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Due to pancreatic islet B cell destruction by an autoimmune process
these patients are prone to ketoacidosis
Children and young adults with a peak incidence before school age and again at around puberty.
Type 1 DM
Circulating insulin is virtually absent
plasma glucagon is elevated
and the pancreatic B cells fail to respond to all insulinogenic stimuli.
Type 1 DM
The more prevalent form and results from insulin resistance with a defect in compensatory insulin secretion
over 40 years of age and obese
Ketonuria and weight loss generally are uncommon at time of diagnosis.
Type II DM
Ketonemia
ketonuria
or
both may be present in what type of DM?
Type II DM
Primary mechanism is to stimulate insulin release from pancreatic B cells
What drugs?
What type of DM do these tx?
Sulfonylureas

Nm Them?
glyburide
glipizide
glimepiride

Type II DM.
Major adverse effect is causing prolonged hypoglycemia

Contraindications w severe
-liver impairment
-kidney impairment
-Weight Gain
Sulfonylureas

Nm Rx-s
glyburide
glipizide
glimepiride
Structurally similar to glyburide but lacks the sulfonic acid-urea moiety
Undergoes complete metabolism in the liver to inactive biliary products
giving it a plasma half-life of less than 1 hour
Less hypoglycemia then with glipizide
Insulin secretagogues

Repaglinide
Nateglinide
Primary action is on the liver reducing hepatic gluconeogenesis
Particularly good for those type 2 pts that are obese and are not responding to sulfonylureas.
Metformin
Tends to improve fasting and postprandial hyperglycemia in obese pts without weight gain associated with sulfonylureas and insulin
Hypoglycemia does not occur
Metformin
Contraindications:
diabetics with serum creatinine of 1.5 mg/dl or higher
hepatic insufficiency
alcoholism
or
propensity to develop tissue hypoxia
Not for type 1
Metformin
Gastrointestinal symptoms (anorexia
nausea
vomiting
abdominal discomfort
diarrhea)
which occur in up to 20% of patients
These effects are dose-related
tend to occur at onset of therapy
and often are transient
Adverse affects of metformin
-Sensitize peripheral tissues to insulin

-result in lower doses of insulin needed

can lower
-cholesterol
-triglycerides
-Improvement of nonalcoholic fatty liver disease
Thiazolidinedione
Nm Rx-s ?

The Representative drugs are:

~MOA
~Results in?
~Benefits Are:
Rosiglitazone
Pioglitazone


-Sensitize peripheral tissues to insulin

-result in lower doses of insulin

can lower
-cholesterol
-triglycerides
-Improvement of nonalcoholic fatty liver disease
Safety concerns and troublesome side effects limit their use
May increase risk of MI
or
Angina
Decrease in bone density
Anemia
Weight gain in combo with sulfonylurea
Caution in pts with liver disease.
Thiazolidinedione
(“Glitazone”)

Rosiglitazone

Pioglitazone
Inhibit the alpha-glucosidase enzymes in the gut that digest dietary starch and sucrose
Lower postprandial glycemic excursion
Flatulence 20-30% - by 3 years 60% had discontinued drug due to this.
Alpha-Glucosidase Inhibitors

Acarbose

Miglitol
Gut hormone that is released on glucose ingestion that amplifies insulin release.
Glucagon-like-peptide (GLP)
GLP-1 receptor agonist
Exenatide

Class?

isolated from the saliva of
(an incretin)

the Gila Monster
When this drug is given to patients with type 2 diabetes
by subcutaneous injection twice daily

It lowers blood glucose and hba1c levels

Appears to have the same effects as GLP-1 on
-Glucagon suppression and gastric emptying.
Exenatide

Class?

When this drug is given to patients with type ? DM
Incretin
-Type 2...
-....It lowers blood glucose and hba1c levels

Same effect as GLP-1 on
-Glucagon suppression
-Gastric emptying.
Advantages include weight loss

Adverse effects are:

-nausea
-pancreatitis
-delay of gastric emptying
Incretins (exanatide)


-Advantages include:

-A/E?
3ct
~weight loss

-nausea
-pancreatitis
-delay of gastric emptying
~Which incretin causes weight loss?

~Which increases incidence of URI?
-Exenatide

-Sitagliptin
Given subcutaneously
it delays gastric emptying
suppresses glucagon secretion
and decreases appetite
It is approved for use in both types of DM

Short-acting or premixed insulin doses be reduced by 50% when the drug is started.
Pramlintide
Insulin preparation used by most diabetics
U100
Used by persons with insulin resistance who require more than U100 as a single injection
U500
Rapid
short
intermediate
or
long acting?
Lispro
Rapid
Rapid
short
intermediate
or
long acting?
Regular insulin
Short
Rapid
short
intermediate
or
long acting?
NPH insulin
Intermediate
Rapid
short
intermediate
or
long acting?
Glargine
Long
Rapid
short
intermediate
or
long acting?
Detemir
Long
Which type of insulin can be administered IV
and describe clinical circumstances when this route would be indicated
Regular Insulin can be given intravenously and is used in treating patients with diabetic ketoacidosis.
Which insulins can be obtained in premixed preparations?
NPH/regular
70-30
50-50

