Diagnostic criteria for diabetes diagnosis?
-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
What conditions can lead to tranisent hypeglycemia?
acute stresses such as severe infections, burns or trauma
SO confirm initial diganosis with at least 2 readings
What is the major insulin-responsive site for postprandial glucose utilization?
Oral sulfonylureas target what part of B cells?
ATP-sensitive K+ channels
What are the incretins?
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
How do incretins affect glucose release?
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
How are incretins removed from the body?
didpeptidyl peptidases (DPPs), especially DPP-4.
T or F. Glucose uptake in the brain is insulin independent
Describe the GLUT-4 pathway of insulin
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
Most important genetic susceptibility of type I diabetes?
HLA cluster on chromosome 6, especially with DR3 or DR4 haplotypes
Other genetic susceptibilities for type I diabetes?
CTLA4 and PTPN22
Lack of insulin causes failure to inhibit lipoprotein lipase leading to increased free fatty acid. How does this cause insulin resistance?
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
How does insulin inhibit gluconeogenesis in the liver?
It blocks phosphoenol-pyruvate carboxykinase
How does obesity lead to insulin resistance?
-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
T or F. B cell function is transiently increased early in type II diabetes pathogenesis
T. as a compensatory mechanism
Gestational diabetes, or the development of diabetes during pregnancy, is typically corrected following birth BUT ____.
The vast majority of these women go on to develop overt diabets over the next 10-20 years
Why is polydipsia a symptom of diabetes?
The obligatory osmotic-induced water loss combined with the resulting hyperosmolarity triggers osmoreceptors of the thirst centers of the brain
Diabetic ketoacidosis is a common, serve acute complication of type I diabetes (and type II to some extent). How does this occur?
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
How does DKA present?
fatigue, N/V, SEVERE abdominal pain, a characteristic fruity odor, and Kussmaul breathing and eventually coma
T or F. Pyelonephritis is more common in diabetics than non-diabetics
T. Especially the necrotizing papillitis pattern
What causes the common retinopathy seen in diabetes?
Neovascularization is caused by hypoxia-induced overexpression of VEGF in the retina
T or F. Insulin can pass the placenta
Which of the following, alpha or beta agonists, stimulates insulin release?
B-agonists stimulate and alpha agonists inhibit insulin secretion
T or F. C peptide can used to measure exogenous insulin
What are the insulin independent organs for glucose uptake?
Brain, RBCs, Intestine, Cornea, Kidney, and Liver