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Chronic Care Programme
Treatment guidelines
Diabetes MellitusType 1
Chronic condition
Consultations protocols
Preferred treating provider
Notes
 preferred as indicated by option
 referral protocols apply
Maximum consultations per annum
 Initial consultation
 Follow-up consultation
Tariff codes
Consultation: Ophthalmologist
 Initial consultation
 Follow-up consultation
Tariff codes
Regular care primary consultation:
Dietician
 Initial consultation
 Follow-up consultation
Tariff codes
Regular care secondary consultation:
Dietician
 Initial consultation
 Follow-up consultation
Tariff codes
Podiatrist
 Initial consultation
 Follow-up consultation
Tariff codes
Podiatrist
Option/plan
Provider
GMHPP
Gold Options
G1000, G500 and
G200.
Blue Options
B300 and B200.
GMISHPP
General Practitioner
Physician
Paediatrician
Cardiologist
Neurologist
Pulmonologist
Gastroenterologist
Surgeon
New Patient
All Severity Levels
Existing patient
Controlled /
Uncontrolled / Target
Stable
Organ Disease
1
1
3
1
0183; 0142; 0187; 0108
New Patient
All Severity Levels
1
0
1
3
Existing patient
Controlled /
Uncontrolled / Target
Stable
Organ Disease
1
0
1
0
0142
New Patient
All Severity Levels
1
0
Existing patient
Controlled /
Uncontrolled / Target
Stable
Organ Disease
1
0
1
0
051
New Patient
All Severity Levels
1
0
Existing patient
Controlled /
Uncontrolled / Target
Stable
Organ Disease
1
0
1
0
053
New Patient
All Severity Levels
1
0
Existing patient
Controlled /
Uncontrolled / Target
Stable
Organ Disease
1
0
1
0
012
New Patient
All Severity Levels
Existing patient
Controlled /
Uncontrolled / Target
 Initial consultation
 Follow-up consultation
Tariff codes
1
0
Stable
Organ Disease
1
0
1
0
001
Investigations protocols
Type
Provider
Tariff
code
Peripheral fundus examination
with indirect ophthalmoscope
(ophthalmologist)
Urine dipstick
Glucose tolerance test
(2 specimens)
Microalbuminuria: thin layer
chromatography one way
Blood glucose
ECG
HbA1C
Chol/HDL/LDL/Trig
Serum urea
Serum creatinine
Serum potassium
Serum Sodium
Ketones: excluding dipstick
method
ICD 10 coding
Ophthalmol
ogist
GP;
Pathologist;
Specialist
Pathologist
GP;
Pathologist;
Specialist
GP;
Pathologist;
Specialist
GP;
Specialist
(see list)
Pathologist
Pathologist
Pathologist
Pathologist
Pathologist
Pathologist
Pathologist
Maximum investigations per annum
New patient
Existing patient
Stable
Unstable
Controlled
Uncontrolled
3004
1
1
1
4188
4
2
4
4049
1
0
0
4265
1
1
1
4
2
4
1
1
1
4
1
1
1
1
1
2
2
1
1
1
1
1
1
4
1
1
1
1
1
2
4057
or
4050
1232
or
1233
4064
4025
4151
4032
4113
4114
4247
E10.
General
Diabetes mellitus type 1 (Type 1 diabetes, Type I diabetes, T1D, T1DM, IDDM, juvenile
diabetes) is a form of diabetes mellitus. Type 1 diabetes is an autoimmune disease that results in
the permanent destruction of insulin producing beta cells of the pancreas. Type 1 is lethal unless
treatment with exogenous insulin via injections replaces the missing hormone.
Type 1 diabetes (formerly known as "childhood", "juvenile" or "insulin-dependent" diabetes) is
not exclusively a childhood problem: the adult incidence of Type 1 is noteworthy — many adults
who contract Type 1 diabetes are misdiagnosed with Type 2 due to the misconception of Type 1
as a disease of children — and since there is no cure, Type 1 diabetic children will grow up to be
Type 1 diabetic adults.
There is currently no preventive measure that can be taken against type 1 diabetes. Most people
affected by type 1 diabetes are otherwise healthy and of a healthy weight when onset occurs, but
they can lose weight quickly and dangerously, if not diagnosed in a relatively short amount of
time. Diet and exercise cannot reverse or prevent type 1 diabetes. Although there are clinical trials
ongoing that aim to find methods of preventing or slowing its development, so far none has
proven successful.
The most useful laboratory test to distinguish Type 1 from Type 2 diabetes is the C-peptide assay,
which is a measure of endogenous insulin production since external insulin (to date) has included
no C-peptide. However, C-peptide is not absent in Type 1 diabetes until insulin production has
fully ceased, which may take months[citation needed]. The presence of anti-islet antibodies (to
Glutamic Acid Decarboxylase, Insulinoma Associated Peptide-2 or insulin), or lack of insulin
resistance, determined by a glucose tolerance test, would also be suggestive of Type 1. As
opposed to that, many Type 2 diabetics still produce some insulin internally, and all have some
degree of insulin resistance.
Testing for GAD 65 antibodies has been proposed as an improved test for differentiating between
Type 1 and Type 2 diabetes.
