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210 Cards in this Set
- Front
- Back
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What is the end product of aerobic glycolysis?
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Pyruvate
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For what is oxygen required in aerobic glycolysis?
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oxygen is required to reoxidize NADH to NAD
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What are the two transport mechanisms by which glucose can enter a cell?
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Na-independent facilitated diffusion
Na-monosaccharide cotransport |
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What is the primary transporter of glucose in skeletal muscle and adipose tissue?
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GLUT-4
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What is the primary transporter for fructose across the cell membrane?
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GLUT-5
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What type of glucose transport is most common in the GI, renal tubules and choroid pexus?
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Na-monosaccharide cotransport
(SGLT) |
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What are the two phases of glycolysis and what is the net energy expediture/acquisition for each phase?
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Energy investment phase: use 2 ATP to generate 2 ADP
Energy generation phase: use 4 ADP and 2 NAD to yield 4 ATP and 2 NADH |
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What are the 6 key steps to glycolysis?
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1. glucose > G6P
2. G6P > F6P 3. F6P > F1,6P 4. Glyceraldehyde-3P > 1,3 bisphosphoglycerate 5. 1,3 bisphosphoglycerate > 3 phosphoglycerate 6. Phosphoenolpyruvate > pyruvate |
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What two enzymes are responsible for the phosphorylation of glucose?
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Hexokinase and Glucokinase
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Which enzyme is involved in the phosphorylation of glucose in the liver parenchyma and islet cells of the pancreas?
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Glucokinase
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What inhibits hexokinase?
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glucose 6-phosphate (the rxn product in the phosphorylation of glucose)
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What is the role of glucokinase in the islet cells of the pancreas?
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glucose sensor to determine the secretion of insulin
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When is glucokinase activated in the liver?
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In periods of hyperglycemia (fed-state), limiting the affects of hyperglycemia during the absorptive period
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What inhibits glucokinase?
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indirect inhibition by fructose 6-phospaste (which is in equilibrium with G6P due to carbon rearrangement)
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How is glucokinase inhibited in the presence of F6P?
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glucokinase is translocated into the nucleus and binds to glucokinase regulatory protein, rendering it inactive
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What causes the release of glucokinase from the regulatory protein?
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increased blood glucose levels
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What is the rate limiting and committed step in glycolysis?
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the phosphorylation of fructose 6-phosphate to frucose 1,6-bisphosphate by PFK1
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The irreversible phosphorylation of F6P is catalyzed by what enzyme?
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phophofructokinase 1 (PFK1)
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How is PFK1 regulated in the cell?
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1. concentrations of the substrate F6P
2. concentrations of ATP, AMP, and citrate (ATP and citrate inhibits, AMP activates) 3. presence of fructose 2,6-bisphosphate will activate PFK1 even with high ATP concentrations) |
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What enzyme can convert F6P to F2,6BP and back again (ie, has both kinase and phosphatase functions)?
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PFK-2
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In a well fed state, when insulin levels > glucagon levels, what happens to the concentration of F2,6BP?
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it increases signaling to PFK1 that glucose is abundant = increased glycolysis in the liver
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In a fasting state, when insulin levels < glucagon levels, what happens to the concentration of F2,6BP?
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decreases and thus leads to a decrease in glycolysis in the liver
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Which enzyme catalyzes the conversion of glyceraldehyde 3-phosphate to 1,3 bisphosphoglycerate?
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glyceraldehyde 3-phosphate dehydrogenase
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Describe the kinetic differences between glucokinase and hexokinase in response to glucose?
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Hexokinase: low Km(=high affinity), low Vmax (cannot phosphorylate more sugar than the cell can use)
Glucokinase: high Km (low affinity, needs more glucose in the cell), high Vmax (allows liver to remove the flood of glucose delivered by portal blood - preventing hyperglycemia after a meal) |
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Which reaction is the first to produce ATP in glycolysis?
