—
metformin alone does not cause hypoglycemia)
2) administered insulin without eating
3) Didn’t eat enough food for the amount of insulin given; snack or
meal was delayed after giving insulin
4) Illness
5) Alcohol
6) Took insulin and then purged (teenage girls)
Medic Alert bracelet or a tattoos on the wrist
Awareness of hypoglycemia
• Awareness differs between patients and duration of diabetes
• The usual signs of hypoglycemia are the result of a surge in the
sympathetic nervous system “sensing” the low blood sugar—include
tachycardia, tremor, light-headedness, sweating
• Long-standing diabetics may have hypoglycemic “unawareness”– not
the usual SNS signs
• May describe it as tingling and numbness around lips, extremities as
feeling “heavy”
Sugar sources to have handy for
hypoglycemia
• Each of the following = 15 grams of carbohydrate for BS ranging between 51-70
mg/dl (2.83 – 3.88 mmol/L)
• 3 glucose tablets or 4 dextrose tablets
• glucose gel
• 4 ounces of fruit juice
• ½ can of Coca- cola or Pepsi (not DIET)
• 7-8 Life Savers
• 2 Tbs. raisins
• 1 Tbs. sugar or jelly
• YOU DON’T NEED 6 packs of sugar in an 8 ounce glass of orange juice!!
• NO CANDY BARS (fat inhibits the rapid absorption of sugar)
Hypoglycemia
• If the BS is ≤ 50 mg/dl (2.77 mmol/L) consume 30 grams carbohydrate
• If BG is <70 mg/dl (3.88 mmol/L) or sx of hypoglycemia—15 gm of
CHO; wait 15’ & repeat BG; give another 15 gm if still less than 70
mg/dl (3.88 mmol/L)
• I mg IM of glucagon (glucagon raises BS in 5-15 minutes) or IV D50 if
unconscious 10-25 g (ie, 20-50 mL 50% solution or 40-100 mL of 25%)
Hyperglycemia
• Is not considered an emergency unless signs and symptoms of
diabetic ketoacidosis are present—especially if alterations in
respiratory status are present (Kussmaul respirations)—rapid, deep
breathing or mental status alterations (confused, unconscious);
• Are ketones in the urine?
• However, it IS important to treat hyperglycemia immediately if
ketoacidosis is present
Hyperglycemia--causes
• Too little insulin (pump malfunction)
• Too much food
• Decreased activity
• Illness, infection
• Menses (decreased insulin sensitivity with E & P fluctuations)
• Stress
• Insulin resistance
• Some medications—ginseng, glucosamine, diuretics, niacin, steroids
Ketoacidosis (DKA) in Type 1 diabetes
• Diabetic ketoacidosis is an exaggerated, prolonged fasting state with
an absolute deficiency of insulin;
• Glucagon is working overtime—glycogenolysis (hyperglycemia);
lipolysis (increased free fatty acids); and gluconeogenesis (proteins to
sugar--hyperglycemia) PLUS…
• Increased counterregulatory activity (stress hormones)—↑ cortisol,
↑ catecholamines, ↑ growth hormone
• All contribute to hyperglycemia with osmotic diuresis, and fatty acid
release (ketones in the urine—osmotic diuresis)--ketoacidosis
Diabetic ketoacidosis (DKA)
• One in four cases of Type 1 diabetes presents with DKA (an infection
is the most common precipitating cause)
• Blood sugar > 16.7 mmol/L (300 mg/dL) (fruity breath odor)
• Significant ketosis –ketonuria
• Acidosis (pH< 7.3 or HC03 < 15)
(mild – 7.2 – 7.3; moderate 7.1 – 7.2; severe < 7.1 or less than 7.2 in
a child less than 5)
DKA – presenting complaints
• Gastroenteritis—abdominal pain; vomiting but NO diarrhea
• Dehydration (usually 7-10%)—with excessive urine output due to the
osmotic diuresis; may also have tachycardia and hypotension
• Respiratory distress—but no adventitious sounds such as coarse or
fine crackles—unless the patient has pneumonia as the precipitating
event); Kussmaul’s respirations (acidosis)(hyperventilation with slow,
deep sighing breathing)
• Confusion, decreased reflexes, coma
Treatment of DKA—it’s complicated
• Dehydration is your biggest concern initially --GIVE FLUIDS…what
kind? NS; change to ½ or ¾ depending on clinical status
• CHECK ELECTROLYTES & pH
• Add K+ if serum K+ less than 5.5 and the patient is urinating;
• Regular insulin IV (0.1 U kg/hr)
• Then what? Check electrolytes and pH (Blood gases every hour)
• Should bicarb be given? RARELY, if EVER
Type 2 diabetes—let’s review the “Ominous
Eight”
• Type 2 has 8 basic defects going on…“the Ominous Eight”
1. insulin resistance in peripheral tissues—muscle, liver, fat cells
2. pancreatic beta cell dysfunction—abnormal release of insulin in
response to a glucose load
3. Increased hepatic glucose production due to glycogenolysis—
increasing fasting blood sugars, especially overnight—contributing
to high early morning sugars (the Dawn Phenomenon)
There’s MORE.
