FINAL REVIEW Flashcards
What disease is associated with the body producing less insulin and the insulin produced is not effectively binding to the receptor?
T2DM
What ratio causes insulin resistance?
Low insulin: glucagon ratio
What are the modifiable risk factors for T2DM
impaired fasting glucose (hyperglycemia and insulin resistance
What are the dietary goals for prevention of T2DM
reduce insulin resistance, improve insulin sensitivity
body weight control (adiposity)
reduce risk of CVD
What three factors affect the relationship between CHO and T2DM?
Sugars
High GI/GL Diet
Fiber
What are two mechanisms of sugar increasing the risk of T2DM
- insulin receptor inactivation
2. excess calories - adiposity
Explain the sugar mechanism of insulin receptor inactivation and T2DM
Sugar overload increases lipogenesis (TAG), which decreases tyrosine phosphorlation of insulin receptors. This inhibits the PIP cascade, where GLUT 4 is not translocated and is not engaged in glucose clearance
Explain the sugar mechanism of excess calories and T2DM
The intake of sugar provides a low satiating food, which leads you to eat more calories which leads to weight gain. Which leads to insulin resistance and dyslipidemia.
What are two mechanisms of High GI/GL diet causing hyperglycemia leading to T2DM
- Beta cell exhaustion and 2. adiposity and insulin resistance
Explain the High GI/GL mechanism of beta cell exhaustion of and increasing hyperglycemia in T2DM
A high GI/GL diet leads to increased postprandial glucose, and increased insulin demand, which leads to beta cell exhaustion and hyperglcemia
Explain the High GI/GL mechanism of adiposity and insulin resistance and increasing hyperglycemia in T2DM
A high GI/GL diet increases plasma FFA which increases ectopic fat deposits, leading to increased insulin resistance and hyperglycemia.
What are two mechanisms of a fiber diet reducing the risk of T2DM
- Satiety and body weight and 2. fermentation
Explain the fiber mechanism of adiposity and satiety and body weight and reducing the risk of T2DM
Fiber intake increases post meal satiety, which possibly decreases caloric intake of subsequent meals, which leads to decreased body weight, improved insulin sensitivity and decrease risk of T2DM
Explain the fiber mechanism of fermentation and reducing risk of T2DM
Fiber intake increased fiber fermentation in the gut which leads to the production of SCFA. This acts as an allosteric inhibitor of gluconeogenesis which decreases hepatic glucose output. Then this acts as a ligand to stimulate PPAR, which up-regulates GLUT 4 expression and increases glucose uptake
What are the overall recommendations for beneficial effects of CHO and T2DM
- Increase dietary fiber, cereal fiber, fruit fiber (MetS)
- Increase whole grain intake: at least 3 serv/d
- Increase legumes and bean consumption
- Fiber, low GI/GL, other nutrients/non-nutrients - Focus on a low GI/GL diet
What are the overall recommendations for detrimental effects of CHO and T2DM
- Consumption of High GI/GL foods recommendation is toDecrease consumption of high GI/GL foods
- Decrease intake of Potatoes, white rice, noodles, other high GI/GL foods
- Decrease consumption of SSB and added sugars
What three factors affect the relationship between FA and for T2DM?
Palmitic acid/Stearic acid Vaccenic acid Oleic acid N-3 ALA N-6 LA Red Meat, Processed Meat Egg Dairy Nuts
What is a mechanisms of Palmimtic and stearic acid increasing the risk of T2DM
- Biomarker for palmitic and stearic acids do not correlate to SFA intake, instead act as CHO
Explain Palmitic and stearic acid intake increasing risk of T2DM
Mimics high GI CHO intake, high GI CHO intake increases lipogenesis, producing palmitic and stearic acids. This increases TAG which increases insulin resistance
What is the association between Vaccenic acid and T2DM
Vaccenic acid is Inversely related to T2DM, inconsistent findings
What is the association between Oleic acid and T2DM
Insignificantly protective, source matters
Oleic is also synthesized from stearic acid, which is detrimental for T2Dm risk
What are two mechanisms of N-3 ALA consumption reducing the risk for T2DM
- Increase membrane fluidity 2. rapid oxidation
Explain the n-3 ALA mechanism of increased membrane fluidity on reducing the risk of T2DM
ALA increases membrane fluidity which improves the insulin binding to receptor tyrosine kinase which decreases insulin resistance.
