Pathophysiology Flashcards
How many hours of sleep do 35% of adults get?
<7 hours
How many hours of sleep in adults correlated with the lowest BMI?
7.7 hours
What kind of curve scene between the correlation of sleep and obesity?
You shaped curve
What hormonal changes are seen in people who have sleep disorders that increase for hunger?
Increase Ghrelin and decrease Leptin
What hormonal changes are seen with sleep deprivation?
Decrease leptin
Increased ghrelin, orexin and neuropeptide y
This leads to increased appetite and decreased energy expenditure.
Changes in light dark cycle and meal timing can affect which hormone level?
Leptin
How does reduce sleep time affect risk of diabetes?
It is associated with diabetes and if you get six hours of sleep you had a 1.7 times greater risk of diabetes and five hours of sleep had 2 1/2 times greater risk of diabetes compared to those who get 7 to 8 hours of sleep per night.
What did the American Cancer Society and cancer prevention study show in regards to sleep duration and mortality?
It followed 1.1 million men and women over six years and the highest survival was not a month those sleeping seven hours. Mortality was less than 4 1/2 hours and greater than 10 hours of sleep.
What is the strongest risk factor of sleep apnea?
Obesity
What is a sleep apnea profile show?
Loss of deep sleep in stages three and four and increased a light sleep in stages one and two
How does sleep apnea affect your A1c?
Mild sleep apnea associated with increased A1c by 1.49%
Moderate sleep apnea associated with an A1c by 1.93%
Severe sleep apnea associated with increase A1c 3.69%
And diabetics increasing severity of OSA associate with poor glucose control independent of weight
How long does it take to see improvement in glucose metabolism and prediabetics with treated sleep apnea?
Two weeks of eight hours a night of sleep. Also have reduced catecholamines, increased insulin sensitivity reduce glucose and improved glucose disposal
Do you study show that treating sleep apnea improves diabetic control?
Conflicting data. It did not show the benefit but could be from low compliance rate. Patient with greater than four hours of CPAP per night improved and less than four did not show any changes.
How does sleep apnea use of cpap affect obesity?
If using less than 5 hours of sleep a night, increased BMI in those w/o CVD or hyperglycemia. If over 5 hours a night, decrease d/t leptin sensitivity being improved.
What are CLOCK genes?
Circadian locomotor output cycles kaput
What are 2 of components of CLOCK genes?
1)Scn(Suprachiasmatic nucleus) - centrally located
2)Peripheral clocks - located w/in all tissues/organs
How does circadian rhythm disruption affect our hormones?
Lower melatonin
Higher postprandial glucose, insulin and TGL
Blunted post meal ghrelin suppression
What did forced circadian malalignment studies show?
Leptin reduced
Glucose/insulin increased
Cortisol rhythm was reversed
BP increased
<5.6 hours of sleep caused reduction in metabolic rate
What did multiple studies show in healthcare night shift workers?
Increased incidence of Obesity, HTN, HLD
What are the effect of sleep disorders on obesity and DM?
Increased appetite
Increased IR
Decreased EE(energy expenditure/metabolism)
What hormonal changes do you see in sleep disorders on obesity/DM that increase appetite?
I
Increased Ghrelin
Increased Orexin
Decreased Insulin
What hormonal changes do you see in sleep disorders on obesity/DM that decrease EE?
Decreased melatonin
Decreased TSH
What hormonal changes do you see in sleep disorders on obesity/DM that increase IR?
Decreased Adiponectin
Increased sympathovagal balance
Increased Cortisol
Increased inflam cytokines(Il-6, Il 1beta)
Increased GH
What makes brown adipose tissue brown?
Mitochondria
What is function of WAT vs BAT
WAT: energy storage
BAT: heat production(non shivering)
Which type of fat has UCP1?
BAT
How do lipids store in WAT vs BAT?
WAT: One single vacuole
BAT: Multiple vacuoles
Who has greater BAT? Men or Women
Women
What happens to WAT and BAT with aging?
WAT: increases
BAT: decreases
What proteins are predominant in WAT vs BAT?
WAT: Leptin
BAT: UCP1
Which type of fat has denser nerve supply and innervated by SNS?
BAT
Where is BAT located?
cervical, supraclavicular, axillary, paravertebral, mediastinal and upper abdominal regions
What stimulates UCP1?
Thyroid hormone, TDZs, retinoic acid, nicotine
What is more accurate measurement of metabolic phenotype than BMI?
Total fat mass
What does chronic positive energy balance lead to?
Adipocyte hyperplasia or Adipocyte hypertrophy
Comment on adipocyte morphology and metabolic disease
Adipocyte hyperplasia - many small adipocytes - normal insulin, glucose and lipids
Adipocyte hypertrophy - large and fewer adipocytes - increased insulin, glucose and TGL, IR
What is the criteria for Metabolic Syndrome?
3 of the 5:
1. WC >40 for men >35 for women
2. BP >130/85
3. TGL >150
4. HDL <40 for men, <50 for women
5. Glucose >100(updated in 2004, used to be 110)
What is the resting metabolic rate?
Metabolic rate required to maintain vital physiologic functions at rest
What is the biggest predictor of resting metabolic rate?
Lean body mass/fat free mass
What is thermic effect of food?
Energy required for digestion/absorption and storage of food. Protein>carb>fat
What is the increased risk of diabetes for every 2.2 lbs(1 kg)of excess weight?
9%
What is the reduction of developing diabetes per Diabetes prevention program study of metformin vs intensive LS changes?
metformin reduced by 31%
ILS by 58% with a 6% weight loss
What is the biggest cost to the healthcare system in regards to Medicare?
Diabetes
What is the 8th leading cause of death in the US?
Diabetes
How many adults have prediabetes?
96 million(38% Adults)
How many people younger than 20 have Diabetes?
