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106 Cards in this Set
- Front
- Back
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Complications
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Macrovascular
CVD, PVD, CVA Microvascular Retinopathy non-inflammatory damage to the retina Nephropathy damage to or disease of the kidney Neuropathy damage to nerves Other: Sexual dysfunction, gastroparesis reduces the ability of the stomach to empty |
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Macrovascular: HTN Management
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Goal <130/80
ACE inhibitor or an ARB If second agent needed, thiazide or loop diuretic depending on CrCl Goal of 110-129/65-79 in GDM ACE inhibitor and ARB’s CI in pregnancy |
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Macrovascular: Lipid Management
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TLC for all
DM with CVD or > 40yo + 1 risk factor Statin therapy to reduce LDL by 30-40% regardless of baseline LDL levels along with lifestyle changes* Consider statin if < 40 if multiple CVD risk factors |
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Macrovascular: Lipid Management Goals
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Type 1 or type 2 without CVD
LDL goal <100 mg/dL HDL goal > 40mg/dL in Men > 50mg/dL in Women Type 1 or type 2 with CVD LDL goal <70 mg/dL |
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Macrovascular: Antiplatelet
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Primary Prevention: Type 1 or Type 2 DM
High cardiovascular risk (>10% risk in 10 years) Includes most men > 50 and women > 60 ASA 75-162 mg/day (Clopidogrel if ASA allergy) Low cardiovascular risk (< 5% risk) ASA not recommended Includes most men <50 and women <60 Moderate cardiovascular risk (between 5% - 10%) Clinical judgment for ASA initiation |
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Creatinine Clearance CCr
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(140-age) X Mass (kg)X {.85 if female}
________________________________ 72 X Serum Creatinine |
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Microvascular: Nephropathy
Protein in Urine |
Normal <30
Microalbuminurea 30-299 Macroalbuminuria ≥ 300 |
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Microvascular: Nephropathy
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Goal is to reduce/slow progression
Tight glycemic control Optimize blood pressure control If micro or macroalbuminuria start either… ACE inhibitor or ARB Non-DCCBs may reduce albuminuria in patients, but not preferred over ACE inhibitors or ARBs Can be an alternate is ACE or ARB can’t be used |
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Microvascular: Nephropathy
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Screening
Albuminuria Type 1: after diagnosed 5 years, then annually Type 2: upon diagnosis, then annually Serum Creatinine Annually in type 1 and type 2 eGFR may be more accurate with MDRD equation than with Cockroft-Gault |
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Microvascular: Retinopathy
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Screening
Type 1 All > 10 yo should have an initial, dilated exam within 5 years of diagnosis, then annually Type 2 “initial, dilated exam shortly after diagnosis”, then annually |
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Diabetic Peripheral Neuropathy (DPN)
Screening |
Type 1
All > 10 yo should have an initial, dilated exam within 5 years of diagnosis, then annually Type 2 “initial, dilated exam shortly after diagnosis”, then annually |
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DPN Treatment
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Optimal glycemic control slows the progression
No therapy to reverse the damage Pain control with anticonvulsants/antidepressants Gabapentin Pregabalin Duloxetine |
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DPN Foot Care
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Annual examinations by provider
Self examinations by patient daily Use lotion to prevent dryness and cracking File calluses with a pumice stone Cut toenails Always wear socks and well fitting shoes Notify provider if any problems occur immediately |
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Chemically Induced Diabetes
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b-adrenergic agonists
Thiazides Dilantin a interferon Atypical antipsychotics Pentamidine Nicotinic Acid Glucocorticoids Thyroid hormone |
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Diabetes screening (I and II)
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Type 1:
Not recommended Too small a population Symptomatic enough to seek medical assistance Type II: Adults 45 years of age BMI > 25 kg/m2 with risk factors for DM Monitor every 3 years |
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BMI
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BMI = ( Weight in Kilograms / ( Height in Meters x Height in Meters ) )
or ( Weight in Pounds / ( Height in inches x Height in inches ) ) x 703 |
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Screening for Type 2 DM in Children
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Overweight
