Transcript Slide 1
Reducing Risk in Type 1 Diabetes – A Practical Approach
Jay S Skyler on behalf of the
Global Partnership for Effective Diabetes Management
This slideset was developed in 2009 with support from GlaxoSmithKline
Global Partnership for Effective Diabetes Management
: Identifying and addressing gaps in T1DM care
• There are considerable gaps in care of adults with T1DM:
– High proportion continue to develop complications – Majority do not achieve glycemic goals – Patients face many challenges e.g. insulin dose adjustment, hypoglycaemia, impact on daily life Aschner P,
et al. Int J Clin Pract
2009: in press.
Global Partnership for Effective Diabetes Management
: Identifying and addressing gaps in T1DM care
•
The Global Partnership
has developed practical guidance to improve care in T1DM by addressing:
– management of hyperglycemia – insulin therapy – management of CV risk factors – psychological aspects – team approach to care Aschner P,
et al. Int J Clin Pract
2009: in press.
Importance of management of hyperglycemia
DCCT: Early intensive therapy reduced the incidence of retinopathy and microalbuminuria in T1DM
Cumulative incidence of retinopathy progression Cumulative incidence of microalbuminuria 60 50 40 30 20 10 0 0 1 2 54% risk reduction* Conventional 3 4 5 Intensive 6 Time (years) 7 8 9 60 50 40 30 20 10 0 0 1 2 39% risk reduction* 3 Conventional 4 5 6 Intensive Time (years) 7 8 9
*Intensive vs conventional treatment Median HbA1c during 6.5 year follow-up period: intensive group, 7.3%; conventional group, 9.1%. N = 1441 DCCT Research Group.
N Engl J Med
1993;
329:
977 –986.
Copyright 1993 Massachusetts Medical Society. All rights reserved.
Cumulative incidence of retinopathy over 10 years in EDIC following DCCT: the ‘legacy effect’ Error bars are 95% CI. N = 1211 60 50
53% risk reduction with intensive therapy, 95% CI, 43% –61%; P <.001
40 30 20 10 0 12 0 10 8 6 + + 1 + + 2 3 + + + + 4 5 + + + + 6
P
<.001
<.001 <.001
.002
DCCT closeout 1 2 .08
.12
.12
3 4 5 6 EDIC study year 7 + + + + + + .64
7 8 .84
8 9 + + + + .36
9 10 .01
10 Conventional Intensive Conventional Intensive White NH,
et al
.
Arch Ophthalmol
2008;
126:
1707 –1715.
Copyright © 2008 American Medical Association. All rights reserved.
DCCT/EDIC: glycemic control reduces macrovascular complications in T1DM
0.06
57% risk reduction in non-fatal MI, stroke or CVD death* 0.04
Conventional treatment 0.02
Intensive treatment 0.00
0 1 2 3 4 5 6 7 8 DCCT (intervention period) 9 10 11 12 13 14 15 16 17 18 19 20 21 EDIC (observational follow-up) Years
*Intensive vs conventional treatment. N = 1441 DCCT/EDIC Study Research Group.
N Engl J Med
2005;
353:
2643 –2653.
Copyright 2005 Massachusetts Medical Society. All rights reserved.
Clinic vs ‘real-world’ data: incidence of
proliferative retinopathy (
DCCT-EDIC/EDC) 70 60 50 40 30 20 10 EDC DCCT DCCT – Conventional therapy – Intensive therapy 0 1 3 5 7 9 11 13 15 17 19 Diabetes duration, years 21 23 Cumulative incidence of proliferative retinopathy or worse 25 27 29 DCCT/EDIC Research Group.
Arch Intern Med
2009;
169
:1307 –1316.
Copyright © 2009 American Medical Association. All rights reserved.