Pathophysiology
The cause of Type 1 diabetes is still not understood. Type 1 diabetes could be a virally induced
autoimmune response. Autoimmunity is a condition where one's own immune system "attacks"
structures in one's own body either destroying the tissue or decreasing its functionality. In the
proposed scenario, pancreatic beta cells in the Islets of Langerhans are destroyed or damaged
sufficiently to abolish endogenous insulin production. This etiology makes type 1 distinct from
type 2 diabetes mellitus. It should also be noted that the use of insulin in a patient's diabetes
treatment protocol does not render them as having type 1 diabetes, the type of diabetes a patient
has is determined only by disease etiology. The autoimmune attack may be triggered by reaction
to an infection, for example by one of the viruses of the Coxsackie virus family or German
measles, although the evidence is inconclusive.
This vulnerability is not shared by everyone, for not everyone infected by these organisms
develops Type 1 diabetes. This has suggested a genetic vulnerability and there is indeed an
observed inherited tendency to develop Type 1.[1] It has been traced to particular HLA
phenotypes, though the connection between them and the triggering of an auto-immune reaction
is poorly understood.
Some researchers believe that the autoimmune response is influenced by antibodies against cow's
milk proteins.[2] A large retrospective controlled study published in 2006 strongly suggests that
infants who were never breast fed had twice the risk for developing Type 1 diabetes as infants
who were breast fed for at least three months. The mechanism, if any, is not understood. No
connection has been established between autoantibodies, antibodies to cow's milk proteins, and
Type 1 diabetes. A subtype of Type 1 (identifiable by the presence of antibodies against beta
cells) typically develops slowly and so is often confused with Type 2. In addition, a small
proportion of Type 1 cases have the hereditary condition maturity onset diabetes of the young
(MODY) which can also be confused with Type 2.
Vitamin D in doses of 2000 IU per day given during the first year of a child's life has been
connected in one study in Northern Finland (where intrinsic production of Vitamin D is low due
to low natural light levels) with a reduction in the risk of getting Type 1 diabetes later in life (by
80%).
Some suggest that Vitamin D3 (one of several related chemicals with Vitamin D activity) may be
an important pathogenic factor in Type 1 diabetes independent of geographical latitude.
Some chemicals and drugs specifically destroy pancreatic cells. Vacor (N-3-pyridylmethyl-N'-pnitrophenyl urea), a rodenticide introduced in the United States in 1976, selectively destroys
pancreatic beta cells, resulting in Type 1 diabetes after accidental or intentional ingestion. Vacor
was withdrawn from the U.S. market in 1979. Zanosar is the trade name for streptozotocin, an
antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer, that kills beta
cells, resulting in loss of insulin production.
Other pancreatic problems, including trauma, pancreatitis or tumors (either malignant or benign),
can also lead to loss of insulin production. The exact cause(s) of Type 1 diabetes are not yet fully
understood, and research on those mentioned, and others, continues.
In December 2006, researchers from Toronto Hospital for Sick Children revealed research that
shows a link between type 1 diabetes and the immune and nervous system. Using mice, the
researchers discovered that a control circuit exists between insulin-producing cells and their
associated sensory (pain-related) nerves.[3] It's being
Treatment
Type 1 is treated with insulin replacement therapy — usually by injection or insulin pump,
dietary control, typically including carbohydrate tracking, and careful monitoring of blood
glucose levels using Glucose meters.
Untreated Type 1 diabetes can lead to one form of diabetic coma, diabetic ketoacidosis, which
can be fatal. At present, insulin treatment must be continued for a lifetime; this will change if
better treatment, or a cure, is discovered. Continuous glucose monitors have been developed
which can alert patients to the presence of dangerously high or low blood sugar levels, but the
lack of widespread insurance coverage has limited the impact these devices have had on clinical
practice so far.
In more extreme cases, a pancreas transplant can help restore proper glucose regulation.
However, the surgery and accompanying immunosuppression required is considered by many
physicians to be more dangerous than continued insulin replacement therapy and is therefore