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1,3 bisphosphoglycerate > 3-phosphoglycerate via phosphoglycerate kinase
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What makes phosphoglycerate kinase different from most other enzymes in glycolysis?
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it is fully reversible
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After the first substrate-level phosphorylation, what is the net ATP yield in glycolysis?
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1,3 biphosphoglycerate + 2ADP > 3-phosphoglycerate + 2 ATP
net yield = 0 |
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The conversion of phosphoenol pyruvate to pyruvate is catalyzed by what enzyme?
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Pyruvate kinase
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What activates pyruvate kinase in glycolysis?
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fructose 1,6-bisphophate, the product of the PFK reaction
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What inactivates pyruvate kinase in glycolysis?
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phosphorylation of pyruvate kinase by a cAMP-dependent protein kinase in the presence of elevate glucagon (low blood sugar)
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What is the fate of phosphoenolpyruvate (PEP) in the fasting state (low blood glucose)?
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pyruvate kinase is inactivate and thus PEP cannot continue in glycolysis and goes to gluconeogenesis
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How is pyruvate kinase dephosphorylated and thus activated?
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phosphoprotein phosphatase
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enzyme deficiency hemolytic anemia is caused by depletion of which 2 enzymes (1st and 2nd most common, respectively)?
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1. glucose 6-phosphate dehydrogenase
2. pyruvate kinase |
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What enzyme catalyzes the formation of lactate from pyruvate?
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lactate dehydrogenase
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What two factors determine the direction of the lactate dehydrogenase reaction?
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1. IC concentrations of pyruvate and lactate in the cell
2. ratio of NADH/NAD in the cell (elevated ratio = generation of more lactate) |
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What are the alternate fates for Pyruvate at the end of glycolysis?
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1. converted to Acetyl CoA in the mitochondria for fatty acid synthesis or TCA cycle
2. converted to ethanol for alcohol fermentation 3. converted to lactate in anaerobic conditions 4. converted oxaloacetate to provide substrates for gluconeogenesis |
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What are the 3 functions of the Pentose Phosphate Pathway (Hexose monophsphate shunt)?
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1. produces NADPH for reductive biosynthesis for fatty acids and steroids
2. produces ribose-5-phosphate for synthesis of nucleotides 3. produces glycolytic intermediates (F1,6BP) |
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Which step in the pentose phsophate pathway is the rate limiting step?
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The first reaction. The generation of the first NADH
G6P -> 6-phosphogluconolactone via G6DH |
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What enzyme catalyzes the rate-limiting step in the pentose phosphate pathway?
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glucose-6-phosphate dehydrogenase (G6PDH)
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Are the reactions in the non-oxidative phase of the pentose phosphate pathway reversible or irreversible?
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all of the reactions on the nonoxidative (synthesis of ribose-5-phosphate) phase are fully reversible
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When taking a dietary assessment from a patient for what does WAVE screen?
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Weight
Activity Variety Excess Screens for CV risk factors |
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Which dietary reference intakes are higher: estimated average requirement (EAR) or recommended dietary allowance (RDA)?
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The RDA is usually 2 std deviations above the EAR
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What is the difference between the estimated average requirement(EAR) and recommended dietary allowance (RDA)?
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EAR: used to assess inadequate intakes and planning goal intake for mean intake of an individual
RDA: assess inadequate intake and planning intake for a group |
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What is the BMI range for acceptable weight?
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19-26
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Obesity is defined as a BMI between what range?
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30-40
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The resting metabolic rate (RMR) accounts for what percentage of total energy expenditure in sedentary people?
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75%
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What is the primary determinant of RMR?
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Fat free mass (lean body mass)
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What activity would constitute non-exercise activity thermogenesis (NEAT)?
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fidgeting
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By what percentage do most people under report food intake?
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20-40%
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T/F: obese people who lose weight become more energy efficient than lean people at the same weight?
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True
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Comparison of the Pima Indians in Mexico and Arizona demonstrate the interaction between _____ and ______.
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Genetics and environment
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Which people are at risk for being in negative energy balance?
