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Causes of Diabetic Keto-Acidosis (DKA)

Question:

Discuss about the Type 1 and Type 2 Diabetes.

DKA is a major, acute life threatening condition that is normally associated to patients with type 1 diabetes. It is rarely seen in patients having Type 2 diabetes.

DKA is normally caused due to the active or the relative deficiency of insulin, accompanied by the increase of counter regulatory hormones involved in DKA, such as cortisol, glucagon, epinephrine growth hormone (Atkinson et al., 2014). This type of imbalance of the hormones of our body leads to hepatic gluconeogenesis (generation of glucose from non carbohydrate substrate), lypolysis (breaking down of lipids) (Knip & Siljander, 2008).

The excessive counter regulatory hormones, hepatic gluconeogenesis, glycogenolysis leads to severe hyperglycemia. Lack of insulin results in the release of fatty acid from the adipose tissue (lypolysis), increasing the amount of free fatty acids in the serum. Hepatic Metabolism of the fatty acids leads to the formation of the acidic intermediates and metabolites such as ketones and ketoacids (Atkinson et al., 2014).

Hormonal imbalance causes increased gluconeogenesis, renal and hepatic production of glucose and impaired utilization of glucose by the peripheral tissues. This results in hyperglycaemia and hyperosmolarity. Studies have revealed that the inflammatory biomarkers (e.g., C-reactive protein [CRP], oxidative stress markers, pro-inflammatory cytokines, cardiovascular risks and, lipid peroxidation is also associated with hyperglycemic risks. when the accumulated ketone bodies in the body exceeds the maximum capacity they are then found in the urine (Ketonuria) (Knip & Siljander, 2008).

Greater accumulation of the acids leads to acidosis, which can cause respiratory distress such as shallowed breathing (Kassmaul respiration). Normally kidney has a low threshold value for the keto-acids which gets excreted out through the urine. More amount of ketoacids leads to electrolyte loss resulting in acute dehydration with a large loss of sodium ions.

The common early signs and symptoms associated to DKA is polyuria. other signs and symptoms of this clinical condition involves malaise, fatigue, vomiting ,nausea, can have abdominal or muscular cramps, anorexia, loss of appetite, drastic weight loss in some patients, reduces perspiration, coma can occur at severe stages of the disease (Padgett et al., 2013). Fever, chills, chest pain, arthralgia and dyspnea can also occur. Unusual smell in the breadth is often found.

Causes

Type 1 diabetes is an autoimmune disease, where the immune system of the body mistakenly attacks the beta cells of the pancreas that is responsible for producing insulin. There are some genetic markers that are responsible for the T1D.

Symptoms of Diabetic Keto-Acidosis (DKA)

In type 2 diabetes the beta cells are not attacked by the immune system of the boy, rather the body normally stops responding to the secreted insulin and becomes insulin resistance. The body tries to compensate this condition and tries to produce more insulin, eventually it creates stress on the beta cells which may lead to their destruction, ceasing insulin production (Knip & Siljander, 2008). T2D is a life style disease and is mainly caused due to improper diet, obesity, use of alcohol, excessive consumption of the fatty food, excessive consumption of carbohydrate rich food. Stress can worsen the effects of T2D. Patients having family history of T2D are more likely to have T2D in future. Genetic factors obviously play a role in diabetes, although 2 persoms having same genetic mutation might not have the same effects of diabetes as diabetes largely depends on the life style.

Type 1Diabetes – T1D is an autoimmune disease caused due to the development of an autoimmune response against the Beta cells antigen due to which very less amount of insulin is produced inside the body, due to which the plasma glucagon level is increased. Increase in the counter regulatory hormones causes volume depletion of the extracellular fluids, hyperglycemia, and decreased potassium ions in the body. Hormonal imbalance increases the rate of gluconeogenesis, renal and hepatic glucose production, impaired utilization of glucose by the body tissues leads to hyper glycemia (Knip & Siljander, 2008). Free fatty acids are released into the serum from the adipose tissues. Hepatic metabolism of the fatty acids leads to the formation of the ketone bodies. Greater accumulation of the acids leads to acidosis, which can cause respiratory distress such as shallowed breathing or Kussmaul respiration.