Clinic vs ‘real-world’ data: incidence of
nephropathy (
DCCT-EDIC/EDC) 40 35 30 25 EDC DCCT DCCT – Conventional therapy – Intensive therapy 20 15 10 5 0 1 3 5 7 9 11 13 15 17 19 Diabetes duration, years Nephropathy was defined as albumin excretion rate ≥ 300 mg/24 h, serum creatinine ≥ 2 mg/dl, or dialysis or renal transplant 21 23 25 27 29 DCCT/EDIC Research Group.
Arch Intern Med
2009;
169
:1307 –1316.
Copyright © 2009 American Medical Association. All rights reserved.
Clinic vs ‘real-world’ data: incidence of
CVD (
DCCT-EDIC/EDC) 20 18 15 13 EDC DCCT DCCT – Conventional therapy – Intensive therapy 10 3 0 8 5 1 3 5 7 9 11 13 15 17 19 Diabetes duration, years 21 23 CVD was defined as: non-fatal myocardial infarction or stroke, CVD death, subclinical MI, angina, angioplasty or coronary artery bypass 25 27 29 DCCT/EDIC Research Group.
Arch Intern Med
2009;
169
:1307 –1316.
Copyright © 2009 American Medical Association. All rights reserved.
Management of hyperglycemia
Glycemic targets for individuals with T1DM
Characteristic HbA1c Fasting⁄ preprandial glucose, mg⁄dl (mmol/l) Postprandial glucose, mg⁄dl (mmol/l) ADA < 7.0%
70 –130 (3.9
–7.2) < 180* (< 10.0)
CDA ≤ 7.0%
72 –126 (4.0
–7.0) 90 –180 † (5.0
–10.0)
IDF 6.2
–7.5%
91 –120 (5.1
–6.5) 136 –160 ‡ (7.6
–9.0)
NICE (UK) ≤ 6.5–7.5%
72 –144 (4.0
–8.0) < 180 ‡ (< 10.0) ADA = American Diabetes Association; CDA = Canadian Diabetes Association; IDF = International Diabetes Federation; NICE = National Institute for Health and Clinical Excellence The CDA guidelines note that HbA1c goals and strategies must be tailored to the individual with diabetes, with consideration given to individual risk factors.
ADA and CDA glycaemic targets are for type 1 and type 2 diabetes.
* Peak postprandial capillary plasma glucose. † 90–144 mg/dl (5.0–8.0 mmol/l) if HbA1c target not being met.
‡ Capillary postprandial glucose 1–2 h after meal.
ADA.
Diabetes Care
2009;
32
(Suppl. 1)
:
S13 –S61. CDA.
Can J Diabetes
2008;
32
(Suppl. 1)
:
S1 –S201. IDF. Desktop guide to Type 1 (insulin-dependent) diabetes, 1998; Brussels: IDF. NICE. Clinical Guideline
15.
2004; London, UK: NICE.
Majority of patients with T1DM do not reach glycemic targets
100 90 80 70 60 50 40 30 20 10 0
74% 81% 83% 87%
UK 1 HbA1c > 7.5%
DCCT-EDIC Intensive EDC DCCT-EDIC Conventional
US 2 HbA1c > 7.0%
1. Calvert M,
et al. BMJ
2009;
338:
b1870.
2. DCCT/EDIC Study Research Group.
Arch Intern Med
2009;
169:
1307 –1316.
Managing hyperglycemia in type 1 diabetes
The Global Partnership recommends:
Aim for as good glycemic control as possible while minimizing the risk of hypoglycemia Ensure regular and appropriate monitoring for complications Aschner P,
et al. Int J Clin Pract
2009: in press.
Insulin therapy
Intensive insulin therapy using a basal-bolus approach: considered best treatment in T1DM • Intensive insulin therapy using a basal-bolus approach, whether as multiple daily injections or pump therapy, is considered best treatment for individuals with T1DM regardless of age – Provides greater glycemic control, reduces risk of complications, preserves β-cell function (DCCT) 1-3 • Choice of insulin/mode of delivery should be guided by factors such as: – hypoglycemia, age, lifestyle, general health, motivation, ability for self-management and diet, availability/accessibility 1. DCCT Research Study Group.
