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48 Cards in this Set
- Front
- Back
Goals of Medical nutrition therapy: 4
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*Achieve and maintain
1) Blood glucose as normal as safely possible 2) Lipid profile that reduces vascular risk 3) Blood pressure as normal as safely possible (<130) 4) Prevent or slow the development of diabetes complications (retinopathy, neuropathy, nephropathy) *Individualizing therapy--each pt is unique |
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MNT Recommendations: Carbohydrates--
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*Generally 45-65% of diet
*Prefer carbs from fruits, vegetables, whole grains, legumes, low-fat milk *Monitor carbs -Carbohydrate counting -Exchanges (1ex = 15g CHO) -Experience-based estimation -Glycemic index? |
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MNT Recommendations: Fat and cholesterol--
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*Total dietary fat < 30%
*Limit saturated fat to <7% of total calories Also minimize trans fats *Limit dietary cholesterol < 200 mg/d |
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MNT Recommendations: Protein--
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*Generally 15-20% of energy requirements
*“Good-quality” sources (provide all 9 essential amino acids): milk, cheese, soy, MEAT. |
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Exercise: Benefits: 4
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*Improve blood glucose control
-Exercise increases movement of GLUT4 to cell surface in skeletal muscle -Exercise improves insulin sensitivity (mechanisms still being defined) *Reduce cardiovascular risk *Contribute to weight loss *Improve well-being |
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Exercise recs for DM patients:
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*At least 150 minutes/week of moderate intensity aerobic physical activity (50-70% of maximum heart rate)
[MHR= 220 - age] *Resistance training 3x/week |
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Weight loss recs:
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*Modest (5-10%) weight loss reduces insulin resistance in overweight/obese individuals
*The key is CALORIE-RESTRICTION, not nutritional content *The best “diet” is one that a patient can maintain longterm! *Physical activity is an important component in maintenance of weight loss |
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Pathophysiology of Type 2 DM: 3
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1) Insulin resistance
2) Defective insulin secretion 3) Other issues: Defective glucagon regulation |
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UKPDS (study): Progressive Deterioration in b-Cell Function Over Time--
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50% loss of ß cells at diagnosis of DM2.
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Insulin Secretory Pathway in the Pancreatic b-Cell:
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*Sulfonylurea receptor is near Katp channel; causes release of insulin.
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Sulfonylureas: 3 TO REALLY KNOW
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INSULIN SECRETAGOGUES!
*“First-generation” -Tolbutamide -Chlorpropamide -Tolazamide -Acetohexamide *“Second-generation” -Glyburide** -Glipizide** -Glimepiride** -More potent -Fewer side effects -Fewer drug interactions **=most important ones |
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Side effects of sulfonylureas: 2
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Hypoglycemia
Weight gain Of the 2nd-generation SUs, GLYBURIDE causes the most hypoglycemia |
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Short-acting insulin secretagogues: diagram--
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*Netaglinide binds to the same site as sulfonylureas
*Repaglinide binds a different site |
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Describe short-acting insulin secretagogues:
"best" one? what's a main drawback to these? |
*Shorter duration of action
-Take 3x/day with meals *Major action is to lower postmeal glucose excursions -REPAGLINIDE also lowers fasting glucose -REPAGLINIDE lowers A1c more than nateglinide *Hypoglycemia and weight gain -Less than sulfonylureas *Significantly more expensive than sulfonylureas |
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Biguanides structure:
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METFORMIN FREAK!!!!
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How does metformin work? 2
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1) Metformin works primarily by increasing insulin sensitivity in the liver
2) Decrease hepatic gluconeogenesis |
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Treatment With Metformin in Type 2 Diabetes-- plasma glucose levels throughout the day--
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*MAIN ACTION IS TO INCREASE INSULIN SENSITIVITY AND DECREASE LIVER GLUCONEOGENESIS IN LIVER
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Metformin side effects:
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*Gastrointestinal distress
-Minimized by slow titration of dose and administration with food *Some interference with vitamin B12 absorption, usually not clinically meaningful *Does NOT cause weight gain *Does NOT cause hypoglycemia (used alone) |
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Metformin's serious complication:
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*Lactic Acidosis!!!
*Serious metabolic complication due to metformin ACCUMULATION *Incidence of 0.03 cases per 1,000 patient-years but fatal in ~50% of cases *Risk RISES with increasing RENAL dysfunction and advancing AGE. |
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Metformin Prescribing Considerations: when should you not Rx it? 7
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*Metformin should be avoided in
-renal dysfunction (what degree??) -Uncompensated CHF -Use of iodinated contrast materials for radiologic studies (“hold” for 48 hours) -acute or chronic metabolic acidosis, INCLUDING DKA (but that occurs in DM1 only, and DM1 patients SHOULD NOT be Rxd Metformin, so this should be a non-issue) -Significant hepatic dysfunction -Alcohol abuse (etoh damage to liver) -Acute serious illness |
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UKPDS: Effects of Intensive (Metformin) Treatment:
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*Intensive = Metformin + a SU or insulin
*Bottom line--Metformin works |
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Metformin: other uses--
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*Improves ovulatory function in women with polycystic ovary syndrome
*Decreases risk of progression to diabetes in patients with prediabetes (used off-label for this purpose) |
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Structures of Thiazolidinedione Agents:
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*Pioglitazone still used.
