diabetes patho and epidemiology Flashcards
1
Q
what happens to the majority of glucose that you eat from meals
A
2/3 is stored and released later
2
Q
if the liver and skeletal muscle are both already saturdated with glucose, what happens to it?
A
excess glucose gets turned into fatty acids and then into triglycerides
3
Q
gluconeogenesis
A
hepatic synthesis of glucose from amino acids, glycerol and lactic acid
4
Q
what is the most efficient form of fuel storage
A
fat metabolism
5
Q
what are triglycerides converted into and what is the enzyme used to do so
A
fatty acids and glycerol
enzyme used is lipase
6
Q
how is glycerol used
A
used directly for energy or converted to glucose
7
Q
how are fatty acids used
A
converted to ketones by the liver then released for energy
CANNOT be made directly into glucose.
8
Q
what can be used by the brain for energy when glucose is unavailable
A
ketones (from fatty acids)
9
Q
converted to ketones by the liver then released for energy
A
fatty acids (from TG)
10
Q
used directly for energy or converted to glucose
A
glycerol
11
Q
excess of this is turned into fatty acids, ketones or glucose
A
amino acids from proteins
12
Q
secretes digestive juices into duodenum
A
pancreatic acini
13
Q
hormone secretion portion of pancretic cells
A
islets o langerhands
14
Q
secretes insulin
A
beta cells
also secretes amylin
15
Q
secretes amylin
A
beta cells
also secretes insulin
16
Q
secretes glucagon
A
alpha cells
17
Q
initial polypeptide chain synthesized by beta cells with signal peptide present
A
preproinsulin
18
Q
created by removal of signal peptide and linkage between A and B chains
A
proinsulin
19
Q
created by cleavage and removal of C-peptide chain
A
insulin
20
Q
used to assess active insulin
A
C-peptide
21
Q
glucose transporter for most body cells
A
GLUT 2
22
Q
glucose transporter for skeletal muscle and adipose tissue
A
GLUT 4
23
Q
What happens to glucose in a beta cell?
A
- Phosphorylation of glucose
- ATP generation
- Inhibition of ATP-sensitive K+ channel
- Sulfonylureas can bind to this channel to stimulate insulin release
- Beta cell is depolarized, resulting in opening of the voltage-gated calcium channel
- Insulin is released.
24
Q
three things released from beta cells when depolarized
A
C - peptide
IAPP (amylin)
25
what channel can sulfonylureas bind to in order to depolarize beta cells and therefore stimulate insulin release
ATP sensitive potassium channels!
26
how does insulin affect glucose metabolism
1. increases glucose transport into skeletal and adipose tissue
2. increases glycogen synthesis
3. decreases gluconeogenesis
27
how does insulin affect fat metabolism
1. inceases transpot of FAs into adipose cells
2. increases synthesis of FAs and TGs
3. decreases TG breakdown
28
how does insulin affect protein metabolism
1. increases transport of AAs into cells
2. increases synthesis of proteins
3. decreases breakdown of proteins
29
what are the effects of glucagon on glucose metabolism
1. increases gluconeogenesis
2. increases glycogen breakdown
30
what are the efects of glucoagon on fat metabolism
1. increases adipose tissue breakown
31
what activates lipade in adipose tissue
glucagon
32
how does glucagon affect protein metabolism
increases transport of amino acids into liver cells for use in gluconeogenesis
33
functions of amylin
1. works with insulin to regulate plasma glucose
2. decreases postprandial glucagon secretion
3. slows gastric emptying and increases satiety
34
secreted by delta cells
somatostatin
35
job of somatostatin
inhibition of insulin and glucagon release
36
these gut derived hormones accounts for 50% of postprandial insulin secretion
incretins
also slows gastric emptying/increases satiety
37
what are the effects of epi on glucose
1. increases glycogenolysis in liver and muscles
2. increases lipolysis in adipose tissues
3. decreases release of insulin
38
what can result as a chronic hypersecretion of GH
1. insulin resistance
2. elevated glucose
3. inceased DM risk
39
what is the effect of glucocorticoids on glucose levels
1. increases gluconeogenesis in the liver
40
what does the term "diabetes" mean
siphon
(related to excessive urination)
41
what does the word "mellitus" mean
sweet
42
what is the estimated US pevelance of DM, what about the worldwide prevelance?