2. DCCT/EDIC Research Study Group.
N Engl J Med
1993;
N Engl J Med
329:
977 –986.
2005;
353:
2643 –2653. 3. DCCT Research Study Group.
Ann Intern Med
1998;
128:
517 –523.
DCCT: C-peptide levels decrease with increasing duration of T1DM
0.6
0.5
Basal C-peptide Stimulated C-peptide
0.4
0.3
0.2
0.1
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Duration of T1DM (years)
Mean ± SEM basal (solid) and stimulated (stripes) C-peptide levels shown for 610 patients, mean age 25 years (range 13 –39 years). C-peptide levels measured following meal challenge Reproduced with permission from DCCT Research Study Group.
J Clin Endocrinol Metab
1987;
65:
30 –36.
DCCT: Intensive therapy preserves residual β-cell function
1 0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0 Intensive therapy Conventional therapy Intensive Conventional Eligibility Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Number of patients in each treatment group who were evaluated 138 131 80 53 32 8 2 165 150 63 32 22 3 0
DCCT Research Study Group.
Ann Intern Med
1998;
128:
517 –523.
Copyright © 1998 American Medical Association. All rights reserved.
HbA1c in T1DM is better with continuous subcutaneous insulin infusion (CSII)
Study
Berg 1998 Ciavarella 1985 DeVries 2002 Ziegler 1990 Oslo Study 1985 –1988 Chiasson 1984 Hanaire-Broutin 2000 Home 1982 Hoogma 2006 Saurbrey 1988 Schiffrin 1982 Scmitz 1989 Total (95% CI)
SMD (random (95% CI) -5.00
-4.00
-3.00
-2.00 -1.00
Favors CSII 0 1.00
2.00
Favors MDI Weight (%)
7.90
4.46
10.17
9.67
7.90
7.21
10.41
6.62
12.35
8.60
8.10
6.62
SMD (95% CI)
-0.92 (-1.64, -0.20) -3.19 (-4.43, -1.95) -0.81 (-1.28, -0.35) 0.16 (-0.36, 0.68) -0.29 (-1.01, 0.42) 0.33 (-0.47, 1.13) -0.56 (-1.00, -0.12) -0.84 (-1.72, 0.04) -0.22 (-0.40, -0.04) 0.00 (-0.64, 0.64) -0.41 (-1.10, 0.28) -1.36 (-2.24, -0.48) 100.00
-0.55 (-0.87, -0.22) Jeitler K,
et al. Diabetologia
2008;
51:
941 –951.
Incidence of severe hypoglycemia is reduced with CSII
Study Severe hypoglycemia rate ratio Weight (%) SMD (95% CI)
Bode (poor control) Bode (good control) Kaderman Maniatis Rizvi Litton Linkeschova Bruttomesso Rudolph, Hirsch Plotnik Cohen Hunger-Dathe Weintrob Weinzimer McMahon Siegel-Czarkowski Alemzadeh Mack-Fogg Sciaffini Rodrigues Lepore Hoogma Overall (
l
2 = 84.2%,
P
= 0.00)
0.5
Favors MDI 1.0
2.0
5.0
10 Favors CSII
5.84
4.66
5.11
3.34
3.26
2.19
5.23
5.07
5.87
5.13
2.04
5.75
3.04
6.03
5.60
2.17
3.58
5.40
3.61
5.75
5.61
5.73
100.00
5.55 (3.57, 8.61) 10.50 (4.24, 26.01) 6.47 (3.09, 13.55) 1.29 (0.31, 5.42) 8.00 (1.84, 34.79) 5.75 (0.72, 45.97) 13.92 (6.95, 27.86) 3.44 (1.62, 7.33) 3.81 (2.49, 5.84) 2.18 (1.05, 4.52) 4.69 (0.52, 41.98) 3.62 (2.23, 5.85) 3.00 (0.62, 14.44) 2.11 (1.50, 2.96) 2.89 (1.67, 4.98) 7.07 (0.87, 57.46) 2.51 (0.67, 9.47) 2.09 (1.12, 3.92) 1.25 (0.34, 4.65) 35.41 (29.94, 57.15) 3.50 (2.04, 6.01) 2.50 (1.53, 4.08) 4.19 (2.86, 6.13)
25
Pickup JC & Sutton AJ.
