when to start insulin doctors and nurses working together dr ketan dhatariya consultant in diabetes...
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When to Start InsulinWhen to Start Insulin Doctors and Nurses Working Doctors and Nurses Working
TogetherTogether
Dr Ketan DhatariyaDr Ketan DhatariyaConsultant in Diabetes and EndocrinologyConsultant in Diabetes and Endocrinology
Norfolk and Norwich University Hospital NHS TrustNorfolk and Norwich University Hospital NHS Trust
Good Timing!Good Timing!
Why is it the 14Why is it the 14thth of of November?November?
Fred Banting – one Fred Banting – one of the co-of the co-discoverers of discoverers of insulin insulin
Born on 14Born on 14thth November 1891November 1891
We’re All Trying to Achieve The We’re All Trying to Achieve The Same Thing – But Using Different Same Thing – But Using Different
ApproachesApproaches
Some DefinitionsSome Definitions
Type 1Type 1
Type 2Type 2
Others (not mentioned any more)Others (not mentioned any more)
Two Main TypesTwo Main Types
Type 1Type 1 Autoimmune destruction of the Autoimmune destruction of the ββ cells of cells of
the Islets of Langerhans in the pancreas. the Islets of Langerhans in the pancreas. This leads to an absolute insulin This leads to an absolute insulin deficiency. Insulin treatment is therefore deficiency. Insulin treatment is therefore mandatorymandatory
Previously known as IDDM or juvenile Previously known as IDDM or juvenile onset diabetesonset diabetes
Two Main TypesTwo Main Types Type 2Type 2
Impaired insulin action (insulin Impaired insulin action (insulin resistance) and eventually, impaired resistance) and eventually, impaired insulin secretion as wellinsulin secretion as well
Usually treated with oral medication Usually treated with oral medication initially, then may move onto insulininitially, then may move onto insulin
Formerly known as NIDDM or maturity Formerly known as NIDDM or maturity onset diabetesonset diabetes
EpidemiologyEpidemiology
Diabetes currently affects approximately 3 Diabetes currently affects approximately 3 to 4% of the populationto 4% of the population
90% of whom have type 2 diabetes90% of whom have type 2 diabetes
Lifetime risk of developing diabetes is Lifetime risk of developing diabetes is about 10%about 10%
Why is it Important?Why is it Important?
Poorly controlled diabetes leads to Poorly controlled diabetes leads to accelerated cardiovascular morbidity and accelerated cardiovascular morbidity and mortalitymortality
A combination of microvascular and A combination of microvascular and macrovascular diseasemacrovascular disease
Thom T et al Circulation 2006;113(6):e85-151
Some Good NewsSome Good News
Health Consumer Power House Euro Consumer Diabetes Index Sept 2008
UKPDS HbA1c Median Values
06
7
8
9
0 3 6 9 12 15
Hb
A 1c (%
)
Years from randomisation
Conventional
Intensive
6.2% upper limit of normal range
Data From 3.3M DanesData From 3.3M Danes
Schramm TK et al Circulation 2008;117:1945-1954
An (?Uncontroversial) An (?Uncontroversial) Starting PointStarting Point
People with type 1 diabetes need to be People with type 1 diabetes need to be referred to the specialist hospital team at referred to the specialist hospital team at the time of suspected diagnosisthe time of suspected diagnosis
Many people continue to be followed up in Many people continue to be followed up in secondary care. secondary care. This depends heavily on the competence and This depends heavily on the competence and
confidence of the primary care team – and the confidence of the primary care team – and the support offered by secondary caresupport offered by secondary care
