Gerry Rayman Initiating and Adjusting Insulin
Transcript of Gerry Rayman Initiating and Adjusting Insulin
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Initiating and adjusting
insulinGerry Rayman
The Diabetes CentreIpswich Hospital
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1922 Elizabeth Hughes
age 14, wt 45 lb., height 5 ft.,
extermely emaciated, oedema of ankles, skin dry & scaly, hair brittle,
muscles extremely wasted, sc tissue
almost completely absorbed, scarcelyable to walk on account of weakness.
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1922 Elizabeth Hughes
Imagine, I have to take 5cc at a time.
Isn’t it awful. We only have a 2ccsyringe. Blanche gives it to me...
unscrews the needle which is left
sticking in me, fills it again.. and thenthe fifth cc.... My hip feels as if it would
burst.
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1922 Elizabeth Hughes
I experienced a severe anaphylactic
reaction...persisting for 2 days.....generalized skin eruption, nausea,
vomiting, profound weakness. I thought I
was going to die.
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Barriers to insulin therapy
in Type 2
Fear of injections/needles/syringes
6mm length, 30g siliconised needles
Pens (autoinjectors & needle guards)
Weight gain
Coma
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Barriers to intensified insulin
therapy in Type 1
Additional injections and testing
6mm length, 30g siliconised needles
Pens (autoinjectors & needle guards)
Weight gain
Hypoglycaemia
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Hypoglycaemia - RD Lawrence
Listlessness, shakiness, nervousness,
apprehension, irritability palpitations,
mental vagueness and confusion. Thepatient may stagger like a drunken
man and appear quite intoxicated and
perhaps confused, delirious or maniacal. Complete coma is the end
result.
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Do you start the following people
with diabetes on insulin?
Type 2 patientsType 2 patients
Children with diabetesChildren with diabetes
People w ith Type 1 diabetesPeople w ith Type 1 diabetes
Not involved in starting insulinNot involved in starting insulin
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Do you regularly advise on insulin dose
adjustment in the following groups?Type 2 patientsType 2 patients
Children with diabetesChildren with diabetes
People w ith Type 1 diabetesPeople with Type 1 diabetes
Not regularly advising on dose adjustmentNot regularly advising on dose adjustment
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Making the diagnosisType 1 or Type 2
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Type 1 vs Type 2
More dramaticpresentation- shorthistory of severepolydipsia & polyuria
Younger
Weight loss
Ketones
Strong FH of Type 1
Often no osmoticsymptoms
Age related
More commonamongst certainethnic groups
Central obesity &
other features of metabolic syndrome
FH of Type 2
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Type 1 or Type 2
32 yr old woman presents with lethargy,
recurrent thrush, blurred vision
Blood glucose 12 mmol/l, BMI 27
FH of type 2 diabetes in both parental GM
No ketones
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18 months later
Weight loss of 3 stone
On maximum doses of metformin &gliclazide
Still feeling unwell
Thrush persists
Frequently off work
Fasting blood glucose ~10
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Type 1 or Type 2
14 yr old caucasian girl presents with
moderate thirst, polyuria, nocturia X3-4,
listleness
Blood glucose 32 mmol/l
Ketones ++
BMI 32
Mother Type 2 diabetes BMI 34
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What would be the correct
approach?
Treat as type 1 diabetesTreat as type 1 diabetes
Type 2 diabetesType 2 diabetes
Not sure- start on insulinNot sure- start on insulin
Not sure- diet and sulphonylureaNot sure- diet and sulphonylurea
Not sure- diet and metforminNot sure- diet and metformin
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Type 2 diabetes
Very high c-peptide and insulin levels
Negative insulin anti-bodiesManaged on insulin and metformin
Acanthosis Nigricans
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Insulin initiation and dose
adjustment
There is no one perfect insulin regimen for either
Type 1 or Type 2 diabetes (hence the different
regimens used across the globe)
There are a number of simple principles whichcan guide insulin initiation but an individual‘s
response cannot be predicted
Similarly for dose adjustment one can follow
simplified guidelines but these must be modified
depending on an individual‘s response
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Insulin Species
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0 6 12 18 24
0 6 12 18 24
Regular (short acting) Actrapid, Humulin
Rapid acting Analogues Humalog, Novorapid
Isophanes/NPH(Intermediate) Insulatard, Humulin I
Basal analogues Glargine, Detimer
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Plasma Insulin
Normal 24 Hr Insulin Profiles & Bd premix
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Plasma Insulin
Normal 24 Hr Insulin Profiles & basal bolus
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When initiating insulin in Type 1
diabetes do you use?
