Diabetes Management and Therapeutics Flashcards by Hannah Meiklejohn

What are the 4 aims of blood glucose Mx in diabetes?

Relieve symptoms

Prevent or delay long term complications

Avoid adverse effects of treatment (esp hypoglycaemia)

Assist psychological adjustment and improve QOL

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What is the effect of intensive glycaemic control (HbA1c less than 6.5%) of long term diabetic complications?

Reduces complications including nephropathy, neuropathy, retinopathy and CVD

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What were the implications of the DCCT-EDIC study?

Good glycaemic control leads to reduced complications years later (legacy effect)

Also shown in a T2DM study SO we should aim for very good control early in the course of DM (first decade)

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What are the potential hazards of intensive glycaemic control, as illustrated by the ACCORD trial?

Increased mortality in intensive group

Cause not clear but hypoglycaemia may have been a factor

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Taking into account both the DCCT-EDIC and ACCORD study, what should we aim for with DM Mx as reflected by the HbA1c?

Aggressive treatment needs to be balanced against individual risk of hypoglycaemia (lower target in young people with short duration DM, higher target in older people or those with multiple medical problems where hypoglycaemia poses a risk)

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Jane Smith, 23 years old, developed T1DM 4 years ago

Has recently moved to continue her studies and has come to you for assessment and advice

Ms Smith has had regular eye check and reports “all clear”

O/E: no evidence of complications

Rx: novomix (30% insulin aspart, 70% NPH insulin), 20U before breakfast and 14U before dinner

HbA1c: 7.8% 2/12 ago

Testing: tests BSL at home 2-3 times/day, before meals and occasionally before bed

Pre-breakfast: 5.5-7.6

Pre-lunch: 4.1-7.8

Pre-dinner: 8.1-12.7

Pre-bed: 6.8-9.2

What is the prominent pattern of BSL elevation? What could be done to improve that?

Readings too high before dinner with a trend towards low readings before lunch Increasing morning insulin will reduce pre-dinner readings but will increase changes of a pre-lunch hypo; a dietitian referral may be helpful!

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Jane, 23 years old and T1DM of 4 years, referred to dietitian for advice

Jane has a high GI cereal and 1 slice of toasted white bread for breakfast and then does not eat until lunch

Dietary advice?

Switch to lower GI foods (whole grain bread, low GI cereal, porridge, baked beans, etc) should result in slow CHO absorption and higher pre-lunch glucose

A mid-morning snack may also be helpful

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Describe the “basal bolus” regimen for insulin use

What is the rationale behind the use of the “basal bolus” regimen in diabetes?

Rapid acting insulin analogue with meals (bolus)

Long acting insulin once or twice a day to provide background (basal) insulin level

Mimics normal insulin production and controls post-prandial hyperglycaemia, which is a major contributor to HbA1c (esp at lower HbA1c)

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Jane, 23 years old and T1DM of 4 years, referred to dietitian for advice

Treatment: Novomix 30 20U before breakfast, 14U before dinner

Pre-breakfast: 5.5-7.6

Pre-lunch: 4.1-7.8

Pre-dinner: 8.1-12.7

Pre-bed: 6.8-9.2

What is the most optimal solution to achieving better glycaemic control?

Changing to more frequent insulin administration with a basal bolus regimen

E.g. insulin aspart (Novorapid) 6U before breakfast, lunch and dinner, glargine insulin (Lantus) 14U before bed

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List 3 rapid-acting insulins

Aspart

Glulisine

Lispro

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How long do short-acting insulins take to work? When are they at their peak? How long do they last?

Onset: 10-20 mins

Peak: 1-3 hrs

Duration: 3.5-4.5 hrs

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List 2 long-acting insulins

Detemir

Glargine

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How long do long-acting insulins take to start working? When are they at their peak? How long do they last?

Onset: 2-4 hrs

Peak: 8-10 hrs detemir, variable for glargine

Duration: 14-16 hrs detemir, 16-24 hrs

NB True “peakless” insulins are currently in development

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What are the mainstays of T2DM management?