Non-Insulin Hypoglycaemic Non-Insulin Hypoglycaemic AgentsAgents
αα glucosidase inhibitors glucosidase inhibitors
MetaglinidesMetaglinides
MetforminMetformin
SulphonylureasSulphonylureas
ThiazolidindionesThiazolidindiones
GLP – 1 analoguesGLP – 1 analogues
DPP IV inhibitorsDPP IV inhibitors
αα Glucosidase Inhibitors Glucosidase Inhibitors
There is only 1 – acarbose There is only 1 – acarbose
Intestinal disaccharidase inhibitor Intestinal disaccharidase inhibitor
Taken one with each mealTaken one with each meal
If they don’t eat, no need to take the If they don’t eat, no need to take the tablettablet
HbA1c reduction of 0.5 - 0.8%HbA1c reduction of 0.5 - 0.8%
MetaglinidesMetaglinides
There are 2 – repaglinide and nateglinideThere are 2 – repaglinide and nateglinide
Work by binding to the sulphonylurea Work by binding to the sulphonylurea receptor and ‘squeezing’ the receptor and ‘squeezing’ the ββ cell to release cell to release insulininsulin
They stimulate first-phase insulin release in a They stimulate first-phase insulin release in a glucose-sensitive mannerglucose-sensitive manner
HbA1c reduction of 0.5 - 1.5%HbA1c reduction of 0.5 - 1.5%
MetforminMetformin
Derived from the plant known as Goat's Rue, French Lilac, Italian Fitch or Professor-weed (Galega officinalis)
MetforminMetformin First choice oral hypoglycaemic agent for First choice oral hypoglycaemic agent for
people with type 2 diabetes, regardless of BMIpeople with type 2 diabetes, regardless of BMI
Works by decreasing hepatic Works by decreasing hepatic gluconeogenesis, decreasing gut glucose gluconeogenesis, decreasing gut glucose uptake and increasing peripheral insulin uptake and increasing peripheral insulin sensitivitysensitivity
Metformin does not (or very rarely) give Metformin does not (or very rarely) give people hypos, because it works by preventing people hypos, because it works by preventing blood glucose levels rising rather than by blood glucose levels rising rather than by lowering glucose levels lowering glucose levels
HbA1c reduction of 1.0 – 2.0%HbA1c reduction of 1.0 – 2.0%
SulphonylureasSulphonylureas
• Have been around since the 1950’sHave been around since the 1950’s
• Act by binding to the SU receptor causing Act by binding to the SU receptor causing an influx of Caan influx of Ca2+2+ and an exocytosis of and an exocytosis of insulin containing vesiclesinsulin containing vesicles
• Use limited to individuals with a BMI < 25 Use limited to individuals with a BMI < 25 or in whom metformin is contraindicatedor in whom metformin is contraindicated
HbA1c reduction of 1.0 – 2.0%HbA1c reduction of 1.0 – 2.0%
ThiazolidinedionesThiazolidinediones Work by increasing peripheral insulin Work by increasing peripheral insulin
sensitivity at a nuclear level on peroxisome sensitivity at a nuclear level on peroxisome proliferator-activated receptor proliferator-activated receptor γγ (PPAR(PPAR γγ))
HbA1c reduction of 0.5 - 1.4%HbA1c reduction of 0.5 - 1.4%
Several controversies thus use is decliningSeveral controversies thus use is declining Increased CV death ratesIncreased CV death rates Increased fracture ratesIncreased fracture rates Increased rates of macular oedemaIncreased rates of macular oedema
Nissen SE NEJM 2007;356(24):2457-2471Loke Y et al In press
Ryan EH et al Retina 2006; 26(5):562-70
GLP-1 and DPP-IVGLP-1 and DPP-IV
Nauck MA et al. Diabetologia 1993;36:741–744; Larsson H et al. Acta Physiol Scand 1997;160:413–422; Nauck MA et al. Diabetologia 1996;39:1546–1553; Flint A et al. J Clin Invest 1998;101:515–520; Zander et al. Lancet
2002;359:824–830.
