34 Pathophysiology of Type 2 Diabetes Mellitus Flashcards
Primary site for de novo lipogenesis
Liver
Primary storage for triglycerides
Adipose tissue
Main effects of insulin signaling in the muscle (3)
Glucose uptake/metabolism
Protein synthesis/growth
Suppression of atrophy/autophagy
Main effects of insulin signaling in adipose tissue (4)
Glucose uptake
Lipogenesis
Gene regulation
Suppression of lipolysis
Main effects of insulin signaling in the liver (2)
Lipogenesis
Suppression of glucose production
Predominant glucose transporters in the brain (2)
Glut1 and Glut3
Abdominal fat vs subcutaneous fat:
More lipolytically active
Abdominal fat
Abdominal fat vs subcutaneous fat:
Greater complement of adrenergic receptors
Abdominal fat
Abdominal fat vs subcutaneous fat:
Resistant to antilipolytic effects of insulin
Abdominal fat
Abdominal fat vs subcutaneous fat:
Releases more adiponectin
Subcutaneous fat
Abdominal fat vs subcutaneous fat:
High levels of HSD11B1
Abdominal fat
Abdominal fat vs subcutaneous fat:
Increased local cortisol production
Abdominal fat
Predominant insulin receptor isoform in the brain
IR-A
Primary site of glucose disposal after a meal
Skeletal muscle
Maternal insulin secretion increases by how much in pregancy
250%
Mechanism as to how calcineurin inhibitor contributes to diabetes
Decreased insulin secretion
Most common adverse effect of bromocriptine use in diabetes
Nausea
Onset of action of rapid acting insulins
<5 mins: Aspart (Fiasp)
10-20 mins: Aspart (Novolog), Lispro (Humalog), Glulisine (Apidra)
Time to peak of rapid acting insulins
0.5-1.5 hours
Duration of action of rapid acting insulins
3-5 hours
Onset of action of regular human insulin
30-45 mins
Onset of action of NPH insulin and long acting insulins
60-120 mins
Time to peak of regular human insulin
2-4 hours
Duration of action of regular human insulin
4-8 hours
Time to peak of NPH insulin
4-8 hours
Duration of action of NPH insulin
12-20 hours
Three cardinal abnormalities in T2DM
Resistance to action of insulin in peripheral tissues
Defective insulin secretion
Increased glucose production by the liver
Earliest detectable abnormality in those predisposed to T2DM
Insulin resistance
This monogenic form of diabetes is characterized by the presence of insulin resistance, acanthosis nigricans, and hyperandrogenism
Type A insulin resistance
This monogenic form of diabetes is characterized by severe intrauterine growth restriction, abnormal facies, and death within 1-2 years of life
Donohue syndrome (leprechaunism)
This monogenic form of diabetes is associated with short stature, protuberant abdomen, and abnormalities of teeth and nails. Pineal hyperplasia was a characteristic in the original description of this syndrome.
Rabson-Mendenhall syndrome
Mutation in the lamin A gene can cause a face-sparing familial partial lipodystrophy, also commonly referred to as:
Dunningan syndrome
Mutation in the lamin A gene can cause this syndrome characterized by partial lipodystrophy, postnatal growth retardation, and craniofacial and skeletal malformations.
Mandibuloacral dysplasia syndrome
Acquired generalized lipodystrophy is also known as:
Seip-Lawrence syndrome
First polymorphism identified for T2DM
Gly972Arg in IRS1
Mutations in these genes are thr most common cause of neonatal diabetes
KCNJ11 and ABCC8
A variant in this gene found almost exclusively in the Samoan population is associated with a large increase in BMI per risk allele and is also associated with a paradoxical decrease in risk of developing T2DM
CREBRR
Main glucose transporter involved in uptake in muscle and dipose
GLUT4
Effect of insulin action on the endothelium
Vasodilation
Effect of insulin stimulation on cardiomyocyte (2)
Increased glucose oxidation and hypertrophy
Suppressed fatty acid oxidation and autophagy
Primary site of glucose disposal after a meal
Skeletal muscle
Primary deacetylase of mitochondria
Sirt3
Enzyme that catalyzes the transfer of acyl chain from carnitine to CoA
CPT2
Enzyme that mediates the uncoupling of oxidative phosphorylation in brown adipose tissue for thermogenesis
UCP1
Lipoatrophy in HIV is primarily associated with the use of:
Older thymidine analogue NRTIs