Achieving ISPAD Clinical Guidelines Offers

Cardiorenal Protection for Youth with

Type 1 Diabetes
Petter Bjornstad, M.D.; Laura Pyle, Ph.D; Nhung
Nguyen, M.P.H.; Janet K. Snell-Bergeon, Ph.D.,
M.P.H.; Franziska K Bishop, M.S; R. Paul Wadwa,
M.D.; David M. Maahs, M.D., Ph.D.

Presenter Disclosures
Petter Bjornstad, M.D.
No conflicts to disclose

Cardiorenal Complications in T1D

CVD and DN remain the leading causes of
morbidity and mortality in T1D
Glucose, BP, and lipid control are considered
the major contributory factors
Unknown whether risk factor control offers
cardiorenal protection in adolescents with
T1D

Objectives and Hypotheses

To investigate the associations between
achievement of ISPAD goals (HbA1c, SBP, DBP,
LDL-C, TG, HDL-C and BMI) with:
Baseline and 2-year follow-up cardiorenal health

We hypothesized:
ISPAD goal achievement at baseline would be
associated with lower odds of cardiorenal risk
factors at baseline and 2-year follow-up

Determinants of Macrovascular
Disease in Type 1 Diabetes
CVD risk factors were measured in a cohort of
300 adolescents with T1D:
Age 12-19 years
T1D for > 5 years duration
Recruited from BDC clinical population

Methods
Relationships between ISPAD goal
achievement at baseline and cardiorenal
health at baseline and 2-year follow-up
(n=297; 15.42.2 years; duration 8.83.0 years;
50% males; 80% NHW; HbA1c 8.91.6%)
Goal achievement was defined as:
- HbA1c<7.5% (58.5mmol/mol)

- HDL-C >35mg/dL (>1.1 mmol/L)

- BP<90% for age, sex and height

- TG <150mg/dL (<1.7 mmol/L)

- LDL-C <100mg/dL (<2.6mmol/L)

- BMI <85% for age and sex

Cardiovascular outcomes
Cardiovascular (measures of arterial stiffness)
PWV
AIx
BrachD

Measured by Sphygmocor
Measured by DynaPulse

Wilkinson, et al. , J Hypertension 1998

Renal outcomes
Renal
Continuous
eGFR by Schwartz (36.5 * height/creatinine)
eGFR by Bouvet (63.2 *[1.2/cystatin C]0.56 * [(96/88.4)/creatinine]0.35 *
[weight/45]0.30 * [age/14]0.40 )

ACR

Dichotomous
Elevated ACR (30mg/g)
Hyperfiltration (135mL/min/1.73m2)

Schwartz et al. CJASN 2009; Sharma et al. , CJASN 2011

Results
We stratified the BDC cohort into participants
who:
Met 1-3 goals (n=222)
Met 4-6 goals (n=75)

Participants who achieved 4-6 goals at

baseline were:
Younger (15.12.0 vs. 16.52.2 years, p<0.0001)
Less advanced pubertal status
(Tanner 4-5: 74.8 vs. 92.0%, p=0.002)

Univariate models
Variables

ISPAD goals attained at

baseline
1-3 goals
4-6 goals
(n=75)
(n=222)

P-value

Cardiovascular variables
PWV at baseline (m/s)
5.70.7
5.20.6 <0.0001
PWV at follow-up (m/s)
6.10.8
5.70.7 0.0001
BrachD at baseline (%/mm Hg)
6.41.1
6.91.3 0.004
BrachD at follow-up (%/mm Hg)
0.81
6.61.2
6.71.2
AIx* HR75 at baseline (%)
2.0 (-2.7-9.0) 2.7 (-3.0-9.0)
0.85
AIx* HR75 at follow-up (%)
6.5 (-0.8-10.5) 4.7 (-2.2-10.0)
0.17
Renal variables
Baseline eGFR by Bouvet
13422
11617 <0.0001
Follow-up eGFR by Schwartz
10923
9915 0.0003
Baseline eGFR by Schwartz
0.97
10921
10820
Baseline ACR* (mg/g)
7 (5-15)
7 (4-13)
0.98
Follow-up ACR* (mg/g)
7 (4-16)
6 (4-13)
0.12

Least square means

Variables

Model adjusted for baseline Tanner

stage, sex, and baseline T1D duration
1-3 goals
4-6 goals P-value
attained at
attained at
baseline
baseline
(n=75)

Cardiovascular variables
Baseline PWV (m/s)
5.40.1
Follow-up PWV (m/s)
5.70.1
Baseline BrachD (%/mm Hg)
6.90.2
Follow-up AIx HR75 (%)
8.41.6
Renal variables
Baseline eGFR Bouvet
1273
(mL/min/1.73m2)
Follow-up eGFR Schwartz

(mL/min/1.73m2)

1163

(n=222)
5.10.1 0.0001
5.50.1
0.03
7.30.1
0.02
5.41.0 0.0498
1142 <0.0001
1042 <0.0001

Odds of hyperfiltration at baseline in

subjects who met 1-3 vs. 4-6 goals

N=56

N=36

Odds of hyperfiltration
at follow-up in
O d d s o f h y p e r f ilt r a t io n a t f o llo w - u p in s u b je c t s w
t 1 - 3 g o a ls v s 4 - 6 g o a l s
subjects who metm e1-3
vs. 4-6 goals

O R : 2 0 .0 ( 9 5 % C I 3 .8 - 1 0 5 .2 , p = 0 .0 0 0 4 )

F o llo w - u p h yp e r f ilt r a t io n ( S c h w a r t z )

0
1

0
1

0
9

0
8

0
7

0
6

0
5

0
4

0
3

0
2

0
1

N=11

O d d s r a t io s
( A d ju s te d fo r a g e , s e x a n d T 1 D d u r a tio n )

Limitations
Observational design
Mostly post-pubertal cohort not applicable
to pre-pubertal adolescents
Estimated rather than measured GFR
Cystatin C only available at baseline visit
Surrogate outcomes (risk factors of cardiorenal health)

Conclusions
7% of participants met all ISPAD goals
25% met 3 ISPAD goals
>3 goals at baseline associated with
cardiorenal protection at baseline and 2-year
follow-up
Achieving ISPAD goals in adolescence may
translate to better long-term health.

Acknowledgements
Special thanks to the patients and their family
for their participation.
Study supported by JDRF (11-2007-694),
NIDDK (DK075360) and NIH/NCATS Colorado
CTSI Grant Number (UL1 TR000154)

Thank you

Results: ISPAD Targets Attainment

BDC Cohort
73%

94% 94%

T1DX
78%

91% 89%

73%

69% 69%
62%

21%
15%

HbA1c <7.5%

BP <90th

LDL-C
<100mg/dL

HDL-C >
35mg/dL

TG<150mg/dL

BMI <85th
percentile

PWV and AIx