Diabetes Mellitus type 1

Diabetes Mellitus type 1

Muhamad Na’im B. Ab Razak

Diabetes Mellitus is a heterogenous group of disease characterized by hyperglycemia which could be due to defect in production and secretion of insulin, insulin action or both

Both DMT1 and DMT2 have affected 135 million people worlwide according to World Health Organization and it is believed that this number will increase to 300 million individuals in 2025.

Previously, the classification of diabetis melitus is based on juvenile onset and adult onset but this classification was abolished in 1979. Then, the classification is made by WHO in 1980 based on Insulin dependent diabetes melitus or non insulin dependent diabetes melitus. In 1997, the experts from American Diabetes Association have abandoned this classification and introduce a new classification which has been used now adays; Type 1 and Type 2 diabetes.

DMT1 accounts for approximately 10% of all cases of DM and the peak age for this disease is around 14 yr. It is a multifactorial autoimmune disease for which susceptibility is determined by genetic, environmental and immunologic factors that lead to T-cell mediated autoimmune disease characterized by the destruction of insulin-secreting beta cells in the islet of langerhans cell; possibly due to molecular mimicry. However, it may also cause by trauma or cancer which damage the islet of langerhans in pancreas.

There is no definate guideline to define DMT1. Most of the diagnosis of DMT1 is often made when the patient presented to the hospital with the signs of Diabetic Ketoacidosis (DKA) as it is usually asymptomatic until there is a stressor to trigger the attack.

However, most of it can be diagnosed based on history whereby patient commonly presented with clasical triad of diabetes melitus which is polydypsia, polyuria and nocturia.

When CBS is done, the level of blood is high. There is also the present of glucose and ketone in urine

The mainstay treatment for DMT1 since its discovery is insulin and it remains as the only pharmaologic therapy for this disease. This is due to autoimmune disease in which autoreactive T cells specifically kill the Islet of Langerhans of Pancreas. The treatment is to maintain the level of HbA_1c below than 6.5%.

Oral hypoglycaemic agent is not indicated in the treatment of DMT1. 1) Sulfonylurease stimulates insulin release from pancreatic islet of langerhans. However, in DMT1 most of the islet of langerhans cell has been destroyed. 2) Metformin is an antihyperglycemic drug and could potentially helpful to reduce the glucose by decrease hepatic glucose production and increase insulin action in muscle and fat. These drugs however can cause lactic acisosis which is harmful in DKA patient as DKA also cause lactic acidosis.

However, Insulin is not a cure for the DMT1 as it fails to replace or maintain the functional integrity of islet of Langerhans can not control or eliminate the autoimmunity and not easily apply to the large number of patient.

Research has been done to use the immunological basis treatment for DMT1 due to complication arise instead of continuous treatment with Insulin. Currently, a clinical trial has been conducted whereby Antisense-oligonucleotide-formulated microsphere-based is being tried for the treatment DMT1

DMT1 can progress to diabetic ketoacidosis which is the state of absolute or relative insulin bancruptcy whereby diagnosis is made when blood glucose > 14 mmol/L, acidosis (pH <7.3,>

K Nair et all has reported an uncommon causes of diabetic ketoacidosis in Bipolar manic disorder patient which is believed to be induced by anti- psychotic (Olanzapine) as it cause the development of metabolic abnormalities. Even the schizophrenia and other psychiatry illness itself have long being associated with metabolic disorder.

Rhamdomyolysis occur in as many as 50% of patient presenting with DKA or HHNK and varies in severity from mildly elevated CK level without symptoms to markedly elevated CK with acute renal failure, possibly requiring hemodylisis. DKA and HHNK patients with rhabdomyolysis have higher blood glucose concentrations, serum osmolalities, and serum creatinine measurements than do those without rhabdomyolysis. [Hylton V and Martin J]

The exact pathopysiology for this condition is not well established. Patient with DKA and severe rhabdomyolysis have higher short term mortality rates than patient presenting with only DKA. Serum CK is therefore recommended for patient with high risk of developing rhabdomyolysis (prolonged bed rest, significant alcohol consumption, drug use, and toxin exposure) or signs and symptoms of rhabdomyolysis (myalgias, urine dipstick with heme but no red blood cells, or tea-colored urine)

Eventhough DKA is often associated with DMT1, there are several reports shows that it can also occur in severe DMT2 patient with the present of stressor.Brian J. Welch, MD, and Ivana Zib, MD has shows two cases of DKA in DMT2 patient which is due to persistent lower back pain and sudden discontinuation of oral hypoglycaemic agent.

