LAB - Glucose Tolerance Test Lab

Question 1

How much Glucose is in the drink ?

Answer 1

75g

Question 2

How long should your fast be for ?

Answer 2

10-12 hrs

Question 3

What is Elizabeth’s body mass index (BMI) ?
- Height 1.54 m
- Weight 81.3 kg

Answer 3

BMI = weight/height2

34.3kg/m2

Question 4

According to the WHO criteria, how would you classify Eilizabeth’s glucose homeostasis?

Plasma glucose – Sample A = Approximately 9 mmol/L (random plasma glucose value)

Plasma glucose – Sample B-0 = Approximately 8.5 mmol/L
(Fasting value)

Plasma glucose – Sample B-120 = Approximately 13.5 mmol/L (2hrs after 75g glucose)

Answer 4

Diabetic as Fasting was greater than 7.0 and after 2 hours greater than 11.1

Question 5

Give the criteria for Random Glucose, Fasting Glucose and OGTT for normal, impaired and diabetic patients?

Answer 5

Random Glucose;
- Diabetes Excluded = <5.5mmol/l
- More testing required = 5.6-11.0mmol/l
- Diabetes = >11.1mmol/l

Fasting glucose;
- Diabetes Excluded = <6.1mmol/l
- More testing required (OGTT) = - 6.1 – 6.9 mmol/l
- Diabetes = >7.0mmol/l

Oral Glucose Tolerance Test (OGTT) - 2-h plasma glucose after ingestion of 75g glucose;
- Diabetes Excluded = <7.8mmol/l
- Impaired Glucose Tolerance/Pre-diabetes = - 7.8-11 mmol/l
- Diabetes = >11.1mmol/l

Question 6

What is the HbA1c target for Type 2 diabetics to reduce the risk of complications ?

Answer 6

HbA1c target of <7.0% (53 mmol/mol)

Question 7

What should be the 1st line of therapy in people with type 2 diabetes ?

Answer 7

Metformin

Question 8

What should be the 1st line of therapy in people with type 2 diabetes who are intolerant or have contraindications to metformin ?

Answer 8

Sulphonylurea

Question 9

What should be the 2nd line of therapy in people with type 2 diabetes ?

Answer 9

Second line therapies (Sulphonylurea, Pioglitazone, SGLT2 inhibitor, or DPP-4 inhibitor) may be used to improve blood glucose control in people with type 2 diabetes if not reaching targets after 3-6 months.

Question 10

When would you use a GLP-1 agonist ?

Answer 10

GLP-1 agonists may be used to improve glycaemic control in obese adults (BMI ≥ 30 kg/m2) with type 2 diabetes. A GLP-1 agonist will usually be added as a third line agent in those who do not reach target glycaemia on dual therapy with metformin and sulphonylurea (as an alternative to adding insulin therapy).

Question 11

When would you use a NPH insulin ?

Answer 11

Once daily bedtime NPH insulin should be used when adding insulin to metformin. Basal insulin analogues should be considered if there are concerns regarding hypoglycaemia risk.

Question 12

What order should you follow when looking to administer medication to type 2 diabetics ?

Answer 12

Note: Metformin or Sulphonylurea would be considered first-line treatments. If the individual is not achieving adequate glycaemic control Pioglitazone, SGLT2 inhibitors, or DPP4- inhibitors may be added. GLP-1 agonists may be added as a third line therapy to obese patients not achieving targets. In non-obese targets insulin injectables are suggested third line therapy.

Question 13

What is HbA1c? Why is it a useful marker for glucose homeostasis? If you had tested Elizabeth today, when would be a good time to test her again (and why), in order to monitor her glucose homeostasis using HbA1c?

Answer 13

The level of glycated haemoglobin (HbAIc) is proportional to the levels of glucose in the blood over a period of approximately 3 months. To answer when it might be good to test Elizabeth again, think how long a red blood cell lasts (~120 days)(and therefore how long it would be before you are testing new Hb)

Question 14

What is DPP-4? How will inhibiting it improve blood glucose control?

Answer 14

DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys GLP-1 (an incretin). Incretins help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. These hormones are released throughout the day and levels are increased at meal times.

Question 15

How do sulphonylureas help in the treatment of diabetes mellitus? Which cell types do they act on? What is their mechanism of action?

Answer 15

These drugs act on β-cells and inhibit the ATP-sensitive K+ channel.

Question 16

What type of drug is metformin? Which cell type(s) does it act on? What is its mechanism of action?

Answer 16

Biguanide. Causes an increase in the uptake of glucose in skeletal muscle and in liver, it increases insulin sensitivity, it increases the storage of glucose and decreases gluconeogenesis. It also decreases glucose uptake from the gut and suppresses appetite (making it useful to use with sulphonlyureas which increase appetite)

Question 17

What are GLP-1 agonists acting on? How does this help with the control of glucose homeostasis?

Answer 17

GLP-1 receptor on β-cells. Only useful if glucose is present as it uses ATP to make cAMP. Ultimately (check the detail in your pharmacology lectures) this intensifies insulin secretion.