Type 2 Diabetes- T2D is mainly caused due to the combination of insulin resistance and decreased secretion of insulin by the beta cells of pancreas, impaired regulation of glucose production in the liver. Beta cell glucotoxicity is caused by the inhibitory effect of the glucose secretion upon the release of insulin. Glycogen is accumulated in the beta cells due to prolonged glycemia (Kahn et al., 2014).

T1D

Medications such as Insulin, short acting insulin like novolog and humulin, rapid acting insulins such as insulin aspart, Angiotensin converting enzyme can be given. Amylinomimetic drugs such as pramlintide acetate can be given that elicit endogenous amylin by decreasing the postprandial glucagon release. (Padgett et al., 2013).

Treatments for Diabetic Keto-Acidosis (DKA)

Fibrous food, cereal with milk without fat, whole grain fibers, carbs, fruits, and lentils can serve to be best for the type 1 diabetes patients. Sugary drinks, trans-fats, simple carbohydrates like processed and refined sugars, foods containing saturated fats should be avoided should be avoided. It is advisable to eat smaller portion of well balanced meals for about six times a day (Knip & Siljander, 2008).

Aerobic exercises like walking, jogging, strength training exercises for about 30-40 minutes a day can be done for efficient muscles and strong bones. Stretching exercises can be done to maintain flexibility in the body. Other than this, games such as badminton, volleyball can be played to maintain fitness and to burn the extra calories.

T2D

Oral hypo-glycaemic class of medications is used in case of T2D. Alpha glucosidase inhibitors like acarbose and miglitol, which helps to break down the starchy food. Biguanides, dopamine agonist, DPP-4 inhibitors like alogliptin, Incretin mimetics increases the B- cell growth, meglitinides, sodium glucose transporter (SGLT) 2 inhibitor. Sulphonylureas stimulates the pancreas for secreting insulin, thiazolidinediones (Knip & Siljander, 2008).

Food- diet for Type 2 diabetes includes carbs, non-starchy vegetables, and complex carbohydrates such as brown rice, whole wheat, lentils beans and fruits. Sugary beverages, high-calorigenic food, saturated and Trans fats should be avoided. It is advisable to avoid alcoholic drinks (Padgett et al., 2013).Repeated eating with balanced meal is advisable rather than large single meal.

Exercises- Daily exercises such as running, aerobics and yoga for about 30-40 minutes in about 5 days a week can be done to maintain T2D.

Diabetic Keto-acidosis

This condition occurs when the body cannot produce enough insulin. Absence of insulin and the increase in the glucagon level results in the release of glucose by the liver.

Insufficient insulin does not allow enough glucose to enter the cells, as a result the fatty acids are broken down as an alternative energy source, producing acidic ketone bodies. DKA is mainly caused in people with T1D (Kahn et al., 2014).It can cause excessive urination, flushed and dry skin, drowsiness and rapid breathing, fruity smell breath. It can also cause severe illness or coma.

This condition occurs when there is extremely high blood sugar level (Plasma glucose level of 600mg/dL or more) caused due to insulin deficiency. Due to this the serum osmolarity level is greater than 320 mOsm.  Excessive urination occurs due to this condition, which leads to hemo-concentration and volume depletion that further increases the blood sugar concentration (Padgett et al., 2013).

Type 1 Diabetes (T1D)

It can cause motor and sensory impairment. Hyper viscosity can increase the risk of clotting of bloods, which can be linked to cardiovascular diseases.

In this case ketoacidosis does not occur because the insulin inhibits the fatty tissue breakdown by the hormone sensitive lipase. It is found mainly in patient with type 2 diabetes.

 OGTT

Procedures for OGTT (Stumvoll et al., 2010)

  1. The patient should be abstained from food 8 hours before the test.
  2. Patient should fast for 8-12 hours before the conduction of the test.
  3. A fasting sample of venous blood is extracted in a vial and tested for glucose level.
  4. The patient is given aqueous solution of glucose of about 50 gram. The time is noted.
  5. 6. A fasting blood glucose is at first taken. The patient is then administered glucose drink orally and then after 2 hours another blood sample is taken and measured.
  6. The blood sample is tested in the laboratory and a curve is plotted by taking time on the x axis and plasma glucose level on the Y axis and a glucose tolerance curve is made.

