Diabetes Care Improvement Packages.

Role of Primary Care

Dr Jeremy Krebs Clinical Leader and Endocrinologist

Wellington Hospital

Diabetes Mellitus

How big is the problem?

Diabetes Care Improvement Packages

Does hyperglycaemia matter?

Management Goals

Insulin

New Zealand Virtual Diabetes Register end-2005 to end-2012 – latest data

0

50000

100000

150000

200000

250000

2005 2006 2007 2008 2009 2010 2011 2012

Increase is in both genders,

also across all ethnicities

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

45.00%

50.00%

00-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Rate

(B

ase=

Pra

cti

ce e

nro

lled

po

pu

lati

on

)

Age group

New Zealand Diabetes Prevalance Rate as of 31 Dec 2006

European/Other Mäori Pacific people Indian

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

45.00%

50.00%

00-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Rate

(B

ase=

Pra

cti

ce e

nro

lled

po

pu

lati

on

)

Age group

New Zealand Diabetes Prevalance Rate as of 31 Dec 2007

European/Other Mäori Pacific people Indian

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

45.00%

50.00%

00-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Rate

(B

ase=

Pra

cti

ce e

nro

lled

po

pu

lati

on

)

Age group

New Zealand Diabetes Prevalance Rate as of 31 Dec 2008

European/Other Mäori Pacific people Indian

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

45.00%

50.00%

00-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Rate

(B

ase=

Pra

cti

ce e

nro

lled

po

pu

lati

on

)

Age group

New Zealand Diabetes Prevalance Rate as of 31 Dec 2009

European/Other Mäori Pacific people Indian

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

45.00%

50.00%

00-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Rate

(B

ase=

Pra

cti

ce e

nro

lled

po

pu

lati

on

)

Age group

New Zealand Diabetes Prevalance Rate as of 31 Dec 2010

European/Other Mäori Pacific people Indian

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

40.00%

45.00%

50.00%

00-04 05-09 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

Rate

(B

ase=

Pra

cti

ce e

nro

lled

po

pu

lati

on

)

Age group

New Zealand Diabetes Prevalance Rate as of 31 Dec 2011

European/Other Mäori Pacific people Indian

Direct same-scale comparison of prevalence curves 2005 and 2011

VDR 2012: major points

Diagnosed diabetes prevalence at December 2012 is 225,731, an increase of 8.5% above December 2011 (17,600, ≈ 50 per day) .

All DHBs showed increases – from 3 - 13%.

Peak prevalence in Pacific and Asian groups is now at 45% in older adults. In Maori is now at 35% in older adults.

The majority of diabetes (69%) is still within the European/Other community.

Diabetes Mellitus

How big is the problem?

Diabetes Care Improvement Packages

Does hyperglycaemia matter?

Management Goals

Insulin

Traditional Model of Diabetes Care

Secondary Care

Primary Care

Gestational DM

Type 1 Paediatrics

• Access to specialist advice / services

• Limited input to overall population

• Disparities in Access / Care

• Information sharing

Type 2

How can we improve diabetes care?

What? (Primary and Secondary Care)

– Improved Communication

– Improved Sharing of Data

– Improved Two-way Flow of Patients

How

– Shared Care

– Combined Community Clinics

– More Multi-Disciplinary Approach

– Acceleration of therapy in primary care

Diabetes Care Improvement Plan

– Prevent and slow progression of diabetic complications, especially heart disease, renal failure, impaired vision and lower limb amputations

– Reduce disparities between different population groups

– Reduced frequency of diabetes-related presentations to hospital emergency departments

– Reduce rates of hospital admission for diabetes and related complications

– Prevent or delay the onset of diabetes

The CCDHB model’s key components

Combined Primary and Secondary Diabetes Clinical Network

Practice population management

Performance measures

Collaborative case service in priority practices

Workforce development

Nurse practice partnership

Self Management Groups

Hospital specialist service focused on complex, Type 1, paediatric, gestational and renal diabetes

Key Goals

Get quality services to the population that need it

Foster patient self management

Maximise the skills and confidence of the workforce

Traditional Model of Diabetes Care

Secondary Care

Primary Care

Gestational DM

Type 1 Paediatrics

• Access to specialist advice / services

• Limited input to overall population

• Disparities in Access / Care

• Information sharing

Type 2

Primary Care

Secondary Care

Paediatrics

Practice

Practice

Gestational DM

Type 1

Practice

Practice

Practice

Practice

Practice

Practice

Practice

Practice

New Model for Diabetes Management in the Wellington Region

Clinical Network

Outreach

Self Management

Groups

Diabetes Mellitus

How big is the problem?

