Endo - Type Ii Diabetes/obesity

Front 1

BMI - equation?

Back 1

= estimates body weight relatively independent of height

BMI = weight (kg)/[height (m)]2

Front 2

BMI
- normal?
- overweight?
- obese?
- extremely obese?

Back 2

Normal: 18.5-24.9
Overweight: 25-29.9
Obese (2 stages): 30-34.9; 35-39.9
Extremely Obese: >40

Front 3

What are causes of obesity?

Back 3

- complex genetics (rare, monogenic causes - e.g., heterozygous melanocortin receptor 4 mutations)
- ENVIRONMENT (diet, lack of exercise. etc.)

Front 4

Explain the "set point" of weight

Back 4

As one loses weight:
- reduced energy expenditure
- reduced basal metabolic rate
- reduced SNS tone

As one gains weight...
- opposite

Front 5

What are some of the medical complications of obesity?

Back 5

- Type II DM
- Decreased life expectancy
- Metabolic Syndrome - increased CV risk
- HTN, hypercholesterolemia, atherosclerosis
- Gallstones
- Endocrine dysfunction (amenorrhea, PCOS)
- Cancers of GI and Repro
- Hypoventilation, sleep apnea
- Osteoarthritis, degenerative joint disease

Front 6

What are the 2 different adipose tissue distributions?
- associated metabolic effects?

Back 6

ANDROID = visceral adiposity = "apple"
- turns over more rapidly
- BUT more adverse metabolic effects (increased risk of insulin resistance, DM type II, metabolic syndrome)

GYNOID = subcutaneaous adiposity = "pear"
- tends to serve as a storage depot
- less adverse metabolic effects

Front 7

How does visceral fat/android distribution contribute to insulin resistance?

Back 7

Adipose tissue is a secretory organ!

- FFAs and Cytokines (TNF-alpha) --> induce insulin resistance

- REDUCES Adiponectin (which enhances insulin sensitivity) --> increased insulin resistance in liver and muscle; development of atherosclerosis

Front 8

Adiponectin
- secreted by?
- function?

Back 8

- secreted by adipose tissue
- increases insulin senstivity (good!)
- vascular protective effects
- VISCERAL adiposity - REDUCES adiponectin

Front 9

What is Metabolic Syndrome?

Back 9

= combo of disorders that increase risk of developing CV disease (increased 2-4x risk) and diabetes

- Glucose intolerance/Frank 2 diabetes
- Dyslipidemia (low HDL, high TGs, LDL becomes small and dense)
- Abnormal thrombolysis (increased plasminogen-activator-1)
- Endothelial dysfunction (abnormal vascular reactivity/inflamm)
- Hypertension (usually relatively mild)

Front 10

What are the criteria for Metabolic Syndrome?

Back 10

At least 3 of the 5 folliwing:

1. abdominal obesity
2. TGs > 150
3. low HDL
4. BP > 130/85 (one or other)
5. Impaired Fasting Glu or Severe Hyperglycemia

Front 11

What is a common clinical sign of insulin resistance?
- explain

Back 11

ACANTHOSIS NIGRICANS
- velvety, hyperpigmented, hypertrophic change in epidermis
- usually on back of neck, axilla, other skin folds
- due to high levels of circulating insulin that interact with IGF-1 receptors and enhance skin growth

Front 12

TYPE II DIABETES
- ethnic distribution?

Back 12

- In US, all ethnic minorities have 2-3-fold higher prevalence than non-hispanic whites
- Highest prevalence in world is Pima Indians of Arizona

Front 13

TYPE II DIABETES
- pathogenesis?

Back 13

Multiple hormonal defects:

- obesity-related insulin resistance
--- affects glucose and lipid metabolism in liver, muscle, adipose tissue

- inadequate B-cell secretion of
insulin
--- first, insulin secretion increases in response to insulin resistance
--- then, insulin secretion declines --> becomes grossly deficient (late-stage patients need to take insulin injections)
--- Beta-cell function declines over time, but resistance remains stable

- Excessive alpha-cell secretion of glucagon
--- increased hepatic glucose production

Front 14

Explain the onset of type II Diabetes

Back 14

- develops gradually
- can be asymptomatic for many years (30-40% undiagnosed)
- at diagnosis, > 50% patients have evidence of complications of diabetes - retinopathy, neuropathy, nephrophaty, CV disease

Front 15

What causes B-cell impairment in Type II Diabetes?

Back 15

- Glucotoxicity - elevated glu impairs inslulin secretion

- Lipotoxicity - high free FAs and islet accum of lipids impair insulin secretion; lipid accumulation in liver and skel muscles impairs insulin secretion

- Deficient stores of incretins

Front 16

Incretins
- what are?
- function?
- names?

Back 16

= intestinal hormones released after meal ingestion
- help regulate insulin release in a glucose-dependent manner

=Glucagon-like Peptide (GLP-1) and Gastric Inhibitory Polypeptide (GIP)

*** Lost in decreased in Type II DM due to insufficient GLP-1 secretion
*** Lost when give injected insulin bc passes gut

Front 17

GLP-1
- what is?
- where is it secreted from?
- functions?

Back 17

= Glucagon-Like Peptide-1
= Incretin

- released from L cells in ileum and colon
- stimulates insulin response from B cells (glu-dependent)
- inhibits glucagon secretion from A cells (glu-dependent)
- Inhibits gastric emptying (increased satiety --> eat less --> lose weight)

Front 18

GIP
- what is?
- where is it secreted from?
- functions?

Back 18

= Gastric Inhibitory Polypeptide
= Incretin

- released from K cells in duodenum
- stimulates insulin response (glu-dependent)
- does NOT inhibit glucagon secretion from A cells
- minimal effects on gastric empyting, satiety, weight

Front 19

What can meds do to fix the incretin problem in Type II DM?

Back 19

Incretins are naturally, rapidly degraded by DPP-4 (dipeptidyl peptidase) in bloodstream - short t1/2

- Gliptins - drugs that inhibit DDP --> enhance incretin effect and treat hyperglycemia in Type II DM

Front 20

Amylin
- what is?
- function?
- association with diabetes?

Back 20

- cosecreted with Insulin from B-cells
- helps regulate post-prandial Glu
- suppresses inappropriately elevated glucagon secretion
- slows gastric emptying
- promotes satiety - reduces caloric intake
- reduces blood glucose peak after meal times

***Deficient in Type I AND II DM!!!

Front 21

Diabetes
- microvascular complications?
- macrovascular complications?

Back 21

Microvascular (due to high glucose):
- retinopathy
- nephropathy
- neuropathy

Macrovascular (high risk bc patients typically have other risk factors):
- CAD
- amputations
- stroke
- associated with Metabolic Syndrome/Insulin Resistance Syndrome