Explain the n-3 ALA mechanism of rapid oxidation on reducing the risk ofT2DM
ALA is rapidly oxidized for energy and used less for storage, which lowered adiposity, therefore decreased insulin resistance
What is the potential mechanism of n-6 LA on reducing risk of T2DM
n-6 may influence membrane fluidity, which improves the insulin binding to receptor tyrosine kinase which decreases insulin resistance.
What are the two mechanisms of Red meat/processed meat on increasing risk of T2DM
- synergistic effect of cholesterol and SFA
2. Non lipid factors of heme iron
Explain the mechanism of red meat/ processed meat on synergistic effect of cholesterol + SFA on in increasing risk of T2DM
Increased meat consumption increased inflammation and endothelial dysfunction which increases insulin resistance
Explain the mechanism of red meat/ processed meat on lipid factors of heme iron on increasing risk of T2DM
Increased meat consumption leads to increase in advanced glycation products, which then leads to AGE the increase of oxidative stress and inflammation which increases insulin resistance.
What is the potential mechanism for 3 or more eggs per week in increasing T2DM
Cholesterol has no effects glycemic control and IR
possible background diet i.e. bacon and eggs potential Choline derivative trimethylamine oxide
What are two mechanisms of 400 g/d of dairy on lowering risk of T2DM
- Fermentation of dairy reduces inflammation
2. SCFA and MCFA
Explain the total dairy mechanism of fermentation of dairy which lowers risk of T2DM
fermentation of dairy reduces inflammation by modifying colonic bacteria profile (prebiotics), which may reduce inflammation and therefor lowering IR
Explain the total dairy mechanism of SCFA and MCFA on reducing the risk for T2DM
Increases fat oxidation pathway uncertain, which reduces adiposity and lowers IR
What is the mechanism for Nuts insignificantly reducing risk for T2DM
- fiber, nutrients (Mg, and K), antioxidants may reduce inflammation, oxidative stress, endothelial dysfunction, IR, and insulin secretion
What are beneficial dietary lipid foods affecting T2DM
- fermented dairy products, 2. tree nuts, especially walnuts
What are detrimental dietary lipid foods affecting T2DM
- SFA (palmitic and stearic especially),
- Recommended to reduce egg intake to below 3-5 per week,
- Recommended to reduce red and processed meat intake
Which dietary lipid foods have neutral effect on T2DM
fatty fish or EPA, DHA
What are the two fiber mechanisms that lowers risk of CVD and blood lipids
- increased viscosity
2. fermentability
Which type of fiber specifically lowers blood lipids
soluble fiber
Explain the fiber mechanism of increased viscosity on lowering blood lipids
Soluble fiber intake has gel like material that interferes with micelle formation. Which creates an increase in bile acid and free cholesterol that is then excreted into feces. There is an increased conversion of cholesterol in the liver to replenish the bile. There is then a decreased intracellular cholesterol pool which influences the up regulation of LDL receptors and increased clearance of plasma LDL-c
Explain the fiber mechanism of fermentability fermentability on lowering blood lipids
Soluble fiber intake creates fermentation by colocnic bacteria that produces SCFA. The propionate from SCFA is taken up by the liver where it allosterically inhibits HMG CoA reductase. This causes the intracellular cholesterol pool to decrease, causing up regulation of LDL receptors and increased clearance of plasma LDL-c
What are the factors that influences Plasma TAG
- CHO
2. SUGAR
What is the sugar mechanism that increases plasma triglycerides
- Fructose increasing de novo lipogenesis
2. insulin resistance
Explain the sugar mechanism of fructose increasing lipogenesis and its increase on TAG
High fructose consumption is independent of insulin cell uptake, so it bypasses PFK-1 regulation where is is phosphorlyated to fructose 1-P and converted to glycerol 3-P. Glycerol 3-P is the backbone for TAG formation. Then there is an up regulation of CoA carboxylase via stimulating SREBP, and there fore there is an overall TAG synthesis and VLDL synthesis.