4) accelerated lipolysis in the fat cells—high TG = small, dense LDLs—
PACKING THE ARTERIES!!
5) incretin resistance/deficiency in the small intestine—WTF are
incretins? Increased appetite—weight gain
6) hyperglucagonemia (alpha cell failure)—increasing hyperglycemia
7) increased glucose absorption by the proximal convoluted tubule of
the kidney—increasing hyperglycemia
8) insulin resistance in the brain (reducing the feeling of satiety and
contributing to dementia of the Alzheimer’s type) – weight gain,
amyloid plaque deposition
Type 2 diabetes—initial S & S
• Metabolic derangements aren’t usually as severe as Type 1
• Few symptoms initially, 2 P’s –polyuria and polydipsia due to
hyperglycemia), weight gain
• Other symptoms—fatigue (can’t use glucose), diplopia, nocturia
• Skin infections with poor wound healing with BS ≥180 mg/dL)(10
mmol/L) , neuropathy (BS ≥ 140 mg/dL)(7.77 mmol/L)
• Vaginal yeast infections; scrotal yeast infections; yeast in skin folds
• May be “silent” for a full decade in some individuals
Treatment: Lifestyle changes
• Must be a part of any intervention
• Exercise 30 minutes daily (at least 5 days a week)
Treatment: Lifestyle changes
• And, nutritional counseling with reduced calorie diet—if
weight loss is necessary (more later)
• Carb and insulin ratios if on insulin
• More on diabetes and diet later
DRUGS, DRUGS, and MORE DRUGS
• 10 classes of oral drugs + insulin…zowee!
So, the traditional therapies were based on the
first 3 core defects...
• THROW EVERYTHING YOU HAVE LEARNED ABOUT
TREATING TYPE 2 DIABETES OUT…now, now and
now...
• OLD—treatment was based on the initial 3 core
defects in diabetes...
So, the traditional therapies were based on
the first 3 core defects...
1) impaired insulin secretion secondary to beta cell dysfunction (by the
time the average patient is diagnosed with T2DM 80% of pancreatic
beta cell dysfunction is kaput)—so we traditionally STARTED with the
sulfonylureas (glyburide/Micronase/DiaBeta and glipizide/Glucotrol)
to BOOST whatever is left...but the sulfonylureas accelerate beta cell
destruction, increase the risk of CV events, cause weight gain and
hypoglycemia...OH MY...
• TIME TO TOSS THE SULFONYLUREAS into the proverbial TRASH CAN
So, the traditional therapies were based on
the first 3 core defects...
2) increased hepatic glucose production—in the past, metformin was
added if the sulfonylureas didn’t do the trick (metformin is currently
the first line oral therapy today)
3) insulin resistance in muscle—a second function of metformin
• AND WHEN ALL ELSE FAILED... patients were started on insulin...
Today? Start patient’s on a “cocktail” of
drugs…not just one.
• Effective treatment requires multiple drugs used in combination to
correct the multiple underlying defects
• Treatment should be based on the reversal of the underlying
defects, NOT just lowering the hemoglobin A1C
• Start treatment early to prevent or slow progressive beta cell failure
that is already well established in patients with impaired glucose
tolerance...
• Winters CH. A Dynamic Duo for T2DM. Nurse Practitioner Perspective.
July/August 2015.
