Diabetes

Question 1

Diagnostic criteria for diabetes diagnosis?

Answer 1

• fasting glucose of 126+ mg/dL
• random glucose of 200+ mg/dL
• 2-hr glucose 200+ during an OGTT with a 75gm loading dose
• A1c over 6.5

Question 2

What conditions can lead to tranisent hypeglycemia?

Answer 2

acute stresses such as severe infections, burns or trauma

SO confirm initial diganosis with at least 2 readings

Question 3

What is the major insulin-responsive site for postprandial glucose utilization?

Answer 3

skeletal muscle

Question 4

Oral sulfonylureas target what part of B cells?

Answer 4

ATP-sensitive K+ channels

Question 5

What are the incretins?

Answer 5

glucose-dependent insulinotropic polypeptide (GIP) secreted by enteroendocrine K cells in the proximal small bowel

-glucagon-like peptide-1 (GLP-1) secreted by L cells in the distal ileum and colon

Question 6

How do incretins affect glucose release?

Answer 6

The elevation in GIP and GLP-1 levels following oral food intake stimulates insulin secretion, attenuates glucagon secretion, and delays gastric emptying to promote satiety

Question 7

How are incretins removed from the body?

Answer 7

didpeptidyl peptidases (DPPs), especially DPP-4.

Question 8

T or F. Glucose uptake in the brain is insulin independent

Answer 8

T.

Question 9

Describe the GLUT-4 pathway of insulin

Answer 9

Insulin binds to insulin receptors which are composed of two a- and two B- subunits. The B-subunit has tyrosine kinase activity and insulin binding to the a-subunit activates the B-subunit which causes phosphorylation of many residues including the P13K and MAP kinase pathways which results in trafficking and docking of GLUT-4 receptors to the cell membrane, mediated by both CBL and AKT

Question 10

Most important genetic susceptibility of type I diabetes?

Answer 10

HLA cluster on chromosome 6, especially with DR3 or DR4 haplotypes

Question 11

Other genetic susceptibilities for type I diabetes?

Answer 11

CTLA4 and PTPN22

AIRE

Question 12

Lack of insulin causes failure to inhibit lipoprotein lipase leading to increased free fatty acid. How does this cause insulin resistance?

Answer 12

Excess free fatty acids overwhelm the fatty acid oxidation pathways, leading to accumulation of toxic intermediates which impair insulin signaling

They also compete with glucose for substrate oxidation, leading to feedback inhibition of glycolytic enzymes

And they cause secretion of inflammatory molecules

Question 13

How does insulin inhibit gluconeogenesis in the liver?

Answer 13

It blocks phosphoenol-pyruvate carboxykinase

Question 14

How does obesity lead to insulin resistance?

Answer 14

• central fat is more lipolytic and thus leads to increased fatty acids
• Adiponectin, an adipokine secreted by fat to increase insulin sensitivity is down-regulated
• this promotes inflammation

Question 15

T or F. B cell function is transiently increased early in type II diabetes pathogenesis

Answer 15

T. as a compensatory mechanism

Question 16

Gestational diabetes, or the development of diabetes during pregnancy, is typically corrected following birth BUT ____.

Answer 16

The vast majority of these women go on to develop overt diabets over the next 10-20 years

Question 17

Why is polydipsia a symptom of diabetes?

Answer 17

The obligatory osmotic-induced water loss combined with the resulting hyperosmolarity triggers osmoreceptors of the thirst centers of the brain

Question 18

Diabetic ketoacidosis is a common, serve acute complication of type I diabetes (and type II to some extent). How does this occur?

Answer 18

Some stressor (i.e. failure to take insulin, trauma, illness, etc.) is thought to promote the release of epinephrine which promotes glucagon action promoting a highly hyperglycemic state AND

the excess of free fatty acids (causes by failure to inhibit lipoprotein lipase) causes esterification to fatty acyl coenzyme A which is oxidized to form ketone bodies

Question 19

How does DKA present?

Answer 19

fatigue, N/V, SEVERE abdominal pain, a characteristic fruity odor, and Kussmaul breathing and eventually coma

Question 20

T or F. Pyelonephritis is more common in diabetics than non-diabetics

Answer 20

T. Especially the necrotizing papillitis pattern

Question 21

What causes the common retinopathy seen in diabetes?

Answer 21

Neovascularization is caused by hypoxia-induced overexpression of VEGF in the retina

Question 22

T or F. Insulin can pass the placenta

Answer 22

F.

Question 23

Which of the following, alpha or beta agonists, stimulates insulin release?

Answer 23

B-agonists stimulate and alpha agonists inhibit insulin secretion

Question 24

T or F. C peptide can used to measure exogenous insulin

Answer 24

F.

Question 25

What are the insulin independent organs for glucose uptake?

Answer 25

Brain, RBCs, Intestine, Cornea, Kidney, and Liver

BRICK L