What are recommendations for sugar and TAG
- quantity matters
- <55-60% CHO - Quality matters (low Gi /GL foods)
- Limited added sugars to 10% or less
- avoid HFCS, high GI foods/diet, SSB
-Increase whole grains
Factors to consider: Apo E, Gender, abdominal obesity
What two mechanisms explain how UFAs lowers Total cholesterol and LDL-C
- UFAs are preferred substrate for ACAT
2. PUFAs Molecular Mechanism
Explain the UFAS mechanism of UFAs as preferred substrate for ACAT for lowering Total C and LDL-C
ACAT prefers 16-18 c fatty acids so FA are used to esterify C to CE, so when the cholesterol pool reduces, it up regulates the LDL receptors and promotes greater uptake of LDL-C into cell and thus reducing plasma LDL-C
Explain the UFAs Molecular Mechanism of PUFAS on lowering total cholesterol and LDL-c
PUFAS are ligands for LXR. The LXR and RXR dimer binds to LXRE which up regulates CYP7. More CYP7 means more cholesterol converted to bile acids. Intracellular cholesterol pool decreases, which intern reduces plasma LDL-c because of increased clearance
What are two mechanisms for UFAs lowering TAG?
- Membrane fluidity
2. LPL gene n-3 pufa
Explain the UFA mechanism of membrane fluidity on lowering TAG?
UFA intake increases fluidity of membrane by creating a less ridged membrane, which increases insulin sensitivity. There is an increased action of LPL and clearance of VLDL-TAG from plasma. This lowers plasma TAG
Explain the UFA molecular mechanism of LPL gene n-3 PUFA on lowering TAG
N-3 UFA is a ligand for PPAR, PPAR binds to PPRE which up regulates LPL expression. The LPL then clears TAG from CM and VLDL, which lowers plasma TAG
What are beneficial dietary FAs foods that affect blood lipids
- Low fat dairy
- UFA rich plant oils, olive oil
- Nuts, seeds in variety
What are detrimental dietary FAs foods that affect blood lipids
- Red meats (palmitic acid), recommendation is to reduce and eat more lean meats
- processed foods (trans fat) eliminate completely
What are beneficial/detrimental dietary FAs foods that affect blood lipids
tropical oils based on amount
What are two mechanisms in which phytosterols lower cholesterol ?
- Bile acid excretion
2. Down regulation of NPC1L1
Explain the mechanism of bile acid excretion for phytosterols lowering cholesterol
High intake of phytosterols, help bind to bile and cholesterol. This increases the excretion, and increased cholesterol is used in the liver to replace loss. There is then a decreased intracellular cholesterol pool, which increases the uptake of LDL-C via LDL-R, which decreases plasma LDL-C
Explain the mechanism of down regulation of NPC1L1 for phytosterols lowering cholesterol
High intake of phytosterols down regulates the expression of NPC1L1. This causes less cholesterol and phytosterol to be absorbed. The exact repression mechanism is unclear, but less absorption of cholesterol would lead to lower plasma LDL-C
Frequent consumption of nuts lowers risk of T2DM by lowering fasting insulin, IR and HBA1C in which individuals?
Normal BMI individuals
Explain the sugar mechanism of insulin resistance increasing plasma TAG
Chronic exposure to high GI diet/glucose leads to hyperinsulinemia. Chronic hyperinsulinemia leads to IR. Insulin is required for LPL activity, so decreased clearance of CM - Tag and VLDL - Tag
What are two mechanisms of SFAs and TFAs increasing plasma LDL-C?