Bottom line? Start with triple combination therapy and lifestyle
changes—an EXAMPLE
1. TZD—pioglitazone (Actos)—decreases insulin resistance in
muscle, fat, and liver cells (Core defect #1)
2. Metformin – decreases insulin resistance in muscle cells
and prevents the glycogenolysis in the liver (Core defect #1
& #3)
3. GLP-1 agonist (glucagon-like peptide – 1 agonist…one of
the “glutides” – liraglutide (Victoza) for example...boosts
incretin release from the intestine after a meal which in
turn boosts insulin release* (Core defect #5)
Something NEW…INCRETINS
• HUH? Mid 1990s the hormone incretin was found—researching for a
weight loss drug
• Incretins are responsible for approx. 60%* of the post-meal insulin
secretion, but the action of the incretins is impaired in diabetics
(*73% in normal w/o T2DM vs. 36% w/ T2DM)
• Meanwhile, back at the Gila Monster—research on satiety and weight
loss
• Gila Monsters only eat two times a year
GLP-1 agonists (Medical Letter April 2011)
GLP-1 Agonist
~A1C
~Weight loss
Decrea
se
~Cost/month
Dosing
Frequency
Abliglutide/Tanzeum
1%
2 lbs
$330
Q week
Exenatide/Byetta
1%
4 lbs
$430
Twice daily
Exenatide ER
/Bydureon
1.5%
6 lbs
$440
Q week
Dulaglutide/Trulicity
1.5%
6 lbs
$500
Q week
Liraglutide/Victoza/
Saxenda
1.5%
6 lbs
$400-$600
Q day
Speaking of incretins…The oral “gliptins”—the
DPP-4 inhibitors--2006
• Inhibit dipeptidyl peptidase, an enzyme in the intestines responsible
for breaking down incretins; incretins potentiate insulin release (Core
defect #5)
• Sitagliptin/Januvia; Saxagliptin/Onglyza; Linagliptin/Tradjenta ;
Alogliptin/Nesina
• Small reductions in HbA1C—only 0.5% (Prescriber’s Letter July 2015)
• Weight neutral – no gain, no loss
• Best used as add-on therapy with metformin
DDP-4 inhibitors used as add-ons to
metformin (Core defects #1, #3, #5)
• Janumet (sitagliptin/Januvia and metformin)
• Kombiglyze (saxagliptin/Onglyza + metformin)
• Kazano (alogliptin/Nesina + metformin)
Reduction in hemoglobin A 1 C with
• saxagliptin + metformin ~2.5% change
• Saxagliptin + placebo ~1.7%
• Metformin + placebo ~2.0%
(Saxagliptin (Onglyza) for type 2 diabetes. Med Letter Drug
Therapy, 2009:51:85)
STILL #1 for Type 2 diabetes
• Metformin decreases A1C by 1.5-2%
• Core defects #1 & #3
• And soooo much more…
Oral Drugs—the #1 choice for T2DM
• Metformin (Glucophage, Glucophage XR, Fortamet,
Glumetza, Riomet) 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 increases receptor sensitivity of insulin in various
tissues
Side effects of metformin?
• GI blues (titrate slowly; nighttime dosing/give with food, use the longacting forms of metformin to reduce GI side effects), need functioning
organs--kidneys especially (the lab will determine the eGFR (see next
slide)
Metformin and the kidney
• Newest evidence states that metformin may be safe in patients with
mild-moderate but stable chronic kidney disease (CKD) with dose
adjustments to account for reduced renal clearance (Lipska, Nye,
Pilmore) (JAMA 2014;312:2668
• If the kidney isn’t filtering adequately, metformin can be retained,
increasing the risk for lactic acidosis—rare occurrence but the risk
increases with renal insufficiency
Metformin, dose adjustments and kidney
disease
eGFR (mL/min)
Maximun daily dose
Recommended
monitoring
≥60
2550 mg
Monitor renal function
annually
45-59
2000 mg
Monitor renal function
every 3 to 6 months
30-44
1000 mg
2-4 fold risk of lactic
acidosis~10/100,000
<30
Do not use
6-7 fold risk of lactic
acidosis in this group
Metformin—what else?
• Cardiovascular benefits: lowers BP, increases HDL, lowers LDL
• Weight loss (varies among patients)
• Metformin reduces breast cancer and prostate cancer risk by ~ 54%—
Diabetes Care December 2010
• Metformin slows the aging process by slowing telomere shortening
• Boosts neurogenesis
• Metformin and PCOS
• Metformin and NASH (Hepatology Vol. 55 (6): 2012)
• B12 deficiency may occur
• Contrast dye administration and stopping metformin
Maybe we don’t even need to prescribe it!!
• Because of its high prescription rate—the U.S. alone dispensed 76.9
million metformin prescriptions in 2014—it’s not surprising that the
drug is abundant in the environment.
• Testing the waters…Metformin was present in every water sample
tested, including tap water in Germany, at concentrations exceeding
environmental safety levels proposed by an international Rhine River
Basin agency by 50 percent. When publishing the results in 2014,
Klaus Kümmerer (University of Lüneburg, Germany)and his coauthors
concluded that the drug is likely “distributed over a large fraction of
the world’s potable water sources and oceans.”
OLD Drugs…effective and cheap drugs
• Oral sulfonylureas—Glipizide (Glucotrol) usually BID
and *glyburide QD (Diabeta, Micronase, Glynase)
(*used for gestational diabetes)and glimipiride
(Amaryl; less hypoglycemia)…decrease A1C by 1.5-2%
• Core defect #1
• Increase the secretion of insulin from the pancreas and
increase receptor sensitivity; ? Promote beta cell
failure??
• Problem? Weight gain, hypoglycemia, cardiovascular
risk
Thiazolidinediones (right???)—aka TZDs
• Only one drug in this class is left…pioglitazone (Actos is the brand
name); however, pioglitazone is now available in generic form,
decreasing cost.
• Core defect #1
• Actoplus Met (Pioglitazone + metformin)
SGLT2 inhibitors (Core defect #7)
• Sodium glucose co-transporter 2 inhibitors (SGLT2); lower HbA1c by
1%; Reduce renal glucose reabsorption and increase urinary glucose
excretion with osmotic diuresis
• SGLT2 inhibitors may be used at any stage of T2DM because their
mechanism is independent of insulin.
