Week 6- Etiology and Diagnosis of Diabetes Flashcards
With increases in BMI, the incidence of….
diabetes, asthma, arthritis, high BP and cancer all increase
With increasing BMI we see increased…
mortality. Decreased life expectancy and increase years of life lost with obesity
Life expectancy of a 20 yr old who is morbidly obese is how much shorter?Why?
13 years shorter than a normal weight 20 yr old male. This is because the younger a person is, the long they are exposed to excess weight, there are detrimental effects on longevity
A BMI <20
Also sees slightly increased mortality
Can you be obese and metabolically healthy?
Yes but, there is only a small percentage of obese individuals who are considered to metabolically healthy.
- These healthy individuals don’t have an increased risk of morbidity and mortality as they aren’t at risk of developing disease
Risk factors of metabolic syndrome and associated disease
Diagnostic criteria for metabolic syndrome
need to have an indication of accum of visceral fat:
waist circumference of :
- men: greater than or equal to 85cm
- women:greater than or equal to 90cm
and 2 or more of the following:
- blood sugar( fasting hyperglycemia greater than or equal to 110mg/dL
- blood pressure( systolic BP is greater than or equal to 130mmHg and diastolic BP is greater than or equal to 85mmHg)
- dyslipidemia/serum lipids( hypertriglyceridemia greater than or equal to 150 mg/dL or Low HDL cholesterol less than 40 mg/dL)
- these all show early signs of metabolic disease
Roles of insulin
- liver
- decreases hepatic glucose production via inhib of gluconeogeneiss
- muscle
- increases glucose uptake via GLUT4 translocation to produce glycogen, creation of muscle(uptake of AAs)
- adipose
- increases glucose uptake in fact cells
- decreases inhibition of lipolysis to produce fat and enhance storage
Affects of insulin resistance in tissues
liver: increased hepatic glucose production which contributes to hyperglycemia
muscle: decreased glucose uptake contributes to hyperglycemia
adipose: increased lipolysis leads to increased circulated FFA which increases stroke ris
Pathophysiology of Diabetes
One of the first things seen is a decline in insulin sensitivity. To compensate we see increases n insulin section. In the short-term this maintains hyperglycemia but when the pancreatic cells begin to fail we see onset of T2DM.
Decreased insulin–> hyperglycemia–> marks T2DM
What is true T2DM
How many poeple with diabetes dont know they have it?
1/3
Reccomendation to diagnose diabetes?
every 3 years, it is recommended that people over 45 are tested
The tests to diagnose diabetes
% of diabetes patients who are over 45?
92%. this indicates there is an increased susceptibility to developing T2DM with age
Heritability of T2DM
How does fat mass correlate to insulin sensitivity
inversely
Trends in glucose metabolism
results of glucose metab are offset in obese individuals as we see intolerance as more insulin is required for metabolism to occur
2 characterisations of T2DM
- Insulin resistance( manifests in peripheral tissues)
- b cell dysfunction ( loss of compensation by insulin secreting B cells to systemic insulin resistance )
Degrees of progression to T2DM
Insulin resistance in peripheral tissue
What happens in obesity to cause insulin resistance?
Lipotoxicity
this is when we see ectopic lipid deposition. The adipose tissue reaches a max point where no more lipids can be stored and this leads to lipid spill over in liver and muscle(peripheral tissues)–> causes state of lipotoxicity
How do long-chain fatty acids block insulin signaling in skM?
LCFA–> either impair ability to phosphorylate IRS1 or impacts ability of GLUT4 to be translocated
Low grade inflammation in obesity
How M1 macrophages are recruited as an inflammatory hallmark in the obese state
How proinflamm cytokines impair insulin signalling
Adipose centric view
what is considered a healthy adipokine?
adiponectin.
what is a bad adipokine?
resistin
obesity and changes in adipokine profile
Mitochondrial dysfunction in diabetes
