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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

Diagnosing: 1979: original WHO criteria-

FBS >140 2 hour >200

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

insulin usage

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

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

Type 2 Diabetes Mellitus

Metabolic Defects: 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

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

thrombotic Hypertension Acanthosis

Type 2 Diabetes Mellitus

Syndrome Features: PCOS Hyperuricemia Pre-diabetes

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

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

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

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Type 2 Diabetes Mellitus

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

Regular Given in patterns to mimic mother

nature

Type 2 Diabetes Mellitus

Thank you very much for your attention!

Questions?