Therapeutics Question (DKA)

A 50-year-old gentleman, Mr Adam, was brought in to the Emergency Department by his friends. He was found to have collapsed at work. He is known to have diabetes mellitus for the past 10 years, on oral hypoglycaemic agents. According to his friends, he has been feeling unwell for the past 2 days, complaining of chills, rigors and vomiting. Upon examination, he is drowsy with a GCS of 12/15. He was breathing rapidly and his tongue was dry and coated. There was infected ulcer on his right foot with surrounding erythema and pus discharge. Physical examination did not reveal any other abnormality.

Initial blood investigations results: 

Random blood glucose 27.2mmol/L

pH 7.21

PaO2 10.8kPa

PaCO2 5.1kPa

HCO3 11mmol/L

Urine ketone +++

Q1. What is criteria for the diagnosis of diabetes mellitus?

Answer for Q1

ANSWER: Criteria for the diagnosis of diabetes1. HbA1C ≥6.5%. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.*

OR 2. FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*

OR 3. 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*

OR 4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l). 

↵*In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing.

Q2. What is the most likely diagnosis for the presentation of Mr Adam?

Diabetic ketoacidosis with an infected foot ulcer. DKA is characterized by hyperglycaemia, acidosis and ketonaemia. It usually occurs in Type 1 diabetics, but may occur in type 2 diabetics, too.

Q3. What other investigations should be performed?

full blood count, blood culture and sensitivity, swab from foot ulcer for culture, renal profile, ECG

Q4. Outline the initial management of this patient.

Correction of fluid loss with intravenous fluids monitoring of input and output. CVP monitoring might be necessary in those with renal failure and congestive cardiac failure to monitor fluid replacement.Correction of hyperglycemia with insulin infusion.Correction of electrolyte disturbances, particularly potassium loss. Potassium can be started with fluid replacement unless there is hyperkalaemia.Treatment of the infected foot ulcer with intravenous antibiotics eg. UnasynBlood glucose levels should be monitored regularly (hourly) to prevent hypoglycaemia , as this may lead to rebound ketosis, necessitating a prolonged duration of treatment.

Mr Adam’s condition gradually improves. The next day, he is conscious and orientated. His blood glucose levels have improved and single digit readings recorded. Urine ketone levels , when checked, were not detected. However, a call from the lab assistant was received, to inform that Mr Adam’s latest potassium level is 7.0mmol/L. 

Q5.What should be the immediate management?

Stop any potassium replacement and medication that may contribute to the hyperkalaemia. Perform an urgent ECG looking for signs of hyperkalaemia (tall,tented T waves, increased PR interval, wide QRS complex, VF). 10mls of Calcium gluconate is cardioprotective. Short acting insulin and glucose is also administered to move potassium into the cells. Calcium resonium aids in the removal of potassium from the body. Potassium levels should be repeated after that.

Mr Adam is discharged after one week. He is reviewed in the clinic two months later. He is currently on Metformin 1g bd . He has no immediate complaints and says that he is compliant to his medication. He has also had no hypoglycaemic symtoms. His HbA1C is 8 % and fasting blood glucose is 12mmol/L. 

Q 6. Which group of drugs does metformin belong to? What is the mechanism of action?

Metformin is a biguanide anti-diabetic medcation. Metformin is effective only in the presence of insulin, and its major effect is to decrease hepatic glucose output . Metformin increases insulin-mediated glucose utilization in peripheral tissues (such as muscle and liver), particularly after meals, and has an antilipolytic effect that lowers serum free fatty acid concentrations, thereby reducing substrate availability for gluconeogenesis . As a result of the improvement in glycemic control, serum insulin concentrations decline slightly. Metformin also increases intestinal glucose utilization via nonoxidative metabolism.

Q7. What is the target for his blood sugar control?

Glycemic targets must be individualized. However, therapy in most patients with type 2 diabetes should be targeted to achieve an HbA1C ≤7.0% in order to reduce the risk of microvascular and macrovascular complications. Patients with type 2 diabetes should aim for fasting plasma glucose (FPG) target of 4.0 to 7.0 mmol/L and 2-hour postprandial PG targets of 5.0 to 10.0 mmol/L.

Q8. What is the next step in his management?

Addition of one of the other classes of oral anti-diabetic agent at a low dose and increasing the dose to obtain optimal control. An alternative would be to add on insulin.

Mr Adam asks about his blood pressure, which is noted to be 160/90mmHg in the clinic. Q9. What should be the advice given?

Systolic BP should be targeted to <130 mmHg and diastolic pressure <80 mmHg. The BP should be lowered even further to ≤125/75 mmHg in the presence of proteinuria of >1g/24 hours. ACE inhibitors and ARB’s are the drugs of choice, however, tight BP control should take precedence over the class of antihypertensive drug used. This often will require combination therapy. A lower target BP may be necessary to maximally protect against the development and progression of cardiovascular and diabetic renal disease.

Q10. He also asks about his diet and asks regarding lifestyle modification. What should be the advice given?

He should be advised to increase physical activity(exercise about 5 times aweek) and lose weight (if indicated). A diet low in saturated fats, trans fat and cholesterol should be advocated. His meals should be regular and the diet should consist of carbohydrate from cereals (preferably whole grain), fruits, vegetables, legumes, and low-fat or skimmed milk. Total carbohydrate intake should be consistent and evenly distributed throughout the day i.e. 3 main meals with 1 or 2 snacks in between without incurring any excess calorie intake.

Smoking cessation and reduction of alcohol intake should be encouraged.