Type II and gestational diabetes

Question 1

Type II diabetes Represents about 90% of all cases of diabetes. what age is it most commonly diagnosed at?

Answer 1

1) Most commonly diagnosed after 40 years of age but incidence in children and young adults is rising
- Incidence Type II diabetes is increasing

Question 2

What causes Type II diabetes?

Answer 2

1) Type II diabetes is characterised by a reduced insulin secretion and insulin resistance
- “normal” biological effects of insulin are not observed at physiological insulin concentrations.
2) Relative insulin deficiency results from beta-cell dysfunction : At type II diabetes diagnosis, a 50% reduction in beta cell mass is common
3) We do not understand what initiates disease in genetically susceptible individuals

Question 3

does insulin resistance always lead to diabetes?

Answer 3

1) Insulin resistance does not always lead to diabetes (only 20% develop diabetes)
2) Glucose intolerance can often be reversed by lifestyle intervention

Question 4

what are the symptoms of Type II diabetes?

Answer 4

1) Gradual and insidious onset of illness (months-years) or asymptomatic
2) Increased thirst and hunger
3) increased frequency of urination (especially at night)
4) Fatigue
5) Blurred vision
6) Infection
7) Hyperosmolar Hyperglycaemic State (HHS): a medical emergency involving hyperglycaemia, dehydration and uraemia.

Question 5

how can Type II diabetes be prevented?

Answer 5

1) can be prevented (or at least delayed) by lifestyle intervention
2) Lifestyle intervention to reduce weight, reduce fat intake, increase dietary fibre, and exercise can halve the incidence of diabetes

Question 6

outline the Risk factors for Type II diabetes

Answer 6

1) Family history (i.e. parent or sibling with diabetes)
2) Ethnicity (i.e. African, Afro-Carribbean, South Asian)
3) Age (40yr+ if caucasian or 25yrs+ from high risk ethnic group)
4) BMI (25kg/m2 or greater) with sedentary lifestyle
Waist measurement
5) Past history of gestational diabetes
6) Other medical conditions (i.e. history of stroke, hypertension, CHD or peripheral artery disease

Question 7

Why is Type II diabetes screening imperative?

Answer 7

1) Patients can have diabetes for up to a decade before they have overt symptoms
2) Diabetic complications can develop in asymptomatic diabetics
- diabetes is commonly diagnosed by cardiac units treating a patient following a MI
- 20% people with newly diagnosed diabetes have retinopathy

Question 8

discuss the treatment goals of Type II diabetes

Answer 8

1) Preserve life
2) Alleviate symptoms
3) Achieve good glycaemic control to avoid long-term complications
4) Avoid iatrogenic side effects (i.e. hypoglycaemia)

Question 9

discuss the management of type II diabetes

Answer 9

1) Dietary modification
2) Exercise
3) Education (long term morbidity and mortality rates motivate patients to comply to lifestyle modification)
4) Drug treatment

Question 10

explain why Education is important for the type II diabetic patients

Answer 10

1) Successful lifestyle modification and maintaining good glycaemic control is key to avoiding diabetic complications
2) Education about complications can improve compliance

Question 11

outline the diabetic diet

Answer 11

1) The diet that should be adopted by the type II diabetic are identical to that of the type I diabetic
low fat, low refined sugar, increase complex carbohydrates and fibre
2) If overweight, the diet should also have a moderate calorie deficit to promote weight loss.

Question 12

discuss the benefits of exercise for the type II diabetic patients

Answer 12

1) Type II diabetics should be encouraged to exercise at least 30 minutes each day
2) In addition to promoting weight loss, exercise improves glycaemic control, reduces CVD risk (reduces BP and improves lipid profiles) and improves insulin sensitivity

Question 13

outline the Drug treatments available to Type II diabetics

Answer 13

If diet and exercise alone fails, oral hypoglycaemic agents are added to the patient’s treatment plan

1) Categories of oral hypoglycaemics are used:
- Insulin secretagogues
- Insulin sensitisers
- Inhibitor of glucose absorption from GI tract
- Inhibitor of renal glucose uptake

Question 14

outline the mode of action of Insulin secretogogues

Answer 14

1) Stimulate insulin release from the pancreas
Ideally restore early phase insulin release and return plasma insulin levels to pre-prandial levels rapidly to avoid post-meal hypoglycaemia
2) Sulphonylureas and meglitinides are insulin secretogogues

Question 15

1) explain how Sulphonylureas work

2) give examples of Sulphonylureas

Answer 15

1) Increase insulin release from the pancreas by binding to sulphonylurea receptor, closing the K+ ATP channel, which causes a rise in intracellular calcium and insulin release
2) short-acting gliclazide or tolbutamide or long-acting glibenclamide
3) Typically will reduce HbA1c by 1.5-2%.

