Type II DM Flashcards
What is the pathology/presentation of DM type II?
Insulin resistance
Relative insulin deficiency
Gradual onset
Patient often obese or history of obesity
Often asymptomatic
Mico/macrovascular complications often present at diagnosis
What are the other physiologic issues in Type II DM?
Reduced circulating levels of Glucagon-like peptide (GLP-1)
GLP-1 released from distal ileum and colon in response to food containing carbs and fats
Loss of first-phase insulin response
Loss of Amylin
Amylin and insulin secreted from beta-cells
Absent in Type I; same fate as insulin in Type 2
How is type II diabetes diagnosed?
FPG >/= 126mg/dL (preferred test)
OR
Symptoms of diabetes + casual plasma glucose >/= 200 mg/dL
OR
Oral glucose tolerance test (OGTT):
2hr-postload glucose >/= 200 mg/dLWhat is the definition of Pre-Diabetes?
Impaired fasting glucose (IFG) = FPG 100-125 mg/dL
Impaired glucose tolerance (IGT) = 2-hr post-load glucose 140-199 mg/dL
IFG and IGT indicate a risk factor for diabetes and cardiovascular disease
Who should be screened for diabetes and how should it be done?
-Screening identifies asymptomatic patients who might have diabetes
-Consider in patients of any age if their BMI ≥ 25 kg/m2 and they have an additional risk factor for diabetes
-If no risk factors are present, begin at age 45
FPG (fasting plasma glucose) should be done initially
-Repeat screening every 3 years
When should you screen children for type II DM?
Overweight: BMI >85th percentile for age and sex, wt for height >85th percentile, or weight >120% of ideal for height
Plus 2 of the following
FH of type 2 diabetes in 1st or 2nd degree relative
Native American, African American, Latino, Asian American, Pacific Islander
Signs of insulin resistance ( acanthosis nigricans, hypertension, dyslipidemia, or PCOS)
Maternal history of diabetes or gestational diabetes
Start testing at age 10 or onset of puberty
Test FPG every 2 years
What are the three major metabolic abnormalities that contribute to hyperglyceemia in NIDDM?
Defective glucose-induced insulin secretion
Increased hepatic glucose output
Inability of insulin to stimulate glucose uptake in peripheral target tissues.
These abnormalities involve the cellular glucose transport in cells, liver, adipose tissue and skeletal muscle.
Also reduced sensitivity of fat and muscle cells to the effects of insulin (insulin resistance).
What are the other causes of insulin resistance?
Cushing’s Syndrome (excessive corticosteroids) Acromegaly (excessive growth hormone) Polycystic ovarian syndrome Hyperandrogenism Hirsutism Menstrual irregularities Obesity infertility
What are the microvascular complications of DM?
Retinopathy-occurs when microvasculature that supplies the retina becomes damaged
Nephropathy-most common complication reported in type II, pain, tingling, or numbness in the extremeties
Neuropathy
What are the macrovascular complications of DM?
Atherosclerotic Cardiovascular diagnosis
Dyslipidemia
What is the A1C goal for adults in general?
A1C goal for adults in general is < 7.0%
What is used for diabetes prevention in patients with IGT or IFG?
Weight loss (7% of body weight) and ↑ physical activity (150 min/week) Helps patients from progressing from pre-DM to DM. 14 g dietary fiber/1000 kcal Drugs studied for prevention Metformin Rosiglitazone Acarbose Troglitazone Orlistat
What is gestational diabetes mellitus (GDM)?
Glucose intolerance with onset or first detection during pregnancy
Associated with maternal morbidity
Fetal macrosomia
Higher rate of pre-eclampsia
Mother is then at risk for developing type 2 diabetes later on
Who is at very high risk for GDM?
Severe obesity Prior history of GDM or delivery of large-for-gestational age infant Presence of glycosuria Diagnosis of polycystic ovarian syndrome Strong family history
When should women be screened for GDM?
Women at very high risk should be screened as soon as possible after confirmation of pregnancy
All other women should be screened at 24-28 weeks of gestation
What diagnosis a woman with GDM?