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pts with medical illness, surgery, chronic illness(increases RMR); hospitalized paitents with feeding tubes; elderly
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What is the function of the TCA cycle?
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oxidation of carbs, amino acids and fatty acids to producte energy (ATP)
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Where does the TCA cycle take place?
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mitochondria
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What does an anaplerotic reaction produce?
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intermediates for another metabolic pathway
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What enzyme converts pyruvate to Acetyl CoA in the mitochondrial matrix?
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pyruvate dehydrogenase complex
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Why can't glucose be formed from Acetyl CoA via gluconeogenesis?
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because the pyruvate dehydrogenase reaction is irreeversible; Acetyl CoA stays in the mitochondria
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High levels of pyruvate in the blood are diagnostic feature of what vitamin deficiency?
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Thiamine deficiency (Beri, Beri)
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What signals inhibit the pyruvate dehydrogenase complex, thereby inhibiting the TCA cycle?
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ATP, acetyl CoA, NADH
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Pyruvate dehydrogenase deficiency causes what symptoms?
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Lactic acidosis (developmental defects of brain and nervous system), muscular spasticity, early death
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Which enzyme catalyzes the synthesis of citrate from Acetyl CoA and OAA?
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citrate synthase
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What inhibits citrate synthase?
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Citrate, NADH, succinyl CoA, amount of substrate
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Aside from citrate synthase, what other enzymes does citrate inhibit?
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PFK - the rate setting enzyme of glycolysis
Acetyl CoA carboxylase - rate limiting enzyme of fatty acid synthesis |
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What is the rate limiting step in the TCA cycle?
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the oxidation and decarboxylation of isocitrate to a-ketoglutarate
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How many NADH molecules are produced in the TCA cycle and where are they formed?
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3
1. isocitrate to a-ketoglutarate 2. a-ketoglutarate to succinyl CoA 3. Malate to OAA |
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The TCA reaction converting succinyl CoA to succinate is an example of what type of reaction?
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substrate level phosphorylation
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What is the only enzyme in the TCA cycle that is embedded in the inner mitochondrial membrane, allowing it to function in the ETC?
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succinate dehydrogenase
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How many ATP molecules are produced from the oxidation of one molecule of acetyl CoA using substrate level and oxidative phosphorylation?
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12
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What factors activate the TCA cycle?
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ADP, Ca
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Chemiosmotic coupling leads to the formation of ATP in oxidative phosphorylation via what mechanism?
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the proton gradient across the inner mitochonrial membrane (via the conversion of NADH to NAD+)
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Which complexes in the ETC establish the proton gradient?
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I, III, IV
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How does Oligomycin inhibit ATP synthesis in the ETC?
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binds to the Fo domain of ATP synthase, closing the H channel preventing the re-entry of protons into the matrix --> can't phosphorylate ADP to ATP
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What percentage of ATP is generated from oxidative phosphorylation?
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85%
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Inherited defects in oxidative phosphorylation lead to what general category of diseases?
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Muscle myopathies
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What are the 4 different cell types inthe Islets of Langerhans and what do they do?
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1. B-cells (60%) - insulin
2. a-cells (25%) - glucagon 3. D-cells - somatostatin 4. F or PP cells - pancreatic polypeptide |
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How is insulin synthesized in the B-cells?
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preproinsulin -> cleavage of C-peptide into secretory vessicle (granules) --> left with alpha and beta chains joined by disulfide bonds
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T/F: C-peptides remain in the blood longer than insulin and are therefore a good measure of insulin secretion for recombinant insulins in diabetics.
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False: recombinant insulins do not contain C-peptides (however Cpeptide measures are a good gauge for biological insulin secretion)
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What is the role of C-peptide in the synthesis of insulin?
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proper folding
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What factors increase the secretion of insulin from the b-cells?
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Glucose (converted into ATP > sends signal)
Intracellular Ca Gastrointestinal peptides glucagon |
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What factors inhibit the secretion of insulin?