Question 18

What is NPH insulin?

Answer 18

NPH insulin is an insulin with an intermediate duration of action. NPH stands for neutral protamine Hagedorn insulin. It is insulin which has been made intermediate-acting by adding a protein (protamine) in complex with zinc.

Question 19

What dietary advice would you give Elizabeth to help her to control her condition?

Answer 19

• Decrease intake of processes carbohydrate
• Increase intake of fibre and complex carbohydrate to 50% of calorie intake (low glycaemic index foods)
• Decrease intake of fat, especially saturated fat
• Decrease alcohol consumption
• Eat small, regular, frequent meals, to avoid glucose spikes
• Take more exercise

Question 20

According to the SIGN Gestational Diabetes criteria, how would you classify Isabelle’s glucose homeostasis?

Plasma glucose – Sample C = Approximately 9 mmol/L (random plasma glucose value)

Plasma glucose – Sample D-0 = Approximately 4.9 mmol/L
(Fasting value)

Plasma glucose – Sample D-120 = Approximately 10 mmol/L (2hrs after 75g glucose)

She is pregnant

Answer 20

Isabelle’s fasting blood glucose level is normal but after the OGTT her 2 hr reading is >8.5 mmol/L. This would classify her as having GDM.

Question 21

What is the criteria for Gestational Diabetes Mellitus (GDM)?

Answer 21

Gestational Diabetes Mellitus (GDM);

• Fasting plasma glucose = ≥ 5.1 mmol/L
  or
• 1-h plasma glucose after ingestion of 75g glucose = ≥10.0 mmol/L
  or
• 2-h plasma glucose after ingestion of 75g glucose = ≥8.5 mmol/L

Question 22

What are the recommendations for women with GDM?

Answer 22

SIGN recommended interventions for women with Gestational Diabetes mellitus;

• Explain that good blood glucose control throughout pregnancy will reduce the risk of fetal and neonatal complications (e.g. congenital malformation, late intrauterine death, fetal distress), obstetric complications (e.g. miscarriage, pre-eclampsia, premature labour) and complications from diabetes.
• Teach women with GDM about glucose self-monitoring and target levels.
• Metformin or glibenclamide may be considered as initial pharmacological glucose lowering
  treatment in women with gestational diabetes.
• Advise women with GDM to eat a healthy diet during pregnancy (foods with a low glycaemic
  index), weight control, and recommend regular exercise.
• Women should have plan for insulin management at delivery or immediately after.

Question 23

What is Isabelle’s body mass index (BMI)?
Height: 1.60 m
Weight: 78.1 kg

Answer 23

BMI = weight/height2 = 30.5kg/m2

Question 24

What risk factors for gestational diabetes mellitus (GDM) does Isabelle present?

Isabelle is 35-year-old Middle Eastern woman attending a pre-natal GP appointment. No abnormalities were detected at her ultrasound anomaly scan at 20 weeks. She is now at 25 weeks gestation and her uterus size is appropriate for the gestational age. Her past obstetric history includes spontaneous vaginal delivery of a 4.6 kg male infant at 40 weeks gestation, 4 years ago in Dubai. She reports that the child is doing well. Her family history reveals that her mother has type 2 diabetes mellitus.

Signs;
- Blood pressure: 130/80 mmHg
- BMI = 30.5kg/m2
- Glucose: +

Answer 24

Isabelle has a BMI above 30 kg/m2 (obese), has had a baby weighing 4.5 kg or above (might have had macrosomia), family history of diabetes, minority ethnic family origin with high prevalence of diabetes.

Question 25

What are the underlying causes of GDM?

Answer 25

Gestational diabetes is caused by insulin resistance in combination with insufficient insulin secretion. The exact mechanisms are unknown but pregnancy hormones are thought to interfere with the action of insulin receptor signalling.

Question 26

If you had access to Isabelle’s blood sample from her first GP visit (6-8 wks gestation), how would you test if Isabelle had pre-existing diabetes?

Answer 26

Measuring HbA1c in the first trimester is likely to diagnose T2 DM present before pregnancy as this will give an indication of average blood glucose concentrations over the previous 6-8 weeks.

Question 27

Why is performing the OGTT to diagnose GDM preferred and why is it performed between 24-28 weeks gestation?

Answer 27

The onset of GDM may be acute so an OGTT is the most effective means to diagnose real-time glucose metabolism. HbA1c measures would not be as effective because it measures the average levels of blood glucose over the prior 3-4 months and might miss an acute onset of GDM. Slight Insulin resistance is a natural phenomenon that emerges in the second trimester of a normal pregnancy, so if a woman will have GDM then it will most likely appear in the second and third trimester.

Question 28

What advice would you provide Isabelle on how to control her condition and what should be her blood glucose target levels?

Answer 28

Isabelle’s fasting blood glucose levels are below 7 mmol/L so promoting a healthy lifestyle would be recommended. Diet consisting of low glycaemic foods as well as getting at least 30 min of exercise daily. See table above for target levels.

