Hypoglycemia

Question 1

What is diabetes?

Answer 1

Chronic metabolic disease characterised by elevated levels of blood glucose

Question 2

How many people are affected by diabetes worldwide?

Answer 2

425 million people

Question 3

How is hypoglycemia defined?

Answer 3

Plasma glucose level ≤ 70mg/dL or ≤ 3.9mmol/L

Question 4

What is the standard concentration of glucose in plasma?

Answer 4

60 to 100 mg/dL

Question 5

What two hormones are involved in the regulation of blood glucose levels?

Answer 5

Insulin and glucagon

Question 6

What is glycogen?

Answer 6

A polysaccharide that is made and stored in the liver

Question 7

What is the physiological role of glycogen?

Answer 7

It is an energy reserve that can be quickly mobilised if there is a sudden need for glucose

Question 8

What occurs in the body when blood glucose levels rise?

Answer 8

Insulin secretion from beta cells in the pancreas increases, glucagon production in the liver is inhibited

Question 9

How is glycogen synthesised?

Answer 9

Glucose enters liver cells from the blood stream and stimulate enzymes to convert glucose to chains of glycogen (glycogenesis)

Question 10

What are the symptoms of hypoglycemia?

Answer 10

Tremor, tachycardia, hyperphagia, diaphoresis, disorientation, delirium,

Question 11

At what blood glucose concentration is decreased insulin secretion seen?

Answer 11

~80mg/dL

Question 12

At what blood glucose concentration is increased glucagon and epinephrine secretion seen?

Answer 12

~70mg/dL

Question 13

At what blood glucose concentration do symptoms of hypoglycemia tend to be seen?

Answer 13

~55mg/dL

Question 14

At what blood glucose concentration is functional brain failure seen?

Answer 14

Less than 50mg/dL

Question 15

What is meant by functional brain failure in hypoglycemia?

Answer 15

Decreased cognition, aberrant behavior, seizure, coma

Question 16

At what blood glucose concentration is neuronal death seen?

Answer 16

Below 20mg/dL

Question 17

What neurodegenerative condition is associated with diabetes due to episodes of severe hypoglycemia?

Answer 17

Dementia - Alzheimer’s and vascular

Question 18

What is meant by the term neuroglycopenia?

Answer 18

Low blood glucose levels in the brain

Question 19

What pathophysiological process occurs with the hypoglycemic cognitive deficit in diabetic rat models?

Answer 19

Oxidative stress

Question 20

What is a common rat model of type 1 diabetes and how is it induced?

Answer 20

Streptozotocin - drug mediated depletion of beta cells (necrotic death) followed by insulin injections to induce hypoglycemia

Question 21

Which brain regions were shown to have an increase in oxidative stress in a rat model of T1D?

Answer 21

Hippocampus, cortex

Question 22

What rescues the oxidative damage in the hippocampus seen in recurrent moderate hypoglycemic rats?

Answer 22

NOX2 inhibition

Question 23

What changes to glucose transporters are observed due to hypoglycemia?

Answer 23

Increased GLTU1 mRNA and protein in brain and capillaries/BBB (to increase glucose trafficking to the brain)

Upregulation of GLUT3 (neuronal transporter) and MCT2

Question 24

What is the typical response to hypoglycemia in healthy individuals?

Answer 24

Initial decrease in cerebral glucose consumption which is more prominent in regions of the brain that is active. Glucose transporters are upregulated. Further hypoglycemic events result in adaptive glucose uptake

Question 25

How do patients with uncontrolled T1D respond to recurrent hypoglycemic events?

Answer 25

Impaired simulation of hyperinsulinemic hypoglycemia-induced glucose oxidation, poor glucose uptake

Question 26

How does hypoglycemia impact glycolysis in murine models?

Answer 26

Fasting decreases glucose metabolism and malonyl-coenzyme A production in hypothalamus and cortex which reprograms substrate utilisation from glycolysis to lipid oxidation

Question 27

What changes to glycolytic enzymes are observed due to hypoglycemia?

Answer 27

Decreased levels of rate-limiting enzymes in the brain

Question 28

How does hypoglycemia impact the TCA cycle in T1D patients compared to healthy individuals?

Answer 28

Increase in TCA cycle flux

Question 29

What changes in mitochondrial respiration are induced by hypoglycemia?

Answer 29

Impairment of electron transport chain Decreases respiratory control ration

Question 30

What are alternate sources of energy for brain during hypoglycemia?

Answer 30

Lactate and ketone bodies

Question 31

What are the benefits of utilising alternative fuels during hypoglycemia?

Answer 31

Increase oxidative metabolism Decrease autonomic and neuroglycopenic symptoms Enhance glucose counter regulatory mechanisms

Question 32

What are the energy sources in the initial phases of hypoglycemia?

Answer 32

Lactate initially, then glutamate and glutamine, then aspartate

Question 33

What are ketone bodies the products of?

Answer 33

Fatty acid metabolism

Question 34

How do ketone bodies feed into the TCA cycle?

Answer 34

Metabolised into acetyl-CoA

Question 35

What are the main two ketone bodies used as energy sources?

Answer 35

3-b-hydroxybutyrate and acetone

Question 36

b-hydroxybutyric acid contributes to the neuronal synthesis of which amino acids?

Answer 36

Glutamate and glutamine

Question 37

What is glycogen?

Answer 37

Reserve respiratory substrate for the brain during metabolic stress

Question 38

Where is glycogen stored?

Answer 38

In astrocytes adjacent to synthesis and degradation enzymes

Question 39

How is glycogen mobilised during hypoglycemia?

Answer 39

Acted upon by glycogen phosphorylase in astrocytes and converted to glucose-1-phosphate and glucose-6-phosphate to feed glycolysis

Question 40

What is the glycogen supercompensation phenomenon?

Answer 40

Glycogen levels exceeding pre-hypoglycemia levels for a few hours following restoration of euglycemia after hypoglycemia