283,000
Of those older than 65, what percent has diabetes?
33%
How many regardless of age in the US does DM affect?
37.3 million(11.3% of population)
What is the guideline treatment for Prediabetes?
Intensive lifestyle behavioral change with >=7% reduction in body weight thru diet/exercise(150 min/week)
When should metformin be considered for Prediabetes?
Ages 25-59 and BMI >=35, higher FBG >=110 or A1c>=6 and women with prior GD.
Discuss hyperglycemia and microvascular and macrovascular changes in DM?
Hyperglycemia - leads to microvascular changes which are Retinopathy, Neuropathy and Nephropathy
But only partly to macrovascular changes(CAD, Stroke, Atherosclerosis) as hyperinsulinemia and metabolic syndrome risk factors also contribute.
What is the goal for physical activity for Diabetics?
1)150 minutes mod to vigorous activty per week spread over 3 days with no more than 2 consecutive days w/o activity. Alt is 75 min/week of vigourous activity for younger and more fit individuals
2)2-3 sessions resistance training on nonconsecutive days
3)Get up every 30 minutes for BG control
4)Flexibility training and balance training 2-3 times a week for older adults with diabetes
Which diabetes drugs cause weight loss?
Metformin(biguinide), GLP1s, Amylin analogues, SGLT2 inhibitors
Which diabetes drugs are weight neutral?
DDP-IV(gliptins), alpha glucosidase inhibitors(acarbose), Bile acid sequestrants, Dopamine agonist(bromocriptine)
Which diabetes drugs cause weight gain?
Insulin, sulfonylureas, meglitinides(repaglinide, natoglinide - prandin/starlix), TZDs,
How does gastric bypass affect diabetes?
It reversed DM in 79% patients. 10 years after diabetes was significantly lower than non-surgery patients
When is metabolic surgery expedited in diabetic patients?
If BMI is >= 40
What is the recommendation on metabolic surgery if your BMI is 35-39.9(class 2 obesity)?
Optimize lifestyle and medications but if still has poor glycemic control then recommend surgery. If adequate control, can still consider it.
What is the recommendation on metabolic surgery if your BMI is 30-34.9(class 1 obesity)?
Optimize lifestyle and medications but if still has poor glycemic control then consider surgery. If adequate control, then nonsurgical tx.
What kidney conditions do obesity increase risk for?
CKD, Kidney stones, Kidney cancer
Why is there an increased risk of kidney stones with obesity?
Obesity is linked to increased excretion of calcium, uric acid, sodium and lower urine pH(acidic)
What is risk of kidney cancer in obesity ?
A 5kg/m2 increase in BMI is associated with a 25% higher risk of RCC.
What percentage of kidney cancers in men/women were associated with obesity?
17% in men and 26% in women
In men what are the top types of cancer in obese patients?
Esophageal
Thyroid
Kidney
In women what are the top types of cancer in obese patients?
Endometrial
GB
Esophageal
Kidney
Why does adipose tissue endocrine activity production increase risk for CKD?
You have decreased adaponectin and increased leptin and resistant. This increases inflammation and oxidative stress, abnormal lipid metabolism, activates the RAAS, increases IR and hyperinsulinemia
How does ectopic fat in the kidney cause chronic kidney disease?
You have increased deposition of renal sinus fat which leads to the development of glomerular hypertension and increased glomerular permeability which leads to a glomerulopathy
What are mechanisms for the pathogenesis of obesity related HTN?
Central adiposity - IR, compression around kidneys, high leptin levels. Both leptin and insulin trigger SNS which stimulates renin release. You also have increased aldosterone and thus increased reabsorption of sodium in kidneys. Angiotensinogen from intraabd adipocytes is released as well.
What parameters on the cholesterol panel are likely to be Abnormal in obese patients?
High triglycerides, VLDL, ApoB, and non-HDL cholesterol. Low HDL and ApoA-1
Are obesity effects on lipid metabolism dependent on location of adipose tissue?
Yes
If you have increased visceral and upper trunk subcutaneous adipose tissue, what is that associated with and what will your lipid profile look like?
IR, Elevated triglycerides and low hdl
If you have increased leg subcutaneous adipose tissue, are your TGL likely to be high or low?
Lower TGL
What is the most common cause of mortality in obese pts?
Cardiovascular disease(Its an independent risk factor)
What is a primary contributor of obesity to developing cardiovascular disease?
Inflammation. If you have visceral fat then you have increased IL6, tnf alpha, leptin, CRP
What is the risk of Atrial Fibrillation in those who are obese vs those who are not?
1.52 x higher risk
What is the difference between hepatic steatosis vs hepatic steatohepatitis?
Both have >5% liver weight is fat but steatosis(rarely progresses to cirrhosis) is without inflammation and steatohepatitis is with(+/- fibrosis, can lead to cirrhosis- 25% over 9 years).
What is the prevalence of low testosterone in men with Diabetes?
40%
How are waist circumference/obesity related to testosterone, SHBG?
Inversely
What are the two mechanisms of obesity causing testosterone deficiency?
- Increased aromatase activity which converts testosterone to estradiol
- Reduced hypothalamic GnRH and pituitary LH function
What is the most common obesity associated cancer among women after menopause?
Breast Cancer
What is the most common obesity associated cancer among men?
Colorectal Cancer
What is the risk of endometrial cancer in overweight/obese women?
Overweight/obese(BMI 25-35) - 2-4 x
Severely Obese(BMI>40) - 7 x
What are the 13 cancers that are associated with obesity?
Meningioma, esophageal adenocarcinoma, multiple myeloma, kidney, utering, ovarian, thyroid, breast, liver, gallbladder, upper stomach, pancreatic and colorectal
What percentage of cancers are due to overweight /obesity?
40%