Diabet Med
2008;
25:
765 –774.
Reprinted by permission of John Wiley & Sons, Inc.
Initiation of insulin
The Global Partnership recommends:
Initiate basal-bolus regimen as early as possible Provide all patients with a structured educational programme at initiation of insulin and thereafter Aschner P,
et al. Int J Clin Pract
2009: in press.
Adjusting insulin dosages: practical barriers facing individuals with T1DM • Patients must adjust insulin doses in response to many factors to minimize risk of hypo- or hyperglycemia: – carbohydrate intake, lifestyle, exercise, intercurrent illness • Modification of insulin dosages based on diet and exercise should be considered an essential part of patient education – adapted to local diet and lifestyle • Patients may not know the effect of factors such as exercise or alcohol on glucose levels and need for appropriate adjustment of insulin therapy – 64% of patients with T1DM do not achieve recommended physical activity levels due to barriers such as fear of hypoglycaemia 1,2 1. Brazeau AS,
et al. Diabetes Care
2. Plotnikoff RC,
et al. Med Sci Sports Exerc
2008;
31:
2108 –2109. 2006;
38:
1526 –1534.
Modification of insulin dosages based on diet and exercise: DTTP study
HbA 1c 10 9 8 7 6 5 Baseline 1 year Mean difference: –0.7% (95% CI –0.9 to –0.6%, P < 0.0001) Severe hypoglycemia 0.7
0.6
0.5
0.4
0.3
0.2
0.1
0 Baseline 1 year Mean difference: −0.21 events per patient-year (95% CI −0.32 to −0.11, P = 0.0001)
Dusseldorf Diabetes Treatment and Teaching Programme (DTTP): N = 9,583.
Samann A,
et al. Diabetologia
2005;
48:
1965 –1970.
Precipitating causes of DKA
Precipitating factor Infection Omission/reduction of insulin dose First presentation of diabetes Myocardial infarction No cause identified Percentage of cases
28 –43% 13 –45% 10 –20% 1% <40% Wallace TM & Matthews DR.
QJM
2004;
97:
773 –780.
Reprinted by permission of Oxford University Press.
Self-monitoring blood glucose (SMBG): a fundamental aspect of insulin therapy • SMBG is so fundamental that insulin therapy should always comprise insulin therapy
plus
SMBG • Despite clear benefits, up to 64% of patients do not regularly self-monitor 1 • Barriers include patient motivation, psychological barriers, cost, socioeconomic status, education • Patients should receive appropriate training in SMBG when insulin therapy is initiated and periodically thereafter 1. DCCT/EDIC Research Study Group.
Arch Intern Med
2009;
169:
1307 –1316.
SMBG ≥ 3-times per day associated with better glycemic control in T1DM
9.5
9.0
8.5
8.0
7.5
7.0
No utilization Less than daily Daily At least 3x daily Adjusted HbA1c by strip use (average strips per day)
Reproduced from Karter AJ,
et al. Am J Med
2001;
111:
1 –9.
Copyright 2001 with permission from Elsevier.
JDRF study: Sustained HbA1c lowering in T1DM patients with HbA1c >7.0% using CGM
Treatment time (months)
JDRF CGM Study Group.
Diabetes Care
2009;
32:
2047 –2049.
JDRF study: Maintained HbA1c with less hypoglycemia in T1DM patients with HbA1c < 7.0% using CGM
Treatment time (months)
JDRF CGM Study Group.
Diabetes Care
2009;
32:
2047 –2049.