Weight loss (80% + overweight)

Exercise

Oral anti-diabetic agents (monotherapy, dual oral therapy, triple oral therapy sometimes used, insulin)

Mx of CV risk factors: lipids, HTN, smoking, etc

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List 7 classes of oral anti-diabetics

Metformin (biguanides)

Sulphonylureas

a-glucosidase inhibitors

Thiazolidinediones

DPP4 inhibitors

GLP-1 analogues

SGLT2 inhibitors (only recently became available)

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When should caution be applied to the use of metformin?

With renal impairment

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What anti-diabetic therapies carry a risk of hypoglycaemia?

Insulin

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What anti-diabetics are good for weight loss?

GLP-1 agonist

DPP4 inhibitor

Metformin

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What anti-diabetics can cause weight gain?

Glitazones

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Describe what diabetes treatments are effective at different stages of diabetes

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How should the metformin dose be adjusted in renal impairment?

Reduce dose is eGFR less than 40

Cease if eGFR less than 30

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When should double therapy be considered in management of T2DM?

If HbA1c above target on maximal tolerated metformin (up to 2000mg), add sulphonylurea

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What is the SU of choice? Why?

Gliclazide

Same efficacy but less hypoglycaemia than comparable SUs

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In what circumstances are SUs contraindicated?

Can cause hypoglycaemia so are contraindicated or use with caution in pilots, professional drivers, etc

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What is the next step in a type 2 diabetic when HbA1c is above target on metformin but SU is contraindicated?

DPP4 inhibitor: efficacy is fair, no hypos, no weight gain GLP-1: efficacy good, no hypos, weight loss BUT requires injection Glitazone (pioglitazone): efficacy good, no hypos BUT weight gain, fluid retention, bone loss, etc

Mr JM, 54 year old accountant, type 2 diabetic for 1 year, currently taking metformin 1000mg BD BMI 24.2, mild HTN on ramipril 5mg daily Otherwise well HbA1c 7.9% What additional treatment would be appropriate for Mr JM?

Mr JM has HbA1c above target, he is not overweight and his occupation does not place him at special risk should he experience hypoglycaemia Most Aus physicians would recommend a SU Mr JM was commenced on gliclazide MR 30mg mane, in addition to his usual dose of metformin

Mr AR, 54 year old taxi driver and type 2 diabetic for 1 year, currently taking metformin 1000U BD BMI 29.2, abdominal obesity PHx: angina 3 years ago, treated with coronary stent, CV risk factors now well controlled HbA1c 7.9% What additional treatment would be appropriate for Mr AR?

Mr AR has an HbA1c above target and is significantly overweight; also, his occupation puts him at significant risk should he experience hypoglycaemia Most Aus physicians would recommend weight loss and exercise initially If diet is ineffective, a DPP4i could be added (weight neutral, low hypo risk) GLP1 agonist would also be appropriate (low risk of hypo, causes some weight loss, but requires injection)

Mrs JS, 66 year old retired teacher and type 2 diabetic for 14 years, currently managed with gliclazide MR 120mg mane and metformin 1000mg BD BMI 26.3 PHx: previous AMI, on treatment for CCF HbA1c: 9.4% What additional treatment would be appropriate for Mrs JS?

Mrs JS has an HbA1c well above target She has a long duration of diabetes suggesting B cell function has declined Hx of CCF means pioglitazone is contraindicated (TZDs may worsen HF; pioglitazone is contraindicated in NYHA class II–IV, and should be used cautiously in NYHA class I; start with a low dose and monitor carefully) Mrs JS should be referred to a diabetes educator for commencement of glargine (Lantus) insulin, 12U at bed time; metformin and gliclazide should also be continued

Should a patient continue taking metformin and SUs after commencement of insulin? Give an example of once and twice daily insulin regimens in T2DM

Usually metformin is continued SUs are continued if once daily insulin is started Once daily: pre-mixed insulin pre-dinner or glargine at bed time and continue oral agents Twice daily: BD pre-mixed insulin and continue metformin

What is the mechanism of action of metformin?

Inhibits hepatic glucose production

What is the main SE of metformin? How can this SE be minimised?