BMI > 85th percentile (age, gender, or weight for height) Weight >120% IBW Plus 2 of the following: Family History of DM in 1st or 2nd degree relative Race Signs of insulin resistance Mother with GDM during gestation Monitor fasting blood glucose every 3 years at puberty onset or 10 years of age |
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Clinical Presentation
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Polyuria Pee
Polydipsia Drink Polyphagia Eat Weight loss (more common with type 1), Dry skin, Weakness, Nocturia, Blurred vision, Fatigue, Persistent recurrent infections DKA (type 1) HHS (type 2) Hyperglycemic Hyperosmolar Syndrome |
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C-peptide
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Type 1:
Low C-peptide level = little or no insulin production Normal is 0.5 – 2 ng/ml Type 1 levels < 1ng/ml Type 2 levels > 1ng/ml Type 2: Proinsulin is cleaved in the pancreas insulin + C-peptide molecules |
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Plasma Glucose Definitions
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Pre-prandial
plasma glucose measured before meals Peak post-prandial plasma glucose measured 1-2 hours after the beginning of the meal Fasting plasma glucose after at least 8 hours without food |
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Diagnosis******
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Any ONE of the following:
1. A1C 6.5%. Must be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* 2. FPG 126 mg/dL 3. 2-hour postload glucose 200 mg/dL during an OGTT 4. With classic symptoms of hyperglycemia or hyperglycemic crisis, a random glucose 200 mg/dL Criteria 1-3 should be confirmed with repeat testing in the absence of unequivocal hyperglycemia |
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Pre-diabetes markers***
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Pre (normal)
A1C - 5.7%-6.4% (4%-5.6) FPG - 100-125mg/dl ( <100) OGTT - Gluc Tol Test - 140-199 mg/dl ( <140mg/dl) |
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A!C and Average Glucose Formula
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(A1C-2) X 30
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Goals Of Treatment******
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A1C: < 7% for most
Pre-prandial (plasma): 70-130 mg/dL Peak post-prandial: <180 mg/dL |
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Pre-diabetes Management
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Weight Reduction program
Target 7% loss Increase Physical Activity 150 minutes/week of moderate activity |
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Pre-diabetes Management
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Metformin to be considered if:
High risk patients Multiple risk factors for DM (FH, TG, HDL,HTN) Progressive hyperglycemia, despite lifestyle interventions A1C 6% EBM Most effective if BMI 35 and < 60 yo Follow up in 1 year to prevent the progression to diabetes |
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Nonpharmacologic Treatment
Medical Nutrition Therapy (MNT) |
↑ in vegetables, whole grains, fiber, and ↓fat
Carbohydrates: 45 – 65% of total calories Do not restrict to < 130g/d Protein: 15 – 20% of total calories Saturated fat: < 7% of tot. cal with min. trans fat Fiber: 20-30g/d Nonnutritive sweeteners are safe 1 alcoholic drink per day & 2 per day for |
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o Glipizide
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(Glucotrol®) 2nd Generation SU
Initial dose is 5 – 10 mg daily (max 40 mg/day) Little additional benefit between 20mg and 40mg Some additional benefit if dosed twice daily > 15mg/d need to take twice daily Take 30 min before meals Liver disease 2.5 mg daily |
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o Glimepiride
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(Amaryl®) 2nd Generation SU
Initial dose is 1 – 2 mg daily (max 8 mg/day) Take 30 min before meals Liver or renal disease = 1 mg daily initially |
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o Glyburide
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(Diabeta®) 2nd Generation SU
Initial dose is 2.5 – 5 mg daily (max 20 mg/day) >10mg/day may need to take twice daily ↑incidence of hypoglycemia CrCl < 50 ml/min – Avoid use Avoid in hepatic disease |
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SU Things to consider
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Renal and hepatic adjustments required
Sulfa allergy Risk of skipping meals or binge eating Hypoglycemia Drug interactions Greater efficacy in patients with high C-peptide levels Small additional benefit beyond 60-75% of max dose |
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SU ADRs
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ADR’s: hypoglycemia, weight gain, rash
Metabolized via CYP 450 Interact with many antibiotics Elimination: All require dose adjustment or avoidance in renal failure except tolbutamide and glipizide |
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Metformin
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(Glucophage®)
Efficacy First line in ALL patients in absence of C/I Favorable effect on body weight (stomach issues) Beneficial effects on lipids |
