Diabetes management overview - Australian Perspective

7/27/2019 Diabetes management overview - Australian Perspective

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Diabetes Mellitus


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What is Diabetes Mellitus?

Diabetes = to pass through

Mellitus = from honey, sweet

A chronic metabolic disease characterized by

high glucose levels in blood

Results from a lack of or reduced effectiveness

of endogenous insulin

This results in high blood glucose levels


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4% of Australians have diabetes and this

proportion is increasing every year

Carries risk of significant cardiovascular

morbidity and mortality

Affects multiple systems:

Neuropathy, retinopathy, vascular disease,

kidney disease, IHD


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Three Main Types of Diabetes

Type 1 DM

Type 2 DM

Gestational Diabetes


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Type 1 DM

Autoimmune destruction of insulin

producing pancreatic B cells in the islet of

Langerhan by T cells

Results in insufficient insulin production

Can occur at any age, but more common

in children, teenager, and young adults

Daily insulin injections are required


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In adults, Type 1 DM can develop as

Latent Autoimmune Diabetes of Adults

Slower disease progression to insulin

dependence


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Type 2 DM

A progressive loss of pancreatic beta cells

with insulin resistance

Usually occurs later in life however it is

becoming more prevalent in the younger

population due to obesity

Due to a combination of genetic and

environmental factors

Up to 60% can be prevented by diet and

exercise


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Type 2 DM Statistics

Accounts for over 90% of all diabetesAs at 30 June 2014 in Australia:

188 new diagnoses of Type 2 DM per day

68% > 60yo 23% 40 - 59yo

3% 20 - 39yo


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Type 2 DM Statistics

3 in 5 people have cardiovascular disease2/3 of people who die of a myocardial

infarction or stroke also have diabetes or

impaired glucose tolerance10% have long term vision loss

0.6% have ESKD


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Type 2 DM

Associated with:

Obesity

Lack of exercise

Excess alcohol intake

Excess calorie intake


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Type 2 DM

metformin

reduces hepatic gluconeogenesis and

hence insulin requirements

Does not cause weight gain

Gastrointestinal SE limit dosing - may be

better tolerated if slowly titrate dose upand taking it with food

Rare SE lactic acidosis


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Type 2 DM

sulfonylureas (eg gliclazide, glipizide,

glibenclamide, glimepiride)

increase insulin secretion

Cheap

Many years experience of use

Weight gain


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Type 2 DM

incretin-based therapies:

dipeptidyl peptidase-4 (DPP-4)

inhibitors (eg linagliptin, saxagliptin,

sitagliptin, vildagliptin)

increase the concentrations of incretin

hormones (GLP-1 and GIP) that are

produced in the gut following ingestion of

food; GLP-1 stimulates insulin release,

and reduces glucagon secretion


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Type 2 DM

thiazolidinediones (eg pioglitazone,

rosiglitazone)

reduce hepatic glucose output and

peripheral insulin resistance and hence

insulin requirements

weight gain and swollen feet are common

adverse effects - assess risk of fluid

retention before increasing dosage

Avoid in heart failure


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Type 2 DM

dipeptidyl peptidase-4 (DPP-4)

inhibitors (eg linagliptin, saxagliptin,


Well tolerated

No weight gain or hypoglycemia

SE: common - headache, musculoskeletalpain

Rare S/E pancreatitis

No long term safety data


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Type 2 DM

dipeptidyl peptidase-4 (DPP-4)inhibitors (eg linagliptin, saxagliptin,


All appear to have similar efficacy


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Type 2 DM

Glucagon-like peptide-1 (GLP-1)

receptor agonists (eg exenatide,

liraglutide)

synthetic analogues of GLP-1; increase

insulin secretion and reduce glucagon

secretion; also cause a small reduction in

appetite

Given S/C

Improves satiety and weight loss

Si nificant nausea that im roves with time


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acarbosealpha-glucosidase inhibitor

reduces the breakdown of complex

carbohydrate in the gut, thereby reducing

absorption of carbohydrate and hence

insulin requirements


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Acarbose has been shown to improve

HbA1c when added to other noninsulin

antihyperglycaemic drugs.

Poorly tolerated - it is taken with food,

begin at a low dose to minimise

gastrointestinal adverse effects such as

flatulence, bloating and diarrhoea.


