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DEPARTMENT OF BIOCHEMISTRY
SCHOOL OF HEALTH SCIENCES
INVESTIGATOR
DR. NGWEINA FRANCIS MAGITTA, MD, PHD
ABSTRACT
Type 1 diabetes (T1D) is an important childhood illness that causes significant morbidity and
mortality in developing countries. The mainstay for management of T1D is the daily
administration of insulin preparations. Insulin preparations require appropriate handling and
storage at temperatures that ensures preservation of their biological and therapeutic potency.
Typically the storage requires the use of refrigerators which are often not available in the
majority of households in the rural settings in Tanzania.
Previous reports indicate that most countries in Africa, have adapted the use of diverse
traditional methods for storage of insulin preparations. However, the efficacy of these
methods on the preservation of insulin potency has not been systematically evaluated for
validation. The proposed study aims to investigate the effect of these storage methods by
indirect assessment of patients glycaemic control based on three-point measurements of
Fasting Blood Glucose (FBG). The proposed cross-sectional descriptive study, involving
patients aged 35 years solely on insulin therapy for T1D, will be conducted within
Outpatient Department (OPD) at Chamwino District Hospital in Dodoma, Tanzania.
All eligible patients receiving care at the health facility will be recruited into the study prior
to obtaining consent from the patient or where necessary from patients parents or relatives.
Important demographic variables and clinical data will be collected from patients using
structured Clinical and Laboratory Data Sheets together with supplemental data obtained
from case notes and patients guardians and relatives. Data will be analyzed using Excel
spreadsheet software and a p-value of less than 5% will be considered statistically significant.
Ethics approval will be sought from UDSM and Chamwino District Health Authority. The
fieldwork will be conducted for one month at an estimated budget of TZS 850,000. The
findings from this study will provide evidence and opportunity for improving the
management of T1D in rural settings in Tanzania.
TABLE OF CONTENTS
ABSTRACT ................................................................................................................................................. 2
List of Abbreviations and Acronyms ....................................................................................................... 4
1.
BACKGROUND .............................................................................................................................. 5
2.
3.
4.
RATIONALE .................................................................................................................................... 8
5.
5.2.
6.
6.2.
6.4.
7.
8.
9.
10.
11.
12.
REFERENCES ............................................................................................................................ 12
AIDS
CDC
CID
CIP
DNA
Deoxyribonucleic acid
FBG
HIV
HMWT
IDF
NCDs
Non-Communicable Diseases
NPH
OHAs
OPD
Outpatient Department
UDSM
SoHS
TID
Type 1 diabetes
TZS
Tanzanian Shillings
WHO
1. BACKGROUND
Rural areas in developing countries are frequently challenged by the existing cold-chain
delivery and maintenance systems required for preservation of potency for specific drugs,
vaccines and other biologics. In particular, insulin which is required by patients suffering
from T1D requires storage at appropriate temperatures in order to ensure preservation of their
therapeutic potency.
available. Thus patients struggle to store their insulin preparations in facilities that might
expose insulin to increased biodegradation and progressive loss of biological and therapeutic
efficacy.
2. LITERATURE REVIEW
The incidence of diabetes and other chronic non-communicable diseases (NCDs) is
increasing world-wide. The on-going transition in the disease pattern from infectious disease
to chronic non-communicable diseases is currently the global health focus. There is lack of
data on diabetes in countries in Africa including Tanzania. However, the available evidence
indicates that the majority of patients with diabetes typically remain in the community
undiagnosed or those diagnosed usually present late to the health facilities often with
complications or dies outside hospitals
The 7th Edition of the International Federation on Diabetes (IDF) and World Health
Organization (WHO) report indicates that a total of 415 million people are estimated to have
with diabetes worldwide, representing 1 person out of 11 living with diabetes. Further, it is
noted that every 6 seconds a person dies from diabetes representing about 5 million deaths
globally. An estimated 14.2 million adults aged 20-79 years have diabetes in the IDF Africa
region, representing a regional prevalence of 3.2% (with range of 2.1-6.7%). Notably,
diabetes contributes about 321,100 deaths in the IDF Africa region. In IDF Africa region,
T1D among children aged below 15 years is estimated to affect about 46,400 children; with
about 7,600 children being diagnosed annually. However, these figures are mere estimates
are likely to be grossly underestimated due to the fact that the mortality of children with T1D
is estimated to be significantly in Africa. Typically many children with T1D lack access to
insulin, glucose test-strips and appropriately-trained health professionals. These factors
together with other prevalent diseases contribute to the increased vulnerability of children to
5
poor glycaemic control and subsequent higher mortality. The prevalence of diabetes in
Tanzania is estimated at 3.5% in a total adult population of 23,514 aged 20 79 years. The
prevalence of Type 1 diabetes in most African populations is largely unknown. However,
several studies have shown a very low glycaemic control based on HB1c measurements. For
instance, a study Muze CK et al conducted in Tanzania indicates prevalence of glycaemic
control of about 49.8% based on HbA1c < 11% criteria [1].
