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Update : Patophysiology DM type II, Goal Therapy, and Drugs

Posted by dokterhasan on November 11, 2009

PATOPHYSIOLOGY DM TYPE II
————————————
PRIMARY :
Peripheral insulin resistance; is the inability of skeletal muscle, liver, and adipose tissue to elicit an adequate response (ie, glucose clearance) to circulating insulin.

Insulin Relative Deficiency as the result of declining Beta cell Pancreas function and mass.

OTHER ABNORMALITIES :
Excessive hepatic glucose production, and increased glucagon secretion from pancreatic α cells.

Deficiencies in hormones responsible for regulating glucose homeostasis, specifically amylin and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), also occur.

Amylin is a hormone co-secreted with insulin from pancreatic β cells that suppresses postprandial glucagon secretion and hepatic glucose production.

GLP-1 and GIP both aid in stimulating glucose-dependent insulin secretion from pancreatic β cells and GLP-1 aids in suppressing glucose-dependent glucagon secretion from pancreatic α cells.

GOALS OF THERAPY
————————
According to the ADA and the Joslin Diabetes Center at Harvard Medical School, the primary goal of therapy in most patients with type 2 diabetes is attainment and maintenance of an A1C (Glicated Haemoglobin) below 7.0%.

AACE and the International Diabetes Federation (IDF) advocate a lower A1C goal of ≤6.5%.

This A1C level is associated with prevention of neuropathic and microvascular complications.

MONITORING
—————-
A1C is the primary measurement for evaluating long-term glycemic control (ie, over a period of 2 to 3 months).

As such, nationally recognized treatment guidelines recommend obtaining an A1C level 2 times per year in patients who are at or below goal and who are on a stable drug regimen.

PHARMACOLOGYC INTERVENTION
—————————————–
As we know that oral hypoglycemic drugs include :

Biguanide (Metformin), Thiazolidinedions (Pioglitazone, Rosiglitazone), Both of these act as Insulin sensitizer.

Insulin secretion enchancements (Secretagoug) : Sulfonylurea (Glimepiride, Glipizide, glyburide, Glibenclamide), Glinides (Repaglinide, Nateglinide).

Glucose Absorption Reductor : α-glucosidase inhibitors (Acarbose).

There are other drugs that better we know :

Restore Incretin Function : Dipeptidyl-peptidase 4 inhibitors (Sitagliptin, Saxagliptin) , Injectable GLP-1 agonists (Exenatide).

Restore Amylin Function : Injectable Amylin analogs (Pramlintide).

Unknown Mechanism : Bile-acid sequestrants (Colesevelam).

INSULIN THERAPY
———————-
They divided based on half time / Speed of act :

Rapid Acting : Onset 10-30 min, Duration 0.5-3 hours
Product : Novolog, Apidra, Humalog

Short Acting : Onset 0.5-1 hours, Duration up to 12 h.
Regular Insulin Product : Humulin R, Novolin R

Intermediate Act : Onset 1.5-4 h, Duration up to 24 h.
NPH Insulin Product : Humulin N, Novolin N

Long Act : Onset 0.75-4 h, Duration up to 24 h.
Product : Levemir, Lantus.

REFFERENCE :

Paul S. Jellinger MD, MACE; Kenneth J. Snow, MD. Advancing Therapies for Type 2 Diabetes: Physiologically Based Approaches. Published : October 2009.

Download link : http://cme.medscape.com/viewarticle/709459

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