Diabetes Care Improvement Packages

Does hyperglycaemia matter?

Management Goals

Insulin

Skyler JS. Endocrinol Metab Clin 1996;25:243–254.

HbA1c and Risk of Diabetes Related

Complications

Target

HbA1c <7%

17

15

13

11

9

7

5

3

1

6 7 8 9 10 11 12 HbA1c (%)

Rela

tive r

isk

Retinopathy

Nephropathy

Neuropathy

Microalbuminuria

Incidence rates of MI and microvascular endpoints by mean HbA1c (UKPDS)

20

40

60

80

Incid

en

ce p

er

1,0

00 p

ati

en

t-years

Study population: white, Asian Indian, and Afro-Caribbean UKPDS patients (n = 4,585)

Adjusted for age, sex, and ethnic group

5 6 7 8 9 1 0 1 1

Myocardial

infarction

Microvascular

disease

Updated mean HbA1c (%)

Error bars = 95% CI

Adapted from Stratton IM, et al. Br Med J 2000; 321:405–412.

0 0

UKPDS: Improving HbA1c Control Reduced Diabetes-Related Complications

UKPDF=United Kingdom Prospective Diabetes Study.

Data adjusted for age, sex, and ethnic group, expressed for white men aged 50–54 years at diagnosis and with mean duration of diabetes of 10 years.

Stratton IM et al. UKPDS 35. BMJ 2000;321:405–412.

EVERY 1%

reduction in HbA1c

REDUCED RISK

(P<0.0001)

1%

Diabetes-

related

deaths

Myocardial

infarctions

Microvascular

complications

Amputations or deaths

from peripheral

vascular disorders

Relative Risk N=3642

14

After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007

Any diabetes related endpoint RRR: 12% 9%

P: 0.029 0.040

Microvascular disease RRR: 25% 24%

P: 0.0099 0.001

Myocardial infarction RRR: 16% 15%

P: 0.052 0.014

All-cause mortality RRR: 6% 13%

P: 0.44 0.007

RRR = Relative Risk Reduction, P = Log Rank

Figure 4:Legacy Effect of Earlier Glucose Control

0

10

20

30

40

50

60

70

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Numbers at risk

Conventional

Intensive

Steno-2 Post Trial: Mortality of any cause

80

80

80

78

77

75 69

72

63

65

51

62

43

57

Log-rank P=0.015

30

39

Years of follow-up

Cu

mu

lati

ve

in

cid

en

ce

of

de

ath

(%

)

Gaede et al. NEJM 2008

Steno-2 Post Trial: Any CVD events

0

10

20

30

40

50

60

70

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Numbers at risk

Conventional

Intensive 80

80

70

72

60

65

46

61

38

56

29

50

25

47

14

31

Years of follow-up

Cumulative incidence of patients with a major CVD event during follow-up

Log-rank P=0.0002

Cu

mu

lati

ve

in

cid

en

ce

of

CV

D e

ve

nts

(%

)

Gaede et al. NEJM 2008

7 patients Laser treatment

16 patients Dialysis

5 patients Progression to nephropathy

3 patients Major cardiovascular event

8 patients Cardiovascular death

5 patients Death

Number of patients with type 2 diabetes and

microalbuminuria needed to treat for 13 years to

prevent one...