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Metformin C/I
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Absolute:
Radiographic contrast dye Renal disease (<60ml/min) Male: SCr 1.5 mg/dL Female SCr 1.4 mg/dL Relative: Liver disease Hypoxic states Acute MI, heart failure… |
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Metformin Dose Titration
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Start with:
500 mg once or twice per day with meals 850 mg once per day with meals Titrate after 5–7 days, if no GI side effects, to: 850 mg or 1000mg twice per day GI side effects: Decrease to previous lower dose Try to advance the dose at a later time (at least 1 week) Maximum effective dose 1,000 mg twice per day 850 mg twice per day Some respond to 2500 mg per day |
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Metformin ADRs
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ADRs:
Lactic acidosis, nausea, diarrhea, ↓ B12 absorption Lactic acidosis Rare, but deadly ADR Form of metabolic acidosis Symptoms are nonspecific anorexia, nausea, vomiting, altered level of consciousness, hyperpnea, abdominal pain and thirst 50% fatality rate |
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Metformin Renal Function
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Risk to benefit decision to initiate or
continue with est. GFR 31 ml/min' Exercise caution in situations where renal function may be temporarily compromised Temporarily discontinue in these circumstances |
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Pioglitazone
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(Actos®) TZDs 15 mg po daily (max 45mg/day)
ADRs: Hepatoxicity – discontinue if ALT >3 times UNL female: 38 i.u./l male: 50 i.u./l Fluid retention Weight gain 1.5-4 kg Increases ovulation in females |
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Rosiglitazone
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(Avandia®)- TZDs Being taken off market
as of November 2011 Rosiglitazone – Increased risk of MI, HF, and mortality |
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Pioglitazone Contraindications:
Pioglitazone Monitoring parameters |
Absolute:
NYHA Class III-IV HF Hepatic or liver failure Relative: NYHA Class I-II HF Check LFTs every 2 months for the 1st year, then periodically thereafter |
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Class I (Mild)
No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath). Class II (Mild) Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. |
Class III (Moderate)
Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV (Severe) Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased. |
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Exenatide
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(Byetta®) Incretin Mimetics
Dosing: Start 5 mcg SQ BID Must give within 60 minute period before morning and evening meals May increase to 10 mcq SQ BID after 1 month of therapy Inject in abdomen, thigh, or upper arm Prior to first use store in refrigerator, then room temperature NTE 77 F Discard after 30 days of first use |
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Liraglutide
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(Victoza®) Incretin Mimetics
Start 0.6 mg SQ daily May increase to 1.2 mg SQ daily after 1 week of therapy Maximum dose is 1.8 mg SQ daily Inject in abdomen, thigh, or upper arm Prior to first use store in refrigerator, then room temperature NTE 86 F Discard after 30 days of first use |
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Exenatide ADR, C/I
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ADRs:
Nausea/vomiting (44%/13%), diarrhea, weight loss, hypoglycemia (rare*), acute pancreatitis CI: Type 1 DM, renal impairment (CrCl < 30 ml/min) and severe GI disease |
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Liraglutide ADR, C/I
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ADRs:
Nausea/vomiting (28%/10.9%), diarrhea (17%), weight loss, hypoglycemia (9.7%), acute pancreatitis, C cell hyperplasia of the thyroid CI: medullary thyroid cancinoma, multiple endocrine neoplasia syndrome, thyroid cancer |
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Sitagliptin
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(Januvia®) Dipeptidyl peptidase IV
(DPP-IV) Inhibitors Dosing: 100 mg po daily Renal Dosing: CRCL 30-49 mL/min – 50 mg daily CRCL <30 mL/min – 25 mg daily ADRs: nasopharyngitis, upper respiratory tract infection, headache Weight neutral |
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o Saxagliptin
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(Onglyza®) Dipeptidyl peptidase IV
(DPP-IV) Inhibitors Dosing: 2.5 or 5 mg po daily Renal Dosing: CRCL <50 mL/min – 2.5 mg daily ADRs: nasopharyngitis, upper respiratory tract infection, headache, possible facial edema? Weight neutral |
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o Linagliptin
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(Tradjenta®) Dipeptidyl peptidase IV
(DPP-IV) Inhibitors Approved May 2011 Dosing: 5 mg po daily Renal Dosing: No dosage adjustment ADRs: Nasopharyngitis Weight neutral |
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Acarbose
not used very much |
(Precose) Alpha-glucosidase inhibitors