The mainstay for management of T1D is the daily administration of insulin preparations.
Preservation of therapeutic potency of insulin preparations requires handling and storage at
appropriate temperatures. It is well-known that many drugs, biological products, and vaccines
are temperature-sensitive. One life-saving drug, which needs to be stored under temperatureregulated condition, is insulin [2]. Insulin is a life-saving product used for the management
of all type 1, and many type 2 diabetes patients. It is a polypeptide, produced by recombinant
DNA technology, using either E. coli or Saccharomyces sp [3]. Insulin analogs or modern
insulins are also available, which are produced by changing the chemical structure of the
insulin molecule. Insulin can be classified as rapid or fasting acting, e.g., human insulin,
aspart insulin, lispro insulin, and glulisine insulin; pre-mixed e.g., pre-mixed human insulin,
aspart and lispro; intermediate- acting, e.g., neutral protamine hegedorn (NPH) or iSoHSane
insulin, and long acting, e.g., detemir and glargine insulin.
For optimal effect, insulin need to be stored under refrigerated conditions, between 2 and
8C, and be protected from light when vials or pens are unopened. Pens or vials in use may
be kept at room temperature, protected from sunlight, up to 25C. A refrigerator is the best
place to store insulin in. Insulin should never be frozen as this will make it lose its potency.
Unopened insulin is best kept at 2-8C temperature. This temperature is maintained below the
freezer or in the butter compartment of most fridges. Opened insulin may be kept at room
temperature, or in the vegetable compartment of the fridge, where temperature is maintained
at a stable 14C [4]. It is further advised to avoid keeping insulin in the door of the fridge, as
this area is most prone to temperature fluctuations. Exposure to higher temperatures during
storage and use may degrade insulin by hydrolysis, or transform it to higher molecular weight
components [5]. A study conducted in India Vimalavathini R et al showed that storage of
regular and biphasic insulin at 32C and 37C decreased the potency of insulin by 14 to 18%
[6].
3. PROBLEM STATEMENT
T1D is a common childhood endocrine disorder that require prompt daily administration of
potent insulin preparations to achieve adequate glycaemia. Often, the storage of insulin
preparations poses significant challenges particularly in the rural settings in the tropics. The
existing practice of storage of insulin in poorly evaluated methods may contribute to poor
glycaemic control together with morbidity and mortality associated with T1D.
4. RATIONALE
To our understanding this is the first proposed survey for insulin storage modalities in
Tanzania. This survey is therefore expected to generate evidence for various storage
modalities of insulin rural settings and provide opportunity for improvement of T1D in
Tanzania. This approach will provide opportunity for optimizing the existing traditional
insulin storage modalities in order to prevent T1D-associated morbidity and mortality in
Tanzania.
5.1.
BROAD OBJECTIVE
To determine the type of insulin preparations, modalities of insulin storage and its impact on
the glycaemic control among patients receiving care at a secondary care health facility in
Tanzania.
5.2.
SPECIFIC OBJECTIVES
In order to achieve the above goal, we plan:1) To identify various types of insulin preparations prescribed for treatment of patients
with T1D receiving care at Chamwino District Hospital, Dodoma, Tanzania.
2) To determine various insulin storage modalities used by patients with T1D receiving
care at Chamwino District Hospital, Dodoma, Tanzania.
3) To assess the therapeutic efficacy of insulin preparations used for treatment of
patients with T1D in relation to glycaemic control based on FBG measurements
among patients receiving care at Chamwino District Hospital, Dodoma, Tanzania.