Question 29

Which medication would be first recommended if Isabelle is unable to control her blood glucose levels within 1-2 weeks? What combined therapies would be recommended if the first therapy is inadequate?

Answer 29

If Isabelle’s blood glucose levels can’t be controlled with changes to diet and exercise, then metformin would be recommended unless this is contraindicated. If Metformin alone is unable to adequately control her diabetes, then rapid acting insulin analogues would be recommended.

Question 30

Which form of insulin would be classed as a ‘rapid-acting’ insulin analogue? What are some examples?

Answer 30

Lispro or aspart insulin. These are analogues that rapidly dissociate into monomers and dimers on s.c. injection, so are absorbed faster, but are also have a shorter duration of activity.

Question 31

What is meant by a ‘basal analogue’ of insulin? What are some examples?

Answer 31

Basal analogues are forms of insulin that have a long-lasting duration of activity (often maintained for >20 hours) often without a significant peak that help maintain a basal level of insulin throughout the day. These forms of insulin either have much slower release from the injection site or have modifications that increases circulating half-life. Examples of basal analogues include: Detemir, Glargine or Degludec.

Question 32

Which form of insulin is intermediate-acting? How is insulin made intermediate-acting?

Answer 32

NPH. Made intermediate acting by adding protamine

Question 33

What dietary advice would you give George and his parents to help George to control his condition?

Answer 33

Similar advice as would be given to Isabelle except without advice on weight loss.

Question 34

How should you manage type 1 diabetes ?

Answer 34

Management of type 1 diabetes;
* An intensified treatment regimen for adults with type 1 diabetes should include either regular human or rapid-acting insulin analogues.
* Basal insulin analogues are recommended in adults with type 1 diabetes who are experiencing severe or nocturnal hypoglycaemia and who are using an intensified insulin regimen. Adults with type 1 diabetes who are not experiencing severe or nocturnal hypoglycaemia may use basal analogues or NPH insulin.
* Children and adolescents may use either insulin analogues (rapid-acting and basal), regular human insulin and NPH preparations or an appropriate combination of these.
* The insulin regimen should be tailored to the individual child to achieve the best possible glycaemic control without disabling hypoglycaemia.
* CSII [continuous subcutaneous insulin infusion] therapy is associated with modest improvements in glycaemic control and should be considered for patients unable to achieve their glycaemic targets.
* CSII therapy should be considered in patients who experience recurring episodes of severe hypoglycaemia.
* To reduce the risk of long-term microvascular complications, the target for all young people with diabetes is the optimising of glycaemic control towards a normal level.

Question 35

List three other hormones that affect gluconeogenesis or glycogenolysis or glucose-uptake by cells?

Answer 35

Growth hormone, adrenaline, glucagon, somatostatin, thyroid hormones, cortisol (to name just some). Make sure you know how each of these hormones interacts with the normal glucose homeostasis pathways.

Question 36

Name two conditions that would affect an oral glucose tolerance test because there is an imbalance with these hormones.

Answer 36

Cushing’s and Addions?

Question 37

In the morning (after an overnight fast) before George sits down to eat his usual Crunchy Nut Corn Flakes Cereal (just before the glucose is consumed):
a) What is happening in the α-cells of the pancreatic islets?
b) What is happening in the β-cells of the pancreatic islets?
c) Where is the circulating glucose originating from?
d) If the fast continued for another 6 hours, would that origin change?

Answer 37

For diabetic patients with a fasting glucose that is high, you should be able to work out whether the α and β cells would be being stimulated or not.

For a non-diabetic, with normal fasted glucose levels, you again should be able to work out whether the α and β cells are being stimulated or not.

For diabetic patients, the glucose may well still be coming from their last meal. For non- diabetics it would be the release of glucose from stores (glycogenolysis) or production of new glucose (gluconeogenesis). Note that diabetic patients (especially type I) may not have large stores of glycogen.

If the fast continued, the stored glucose (as glycogen) may be less easy to liberate and the production of glucose would rely more on gluconeogenesis. The body would use fat preferentially over amino acids for this.

Question 38

After George has finished his first bowl of cereal (15 minutes after the ingestion of the glucose):
a) What is happening in the α-cells of the pancreatic islets?
b) What is happening in the β-cells of the pancreatic islets?
c) What is happening to the ingested glucose in the GI tract?

Answer 38

Again, these should be fairly easy to tackle! As the stomach is empty and the glucose is soluble, the glucose load will not stay in the stomach for long (there is no high amino acid or high fat level inhibiting gastric emptying). In the small intestine the glucose is transported into the epithelial cells by secondary active transport (secondary to what? What ion is also moving and why? Na+, co-transporter). The glucose then moves out of the epithelial cell towards ISF through facilitated diffusion (and then to plasma through simple diffusion through the capillary fenestrations).

Since glucose levels in the blood will be rising, you should be able to work out what that is doing to the α and β cells in both diabetic and non-diabetic patients.