• Used as an add on; canagliflozin (Invokana), dapagliflozin (Farxiga)
and empagliflozin (Jardiance)
• Also combining these with metformin -- SYNJARDY is a combination
of empagliflozin and metformin; INVOKAMET
(canagliflozin/metformin); XIGDUO (dapagliflozin/metformin)
SGLT2 inhibitors
• SE? modest weight loss and reduction in blood pressure, watch out
for hypovolemia/hypotension (especially elderly, patients already
taking diuretics, and anyone with a tenuous intravascular volume
status),
• Keep an eye on K+ and serum creatinine—hyperkalemia and
increased serum creatinine
• Genital yeast infections are common in patients on the SGLT2
inhibitors (1 in 19 females, 1 in 38 males)
• Increased risk of hypoglycemia with insulin (may need to reduce the
dose of insulin)
The discovery of insulin (“pancreatic extract”)
• 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, age 11, daughter of Justice
Charles Evans Hughes, traveled to Toronto to receive insulin; she
weighed 49 pounds when she arrived
• Shortly after starting insulin she weighed 60 pounds
• She lived another 60 years—By the time she died in 1981, at age 74,
she had received 42,000 insulin shots
Insulin
• Prior to the discovery of insulin, diabetic children rarely survived
more than 3 years
• The first child to use insulin in the U.S. was the son of an executive for
Eastman Kodak—his insulin was smuggled across the Canadian/U.S.
border
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 Indianapolis.
• By 1932 insulin’s price had fallen by 90 percent
Insulin
• Insulin is the number one choice for type 1 diabetes
due to the absolute deficiency of this hormone when
diagnosed
• However, the pancreas will eventually give out in
patients with T2DM and the oral agents will no longer
work
• OR, it’s not unusual to start a long-acting insulin +
metformin in patients with T2DM--If the blood sugars
are mild to moderately high “around the clock,” the
addition of a daily basal insulin is indicated
Insulins
• Rapid-acting insulins include aspart (Novolog), glulisine (Apidra),
lyspro (Humalog) (10-15 minutes)—can also be used with the meal or
immediately afterwards—make sure there is access to food without
delay
• Regular insulin—Novolin R and Humulin –R (30-45 minutes)—the
cheapest of the insulins that work within 60 minutes; used in the
pump and in patients w/ DKA
Insulins
• Intermediate acting insulin (1935)—neutral
protamine Hagedorn (NPH)—Humulin N, Novolin N
(2-4 hours)(PEAK 6-10)
• Long-acting insulins include detemir (Levemir)(16-24
hours) , glargine (Lantus/Basaglar/Toujeo – 300 u/ml)
(24 hours)—steady state background insulin
• Ultra long-acting—insulin degludec (Tresiba) up to 42
hours
Starting a patient on insulin
• Blood sugar diary—blood sugar readings at different times of the
day—fasting, before meals, two-hour postprandial, bedtime, upon
awakening—to isolate when non-goal blood sugars are occurring
• A common starting dose for insulin therapy in patients with type 2
diabetes is 0.15 units/kg body wt/day; however, because > 90% of
patients with type 2 diabetes are insulin resistant, significantly higher
doses are often required to achieve glycemic targets
• 0.5-1 u/kg/day for type 1 to start (may be lower)
• Are they having trouble with the early morning rise in glucose, the
“dawn” phenomenon?
NPH continues to have some usefulness, and,
it’s CHEAP
• Used to cover the DAWN phenomenon in patients – either type 1 or
type 2; some type 2 patients have normal BS all day with oral agents,
but their early morning rise isn’t controlled; NPH at 10 – 11 p.m. to
maximize its glucose-lowering effects in the dawn hours (~3 to 8 a.m.)
when there is a natural increase in the “counter-regulatory”
hormones—cortisol, GH, epinephrine—to get your tired old derriere
outta bed)
NPH continues to have some usefulness, and,
it’s CHEAP
• Don’t use it too early (6 p.m.) as this will increase
the risk for nocturnal hypoglycemia (Somogyi effect
with rebound hyperglycemia at 3 a.m. in the
morning);
• S & S of nocturnal hypoglycemia--waking with a
headache; nightmares; feeling unusually tired upon
awakening; waking with damp bed clothes and
sheets from sweating; having a clammy neck can be
a particular indication of night time hypoglycemia.
