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Flashcards in Type 1 Diabetes Deck (45):
1

What are the 4 cell types of the islets?

1. Beta (60-80%)
2. Alpha (20-30%
3. Delta (somatostatin, suppresses insulin and glucagon)
4. Pancreatic polypeptide (unknown fxn)

2

What inc risk of CV dis do you have with diabets?

2-4X inc risk

3

Describe the processes of insulin processing

1. Insulin is synth as inactive precursor form (preproinsulin)
2. A signal sequence is removed from preproinsulin following insertion into the endoplasmic reticulum, resulting in proinsulin
3. Proinsulin is further processed to form insulin and a byproduct C peptide, both of which are packaged into secretory vesicles (proteolytic cleavage by trypsin, chymotrypsin-->removal of basic AAs)
4. Mature insulin is comprised of an A and B peptide chain, linked together by two disulfide bonds

4

What kind of hormone is insulin?

Peptide hormone

5

What does insulin do?

Key anabolic hormone critical for glucose uptake and utilization, lipid and protein synth, and an essential growth factor for normal development

6

What needs to be intact for insulin to do all of its jobs?

-Islet b cell mass
-insulin synthesis
-glucose-dep insulin secretion
-insulin signaling at target cells

7

What is often used to measure endogenous insulin production?

Amount of C peptide (which was cleaved during to production of insulin)

8

What is the turnover rate of insulin?

2-4hrs

9

What is amylin?

Amylin (IAPP) is a substance also in secretory granules with insulin, proinsulin, proteolytic enzymes and Zn. It inhibits glucagon secretion after a meal. In diabetics, there is less amylin and therefore inc glucagon concentrations

10

What 3 things are stimulatory for insulin secretion?

1. Nutrient load (glucsoe the most, but fat and protein also stimulate its release)
2. Autonomic NS (vagus-->stim, sympathetic-->Inhibits and cephalic phase-->stim)
3. Hormones (GLP-1 and GIP gut hormones stim)

11

What 2 things inhibit insulin secretion?

1. Starvation/hypoglycemia
2. Hormones (glucagon, epinephrine, growth hormone, cortisol)

12

How does glucose work to regulate insulin secretion?

Directly and by augmenting the action of other insulin secretagogues

A rise in blood glucose levels causes an immediate release of insulin from granules. If the secretory stimulus persists, a delayed response follows causing more insulin to be produced.

13

What other agents regulate normal insulin metab?

GLP1, leucine, arginine, sulfonylureas stim inuslin reslease

14

What is insulin necessary for?

-Transmembrane transport of gluc and AAs
-Glycogen formation in the liver and skeletal muscles
-Glucose conversion to TGs
-Nucleic acid synth
-Protein synth

-Principle fxn is to inc rate of glucose transport into striated muscle cells

15

How are type 1 and type 2 different in their insulin production?

T1: absolute insulin def
T2: insulin resistance with relative insulin deficiency

16

How are type 1 and type 2 different in their onset of symptoms?

T1: Abrupt onset of hyperglycemia and propensity for dev of DKA
T2: Hyperglycemia dev gradually with progressive decline in beta cell fxn (ie initially silent)

17

How are type 1 and type 2 different in treatment?

T1: lifelong insulin injection required
T2: can be treated with oral meds

18

How are type 1 and type 2 different in cause?

T1: Associated with auto-antibodies
T2: Associated with increasing age and obesity
(hyperosmolar hyperglycemic non-ketosis (HHNK), can dev DKA)

19

How are type 1 and type 2 different in age?

T1: predominant type of diabetes diagnosed <30y/o

20

How are type 1 and type 2 different in family hx

T1: rare
T2: 95%, common

21

How are type 1 and type 2 different in mechanism

T1: autoimmune destruction of beta cells
T2: unknown

22

How are type 1 and type 2 different in first functional abnormality?

T1: dec in insulin sec
T2: dec insulin sec and response to insulin

23

How are type 1 and type 2 different in initial pathology

T1: insulinitis
T2: little/none

24

How are type 1 and type 2 different in late pathoogy

T1: absence of beta cells, inc in alpha and gamma
T2: Amyloid deposition, fibrosis. Beta cell mass reduction

25

What is the criteria for diagnosis of diabetes?

