- Every three year starting at age 45

- If risk factors, should be started earlier (risks include family history, obesity, and signs of insulin resistance)

- Sx of diabetes plus casual plasma glucose concentration of >200mg/dL

or

FPG > 126mg/dL

or

2 hour post-load glucose > 200mg/dL during OGTT

For the ADA:

Hemoglobin A1C - <7%

Preprandial plasma glucose - 90-130 mg/dL

Postprandial plasma glucose < 180mg/dL

ACE and AACE:

A1C - <6.5%

Preprandial plasma glucose - <110 mg/dL

Postprandial plasma glucose - <140mg/dL

- Near normal glycemic levels reduces risk of microvascular complications, but aggresive management of cardiovascular  risk factors (smoking, blood pressure, etc) is needed to reduce macrovascular complications

- Set goals for each parameter and monitor accordingly

- Medical nutrition therapy for all patients

- For T1DM, regulating insulin administration and a meal plan moderate in carbs and low in saturated fat to maintain a healthy weight

- T2DM, Caloric restriction to promote weight loss

- Aerobic exercises can improve insulin resistance and glycemic control, reduce the incidence of cardiovascular complications, help with weight loss, and improve well-being.  Start program slowly in sedentary individuals and do appropriate screening in those with medical complications before starting a regimen

Humalog - insulin lispro

Novolog - Insulin aspart

Apidra - Insulin glulisine

All are insulin analogs made from recombinant DNA technology

Humulin R (Regular)

Novolin R (regular)

These are NOT insulin analogs

- Humulin N

- Novolin N

these are NOT insulin analogs

- Lantus (insulin glargine)

- Levemir (Insulin detemir)

Both insulin analogs

Humalog mix 75/25 - 75% neutral protamine lispro, 25% lispro

Novolog Mix 70/30 - 70% aspart protamine suspension, 30% aspart

Humalog mix 50/50 - 50% neutral protamine lispo, 50% lispro

NPH regular combos - Humulin 70/30, Novolin 70/30, Humulin 50/50

Onset - 15-30 minutes

Peak - 1-2 hours

Duration - 3-4 (aspart 3-5)

Max duration - 5-6 hours (Lispro 4-6)

Appearance - clear

Onset - 30-60 minutes

Peak - 2-3 hours

Duration - 3-6 hours

Max duration - 6-8 hours

Appearance - clear

Onset - 2-4 hours

 Peak - 4-6 hours

Duration - 8-12 hours

Max duration 14-18 hours

Appearance - CLOUDY

NPH insulin is Not Particularly Heaven-like (as in cloudy, not clear)

Glargine:

Onset - 4-5 hours

Peak -----

Duration - 22-24 hours

Max duration - 24 hours

Appearance - Clear

Detemir:

Onset - 2 hours

Peak - 6-9 hours

Duration 14-24 hours

Max duration - 24 hours

Appearance - clear

- Glucose 10-15g in conscious patients

- Dextrose IV in patients who have lost consciousness

- Glucagon 1g intramuscular in unconscious patients where IV access cannot be established

T1DM - 0.5-0.6 units/kg

 (0.1-0.4units/kg in "honeymoon phase")

Acute illness or ketosis (0.5-1unit/kg)

T2DM - 0.7-2.5units/kg in significant insulin resistance

- Synthetic analog of exendin-4, 39 amino acid peptide from the saliva of the Gila monster (a kind of lizard)

- Enhances glucose-dependent insulin secretion, reduces hepatic glucose production

- Decreases appetite, slows gastric emptying

- Because of mechanism, significantly affects postprandial glucose levels but much smaller effect on FPG.

- Average A1C reduction of 0.9%

- Adverse rxns n/v/d

- Start with 5mcg bid, then increase to 10mcg bid 0-60 minutes before morning and evening meals

- Used as an adjunct in patients who have not achieved adequate results with metformin, a sulfonylurea, and/or a thiazolidinedione

- Synthetic analog of amylin, a neurohormone cosecreted from beta-cells with insulin

- Pramlinitide suppresses high postprandial glucagon secretion, reduces food intake, and slows gastric emptying

- Average A1C reduction 0.6%, but optimizing insulin therapy could lower A1C even further

- Most effect on prandial levels, little effect on FPG

- Best effects in T1DM, stabilizes wide postprandial swings

- Adverse rxns of n/v/anorexia

- ONLY indicated in patients on insulin therapy, reduce prandial dose by 30-50% at first to reduce hypoglycemia