• “Wake up dead” syndrome aka “dead in bed” w/
hypoglycemia causing cardiac arrhythmias
(prolonged QT interval
Daily basal/background insulins
• LANTUS (insulin glargine) or LEVEMIR (insulin
detemir)—long-acting basal insulins; they don’t have a
peak; provide constant levels over 24 hours; (0.1-0.2
u/kg/day)
• 2015—insulin degludec – ultra-long acting insulin—up
to 40 hours
Daily basal/background insulins
• How do you switch from NPH to Lantus? Easy; if you
are only on 1 dose of NPH, that’s the dose of Lantus; 2
doses of NPH? Add together, subtract 20%--that’s the
dose of Lantus
• 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; Both decrease nocturnal
hypoglycemia; less wt gain with Detemir (but you
might need 2 doses)
Basal-Bolus Insulin
• Basal /background insulin
• Bolus to cover carbohydrate intake or to correct high blood sugars
• MUCH BETTER CONTROL of blood sugars?
• Need to fine tune and add meal-time bolus
• Insulin-to-carbohydrate ratio is usually 1 unit of rapid acting insulin
to 10 grams of carbohydrates—60 gram CHO meal? Need 6 units of
rapid acting insulin
• To correct high blood sugars? 1 unit of rapid acting will drop the blood
sugar by 50 mg/dl (range 30-100)—lower end of the range for type 2
and mid- to high- range for type 1
Before we get to the complications
of diabetes
• First of all, not all complications are inevitable
• Better control, and a better understanding of the
disease process decreases “inevitable” complications
• The death rate from diabetes has been DECREASING
even though the numbers of patients are increasing
• SO, somebody out there is listening!!! YEAH
• Since we KNOW what the complications can be, let’s
start working on prevention as soon as the disease is
diagnosed
Long-term complications—
some new GOOD news:
• The number of people with Type 1 diabetes developing
proliferative retinopathy decreased by 77% between 1980 and
2007. (Ophthalmology October 31, 2009)
• Kidney disease in diabetes dropped 21% from 2000-2007.
(National Chronic Disease Fact Sheet, 2010)
• The portion of adults with one or more heart disease risk factors
decreased from 58% in 1999-2000 to 47% in 2009-2010. (NCHS
Data Brief, August 2012)
• The number of diabetes-related non-traumatic lower-extremity
amputations dropped from 83,153 in 1996 to 70,139 in 2008.
(Diabetes Care, February 2012)
Some BAD news…
• Adolescents and young adults who develop TYPE 2 DIABETES
between the ages of 15 and 30 have worse complications that those
who experience disease onset between ages 40 and 50
• After 11 years of T2DM, patients dx’d between 15 and 30 had more
severe proteinuria and neuropathy scores
• Patients between 15 and 30 were less likely to be treated with a statin
or antihypertensive agent despite having more obesity, higher TG and
higher total cholesterol levels than the over 40 group
• Age of death? 15 years earlier than the over 40 group (Al-Sayeed AH)
Cardiovascular disease—accelerated
atherosclerosis
• Coronary artery disease, cerebrovascular disease, peripheral vascular
disease—diffuse disease; triple vessel CAD—CABG and stents are
common in diabetics (silent ischemia)
• 10x greater risk of CHF in females with diabetes and a 6x greater risk
of CHF in males with diabetes
• Diabetes is the number #1 cause of heart failure in the U.S. today!!
• Risk of stroke is 2.5-4x greater in diabetics
Peripheral Arterial Disease (PAD)
• Absence of both dorsal pedal pulses
• Presence of any limb bruit
• Presence of wounds or sores on the feet
• Absence of the femoral pulse
• Presence of asymmetric coolness of the foot
• McGee S. Evidence-Based Physical Diagnosis. WB Saunders, Co. 2012
What did I learn in Nursing school (1972)?
• Major findings for PAD were:
• Shiny atrophic skin
• hairless lower limbs
• prolonged capillary refill time ≥ 5 seconds
• WORTHLESS!!
Peripheral arterial disease (PAD)
• Approximately 25 percent of patients with diabetes will
develop a foot ulcer.
• Risk of amputation is 15-40 x higher in the diabetic
• A diabetic foot ulcer precedes amputation 85% of the time
• FOOT CARE!! (2 p.m. sense of smell)
• Stop smoking
Wound care: What do they do with all of that
circumcised foreskin?
• Apligraf—cells from circumcised foreskin
• And the WOCN’s have all sorts of tricks and other goodies in their bag
of goodies
• Regranex (PDGF)—platelet derived growth factor
• Medi-honey…
• New drug from CUBA!! Cures foot ulcers 80% of the time; HeberprotP contains EGF (epidermal growth factor) for grades 3, 4, 5 of
Wagner’s Classification with average ulcer size of greater than 20 cm
• Stabilize the extremity
Are they on a “Statin” to prevent cardiovascular complications?
