Ward 8

Question 1

When, how, and who discovered insulin?

Answer 1

In 1921 by Canadian physician and his medical student finding it in pancreatic extracts of dogs. They injected the hormone into a dog and found that it lowered high blood glucose levels

Question 2

What is a person on type 1 and type 2 diabetes usually on insuln wise?

Answer 2

• In type 1 diabetes, Either an insulin pump, and if not they will always need to inject a combination of intermediate or long-acting insulin, as well as a rapid acting insulin
• In type 2 diabetes, insulin is used if other therapies are not effective

Question 3

What are common conditions that cause secondary diabetes?

Answer 3

They include cushing syndrome, acromegaly (too much GH), cystic fibrosis, glucocorticoid treatment, pancreatic diseases (such as pancreatitis), use of some antipsychotics, maternal diabetes

Question 4

Type 1 vs Type 2 diabetes split in the UK

Answer 4

About 90% have type 2 diabetes while 10% haave type 1 diabetes

Question 5

Where is insulin sourced nowadays?

Answer 5

• Animal insulin products are rarely used now
• Human and analogue insulin is most often prescribed - Biosimilar insulin is now available in the UK

Question 6

Units used when prescribing insulin

Answer 6

Most insulin is prescribed as 100 units per mL (U100). Other concentrations of insulin are now available including U200 (200 units per 1 mL) and U300 (300 units per 1 mL)

Question 7

Insulin regimens

Answer 7

• Once daily: Involving intermediate or longer acting insulin
• Twice daily
• 3x per day: Offers a basal intermediate acting insulin with short or fast acting insulin with meals
• Basal bolus- intermediate or ultra long acting insulin
• IV insulin infusion: insulin pump and only used in the hospital setting
• Continuous insulin pump therapy: Insulin given over 24 hour period visa an insulin pump and self inserted cannula (for type 1 diabetics and are managed by themselves)

Question 8

What is diabetes

Answer 8

spectrum of metabolic disorders arising from myriad pathogenic mechanisms, all resulting in hyperglycemia.

Question 9

Pathogenic mechanisms leading to diabetes

Answer 9

involves insufficient insulin secretion, reduced responsiveness to endogenous or exogenous insulin, increased glucose production, or abnormalities in fat and protein metabolism

Question 10

Complications of diabetes

Answer 10

• Major sources of the morbidity of diabetes are the chronic complications
  that arise from prolonged hyperglycemia, including retinopathy, neuropathy, nephropathy (diabetic nephropathy), and cardiovascular disease (atherosclerosis)
• Untreated diabetes can lead to severe metabolic disturbances that can be
  acutely life threatening, such as diabetic ketoacidosis and a hyperglycemic
  hyperosmolar state. These require hospitalization for insulin administration,
  rehydration with intravenous fluids, and careful monitoring of electrolytes and metabolic parameters

Question 11

What is glucose tolerance

Answer 11

Maintenance of glucose homeostasis

Question 12

Where is insulin produced in the body and what do they do?

Answer 12

The pancreatic β cell, adjusting the amount of insulin secreted very precisely to promote glucose uptake after meals and to regulate glucose output from the liver during fasting

Question 13

How is fuel demand met in the fasting state?

Answer 13

In the fasting state , the fuel demands of the body are met by the oxidation of fatty acids. The brain does not effectively use fatty acids to meet energy needs and in the fasting state requires glucose for normal function

Question 14

Where is a lot of the glucose in the body used?

Answer 14

To supply the CNS

Question 15

Which source provides fasting glucose requirements?

Answer 15

Primarily provided by the liver through glycogen stores, with some of it also from conversion of lactate, alanin, and glycerol into sugar

Question 16

What regulates glucose homeostasis in the liver?

Answer 16

The dominant regulation of hepatic glycogenolysis and gluconeogenesis is controlled by the pancreatic islet hormones insulin and glucagon

Question 17

Insulin role in the body

Answer 17

• The actions of insulin are anabolic, and insulin signaling is critical
  for promoting the uptake, use, and storage of the major nutrients: glucose,
  lipids, and amino acids. Insulin stimulates glycogenesis, lipogenesis, and
  protein synthesis; it also inhibits the catabolism of these compounds
• Elevated circulating insulin concentrations lower glucose in blood
  by inhibiting hepatic glucose production (HGP) and stimulating the
  uptake and metabolism of glucose by muscle and adipose tissue
• Insulin inhibits hepatic glucose production, and the decline of circulating insulin concentrations in the postabsorptive state (fasting) is permissive for higher rates of glucose output
• Insulin also promotes glucose, lipid, and protein anabolism

Question 18

Glucagon role in the liver

Answer 18

Glucagon maintains blood glucose concentrations at physiological
levels in the absence of exogenous carbohydrate (overnight and in between
meals) by stimulating gluconeogenesis and glycogenolysis by the liver

Question 19

What stimulates insulin secretion?