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somatostatin
EPI alpha-adrenergic agonists Diazoxide Cortisol Growth Hormone |
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What are the effects of insulin on muscle cells?
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when insulin binds to its receptor, it recruits Glut-4 receptors to the surface to bring more glucose into the cell -> increasing glycogen synthesis
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What are the effects of insulin on adipose tissue?
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insulin drives glucose toward triacylglycerol (TAG) synthesis and decreased TAG degradation
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What are the effects of insulin receptor activation on insulin receptor substrates (IRS)?
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phsophorylation of tyrosine residues allowing for SH2 domain proteins to dock there
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What are the 2 major pathways triggered via IRS activation?
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1. PI-3 kinase
2. GRB2 activation |
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Outline the path by which IRS activation of PI-3 kinase leads to glycogen synthesis
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IRS -> PI-3-k -> PDK (phospholipid-dependent kinase) -> PKB -> inactivation of glycogen synthase kinase (phosphorylation) -> Glycogen synthase allowed to stay active -> synthesis of glycogen from glucose
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Outline the path by which IRS activation of GRB2 leads to gene expression
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IRS -> GRB2 -> SOS (son of sevenless) -> Ras/Raf ->MAPKK -> MAPK or JNK -> gene expression
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Along with glucagon, what other counter-regulatory hormones oppose many of the actions of insulin?
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EPI, cortisol, growth hormone
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What is the function of glucagon?
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acts to maintain blood glucose levels by activating hepatic glycogenolysis and gluconeogenesis
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What factors stimulate the secretion of glucagon?
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1. low blood glucose
2. protein rich meal (counters hypoglycemia from low carbs) 3. EPI |
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What 2 factors inhibit glucagon secretion?
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1. insulin
2. elevated blood glucose |
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What is the rationale for glucagon stimulation of insulin production?
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to maintain basal insulin levels during fasting states
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Both cortisol and growth hormone have diabetogenic effects by inhibiting insulin at what level of the pathway?
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post-receptor, leading to increased insulin resistance/decreased sensitivity
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What are the roles of K and Ca channels on insulin secretion?
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The ATP generated from increased TCA activity closes the K-ATPase pump causing a depolarization of the b-cell and an influx of Ca through voltage gated channels. It is the increase in IC [Ca] that brings Insulin vessicles to be exocytosed into the portal blood
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How do you explain the biphasic response of insulin secretion to a prolonged infusion of glucose?
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1st phase is caused by vessicles already "docked" at the membrane; 2nd pahse involves recruitment of vessicles to the "docked" position
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Insulin concentrations is coupled to glucose concentrations, what is the effect of this coupling in the case of non-compensated insulin resistance?
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increased fatty acids disrupt insulin receptor-mediated glucose uptake -> loss of glucose clearance -> increased insulin secretion = normoglycemia with increased insulin -> eventual uncoupling resulting in hyperglycemia
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What is gluconeogenesis and where does it occur?
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synthesis of glucose from non-carbohydrate precursors; occurs in the liver
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What are the three precursors for gluconeogenesis?
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1. lactate
2. glucogenic amino acids (alanine, glutamate) 3. Glycerol |
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The Cori cycle uses which gluconeogenetic precursor to form glucose?
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Lactate
Lactate (muscle) -> converted to glucose in liver -> glucose to muscle -> broken down to lactate |
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What is the first reaction needed in gluconeogenesis to get pyruvate out of the mitochondria?
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pyruvate -> [pyruvate carboxylase] -> OAA -> [malate dehydrogenase] -> Malate -> [malate dehydrogenase] -> OAA -> [PEPCK] -> PEP
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At what stage in the conversion of Pyruvate to PEP in gluconeogenesis is the pyruvate product out of the mitochondria?
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in the rxn of malate to OAA
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Why can't adipocytes use glycerol as a precursor for gluconeogenesis?
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they lack glycerol kinase so they cannot phosphorylate glycerol
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How is lactate converted to glucose in gluconeogenesis?
