TYPE 2 DIABETES MELLITUS Cynthia Brown, MN, ANP, CDE

TYPE 2 DIABETES MELLITUS

Cynthia Brown, MN, ANP, CDE

Type 2 Diabetes Mellitus

Epidemiology: 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


Epidemiology: Leading cause of ESRD, blindness,

amputation, & impotence Heart disease & stroke 2-4 times more

common 90-95% of persons with diabetes have

Type 2


Populations at risk: Those older than 30 Some children now diagnosed African Americans Native Americans Hispanics Asians Pacific Islanders


Populations at risk: 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


Diagnosing: 1979: original WHO criteria-

FBS >140 2 hour >200

1997: ADA Type 1 Type 2 Eliminated all other references to age,

insulin usage


Diagnosing: 1998: ADA

Lowered FBS to 126 Based on association between glucose

levels & development of retinopathy 2011: ADA accepted A1c >6.5% as

diagnostic; <6.5% does not exclude diagnosis


Today’s testing methods: Fasting plasma glucose 1-2 hour post meal can be used; if

>140, further testing indicated FPG <100mg/dl=normal FPG >100 & <126 = IFG & pre-diabetes FPG >126=diabetes


Oral glucose tolerance test still the gold standard 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


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


When to screen: 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


Metabolic Defects: Cellular resistance to effect of insulin Failing beta cells Loss of first phase response Decreased secretion of amylin Decreased secretion of incretins


Each metabolic defect causes a different problem 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


Chronic disease syndrome associated with insulin resistance: Metabolic Syndrome Dysmetabolic Syndrome Syndrome X


Syndrome features: Central or visceral obesity Dyslipidemia Atherosclerosis Endothelial dysfunction Decreased fibrinolytic activity=pro-

thrombotic Hypertension Acanthosis


Syndrome Features: PCOS Hyperuricemia Pre-diabetes


Inherited defect in insulin action Abnormal insulin signaling Abnormal glucose transport Abnormal glycogen synthesis Abnormal mitochondrial oxidation

Hyperinsulinemia by downregulation of insulin receptor numbers & post-receptor events


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


Impaired glucose tolerance & overt diabetes develop when beta cells fail

Cause of “pancreatic exhaustion” unknown

When FBS 115, first phase insulin secretion lost


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


Insulin resistance: Start with insulin sensitizers-

Metformin (biguanide) Actos (TZD) Both re-sensitize person to own insulin Very different mechanisms Work at liver, muscle, islet cell


Pancreatic stimulators: Glipizide, glyburide, glimepiride

(sulfonylureas) Prandin, Starlix (secretagogues) Rapid acting beta cell stimulators Interact with ATP-dependent potassium

channels of beta cells Glucose dependent action


Januvia, Onglyza, Tradjenta (DPP-4 inhibitors) Slows inactivation of incretin hormones Concentrations of GLP-1 & GIP increase Enhances insulin release in glucose-

dependent manner Suppress hepatic glucose production Lowers post-meal glucose levels


Byetta, Victoza (incretin mimetics) 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


Precose, Glyset (alpha glucosidase inhibitors) Act locally in intestine Slows digestion of carbohydrates Delays absorption of glucose GI side effects


Insulins: Basal: Lantus, Levemir, NPH Bolus: Humalog, Novolog, Apidra,

Regular Given in patterns to mimic mother

nature


Thank you very much for your attention!

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TYPE 2 DIABETES MELLITUS Cynthia Brown, MN, ANP, CDE