• If not, why
not? REMEMBER…All diabetics ages 40-75 should
automatically started on a STATIN drug regardless of their LDLs
• Statins are anti-inflammatory, anti-lipid, decrease plaque formation,
stabilize plaques and prevent plaque rupture
• Statins may also slow the progression of chronic renal disease (Fried)
• Statins reduce the risk of a first MI, a second MI, and ischemic strokes
• And DON’T forget Aspirin! And clopidogrel (Plavix)
Who are the statins? What are their LDL-lowering
effects?—dose-dependent
High intensity statins: > 50% reduction
• Atorvastatin/Lipitor 40-80 mg
• Rosuvastatin/Crestor 20-40 mg
Moderate intensity statins: 30-40% reduction
• Pitavastatin/Livalo 2 – 4 mg
• Rosuvastatin/Crestor 5 – 10 mg
• Simvastatin/Zocor 10 – 20 mg
• Pravastatin/Pravachol 40 – 80 mg
• Lovastatin 40 mg
• Fluvastatin 80 mg
(Circulation 2004;110:227-239; Prescriber’s Letter January 2014))
Statin focus
• No longer looking at LDL “goals” as this approach was not based
on evidence
• No need to do fasting lipid levels
• FOCUS is now on % reduction to improve CV outcomes. CV
disease present? Use high-intensity statins for younger patients;
moderate-intensity statins for over 75 y.o.
• High-intensity statins if LDL is ≥ 190 mg/dL (10.55 mmol/L)
• All diabetics over 40
• Recheck LDL after 4-12 weeks; then annually
• Lower dose w/ muscle pain (BUT first find out what might be
causing that muscle pain—it’s not ALWAYS the statin)
Digression: what else causes muscle aches
and pains?
• Exercise
• Vitamin D deficiency
• Thyroid dysfunction – hypo- and hyper—check the TSH
• Osteoarthritis
• ED drugs (especially tadalfil/Cialis)
Statin drugs and LDL particle size
• LDLs come in two sizes—small and dense (damage the arterial walls
and pack with fat plaque) and large and loose (too big to pack the
arteries)
• Even if the LDL level is normal, the diabetic tends to have LDLs that
are 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)!
LDL-particle size measurement
• 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 for determining
particle size, 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)(0.46 mortality rate per 1 billion
prescriptions from rhabdomyolysis)
• About 1/20 patients experiences muscle pain or weakness
• Reduce the dose, don’t stop the drug
• Change to rosuvastastin (Crestor)? Give the statin every other day?
• Check the creatine kinase (CK) if muscle aches and pains are severe
Do the statin drugs increase the risk of type 2
diabetes? Yes, but…
• …the statins’ proven power to prevent heart attacks and strokes
outweighs ANY potential increase in type 2 diabetes risk especially in
high-risk patients
• Study of postmenopausal women—6.4% not taking statins developed
type 2 DM vs. 9.9% among statin users (over an 8 year period)
• In another study 2.4% using statins developed diabetes vs. 2.1%
among control group
• Manson J. Harvard Medical School, 1/10/12; Wang K-L et al. J Am Coll Cardio
2012 Aug 2)
If the statins increase the risk slightly, eat
walnuts to reduce that risk!
• Walnuts may protect women from getting diabetes (Journal of
Nutrition, April 2013)
• Walnuts are uniquely high in omega-3’s and omega-6 fatty acids—
which may be protective
• Study of 138,000 women
• Women who consumed 8 ounces or more a month of walnuts
reduced their risk of diabetes by 24%
• (DISCLOSURE: This study was partially funded by the California
Walnut Commission in conjunction with NIH)
Are they on aspirin and/or clopidogrel (Plavix) or
pasugrel (Effient)?
• 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
CONTROVERSIAL!
• Plavix/Effient after a coronary event or cerebral event
• Plavix/Effient with a stent
• Diabetes Care , June 2010
Hypertension and the diabetic
• Keep the BP below 140/80 in diabetics (any lower doesn’t improve
outcomes)(Diabetes Care January 2013)
• However, the 2012 guidelines say keep the BP below 130/80
• NEW revised BLOOD PRESSURE guidelines—raised ceiling for systolic
BP to 140 mm Hg; Studies showed that intensive blood pressure
control—less than 130 mm/Hg did not decrease deaths or heart
attacks in diabetics, and only lowered the risk of stroke a little itsy bit,
when compared to less-intensive control (Diabetes Care, January
2013)
Choose a Pril OR an ARBs
•
•
•
•
•
•
•
•
•
Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moxepril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
• *Do not use together
•
•
•
•
•
•
•
•
losartan—Cozaar
valsartan—Diovan
candesartan—Atacand
irbesartan—Avapro
telmisartan—Micardis
olmesartan—Benicar
Eprosartan—Tevetan
Azilsartan--Edarbi
What should the 2nd anti-hypertensive drug be if
needed?