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The Cori cycle
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How are amino acids converted to glucose in gluconeogenesis?
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a-ketoacids can enter the TCA cycle and form OAA -> direct precursor to phosphoenolpyruvate (PEP)
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In gluconeogenesis, what is the first "roadblock" to overcome in the synthesis of glucose and what 2 steps are required to bypass that roadblock?
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Roadblock: the irreversible conversion of PEP to pyruvate by pyruvate kinase
Bypass: (1) carboxylation of pyruvate to OAA with pyruvate carboxylase and (2) OAA converted to PEP with PEP-carboxykinase |
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What reaction in gluconeogenesis bypasses the irreversible glycolysis rxn, F6P -> [PFK1] -> F1,6BP?
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F1,6BP -> [F1,6BPtase] -> F6P
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What factors inhibit F1,6BP in gluconeogenesis?
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(1)High insulin/glucagon ratio -> increased F2,6BP
(2) high levels of AMP |
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Under what conditions is PFK2 a kinase? A phosphatase?
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PFK2 as a kinase: in the fed state, insulin/glucagon ration is high PFK2 is dephosphorylated and synthesizes F2,6BP (plenty of glucose to burn)
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Under what conditions is PFK2 a phosphatase?
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PFK2 as phosphatase: fasting state, PFK2 phosphorylated by cAMP-dependent PKA -> F2,6BPtase activity -> F2,6BP is converted back to F6P -> gluconeogenesis
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What bypass reaction overcomes the irreversible glycolysis reaction: glucose -> [hexokinase] -> G6P?
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In liver and kidney: G6P ->[G6P translocase] -> crosses into ER membrane -> [G6Ptase]-> free glucose
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What regulates moment-to-moment gluconeogenesis?
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glucagon levels and substrate availablility
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Von Gierke's disease, characterized by severe fasting hypoglycemia, ketosis, hyperlipidemia, lactic acidosis, and enlarged liver and kidneys, is an AR deficiency of what enzyme?
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G6P-tase in the liver
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What are 3 ways in which blood glucose can be obtained?
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1. diet
2. degradation of glycogen 3. gluconeogenesis |
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What is the function of glycogen in the muscle? Liver?
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Muscle: fuel reserve for the synthesis of ATP during muscle contraction
Liver: maintain blood glucose concentration during early fasting stages |
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Where in the cell does glycogenesis occur?
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cytosol
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What is the immediate donor to glycogen synthesis?
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UDP glucose
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What is the key regulatory enzyme in glycoenesis?
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glycogen synthase: transfers glucose from UDP-glucose to a growing 1,4 glucose chain
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How many residues must a polysaccharide chain already have for glycogen synthase to be able to add glucose residues?
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4
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In the absence of a glycogen primer, what other protein can serve as an acceptor of glucose residues from UDP-glucose?
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glycogenin; rxn catalyzed by glycogenin itself (autoglucosylation)
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What happens to the glycogen molecule after approximately 11 glycosyl residues have been added to the chain?
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branching enzymes move 6 to 8 residues and attach it to another chain with 1,6 linkages
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What enzyme converts G1P to G6P in glycogen degradation?
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phosphoglucomutase
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Pompe Dz, characterized by nml blood sugar levels, massive cardiomegally, and early infant death from heart failure, is a glycogen storage dz caused by what defect?
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Lysosome storage
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In a well-fed state, how are glycogen synthesis and degradation regulated in the liver?
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elevated G6P and ATP activates glycogen synthase and inhibits glycogen phosphorylase
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How does Ca activate glycogen degradation in muscle?
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1. Ca: during muscle contraction Ca binds to calmodulin, activating phosphorylase kinase without phosporylating it. Phosporylase kinase activates glycogen phosporylase -> degradation
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How does AMP activate glycogen degradation in muscle?
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under extreme conditions of anoxia and depletion of ATP, AMP activates glycogen phosphorylase b without it being phosporylated -> degradation
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In the fed state which carbohydrate pathways/enzymes are activated?