(from Gaede et al 2008 Steno 2, 13 year study)

Recent Trials of Glycaemic Control

Advance, Accord

10 year post diagnosis, middle age

Despite intensive HBA1c management have failed to show CVD benefit

Accord The Action to Control Cardiovascular Risk in Diabetes Study Group

N=10,000

– 1/3 already on insulin

– 1/3 prevalent CVD events

– Age 62

– Diabetes for 10 years

– HbA1c 8.3

Strategy of (ultra) intensive glycaemic control aiming for HbA1c 6 (achieved 6.3)

The mean difference during the trial was 1.1%

Accord

Accord June 2008 Primary Outcome: First occurrence of nonfatal MI, stroke or death from

Cardiovascular cause

352 vs 371

events

HR 0.9 (0.78-

1.04, p=0.16)

Intensive N (%)

Standard N (%) HR (95% CI) P

Primary 352 (6.86) 371 (7.23) 0.90 (0.78-1.04) 0.16

Secondary

Mortality 257 (5.01) 203 (3.96) 1.22 (1.01-1.46) 0.04

Nonfatal MI 186 (3.63) 235 (4.59) 0.76 (0.62-0.92) 0.004

Nonfatal Stroke 67 (1.31) 61 (1.19) 1.06 (0.75-1.50) 0.74

CVD Death 135 (2.63) 94 (1.83) 1.35 (1.04-1.76) 0.02

CHF 152 (2.96) 124 (2.42) 1.18 (0.93-1.49) 0.17

Year Post-

randomization

% o

f P

art

icip

ants

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

1st 2nd 3rd 4th 5th 6th

Intensive

Standard

Diabetes Mellitus

How big is the problem?

Diabetes Care Improvement Packages

Does hyperglycaemia matter?

Management Goals

Insulin

Treatment Targets NZ Primary Care Handbook 2012

Less than 50% of Adults With Type 2 Diabetes Have Achieved HbA1cGoals

NHANES=National Health and Nutrition Examination Survey of a US population.

Adapted from Saydah SH et al. JAMA. 2004;291:335–342.

HbA1c level

<7%

Blood pressure

<130/80 mmHg

Total cholesterol

<200 mg/dl

Achieved all 3

treatment goals

CV Risk Factors

44.3

29.0 33.9

5.2

37.0 35.8

48.2

7.3

0

10

20

30

40

50

60

Ad

ults, %

NHANES III (1988–1994) (n=1204)

NHANES 1999–2000 (n=370)

US Population

13

Glycaemic Control Target HbA1c 48-58 mmol/mol

(6.5 - 7.5%)

Diet and Lifestyle

Oral Hypoglycaemics

Monotherapy

Combination therapy

Insulin

Management Strategy

Natural History of Type 2 Diabetes

cross-sectional, median values

06

7

8

9

0 3 6 9 12 15

HbA

1c (

%)

Years from randomisation

Conventional

Intensive

6.2% upper limit of normal range

Clinical Inertia

aUS Physicians; 1994–2002 bMean number of months that elapsed until a new or additional treatment was started. cMonotherapy switched to another agent or additional agent added.

Brown JB et al. Diabetes Care. 2004;27:1535–1540; American Diabetes Association. Diabetes

Care. 2007;30(suppl 1):S4–S41; Nathan DM et al. Diabetologia. 2006 Aug;49(8):1711–21.

First HbA1c on

Treatment

Best HbA1c on

Treatment

Last HbA1c before

Switch or Additionc

ADA goal

EASD goal

27b

months

35b

months

8.2

7.7

8.8

7.6

7.1

9.1

6

7

8

9

10

Metformin monotherapy (n=513 episodes)

Sulfonylurea monotherapy (n=3394 episodes)

0

Hb

A1c,

%

ADA=American Diabetes Association. EASD=European Association for the Study of Diabetes.

11

Traditional Type 2 Diabetes Management: A “Treat-to-Fail Approach”

OAD=oral anti-hyperglycaemic drug.

Adapted from Campbell IW. Need for intensive, early glycaemic control in patients with type 2 diabetes. Br J Cardiol. 2000;7(10):625–631.

Del Prato S et al. Int J Clin Pract. 2005;59:1345–1355.

7

8

6

9

10

OAD

monotherapy

Diet and

exercise

OAD

combination

OAD

up-titration

OAD plus

multiple daily

insulin

injections

OAD plus

basal insulin

Hb

A1c,

%

Mean HbA1c

of patients

Duration of Diabetes

Published Conceptual Approach

Time

12

The Therapeutic Challenge in Managing Type 2 Diabetes

We need treatments that:

– Additive to traditional treatments

– Can be used in presence of complications (eg kidney failure, heart disease)

– Acceptable to patients

– Minimise rather than worsen complications of diabetes

– (preferably) not increase weight

– (ideally) not cause hypos

Type 2 Diabetes

De Fronzo J. Diabetes 1998; 37:667–687.