Question 16

what are the side effects of Sulphonylureas?

Answer 16

1) Common side effects include weight gain (not first choice for overweight patients).
2) Can cause hypoglycaemia

Question 17

1) explain how Meglitinides work

2) give examples of Meglitinides

Answer 17

1) Increase insulin release from the pancreas by binding to a different but closely related receptor to that recognised by sulphonylueas, closing the K+ ATP channel, which causes a rise in intracellular calcium and insulin release
2) nateglinide and repaglinide
3) Less marked effects on glycaemic control so reduced place in therapy.

Question 18

what are the side effects of Meglitinides?

Answer 18

1) Side effects reduced compared to other insulin secretogogues
2) short-acting so reduced risk of hypoglycaemia and reduced need to snack, less weight gain

Question 19

Gliclazide is a sulphonylurea. outline the MOA of Gliclazide

Answer 19

1) promotes insulin secretion from pancreatic beta-cells. It binds to the sulfonyl urea receptor (SUR1), which binding subsequently blocks the ATP sensitive potassium channels.
2) Decrease in potassium efflux leads to depolarization of the β cells, opens voltage-dependent calcium channels and activation of calmodulin, which leads to release of insulin-containing secretory granules.

Question 20

what is the counseling for gliclazide

Answer 20

1) Risk of hypoglycaemia should be discussed with the patient, esp. if concomitant glucose-lowering drugs are prescribed.
2) Associated with weight gain (use alternative in obese patients)
3) Hepatic impairment increases risk of hypoglycaemia so should be used with caution or avoided; glicazide is principally metabolised in the liver.

Question 21

1) how do Insulin sensitisers work?

2) give examples of insulin sensitiser drugs

Answer 21

1) Enhance the effect of endogenous circulating insulin, reducing insulin resistance, and decrease hepatic glucose production
2) Biguanides and thiazolidinediones (“glitazones”) are insulin sensitisers

Question 22

Metformin is the only biguanide currently available and is the first line treatment for type II diabetes. what is the MOA of metformin?

Answer 22

1) Reduces glucose production in the liver, decreases glucose absorption and improves insulin sensitivity by increasing uptake and utilisation in the periphery. Mechanism involves activation of AMP-activated protein kinase in liver and skeletal muscle.

Question 23

what are the benefits of using metformin?

Answer 23

1) Suppresses appetite, helps achieve weight loss and has a cardio-protective effect (reduced mortality and morbidity)
2) Typically will reduce HbA1c by 1.5-2%

Question 24

discuss the Side effects of metformin

Answer 24

1) Metformin is associated with GI side effects (i.e. anorexia, nausea, abdominal pain and diarrhoea) that can limit its use.
2) GI side effects can be minimised by gradual increases to reach therapeutic dose or by a modified release formulation
3) Metformin cannot be used in patients with renal impairment, cardiac failure or liver failure as it is associated with lactic acidosis (potentially fatal). inhibits pyruvate metabolism

Question 25

what is the counseling for metformin?

Answer 25

1) Lower incidence of weight gain and hypoglycaemia
2) Can rarely cause lactic acidosis, esp. in renal impairment so need to regularly monitor renal function
3) Needs the presence of endogenous insulin to act so only effective if have some functioning beta cells.

Question 26

Pioglitazone is the only thiazolidinedione currently available for clinical used in the UK. what are the problems surrounding the use of this drug?

Answer 26

1) Link between the “glitazones” and increase risk of cardiovascular disease
2) Pioglitazone associated with increased risk of heart failure (especially when combined with insulin) and bladder cancer.

Question 27

summarise the Mechanism of action for thiazolidinediones

Answer 27

1) Bind to peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and, through regulation of gene transcription, enhance glucose and fatty acid uptake and utilisation in adipocytes, reduce secretion of cytokines that inhibit insulin action
2) Reduced availability of fatty acids in muscle improves insulin sensitivity
3) Reduce glucose output of liver

Question 28

discuss the benefits and side effects of thiazolidinediones

Answer 28

1) Can take up to 3 months to see maximal effect as has an indirect effect on blood glucose but, once achieved, effect is comparable to metformin and sulphonylureas
2) Pioglitazone has added benefit of improving diabetic dyslipidaemia (reducing triglycerides and increasing HDL levels)
3) Induces weight gain but weight gain is limited to hips and thighs
4) Associated with fluid retention (precipitating heart failure)

Question 29

what is the MOA of Pioglitazone?

Answer 29

Reduces peripheral insulin resistance and hepatic glucose production by stimulating PPAR gamma, which modulates the expression of insulin-sensitive genes that control glucose production, transport and utilisation in adipose tissue, muscle and the liver.

Question 30

how do Inhibitors of gastro-intestinal

glucose absorption work?