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In the fed state insulin is increased and we want to increase glycogenesis, glycolysis and the pentose phosphate shunt. Most of the ezymes are dephosphorylated and active.
1. glucokinase/hexokinase (glycolysis) 2. glycogen synthase (glycogenesis, increased availability of G6P) 3. increased G6P also activates the pentose phosphate shunt 4. all the rate-limiting enzymes of glycolysis (PFK, PDH |
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In the fasting state which carbohydrate pathways/enzymes are activated?
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In the fasting state insulin levels are low/glucagon high and we want to increase gluconeogenesis and glycogen degradation. Most of the enzymes are phosphorylated and active.
1. glycogen phosphorylase kinase which activates glycogen phosphorylase (degradation) 2. cAMP-dependent protein kinase (PKA) (phosphorylation of many substrates) 3. F2,6BP > F2,6BPtase > F6P (gluconeogenesis) 4. PEPCK (gluconeogenesis) |
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How much glucose would you need to give a neonate with hypoglycemia?
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8-12 mg/kg/min
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How much glucose would you need to give an infant with hypoglycemia?
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6-8 mg/kg/min
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How much glucose would you need to give a child with hypoglycemia?
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4-6 mg/kg/min
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How much glucose would you need to give an adult with hypoglycemia?
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2-4 mg/kg/min
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T/F a D-5 glucose solution will not be enough glucose to reach the basal glucose production rate in a pt
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True: you need to give a10% glucose solution
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What population is most vunerable for hypoglycemia?
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Neonates
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At what glucose level is a child diagnosed as hypoglycemic? an adult?
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Child: 45 mg/dL
Adult: 60 mg/dL |
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T/F: Glucagon is the gold standard of treatment for pts with hypoglycemia?
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False: glucagon only works for diabteics. You need to give glucose.
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What are the 3 routes of administration for glucose in a pt with hypoglycemia?
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1. orange juice
2. D10, IV glucose 3. IV glucose as recommended by age |
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If a pt presents with hypoglycemia within the 1st 2-4 hours after a meal, what is the likely pathophys?
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post absorption: hyperinsulinism
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If a pt presents with hypoglycemia 3-8 hours after a meal, what is the likely pathophys?
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glycogenolysis and severe forms of glycogen storage dzs
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If a pt presents with hypoglycemia 8 to 12 hours after a meal, what is the likely pathophys?
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gluconeogenesis disorders or mild glycogen storage dzs
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If a pt presents with hypoglycemia 12to 15 hours after a meal, what is the likely pathophys?
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fatty acid oxidation disorders, mild glycogen storage dzs
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If a pt presents with hypoglycemia 20 or more hours after a meal, what is the likely pathophys?
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idiopathic
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What is the definition of diabetes?
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blood glucose that is increased to a point that it would cause microvascular disease
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Pts with abnml carbohydrate metabolism, but who are not yet diabetic are at risk for what category of dz?
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Macrovascular (CAD, cerebrovascular dz)
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What are the 4 sympoms of high glucose?
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polyuria: frequent urination, nocturia
Polydypsia: excessive thirst and drinking Blurry vision Weight loss |
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What is the main difference between Type 1 and Type 2 diabetes?
|
Type 1: autoimmune destruction of b-cells; insulin deficiency with presumed insulin sensitivity
Type 2: insulin resistance; insulin is secreted but not sufficient to control the blood sugar |
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Which form of diabetes is more common, Type 1 or Type 2?
|
Type 2
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Which form of diabetes is more likely to occur with a positive family hx?
|
Type 2
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Diabetes is characterized by what lab values?
|
Fasting glucose >125 mg/dL
OGTT > 200 mg/dL |
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Production of what insulin byproduct is a clinical marker for a positive prognosis in diabetes?
|
C-peptide
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Pts with Type 1 diabetes will be asymptomatic until how many b-cells are destroyed?