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TZDs/Glitazones:
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*Improve insulin sensitivity in adipose tissue and skeletal muscle
-Concentration of PPARγ is high in adipose tissue but low in skeletal muscle -TZD’s interact with PPARγ in the cell nucleus (intranuclear), and certain genes are expressed -Decreased insulin resistance |
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*TZD action
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TZD side effects:
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*Fluid retention/edema
*Weight gain *Congestive heart failure Especially in combination with insulin *Increased risk of heart attack (rosiglitazone) *Increased risk of fractures *Increased risk of bladder cancer? *Hepatotoxicity (troglitazone) *Expensive *No hypoglycemia (when used alone) |
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TZDs: Other uses--
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*Used in PCOS
-Less frequently than Metformin *Used in DM prevention in high risk patients -Less frequently than Metformin *Role in treatment of Nonalcoholic Steatohepatitis? |
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Alpha-glucosidase inhibitors:
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*Competitively inhibit (1) alpha-glucosidase enzymes in brush border of small intestine; and (2) pancreatic alpha-amylase
*Delay the breakdown of oligosaccharides to monosaccharides *Take 3x/daily with meals *Delayed glucose absorption results in lower postprandial hyperglycemia |
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Alpha-glucosidase inhibitors: Side effects--
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*GI side effects
-Undigested carbohydrate that enters large intestine is metabolized by bacteria to short-chain fatty acids, hydrogen, carbon dioxide and methane -FLATULENCE is very common *No weight gain *No hypoglycemia (when used alone) |
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Antihyperglycemic Agents: Major Sites of Action (the story as of 2006)--
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*Know sites of action
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The Incretin Effect in Healthy Subjects:
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ORAL intake promotes higher release of insulin than IV glucose= incretin effect
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The Incretin Effect in Subjects Without and With Type 2 Diabetes:
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*Incretin effect is blunted in DM2 as compared to DM1
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Both insulin secretion and glucagon suppression are impaired in type 2 diabetes after a meal--GLP 1
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Effects of GLP-1:
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*This is an Incretin--helps cause incretin effect.
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Decreased Postprandial Levels of the Incretin Hormone GLP-1 in Patients With Type 2 Diabetes:
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dark line= pre-diabetic pt
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Role of Incretins in Glucose Homeostasis:
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DPP-IV breaks down GLP-I
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Mechanism of Action of DPP-IV Inhibitors:
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DPP-4 inhibitors (SitaGLIPtin, SaxaGLIPtin, LinaGLIPtin):
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*No hypoglycemia when used alone
*No weight gain *May need dose adjustment if taking drugs that inhibit CYP3A4/5 or if renal dysfunction *More nasopharyngitis and URIs in clinical trials *Hypersensitivity reactions? *Pancreatitis? *More expensive *New drug, so long term side effects UNKNOWN |
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Colesevelam:
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*Bile-acid-binding resin
*Used as LDL-lowering therapy *Mechanism by which it lowers blood sugar is under investigation |
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NORMAL
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Colesevelam ACTION TO LOWER LDL.
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Colesevelam: Side effects--
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*GI side effects (esp. constipation)
*Worsen hypertriglyceridemia *Reduce absorption of fat-soluble vitamins *Reduce absorption of drugs (inc. levothyroxine and OCPs) |
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Bromocriptine:
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*Quick-release formulation
*Pulse of DA agonist to brain centers regulating peripheral fuel metabolism *Reduce postprandial glucose without increasing insulin |
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Bromocriptine: Cautions--
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*Typical side effects: nausea, dizziness (orthostasis), somnolence
*Potential to exacerbate psychosis *Other concerns -Highly bound to serum proteins -CYP3A4-metabolized |
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Oral Agents 20 years ago--
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Sulfonylureas
Biguanides |
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Oral Agents available now:
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*Sulfonylureas
*Metformin *Thiazolidinediones *Short-acting insulin secretagogues *DPP4 inhibitors *Alpha-Glucosidase inhibitors *Colesevelam *Bromocriptine |
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Sites of Action of:
SUs short acting insulin secretagogues a-glucosidase inhibitors biguanides TZDs bromocriptine Colesevelam DPP4 inhibitors |
SUs: ß cells--have own receptor, near Katp channel
Short acting insulin secretagogues: ß cells--bind same site as SUs, except Repaglinide, which has its own binding site. a-glucosidase inhibitors: alpha-glucosidase enzymes in brush border of small intestine; and pancreatic alpha-amylase Biguanides: Liver TZDs: PPARγ in adipose tissue and skeletal muscle bromocriptine: BRAIN Colesevelam: Intestines--bile acid binding DPP4 inhibitors: Intestines |