- Membrane Fluidity
2. Trans fats up-regulating CETP
Explain how SFA and TFA mechanism of membrane fluidity increases plasma LDL-C
SFA and TFA make membranes more rigid. The rigidity of membranes decreases the binding of api B-100 to LDL-R. This reducers LDL-C uptake and clearance which in turn increases plasma LDL-C
Explain how Trans Fat mechanism of up regulation of CETP increases plasma LDL-C
Trans fat, specifically elaidic acid consumption increases the up regulation of CETP. This allows for more transfer of lipids between HDL and IDL. This increase transfer causes an decreased HDL-C and increased LDL-C
Small dense LDL
o Increase presence of small dense LDL increases risk of CHD
o Shift in LDL size from large to small increases risk of IHD 2-3 fold
o Small dense LDL almost always accompanies high triglyceride levels
Why is small dense LDL more atherogenic?
• Remains in plasma longer (decreased affinity of apo B-100 to LDL-R) , which increases transport into subendothelial space, increased susceptibility for lipid per oxidation. this Increases affinity for scavenger receptor which increases endothelial dysfunction and stimulates TXA2.
Explain hypertriglyceridemia
more VLDL molecules and more TAG per IDL particles
o When VLDL is saturated with TAG, affinity of apo proteins B-100 and C-II decreases → Apo C-II is not very efficient in stimulating LPL → not clearing TAG as quickly as should → CETP is accelerated to compensated (lowers HDL-C) → IDL: CE levels increase and TAG goes down, but only slightly → Hepatic lipase increases and more TAG is removed → increased LDL B: smaller LDL in size that has more protein and still has more CE and TAG per space → smaller it is the easier it can go through endothelial space → more likely to be oxidized (lingers in plasma longer)
What is role of food on Small dense LDL and oxidized LDL
more VLDL molecules and more TAG per IDL particles
o When VLDL is saturated with TAG, affinity of apo proteins B-100 and C-II decreases → Apo C-II is not very efficient in stimulating LPL → not clearing TAG as quickly as should → CETP is accelerated to compensated (lowers HDL-C) → IDL: CE levels increase and TAG goes down, but only slightly → Hepatic lipase increases and more TAG is removed → increased LDL B: smaller LDL in size that has more protein and still has more CE and TAG per space → smaller it is the easier it can go through endothelial space → more likely to be oxidized (lingers in plasma longer)
oxizined LDL • High plasma LDL-C • Especially high small dense LDL • Increased oxidant stress • Smoking, alcohol, drugs, pollution, oxidized food intake • Low antioxidant status • Low intake of fruits and vegetables • Low intake of vitamin E, C, beta carotene
What are the food factors that affect blood pressure
- sugar
- Fiber
- GI/GL
- N-3 PUFAs
What are the two sugar mechanisms on increased HTN
- Uric acid Pathway (fructose)
2. Salt retension
Explain the sugar mechanism of Uric acid pathway of fructose on increasing HTWN
Consumption of fructose increases conversion to fructose 1 -P, phosphate is trapped and does not regenerate ATP from ADP. There is a ADP build up that leads to lots or uric acid. This uric acid inhibits conversion of arginine to nitric acid. Nitric acid is an inhibitor to nitric oxide production, when Nitrric oxide is inhibited there is vasoconstriction and increased BP
Explain the sugar mechanism of salt retention on increasing HTN
Salt and sugar consumption is typically correlated. When sugar is consumed it stimulates the sympathetic nervous system which increases Angiotensin II, which stimulates aldosterone leading to increase sodium retention and high BP
What is the relationship of dietary fiber and BP
inverse association, insoluble fiber especially helpful (raw fruit, whole grains and vegetables), most effective soluble is beta glucan
What are the two mechanisms of GI/GL lowering BP
- Low GI/GL fiber diet
2. Beyond fiber
Explain the GI/GL mechanism of a low GI/GL fiber diet on lowering BP
Fiber delays gastric emptying which produces a low glycemic response. Overtime this improves insulin sensitive, IS blunts the sympathetic nervous system which stimulates aldosterone release resulting in a decrease in sodium retention and lowered BP.
