Diabetes mellitus:
Metabolic disorder characterized by hyperglycemia
Associated with abnormalities in carbohydrate, fat, and protein metabolism
Leading cause of blindness and kidney failure
7th leading cause of death
Classification Type 1 Diabetes:
Immune mediated or idiopathic ?-cell destruction within the pancreas
Absolute insulin deficiency
5-10% of cases
Classification Type 2 Diabetes:
Progressive insulin secretory defect with a background of insulin resistance
90% of cases
More common in women than men
Classification Gestational Diabetes:
Diabetes diagnosed during pregnancy that is clearly not overt diabetes
Occurs in 7% of pregnancies
Most women return to normoglycemia postpartum
30-50% will develop type 2 diabetes or glucose intolerance
Patho of Type 1 Diabetes:
Absolute pancreatic ?-cell function deficiency
Immune mediated destruction of ?-cells
Idiopathic
Normal Insulin Action:
75% of the body's glucose disposal occurs in non-insulin- dependent tissues
-Brain
-Liver and other GI tissues
25% glucose metabolism occurs in muscle which requires insulin
Carbohydrate ingestion increases the plasma glucose concentrations
Insulin is rel
Pathophysiology-Type 2:
Progressive insulin resistance
Liver:
-Continues to secrete glucose with food intake
Muscle:
-Action of insulin is delayed at muscles resulting slower glucose uptake of cells
Fat:
-Increased fat stores lead to insulin resistance and impaired insulin secre
Risk Factors:
BMI? 25 mg/m2
Physical Inactivity
First degree relative with diabetes
High risk ethnicity:
-African American
-Latino
-Native American
-Asian American
-Pacific American
Delivered baby >9 lbs or diagnosed with GDM
History of CVD
Hypertension
Lipid disorders
Symptoms of Hyperglycemia:
3 P's:
-Polyuria
-Polydipsia
-Polyphagia
Lethargy
Nocturia
Blurred vision
Weight loss
A1c:
Glycosylated A1c
-Glucose is irreversibly bound to hemoglobin in relation to the average serum glucose
-Provides average blood glucose in 2-3 month time period
Glucose over a period of time
Goal is 6 or 6 1/2
Categories of Increased Risk:
Impaired fasting glucose
-FPG 100 mg/dL to 125 mg/dL
Impaired glucose tolerance
-2 hour plasma glucose in 75 g OGTT 140 mg/dL to 199 mg/dL
A1c 5.7%-6.4%
Diagnosis:
Any 1 of the following:
-A1c ?6.5%*
-FBG ?126 mg/dL (no calorie intake >8 hours)*
-2 hr plasma glucose ?200 mg/dL during a 75 g OGTT*
-Random plasma glucose ?200 mg/dL and classic symptoms of hyperglycemia or hyperglycemic crisis
* Must be repeated in abs
Complications of diabetes:
Hypoglycemia
Microvascular complications
-Nephropathy
-Retinopathy
-Neuropathy
Macrovascular complications
-Coronary heart disease
-Cerebrovascular disease
-Peripheral vascular disease
Diabetic foot infections
Hypoglycemia:
Blood glucose <70 mg/dL
Symptoms:
Dizziness
Shaky
Fatigue
Sweating
Anxious
Rapid heartbeat
Irritability
Headache
Pale skin
Seizure
Potential causes of Hypoglycemia:
Decreased caloric intake
Delayed or skipped meals
Too much insulin or other diabetes medications
Increased exercise
Treatment of Hypoglycemia
Eat approximately 15 grams of carbohydrates
� cup juice
8 oz. skim milk
4 teaspoons of sugar
6-7 pieces of hard candy
3 glucose tablets
Nephropathy:
Persistent hyperglycemia results in kidney's overworking to filter blood resulting in protein in urine