The possible mechanism of DKA in DMT2 is probably due to the combination of relative insulin deficiency and increased secretion of glucagon (as well as other counteregulatory hormones such as cortisol, catecholamines, and growth hormone) in response to stress from 1) overwhelming infection, 2) infarction of tissue, or 3) other severe illness. The elevated catecholamines further suppress insulin secretion to perpetuate a downward spiral. The increased glucagons-to-insulin ratio causes a mismatch that promotes unregulated lipolysis and proteolysis with subsequent uninterrupted formation of ketoacids. [Brian J& Ivana Zib]

Diabetic ketoacidosis is worrisome as it can cause cerebral edema which occur more frequently in children and newly diagnosed diabetes. This is often due to low PCO2 level, high serum urea and bicarbonate therapy. The mortality rate is around 25%. Besides that, DKA can also cause hypokalaemia and acidosis which can lead to multiple organ disturbances. Patient who is unconscious, especially children is easily get aspiration pneumonia; hence requiring airway management aggressively.

Pneumomediastinum is a benign, self-limiting complication of diabetic ketoacidosis. Acidotic (‘Kusmaul’) breathing alone may apparently induce transalveolar pressure swings that are sufficient to cause alveolar rupture. Intervention is not needed unless there is high suspicious that it is due to the rupture of esophagus or can cause life threatening condition.

Aggressive management of hyperglycemia, electrolyte loss and dehydration, avoidance of hyperglycaemia and metabolic acidosis and anticipation of the diabetic system complication need to be done in order improve patient outcome.

The decision to start bicarbonate therapy for the management of metabolic acidosis should only be justify in severe acidosis (pH<6.90)>

Outlines of management of DKA

1) Investigation- FBC, BUSE, Investigation to delienate causes (CXR, infective screen, ECG, urine FEME)

2) Goal of management- To correct (fluid loss, electrolyte loss esp pottasium, Hyperglycaemia, acidosis, Presipating factor)

Bibliography

1) British Society of Paediatric Endocrinology and Diabetes (BSPED) Recommended DKA Guidelines 2009, Julie A Edge, Oxford, May 2009

2) Case Report "An Uncommon Cause of Diabetic Ketoacidosis, Twice", K Nair et all, department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia

3) Case Study: Diabetic Ketoacidosis in Type 2 Diabetes: “Look under the Sheets”, Brian J. Welch, MD, and Ivana Zib, MD, CLINICAL DIABETES V22: No 4:2004.

4) Case Study: "Tea-Colored Urine in a Patient with Diabetic Ketoacidosis", Hylton V. Joffe, MD, and Martin J. Abrahamson, MD, CLINICAL DIABETES V22: No 4:2004.

5) Clinical Study "Bicarbonate Therapy in Diabetic Ketoacidosis", Ozlem Guneysel, Idil Guralp & Ozge Onur, Marmara University, School of Medicine Department of Emergency Medicine, Istanbul Turkey, Bratisl Lek Listy 2008;109(10) page 453-454.

6) “Clinical Practice Guidelines for Type 2 diabetes Mellitus”, The Malaysian Consensus, Ministry of Health Malaysia.

7) "Mediastinal emphysema complicating diabetic ketoacidosis: plea for conservative diagnostic approach", R.G. Pauw ET all, Netherlands: The Journal of Medicine, November 2007, vol 65, no 10.

8) Sarawak Handbook of Medical Emergencies 2^nd edition, Hua-Huat soo, Lee-Gong Lau& Peng-Hong Chew, C.E. Publishing, Sarawak, 2005.

9) "The Challenge of Type 1 Diabetes Mellitus", Larissa Eiselein, Henry J. Schwartz, and John C. Rutledge,ILAR Journal, Volume 45, Number 3 2004

10) "Toward a cure for type 1 diabetes mellitus: diabetes-suppressive dendritic cells and beyond", Nick Giannoukakis, Brett Phillips and Massimo Trucco, Pediatric Diabetes 2008: 9 (Part II): 4–13.