Answer 19

• Pancreatic β cell function is primarily controlled by plasma glucose concentrations. Elevations of blood glucose are necessary for insulin release
  above basal levels, and other stimuli are relatively ineffective when plasma
  glucose is in the fasting range.
• Stimulated by food ingestion, nutrient absorption, and elevated blood glucose

Question 20

Glucose levels during fasting

Answer 20

4.4–5.5 mM or 80–100 mg%)

Question 21

Other factors implicated in insulin regulation

Answer 21

Other stimuli include nutrient substrates, insulinotropic hormones released from the GI tract, and autonomic neural pathways. Neural stimuli cause some
increase of insulin secretion prior to food consumption. Neural stimulation
of insulin secretion occurs throughout the meal and contributes significantly
to glucose tolerance. Arrival of nutrient chyme to the intestine
leads to the release of insulinotropic peptides from specialized endocrine
cells in the intestinal mucosa. GIP and GLP-1, together termed incretins,
are the essential gut hormones contributing to glucose tolerance. They are
secreted in proportion to the nutrient load ingested and relay this information
to the islet as part of a feed-forward mechanism that allows an
insulin response appropriate to meal size

Question 21

Insulin secretiation rates throughout the day and implications

Answer 21

Insulin secretion rates in healthy humans are highest in the early digestive phase of meals, preceding and limiting the peak in blood glucose. This pattern of premonitory insulin secretion is an essential feature of normal glucose tolerance. Mimicking this pattern is one of the key challenges for successful insulin therapy in diabetic patients.

Question 22

Timing of effects seen with insuling

Answer 22

• Some effects of insulin (e.g., activation of glucose and ion transport systems, phosphorylation or dephosphorylation of specific enzymes) occur within seconds or minutes; other effects (e.g., those promoting protein synthesis and regulating gene transcription and cell proliferation) manifest over minutes to hours to days.
• The effects of insulin on cell proliferation and differentiation occur over a longer period of time
• Some of the effects of insulin on the liver occur rapidly, within the first 20 min of meal ingestion, whereas stimulation of peripheral glucose uptake may require up to an hour to reach significant rates.

Question 23

How does insulin promote lipid anabolism?

Answer 23

Insulin has potent effects to reduce lipolysis from adipocytes, primarily through the inhibition of hormone-sensitive lipase; insulin also increases lipid storage by promoting lipoprotein-lipase synthesis and adipocyte glucose uptake

Question 24

How does insulin promote protein anabolism?

Answer 24

In muscle and other tissues, insulin stimulates amino acid uptake and protein synthesis and inhibits protein degradation

Question 25

Glucose support during exercise

Answer 25

The limited glycogen stores in skeletal muscle are mobilized at the onset
of physical activity, but most of the glucose support for exercise comes
from hepatic gluconeogenesis. The dominant regulation of hepatic glucose
production during exercise comes from EPI and NE. The catecholamines
stimulate glycogenolysis and gluconeogenesis, inhibit insulin secretion,
and enhance release of glucagon, all contributing to increased hepatic
glucose output. In addition, catecholamines promote lipolysis, freeing
fatty acids for oxidation in exercising muscle and glycerol for hepatic
gluconeogenesis

Question 26

Insulin synthesis in the body

Answer 26

Insulin is initially synthesized as a single polypeptide chain, preproinsulin
(110 amino acids), which is processed first to proinsulin and then to
insulin and C-peptide

Question 27

Which receptor does insulin act on?

Answer 27

Insulin receptor, bearing functional similarity to the IGF-1 receptor

Question 28

What does insulin binding to its receptor trigger?

Answer 28

Signalling cascade responsible for its actions in cell growth/differentiation/survival, protein synthesis, glycogen synthesis, and translocation of GLUT4 to the membrane which is responsible for taking in extracellular glucose

Question 29

Where is GLUT 4 found?

Answer 29

Expressed in insulin-responsive tissues such as skeletal muscle and adipose tissue

Question 30

What is a normal fasting and impaired blood glucose level?

Answer 30

fasting plasma glucose < 5.6 mmol
Impaired fasting glucose (IFG) : 5.6–6.9 mmol/L

Question 31

What is impaired glucose tolerance defined as?

Answer 31

glucose level between 7.8 and 11.1
mmol/L (140 and 199 mg/dL) 120 min after ingestion of 75 g liquid
glucose solution

Question 32

Criteria for diagnosis of diabetes

Answer 32

• Symptoms of diabetes plus random blood glucose concentration ≥ 11.1 mM (200 mg/dl)
• Fasting plasma glucose ≥ 7.0 mM (126 mg/dL)b or
• Two-hour plasma glucose ≥ 11.1 mM (200 mg/dL) during an oral
  glucose tolerance test
• HbA1c ≥ 6.5%

Question 33

What is fasting blood glucose defined as?

Answer 33

Fasting is defined as no caloric intake for at least 8 h

Question 34

What is type 1 diabates?

Answer 34

β-cell destruction, usually leading to absolute insulin deficiency
A. Immune mediated
B. Idiopathic

Question 35

What is the reason for type 2 diabtes/

Answer 35

• Best thought of as a heterogeneous syndrome of dysregulated glucose homeostasis associated with impaired insulin secretion and action
• results when there is insufficient insulin action to maintain plasma glucose levels in the normal range
• Insulin action is the composite effect of plasma insulin concentrations (determined by islet β cell function) and insulin sensitivity of key target tissues (liver, skeletal muscle, and adipose tissue)

Question 36

Genetic component of diabetes

Answer 36

• Has a strong genetic component. It is a heritable condition with a relative 4-fold increased risk of disease for persons having a diabetic parent or sibling, increasing to 6-fold if both parents have type 2 diabetes

Question 37

What is insulin sensitivity?

Answer 37

• Insulin sensitivity is measured as the amount of glucose cleared from the
  blood in response to a fixed dose of insulin
• The failure of normal amounts of insulin to elicit the expected response is referred to as insulin resistance
• At the cellular level, insulin resistance involves blunted steps
  in the cascade from the insulin receptor tyrosine kinase to translocation
  of GLUT4 transporters, but the molecular mechanisms are incompletely
  defined

Question 38

What are major insulin responsive tissues?

Answer 38

Skeletal muscle, adipose tissue, and liver