Insulin Resistance

hepatic

glucose

production glucose uptake

-cell Dysfunction

impaired

insulin secretion

Genetic Susceptibility

Obesity, Sedentary Lifestyle

Pathogenesis of Type 2 Diabetes: Insulin Resistance and -cell dysfunction

Major Targeted Sites of Oral Drug Classes

Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:1427–1483; DeFronzo RA. Ann Intern Med.

1999;131:281–303; Inzucchi SE. JAMA 2002;287:360-372; Porte D et al. Clin Invest Med. 1995;18:247–254.

DPP-4=dipeptidyl peptidase 4; TZDs=thiazolidinediones.

Glucose

absorption

Hepatic glucose

overproduction

Impaired insulin

secretion

Insulin

resistance

Pancreas

↓Glucose level

Muscle

and fat Liver

Biguanides

TZDs Biguanides

Sulfonylureas

GLP-1 mimetics

TZDs

α-Glucosidase

inhibitors

Gut

DPP-4 inhibitors

DPP-4 inhibitors

Biguanides

15

GLP-1 mimetics

Type 2 Diabetes Algorithm

Diet and Lifestyle

Metformin

GLP-1 Agon DPPIV Ant Glitazone SU Acarbose

Insulin

Weight loss

No hypos

But Injectable

Weight neutral

Oral agent

No hypos

Oral agent

No hypos

But GI side effects

No hypos

But weight gain, heart

failure, fractures,

bladder cancer. ?IHD

risk

Oral agent

Good evidence

But weight gain,

hypos

Diabetes Mellitus

How big is the problem?

Diabetes Care Improvement Packages

Does hyperglycaemia matter?

Management Goals

Insulin

Insulin Therapy

Feel Better

– More energy

– Less infections

Better HbA1c

• Microvascular

• ? Macrovascular

Flexibility

Injections

Weight gain

More hypo’s

Driving issues

Needle phobias

Pro’s Con’s

DCCT Research Group.

N Engl J Med 1993;329:977–986

Trade off of Intensifying Insulin therapy

0

10

20

30

40

50

60

70

80

90

100

5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5

Hypoglycaemia

Complications

HbA1C

Ris

k o

f d

evelo

pin

g

hyp

og

lycaem

ia/c

om

pli

cati

on

s (

%)

Insulin and Type 2 Diabetes: The Who?

Anyone!

– Poor glycaemic control (HbA1c >60 mmol/mol)

– Symptoms of hyperglycaemia

But consider:

– Is it realistic

• Self inject?

• Risk of hypoglycaemia

• Age and Co-morbidities

Glucose

(mg/dl)

50 –

100 –

150 –

200 –

250 –

300 –

350 –

0 –

50 –

100 –

150 –

200 –

250 –

-10 -5 0 5 10 15 20 25 30 Years of diabetes

Adapted from Burger HG, et al. 2001. Diabetes Mellitus, Carbohydrate Metabolism, and Lipid Disorders. In Endocrinology.

4th ed. Edited by LJ DeGroot and JL Jameson. Philadelphia: W.B. Saunders Co., 2001.

Originally published in Type 2 Diabetes BASICS. International Diabetes Center, Minneapolis, 2000.

Relative

function

(%)

Fasting

glucose

Obesity IFG Diabetes Uncontrolled

hyperglycemia

Insulin resistance

Progressive Decline in Insulin Secretion

Postprandial

glucose

Insulin secretion Clinical

diagnosis

Insulin Therapy: The What?

? Once daily intermediate acting insulin

? Twice daily intermediate acting insulin

? Mixed insulins

? Basal bolus regimen

? Regular or analogue

Little evidence to support one over another

in Type 2.

How to Decide on What?

Pattern of hyperglycaemia

• Fasting vs Post-prandial

• Morning vs Evening

What will the patient do?

• Inject once or several times per day?

• Willing to test glucose levels?

• Able to interpret result and modify insulin?