8
This proposed survey is planned to be carried out in Chamwino District Hospital in Dodoma,
Tanzania. The district is located in the central plateau of Tanzania which extends between
Latitude 40 and 80 South and between longitude 35and 37 East. The district is dissected
from Northwest to Southwest by a number of mountain chains, between and around these
mountains and hill ranges there are lower-lying relatively flat areas of about 1200m elevation
[13]. The district has a total area of 8,056 square kilometers with five divisions, thirty two
wards, and seventy eight villages. The district has a dry savannah climate characterized by a
long dry season (April to early December) and a short single wet season (December to April).
The average annual rainfall is 500mm typically raining between December and March. The
major economic activities are cattle rearing and crop husbandry [13].
The proposed study is a cross-sectional descriptive study. In this study the investigator will
recruit eligible patients in the OPD receiving insulin therapy for T1D. In these patients the
investigator will in parallel document the type of insulin preparation received and storage
modality as well as the assessment of the glycaemia based on FBG levels.
6.2.
STUDY POPULATION
The proposed study will recruit patients at OPD receiving insulin therapy for T1D. The
patients with T1D will be seen and interviewed once during the course of this survey.
6.2.1. INCLUSION CRITERIA: All patients, aged 35 years diagnosed with T1D
exclusively receiving insulin therapy for over 3 months.
6.2.2. EXCLUSION CRITERIA: Patients with T1D receiving insulin therapy together with
Oral Hypoglycaemic Agents (OHAs) or those with other severe co-morbid conditions e.g.
advanced stage of HIV/AIDS, tuberculosis and obviously diabetic complications.
6.3.
We plan to recruit patients with T1D previously diagnosed based on the hospitals existing
criteria fulfilling the inclusion criteria. The estimation of sample size will be based on the
previously reported prevalence of glycaemic control among patients with T1D of 49.8%
according to Muze CK et al [1]. In this survey the sample size is calculated using the formula;
Where:
9
6.4.
DATA COLLECTION
Basic demographic variables e.g. patient ID, age and sex and contact will be collected and
documented in routine manner using a standard clinical sheet. Other patient variables related
to diagnosis, treatment, insulin storage modalities together with glycaemic control will be
collected using standard questionnaire. Finger prick blood collection will be performed in a
standard manner in the morning after an overnight fasting for assessment of FBG using the
available rapid glucose meters. In parallel, routine case notes and hospital records will be
provide supplemental data related to glycaemic control.
10
7. ETHICAL CONSIDERATIONS
It is herewith assumed that the majority of patients with T1D are children without legal
power to consent. In this way, therefore, the informed consent to participate into the study
will be sought from the parent or guardian of every participant. Before the participants are
asked to agree or not to agree to be recruited into the study, the information sheet written in
Swahili or local dialect best understood by the guardian of the participant in relation to the
aims, potential risks and benefits of the study. The parents or guardians of each participant
will be given enough time for them to understand the study and think about their options.
They will be told they are free to participate or not in this research and if chooses not to
participate or to withdraw at any time, there will be no complaints. If the participant chooses
for the patient to participate, she/he will be asked to sign the Informed Consent Form
administered by the interviewer. Capillary blood samples will be collected for measurement
of FBG after a finger prick.
10.
May
June
11
July
Aug
Sept
11.
Justification
Sum (TZS)
100,000
Transport and
subsistence
400,000
125,000
Data management
and analysis
Printing and
stationery
Research reports
production
TOTAL
150,000
75,000
850,000
12.
REFERENCES
1.
Muze, K.C. and E.S. Majaliwa, Type 1 diabetes care updates: Tanzania. Indian J
Endocrinol Metab. 19(Suppl 1): p. S12-3.
Chandler, C., et al., Insulin temperature and stability under simulated transit
conditions. Am J Health Syst Pharm, 2008. 65(10): p. 953-63.
Pingel M, V.A., Stability of insulin preparation. Diabetes, 1972. 21: p. 805-13.
IDF, Pocketbook for management of diabetes in childhood and adolescence in underresourced countries. 2013.
Gregory, R., S. Edwards, and N.A. Yateman, Demonstration of insulin transformation
products in insulin vials by high-performance liquid chromatography. Diabetes Care,
1991. 14(1): p. 42-8.
Vimalavathini, R. and B. Gitanjali, Effect of temperature on the potency &
pharmacological action of insulin. Indian J Med Res, 2009. 130(2): p. 166-9.
2.
3.
4.
5.
6.
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8.
9.
10.
11.
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13.
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