-Symp of diabetes plus a random plasma glucose concentration of >200mg/dL
-Fasting plasma glucose concentration >126mg/dL
-2-hr plasma glucose concentration >200mg/dL during an OGTT
-A1c >= 6.5%

26

What are the specific signs and symptoms of diabetes?

-Polyuria/polydipsia
-wt loss (starvation state, not abs calories)
-polyphagia (excessive hunger)
-diabetic ketoacidosis (more common in type 1)
-coma

27

What are the non-specific signs and symp of diabetes?

-Fatigue
-Blurred vision (lens gets distorted due to osmolar effect)
-Dry mouth
-Dry/itchy skin (dehydration)
-Vaginal candidiasis
-Poor healing of wounds (bacteria like diabetic medium)
-Excessive/unusual infections (immunosupp due to hyperglycemia)

28

When do we get glucose in the urine?

When we oversaturate the glucose transporters (Tm) in the glomerular filtrate due to chronically high glucose in the blood (175-200mg/dl)

29

What are the peak ages of onset of T1D?

5-7yr and at onset of puberty. 1/3 of cases after age 18

30

What time of year more likely to have the onset?

Cold season...maybe virus triggers it?

31

Describe the incidence of T1d

Incidence is increasing world wide

32

What are some risk factors for T1d?

-Viral infections (coxsaccie, congenital rubella, enterovirus infections)
-Diet, esp exposure to cow's milk at early age
-High SES
-Obesity
-Vit D def
-Perinatal factors like mat age, hx of preeclampisa, neonatal jaundice. Low birth wt dec risk of dev T1D

33

What serum auto-antibodies have been detected in t1d

-Islet cell Abs (ICA)
-Insulin Abs (IAA)
-Glutamic acid decarboxylase Abs (GAD)
-Tyrosine phosphatase-like proteins like insulinoma associated protein (IA-2)
-Cation efflux zinc transporter (ZnT8) has been indentified as a candidate

34

Describe the relationshipt betw T1 D and other autoimmune dis

Lots of concurrence with other autoimmunity like thyroiditis, addisons or celiac

35

What is Latent Auto-Immune Diabetes of Adulthood (LADA)?

-Intermediate between T1 and T2. Usually presents >25 y.o masquerading as non-obese type 2 (non DKA) with pos auto antibodies seen. It can initially be controlled with meal planning, but insulin dep gradually occurs within months. They have a low peptide C concentration and are unlikely to have a fam hx of t2d.

36

How do we treat T1d?

-Insulin replacement therapy
-Edu
-Adjust doses according to carb intake, exercise, blood glucose profile
-Test blood gluc levels
-Screen for complications

37

By how much does intensive therapy significantly reduce microvascular complications?

-Retinopathy: 76%
-Nephropathy: 50%
-Neuropathy: 60%

38

What is DKA?

Potentially life threatening presentation of T1D where the body perceives a state of starvation Because no insulin is being synth or detected and rallies body stores to compensate. This includes hepatic glucose produc, muscle breakdown and fat breakdown to ketones.

39

What are the symptoms of DKA?

Nausea/vomiting, polyuria, weakness, anorexia, abdominal pain, visual disturbances, somnolence

Signs: tachycardia, hypotension, dehydration, hyperventilation, wt loss, fruity odor on breath, altered mental status

40

What do we do to treat DKA?

Replace insulin 1st! then correct fluid and electrolyte imbalances .

41

What does loss of insulin in DKA effect?

1. Liver: plasma glucose inc, glucosuria, polyuria-->dehydration

2. Muscle: inc plasma glucose and muscle wasting-->wt loss

3. Adipose: inc plasma FFAs-->inc plasma beta hydroxybutyrate and acetoacetate-->acidosos (ketones)

42

What are the urgent problems in DKA?

Hyperosmolar dehydration and acidosis

43

What are some potential treatment adverse events of DKA?

-Cerebral edema and hypokalemia if convert too quickly

44

What is the #1 complication of T1D or pts on insulin?

Hypoglycemia

45

What is the basal bolus approach?

Tries to mimic endogenous insulin production by combining basal dose to suppress hepatic glucose production between meals and bolus dose after meals