TYPE 2 DIABETES MELLITUS
Cynthia Brown, MN, ANP, CDE
Type 2 Diabetes Mellitus
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Epidemiology:
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25 million Americans or 8.3%
7 million undiagnosed
1.9 million older than 20 diagnosed in
2010
7th leading cause of death
In 2007, cost of treating $174 billion
1.5 million >20 diagnosed per year
Type 2 Diabetes Mellitus
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Epidemiology:
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Leading cause of ESRD, blindness,
amputation, & impotence
Heart disease & stroke 2-4 times more
common
90-95% of persons with diabetes have
Type 2
Type 2 Diabetes Mellitus
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Populations at risk:
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Those older than 30
Some children now diagnosed
African Americans
Native Americans
Hispanics
Asians
Pacific Islanders
Type 2 Diabetes Mellitus
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Populations at risk:
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Family history in 1st or 2nd degree
relative
Hx gestational diabetes or baby >9 lbs
Signs of insulin resistance
Hx pre-diabetes
Hx vascular disease
Physical inactivity
Type 2 Diabetes Mellitus
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Diagnosing:
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1979: original WHO criteriaFBS >140
 2 hour >200
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1997: ADA
Type 1
 Type 2
 Eliminated all other references to age,
insulin usage
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Type 2 Diabetes Mellitus
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Diagnosing:
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1998: ADA
Lowered FBS to 126
 Based on association between glucose
levels & development of retinopathy
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2011: ADA accepted A1c >6.5% as
diagnostic; <6.5% does not exclude
diagnosis
Type 2 Diabetes Mellitus
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Today’s testing methods:
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Fasting plasma glucose
1-2 hour post meal can be used; if
>140, further testing indicated
FPG <100mg/dl=normal
FPG >100 & <126 = IFG & prediabetes
FPG >126=diabetes
Type 2 Diabetes Mellitus
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Oral glucose tolerance test still the
gold standard
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150 grams carb for 3 days prior
10-14 hour fast
75 gram glucose load
No activity during test
Do not perform in the ill, malnourished
Type 2 Diabetes Mellitus
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Impaired Glucose Tolerance (IGT)
Impaired Fasting Glucose (IFG)
Glucose higher than normal, but not
diagnostic of diabetes
IGT: random or 2-hour glucose
>140 but <200
IFG: FPG >100 but <126
Type 2 Diabetes Mellitus
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When to screen:
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Start at age 45; every 3 years if
normal
Start younger if overweight or risk
factors present
Anytime fasting blood sugar not normal
Easiest is a fingerstick
Must note time of last food
Type 2 Diabetes Mellitus
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Metabolic Defects:
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Cellular resistance to effect of insulin
Failing beta cells
Loss of first phase response
Decreased secretion of amylin
Decreased secretion of incretins
Type 2 Diabetes Mellitus
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Each metabolic defect causes a
different problem
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Cellular resistance causes high
circulating insulin levels
Leads to fatigue and weight gain
Low amylin-rapid emptying of stomach
Low incretins-no sense of fullness
Also problems with insulin secretion
Type 2 Diabetes Mellitus
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Chronic disease syndrome
associated with insulin resistance:
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Metabolic Syndrome
Dysmetabolic Syndrome
Syndrome X
Type 2 Diabetes Mellitus
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Syndrome features:
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Central or visceral obesity
Dyslipidemia
Atherosclerosis
Endothelial dysfunction
Decreased fibrinolytic activity=prothrombotic
Hypertension
Acanthosis
Type 2 Diabetes Mellitus
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Syndrome Features:
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PCOS
Hyperuricemia
Pre-diabetes
Type 2 Diabetes Mellitus
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Inherited defect in insulin action
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Abnormal
Abnormal
Abnormal
Abnormal
insulin signaling
glucose transport
glycogen synthesis
mitochondrial oxidation
Hyperinsulinemia by downregulation
of insulin receptor numbers & postreceptor events
Type 2 Diabetes Mellitus
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Enhanced lipolysis with elevation of
free fatty acids aggravates insulin
resistance
Impairs glucose uptake at muscle
Enhances hepatic glucose
production
Islet cell impaired in release of
insulin
Type 2 Diabetes Mellitus
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Impaired glucose tolerance & overt
diabetes develop when beta cells
fail
Cause of “pancreatic exhaustion”
unknown
When FBS 115, first phase insulin
secretion lost
Type 2 Diabetes Mellitus
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When FBS 180, all phases of insulin
secretion markedly impaired.
Gastric emptying accelerated
Post prandial hyperglycemia
Defects in appetite control & satiety
All treatments aimed at these
metabolic defects
Type 2 Diabetes Mellitus
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Insulin resistance:
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Start with insulin sensitizersMetformin (biguanide)
 Actos (TZD)
 Both re-sensitize person to own insulin
 Very different mechanisms
 Work at liver, muscle, islet cell
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Type 2 Diabetes Mellitus
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Pancreatic stimulators:
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Glipizide, glyburide, glimepiride
(sulfonylureas)
Prandin, Starlix (secretagogues)
Rapid acting beta cell stimulators
Interact with ATP-dependent potassium
channels of beta cells
Glucose dependent action
Type 2 Diabetes Mellitus
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Januvia, Onglyza, Tradjenta (DPP-4
inhibitors)
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Slows inactivation of incretin hormones
Concentrations of GLP-1 & GIP increase
Enhances insulin release in glucosedependent manner
Suppress hepatic glucose production
Lowers post-meal glucose levels
Type 2 Diabetes Mellitus
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Byetta, Victoza (incretin mimetics)
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Glucoregulatory effects similar to
glucogon-like peptide-1 (GLP-1)
Secreted by gut in response to food
Very short half-life
Restore first-phase insulin response
Suppress post-meal glucagon
Slows gastric emptying
Type 2 Diabetes Mellitus
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Precose, Glyset (alpha glucosidase
inhibitors)
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Act locally in intestine
Slows digestion of carbohydrates
Delays absorption of glucose
GI side effects
Type 2 Diabetes Mellitus
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Insulins:
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Basal: Lantus, Levemir, NPH
Bolus: Humalog, Novolog, Apidra,
Regular
Given in patterns to mimic mother
nature
Type 2 Diabetes Mellitus
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Thank you very much for your
attention!
Questions?