often used only as a last resort (such as when a kidney must also be transplanted or in cases where
the patient's blood glucose levels are extremely volatile). Experimental replacement of beta cells
(by transplant or from stem cells) is being investigated in several research programs and may
become clinically available in the future. Thus far, beta cell replacement has only been performed
on patients over age 18, and with tantalizing successes amidst nearly universal failure.
Pancreas transplantation
Pancreas transplants are not generally recommended because introducing a new, functioning
pancreas to a patient with diabetes can have negative effects on the patient's normally
functioning kidney. However, they are highly recommended for patients who require a
kidney transplant, and may also be wise in patients with extremely labile diabetes.
Artificial Pancreas
Islet cell transplantation
Less invasive than a pancreas transplant, islet cell transplantation is currently the
most highly used approach in humans to temporarily cure type 1 diabetes.
In one variant of this procedure, islet cells are injected into the patient's liver,
where they take up residence and begin to produce insulin. The liver is expected to
be the most reasonable choice because it is more accessible than the pancreas, and
the islet cells seem to produce insulin well in that environment. The patient's body,
however, will treat the new cells just as it would any other introduction of foreign
tissue. The immune system will attack the cells as it would a bacterial infection or
a skin graft. Thus, the patient also needs to undergo treatment involving
immunosuppressants, which reduce immune system activity.
Recent studies have shown that islet cell transplants have progressed to the point
that 58% of the patients in one study were insulin independent one year after the
operation.[4] It would be best to use islet cells which will not provoke this immune
reaction.
Medicine formularies
Plan or option
[Link to appropriate Mediscor formulary]
GMHPP
Gold Options
G1000, G500 and
G200
Blue Options
B300 and B200
GMISHPP
Blue Option B100
[Core]
n/a
Epidemiology
It is estimated that about 5%–10% of North American diabetes patients have type 1. The fraction
of type 1 in other parts of the world differs; this is likely due to both differences in the rate of type
1 and differences in the rate of other types, most prominently type 2. Most of this difference is not
currently understood. Variable criteria for categorizing diabetes types may play a part.
Prognosis
As of 2008, there is no known cure for diabetes mellitus type 1 used by modern medical institutes
or hospitals.[5] There is ongoing research on various approaches to curing diabetes type 1.
Diabetes type 1 is caused by the destruction of sufficient beta cells in the body; these cells, which
are found in the Langerhans islets in the pancreas, produce and secrete insulin, the single
hormone responsible for allowing glucose to enter from the blood into cells, and also the hormone
amylin, another hormone required for glucose homeostasis. Hence, the phrase "curing diabetes
type 1" means "causing a maintenance or restoration of the endogenous ability of the body to
produce insulin in response to the level of blood glucose". This section does not deal with
approaches other than that (for instance, closed-loop integrated glucometer/insulin pump
products), which could potentially increase the quality of life for some who have diabetes type 1,
and may by some be termed "artificial pancreas". Instead, it only deals with such approaches for
thoroughly curing the underlying condition of diabetes type 1, by enabling the body to
endogenously, in vivo, produce insulin in response to the level of blood glucose.
Reversion
Encapsulation approach
The Bio-artificial pancreas: this diagram shows a cross section of bio-engineered tissue with
encapsulated islet cells which deliver endocrine hormones in response to glucose.
A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet
cells, which would secrete the amounts of insulin, amylin and glucagon needed in response to
sensed glucose.
When islet cells have been transplanted via the Edmonton protocol, insulin production (and
glycemic control) was restored, but at the expense of immunosuppression. Encapsulation of the
islet cells in a protective coating has been developed to block the immune response to
transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of
the transplant.[6]
One concept of the bio-artificial pancreas uses encapsulated islet cells to build an islet sheet
which can be surgically implanted to function as an artificial pancreas.[7]
This islet sheet design consists of:

an inner mesh of fibers to provide strength for the islet sheet;

islet cells, encapsulated to avoid triggering a proliferating immune response, adhered to
the mesh fibers;

a semi-permeable protective layer around the sheet, to allow the diffusion of nutrients and
secreted hormones;

a protective coating, to prevent a foreign body response resulting in a fibrotic reaction
which walls off the sheet and causes failure of the islet cells.
Islet sheet with encapsulation research is pressing forward with large animal studies at the
present, with plans for human clinical trials within a few years.
Islet cell regeneration approach
Research undertaken at the Massachusetts General Hospital in Boston Masschusetts from 2001
and 2003 demonstrated a protocol to reverse type 1 diabetes in mice.[8] Three other institutions
have had similar results, published in the March 24, 2006 issue of Science. A fourth study by the
National Institutes of Health further confirmed the approach, and also sheds light on the
biological mechanisms involved.[9]
Stem cells approach
Research is being done at several locations in which islet cells are developed from stem cells.
In January 2006, a team of South Korean scientists has grown pancreatic beta cells, which can
help treat diabetes, from stem cells taken from the umbilical cord blood of newborn babies.
In April 2007, it was reported by the Times Online that 15 young Brazilian patients diagnosed
with Type 1 diabetes were able to naturally produce insulin once again after undergoing mild
chemotherapy to temporarily weaken their immune systems and then injection of their own stem
cells. This allowed the pancreatic beta cells to produce insulin. Since white blood cells were
blocking the pancreas from producing insulin, Dr. Voltarelli and colleagues killed the immune
cells, allowing the pancreas to secrete insulin once more.
However, there were no control subjects, which means that all of the processes could have been
completely or partially natural. Secondly, no theory for the mechanism of cure has been
promoted. It is too early to say whether the results will be positive or negative in the long run.[10]
Gene therapy approach
Gene therapy: Designing a viral vector to deliberately infect cells with DNA to carry on the viral
production of insulin in response to the blood sugar level.
Technology for gene therapy is advancing rapidly such that there are multiple pathways possible
to support endocrine function, with potential to practically cure diabetes.[11]

Gene therapy can be used to manufacture insulin directly: an oral medication, consisting
of viral vectors containing the insulin sequence, is digested and delivers its genes to the
upper intestines. Those intestinal cells will then behave like any viral infected cell, and
will reproduce the insulin protein. The virus can be controlled to infect only the cells
which respond to the presence of glucose, such that insulin is produced only in the
presence of high glucose levels. Due to the limited numbers of vectors delivered, very few
intestinal cells would actually be impacted and would die off naturally in a few days.
Therefore by varying the amount of oral medication used, the amount of insulin created by
gene therapy can be increased or decreased as needed. As the insulin producing intestinal
cells die off, they are boosted by additional oral medications.[12]

