11/6- Endocrine System and Aging Flashcards
Overview of the areas of endocrinology that change with age (list)?
- Glucose homeostasis
- Thyroid hormones
- Growth hormone/IGF-1
- Adrenal hormones
- Androgens (testosterone)
How does plasma glucose change with aging?
- Fasting glucose increases ~1 mg/dL per decade
- 1 and 2 hr post-prandial glucoses increase 8-10 mg/dL per decade
- For those < 50 yo, upper limit of normal after glucose load is 140 for the 2hr level; this increases 10 per decade after 50
- This means that 100 + age = maximum post prandial glucose
Overview of prost-prandial glucose increases with aging?
- Elderly have higher prost-prandial glucose
- Later peak
- Slower recovery (back to fasting)
These pts are NOT diabetic!!
Plasma insulin levels in elderly ____ after glucose challenge
Plasma insulin levels in elderly increase after glucose challenge
Hyperglycemia in elderly is due to what?
Insulin resistance
- Labeled glucose was infused durin a euglycemic clamp into young and old men; the uptake of glucose as expressed in mg/kg/min of lean body weight was reduced more than 25% in the old. This did not increase with increased glucose
- Therefore it is unlikely that changes in the receptor’s affinity for sugar is modified with age; however, a 65 yo man can = a 25 yo in terms of glucose uptake by increasing his serum glucose by roughly 50%
Glycosylated Hb (HbA1c) increases with age. What is normal for elderly person?
Around 7?
What are some of the mechanisms for insulin resistence of aging?
- Increase in visceral body fat with aging (this effect now seems to be mediated by both inflammation and obesity)
- Decreased lean body weight
- Glucose utilization markedly impaired
- Decreased fat cell insulin dependent (GLUT4) glucose transporters; also muscle in rat
- Sedentary lifestyle is associated with peripheral insulin resistance
- Very small impairment in pancreatic insulin release but higher insulin levels
- Non-insulin mediated glucose uptake is decreased < 10% by age
- Decreased suppression of hepatic glucose output
- Decreased alternative agonist (IGF-1) levels
- Preserved counter-regulatory pathways
- Likely post-receptor lesions including those that keep glucose in cell (glucose monophosphate)
[Note: heart doesn’t need insulin to uptake glucose]
___ may mediate some of adiposity’s effects on insulin sensitivity
Inflammation may mediate some of adiposity’s effects on insulin sensitivity!
- May be easier to get rid of the inflammation component of fat since it’s harder to get rid of the fat itself
How did a 6 mo exercise training program change insulin sensitivity in old men?
Describe the interaction between hepatic glucose output and oral glucose intake in the elderly
Hepatic glucose output is less suppressed by oral gluocse intake in the elderly
- Producing more glucose in their fasting state
- Don’t shut off glucose production quickly with food/glucose intake
- Contributes to post-prandial age-related increased in glycemia (100 + age, remember?)
__% of elderly have glucose intolerance test results indicative of diabetes
41% of elderly have glucose intolerance test results indicative of diabetes
Discuss hyperglycemia vs. hypoglycemia complications in terms of elderly population
- Hyperglycemia complications are long-term (vs. hypoglycemia)
- Most of the bad effects of hyperglycemia require years to manifest
- Hypoglycemia requires minutes..
- If person isn’t going to live long enough to experience these bad health outcomes, don’t worry about it as much
- Hypoglycemia is worse in old than young
- The old heart needs glucose (so does the sick heart)
How does illness relate to glucose tolerance in the elderly?
- Elderly people are more likely to have stress-related hyperglycemia
- Systems inducing hyperglycemia are less altered by aging than the hypoglycemic ones
- Norepinephrine increases with age
- Cortisol is unchanged or increased with age in response to illness
- Glucagon is unchanged with age
- Pro-inflammatory cytokines increase with age
- If a older person has hyperglycemia while ill, do not label them diabetic; reevaluate glucose when they are not sick
Epinephrine normally does what to insulin levels? In elderly?
Epinephrine normally antagonizes insulin
- Increased in elderly
- Epinephrine infusion is model of stress such as that seen in illness
- Old have greater insulin resistance due to catecholamine infusion
Key piont: if an older person has hyperglycemia while ill, treat the hyperglycemia but do not label them diabetic; Reevaluate glucose when they are no longer sick (~6 weeks)
Yup
What is AGE?
Advanced glycosylation end product
- Result of non-enzymatic reactions between glucose and amine groups of proteins
- Hemoglobin A1C is the product of such a non-enzymatic glycosylation (Schiff bases -> Amadori products)
- The AGEs dehydrate, precipitate and may contribute to cataract formation in the lens
- Glucose may form other irreversible cross-links between proteins or nucleic acids that compromise function
- Contributes to very stiff collagen
Where do glycosylated proteins accumulate?
With aging, AGEs accumulate in skin and tendon and some other long-lived protein-rich areas
- Not found in other seemingly similar areas
What can be done to decrease serum glucose (and limit AGE)?
Caloric restriction