Dosing: is weight based ADR’s: Flatulence, bloating, abdominal discomfort, diarrhea Contraindications: Scr >2 mg/dL or CrCl < 25 ml/min IBS Monitoring parameters: LFT’s every 3 months for first year, then annually |
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Repaglinide
Nateglinide |
(Prandin®) Meglitinides
(Starlix®) Meglitinides Dosing: Rapaglinide: 0.5mg PO TID Nateglinide: 120mg PO TID Give 15-30 minutes prior to a meal Skip a meal…Skip a dose Add a meal…Add a dose ADR’s: hypoglycemia, weight gain (1-3 kg) Elimination: hepatic via P450 2C9 and 3A4 |
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Pramlintide
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(Symlin®) Amylin analogues
Indication: Adjunctive Therapy with patients taking INSULIN Dosing: Type 2 DM Start with 60 mcg SQ prior to meal Reduce short acting or meal time insulin by 50% Type 1 DM Start with 15 mcg SQ prior to meal Reduce short acting or meal time insulin by 50% May increase in 3 days if nausea resolved |
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Pramlintide ADRs: Contraindications:
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Severe hypoglycemia (2-4 X’s) and nausea.
Poor compliance with insulin Poor compliance with SMBG A1C >9% Recurrent hypoglycemia within 6 months Hypoglycemia unawareness Diagnosis of gastroparesis Require medication for gastric motility Pediatric patients |
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(GlucovanceÔ)
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Glyburide/Metformin
SU/Biguanides |
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(Metaglip®)
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Glipizide/Metformin
SU/Biguanides |
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Actosplus Met®
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(pioglitazone/metformin)
TZD/Biguanides |
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Prandimet®
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(repaglinide/metformin)
(Prandin®)/Biguanides |
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Janumet®
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(sitagliptin/metformin)
(Januvia®)/Biguanides |
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Duetact®
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(pioglitazone/glimepiride)
(Actos®)/(Amaryl®) |
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Kombyglyze XR
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(saxagliptin/metformin XR)
(Onglyza®)/Biguanides |
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Combination Medications
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Efficacy > than either agent used alone
Combo products enhance compliance and may be less expensive than separate tablets Adverse effects associated with combination products are the same as those noted with either drug alone Difficult to dose adjust |
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Bolus (Pre-meal) Insulin
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Regular (humulin,novolin R)
Aspart (Novalog) Glulisine (apidra) Lispro (humalog) |
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Basal (Maintenance) Insulin
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o NPH (Humilin,Novolin N)
o Detemir (Levimir) o Glargine (Lantus) |
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Insulin conversion Detemir
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Detemir (Levimir)
Dosed once or twice daily dose = duration of action 30% less potent than NPH and glargine Need doses for equivalent control One to one conversion from NPH |
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Insulin conversion Glargine
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Dosed once daily, but need to be consistent
↓ daily dose of insulin glargine when switching from NPH twice daily A1C at goal or < 8% …20% reduction A1C 8 to 9%...10% reduction A1C> 9 %...no reduction |
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Insulin Mixing
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Draw the regular (or rapid acting) insulin
first then the long-acting or basal insulin (cloudy) Mixed insulin should be stored in the refrigerator Glargine or detemir should never be mixed |
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Initiating Insulin, Type 2
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Start by initiating basal therapy
0.2units/kg or 10 units QD of basal insulin Glargine, detemir, NPH Titrate basal insulin based on FBG until reach 70-130mg/dl < 180mg/dL: by 2 units Q 3 days > 180mg/dL: by 4 units Q 3 days Avg 3 reading every 3 days |
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Initiating Insulin, Type 2
If A1C ≥ 7% after 2 – 3 months |
target and intensify regimen
Review SMBG, if FBG is still 70-130mg/dL, and: high pre-lunch: add rapid acting at breakfast high pre-dinner: add rapid acting at lunch If NPH is basal insulin used, could add 2nd NPH dose instead high pre-bedtime: add rapid acting at dinner Add 4 units initially, then ↑ by 2 units Q 3 days |
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Initiating Insulin, Type 2
If A1C continues to be ≥ 7% after 2 – 3 months… |
Review SMBG log and continue to target and
intensify regimen |
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What agents lower the A1C by 1 - 2%?