Normal range level of glucose in blood

Normal range

Fasting

<110mg/dl

(

1 hour after glucose administration

(

2 hours after glucose administration

(

Positive diagnostic marker

  1. Fasting glucose level is higher than 110mg/dl or 6.1mmol/L in the blood.
  2. The highest value of the curve is reached within 1.5 hours.
  3. The blood glucose level does not match the fasting level even after the 2.5 hours.
  4. Over 11.0 mmol/L of Glucose is found in the blood sample.

Procedure (Rohlfing et al., 2002)

  1. The patient should not consume any food or drink for at least 8 hours before the collection of the blood sample.
  2. Blood is collected from the patient and is stored in a vial for the testing of glucose.

  Normal range level

 A blood glucose level of 100–125 mg/dL (5.54 – 6.9mmol/L) determines prediabetes.

Positive diagnostic marker

Blood glucose level of 126 mg/dL (Over 11.0 mmol/L) and higher indicates diabetes.

HbA1c Test

Glycated hemoglobin (A1C) test helps in indicating the average blood sugar level for the past two to three months. It helps to assess the amount of blood sugar linked to hemoglobin.  More the hemoglobin with sugar attached, more is the blood sugar level.

Procedure

 Blood sample is collected from the patient. They can be tested for the presence of glucose with the help of these 3 methods-

  1. Chromatography based HPLC assay (Newman & Turner, 2005).
  2. Antibody based immunoassay
  3. Enzyme based enzymatic assay (International Expert Committee, 2009).

Normal range levels

The normal range for the hemoglobin A1c level for people without diabetes is between 4% and 5.6%.

Positive diagnostic marker

 Hemoglobin A1c levels between 5.7% and 6.4% indicates higher chance of getting diabetes.  6.5% or higher levels that the patient is having diabetes.

In the following case study, James has been newly diagnosed with TID. Management of TID can be done with effective collaborative approach (Barlow et al., 2002)

Diabetes educator- Diabetes educators are the members of the multidisciplinary team who impart education to the patient regarding the pathophysiology and the self management of diseases. A diabetes educator will be able to provide all the information regarding diabetes, to the patient and would help the patient in the self management of diabetes.(Zurich et al., 2003).

Oral care professionals – People suffering from diabetes bears greater chance of periodontal diseases such as dry mouth, gingivitis, thrush .Therefore a dental care doctor would be able to help the patient in managing oral health by frequent checkups such as once in every three months. (Maahs et al., 2010).

Dieticians- The dieticians help to prepare proper diet chart for the diabetic patient. Since diabetes can be managed at large by controlling the food habits and proper exercises, a dietician is professionally qualified to prepare a suitable diet chart for the diabetes patient consisting of non -glycemic food such as fibers, proteins; switching the meal plan from white bread and flour to whole grain, bran, barley, oats and lots of vegetables and maintenance of the electrolyte balance in the body by the intake of oral fluids.

Type 2 Diabetes (T2D)

Eye care professionals- They are responsible for taking care of the eyes, as eyes are largely affected due to diabetes. Persistently high blood sugar level can cause eye diseases such as retinopathy, muscular degeneration, cataract, glaucoma. (Maahs et al., 2010). It is advisable to have an eye check up at least once in every 6 months.

James with diabetes can be vulnerable to nerve damage in his feet, so podiatrists will assess his general foot health and function. They educate him how to prevent feet problem and keeping him healthy. Foot ulcers can cause amputation, so for someone like James it is very important to check his feet regularly. The examination should be done every two to three months.

