Initiating and adjusting insulin

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Initiating and adjusting insulin

• Gerry Rayman
• The Diabetes Centre
• Ipswich 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, scarcely able to walk
on account of weakness.
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1922 Elizabeth Hughes
Imagine, I have to take 5cc at a time. Isnt it
awful. We only have a 2cc syringe. Blanche gives
it to me... unscrews the needle which is left
sticking in me, fills it again.. and then the
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 therapyin 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. The patient 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?
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Do you regularly advise on insulin dose
adjustment in the following groups?
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Making the diagnosis

• Type 1 or Type 2

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Type 1 vs Type 2

• More dramatic presentation- short history of
  severe polydipsia polyuria
• Younger
• Weight loss
• Ketones
• Strong FH of Type 1

• Often no osmotic symptoms
• Age related
• More common amongst certain ethnic 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?
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Type 2 diabetes Very high c-peptide and insulin
levels Negative insulin anti-bodies Managed 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 which can
  guide insulin initiation but an individuals
  response cannot be predicted
• Similarly for dose adjustment one can follow
  simplified guidelines but these must be modified
  depending on an individuals response

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Insulin Species
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• Regular (short acting)
• Actrapid, Humulin
• Rapid acting Analogues
• Humalog, Novorapid
• Isophanes/NPH (Intermediate)
• Insulatard, Humulin I
• Basal analogues
• Glargine, Detimer

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24
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Normal 24 Hr Insulin Profiles Bd premix
Plasma Insulin
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Normal 24 Hr Insulin Profiles basal bolus
Plasma Insulin
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When initiating insulin in Type 1 diabetes do you
use?
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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 and devices
• Makes it easier to gain a feel for these
  variables and is less confusing
• Start low and very gradually build up (Avoid
  hypoglycaemia)
• E.g Mixtard (30) or Novomix (30) 10 units bd
• Regular blood glucose monitoring
• Gradual increase in information
• Patient empowerment

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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 his
own doctor, biochemist and dietitian. R. D.
Lawrence. Assuming four 1 hr visits/yr patients
spend 0.0005 of their time with diabetic staff!
As diabetes does not look after itself the
patient 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
attitudes of 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 30s one on insulin
• Problem- recurrent hypos so patient frequently
  omitting insulin
• HbA1c 6.9 (highest over last 3yr 7.3)
• Treatment- Actrapid 2u pre-meals insulatard
  8u nocte (dose unchanged from diagnosis)

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What would you do?
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Young-adult diabetes (15-30yrs)

• Diabetes is a diagnostic speciality

Type 2
Genetic Syndromes
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HNF1a (MODY3)
Commonest cause of MODY May be misdiagnosed as
type 1 Typically develop 12-30 yr FPG maybe
normal initially Large rise (gt5mmol/l) in
OGTTWorsening glycaemia with age Low renal
threshold (glycosuria)Not obese
(usually) Parents and grandparents usually
diabetic
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HNF1a very sensitive to sulphonylureas
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
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Insulin (mU/mL)
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IGT
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Normal
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Polonsky KS et al. Horm Res 1998 49 17884.
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Glargine (Lantus)
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Insulin (mU/mL)
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IGT
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24-hr insulin profiles in normal, IGT late Type
2 diabetic subjects
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140
120
100
Insulin (mU/mL)
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IGT
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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?
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Group starts vs one to one

• Increasing numbers warrants an alternative to one
  to one
• One to one tends to lead to a dependency model in
  which the patient may not take ownership of
  self-adjustment
• Allows patients to learn from others experiences
  eg how others would adjust their insulin in a
  particular circumstance
• Useful in the community where one practice takes
  on initiation 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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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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Initiating insulin in a 59 yr old man with Type 2
diabetes on max OHA (triple therapy) with a BMI
of 26
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Stop sulphonylurea rosiglitazone continue
metformin
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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?
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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 good
  control
• HbA1c 10.1
• BMI 30
• Fasting glucose 10-15
• 2 severe hypos in last 3 months
• Treatment
• metformin 1gm bd
• mixtard (30)
• 90units bf eve meal
• 60 units lunch

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What would you do?
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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 medium acting
Glargine 10 units Dose for dose switch
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Glargine- Weekly Titration
FPG (mmol/l) 5.5 6.7 6.7 7.8 7.8
10 gt 10

• Glargine dose increase
• 2
• 4
• 6
• 8

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Comparisons insulin regimens
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Comparisons insulin regimens
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Comparisons insulin regimens
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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 30
  minutes with dietician
• Minimum of 4 telephone contacts for dose
  titration
• Requested 4 point SBGM 3 times weekly
• TTT titration protocol

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Comparisons insulin regimens
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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
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MF 1gm
MF 1gm
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What would you do?
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160
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Insulin (mU/mL)
80
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IGT
40
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1600
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2400
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160
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Insulin (mU/mL)
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MF 1gm
MF 1gm
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MF 1gm
MF 1gm
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Glargine
90 units
MF 1gm
MF 1gm
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Glargine
90 units
MF 1gm
MF 1gm
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72yr old female with 18yr of type 2 diabetes on
glargine insulin for 4yr , BMI 26

• Problem- 2 admissions with severe hyperglycaemia
  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 gt15 over last
  day

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What would you do?
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68 yr old man with Type 2 diabetes with a BMI of
34 on Mixtard (30)- 120units bd and metformin 1
gm bd-HbA1c 7.3 metformin stopped since
creatinine gt150Problem- HbA1c 13.0 all
glucose values gt15 mmol/l
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What would you do?
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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