Gene therapy might eventually be used to cure the cause of beta cell destruction,
thereby curing the new diabetes patient before the beta cell destruction is complete and
irreversible.[13]

Gene therapy can be used to turn duodenum cells and duodenum adult stem cells into
beta cells which produce insulin and amylin naturally. By delivering beta cell DNA to the
intestine cells in the duodenum, a few intestine cells will turn into beta cells, and
subsequently adult stem cells will develop into beta cells. This makes the supply of beta
cells in the duodenum self replenishing, and the beta cells will produce insulin in
proportional response to carbohydrates consumed.[14]
Yonsei University study
Scientists in the South Korean university of Yonsei have, in 2000, succeeded in reversing
diabetes in mice and rats. Using a viral vector, a DNA encoding the production of an insulin
analog was injected to the animals, which remained non-diabetic for at least the eight months
duration of the study.[15]
Nanotechnology approach
Under the nanotechnological approach to curing diabetes type 1, many "nanobots" would be
injected into the patient's bloodstream. These nanobots would be able to synthesize insulin, and to
secrete it according to the level of glucose they would sense.[16]
Prevention
"Immunization" approach
If a biochemical mechanism can be found that prevents the immune system from attacking beta
cells, it may be administered to prevent commencement of diabetes type 1. The way several
groups are trying to achieve this is by causing the activation state of the immune system to change
from Th1 state (“attack” by killer T Cells) to Th2 state (development of new antibodies). This
Th1-Th2 shift occurs via a change in the type of cytokine signaling molecules being released by
regulatory T-cells. Instead of pro-inflammatory cytokines, the regulatory T-cells begin to release
cytokines that inhibit inflammation.[17] This phenomenon is commonly known as "acquired
immune tolerance".
DiaPep277
A substance designed to cause lymphocyte cells to cease attacking beta cells, DiaPep277 is a
peptide fragment of a larger protein called HSP60. Given as a subcutaneous injection, its
mechanism of action involves a Th1-Th2 shift. Clinical success has been demonstrated in
prolonging the "honeymoon" period for people who already have type 1 diabetes.[18] The product
is currently being tested in people with latent autoimmune diabetes of adults (LADA). Ownership
of the drug has changed hands several times over the last decade. In 2007, Clal Biotechnology
Industries (CBI) Ltd., an Israeli investment group in the field of life sciences, announced that
Andromeda Biotech Ltd., a wholly owned subsidiary of CBI, signed a Term Sheet with Teva
Pharmaceutical Industries Ltd. to develop and commercialize DiaPep277.[19]
Intra-nasal insulin
There is pre-clinical evidence that a Th1-Th2 shift can be induced by administration of insulin
directly onto the immune tissue in the nasal cavity. This observation has led to a clinical trial,
called INIT II, which began in late 2006, based in Australia and New Zealand.
Denise Faustman research
Tumor necrosis factor-alpha, or TNF-a, is part of the immune system. It helps the immune system
discern between self and non-self. People with type 1 diabetes are deficient in this substance. Dr.
Faustman theorizes that giving Bacillus Calmette-Guérin (BCG), an inexpensive drug, would
have the same impact as injecting diabetic mice with Freund's Adjuvant, which stimulates TNF-a
production. TNF-a kills the white blood cells responsible for destroying beta cells, and thus
prevents, or reverses diabetes.[20] She has reversed diabetes in laboratory mice with this techniqe,
but was only able to receive funding for subsequent research from The Iaccoca Foundation,
founded by Lee Iacocca in honor of his late wife, who died from diabetes complications. Human
trials are set to begin in 2008.
Diamyd
Diamyd is the name of a vaccine being developed by Diamyd Medical. Injections with GAD65,
an autoantigen involved in type 1 diabetes, has in clinical trials delayed the destruction of beta
cells for at least 30 months, without serious adverse effects. Patients treated with the substance
showed higher levels of regulatory cytokines, thought to protect the beta cells. Phase III trials are
under way in the USA and in Europe.[21][22]
Entities involved in research
This section is an incomplete list of mainly commercial companies but also other entities, namely
governmental institutions and individual persons, actively involved in research towards finding a
cure to diabetes type 1.
It does not list research funds, hospitals in which research is undertaken, etc., but only the
industrious, actual developers of such products.
Entities are listed along with their status of research in that field, so that also entities which
ceased research into finding a cure to diabetes type 1 may be listed.
Entities are alphabetically listed.