  1. Traditional home monitoring device-Blood glucose meters contain a test strip for taking the blood and a meter that will calculate the glucose levels (Orchard et al., 2015).
  2. Some glucose monitoring devices tests blood from other parts of the body other than finger tips, although the results are not much reliable.
  3. Continuous glucose monitoring system combined with insulin pumps.
  4. Monthly blood glucose monitoring diary
  5. A daily monitoring diaries to record the doses of the medications.
  6. Suitable syringes (4-5mm long)
  7. Injection aids such as automatic injectors or temporary injection ports (For those who are afraid of needles)
  8. Insulin pen (Prefilled pens- which are disposable insulin pens or Durable pens- they contain replaceable insulin cartridges)
  9. 6

National Diabetes Services Scheme (Australia)

The National Diabetes Services Scheme (NDSS) is an initiative taken up by the Australian government in collaboration with the diabetes Australia (Rabi et al., 2006). The main aim of NDSS is to impart knowledge to the Australian regarding the self management of diabetes. They have also taken initiatives to support the people by providing timely care and management to the patients (Lee et al., 2013).

Registering under NDSS helps the patient to access a wide range of service. For the member ship cost it is advisable to contact the territory organization. Registration to NDSS is free of cost and requires only one time registration (Lee et al., 2013).

Eligibility criteria  (Lee et al., 2013)

  • The patient should be a resident of Australia. If someone is visiting from the other country, he should have a health agreement visa.
  • The patient should have diabetes confirmed by a doctor.
  • They should hold a Department of Veteran's affairs card or a Medicare card.
  • One is not eligible to register if he has impaired glucose tolerance and pre-diabetes.

References

Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014). Type 1 diabetes. The Lancet, 383(9911), 69-82.

Barlow, J., Wright, C., Sheasby, J., Turner, A., & Hainsworth, J. (2002). Self-management approaches for people with chronic conditions: a review. Patient education and counseling, 48(2), 177-187.

International Expert Committee. (2009). International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes care, 32(7), 1327-1334.

Jurik, F. A., Stubbs, A., Dao, M. D., & Chang, C. (2000). U.S. Patent No. 6,162,397. Washington, DC: U.S. Patent and Trademark Office.

Kahn, S. E., Cooper, M. E., & Del Prato, S. (2014). Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. The Lancet, 383(9922), 1068-1083.

Knip, M., & Siljander, H. (2008). Autoimmune mechanisms in type 1 diabetes. Autoimmunity reviews, 7(7), 550-557.

Lee, C. M. Y., Colagiuri, R., Magliano, D. J., Cameron, A. J., Shaw, J., Zimmet, P., & Colagiuri, S. (2013). The cost of diabetes in adults in Australia. Diabetes Research and Clinical Practice, 99(3), 385-390.

Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and metabolism clinics of North America, 39(3), 481-497.

Newman, J. D., & Turner, A. P. (2005). Home blood glucose biosensors: a commercial perspective. Biosensors and Bioelectronics, 20(12), 2435-2453.

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.

Padgett, L. E., Broniowska, K. A., Hansen, P. A., Corbett, J. A., & Tse, H. M. (2013). The role of reactive oxygen species and proinflammatory cytokines in type 1 diabetes pathogenesis. Annals of the New York Academy of Sciences, 1281(1), 16-35.

Rabi, D. M., Edwards, A. L., Southern, D. A., Svenson, L. W., Sargious, P. M., Norton, P., ... & Ghali, W. A. (2006). Association of socio-economic status with diabetes prevalence and utilization of diabetes care services. BMC Health Services Research, 6(1), 124.

Rohlfing, C. L., Wiedmeyer, H. M., Little, R. R., England, J. D., Tennill, A., & Goldstein, D. E. (2002). Defining the relationship between plasma glucose and HbA1c. Diabetes care, 25(2), 275-278.

Shaw, J. E., Sicree, R. A., & Zimmet, P. Z. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes research and clinical practice, 87(1), 4-14.

Steinsbekk, A., Rygg, L., Lisulo, M., Rise, M. B., & Fretheim, A. (2012). Group based diabetes self-management education compared to routine treatment for people with type 2 diabetes mellitus. A systematic review with meta-analysis. BMC health services research, 12(1), 213.

Stumvoll, M., Mitrakou, A., Pimenta, W., Jenssen, T., Yki-Järvinen, H. A. N. N. E. L. E., Van Haeften, T., ... & Gerich, J. (2000). Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes care, 23(3), 295-301.

Worthington, D. R., & Brown, S. J. (2002). U.S. Patent No. 6,379,301. Washington, DC: U.S. Patent and Trademark Office.

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