Twice daily pre-mixed insulinTwice daily pre-mixed insulin
Twice daily intermediate acting insulinTwice daily intermediate acting insulin
Basal bolusBasal bolus
Single daily dose of basal insulin eg glargine or dSingle daily dose of basal insulin eg glargine or d
Any of the aboveAny of the above
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Advantages of BD pre-mix vs basal
bolus
Easy to teach
Does not overload patient
Improves symptoms just as well
Can get excellent control early- honeymoon
period
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Principles
Use a relatively narrow range of insulins, regimens anddevices Makes it easier to gain a ‗feel‘ for these variables and is less
confusing
Start low and very gradually build up (Avoidhypoglycaemia)
E.g Mixtard (30) or Novomix (30) 10 units bd
Regular blood glucose monitoring
Gradual increase in information
Patient empowerment
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4
8
12
16
B’F EM
Humalog Mix 25
10 units 10units 1212
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4
8
12
16
Humalog Mix 25
16 units 14units18
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4
8
12
16
Humalog Mix 25
24 units 14units
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Practical Considerations when
Optimising Control• Set realistic yet changeable targets
• Essential to have more intensive
monitoring- set a trouble shooting period
• Improve control gradually
• avoids severe hypos, hypo unawareness and
loss of confidence
• gives patients time to adjust
• possibly reduces risk of flare up of neuropathy
and retinopathy
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Changing insulin species or
regimen
Always reduce insulin dose by 10-20%
Avoids hypoglycaemia and loss of confidence
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Education
“ the person with diabetes must be hisown doctor, biochemist and dietitian”.R. D. Lawrence.
Assuming four 1 hr visits/yr patients spend0.0005% of their time with diabetic staff!
As diabetes does not look after itself thepatient must make his own decisions.
Education must therefore aim to empower.
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Patients need Motivation
Unlike pregnancy no immediate gains.
Motivating factor include the attitudesof family and diabetes team.
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Patients need Feedback
Blood glucose monitoring
The patient needs to know
his own HbA1c result.
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27 yr female with Type 1 diabetes
of 8yr duration- BMI 20
FH- mother Type 1 diagnosed age 31 &two uncles diagnosed in their 30‘s one oninsulin
Problem- recurrent hypos so patientfrequently omitting insulin
HbA1c 6.9% (highest over last 3yr = 7.3%)
Treatment- Actrapid 2u pre-meals &insulatard 8u nocte (dose unchanged fromdiagnosis)
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What would you do?
Reduce pre meal insulins by 1 unitReduce pre meal insulins by 1 unit
Reduce insulatard by half Reduce insulatard by half
Refer to dietitianRefer to dietitian
Exclude Addison’s diseaseExclude Addison’s disease
Reconsider the diagnosis of Type 1 diabetesReconsider the diagnosis of Type 1 diabetes
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Young-adult diabetes (15-30yrs)
“Diabetes is a diagnostic speciality”
Type 1
Genetic Syndromes
MODY
Type 2
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HNF1a (MODY3)
Commonest cause of MODY
May be misdiagnosed as type 1
Typically develop 12-30 yr
FPG maybe normal initiallyLarge rise (>5mmol/l) in OGTT
Worsening glycaemia with age
Low renal threshold (glycosuria)Not obese (usually)
Parents and grandparents
usually diabetic
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HNF1a: very sensitive to
sulphonylureas
4
6
8
10
12
8 9 10 11 12 13
Glibenclamide stopped
Metformin started
Glibenclamide started
Metformin stopped
HbA1c
(%)
Years since diagnosis
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Insulin therapy in Type 2
diabetes
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24-hr insulin profiles in normal, IGT & late
Type 2 diabetic subjects
160
140
120
100
80
60
40
20
0
Normal
IGT I n s u l i n (m U
/ m L )
0800 1200 1600 2000 2400 0400
Clock time (hours)
Polonsky KS et al. Horm Res 1998; 49: 178 –84.
Type 2 diabetes
Early Type 2
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Glargine (Lantus)
160
140
120
100
80
60
40
20
0
IGT I n s u l i n (m U
/ m L )
0800 1200 1600 2000 2400 0400
Clock time (hours)
Type 2 diabetes
Early Type 2
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24-hr insulin profiles in normal, IGT & late
Type 2 diabetic subjects
160
140
120
100
80
60
40
20
0
IGT I n s u l i n (m U
/ m L )
0800 1200 1600 2000 2400 0400
IGT
Type 2 diabetes
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Target HbA1c
Diabetes UK 7%
NICE 2002 (Type 2 DM) 6.5 – 7.5%
GP Contract 7.4%
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―Effective Diabetes Care: a need for realistic targets‖ (P Winocour, BMJ 2002: 324; 1577-80)
Proposed targets for individuals (Type
2)
6.5% within 3 years if diet only & no
complications
8% at 5 years especially if complications
9% for insulin-treated obese
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66 yr old male, type 2 DM for 10 years, on
metformin & sulphonylurea
Consecutive 6 monthly HbA1c 7.3, 6.9, 7.3,
7.9, 8.9%
BMI 35 and slowly increasing Hypertensive and hyperlipidaemic
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What would you do?