Amylin Pharmaceuticals – is working toward finding a cure, and has a drug on the market
called Symlin (pramlintide acetate) that helps in treating Type 1 diabetes

Cerco Medical [1] – Present status: Unknown

Denise Faustman [2] – Present status: Working on immune modification

DeveloGen [3] – Present status: Developing DiaPep 277

Diamyd Medical [4] – Present status: Developing GAD65-based vaccine (phase III
application approved by the FDA)
 Encelle [5] – Present status: On hold; Awaiting decision on whether to move forward into
encapsulated beta cell transplantation.[citation needed]
References
1. "Donner", "Horst"; "Harald Rau, Paul G. Walfish, Jens Braun, Thorsten Siegmund, Reinhard
Finke, Jürgen Herwig, Klaus H. Usadel and Klaus Badenhoop" ("2007").
["http://jcem.endojournals.org/cgi/content/abstract/82/1/143" "CTLA4 Alanine-17 Confers
Genetic Susceptibility to Graves’ Disease and to Type 1 Diabetes Mellitus"]. "The Journal of
Clinical Endocrinology & Metabolism Vol. 82, No. 1 143-146". "The Journal of Clinical
Endocrinology & Metabolism". Retrieved on 2008-02-06.
2. content.nejm.org
3. Canadian scientists reverse diabetes in mice. Retrieved on 2007-06-04.
4. Islet cell transplant: Experimental treatment for type 1 diabetes - MayoClinic.com. Retrieved on
2007-06-04.
5. Without the use of large doses of immunosuppressants, that causes a multitude of other medical
issues.
6. Cerco Medical: Science: Methods
7. Cerco Medical: Company: Islet Sheet Research
8. November 13, 2003 Regeneration of insulin-producing islets may lead to diabetes cure. Retrieved
on 2007-06-04.
9. Faustman DL, Tran SD, Kodama S, et al (2006). "Comment on papers by Chong et al., Nishio et
al., and Suri et al. on diabetes reversal in NOD mice". Science 314 (5803): 1243; author reply
1243. doi:10.1126/science.1129811. PMID 17124308.
10. Voltarelli JC, Couri CE, Stracieri AB, et al (2007). "Autologous nonmyeloablative hematopoietic
stem cell transplantation in newly diagnosed type 1 diabetes mellitus". JAMA 297 (14): 1568–76.
doi:10.1001/jama.297.14.1568. PMID 17426276.
11. Gene Therapy Approaches to Diabetes
12. Mary Ann Liebert, Inc. - Cookie absent
13. http://www.hopkinsbayview.org/healthcarenews06/060605diabetes.html
14. Engene Inc
15. Gene Therapy for Diabetes: Scientific American
16. http://ieeexplore.ieee.org/iel5/6/29742/1353792/13537927.html
17. jci.org
18. interscience.wiley.com
19. medicalnewstoday.com
20. Shinichiro Ryu, Shohta Kodama, Kazuko Ryu, David A. Schoenfeld & Denise L. Faustman. 2001.
Reversal of established autoimmune diabetes by restoration of endogenous β cell function. J. Clin.
Invest. 108(1): 63-72.
21. Further Evidence for Lasting Immunological Efficacy of Diamyd Diabets Vaccine
22.Diamyd Announces Completion of Type 1 Diabetes Vaccine Trial with Long Term Efficcacy
Demonstrated at 30 Months