8.5-15.9% of adults in US
10.5% wordlwide
43
what is the prevelance of patients w gestational DM? how likely are these pateints to develope DM later on?
7% of US pregnancies
35-60% risk of later developement of DM
44
what is T1DM associated with?
autoantibodies
autoreactive T lymphocytes
45
what form of DM is idiopathic
T1B DM
46
what is the genetic and envrionmental contribution of T1ADM
genetic 1/3 - because of HLA genes
environmental 2/3 - due to cows milkl, hygiene hypothesis, certain viruses
genetic predisposition w an environmental trigger!
47
at what point in T1A DM do clinical S/S begin to show
when 70-80% of the beta cells are destroyed
48
very slow progressing T1ADM is known as
latent autoimmune diabetes in adults (LADA)
49
What is the geneal idea of the process of beta cell destruction in T1ADM
1. islets of langerhans become infiltrated by lymphocytes
2. exact mechanism is not fully understood but T cells are to be primarily responsible.
3. other cells are generally spared!
50
what are the immunoligic abnormalities in T1ADM
1. islet cell autoantibodies
2. activated lymphocytes in islets, peripancreatic lymph nodes and systemic circulation
3. T lymphocytes that proliferate when stimulated w islet proteins
4. release of cytokines w/i infiltrated islets
51
what type of therapy does NOT work for T1ADM
immunosuppression
52
what autoantibodies are positive in >85% of T1ADM patients
1. Anti-GAD65 (MC)
2. Anti-ZnT8
3. Anti-IA2
4. Islet cell autoantibody (ICA)
5. Anti-insulin autoantibody (IAA)
53
what are the limitations to the autoantibody testing in someone with T1ADM?
1. declines with increasing duratio of disease
2. + in about 5% of T2DM and gestational DM
3. low IAA levels in many pts after tx w exogenous insulin
54
What is T3DM/other types of DM associated with?
1. Pancreatic destruction
2. Genetic defects in production of insulin or glucose
3. Gestational DM (7% of pregnancies)
55
what is the pathogenesis of T2DM
insulin insensitivity in tissues which causes inadequate insulin secretion
sufficient insulin to prevent ketosis but not enough to prevent systemic hyperglycemia
56
what are the contributors to T2DM
1. genetic! - family hx
2. environmental - obesity (#1 is visceral), high/low birthweight, lack of phyiscal activity
57
what are the contributors to T2DM
1. genetic! - family hx
2. environmental - obesity (#1 is visceral), high/low birthweight, lack of phyiscal activity
58
what are the metabolic abnormalities seen in T2DM
1. impaired insulin secretion w insulin resistance
2. exessive hepatic glucose production
3. abnormal fat/lipid and muscle metabolism
59
what occurs in early T2DM?
what occurs over time?
what occurs as disease progresses
early - insulin resistance leads to compensatory hyperinsulinemia
over time -
pancreastic beta cells cant maintain hyperinsulinemia which causes pre diabetic s/s such as impaired glucose tolerance and impaired fasting glucose
progression- further decline in insulin secretion and increased insulin resistance causes worsening hyperglycemia until eventually T2DM is reached
60
what is the old diabetes triumvirate theory
major factors contributing to glucose regulation in T2DM were thought to be:
1. abnormal insulin secretion
2. increased hepatic glucose production
3. decreased peripheral glucose uptake
these are still thought to be contributing factors but are no longer thought to be the ONLY contributing factors!
61
what is the ominous octet?
the new theory of T2DM regarding major factors of poor glucose regulation:
1. decreased insulin secretion - d/t loss of B cell function
2. increased hepatic glucose production - d/t insulin resistance and low insulin levels causing loss of negative feedback to suppress gluconeogenesis
3. decreased peripheral glucose uptake - d/t insulin resistance/absence causing inability to absorb glucose into muscles/adipose tissue
4. increased lipolysis - d/t resistance of insulins antilipolytic effect resulting in release of FA's which stimulate gluconeogenesis
5. decreased inccretin effect - incretins cause stimulated insulin release, inhibition of glucagon secretion and promotion of satiety
6. increased glucagon secretion - glucagon promotes gluconeogenesis, glycolysis and lipolysis
7. increased renal glucose absoprtion
8. neurotransmitter dysfunction - insulin normally acts as appetite suppressant. decreased sensistivity = increased appetite.