- in T2DM, dose is 60mcg before major meals, titrate up to 120mcg

- In T1DM, dose is 15mcg, titrate up to 60mcg prior to each meal

- - Exert effect by stimulating pancreatic secretion of insulin

- All equally effective in lowering BG when used in equipotent doses

- A1C will fall by 1.5-2% with FPG  reductions of 60-70mg/dL

- Adverse rxns most common are hypoglycemia, weight gain, rarely skin rash, hemolytic anemia and cholestasis

- hyponatremia most common with chlorpropramide but also reported with tolbutamide

- Titrate every 1-2 weeks (long with chlorpropramide)

- Stimulate pancreatic secretion of insulin similar to sulfonylureas, but insulin release is GLUCOSE dependent and diminishes at low blood glucose concentrations

- Less hypoglycemia than sulfonylureas

- A1C reduction of 0.8-1%

- Best used to increase insulin secretion during meals in those close to glycemic goals

- Only administer with meals. 

- If meal is skipped, skip medication as well

- Repaglinide (Prandin) admin. 0.5mg-2mg with every meal, max dose 4mg, MDD = 16mg

- Nateglinide (Starlix) dosing is 120mg tid with meals, may lower to 60mg if close to A1C goal

- Metformin only biguanide available in US

- Enhances insulin sensitivity of hepatic and musle tissue (increased uptake of glucose)

- Reduces A1C by 1.5-2%, FPG by 60-80mg/dL, and can reduce FPG levels when they are very high (>300mg/dL)

- Also, reduces TG by 8%, LDL by 15%, and increases HDL by 2%

- Metformin should be used first in T2DM if not contraindicated b/c it is only medication proven to reduce mortality and CVD risk

- Adverse reactions are abdominal discomfort, metallic taste, diarrhea, anorexia

- Can reduce side effects by titrating up to dose slowly or using XR

- Lactic acidosis if serum creatinine > 1.4 mg/dL in women and > 1.5 in mean, avoiding in CHF, 

- d/c use 2-3 days before IV radiographic dye studies until normal renal function documented

- Activate PPAR, a nuclear transcription factor important in fatty cell differentiation and fatty acid metabolism

- PPAR agonists enhance insulin sensitivity in muscle, liver, and fat cells indirectly (insulin must be present in great quantities for this to occur)

- After 6 months, reduce A1C by 1.5%, FPG by 60-70mg/dL at max doses; max effects not seen until 3-4 months in to therapy

- Monotherapy generally not effective unless given EARLY in disease state where beta cell function and insulinemia is highest

- Pioglitazone decreases TG by 10-20%

- Rosiglitazone can INCREASE LDL by 5-15%

- Use with EXTREME caution in CHF and other fluid-retaining patients, incidence of edema almost 5% in normal patients, but if using insulin could be 15%

- Hepatotoxicity black box, do not START drug is ALT is 2.5x that of normal, d/c if 3x that of normal

- Rosiglitazone (Avandia) has been associated with angina and MI

- Pio (Actose) start at 15mg qd, mdd 45mg

- Rosi - 2-4mg qd, mdd = 8mg (can divide into bid for maximal A1C effect)

- Prevent breakdown of sucrose and complex carbohydrates in small intestine, prolonging the absorption of carbohydates

- Net effect is reduction in postprandial BG (40-50mg/dL), while FPG relatively unchanged (maybe 10% reduction)

- A1C reduction of 0.3-1%

- Optimal patients are near target A1C with near-normal FPG but high postprandial glucose

- Adverse rxns include flatulance, bloating, abdominal discomfort, and diarrhea, minimize by slow dosage titration

- If hypoglycemia occurs (most likely in combo with other agents), must use oral or parenteral glucose because mechanism will block breakdown of complex carbs (e.g, eating a candy bar won't help)

- Acarbose (precose) and miglitol (glyset) are dosed similarly.  Therapy initiated at very low dose (25mg/one meal a day), increased over several months, to 50mg tid with meals (if < 60kg) or 100mg tid with meals (if over 60kg).