NPH/Lispro
75-25
50-50

Protamine/Aspart 70/30
May be a problem for Type I diabetics due to variability of absorption at different sites
especially with exercise
Best absorption from abdomen.
Insulin
The longer-acting insulin analogs cannot be mixed with
Either regular insulin or
the rapidly acting insulin analogs.
Increases the effectiveness of insulin.
Exercise
Potential complications of insulin therapy- 4 things
Hypoglycemia
allergy
resistance
and lipodystrophy at the injection site.
Rapid
short
intermediate
or
long acting?
Aspart
Rapid
Due to pancreatic islet B cell destruction by an autoimmune process
these patients are prone to ketoacidosis
Children and young adults with a peak incidence before school age and again at around puberty.
Type 1 DM
Circulating insulin is virtually absent
plasma glucagon is elevated
and the pancreatic B cells fail to respond to all insulinogenic stimuli.
Type 1 DM
The more prevalent form and results from insulin resistance with a defect in compensatory insulin secretion
over 40 years of age and obese
Ketonuria and weight loss generally are uncommon at time of diagnosis.
Type II DM
Ketonemia
ketonuria
or
both may be present in what type of DM?
Type II DM
Primary mechanism is to stimulate insulin release from pancreatic B cells
What drugs?
What type of DM do these tx?
Sulfonylureas
representative drugs:
glyburide
glipizide
glimepiride
Type II DM.
Major adverse effect is causing prolonged hypoglycemia
Contraindicated in pts with severe liver kidney impairment
Also weight gain
Sulfonylureas
representative drugs:
glyburide
glipizide
glimepiride
Structurally similar to glyburide but lacks the sulfonic acid-urea moiety
Undergoes complete metabolism in the liver to inactive biliary products
giving it a plasma half-life of less than 1 hour
Less hypoglycemia then with glipizide
Insulin secretagogues (representative drugs:
repaglinide
nateglinide)
Primary action is on the liver reducing hepatic gluconeogenesis
Particularly good for those type 2 pts that are obese and are not responding to sulfonylureas.
Metformin
Tends to improve fasting and postprandial hyperglycemia in obese pts without weight gain associated with sulfonylureas and insulin
Hypoglycemia does not occur
Metformin
Contraindications:
diabetics with serum creatinine of 1.5 mg/dl or higher
hepatic insufficiency
alcoholism
or
propensity to develop tissue hypoxia
Not for type 1
Metformin
Gastrointestinal symptoms (anorexia
nausea
vomiting
abdominal discomfort
diarrhea)
which occur in up to 20% of patients
These effects are dose-related
tend to occur at onset of therapy
and often are transient
Adverse affects of metformin
Sensitize peripheral tissues to insulin
can result in lower doses of insulin needed
Can lower cholesterol and triglycerides
Improvement of nonalcoholic fatty liver disease
Thiazolidinedione (“glitazone”) drugs (representative drugs:
rosiglitazone
pioglitazone).
Safety concerns and troublesome side effects limit their use
May increase risk of MI or
angina
Decrease in bone density
Anemia
Weight gain in combo with sulfonylurea
Caution in pts with liver disease.
Thiazolidinedione (“glitazone”) drugs (representative drugs:
rosiglitazone
pioglitazone).
Inhibit the alpha-glucosidase enzymes in the gut that digest dietary starch and sucrose
Lower postprandial glycemic excursion
Flatulence 20-30% - by 3 years 60% had discontinued drug due to this.
Alpha-glucosidase inhibitors (representative drugs:
acarbose
miglitol).
Gut hormone that is released on glucose ingestion that amplifies insulin release.
Glucagon-like-peptide (GLP)
GLP-1 receptor agonist isolated from the saliva of the Gila Monster
Exenatide (an incretin)
When this drug is given to patients with type 2 diabetes by subcutaneous injection twice daily
it lowers blood glucose and hba1c levels
Appears to have the same effects as GLP-1 on glucagon suppression and gastric emptying.
Exenatide (an incretin)
Advantages include weight loss
Adverse effects are nausea
pancreatitis
delay of gastric emptying
Incretins (exanatide)
Which incretin causes weight loss?
Which increases incidence of URI?
Exanatide
sitagliptin
Given subcutaneously
it delays gastric emptying
suppresses glucagon secretion
and decreases appetite
It is approved for use both in types of diabetes
Short-acting or premixed insulin doses be reduced by 50% when the drug is started.
Pramlintide
Insulin preparation used by most diabetics
U100
Used by persons with insulin resistance who require more than U100 as a single injection
U500
Rapid
short
intermediate
or
long acting?
Lispro
Rapid
Rapid
short
intermediate
or
long acting?
Regular insulin
Short
Rapid
short
intermediate
or
long acting?
NPH insulin
Intermediate
Rapid
short
intermediate
or
long acting?
Glargine
Long
Rapid
short
intermediate
or
long acting?
Detemir
Long
Which type of insulin can be administered IV
and describe clinical circumstances when this route would be indicated
Regular Insulin can be given intravenously and is used in treating patients with diabetic ketoacidosis.
Which insulins can be obtained in premixed preparations?
NPH/regular 70-30 or
50-50
NPL/lispro 75-25 or
50-50
aspart protamine/aspart 70/30
May be a problem for Type I diabetics due to variability of absorption at different sites
especially with exercise
Best absorption from abdomen.
Insulin
The longer-acting insulin analogs cannot be mixed with
Either regular insulin or
the rapidly acting insulin analogs.
Increases the effectiveness of insulin.
Exercise
Potential complications of insulin therapy- 4 things
Hypoglycemia
allergy
resistance
and lipodystrophy at the injection site.
Rapid
short
intermediate
or
long acting?
Aspart
Rapid