GLP-1 secreted upon the ingestion of food
1.-cell:cell:Enhances glucose-Enhances glucose-
dependent insulin secretion dependent insulin secretion in the pancreasin the pancreas
3.Liver:3.Liver: reduces hepatic glucose reduces hepatic glucose
outputoutput
2.2.αα--cell:cell:Suppresses postprandialSuppresses postprandial
glucagon secretionglucagon secretion
4.Stomach:4.Stomach: slows the rate of slows the rate of gastric emptyinggastric emptying
5.Brain:5.Brain:Promotes satiety and Promotes satiety and
reduces appetitereduces appetite
Their Effects Are AdditiveTheir Effects Are Additive
HbA1C
Time
The Goalposts Are ChangingThe Goalposts Are Changing
HbAHbA11C targets are coming downC targets are coming down
The tighter the control, the likelihood of The tighter the control, the likelihood of developing complications reduces – to a developing complications reduces – to a pointpoint
EVERY 1%
reduction in HbA1c
REDUCED RISK*
1%
Deaths from diabetes –21%
Heart attacks –14%
Microvascular complications–37%
Peripheral vascular disorders
UKPDS 35. BMJ 2000;321:405–12
Lessons from UKPDS:Lessons from UKPDS:Better Control Means Fewer Better Control Means Fewer
ComplicationsComplications
–43%
*p<0.0001
How Many Guidelines?How Many Guidelines?
EASD / ADAEASD / ADA Nathan et al Diabetes care 22/10/08 epub Nathan et al Diabetes care 22/10/08 epub
ahead of publication ahead of publication http://care.diabetesjournals.org/misc/dv08-http://care.diabetesjournals.org/misc/dv08-9025.pdf9025.pdf
NICENICE http://www.nice.org.uk/nicemedia/pdf/http://www.nice.org.uk/nicemedia/pdf/
CG66diabetesfullguideline.pdfCG66diabetesfullguideline.pdf
Royal College of PhysiciansRoyal College of Physicians http://www.rcplondon.ac.uk/pubs/contents/http://www.rcplondon.ac.uk/pubs/contents/
14f051f1-8fa4-4d0b-9385-9f2e77edc2ca.pdf14f051f1-8fa4-4d0b-9385-9f2e77edc2ca.pdf
Recent ADA / EASD Recent ADA / EASD GuidelinesGuidelines
Nathan DM et al Diabetes Care 22/10/08 epub online
NICE AdviceNICE Advice
http://www.nice.org.uk/nicemedia/pdf/CG66diabetesfullguideline.pdf Accessed 9th November 2008
RCP Management of Type 2 diabetes – May 2008 Accessed 9.11.08
http://www.rcplondon.ac.uk/pubs/contents/14f051f1-8fa4-4d0b-9385-9f2e77edc2ca.pdf
Tighter ControlTighter Control
This means that oral agents alone may not This means that oral agents alone may not be sufficient and that insulin needs to be be sufficient and that insulin needs to be addedadded
Consider the Following Consider the Following ScenariosScenarios
60 year old, CVA, blind, dense hemiplegia, 60 year old, CVA, blind, dense hemiplegia, lives in a nursing home, fully dependent lives in a nursing home, fully dependent
80 year old, plays golf daily, travels the 80 year old, plays golf daily, travels the world extensively with their 60 year old world extensively with their 60 year old partner looking for ‘excitement’partner looking for ‘excitement’
QOF is not ‘situation specific’QOF is not ‘situation specific’
InsulinInsulin
Should be started when the HbAShould be started when the HbA11C is C is ≥ ≥ 7.5% on maximal oral hypoglycaemics7.5% on maximal oral hypoglycaemics
PregnancyPregnancy
SteroidsSteroids
Intercurrent illnessIntercurrent illness
Now You’ve made Your Now You’ve made Your DecisionDecision
A few questionsA few questions Which insulin?Which insulin?
What dose?What dose?
What regime?What regime?
What do I do with the tablets?What do I do with the tablets?
Should I address their weight first??Should I address their weight first??