-Microalbuminuria and macroalbuminuria
Occurs in 20-40% of patients
Single leading cause of end-stage renal disease
Prevention:
-Glycemic control
-Blood
Retinopathy:
Persistent hyperglycemia damages blood vessels leading to retina
Most frequent cause of new cases of blindness
Prevention:
-Glycemic control
-Blood pressure control
Neuropathy:
Hyperglycemia damages blood vessels to the nerves
Peripheral neuropathy:
-Numbness and tingling of extremities
Autonomic neuropathy:
-Gastroparesis
Prevention:
-Glycemic control
-Annually screening
*Foot exams
Diabetic Foot Infection:
Decreases sensation in extremities, poor blood flow, and structural changes within the foot
-May result in foot ulcers which is complicated by impaired wound healing
Prevention:
-Glycemic control
-Annual foot exam (podiatry)
-Daily self-foot checks
-Diabe
Macrovascular Complications:
Cardiovascular disease:
-Major cause of morbidity and mortality
-Largest contributor to costs related to diabetes
Prevention:
-Glycemic control
-Hypertension
*Blood pressure <130/80 mm Hg
Dyslipidemia and lipid management:
-LDL<100 mg/dL
-HDL>50 mg/dL
-Tr
ADA Treatment Goals:
Glycemic control:
-A1c <7%
-Fasting plasma glucose: 70-130 mg/dL
-2 hour post-prandial glucose <180 mg/dL
Lipids:
-LDL<100 mg/dL
Blood pressure:
-<130/80 mm Hg
Lifestyle Modifications:
Diet:
-Moderate carbohydrate intake
-Saturated fat <7%
-Calorie restriction in Type 2 patients to promote weight loss
Exercise:
-150 minutes/week of moderate aerobic physical activity
-Resistance training twice a week
Oral Medications
Insulin secretagogues
-Sulfonylureas
-Meglitinides
Insulin sensitizers
-Biguanides
-Thiazolidinediones (TZDs)
Alpha-glucosidase inhibitors
Dipeptidyl Peptidase IV (DPP-4) inhibitors
Sulfonylureas drugs:
Second Generation:
Glyburide (Micronase�, Glynase�, Diabeta�)
Glipizide (Glucotrol�, Glucotrol XL�)
Glimepiride (Amaryl�)
Meglitinide meds:
Repaglinide (Prandin�), Nateglinide (Starlix�)
Efficacy:
-Decrease A1c by approximately 1%
Sulfonylureas:
Mechanism of action:
-Increase insulin secretion
Efficacy:
-Decrease A1c by 1.5 - 2%
Adverse Reactions:
-Hypoglycemia
-Weight gain
-Less common: rash, GI upset
-Disulfiram reaction
Clinical Pearls:
-Take in the morning
-Longer the duration of diabetes, be
Meglitinides:
Mechanism of Action:
-Increases insulin secretion
-Very short duration of action (2-4 hours)
Adverse Reactions:
-Hypoglycemia
-Weight gain
Clinical Pearls:
-Take prior to meals
-Insulin secretion increases with meal ingestion
-If meals are skipped, skip m
Biguanides meds
Metformin (Glucophage�)
Thiazolidinediones (TZDs) meds:
Pioglitazone (Actos�)
Rosiglitazone (Avandia�)
Biguanides
Metformin (Glucophage�)
Mechanism of action:
-Decrease hepatic glucose production
Efficacy:
-Decrease A1c by 1.5-2 %
Adverse effects:
-GI upset
-Lactic acidosis (Black Box Warning)
-No hypoglycemia or weight gain
Clinical Pearls:
-Take with food
-Contrain
Alpha-glucosidase Inhibitors meds
Acarbose (Precose�), Miglitol (Glyset�)
Thiazolidinediones (TZDs):
Mechanism of action:
-Increases peripheral insulin sensitivity
-Decrease hepatic glucose production
Efficacy:
-Decrease A1c by 1.5%
Adverse effects:
-Edema
-Weight gain
-Increased risk of fracture
-May induce ovulation
-Bladder cancer?