• Calcium Channel blockers—verapamil or diltiazem for renoprotection
• Thiazide diuretic? (may increase BS but isn’t a deal breaker)
• Beta-blocker but only if they have tachycardia, angina or previous MI
Diabetic nephropathy
• Approximately 3% of newly diagnosed patients with type 2 diabetes
have overt nephropathy
• In patients with type 1 diabetes, the development of nephropathy
usually begins after 5 years of diabetes duration, with an increasing
incidence of nephropathy over the next decade of duration to a peak
at about 15 to 17 years of having had diabetes
The GOOD news…
• Patients who have no proteinuria very low risk of
developing overt renal disease of approximately 1%
per year
The Bad News…
• Kids diagnosed with TYPE 2 diabetes have a 4-fold increase in the risk
of renal failure vs. kids with TYPE 1 diabetes
• Kids with TYPE 2 diabetes have a 23-fold increase of renal failure and
a 39-fold risk of dialysis compared to kids without diabetes
• Dart A. Diabetes Care, June 2012;35(6):1265-1271
Diabetic nephropathy…PREVENTION!!
• Treat high blood pressure! PRIL or ARB
• Use a statin drug
• 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!
Barb’s artwork: 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**
Quick note about PRILS…and ARBs
• Do not use during pregnancy
• May increase potassium levels, especially if used with spironolactone
in heart failure patients
• *UTI? Don’t use TMP-SMX (Septra/Bactrim)
• The combination of the above 3 can cause life-threatening
hyperkalemia
• Cough with prils
• Angioedema with Prils—”does my voice sound funny to you?”
Diabetic peripheral neuropathy— “Now where did I put
that sewing needle?”
Diabetic peripheral neuropathy (DPN)—we’re back
to FOOT CARE
• Monofilament screening for sensory loss at every office visit
• Different forms—can be mononeuropathies or
polyneuropathy
• Distal symmetric polyneuropathy is most common--longest
nerves to feet are involved first
Diabetic peripheral neuropathy (DPN)—we’re back
to FOOT CARE
• Small fiber loss (small, thinly myelinated fibers—Atype delta fibers, and C-type fibers) resulting in the
loss of pain and temperature sensation abnormalities
• Large fiber loss (A-type, alpha and beta fibers)—loss
of vibration (detected with a 128-Hz tuning fork—
early indicator of neuropathy), touch and
proprioception
• Stocking-glove distribution
Diabetic peripheral neuropathy
• Positive symptoms—tingling (my foot is always “asleep”,
pins and needles, burning (walking on hot coals),
stabbing (walking on shards of glass); hyperalgesia,
allodynia (nonpainful stimulus is painful—sheets, socks
can be excruciatingly painful)
• Complete analgesia is a blessing sometimes…
• Motor symptoms—weakness, loss of distal reflexes occur
later in disease process (severe weakness is rare and
suggests a non-diabetic cause as does rapid progression)
Treatment of DPN
• Topical capsaicin—8% patch for 30-60 minutes after a local
anesthetic)
• anticonvulsants (pregabalin/Lyrica) or (gabapentin/Neurontin) –
Lyrica has a more rapid onset than Neurontin; doesn’t require as
much of a dose adjustment as Neurontin; topiramate (Topamax)—
reduces intensity of the pain; causes weight loss, increases density of
nerve fibers
Treatment of DPN
• antidepressants including:
• Nortriptyline (Pamelor, Aventyl) and desipramine (Norpramin) ;
amitriptyline (Elavil) and imipramine (Tofranil)has fallen out of favor
due to side effects)
• SNRI such as venlafaxine (Effexor) and duloxetine/Cymbalta/Yentreve,
• Opiods as necessary—choose your patients carefully, of course; can
also try tramadol (Ultram)
Cardiac autonomic neuropathy
• Resting tachycardia is an important sign of the LOSS of vagal input—if you
lose the vagus you don’t have the capacity to feel chest pain, causing…
• Silent ischemia damages the cardiac muscle resulting in congestive heart
failure
• Need a beta-blocker—metoprolol succinate (long acting, Toprol
XL)(especially useful w/ CHF)
• metoprolol tartrate (shorter acting, Lopressor)(only prescribed for
hypertension or tachycardia)
• Bisoprolol(Monocor/Zebeta)
• carvedilol (Coreg) for diabetics with CHF; nebivolol (Bystolic) also boosts
nitric oxide and lowers SVR)
GI autonomic neuropathy
• Gastroparesis (5-12%)—disorder of the GI tract that causes a
disruption in the motility of gastric contents through the gut—a delay
in gastric emptying
• Results in wide swings in blood sugar with slowed digestion and ,
early satiety, chronic nausea & vomiting of food digested hours
before—miserable
• interferes with the timing of insulin*
GI autonomic neuropathy
• Six small meals per day —eggs, cheese, lean meats; NO high-fat or high
fiber (fruits and veggies)—can cause a bezoar if the bowels are not moving!