Fasting ≥ 95 mg/dL 1h ≥ 180 mg/dL 2h ≥155 mg/dL 3 h ≥ 140 mg/dL Women with GDM should be screened for type 2 diabetes 6-12 weeks postpartum
What is the clinical management of diabetes?
Diet and exercise are the cornerstone of management of diabetes regardless of severity of symptoms.
>7% weight loss
150 min/wk exercise
14 g dietary fiber/1000 kcal
Therapeutic management must be highly individualized.
What is the goal of diabetes management?
Goal: To improve symptoms of hyperglycemia, reduce onset & progression of microvascular and macrovascular complications, reduce mortality & improve QOL.
What is the treatment of DM?
Improve sugars but aggressive management of traditional cardiovascular risk factors is required as well. Smoking cessation Lipid management Blood Pressure control Antiplatelet therapy
When should a patient with DM monitor blood glucose levels?
Self monitoring of blood glucose (SMBG)
At least 3 times/day if on insulin injections
If on orals, just use SMBG to help them achieve their glycemic goals
Use the data to make decisions on what therapy to add
When should a patients A1C be monitored?
At least twice a year in patients at goal
Every 3 months in patients whose therapy has changed or aren’t meeting treatment goals
Secretagogues Sulfonylureas- MOA
Direct stimulation of insulin release from viable pancreatic beta-cells thus reducing blood glucose levels (↑ insulin secretion)
Blocks ATP-sensitive K+ channels, resulting in depolarization and Ca++ influx->release of insulin
At higher doses these drugs also decrease hepatic glucose production
Decreased levels of glucagon
Derivatives of sulfonamides, but no antibacterial activity
Secretagogues Sulfonylureas- Efficacy
↓ A1C 1.5%
What are the drug names of the sulfonylureas?
Glyburide, Glipizide, Glimepiride (Amaryl®)
Glyburide, Glipizide, Glimepiride (Amaryl®)- clinical uses
Mild to moderate Type 2 diabetes
Ineffective in Type I diabetics and severe diabetics as the number of viable beta cells is very small.
Not used in gestational diabetes (not good for the baby)
Glyburide, Glipizide, Glimepiride (Amaryl®)- ADRs
HYPOGLYCEMIA --Elderly, hepatic/renal impairment; combo therapy WEIGHT GAIN Muscular weakness Dizziness Confusion Skin rash Photosensitivity Blood dyscrasias Cholestatic jaundice
Glyburide
Sulfonylureas
Administer with breakfast or first main meal
Greater risk of hypoglycemia than other sulfonylureas: longer half-life
Not recommended if CrCl < 50 ml/min (use a different sulfonylurea)
2009 guidelines do not recommend glyburide as a first line sulfonylurea
Glipizide
Sulfonylureas
Administer 30 min before first main meal
Not recommended if CrCl < 10 ml/min
Glimepiride
Administer with first main meal
Not recommended if CrCl < 22 ml/min
Response of sulfonylureas plateaus after half the max dose
Reduced GI absorption if blood glucose > 250 mg/dL
When should sulfonylureas be administered?
With a meal. Associated with a meal time dose.
Glyburide, Glipizide, Glimepiride (Amaryl®) (sulfonylureas)- Monitoring
FPG in two weeks
A1C in 3 months
Glyburide, Glipizide, Glimepiride (Amaryl®) (sulfonylureas)- Contraindications/cautions
Cross-sensitivity to sulfa
Higher risk w/hypoglycemia in patients w/renal or hepatic disease.
Avoid w/ETOH
Cross placenta and decrease fetal insulin->contraindicated in pregnancy
Glyburide, Glipizide, Glimepiride (Amaryl®) (sulfonylureas)- Drug interactions
may potentiate hypoglycemia via reduced hepatic metabolism, decreased urinary excretion or displacement from plasma proteins Sulfonamide antibacterials Propranolol Salicylates Phenylbutazone ETOH
Meglitinides- MOA
Short-acting secretagogues
Stimulate insulin release from pancreatic beta-cells
Shorter half life than sulfonylureas
Rapid release of insulin that only lasts 1-2 hours
Taken with meals- targets postprandial glucose levels
Meglitinides– efficacy
↓ A1C by 1.5%
Meglitinides- adverse effects
Hypoglycemia- less than with sulfonylureas
Weight gain