Start on glargine insulin and continue MF & gliclStart on glargine insulin and continue MF & glicla
Start bd insulin and continue MFStart bd insulin and continue MF
Re-consider lifestyle issues with patientRe-consider lifestyle issues with patient
Add rosiglitazoneAdd rosiglitazone
Refer to secondary careRefer to secondary care
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Group starts vs one to one
Increasing numbers warrants an alternative to one toone
One to one tends to lead to a dependency model inwhich the patient may not take ownership of self-adjustment
Allows patients to learn from others experiences eg howothers would adjust their insulin in a particular circumstance
Useful in the community where one practice takes oninitiation for a number of practices
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Insulin injection devices
Syringes- 100u, 50u, 30u with varying needle
gauges and lengths
Reusable insulin pens eg NovoPen III, Optipen,HumaPen Ergo.
Disposable pen eg HumaPen, Flexpen
Other devices- Innolet
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Wh t l d ti t
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What else do your patients
need to know?
Inform DVLA
Inform car insurance company
Driving- consider testing before driving,CHO in car
Hypoglycaemic symptoms and
management Identification card/bracelet and carrying
CHO
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Sick Day rules
test blood more often — about four times a day or more if necessary
Test your urine for ketones if you are Type 1, or Type 2 requiring
insulin.
Never stop taking your insulin when you are feeling ill. In fact in
some cases you may even need to increase the dose.
drinking plenty of liquids
replacing your normal meals with carbohydrate containing drinks if
necessary
contacting your GP or diabetes team if you are in any way unsure
about what to do, and especially if you are being violently sick.
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
Initiating insulin in a 59 yr old man with Type 2 diabetes on
max OHA (triple therapy) with a BMI of 26
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
g
12 units 8 units
Stop sulphonylurea & rosiglitazone continue metformin
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
g
12 units 8 units 12
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
g
12 units 12 units 14
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
g
12 units 14 units16
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
g
16 units 14 units18
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
18 units 14 units20
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
20 units 14 units 16
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
20 units 14 units 16
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
20 units 16 units22
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
22 units 16 units
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6 months later
HbA1c 7.1%
FBG 4-6
Post prandial 7-10
Weight gain 4kg
Feeling well
Humalog mix 25 - 30u mane 20u nocte
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18 months later
HbA1c 9.5%
FBG 10-15
Post prandial 15-20
Weight loss 4kg
Nocturia & thirst
Humalog mix 25 - 45u mane 45u nocte
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What would you do?
Continue increasing insulin to achieve FBGContinue increasing insulin to achieve FBGless than 6mmol/l?less than 6mmol/l?
Use glargine insulin together with sulphonylurea?Use glargine insulin together with sulphonylurea?
Start a basal bolus regimen?Start a basal bolus regimen?
Re-educate- emphasising diet and exercise?Re-educate- emphasising diet and exercise?
None of above?None of above?
Male age 44 yr with 9yrs of Type 2
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Male age 44 yr with 9yrs of Type 2
diabetes, insulin treated over last 3yr
Problem- 1 yr poor control after 2 yr of goodcontrol
HbA1c 10.1%
BMI 30
Fasting glucose 10-15 2 severe hypos in last 3 months
Treatment metformin 1gm bd
mixtard (30)90units b‘f eve meal
60 units lunch
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What would you do?
