Intro Flashcards
What are the features of vascular disease in diabetic foot
Pale discoloration
Loss of hair
Absent pulses (begin in foot and proceed to legs)
Reduced capillary refill time
Cool temperature
Evidence of gangrene or infection
Features of neuropathy in diabetic foot?
Clawing of toes, loss of plantar arch
Joint deformity (charcot’s joint)
Glove and stocking sensory loss
Loss of vibration sense, proprioception and pain
Loss of ankle jerk
Neuropathic ulcers
What is the most common cause of death in diabetic patients?
Heart disease
Which molecules are used in gluconeogenesis?
The liver combines three-carbon molecules derived from the break-down of fat (glycerol), muscle glycogen (lactate) and protein into six-carbon glucose molecules.
Organs of gluconeogenesis
Liver
Kidney
Is glucose uptake by the brain insulin-dependent?
No, it is obligatory
Regulated pathway of insulin release
Ribosomes manufacture pre-proinsulin
the hydrophobic “pre” portion allows it to transfer to the Golgi apparatus where it is cleaved off
proinsulin is packaged into secretory granules in the Golgi apparatus
They mature and pass toward the cell membrane where they are stored before release
The proinsulin molecule folds back on itself and stabilized by disulfide bonds
C (connecting) peptide splits off from proinsulin in the secretory process leaving insulin as a complex of two linked peptide chains
Equimolar quantities of insulin and c-peptide are released into the circulation
Regulated pathway of insulin release
Bypasses secretory granules
What happens to glucose taken up by muscles
Stored as glycogen or metabolized to lactate or carbon dioxide and water
What happens to glucose taken up by fat cells
Becomes a substrate for triglyceride synthesis. In the process of lipolyses, fatty acids from triglycerides are released together with glycerol, a substrate for hepatic gluconeogenesis
Which glucose transporter is insulin dependent
GLUT-4
It is normally present in the cytoplasm, but after insulin binds to its receptor, GLUT-4 moves to the cell surface where it creates a pote for glucose entry
Function of insulin in the fasting state?
Regulate glucose release by the liver
Function of insulin in the postprandial state
Promotes glucose uptake by fat and muscles
Counter regulatory hormones that antagonize the action of insulin
Glucagon
NE
Cortisol
Growth hormone
Increase hepatic glucose production and reduce its utilization in fat and muscle for any given insulin concentration
Secondary diabetes can be subdivided into:
Diabetes secondary to genetic defects
Diabetes secondary to exocrine pancreatic disease
Diabetes secondary to endocrine disease
Diabetes secondary to drugs and chemicals
Diabetes secondary to infection
Uncommon forms of immune-mediated diabetes
Other genetic syndromes sometimes associated with diabetes
What is latent autoimmune diabetes in adult (LADA)
Is a slow-burning variant of type 1A diabetes with slower progression to insulin deficiency occurring later in adulthood
Immune mediated organ specific diseases
Type 1 diabetes
Autoimmune thyroid disease
Coeliac disease
Addison’s disease
Pernicious anaemia
Pathophysiology of type 1 diabetes
Triggering of selective autoimmune destruction of the insulin producing cells in a genetically susceptible individuals
Asymptomatic loss of beta cell secretory capacity histologically characterized by a chronic inflammatory mononuclear cell infiltrate of of T lymphocytes and macrophages in the islets, known as insulitis
Diabetes symptoms start to develop when the remaining beta cells are no longer able to produce enough insulin to meet the body’s needs
Autoantibodies are directed against the following islet antigens (in type 1 DM)
Insulin
Glutamic acid decarboxylase (GAD)
Protein tyrosine phosphatase (IA-2, aka ICA512)
The cation transporter ZnT8
Tetraspanin 7
Genes involved in type 1 diabetes
HLA-DR3-DQ2
HLA-DR4-DQ8
Or both
Risk factors for developing type 2 DM
Obesity
Diet
Physical inactivity
Others: urbanization, poverty, abnormal sleep pattern, environmental toxins, mental illness
Pathogenesis of type 2 diabetes
Abnormalities of insulin action (insulin resistance)
Abnormalities of insulin secretion
Other hormonal abnormalities (increased glucagon secretion and impaired incretin effects)
Glucose réabsorption in the kidney
Insulin resistance
Inability of insulin to produce its usual biological effects at physiological concentrations. It is characterized by an impaired ability of insulin to:
-inhibit hepatic glucose output
-stimulate glucose uptake into skeletal muscle, and
-suppress lipolysis in adipose tissue
Incretin effect
Mediated by two hormones, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP), which are released by the GI tract following eating. They increase insulin secretion, reduce glucagon secretion, slow gastric emptying and induce satiety. Both hormones have short half-lives and are degraded within minutes by dipeptidyl peptidase-4 (DPP4)
