Evaluation of differing type 1

diabetes treatment regimens in

youth in Rwanda.
Trevor J Orchard
on behalf of Deborah Edidin, Sara Marshall, Laurien Sibomana
and Rachel Miller (University of Pittsburgh Life for a ChildPitt
Initiative) ; Francois and Crispin Gishoma, Vedaste Kaberuka,
Etienne Uwingabire ( Association Rwandaise des Diabetiques);
Wilson Rubanzana, Bernard Rwabufigiri, Jean-Baptiste Kakoma
(National University of Rwanda/School of Public Health)
and Graham Ogle (Life for a Child).
ISPAD, TORONTO, September 3rd 2014
NIH/NIDDK RC4 DK 090809

Life for a Child (LFAC) is a program operated by the International Diabetes

Federation, an organization that strives to increase access to and advance
treatment, policy, management, education, and prevention for youth with
diabetes.
LFAC supports children with type 1 diabetes through 25 years of age. They
primarily supply insulin and blood testing supplies for youth in developing
countries and are expanding into assistance with education, HbA1c testing
and complication screening e.g. micro-albuminuria.

Rwanda ARD

Started in 2003 with 3 children; grew to 30 by 2006

- 301 in 2009
- 390 in 2010
- 634 in 2011
- 684 in 2012
- 800 in 2013

- Relationship with University of Pittsburgh started

in 2008, with the first Pitt MPH Student Visit in
June-July 2009. This is an annual summer
internship for a 6 week period ; 8 students so far.

The youth onset diabetes problem in Rwanda

Under diagnosis
Cost of treatment
Education
Food insecurity

Background and Rationale

The major challenges to delivering diabetes care in Rwanda, include

limited professional and patient education, lack of insulin and blood
testing supplies, and food insecurity (i.e.uncertainty as to the timing
and content of meals).

We hypothesize that the diabetes care of Rwandese youth can be

improved by implementing a treatment regimen based on initial
basal insulin alone with later introduction of meal time coverage as
the youth and their caregivers become more educated and skilled
with self monitoring techniques. This is in contrast to the current
approach which requires a more rigid diet and has a greater risk of
low blood sugar.

Effects of Regular HbA1c Testing

Clinical characteristics of one- and two- year follow up visits as
compared to baseline (and one-year visit for two-year follow
N=221
N=170
up).

* Indicates significance at = 0.05 to year before

Indicates significance at = 0.05 to two -years before
a - 118 tested; b 180 tested; c 65 tested; d- 85 tested; e -105 tested; f -134 tested; g -47 tested; h -69
tested; k -72 tested; m- 5 tested.

Specific Aim
To compare a simplified diabetes management protocol
based, initially, on a single daily dose of insulin, to current
conventional management involving combined regular and
NPH insulin in youth with Type 1 diabetes in Rwanda.
The initial study was planned as a pilot study (consisting of
50 children) from the ARD and Gisenyi district.
The plan was to develop a nationwide trial based on this
pilot experience
NIH/NIDDK/RC4 funding under the ARRA
Approved by Pitt IRB, Rwanda NEC
Safety Officer : Dorothy Becker
DSMB : Chaired by Larry Deeb
No pharmaceutical input or assistance

Study Population :Inclusion and Exclusion Criteria

Inclusion Criteria:
Resident of Rwanda
Type 1 diabetes (defined as needing continual
insulin therapy within a year of diagnosis)
Aged 24 years or less
Life expectancy of at least 3 years

Exclusion Criteria:
Failure to obtain informed consent
Believed by investigative team to require additional
diabetes management outside the scope of this trial
protocol

Study protocol

5 visits at 6 monthly intervals:

V1- Screening/consent followed by run in
phase
V2- Randomisation to either continuing
NPH/Regular or glargine
V3- Follow up
V4- Outcome HbA1c
V5- Satisfaction/ QOL interview

