Comment: clinical significance of the HbA1c results in this patient

In this case HbA1c was requested to monitor how glycaemic control have been kept in previous months This predictive indicator give a time averaged picture of the patients blood glucose usually over the past 3 months The test result is reported as a percentage. The higher the percentage, the higher a persons blood glucose levels have been. This test therefore reflects a long term management of diabetes mellitus.

HbA1c limitations
Although no single test is exclusively perfect for the diagnosis of diabetes mellitus, the HbA1c and blood glucose tests are thus far the best tools available to diagnose diabetes. HbA1c normal reference range: < 6% The use of HbA1c has few application limitations, since there are some factors that can preclude its accurate measurement: In this particular case glycation due to diabetic nephropathy may influence levels of HbA1c Alterations in blood haemoglobin due to the alpha- toxin disrupting the cell membranes of erythrocytes result in lysis of the cells; this may be the reason HbA1c is 19.5%

HbA1c limitations contd

When the A1C test is used for diagnosis, the blood sample must be sent to a laboratory that uses an NGSP-certified method for analysis and ensure the assay is DCCT standardized.

Comment: triglyceride level seen in this patient

There are two plausible reasons for elevated triglycerides:

1. High Triglycerides
In uncontrolled diabetes mellitus glycogen reserves become depleted then the body begin to metabolize body stores of fat and proteins, how? Triglycerides are released from adipose tissue and become hydrolysed into Free Fatty Acids in circulation These FFAs are converted to Fatty acyl carnitines in the liver cells and further into acetyl CoA which enters the TCA cycle in the mitochondria for generation of energy. All this happens because the body is placing a demand for energy production while muscle tissue cells and other tissues are insensitive to insulin; this result in hypertriglycedaemia.

2. High Triglycerides
The other reason is that C.perfringens produces Lecithinase A an enzyme which removes single residues of fatty acids from Lecithins a group of yellow-brownish fatty substances occurring in animal and plant tissues composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids , triglycerides, and phospholipids; so this could also elevate triglycerides.

@Presentation
History Previous heart attack Takes medication for hypertension Extreme tiredness Polydipsia and Polyuria Frequent micturition

First Clinical Chemistry Lab Result

SERUM TEST Sodium: Potassium: Chloride: CO2 total: Urea Creatinine Cholesterol Triglyceride Glucose (random) RESULT 148 mmol/L 5.8 mmol/L 97 mmol/L 14.0 mmol/L 14.6 mmol/L 248 umol/L 5.8 mmol/L 6.8 mmol/L 24.5 mmol/L

The WHO guidelines dictates that a single abnormal result confirms the diagnosis of diabetes in non-pregnant individuals with classical symptoms of diabetes

First Clinical Chemistry Lab Result

URINE
TEST Glucose Ketones S.G. RESULT 4+ Negative 1.060

The WHO guidelines dictates that a single abnormal result confirms the diagnosis of diabetes in non-pregnant individuals with classical symptoms of diabetes

The reason the doctor requested a UAE in this patient

Standards of diabetic care put forth by the American Diabetes Association 2012 recommends that doctors screen patients for diabetic nephropathy in all type 2 diabetics at diagnosis which is the reason the doctor requested UAE after a review of the initial laboratory results having established that the patient had type 2 diabetes mellitus.

ADA 2012 Guidelines

Second Clinical Chemistry Result

SERUM TEST HbA1c RESULT 19.5 % URINE TEST UAE RESULT 290 mg/24hr

Diabetic Nephropathy
This patient developed Stage II Diabetic Nephropathy because UAE shows microalbuminuria UAE between 30 to 299 mg/24hr Measurement of microalbumin is useful to assist in diagnosis of kidney disease at an early stage before clinical proteinuria develops This condition could have been initiated by Reactive Oxygen Species and some Mediators of Inflammation produced by phagocytic cells and hyperproteinemia resulting from tissue destruction- C.perfringen infection

Clinical Stages of Diabetic Nephropathy

Pathogenesis of DN
Amassing of extracellular matrix Thickening of the Glomerular Basement Membrane (GBM) and Tubular Basement Membrane (TBM) Increased amount of mesangial matrix

Glomerulosclerosis Tubulo-interstitial Fibrosis