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MNT (diet)
Metformin (Glucophage) Sulfonylureas |
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What agents lower the A1C by 1 - 1.5?
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Meglitinides
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What agents lower the A1C by 0.5 to 1.5%
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Thiazoldinediones
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What agents lower the A1C by 0.5 - 1%
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Incretin Mimetics (GLP 1 Receptor Agonist)
DPP-IV Inhibitors |
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What agents lower the A1C by 0.4-0.5%
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Pramlintine (Symlin)
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Pharmacotherapeutic Approach
Tier 1 Step 1 |
(90%)1st line sequence. Best established and most cost-effective sequence according to EBM
1)MNT + Metformin |
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Pharmacotherapeutic Approach
Tier 1 Step 2 (Not at goal) |
(A1C < 8.5%) --- Add SU (done)
(A1C >8.5%) ---Add Basal Insulin If still Not at goal - Basal/Bolus regimin |
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Use Tier 2 Treatment Approach if.............
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Hypoglycemia concerns:
PIOglitazone or Exenatide have low potential to cause this For weight loss: Exenatide or Liraglutide |
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Tier 2 Treatment Approach
Step 1 |
MNT +
Metformin |
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Tier 2 Treatment Approach
Step 2 (Not at Goal) |
Hypoglycemia concerns:
PIOglitazone or Exenatide (A1C Less/EQ 8%) For weight loss: Exenatide (A1C Less/EQ 8%) or Liraglutide |
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Tier 2 Treatment Approach
Step 3 (Not at Goal) |
Add SU or Start Basil Insulin
still not at goal? Intensify Insulin - Basal/bolus |
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Meglitinides
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small role for those who have functioning beta
cells, but need additional postprandial coverage. not substitutions for SU in those patients who have sulfa allergies because they are not as powerful |
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DPP-IV inhibitors
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small role in patients who
1. need a small amount of A1C lowering 2. are dealing with primarily postprandial excursions, 3. need once daily dosing 4. and need some help with satiety. Remember they are weight neutral |
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Type 1 Approach to Treatment
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Replace insulin the body’s not producing
Basal insulin to cover daily insulin production Bolus insulin to cover PPG excursions Reduce microvascular complications |
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Rapid Acting (Onset Peak Duration)
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aspart NovoLog®
lispro Humalog® 5 – 15 min 30 – 90 min <5 hours glulisine Apidra |
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Short Acting (Onset Peak Duration)
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Regular Novolin R®
Humulin R® 30 – 60 min 2 – 3 hours 5 – 8 hours |
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Intermediate Acting (Onset Peak Duration)
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Novolin N®
Humulin N® 2 – 4 hours 4 – 10 hours 10 – 16 hours |
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Long Acting Acting (Onset Peak Duration)
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glargine Lantus 2-4 no peak 20-24
Detimir Levemir 2-4 no peak 6 -23 |
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Humalog Mix
75/25® |
75% lispro protamine
25% lispro |
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Humalog Mix 50/50
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50% lispro protamine
50% lispro |
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NovoLog Mix 70/30
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70% aspart protamine
30% aspart |
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Novolin 70/30®
Humulin 70/30® |
70% NPH (neutral protamine Hagedorn)
30% Regular |
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Premixed Insulin Regimens
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Advantages:
Ease of administration Fewer injections Disadvantages Less flexibility in “tailoring” the regimen Evidence Greater A1C lowering versus glargine QD FBG was higher than with glargine alone ↑ incidence of hypoglycemia and wt gain |
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Insulin dosing Type 1
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Initial dose 0.5-0.6 units/kg/day
Based on physiologic insulin production Several administration regimens based on onset, peak, and duration of insulin |
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2/3 Rule : NPH and Regular ONLY
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Start 0.5 units/kg = (TDD)