Add sulphonylureaAdd sulphonylurea
Switch to basal bolus regimenSwitch to basal bolus regimen
Switch to glargine and continue MF but addSwitch to glargine and continue MF but add
sulphonlyureasulphonlyurea
Continue to increase insulin doses by 4u at aContinue to increase insulin doses by 4u at a
time until FBG ~6time until FBG ~6
None of aboveNone of above
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Injection sites
Abdomen- Fastest
Arm- Intermediate
Leg- Slowest
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Glargine in Type 2
New to insulin
Once daily mediumacting
Glargine 10 units
Dose for dose switch
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Glargine- Weekly Titration
FPG (mmol/l)
5.5 – 6.76.7 – 7.8
7.8 – 10
> 10
Glargine dose increase
24
6
8
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Comparisons insulin regimensRegimen 1 Regimen 2 % achieving HbA1c
<7.0
Yki-Järvinen
Diab Care 2005
Glargine &
SU+MF
Mixtard 30 bd 46 vs. 29%, P = 0.001
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Comparisons insulin regimensRegimen 1 Regimen 2 % achieving HbA1c
<7.0
Yki-Järvinen
Diab Care 2005
Glargine &
SU+MF
Mixtard 30 bd 46 vs. 29%, P = 0.001
Malone JK
Diab Care 2005
Glargine &
SU+MF
Humalog Mix25 bd
18 vs. 42% P < 0.001
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Comparisons insulin regimensRegimen 1 Regimen 2 % achieving HbA1c
<7.0
Yki-Järvinen
Diab Care 2005
Glargine &
SU+MF
Mixtard 30 bd 46 vs. 29%, P = 0.001
Malone JK
Diab Care 2005
Glargine &
SU+MF
Humalog Mix25 bd
18 vs. 42% P < 0.001
Philip Raskin
Diab Care 2005
Glargine &
SU+MF
NovoRapid 30
bd
40 vs. 66%, P < 0.001
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Glargine-T2DM in Wycombe
2003- 2004
105 people with T2 DM
Group starts of 6-10
4 times 2 hour group session with DSN, and 30minutes with dietician
Minimum of 4 telephone contacts for dosetitration
Requested 4 point SBGM 3 times weekly
TTT titration protocol
C i i li i
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Comparisons insulin regimensRegimen 1 Regimen 2 % achieving HbA1c
<7.0
Yki-Järvinen
Diab Care 2005
Glargine &
SU+MF
Mixtard 30 bd 46 vs. 29%, P = 0.001
Malone JK
Diab Care 2005
Glargine &
SU+MF
Humalog Mix25 bd
18 vs. 42% P < 0.001
Philip Raskin
Diab Care 2005
Glargine &
SU+MF
NovoRapid 30
bd
40 vs. 66%, P < 0.001
Gallen 2004 Glargine +MF 17%
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Altering insulin in a 59 yr old man with Type
2 diabetes with a BMI of 29 on Mixtard (30)-62units bd and metformin 1 gm bd-
Problem- HbA1c 8.5% and glucose always
high pre-evening meal
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
62 units 62 units
MF 1gm MF 1gm
Wh t ld d ?
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What would you do?
Switch to basal bolusSwitch to basal bolus
Increase mid morning snack and increase morniIncrease mid morning snack and increase morni
Give mixtard at lunchGive mixtard at lunch
Advise reduce lunch and earlier eve. mealAdvise reduce lunch and earlier eve. meal
Stop morning metformin and increase the morninStop morning metformin and increase the mornin
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160
140
120
100
80
60
40
20
0
IGT I n s u l i n (m U / m L )
0800 1200 1600 2000 2400 0400
IGT
Type 2 diabetes
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160
140
120
100
80
60
40
20
0
I n s u l i n (m U / m L )
0800 1200 1600 2000 2400 0400
IGT
Type 2 diabetes
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
62 units 62 units
MF 1gm MF 1gm
Humalog Mix 25
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
62 units 40 units
MF 1gm MF 1gm
Glargine Plus
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
90 units
MF 1gm MF 1gm
12 units
Glargine Plus
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4
8
12
16
0800 1200 1600 2000 2400 0400
Clock time (hours)
90 units
MF 1gm MF 1gm
12 units
72yr old female with 18yr of type 2 diabetes on
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72yr old female with 18yr of type 2 diabetes on
glargine insulin for 4yr , BMI 26
Problem- 2 admissions with severehyperglycaemia in last 6 weeks- one with
hyperosmolar coma
HbA1c 8% 6 months previously
Discharged after both occasions with BG values
of between 4-10 mmol/l on glargine insulin 34
units daily
Now blood glucose values again all >15 over last day
Wh t ld d ?
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What would you do?
Stop glargine and start bd insulinStop glargine and start bd insulin
Add metforminAdd metformin
Readmit for restabilisationReadmit for restabilisation
None of aboveNone of above
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68 yr old man with Type 2 diabetes with a
BMI of 34 on Mixtard (30)- 120units bd andmetformin 1 gm bd-
HbA1c= 7.3% metformin stopped since
creatinine >150
Problem- HbA1c 13.0% all glucose values>15 mmol/l
What would you do?
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What would you do?
Continue increasing insulinContinue increasing insulin
Readdress diet and lifestyleReaddress diet and lifestyle
Prescribe sulphonylureaPrescribe sulphonylurea
Refer to Diabetes CentreRefer to Diabetes Centre
Give glitazoneGive glitazone
Summary
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Summary
• Diagnostic dilemmas• Normal 24 hr profile
• Profile in Type 2 diabetes
• Insulin species
• Insulin regimens
• New to insulin• Dose adjustment
• Regimen adjustment
Broken pen
Lipohypertrophy
Sick day rules
Stopping metformin
Loss of effect of rosiglitazone