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Type 2 Diabetes Mellitus

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... disease begins with development of key metabolic abnormality, insulin resistance. ... Metabolic abnormality that triggers the onset of type 2 DM ... – PowerPoint PPT presentation

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Title: Type 2 Diabetes Mellitus


1
Type 2 Diabetes Mellitus
  • Aetiology, Pathogenesis, History, and Treatment

2
The Diabetes Mellitus epidemic
  • Estimated 180 million people in the world have
    DM. Thats roughly 6 of the world population.
  • These numbers are estimated to double by 2030.
  • Healthcare costs approaching 92 billion a year
    for the U.S.

3
What is Diabetes Mellitus?
  • A metabolic disorder that results when the body
    is unable to maintain adequate insulin secretion
    to prevent hyperglycemia.
  • Disease classification
  • Type 1 or Type 2
  • 90 of DM cases are Type 2

4
Type 2 DM
  • Inception of disease begins with development of
    key metabolic abnormality, insulin resistance.
  • Integral to understanding of type 2 DM is the
    role of insulin/glucose in the metabolic system.

5
Insulin
  • A polypeptide hormone secreted by the islet of
    Langerhans in ß-cells of the pancreas.
  • First isolated in 1921 by Canadian researchers
    Banting Best
  • Essential in homeostatic regulation of blood
    glucose

6
Insulins function
  • Standard metaphor (Lock Key)
  • Insulin (the key) must be bound to target cell
    (the lock) in order for glucose to enter the
    target cell from the bloodstream.
  • Homeostatic function
  • Signals muscle/adipose tissues and liver to
    absorb glucose and utilize it. When energy
    requirements are met, insulin in the bloodstream
    triggers the liver to absorb glucose and convert
    it into energy saving form glycogen.

7
Insulin Resistance
  • Metabolic abnormality that triggers the onset of
    type 2 DM
  • Normal amount of insulin becomes inadequate for
    proper absorption of blood glucose
  • The bodys energy absorption system becomes
    inept
  • Hypothesized triggers of IR
  • 1 in 10 people have genetic code for IR.
  • Obesity, Aging, Genetics, Diet high in
    sucrose/HFCS

8
Ensuing Hyperglycemia
  • Symptoms
  • Frequent urination
  • (polyuria)
  • Frequent thirst
  • (polydipsia)
  • Excessive hunger
  • (polyphagia)
  • Complications
  • Vascular problems
  • (neuropathy, nephropathy, retinopathy)
  • Cardiovascular disease
  • Wound infection

9
Type 2 DM Diagnosis
  • Fasting blood glucose level - diabetes is
    diagnosed if higher than 126 mg/dL on two
    occasions.
  • Random (non-fasting) blood glucose level -
    diabetes is suspected if higher than 200 mg/dL
    and accompanied by the classic symptoms of
    increased thirst, urination, and fatigue.
  • Oral glucose tolerance test - diabetes is
    diagnosed if glucose level is higher than 200
    mg/dL after 2 hours.

10
Treatment of type 2 DM
  • First goal is to eliminate symptoms and stabilize
    blood glucose levels.
  • If diet/exercise fail, then oral medications are
    used
  • Treatments include
  • agents which increase the amount of insulin
    secreted by the pancreas
  • agents which increase the sensitivity of target
    organs to insulin
  • agents which decrease the rate at which glucose
    is absorbed from the gastrointestinal tract.

11
Oral Medications Overview
  • Sulfonylureas
  • Meglitinides
  • Biguanides
  • Thiazolidinediones
  • a-Glucosidase inhibitors
  • Dipeptidyl peptidase-
  • 4 inhibitors

12
Sulfonylureas
  • Stimulates insulin secretion by ß cells.
  • Binds and closes K channels on ß cells causing
    influx of Ca2 which triggers the release of
    insulin.
  • Not glucose dependent.
  • Cause insulin release regardless of glucose
    level
  • 1st generation
  • Acetohexamide
  • Chlorpropamide
  • Tolbutamide
  • Tolazamide
  • 2nd generation
  • Glipizide
  • Gliclazide
  • Glyburide
  • Glimepiride

13
Meglitinides
  • Also stimulates insulin secretion by ß cells
  • Similar mechanism of action to Sulfonylureas.
    Attaches to K channel at a different binding
    site
  • Insulin efflux is glucose dependent. High glucose
    levels are needed for optimal action.
  • Repaglinide
  • Nateglinide

14
Biguanides
  • Improves insulins ability to move glucose into
    cells (particulary in muscle tissue)
  • Exact mechanism of action is not fully elucidated
  • First-line medication used for treatment of type
    2 DM
  • Metformin

15
Thiazolidinediones
  • Improves insulin sensitivity (adipose tissue)
  • Bind to steroid hormone nuclear receptor family-
    peroxisome proliferator activated receptors
    PPARs- specifically PPAR? isoform.
  • Activated PPAR? causes the transcription of
    specific genes that are intimately involved in
    cellular metabolism.
  • Activated genes regulate glucose/fat metabolism
    and result in increased insulin sensitivity.
  • rosiglitazone (Avandia) pioglitazone (Actos)

16
a-Glucosidase inhibitors
  • Prevents digestion of carbohydrates
  • Thus, they reduce their impact on blood glucose
  • Competitively inhibits enzymes needed for
    carbohydrate digestion
  • Acarbose
  • Miglitol

17
Dipeptidyl peptidase 4 inhibitors
  • Causes increased Incretin levels
  • Vildagliptin
  • Sitagliptin

18
Drug cocktails
  • Combination therapy is sometimes used. Two drugs
    combined into one tablet.
  • Examples include
  • Sulfonylurea Metformin Glucovance
  • Metformin Thiazolidinedione Metaglip

19
Future of type 2 DM
  • Complications can be prevented through proper
    diet and exercise
  • Goal of future drug research is normalizing blood
    glucose and decreasing insulin resistance
  • Proper education is necessary. Majority of
    complications are caused by negligence.
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