Consent Procedures
Informed consent was obtained from either the participant (if
aged 21 or older) or from the participants parent/legal
guardian (if less than 21 years).For those aged 14-20 years, a
child assent was also obtained. The consent/assent form was
translated into Kinyarwanda and additional assistance
provided by a patient advocate for those illiterate.
Three components of consent:

1. Randomization to basal vs current insulin treatment

2. Permission for use of clinical data for research
3. Completion of QOL and satisfaction survey

Demographic Characteristics of the Trial Population to a Comparable Group

(under 26 with more than 1 year duration) from the LFAC Program

Descriptive
N
Age (years)
Diagnosis Age (years)
Duration (years)
Male % (n)
Female % (n)

LFAC
495
20.9+4.5
15.3+5.0
5.5+3.2
54.1 (268)
45.8 (227)

Trial
50
20.5+4.7
14.8+5.0
5.7+3.6
48.0 (24)
52.0 (26)

Our sample is representative of the LFAC population in Rwanda

p-value
0.55
0.50
0.68
0.46
0.46

Diabetes Care
Home glucose monitoring: Both groups provided with a
glucose meter and sufficient strips to test twice daily. These
results will also be made available to and reviewed by the
ARD staff and will be used for further dose adjustments
Diabetes Education: All participants will be provided
information on type 1 diabetes, how to properly use their
glucometers, and how to adjust their insulin doses
appropriately
All participants will then continue to have usual follow up
contact with the ARD in Kigali, and through cell phone
consultations as needed.
Everyone provided with a cell phone if they didnt have
one.

Data Analysis
The primary outcome for this study is the level
of glycemic control as measured by HbA1c at
the 18th month visit (V4)
Secondary outcomes include
microalbuminuria, BMI, diabetes knowledge,
and quality of life
Intention To Treat analysis is used with the last
observation carried forward if needed

Results
Forty eight of the 50 randomized youth completed the
protocol.
One individuals parent refused to continue with glargine
after 3 months
One individual attended V4 out of the time window.
Two died, both were randomized to glargine group.
1st death was probable hypoglycemia. She was a 23 year
old with a diabetes duration of 6 years and randomized
to glargine in Nov 2011. May 2012 had a severe
hypoglycemic event after which she was given a
glucagon kit. June 12th her brother found her at 10 pm
comatose , blood sugar 2.6 mmol/l so he tried the
glucagon without success, and she died at midnight
which is when he called the ARD.

Results (continued)

2nd death was a 20 year old male with a T1D of 4 years

who lived in extreme poverty with a mute grandmother.
His A1c was regularly > 14.0% and he frequently lost
significant weight when food was scarce. He was
randomized to glargine in Nov 2012 . Admission to ARD
in hypoglycemia on April 15th 2013 when he had severe
diarrhoea and vomiting for a month. Early on May 2nd
2013 he died having complained of a headache the
previous day. No contact with ARD or any HCP. Glucose
meter readings were 128 mg/dl at 7.00 pm on May 1st,
177, 572 mg/dl and HI on April 30th and 529 mg/dl
evening April 29th. Cause of death was thought to be
predominately malnutrition though hypoglycemia could
not be excluded.

Rwanda Evaluation of Differing T1D Regimens Pilot Trial 2011-2014:

Baseline Characteristics (Mean SD or % (n)) by Randomized Group (Visit 2)

Overall (n=50)

Glargine (n=26)

NPH/regular
(n=24)

p-value

Age (years)

20.1 (4.6)

19.1 (5.1)

21.2 (3.9)

0.11

Diabetes Duration (years)

5.72 (3.35)

5.21 (2.74)

6.28 (3.90)

0.27

Sex, % female

52.0% (26)

61.5% (16)

38.5% (10)

0.16

HbA1c (%)

9.36 (2.31)

9.28 (2.34)

9.44 (2.32)

0.80

HbA1c<9%

46.0% (23)

50.0% (13)

41.7% (10)

0.55

Height (cm)

161.0 (12.4)

159.1 (13.77)

162.8 (10.7)

0.50

Weight (kg)

55.5 (11.1)

53.9 (12.6)