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Type 2 DM

Sodium-glucose co-transporter 2

inhibitors (eg dapagliflozin)

reduce glucose reabsorption in the kidney

Causes an osmotic diuresis

Their short-term efficacy is modest, and

long-term efficacy and safety are unknown


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Type 2 DM

Insulin

Most people with type 2 diabetes

eventually require insulin treatment due to

the natural history of progressive beta cell

failure

SE: weight gain, hypoglycemia


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Type 2DM

Drug

Metformin

Sulfonylurea

Thiazolidinedione

DPP4-I

Acarbose

SGLT2 inhibitors

GLP1 agonist

Insulin

Effect on weight

Nil (decrease)

Increase

Increase

Nil

Nil

Decrease

Decrease

Increase


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Type 2 DM Management

Pathway1.Diet and exercise

2.Add metformin

3.Add either:Sulfonylurea

DPP4 inhibitor/GLP-1 agonist

Insulin

4.Add insulin +/- remove oral

antihypoglycemics (or triple therapy)

5.More complex insulin dosing required


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Type 2 DM

Addition of basal insulin (vs multiple

doses) to oral anti hypoglycemics causes

less weight gain and hypoglycemia

Basal insulin also gives better glycaemic

control, especially if given in the evening

long-acting insulin is usually given once

daily in the morning or evening. Start with

low dose (eg 10 units SC before evening

meal); increase dose in 24 unit

increments at intervals of 24 days.


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Type 2 DM

Management options should consider:

life-expectancy

glycaemic control risk of hypoglycaemia

comorbidities

preference (consider tolerability,complexity of the regimen, occupation,

and cost barriers for non-subsidised

options)


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Type 2 DM - Hypoglycemia

Symptoms: sweating, hunger, faintness,

palpitations, tremor, headache, visual

disturbance and altered mood

Insulin and sulfonylureas have a high risk

of hypoglycemia

Other drugs are less likely to cause

hypoglycemia alone

Combination of other drugs with insulin or

sulfonylureas can potentiate severe

hypoglycemia


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Type 2 DM

Generally, treatment targets are:

fasting blood glucose, 48 mmol/L

postprandial blood glucose, 6

10 mmol/L glycated haemoglobin concentration

(HbA1c), 53 mmol/mol (7%)

HbA1c(mmol/mol) = 10.93 x HbA1c(%)

23.5


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Type 2 DM

Also consider lowering cardiovascular risk:

Smoking cessation, hypertension, weight

management, hyperlipidaemia

low-dose aspirin in patients with

cardiovascular disease

an ACE inhibitor (or, if intolerant, a sartan)

to delay progression of renal disease in

patients with microalbuminuria or

proteinuria (including normotensive

patients)


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Gestational Diabetes Mellitus

(GDM) High blood glucose levels in a pregnant

woman without preexisting diabetes

Affects 1 in 20 pregnancies

Increased risk of: Miscarriage Preeclampsia

Congenital malformations

Macrosomia 3x need for Caesarean section delivery

4x risk of baby needing ICU care


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Dysregulation of blood glucose levels are

due to human placental lactogen and

progesterone


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Pregnant women are screened for GDM at 24-

28 weeks with an Oral Glucose Challenge Test,

if positive, confirm with an Oral Glucose

Tolerance Test Perform the test earlier if the woman has risk

factors e.g. previous GDM, obesity


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After the baby is delivered, blood glucose levels

usually improve or return to normal

Blood glucose should be tested again six weeks

after delivery If the woman becomes pregnant again, there is

a high chance of having GDM again

There is a 20-50% chance of the womandeveloping T2DM later in life


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Treatment of GDM is with diet control and s/c

insulin if needed

Frequent small meals with complex carbohydrates

Insulin is safe and efficacious Oral hypoglycaemic agents are contraindicated

due to risks to the baby

Metformin and glyburide have been trialed and shown

to be effective with no fetal adverse effects (no longterm data though)


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Summary

Diabetes is increasing in incidence

Carries risk of significant cardiovascular

risk as well as damage to other organs

Insulin is becoming used earlier in

treatment - better glycemic control and

preserves beta cell population


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References

Therapeutic Guidelines

AIHW

Diabetes Australia Australian Medicines Handbook

Diabetes management overview - Australian Perspective

Documents

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