Liquid supplements can help
• Metoclopramide (Reglan), cisapride (special use)
• Erythromycin oral (250 mg/ 5 mL QID) – loses efficacy after 3-4 weeks; or
IV (in-hospital for symptom exacerbation)
• Anti-emetics such as the “setrons”—(ondansetron/Zofran,
granisetron/Kytril, dolasetron)/Aloxi
• Gastric pacer (GES—gastric electrical stimulation)
Fogle CJ. Diabetic Gastroparesis. ADVANCE for NPs & PAs. November 2013)
GU autonomic neuropathy
• Impaired bladder emptying with hydroureter,
hydronephrosis, chronic infection
• Urecholine, DuVoid
Erectile dysfunction
• Atherosclerosis and neuropathy are the 2 major causes
• ED is an accurate indicator of CVD
• The Pfizer riser (sildenafil) (and relatives—vardenafil/Levitra and
tadalafil/Cialis) are effective treatments in 50% of the cases—improve
blood flow only
• The “afils” do NOTHING for neuropathy
• Injections, implants, and suction devices
• VED not TED
Diabetic Retinopathy—number 1 cause of
blindness in U.S.
• SEE the EYE GUY once a year!
• Reducing HbA1c by 1 percentage point lowers the risk of developing
diabetic eye, nerve, and kidney diseases by 40%
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)
In addition to starving, what are the other
diets discussed today?
• Exchange diet
• Counting carbs diet
• Glycemic index diet
• Mediterranean diet
• The ALL YOU CAN EAT diet
The Cardiologist’s diet?
• “If it tastes good, spit it out!”
Say no to the Old Country Buffet Diet
What about the Atkin’s diet to lose weight?
NOOOOOOOO
• The Atkin’s diet is PRO-inflammatory
• Animal protein, animal protein, and more animal protein…
• Saturated and trans fats
• Increases intraglomerular hypertension
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)
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
• DASH diet (Dietary Approaches to Stopping Hypertension)—low sodium,
increased K+ (but NOT if on PRILs, ARBs, spironolactone), increased calciumcontaining foods
• MEDITERRANEAN diet—omega-3s, little or NO red meat, olive oil, fruits,
vegetables, nuts
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…
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 9-pound 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 is not an option.
And lastly…TREAT the DEPRESSION!
• Pick a pill any pill
• Happy patients are compliant patients
• SSRIs improve self-esteem
• Diabetes is not an easy diseases—it’s a
24/7 job
Thank you.
• Barb Bancroft, RN, MSN, PNP
• www.barbbancroft.com
• [email protected]
Bibliography
• Antonetti DA. Diabetic Retinopathy. N Engl J Med 2012 March
29;366;13:1227-39.
• 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;59:2609.
Bibliography
• Feudtner C. Bittersweet: Diabetes, Insulin, and the Transformation of
Illness. (Chapel Hill: The University of North Carolina Press, 2003)
• 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
• Inzucchi SE. Diagnosis of Diabetes. N Engl J Med 2012 Aug
9;367;6:542-550.
• Migrone G, et al. Bariatric surgery vs. intensive medical therapy in
obese patients with diabetes. N Engl J Med 2012; 366:1577-85.
Bibliography
• 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.
• 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.
Bibliography
• Schauer PR, et a. Bariatric Surgery vs. Intensive Medical Therapy in
Obese Patients with Diabetes. N Engl J Med 2012 April
26;366:17:1567-1576.
• Shah AA, Durso SC. Applying clinical practice guidelines in caring for
older adults with diabetes. Patient Care 2007 (February): 18-25.
Bibliography
• 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):1820.
• 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
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Clin Endoc and Metabol (2002); 87(3):978-82.
Bibliography
• Vasconcelos A. Could surgery spell the end of diabetes? New Scientist, Sept 2007
• Vinik AI. Diabetic Sensory and Motor Neuropathy. N Engl J Med April 14 2016;
374(15):1455-1463
• Winters CH. A Dynamic Duo for T2DM. Nurse Practitioner Perspective.
July/August 2015.
• Zimmet P, Alberti KG. Surgery or Medical Therappy for Obese Patients with Type 2
Diabetes? Editorial . N Engl J Med 2012 April 26 ; 366;17:1635
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.
• Reducing HbA1c by 1 percentage point lowers the risk of developing
diabetic eye, nerve, and kidney diseases by 40%
Hypoglycemic syndromes
Mild
Moderate
Severe
Hunger
Shakiness
Weakness
Paleness
Anxiety
Irritability
Dizziness
Sweating
Drowsiness
Personality change
Inability to concentrate
Headache
Behavior changes
Poor coordination
Blurry vision
Slurred speech
Confusion
Loss of consciousness
Seizure
Inability to swallow
Symptoms of hyperglycemia
Mild
Moderate
Severe
Thirst
Frequent urination
Fatigue/sleepiness
Increased hunger
Blurred vision
Weight loss
Stomach pains
Flushing of skin
Lack of concentration
Sweet, fruity breath
Headache
Mild symptoms, plus:
Dry mouth
Nausea
Stomach cramps
Vomiting
Dizziness
Dehydration
Mild + moderate
symptoms, plus:
Labored breathing
Very weak
Confused
Unconscious