Explain the GI/GL mechanism of beyond fiber diet on lowering BP
whole grains that also lower GI may contain other protective nutrients like magnesium as well as increasing satiety which lowers energy intake and reduces BW which improves BP.
What are two mechanism of N-3 consumption lowering BP
- Renin-Angiotensin system
2. Nitric Oxide
Explain the n-3 mechanism Renin-Angiotensin system on lowering BP
N-3 decreases angiotensin converting enzyme activity. The conversion of angiotensin I to II is decreased, which decreases aldosteron, decreasing sodium retention decreasing BP
Explain the n-3 mechanism Nitric Oxide on lowering BP
EPA increases the eNOS activity needed to convert argentine to nitric oxide. Consumption increases production of nitric oxide a vasodilator, which decreases BP
Foods to consider in reducing BP
o Processed meat increases BP
• Synergistic effect of arachidonic acid and salt
• Alters eicosanoid metabolism to make it pro-thrombotic
• Salt: osmolarity of plasma increases causing increase in BP
o Decrease sugar, fructose, SSB
o >3 servings/day of whole grain, increase fiber
o Fatty fish 2-3 servings/week (ALA 2-4g/day)
o Low fat dairy may be beneficial in lowering BP
o Nuts: lower BP
o Eggs: neutral on BP
what causes increase in permeability, decreased vasodilation, and activation of pro-inflammatory and thrombotic pathways
endothelial dysfunction
what factors affect endothelial dysfunction
- CHO and inflammation
- Trans fat
- SFA
- N-6
- n-3
What is the CHO mechanism that effects endothelial dysfunction
Adiposity
explain the CHO mechanism of adiposity that effects endothelial dysfuntion
a. Low GI diet, whole grains, fiber increase satiety
b. Reduce calorie consumption
c. Body weight loss or changes in adiposity
d. Reduces inflammation
e. Sugars, SSB does the opposite
What is the TRANS FAT mechanism that effects endothelial dysfunction
PPAR
Explain how Trans fat mechanism of PPAR effects endothelial dysfunction
• PPAR decreases pro-inflammatory genes indirectly by blocking NFkB – if it doesn’t bind the receptor, no inflammatory response
What is the SAT FAT mechanism that effects endothelial dysfunction
TLR-4
Explain how SAT FAT mechanism of TLR-4 on endothelial dysfunction
- SAT fat induces production of TNF-R
- TNF binds to TNF-R and induces signal transduction cascade
- The inhibitor of NF kappa beta (IkB) is removed
- Allows NFkB to move into nucleus and bind to NFkB response element
- Up-regulates pro-inflammatory genes
What is the N-6 effect on endothelial dysfunction
has no effect or possibly anti-inflammatory but high n-6:n-3 PUFA diet increases inflammatory markers (possible mechanism: eicosanoid metabolism
o High CRP, IL-6, TNF-alpha
o Increase TXA2
What is the N-3 effect on endothelial dysfunction
shown to be anti-inflammatory – lowers CRP, TNF, and IL-6 but only in healthy individuals not in morbidly obese
What are two n-3 mechanism on effecting endothelial dysfunction
- EPA/DHA displaces AA
2. EPA/DHA PPAR
Explain the n-3 mechanisms of EPA/DHA displacement of AA
• EPA/DHA displaces AA → less AA = less eicosanoids coming from AA (pro-inflammatory)
Explain the n-3 mechanism of EPA/DHA PPAR
• PPAR binds to response element and represses inflammatory genes
what is
• Excess body fat (BMI >30)
• Waist circumference (correlates with intra abdominal/visceral fat)
o >40 inches men, >35 inches women
obesity
What are the CHO factors affecting obesity
- Sugar
- High CQI
- Increased whole grain
- Adiponectin
- Leptin
- Wt loss
What is the mechanism for sugar increasing risk for obesity
Less satiation from SSB or high sugar goods
Explain the sugar mechanism for less satiation on increasing risk for obesity
Sugar foods are energy dense, increased energy intake, displaces other beneficial fluids like milk, weight gain
