Type 1 Diabetes: Risk Factors, Aetiology, Pathophysiology, Clinical Manifestations, Diagnostic Tests, and Treatment

This presentation provides an in-depth analysis of the risk factors, aetiology, pathophysiology, clinical manifestations, diagnostic tests, and treatment of type 1 diabetes. The major risk factor for the metabolic disease is the presence of the disorder in the father. The pathophysiology of T1D involves destruction of the beta cells of the pancreas, regardless of the causative entity or risk factor that might have contributed to the disease. Treatment modalities include administration of immunosuppressive agents, anti-CD3 antibodies, and dietary modifications.

5% genetic susceptibility
Geographical contributor
Impact on
immune
system
Insulin production halts
Pathophysiology
Risk Factors
Aetiology
Clinical
manifestations
Diagnostic tests
Treatment
Stay in
Finland
T1D in father
Innate immune
system activated Weight loss
Family history and
environmental factors
polyuria
Insulin injections
Anti-CD3 antibodies
Beta cells of pancreas are
destroyed
Autoimmune response
HLA genetics
HLA-DQA1, HLA-DQB1, and
HLA-DRB1 genes
Excessive hunger
and thirst
expansion of CD4+
and CD8+T cells
Tonsillecto
my and
Celiac
disease
Exercise for maintaining
body weight
Carbohydrate, protein and fat
counting
Frequent blood-
glucose
monitoring
Dietary modifications
polydipsia
Immune system attack cells
of own body
Glycated haemoglobin
tests
Key
Self-management
education
Laboured breathing

750 words explanation
Type 1 diabetes refers to an autoimmune condition that is characterised by activation of the immune system to kills or destroy beta cells in the pancreas, the primary role
of which is to produce insulin hormone (Atkinson, Eisenbarth&Michels, 2014). An analysis of the case study suggests that the major risk factor that accounted for the metabolic disease in
Emilia, is the presence of the disorder in her father. Research evidences have established the genetic association of T1D and also suggest that the risk of a child for developing the condition
is an estimated 5%, if it is present in the father and about 8% and 3%, if found in a sibling or the mother, respectively (Pociot&Lernmark, 2016). Furthermore, Caucasians residing in
different regions of the Europe are more vulnerable to the disorder (Ma & Chan, 2013). This can be considered as a major risk factor since Emilia was born in Finland and stayed there
during her childhood. In addition, Celiac disease (CD) and T1D share some common susceptibility factors, primarily HLA genetics, such as, HLA-DQA1, HLA-DQB1, and HLA-DRB1 genes that
play a crucial role immune system functioning (Lionetti et al., 2014). Furthermore, studies have also illustrated the fact that adenoidectomy and tonsillectomy in childhood create an impact
on the functioning of the immune system and increase the likelihood of a child to suffer from T1D. (Cadario et al., 2017) The surgery activates an autoimmune reaction that results in the
immune system attacking cells of its own body, thereby destroying the beta-cells of islets of Langerhans and impeding production of insulin (Blumenfeld, 2016). Hence, the primary reasons
that might have contributed to the development of type 1 diabetes in Emilia are presence of the disease in her father, her stay at Europe, and history of tonsillectomy and celiac disease.
The pathophysiology of T1D involves destruction of the beta cells of the pancreas, regardless of the causative entity or risk factor that might have contributed to the
disease. Autoimmune response towards the beta cells of the islets of Langerhans is the primary manifestation of the condition and generally involved an expansion of CD4+ and CD8+T
helper cells that are autoreactive in nature, in addition to activating the innate immune system (Sarikonda et al., 2014). One common symptom that arises as a result of this
pathophysiology is drastic weight loss (Chiang, Kirkman, Laffel&Peters, 2014). The symptom of polyuria or frequent urination was exhibited by Emilia, as evident by the reports of excessive
urination. Furthermore, her physical examination revealed weight loss, and rapid breathing.

Sudden weight loss has often been considered as a major manifestation of diabetes owing to the fact that absence of sufficient insulin hormone prevents the body from utilising adequate
glucose from bloodstream into the cells. This is accompanied by a subsequent burning of the muscle fat for energy, thereby resulting in a weight reduction (American Diabetes Association,
2015). In addition, laboured or rapid breathing, often referred to as Kussmaul breathing, is a key symptom found in diabetic ketoacidosis. Ketoacidosis is generally defined as a short term
complication caused due to elevated blood glucose levels that are complemented with high ketone levels in the blood (Couper et al., 2014). This subsequently resulted in continuous vomiting
that occurs with an increase in blood glucose that makes the body more vulnerable to production of ketone. Furthermore, dehydration, and shock made her unresponsive to verbal commands.
The condition is primarily characterised by persistent or recurrent hyperglycaemia and is diagnosed by measuring the fasting plasma glucose levels, at or more than 126mg/dL. Furthermore,
presence of plasma glucose on or above 200mg/dL, two hours after a meal also helps in the diagnosis (Kerner & Brückel, 2014). Glycated haemoglobin tests are another assessment criteria
with HbA1c levels on or above 48 mmol/mol indicating the presence of high blood sugar (American Diabetes Association, 2014). One major treatment modality that can be implemented in this
condition include administration of cyclosporine A, an immunosuppressive agent that halts the obliteration of the beta cells of pancreas. In addition, use of anti-CD3 antibodies such as,
otelixizumab and teplizumab will also help to preserve insulin production (Lind et al., 2014). There is also a need to make Emilia adhere to a gluten free diet in order to improve her diabetes
symptoms and provide her defence against the long term complications of the metabolic disorder (Miller et al., 2015). She should be taught how and when to effectively manage her diabetes,
without any parental assistance. She will be made to adhere to a dietary modification regimen. In addition, upon finding a worsening of her symptoms, she might also be administered with
injections of insulin subcutaneously, while taking into account adjustments made for her food intake, and physical activity levels (Orchard et al., 2015). There is a need for her to attend regular
check-ups for managing the condition and its long term health complications (Nordfeldt, Ängarne-Lindberg, Nordwall & Krevers, 2013).