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80-90% destruction of b-cells
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What does the response look like after an IV Glucose tolerance Test in pts with T1D?
|
you see a low 1st phase response (suggests that there are few "predocked" insulin vessicles in the membrane)
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Which HLA genotype shows the highest risk for T1D?
|
HLA-DR 3/4
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What is a person's risk for T1D if they have HLA-DR 3/4?
|
1:15
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T/F: The more variable number of tandem repeats (VNTR) on the insulin gene, the less of a risk for T1D?
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True, more VNTR (Class III) is correlated to increased exposure in the thymus and more Tcell tolerance to the pancreatic b-cell
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T/F: immunizations have been linked to increasing numbers of T1D.
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False. Get vaccinated, bitches.
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Which treatments are most effective in the prevention of T1D?
|
No treatment has proven effective in the prevention of T1D.
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Name the two pathophysiological components that trigger the development of T2D.
|
beta cell dysfunction (defective insulin secretion)
Insulin resistance |
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What does the response to the IV glucose tolerance test look like in a pt with T2D?
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loss of 1st phase insulin release with a prolonged/exaggerated 2nd phase
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In T2D, insulin resistance leads to what 2 physiological responses in cells?
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1. loss of insulin suppression of hepatic glucose output -> increased glucose pdxn
2. defects in insulin-mediated storage of glucose, fat and protein in muscle |
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What is the body's first defense against hypoglycemia in diabetes?
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EPI
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Which form of diabetes is one more likely to see hypoglycemia as a sx?
|
Type 1
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In early phases of T2D, what treatment has been shown to limit the abnormalities of insulin secretion?
|
Lower blood glucose; it is part of the "glucose toxicity"
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What is the role of zinc in short acting recombinant human insulins (Humulin, Novolin)?
|
increases the shelf-life of the insulin so it can last as long as Twinkies.
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How are short acting recombinant human insulins administered?
|
IV or SQ
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Describe the duration of action of long active insulin analogs (Glagine, Determir).
|
onset at 1-1.5 hours, no peak, lasts 17-24 hours
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What is the standard of care in insulin treatment for pts with T1D?
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basal-bolus therapy (multiple dose insulin therapy) - allows pts to skip meals and vary meal sizes
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What 2 conditions would warrant insulin therapy in T2D?
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1. hospitalization for extreme hyperglycemia/hyperosmo
2. ketoacidosis - acute insulin deficiency |
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What is the protocol for checking blood sugar?
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at least twice a day, optimally 4x/day
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What pancreatic cells are dysfunctional in T2D?
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b-cells (insulin) and a-cells (glucagon)
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Describe the mechanism by which insulin secretagogues enhance endogenous insulin secretion?
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^ b-cell secretion by closing K-ATP channels > depolarization > open VG-Ca channels > ^ IC [Ca] > increased fusion of insulin granules (i.e., stimulate insulin secretion without GLUT2 transport of glucose)
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Which two drugs in the treatment of T2D are useful for insulin resistance?
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Metformin and Thiazolidinediones (TZDs)
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What is the function of the incretin, GLP1.
(Note: T2D pts have elevated GLP1, suggesting resistance to GLP1) |
Secreted by the gut to enhance insulin secretion when blood sugar is high; decreased blood sugar, decreases glucagon secretion, slows gastric emptying
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Which oral agent class for the tx of T2D is effective for T1D?
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Amylin analog (Symlin):
T1D pts are amylin deficient and T2D are amylin resistant |
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What are the target HbA1C levels for pts with diabetes?
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< 7%, general
< 6%, individual (nl HbA1C is about 5%) |
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How often in HbA1C drawn in pts with diabetes?
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At least 2x/year
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How many grams of carbohydrate should a 70Kg man eat (assume that half of his diet comes from carbs)?
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262.5g (70kg * 30kcal/kg = 2100 kcal/day * .5 = 1050kcals from carbs/day divided by 4kcal/g (carb energy density) = 262.5g of carbs
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What category of carbohydrate has greater than 9 monomers?
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polysaccharides
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How many monomers are in an oligosaccharide?