What is the mechanism of high CQI on obesity
- Satiety
2. Gut microbiota
Explain the high CQI mechanism of satiety on reducing obesity
intake of fiber, reduces appetite, reduces energy in both acute and long term, therefore reducing body weight
Explain the high CQI mechanism of gut microbiota on reducing obesity
- Gut microbiota
a. Fiber is a prebiotic
b. May alter gut microbiota
c. Anti-obesogenic environment in the presence of soluble fiber, resistant starch (link unknown)
what is inversely related to insulin resistance
o Levels low in obese individuals (inversely related to adipose fat)
o Levels low following low fiber meals
o Dietary fiber (both soluble and insoluble) increase adiponectin levels
• Implies better blood glucose uptake and increased fat oxidation
• Adiponectin levels
• Weight loss similar in legume rich diet and low carb diet
o Cardiometabolic profile more favorable for legume rich diet
o Mechanisms (whole grains/legumes):
1. Presence of fiber
2. Presence of resistant starch
a. Fecal loss of CHO/calories, weight loss
3. Low GI
a. Blunted insulin response
b. Increase satiety, less calorie intake, weight loss
l
What dietary fat effects obesity
- Low fat diet
- CLA
- SFA
- Dairy
- Nuts
What are two mechanisms of a low fat diet decreasing body weight and obesity
- Excess calories
2. Correlates with SFA
Explain how low fat diet and excess calories increases weight gain
High fat diets, exceeds calories, increases fat storage, and increases weight gain
which FA produces small significant fat loss WITH exercise
CLA
What SFA mechanism increases body fat
obesogenic genes
Explain the SFA mechanism of Obesogenic genes that increases body fat
Intake of SFA increases gene expression of obesogenic genes, may increase adipocyte formation, increase lipogenesis and adipose fat content
What are the two mechanisms for why dairy is protective agains obesity
- Gut microbiota
2. Calcium
Explain the how dairy mechanism of gut microbiota reduces risk of obesity
a. Bacterial strains in yogurt potentially anti-obesogenic, which decreases adipocyte formation, decreasing lipogenesis and adipose fat content
Explain the how dairy mechanism of calcium reduces risk of obesity
Interferes with micelle formation and increases stool fat, possible forming soaps with dietary fat and eliminating it
What are two mechanism of nuts with energy restricted diets lowering obesity risk
- Nuts on appetite
2. Physical Barrier
Explain how nut mechanism of influencing appetite reduces body weight
may increase adiponectin, reduce glucose response and increased satiety, increase thermic effect of food, less calorie consumption over time lower body weight
Explain how nut mechanism of physical barrier reduces body weight
a. Matrix of nuts
b. Physical barrier to full access to enzymes
c. Incomplete mastication and digestion
d. Increase stool fat
e. Body weight loss
What are recommendations for lowering risk for obesity
• Recommendations
o Lower overall fat intake
o Replace saturated fat with PUFA rich plant sources
o Fermented dairy like yogurt may be beneficial to include
o Nuts may be useful in weight loss
FAs and Breast Cancer/Prostate Cancer
• Trans fat increases death risk in general
• Saturated fat increases risk- higher estrogen levels bc hormones are stored in fat tissues → estrogen promotes cell growth → breast cancer
• MUFA from olive oil can be protective – phytochemicals → increases apoptosis and anti-inflammatory
o Decreases mammographic density (high density = higher risk of breast cancer)
• N-3 (EPA/DHA) protective → decreases amount of bioavailable estrogen
• Higher N-3:N:6 protective
o Decreases series 2 (N-6) production of pro-inflammatory eicosanoids
• Low-fat diet may prevent recurrence
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