InsulinsInsulins
Soluble (short acting)Soluble (short acting)
NPH (intermediate)NPH (intermediate)
Once dailyOnce daily
MixturesMixtures
Insulin analogues – ultra short, long and Insulin analogues – ultra short, long and
mixturesmixtures
EASD / ADA EASD / ADA RecommendationsRecommendations
Start with once daily basal insulin Start with once daily basal insulin Which type of insulin depends on when BG levels are highestWhich type of insulin depends on when BG levels are highest
If there are no contraindications – stay on night If there are no contraindications – stay on night time insulin, with day time metformin or SU’stime insulin, with day time metformin or SU’s
Keep regularly increasing the dose until the Keep regularly increasing the dose until the fasting blood glucose is less than 7.0 mmol/Lfasting blood glucose is less than 7.0 mmol/L
Holman RR et al N Engl J Med 2007;357:1716-1730
Bretzel RG et al Lancet 2008;371:1073-1084; Nathan DM et al Diabetes Care 22/10/2008; epub
Riddle MC Endocrine and Metabolic Clinics of North America 2005;34:77-98; Pala L et al Diabetes Res Clin Pract 2007;78:132-135
Other OptionsOther Options
Twice daily mixtures are commonly used Twice daily mixtures are commonly used but may be associated with greater weight but may be associated with greater weight gain than once daily injectionsgain than once daily injections
Three times daily mixtures are also Three times daily mixtures are also common on the continentcommon on the continent
In people who have unpredictable In people who have unpredictable lifestyles, a basal bolus regime may be lifestyles, a basal bolus regime may be appropriateappropriate
ADA/EASD ADA/EASD Insulin Insulin
Initiation Initiation GuidelineGuideline
ss
Nathan DM et al Diabetes Care 22/10/08
epub online
There are Other Algorithms There are Other Algorithms
At:Lantus – starting at 10 IU / dayAt:Lantus – starting at 10 IU / day
Davies M et al Diabetes Care 2005;28:1282-1288
Potential ImplicationsPotential Implications
DrivingDriving
InsuranceInsurance
Recent DataRecent Data
ACCORD ACCORD (Action to Control Cardiovascular Risk in (Action to Control Cardiovascular Risk in Diabetes)Diabetes)
ADVANCE ADVANCE (Action in Diabetes and Vascular Disease: (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Preterax and Diamicron Modified Release Controlled Evaluation)Evaluation)
VADT VADT (Veteran’s Administration Diabetes Trial)(Veteran’s Administration Diabetes Trial)
NEJM 2008;358(24):2545-2559NEJM 2008;358(24):2560-2572
Duckworth WC et al Diabetes Care 2001;24:942-945
Tighter Glycaemic Control Tighter Glycaemic Control Does Does NOTNOT Influence Influence
OutcomesOutcomes Getting HbA1C to less that 7.0% added no Getting HbA1C to less that 7.0% added no
benefitbenefit
In ACCORD it lead to a higher mortality In ACCORD it lead to a higher mortality raterate
Lots of reasons – including better risk Lots of reasons – including better risk factor managementfactor management
Increased Use of Adjunctive Increased Use of Adjunctive AgentsAgents
Charlton J et al Diabetes Care 2008;31(8):1761-1766
Things That Make the Most Things That Make the Most DifferenceDifference
Smoking Smoking OR 2.87OR 2.87 Raised ApoB/ApoA1 ratioRaised ApoB/ApoA1 ratio OR 3.25OR 3.25 History of hypertensionHistory of hypertension OR 1.91OR 1.91 DiabetesDiabetes OR 2.37OR 2.37 Abdominal obesityAbdominal obesity OR 1.12OR 1.12 Psychosocial factorsPsychosocial factors OR 2.67OR 2.67 Daily fruit and veg intakeDaily fruit and veg intake OR 0.7OR 0.7 Regular alcohol consumptionRegular alcohol consumption OR 0.9OR 0.9 Regular physical activityRegular physical activity OR 0.86OR 0.86
Yusuf et al Lancet 2004 364:937-952
In SummaryIn Summary There are a lot of medications to try firstThere are a lot of medications to try first
Weight loss is a cornerstone to delaying Weight loss is a cornerstone to delaying insulininsulin
To ensure the best outcomes for your To ensure the best outcomes for your patients with diabetes patients with diabetes Be Aggressive! Be Aggressive! Treat Early!Treat Early!
Being on insulin is not ‘failure’Being on insulin is not ‘failure’
Thank you for your attention