- Take with first bite of meal because drug must be present to inhibit enzyme

- prolong the half-life of endogenously produced glucagon-like peptide-1 --> reduce the inappropriately elevated glucagon levels postprandially, and stimulate glucose-dependent insulin secretion

- Average A1C reduction of 0.7-1% at dose of 100mg/day

- Only adverse event seems to be mild hypoglycemia

- Sitagliptin (Januvia) dosed at 100mg once daily.  If CrCl 30-50ml/min reduce to 50mg, if <30ml/min reduce to 25mg

- Timing of insulin onset, peak, and duration of effect must match meal and exercise regimen for patient

- Regimen of two daily injections (NPH + regular insulin in the morning and at night)can cover the patient

- Start patients on 0.6units/kg with 66% of dose given in morning, and 33% in the evening, two thirds of that 66% morning dose should be of NPH

- If patient hyperglycemic in the morning, evening NPH can be moved to bedtime

- Good example of dosing would be 50% of daily insulin given as glargine + 20% regular, then 15% regular at lunch and 15% regular at dinner time

1. 2 doses,a R or Rapid acting + N, L, A, GLU R, L, A, GLU + N

+ N

2. 3 doses, R or R, L, A, GLU R, L, A, GLU R, L, A, GLU

rapid acting + N + N

+ N

3. 4 doses, R or R, L, A, GLU R, L, A, GLU R, L, A, GLU N

rapid acting

+ N

4. 4 doses R or R, L, A, GLU R, L, A, GLU R, L, A, GLU N

rapid acting + N

+ N

5. 4 doses,b R R, L, A, GLU R, L, A, GLU R, L, A, GLU G or Db

or rapid acting (G may be given

+ long acting anytime every

Targets - A1C < 6.5%
FPG < 110mg/dL

2-hour PPBG < 140-180mg/dL

- Make initial intervention with education, including nutrition and excercise

- If targets not met within 1 month, initiate monotherapy or dual therapy

-  If mono/dual therapy not met after 3 months, add additional agent (exenatide) if A1C not < 8.5%

- If at any time (beginning of mono/dual therapy) targets are met, reevealuate every 3-6 months

Initial monotherapy options: Metformins, TZD, Sulfonylurea, Insulin (others:repaglinide or nateglinide, alpha-glucosidase inhibitor)

Dual therapy: Sulfonylurea + Metformin, Metformin + TZD, sulfonylurea + Metformin + exenatide

* If initial presentation glucose > 260mg/dL, give dual therapy + insulin

* If initial presentation >210 mg/dL or A1C>9% give dual therapy off the bat
* If obese, start on Metformin and titrate up to 2g/day, near normal weight use an insulin secretagogues 

Retinopathy - exam every 6-12 months.  laser photocoagulation has markedly improved sight in diabets

Neuropathy - Low dose tca, anticonvulsant, duloxetine, effexor, topical capsaicin, tramadal of NSAID

Gastroparesis - Reglan or erythromycin

Orthostatic hypotension - mineralcorticoids or adrenergic agonists

Diabetic diarrhea - 10-14 day course of antibiotic such as doxycycline or metronidazole, octreotide in unresponsive cases

ED - Sildenafil or others

Nephropathy - Glucose and blood pressure control, ACE or ARBS prevent progression of renal disease in diabetics, diuretics as second line therapy

Peripheral  vascular disease and foot ulcers - Claudication and nonhealing foot ulcers may need antiplatelet therapy, smoking cessation, Pentoxyfilene or cilostazol may be useful, or a revascularization procedure, topical treatment or debridement

Coronary Heart Disease - 

- Acetohexamide (Dymelor) DOA16h

- Chlorpropamide (Diabinese) DOA72h

- Tolazamide (Tolinase) DOA24h

- Tolbutamide (Orinase) DOA12h

- Glipizide (Glucotrol, XL) DOA20h

- Glyburide (Diabeta, Micronase) DOA24h

- Glyburide, micronized (Glynase) DOA24h

- Glimepiride (Amaryl) DOA24h

*Do not have to take with food

- Nateglinide (Starlix) DOA4h

- Rapeglinide (Prandin) DOA4h

*Both must be taken with food

*Both metabolized by P4503A4

- Metformin (Glucophage, XR) DOA24h, bid or qd if XR

- IR -> No metabolism, renally excreted

- XR -> Take with evening meal or may split dose

- Pioglitazone (Actos) DOA24h, 2C8 and 3A4, metabolites have longer half-lives than parent drug

- Rosiglitazone (Avandia) DOA24h, 2C8 and 2C9, inactive metabolites renally excreted

- Acarbose (Precose) - with meals, DOA3h, eliminated in bile

- Miglitol (Glyset) - with meals, DOA3h, eliminated renally