References
American Diabetes Association. (2014). Diagnosis and classification of diabetes mellitus. Diabetes care, 37(Supplement 1), S81-S90. https://doi.org/10.2337/dc14-S081
American Diabetes Association. (2015). Standards of medical care in diabetes—2015 abridged for primary care providers. Clinical diabetes: a publication of the American Diabetes
Association, 33(2), 97. doi: 10.2337/diaclin.33.2.97
Atkinson, M. A., Eisenbarth, G. S., &Michels, A. W. (2014). Type 1 diabetes. The Lancet, 383(9911), 69-82. https://doi.org/10.1016/S0140-6736(13)60591-7
Blumenfeld, Z. (2016). Appendectomy, tonsillectomy, and conceptions. Fertility and sterility, 106(5), 1043-1044. https://doi.org/10.1016/j.fertnstert.2016.07.001
Cadario, F., Savastio, S., Rizzo, A. M., Carrera, D., Bona, G., &Ricordi, C. (2017). Can type 1 diabetes progression be halted? Possible role of high dose vitamin D and omega 3 fatty
acids. European Review for Medical & Pharmacological Sciences, 21(7), 1604-1609. Retrieved from- https://www.europeanreview.org/wp/wp-content/uploads/1604-1609-Can-Type-1-
diabetes-progression-be-halted-Possible-role-of-high-dose-vitamin-D-and-omega-3-fatty-acids.pdf
Chiang, J. L., Kirkman, M. S., Laffel, L. M., & Peters, A. L. (2014). Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes care, 37(7), 2034-
2054. https://doi.org/10.2337/dc14-1140
Couper, J. J., Haller, M. J., Ziegler, A. G., Knip, M., Ludvigsson, J., & Craig, M. E. (2014). Phases of type 1 diabetes in children and adolescents. Pediatric diabetes, 15(S20), 18-25.
https://doi.org/10.1111/pedi.12188
Kerner, W., & Brückel, J. (2014). Definition, classification and diagnosis of diabetes mellitus. Experimental and Clinical Endocrinology & Diabetes, 122(07), 384-386.
http://m.ddg.info/fileadmin/Redakteur/Leitlinien/Englische_Leitlinien/Practice_Guideline_Definition__Classification_and_Diagno.pdf
Lind, M., Svensson, A. M., Kosiborod, M., Gudbjörnsdottir, S., Pivodic, A., Wedel, H., ...&Rosengren, A. (2014). Glycemic control and excess mortality in type 1 diabetes. New England Journal of
Medicine, 371(21), 1972-1982. DOI: 10.1056/NEJMoa1408214
Lionetti, E., Castellaneta, S., Francavilla, R., Pulvirenti, A., Tonutti, E., Amarri, S., ...&Castellano, E. (2014). Introduction of gluten, HLA status, and the risk of celiac disease in children. New
England Journal of Medicine, 371(14), 1295-1303. DOI: 10.1056/NEJMoa1400697
Ma, R. C., & Chan, J. C. (2013). Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States. Annals of the New York Academy of
Sciences, 1281(1), 64-91. https://doi.org/10.1111/nyas.12098
Miller, K. M., Foster, N. C., Beck, R. W., Bergenstal, R. M., DuBose, S. N., DiMeglio, L. A., ... &Tamborlane, W. V. (2015). Current state of type 1 diabetes treatment in the US: updated data from
the T1D Exchange clinic registry. Diabetes care, 38(6), 971-978. https://doi.org/10.2337/dc15-0078
Nordfeldt, S., Ängarne-Lindberg, T., Nordwall, M., & Krevers, B. (2013). Parents of adolescents with type 1 diabetes-their views on information and communication needs and internet use. A
qualitative study. PloS one, 8(4), e62096. https://doi.org/10.1371/journal.pone.0062096
Orchard, T. J., Nathan, D. M., Zinman, B., Cleary, P., Brillon, D., Backlund, J. Y. C., &Lachin, J. M. (2015). Association between 7 years of intensive treatment of type 1 diabetes and long-term
mortality. Jama, 313(1), 45-53. doi:10.1001/jama.2014.16107
Pociot, F., &Lernmark, Å. (2016). Genetic risk factors for type 1 diabetes. The Lancet, 387(10035), 2331-2339. https://doi.org/10.1016/S0140-6736(16)30582-7
Sarikonda, G., Pettus, J., Phatak, S., Sachithanantham, S., Miller, J. F., Wesley, J. D., ...& Edelman, S. (2014). CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity
exists in both type 1 and type 2 diabetes. Journal of autoimmunity, 50, 77-82. https://doi.org/10.1016/j.jaut.2013.12.003