57.2 (9.1)

0.49

Any episodes of hypoglycemia

18.2% (8)

22.7% (5)*

13.6% (3)*

0.70

Any episodes of ketoacidosis

15.6% (7)

13.0% (3)**

18.2% (4)**

0.70

* Lantus n=22, NPH n=22; ** Lantus n=23, NPH n=22

Rwanda Evaluation of Differing T1D Regimens Pilot Trial 2011-2014:

Follow up V4 Values by Treatment Group (Mean (SD) and median (IQR) or %(n)

p-value

p-value, adjusted
for duration

p-value, adjusted
for duration and
baseline

9.10 (2.04)
9.05 (7.35-10.05)

0.39

0.77

0.12

46.2% (12)

45.8% (11)

0.98

0.94

0.42

Height (cm)

160.6 (13.0)
162.8 (153.6-168)

163.5 (10.7)
163.9 (156.9-170.3)

0.40

0.40

0.20 (also adjusted

for sex)

Weight (kg)

55.2 (12.0)
56.0 (49-64)

58.2 (8.5)
59.0 (54.0-63.5)

0.30

0.54

0.20 (also adjusted

for sex)

New episodes of
hypoglycemia

9.1% (2)

22.7% (5)

0.41

0.27

New episodes of
ketoacidosis

4.6% (1)

Glargine
(n=26)

NPH/regular
(n=24)

HbA1c (%)

9.68 (2.57)
9.10 (7.6-11.9)

HbA1c<9%

Rwanda Evaluation of Differing T1D Regimens Pilot Trial 2011-2014:

Change Analyses V2 to V4
HbA1c, Height, and Weight Continuous Change Analysis
Glargine (n=26)
Visit 2

Visit 4

Change

Comparison
between
groups

NPH/regular (n=24)
p-value

Visit 2

Visit 4

Change

p-value

p-value

HbA1c
(%)

9.28 (2.34)

9.68 (2.57)

+0.40 (1.65)

0.22

9.44 (2.32)

9.10 (2.04)

-0.34 (1.54)

0.48

0.10

Height
(cm)

159.1 (13.8)

160.6 (13.0)

+1.5 (2.0)

0.001

162.8 (10.7)

163.5 (10.7)

+0.66 (1.48)

0.04

0.20

Weight
(kg)

53.9 (12.6)

55.2 (12.0)

+1.3 (3.9)

0.22

57.2 (9.1)

58.2 (8.5)

+1.1 (3.8)

0.35

0.84

22.5

17.5
15.0

Percent

Glargine

20.0

12.5
10.0
7.5
5.0

group

2.5
0
22.5

17.5
15.0

Percent

NPH/Regular

20.0

12.5
10.0
7.5
5.0
2.5
0
-4.25

-3.75

-3.25

-2.75

-2.25

-1.75

-1.25

-0.75

-0.25

0.25

changeHbA1c

0.75

HbA1c Change

1.25

1.75

2.25

2.75

3.25

3.75

4.25

Conclusions and Future Plans

This is a pilot study and as such was a success showing that a
trial of this nature could be conducted in this setting.
Though not powered for a definitive result, the trends
towards worse control yet less frequent hypoglycemia with
glargine were as anticipated.
The two deaths are of great concern and as both occurred on
glargine treatment (though well after switching regimens)
caution in advocating wide spread glargine use seems
appropriate.
Future analyses include the QOL and satisfaction survey and
trying to identify characteristics of those who did particularly
well or poorly on a specific regimen.

Rwanda Evaluation of Differing T1D Regimens Pilot Trial 2011-2014:

Change Analyses V2 to V4
HbA1c Categorical Change Analysis

HbA1c Reduction 1%

Glargine
(n=26)
19.2% (5)

HbA1c Stable (change of <1% 50.0% (13)

in either direction)
HbA1c Increased 1%
30.8% (8)

NPH/Regular p-value
p-value
(n=24)
difference trend
33.3% (8)
0.48
0.24
45.8% (11)

16.7% (4)