Give 2/3 of total daily dose (TDD) in AM 2/3 of dose= NPH 1/3 of dose = Regular Give 1/3 of TDD in PM 2/3 of dose= NPH 1/3 of dose = Regular |
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50/50 rule
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For all other combinations
Give 50 % of total daily dose to Basal, Long acting insulin Glargine Detemir NPH Give 50% of TDD to Bolus Regular Lispro Aspart Glulisine |
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Insulin adjustment - Basal
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Typically a 10% to 20% range
Pt specific considerations: Insulin sensitivity Weight Duration Age SMBG How much lowering do you need? A1C How much room do you have? |
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Insulin adjustment - Bolus
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Carbohydrate counting
15g = 1 carbohydrate serving calculate how many servings Should be on 1 to 3 units per serving |
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Insulin adjustment
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Step 1: Review the SMBG
Identify areas not at goal Step 2: Determine which injection to adjust Identify if due to basal or meal time excursions Adjust injection before loss of control Don’t forget about rollover BG tends to stay high until an intervention occurs Step 3: Determine dose and new regimen |
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Insulin: Somogyi Effect
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Result of ↑ glucose production by liver
due to nocturnal hypoglycemic episode Hyperglycemia in the morning 6-8 am Hypoglycemia at 2-3 am Signs: nightmares, sweating, hunger, morning headache Result of long-acting insulin or basal insulin Treatment: Monitor 3 am glucose Reduce long-acting or basal nighttime insulin dose by 5-10 units |
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Insulin: Dawn Effect
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Result of insufficient evening or basal
insulin High morning glucose levels (4-8 am) Normal 3 am glucose levels Treatment: Increase long acting or basal insulin dose |
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Hypoglycemia Definition and Ranges
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Hypoglycemia glucose <70 mg/dL
Decrease blood glucose to the brain Two types of symptoms: Autonomic: sweating, intense hunger, palpitations, tremor, tingling, anxiety Neuroglycopenic: lethargy, confusion, agitation, weakness, dizziness, fainting 50-60 mg/dL – symptomatic or asymptomatic <40 mg/dL – symptomatic <20 mg/dL – seizures or coma |
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Hypoglycemia risk factors
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Risk factors for development
Medications which decrease BG or increase effectiveness of drugs which do so Reduced food intake Inadequate SMBG Renal/hepatic dysfunction Alcohol Hypoglycemic unawareness Medication Physiologic adaptation with aging |
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Hypoglycemia Treatment
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Treatment
Glucose tablets (15 – 20 g) preferred O.J., hard candy, regular soda Effects should be apparent in 15 minutes Check sugar and eat a light meal If semi-conscious, give IM glucagon (best) or hard candy between cheek and gum Glucagon should be prescribed for all individuals at significant risk of severe hypoglycemia Caregivers or family should be instructed on administration. |
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Hypoglycemia Treatment
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Raise glycemic target, for at least several
weeks, in individuals with hypoglycemia unawareness or one or more episodes of severe hypoglycemia Must strictly avoid hypoglycemia to partially reverse hypoglycemia unawareness and reduce risk of future episodes Note: Hypoglycemia with oral medications is less common, but due to half-life of drugs, may be more difficult to correct |
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Patient monitoring
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FBG at every visit
SMBG Check before meals or 2 hours after meals Type 1 : Check TID or QID Type 2: No specific recommendation Depends on regimen, presence of adjustment phase, pt control Can vary from once per 2 weeks to QID A1C Every 3 months if uncontrolled Every 6 months if controlled (must be controlled on 2 consec, visits) |
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Patient monitoring
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Blood pressure at every visit (<130/80)
Dental exam every 6 months Annually Microalbuminuria Eye exam Lipids Urine Ketones When glucose >300 mg/dL consistently |
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Preventative & Concomitant Care
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Vaccination
Annual influenza vaccination Pneumococcal vaccination At least one lifetime vaccination Revaccinate if 65yo and initial vaccination was before age 65 and at least 5 years ago Smoking cessation HTN, Dyslipidemia, and CKD Important part of patient care |