Answer 30

1) Acts by binding to alpha-glucosidase with higher affinity than dietary carbohydrates. Therefore, dietary carbohydrate break-down is inhibited
2) Slows digestion and absorption of glucose after a meal, reducing the post-pranial peak in blood glucose, stabilising blood glucose levels throughout the day
3) Acarbose; an alpha-glucosidase inhibitor that reduces glucose uptake in the small intestine

Question 31

what are the disadvantages of Inhibitors of gastro-intestinal glucose absorption?

Answer 31

1) Less effective than metformin etc at reducing HbA1c %

2) Associated with GI disturbance (flatulence, bloating, diarrhoea)

Question 32

what is the key role of Glucagon-like peptide-1 (GLP-1)?

Answer 32

glucagon-like peptide-1 plays a key role in glucose control

1) In the pancreas, it stimulates insulin release from beta-cells and suppresses glucagon release from alpha-cells
2) It slows gastric emptying, slowing digestion and absorption of nutrients, moderating blood glucose levels and blunting blood glucose fluctuations.
3) Reduces appetite

Question 33

1) What is the MOA of Dipeptidylpeptidase-4 inhibitors?

2) give examples of Dipeptidylpeptidase-4 inhibitors

Answer 33

1) this drug class inhibit DDP4, decreasing GLP-1 degradation which leads to increased insulin secretion and decrease glucagon secretion
2) Saxagliptin, sitagliptin, vildagliptin
3) GLP-1 is degraded by DPP-4

Question 34

what does NICE recommend with regards to the ongoing use of Dipeptidylpeptidase-4 inhibitors?

Answer 34

NICE recommends that treatment should only be continued after 6 months if HbA1c reduction of at least 0.5% has been achieved

Question 35

1) Outline the MOA of GLP-1 analogues (mimetics)

2) give examples of mimetics

Answer 35

1) DPP-4 resistant analogues of GLP-1 that bind to and activate the GLP-1 receptor, leading to increased insulin secretion and decrease glucagon secretion, slow gastric emptying, promoting weight loss
2) exenatide and liraglutide (delivered by subcutaneous injection)

Question 36

what does NICE recommend with regards to the use of mimetics?

Answer 36

1) NICE recommends that treatment should only be continued after 6 months if HbA1c reduction of at least 1% has been achieved and 3% weight loss
2) Used in combination with metformin and/or sulfonylurea or pioglitazone or metformin with pioglitazone

Question 37

1) how do Selective sodium-glucose co-transporter 2 (SGLT-2) inhibitors work?
2) give examples of (SGLT-2) inhibitors

Answer 37

1) Independent of insulin-mediated glucose control pathways, SGLT-2 inhibitors block the reabsorption of glucose in the kidney and promote its urinary excretion
2) canaglifozin, dapagliflozin, empagliflozin

-Used as a monotherapy if diet and exercise fail and metformin is inappropriate/contra-indicated or as an add-on therapy

Question 38

discuss the use of Insulin in type II diabetes

Answer 38

1) If it proves impossible to maintain good glycaemic control with oral hypoglycaemic drugs, type II diabetics may need to be treated with insulin
2) In type II diabetes, insulin is often given alongside oral hypoglycaemic drugs

Question 39

1) what is Gestational diabetes?

2) what are the problems associated with this condition?

Answer 39

1) diabetes occurring for the first time during pregnancy affects 2-5% of all pregnancies
2) Increases risk of miscarriage, baby having congenital malformations, still birth or baby dying in first year of life
3) Gestational diabetes puts woman at increased risk of developing type I or type II diabetes- 50% women will develop diabetes within 10 years of the diabetes-affected pregnancy

Question 40

how can the complications of Gestational diabetes be reduced?

Answer 40

1) Complications can be reduced through maintenance of tight glycaemic control
- Risk factors are the same as for type II diabetes (family history, age, weight etc)

Question 41

Pregnancy induces a state of insulin resistance. what can insulin resistance in pregnancy encourage?

Answer 41

1) Insulin resistance encourages nutrient transfer to the growing foetus
2) Maximal insulin resistance is observed in second and third trimesters (requirement for insulin increases by 50-100%)

Question 42

outline the Treatment of gestational diabetes

Answer 42

1) Lifestyle modification
- Diet that stabilises maternal blood glucose levels but provides calories required
2) Exercise (30 minutes daily)
3) Insulin therapy may be required if lifestyle modification is not sufficient
4) Although insulin is drug of choice for gestational diabetes, some oral hypoglycaemic drugs might be considered (i.e. metformin or glibenclamide after 11 weeks gestation (both unlicensed))

Question 43

screening for diabetes is focused on those at risk. list the tests used to identify type II diabetes in patients

Answer 43

Screening tests could include random blood glucose levels, fasting blood glucose levels and HbA1c levels