Gerry Rayman Initiating and Adjusting Insulin

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Initiating and adjusting

insulinGerry Rayman

The Diabetes CentreIpswich Hospital



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.




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.




I experienced a severe anaphylactic

reaction...persisting for 2 days.....generalized skin eruption, nausea,

vomiting, profound weakness. I thought I

was going to die.



Barriers to insulin therapy

in Type 2

Fear of injections/needles/syringes

6mm length, 30g siliconised needles

Pens (autoinjectors & needle guards)

Weight gain

Coma



Barriers to intensified insulin

therapy in Type 1

Additional injections and testing

6mm length, 30g siliconised needles

Pens (autoinjectors & needle guards)

Weight gain

Hypoglycaemia



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.



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



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



Making the diagnosisType 1 or Type 2



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



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



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



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



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



Type 2 diabetes

Very high c-peptide and insulin levels

Negative insulin anti-bodiesManaged on insulin and metformin

Acanthosis Nigricans

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http://www.dermnet.com/image.cfm?passedArrayIndex=15&moduleID=17&moduleGroupID=246



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



Insulin Species



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



Plasma Insulin

Normal 24 Hr Insulin Profiles & Bd premix



Plasma Insulin

Normal 24 Hr Insulin Profiles & basal bolus



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



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



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



4

8

12

16

B’F EM

Humalog Mix 25

10 units 10units 1212



4

8

12

16

Humalog Mix 25

16 units 14units18



4

8

12

16

Humalog Mix 25

24 units 14units



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



Changing insulin species or

regimen

Always reduce insulin dose by 10-20%

Avoids hypoglycaemia and loss of confidence



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.



Patients need Motivation

Unlike pregnancy no immediate gains.

Motivating factor include the attitudesof family and diabetes team.



Patients need Feedback

Blood glucose monitoring

The patient needs to know

his own HbA1c result.



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)



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



Young-adult diabetes (15-30yrs)

“Diabetes is a diagnostic speciality”

Type 1

Genetic Syndromes

MODY

Type 2



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



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



Insulin therapy in Type 2

diabetes



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



Glargine (Lantus)

160

140

120

100

80

60

40

20

0


/ m L )

0800 1200 1600 2000 2400 0400

Clock time (hours)

Type 2 diabetes

Early Type 2



24-hr insulin profiles in normal, IGT & late

Type 2 diabetic subjects

160

140

120

100

80

60

40

20

0


/ m L )

0800 1200 1600 2000 2400 0400

IGT

Type 2 diabetes



Target HbA1c

Diabetes UK 7%

NICE 2002 (Type 2 DM) 6.5 – 7.5%

GP Contract 7.4%



―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



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



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



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



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



Wh t l d ti t



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



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.



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



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



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

g

12 units 8 units 12

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

g

12 units 12 units 14

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

g

12 units 14 units16

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

g

16 units 14 units18

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

18 units 14 units20

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)


Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

20 units 16 units22

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

22 units 16 units



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



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



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



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



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



Injection sites

Abdomen- Fastest

Arm- Intermediate

Leg- Slowest



Glargine in Type 2

New to insulin

Once daily mediumacting

Glargine 10 units

Dose for dose switch



Glargine- Weekly Titration

FPG (mmol/l)

5.5 – 6.76.7 – 7.8

7.8 – 10

> 10

Glargine dose increase

24

6

8



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




<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




<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



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




<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%



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



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 ?



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



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



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



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

62 units 62 units

MF 1gm MF 1gm

Humalog Mix 25



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

62 units 40 units

MF 1gm MF 1gm

Glargine Plus



4

8

12

16

0800 1200 1600 2000 2400 0400

Clock time (hours)

90 units

MF 1gm MF 1gm

12 units

Glargine Plus



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



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 ?



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



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?



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



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

Gerry Rayman Initiating and Adjusting Insulin

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