Self-monitoring of blood glucose
The Global Partnership recommends:
Ensure that self-monitoring is universally adopted as an integral part of insulin therapy Aschner P,
et al. Int J Clin Pract
2009: in press.
Hypoglycemia: can affect many aspects of care in T1DM • In DCCT, severe hypoglycemia three times higher with intensive vs conventional therapy 1,2 • Almost one-third of patients who experience severe hypoglycemia have a second episode within 4 months 2 • Almost half of severe hypoglycemic episodes occur at night 1 • Risk factors include strict glycemic control, prior episode of severe hypoglycemia, longer duration of diabetes, autonomic neuropathy, hypoglycemia unawareness • In the DCCT, intensively treated patients with greater residual β-cell function had a significantly lower rate of hypoglycemia vs those with less/no residual β-cell function 3 1. DCCT Research Study Group.
Am J Med
1991;
90:
450 –459. 2. DCCT Research Group.
Diabetes
1997;
46:
271 –286. 3. Steffes M,
et al
. Diabetes Care 2003;
26:
832 –836.
DCCT: Risk of severe hypoglycemia versus HbA 1c in intensive and conventional groups 100 80 60 40 20 0 5 6 7 8 9 10 11 HbA1c (%) during study Intensive 12 Conventional 13 14 N = 1,441 DCCT Research Study Group.
Diabetes
1997;
46:
271 –286.
Copyright 1997 American Diabetes Association. Reprinted with permission from The American Diabetes Association.
Incidence of hypoglycemia in the DCCT
14.0
12.0
10.0
8.0
6.0
4.0
2.0
0 Undetectable Minimal Baseline-only Sustained Stimulated C-peptide group
*Both treatment groups (intensive and conventional therapy). Undetectable 0.03 nmol/L; minimal 0.04
–0.20 nmol/L; baseline-only (> 0.2 nmol/L at baseline, < 0.2 nmol/L thereafter); sustained (> 0.2 nmol/L at baseline and 1 year later). Rates were compared (horizontally) between stimulated C-peptide groups. Rates between all groups were significantly different (
P
< 0.05), except comparison between minimal and baseline-only group Steffes M,
et al. Diabetes Care
2003;
26:
832 –836.
Copyright 2003 American Diabetes Association. Reprinted with permission from The American Diabetes Association.
Effect of impaired awareness of hypoglycemia in T1DM
Awareness of hypoglycemia: Normal Impaired 100 2.5
80 2.0
60 1.5
40 1.0
20 0.5
0 0.0
Percentage Events
Geddes J,
et al. Diabetic Med
2008;
25:
501 –504.
Hypoglycemia
The Global Partnership recommends:
Provide education about prevention, recognition and treatment of hypoglycemia at initiation of insulin therapy and thereafter Aschner P,
et al. Int J Clin Pract
2009: in press.
Management of CV risk factors
Higher absolute risk of CVD in T1DM at younger age in men and women
Absolute CVD risk per 1000 person-years
T1DM 0.8 (0.4-1.6)
MEN
Without diabetes 0.07 (0.02-0.2)
WOMEN Absolute CVD risk per 1000 person-years
T1DM 0.5 (0.2-1.3) Without diabetes 0.05 (0.01-0.2) ≤35 years 35-45 years 45-55 years 65-75 years >75 years 4.8 (3.2-7.1) 10.6 (7.3-15.2) 35.2 (21.6-57.5) 122.2 (69.4-215.2) 1.1 (0.8-1.6) 3.6 (2.8-4.7) 15.3 (11.3-20.8) 34.2 (23.1-50.6) 3.5 (2.1-6.1) 10.2 (6.7-15.5) 38.7 (24.1-62.3) 87.3 (39.2-194.3) 0.2 (0.09-0.6) 1.1 (0.6-1.9) 4.9 (2.8-8.4) 28.2 (18.0-44.2) Soedamah-Muthu SS,
et al. Diabetes Care
2006;
29:
798 –804.
Copyright 2006 American Diabetes Association. Reprinted with permission from The American Diabetes Association.