-No hypoglycemia
Cl
Sodium Glucose Co-Transporter 2 Inhibitor meds:
Agents
-Canagliflozin (Invokana�)
-Dapagliflozin (Farxiga�)
-Empagliflozin (Jardiance�)
Alpha-glucosidase Inhibitors:
Acarbose (Precose�), Miglitol (Glyset�)
Mechanism of Action:
-Slows intestinal carbohydrate digestion and absorption
Efficacy:
-A1C decreased by 0.3-1%
Adverse Reactions:
-GI side effects
*Flatulence, bloating, diarrhea, and abdominal discomfort
Clinical
Sodium Glucose Co-Transporter 2 Inhibitor
Mechanism of Action
-Inhibits SGLT2 in proximal renal tubule
-Reduces reabsorption of glucose
-Increases urinary glucose excretion and lowers plasma glucose
Efficacy
-0.5 - 1% reduction in A1c
Advantages
-Low risk of hypoglycemia
-Weight loss
-Blood press
DPP-4 Inhibitors meds:
Alogliptin (Nesina�)
Sitagliptin (Januvia�)
Saxagliptin (Onglyza�)
Linagliptin (Tradjenta�)
Combination Products:
Sulfonylureas and metformin
-Glucovance (glyburide/metformin)
-Metaglip (glipizide/metformin)
DPP-4 Inhibitors and metformin
-Janumet (sitagliptin/metformin)
-Kombiglyze XR (saxagliptin/metformin)
Sulfonylurea and TZD
-Duetact (pioglitazone/glimepiride)
DPP-4 Inhibitors:
Mechanism of Action:
-Inhibits DPP-4 activity
*Increase insulin secretion
*Decrease glucagon secretion
Efficacy:
-Decreases A1c by 0.7-1%
Adverse Reactions:
-Headache
-Nasopharyngitis
-Pancreatitis
-Urticaria and/or facial edema
Clinical Pearls:
-Weight n
Insulin Dosing and Adjustment:
Adjust insulin to achieve glycemic goals
-A1c <7%
-Fasting plasma glucose: 70-130 mg/dL
-2 hour post-prandial glucose <180 mg/dL
Steps when reviewing glucose logs:
1.Check for a pattern of hypoglycemia
2.Correct fasting blood glucose first
3.Correct other
Non-Insulin Injectable Medications:
Incretin Mimetic:
Exenatide (Byetta�)
Long acting exenatide (Bydureon�)
Liraglutide (Victoza�)
Albiglutide (Tanzeum�) - discontinue in 2018
Lixisenatide (Adlyxin�)
Dulaglutide (Trulicity�)
Amylinomimetic:
Pramlintide (Symlin�)
Incretin Mimetics:
Mechanism of Action:
GLP-1 Receptor agonist
-Increase insulin secretion
-Decrease glucagon secretion
-Slows absorption of food from GI tract
-Increase satiety
Efficacy:
-Decrease A1c by approximately 1-1.6%
Adverse Reactions:
-Gastrointestinal: nausea, vo
Amylinomimetic:
Pramlintide (Symlin�)
Mechanism of Action:
-Amylin analog
*Delays gastric emptying
Efficacy:
-Decreases A1c by 0.6%
Adverse Effects:
-Gastrointestinal: nausea, vomiting, anorexia
Clinical Pearls:
-GI side effects decrease over time
-Avoid in patients with
Insulin:
Anabolic and anticatabolic hormone with a major role in protein, carbohydrate and fat metabolism
-Binds to cells to allow glucose to enter
Exogenous insulin is given to decrease hyperglycemia in patients with diabetes
Adverse effects:
-Hypoglycemia
-Weigh
Basal Insulin:
Provides consistent insulin level to decrease blood glucose through night and between meals
Decreases fasting blood glucose
Intermediate or long acting insulin
Approximately 50% of daily dose
Bolus Insulin:
Administered to decrease glucose after meals
Approximately 50% of daily dose
Rapid or short acting insulin
Insulin Characteristics:
Onset:
-Length of time insulin enters blood stream and begins lowering blood glucose
Peak:
-Time insulin is at maximum strength in terms of lowering blood glucose
Duration:
-How long insulin lowers blood glucose
Insulin Dosing:
0.5 units/kg/day
-50% basal insulin
-50% bolus insulin divided with meals
Example:
-70 kg patient
-0.5 units/kg: 35 units daily
-Basal insulin is 50%: 18 units
-Bolus insulin is 50%: 18 units
*6 units before breakfast
*6 units before lunch
*6 units before