62
where in the kidney is glucose reabsorbed
in proximal tubule by the SGLT2 transporter protein.
63
pathogenesis of gestational DM
insulin esistance due to metabolic changes of pregnancy
64
poathogenesis of maturity onsetdiabetes of the young
autosomal dominant; genetically mediated impaired insulin secretion in response to glucose
64
pathogenesis of gestational DM
insulin esistance due to metabolic changes of pregnancy
65
what are the 4 main causes of secondary DM
hormonal rumors
liver disease
pharmacologic agents
panceatic disease
66
what pharmacologic agents could cause secondary DM
corticosteroids
thiazides
BB
antipsychotics
67
what are the 2 main incretins
GLP - 1
GIP
68
What is metabolic syndrome
aka syndrome X
a criteria of three of the following:
1. waist circumference of >40 in men and >35 in women
2. fasting TG's >150
3. HDL <40 men, <50 women
4. BP >130 systolic or >85 diastolic
5. fasting plasma glucose >100
it also counts if they are on medication for any of these.
69
people with metabolic syndrome have an increased risk of...
atherosclerosis
heart disease
stroke
cancer
dementia
T2DM
ED
70
what is prevalence of metabolic syndrrome in US
22% of patients
43% of patients 60+
71
what are risks for metabolic sndrome
1. mexican american or black
2. women
3. overweight (central/visceral mostly)
4. physical inactivity
5. aging
6. T2DM
7. CVD
8. Lipodystrophy
72
what has been found to raise metabolic syndrome risk by x2
>4 hours a day o TV/computer time
73
When does BG peak postprandial?
Generally around 2 hours is the peak BG before it drops down to normal.
74
how does insulin resistance correlate with metabolic syndrome
thought to be the primary contributor of metabolic syndrmome
causes inceased circulating FFA's
75
how does glucose intolerance effect metabolic syndrome
increased levels of postprandial and fasting glucose
76
how does hypertension effect metabolic syndrome
insulin resistance leads to loss of insulins normal vasodilatory effect without impacting its mild sodium retention effect.
hyperuricemia also contributes to HTN through activation of the RAAS
77
how does waist circumference effect metabolic syndrome
increased visceral adipose tissue = greater effect of circulating FFA's on hepatic metabolism
78
dyslipidemia
influx of FFA's into the liver = abnormal lipid production
TG increased
HDL decreased
LDL increased
79
how do proinflammatory cytokines effect metabolisc syndrome
increased production due to the increased overall mass of adipose tissue.
IL-1, IL-8, IL-16, TNF alpha, C-reactive protein
80
how does Adiponectin effect metabolic syndrome
anti-inflammatory cytokine produced exclusively by adipocytes (reduced rate of production in pts w metabolic syndrome)
81
what are the PE findings of metabolic syndrome
increased waist circumference and HTN
acanthosis nigricans
hepatic enlargement
82
what are the lab findings in metabolic syndrome
hyperuricemia (w gouty arthritis)
polycystic ovarian syndrome
obstructive sleep apnea
83
how do you treat metabolic syndrome
primary approach = weight reduction
- diet of 500 cal/day low in carbs high in veggies, whole grains and lean proteins
- physical activity of at elast 30 min/day (60-90 is optimal for weight loss)
84
what might be needed prior to physical activity in metabolic syndrome patients
cardiovascular evaluation
85
how do you treat metabolic syndrome w dyslipidemia
restrict dietary cholesterol
use statins IF + DM, CVD or high 10 year CVD risk
fibrates may be considered to help reduce TGs
86
how do you treat metabolic syndrome with HTN
sodium restricted diet
home BP monitoring
ACE/ARB
87
how do you treat metabolic syndrome w hyperglycemia
reduce dietary carbs
TZDs and/or metformin