Blood pressure, lipid and aspirin therapy
Study
ACCORD 1,4 ADVANCE 2,4 VADT 3,4
SBP mmHg
127/67 136/74 127/68
LDL-C mmol/L (mg/dL)
2.35 (91) 2.64 (102) 2.07 (80)
On statins, %
88 47 84
On aspirin, %
76 56 87 SBP = systolic blood pressure; LDL-C = LDL-cholesterol 1. ACCORD Study Group.
N Engl J Med
2. ADVANCE Collaborative Group.
N Engl J Med
2008;
358:
2545 –2559.
2008;
358:
2560 –2572.
3. Duckworth W,
et al. N Engl J Med
4. Skyler JS,
et al. Diabetes Care
2009;
360:
129 –139.
2009;
32:
187 –192.
Managing cardiovascular risk factors Patients with T1DM of ≥ 15 years’ duration and aged >30 should be considered at high risk of CVD
CDA.
Can J Diabetes
2008;
32
(Suppl. 1)
:
S1 –S201.
Other risk factors
The Global Partnership recommends:
Manage all CV risk factors Aschner P,
et al. Int J Clin Pract
2009: in press.
Psychological aspects
Depressive symptoms significantly related to HbA1c in T1DM
Significant positive relationship between BDI score and HbA1c 12 (r = 0.44, P < 0.02) 11 10 9 8 7 6 0 5 10 15 20 Beck Depression Inventory (BDI) score
BDI score ≥16 indicates possible clinical depression Reproduced with permission from Van Tilburg MA,
et al. Psychosom Med
2001;
63:
551 –555.
Disordered eating behavior associated with higher risk of retinopathy & nephropathy in young women with T1DM
Disordered-eating status at baseline
Highly disordered Moderately disordered Nondisordered
Diabetic retinopathy at follow-up*
86% (6/7) 43% (6/14) 24% (12/50) Values are % (n with complications/total n) Mean age at baseline ( ± SD): 15 ± 2 years (range 12 –18)
Abnormal urinary albumin excretion at follow-up
43% (3/7) 20% (3/15) 18% (9/50) Rydall AC,
et al. N Engl J Med
1997;
336:
1849 –1854.
Copyright 1997 Massachusetts Medical Society. All rights reserved.
Psychological aspects of type 1 diabetes
The Global Partnership recommends:
Explore psychological issues associated with type 1 diabetes and treat/refer, as appropriate Aschner P,
et al. Int J Clin Pract
2009: in press.
Team approach to care
A multidisciplinary approach to care
• Many complexities involved in treating patients with T1DM • Adopting a team approach that involves a broad range of disciplines is essential • Where possible, team should include: patient, diabetes specialist, primary care physician, nurse, dietitian, podiatrist and psychologist/psychiatrist, as well as family and friends. • All members of the team should work together to ensure continuity of care Aschner P,
et al. Int J Clin Pract
2009: in press.
A team approach to diabetes care
The Global Partnership recommends:
Adopt a multidisciplinary team approach with shared goals and recommendations Aschner P,
et al. Int J Clin Pract
2009: in press.
Practical recommendations for the management of adults with T1DM • • • • •
Aim for as good glycemic control as possible while minimizing the risk of hypoglycemia Ensure regular and appropriate monitoring for complications Initiate basal-bolus regimen as early as possible Provide all patients with a structured educational programme at initiation of insulin and thereafter Ensure that self-monitoring is universally adopted as an integral part of insulin therapy
Aschner P,
et al. Int J Clin Pract
2009: in press.
Practical recommendations for the management of adults with T1DM • • • •
Provide education about prevention, recognition and treatment of hypoglycaemia at initiation of insulin therapy and thereafter Manage all CV risk factors Explore psychological issues associated with T1DM and treat/refer, as appropriate Adopt a multidisciplinary team approach with shared goals and recommendations
Aschner P,
et al. Int J Clin Pract
2009: in press.