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three to nine
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Name the sub-classes of (simple) sugars:
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monosaccharides, disaccharides, polyols
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An intermedicate glycemic index is defined as what range?
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56-69
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What is the glycemic load of watermelon? (GI = 72, carbs=5%)
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3.6
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Why are whole grains good for you?
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The husk contains fiber, which promotes good digestion (motility, stool volume) and may lower cholesterol
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How much fiber should you eat in a day?
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15-25g
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What is the difference between soluble and insoluble fiber?
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soluble absorbs water (and therfore lowers LDL/post-prandial glucose and increases GI bulk better), insoluble does not
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What are the primary symptoms of lactose intolerance?
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gas and diarrhea (from fermentation of lactos by coloinic flora/osmotic load to the colon)
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What health benefits does eating oligosaccharids and amylose provide?
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incomplete absorption leads to colonic fermentation, which produces short chain fatty acids than help insulin sensitivity and lipid levels
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Why is amylopectin easier to digest than amylose?
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Has lots of "free ends" since its highly branched (amylose is linear and has only 2 ends)
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What is resistant starch?
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slowly absorbed because of prerparation method - similar health benefits to amylose (ie Corn)
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What is aspartame?
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example of "non-nutritive sweetener" - tastes good but unabsorbed
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What are the THREE types of studies used to inform nutritional decisions?
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Animal, Epidimelogicial, RCT (small w/soft endpoints, large w/hard endpoints)
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Which nutritional study type is the "gold standard"
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large RCT with hard endpoints
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Explain the difference between glycemic index and glycemic load:
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Index is the amout of glucose excursion a certain food triggers in a controlled experiment, load is the actual glucose spike produced by the food during normal eating (GI * carb content %)
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What is the most common acute complication of Diabetes?
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Hypoglycemia
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What lab values are necessary to diagnose DKA?
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Blood glucose > 200 mg/dl and positive urine dipstick ketone
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What are the TWO main components of DKA treatment?
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Insulin and Fluid Replacement
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What is the most common cause of DKA?
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infection (often accompanied by misguided omission of insuilin)
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At what level do hypoglycemia symtoms appear?
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Sugar < 50-60 mg/dl
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What are the TWO hypoglycemia symtom categories?
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Adrenergic (from excessive Epi secretion) and Neuroglycopenic (from CNS disfunction)
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Hypoglycemia is more common in which diabetes type?
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Type 1, since they take insulin more
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What is the treatment of hypoglycemic unawerness?
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avoid hypoglycemia for at least 3 weeks
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What are THREE non-diabetes causes of fasting hypoglycemia?
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Insulinoma, B cell tumor, MEN 1
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What is the tell-tale sign of factitious hypoglycemia?
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High insulin but low C peptide
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What are the THREE vascular wall responses to diabetes?
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Abnormal endothelial function, Abnormal smooth muscle function, decreased fibrinolysis
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Hypertension is more common in which diabetes type?
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Type 2 (happens in type 1 only after renal disease onset)
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What are the FOUR main treatments of the macrovascular complications of diabetes?
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aspirin, B blockers, antihypertensives, lipid lowering agents
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What are the FOUR mechanisms for MICROvascular complicaitons of diabetes?
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polyol pathway, non-enzymatic glycosylation, elevation of Protein Kinase C, Osidative/Carbonyl Stress
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What are the FOUR types of Microvasucular diabetes complications?
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Retinopathy, Nephropathy, Neuropathy, Foot Disease
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How do we prevent retinopathy in diabetes?
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Annual exams (track stages), intervene w/laser during mild/severe PREproliferative stages
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How is diabetic nephropathy treated?
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Aggressive control of hyperglycemia and blood pressure (ACE-I and B Blockers)
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What are the FOUR categories of diabetic neuropathy?
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Distal symmetric polyneuropathy, Autonomic neuropathy, Mononueritis multiplex, diabetic amyotrophy
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How can diabetic foot disease be prevented?
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Appropriate footwear, examination, and education
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