53

Role of Self Monitoring of Blood Glucose

Type 2 DM on lifestyle alone/Metformin

– Useful intermittently to establish effect of food/exercise on glycaemia

– Useful to examine pattern of glucose elevation to aid commencement of further treatment

Type 2 DM on oral hypoglycaemic agents

– As above, plus

– Monitoring for hypoglycaemia

Type 1 DM and Type 2 on insulin

– Needed to rationally adjust insulin doses, plus

– Factors above

54

Glucose Focused Testing Examples

Actionable information for informed decision-making

Paired Testing … Testing to explore cause and effect BG

variance related to life events or

activities, such as food, lifestyle, and

current medication. Supports patient

self-learning and engagement.

Adjustment Testing …

BG testing to support activities to determine dose adjustment.

Pattern Testing …

Multi-point BG profiles for a specific

duration to use

pattern analysis to identify problem areas for

remediation.

83 159 134 203 103 178 102 93 201 136 123 156 237 142 90 147 93 138 132 201 173

xx

xx

xx

x

xx x x

xx

x xx x

xx

x

0 0 0 0 0 0 0 00 0 0 00 0 0 0 0 0 0 0 0

4/4/07 4/5/07 4/6/07

0 0 0 0 0 0 0 0 0

7:10 9:20 12:00 2:10 6:45 8:35 11:00 7:00 9:15 12:30 2:20 7:15 9:20 11:41 6:45 9:00 12:00 2:10 7:30 9:45 11:40

x

83 159 134 203 103 178 102 93 201 136 123 156 237 142 90 147 93 138 132 201 173

xx

xx

xx

x

xx x x

xx

x xx x

xx

x

0 0 0 0 0 0 0 00 0 0 00 0 0 0 0 0 0 0 0

4/4/07 4/5/07 4/6/07

0 0 0 0 0 0 0 0 0

7:10 9:20 12:00 2:10 6:45 8:35 11:00 7:00 9:15 12:30 2:20 7:15 9:20 11:41 6:45 9:00 12:00 2:10 7:30 9:45 11:40

x

Types of Insulin

Basal Insulins

• Isophane (Protophane, Humulin N)

• Analogs (Glargine, Detimir)

Bolus Insulins

• Actrapid, Humulin R

• Analogs (Novorapid, Humalog, Apidra)

Mixed Insulins

• Penmix 30/70,

• Humalog Mix 25 and 50

Insulin comparisons

Adapted from Monnier L et al. Diabetes Care 2003;26:881–5

PPG

FPG

50% 55% 60% 70%

50% 45% 40% 30%

30%

70%

<7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2

0

20

40

60

80

100

HbA1c range (%)

% c

on

trib

utio

n to

Hb

A1c

Most insulin is initiated when HbA1c >8.5%

To normalise blood glucose both FPG and PPG must be reduced

Success Comes From Using the Most Appropriate Tools

What about the oral agents? Continue or Stop?

Metformin

– Good evidence to continue

Glitazones

– Some evidence but increased risk of heart failure

Sulphonylureas

– Often continue in short-term

– No real benefit to continue in the long-term?

Most Commonly

Add in once daily intermediate or long acting insulin (NPH insulin or Glargine).

Evening if FPG>6mmol/L

Morning if hyperglycaemia mostly later in day

May need to look at twice daily insulin

• Wean off sulphonylurea

Insulin Therapy: The When?

Poor Glycaemic control:

– HbA1c > 53mmol/mol (7.0%) despite maximal tolerated oral therapy ?

Symptomatic

Insulin Therapy: The When?

Prepare patient in advance.

• Progressive disease. Likely to be needed at some stage.

Don’t use insulin as a threat!

• If you don’t exercise you will need insulin….

When the patient is ready!

• Optimised diet and lifestyle

• Optimised oral hypoglycaemics

• Compliance

• Home glucose monitoring

Insulin Therapy: Summary Why?

• DCCT and UKPDS. Reduced complications

Who?

• All with Type 1 diabetes

• Anyone with Type 2 diabetes, but…

What?

• Anything goes. Start with once daily NPH insulin (protophane/humulin N) or Glargine. Continue Metformin.

When?

• Consider when HbA1c > 53 mmol/mol (7.0%) despite optimal other care

• When the patient is ready