GI intolerance: nausea, diarrhoea Can be minimised by using slow release form (XR)

When is metformin contraindicated and why?

In renal failure due to risk of lactic acidosis

Give 4 examples of SUs

Gliclazide Glipizide Glibenclamide Glimepiride

What is the mechanism of action of SUs?

Stimulate B cell insulin release

Clinical guidelines for commencing SU

Rapidly effective; start with a low dose

What are the SEs of SUs?

Weight gain Hypoglycaemia (gliclazide)

What is the mechanism of action of acarbose?

Inhibits gut a glucosidase, the enzyme that breaks down starches and disaccharides

Does acarbose cause weight gain or hypoglycaemia?

SEs of acarbose

Flatulence (esp with high CHO diet)

Clinical guidelines for commencing acarbose

Must be used with first mouthfuls of food to be effective

What is the mechanism of action of thiazolidinediones (glitazones)?

Stimulate PPAR-y and reverses insulin resistance Effects are additive to metformin and SU (and insulin)

Do glitazones cause hypoglycaemia?

SEs of glitazones?

Many! Weight gain Fluid retention CCF Bone fractures Possible bladder cancer risk (pioglitazone esp) CV event (rosiglitazone - now rarely used)

Give 2 examples of GLP-1 analogues

Exenatide Liraglutide

Mechanism of GLP-1 analogues; SEs and subset of patients they are generally useful for

Improve pancreatic islet glucose sensing and insulin release Slow gastric emptying and improve satiety (leading to weight loss in most patients) Used mainly in obese patients with diabetes Other SEs: nausea, vomiting, ?pancreatitis (no long term data), hypoglycaemia (but rare if used alone)

How are GLP-1 analogues administered?

SC injection before meals (liraglutide daily, exenatide BD)

Give 4 examples of DPP-4 inhibitors

Sitagliptin Vildagliptin Saxagliptin Linagliptin

What is the mechanism of action of DPP-4 inhibitors?

Prolong GLP-1 action, leading to improve B-cell sensing; increase insulin secretion, decrease glucagon secretion

Do DPP-4 inhibitors cause hypoglycaemia?

Not if used alone

When are DPP-4 inhibitors clinically indicated?

Commonly used second line after metformin if SUs are contraindicated

What other anti-diabetic is available in combination with metformin?

DPP-4 inhibitors

SEs of DPP-4 inhibitors

Very rare: occasionally nausea, hypersensitivity (no long term data)

What is the mechanism of action of SGLT2 inhibitors?

Promote glycosuria, thus lowering blood glucose

Do SGLT2 inhibitors cause weight loss or weight gain?

Mild weight lloss

Are SGLT2 inhibitors associated with hypoglycaemia?

Not if used alone

Give an example of a SGLT2 inhibitor

Dapagliflozin

SEs of SGLT2 inhibitors

Candida genital infections increased Long term effects unknown (new drug - no post marketing information available)

List 3 rapidly acting insulin analogues

Insulin aspart (NovoRapid) Insulin glulisine (Apidra) Insulin lispro (Humalog)

Give 2 examples of regular insulins

Actrapid Humulin R

How long does it take for the onset of regular insulins? When is peak action achieved? What is the duration of action?

Onset: 30 mins Peak: 2-4 hrs Duration: 5-8 hrs

What type of insulins are used for IV injections and infusions? Why?

Regular Because rapid acting analogues have no advantage in IV use and cost more

Give an example of a medium-acting insulin?

NPH (neutral protamine Hagedoorn)

How long until the onset of action of NPH? How long does it take until peak action is achieved? How long does the action last?

Onset: 2 hrs Peak: 6-10 hrs Duration: 12-16 hrs

How does NPH appear?

Cloudy insulin; used in "pre-mixes"

What is premix insulin?

Mixture of regular (Mixtard) or short acting analogue (Novomix, Humalog mix) with NPH insulin

How long until onset of action with premix insulin? When is peak action achieved? How long does the action last? When are these insulins typically used?

Onset: 10 mins Double peak action: 1-3 hrs, 6-10 hrs Duration: 12-16 hrs Frequently used BD in T2DM