Diabetes Mellitus: Biochemical Monitoring

• Diabetes mellitus is characterized by abnormal metabolism of glucose, free fatty acids, and amino acids, stemming from a relative or abnormal lack of insulin.
• This chronic disease necessitates long-term management, emphasizing regular biochemical monitoring for glycemic control and early detection of metabolic complications.
• Monitoring typically involves urine and blood samples.

Biochemical Parameters

• Blood samples are used to measure glycemic levels via glucose, glycated hemoglobin and fructosamine.
• Blood samples can assess complications, such as EUCr.
• Urine samples assess glucose, ketones and proteins.

Glycosuria

• Glycosuria is defined as a concentration of urinary glucose detectable through relatively insensitive, yet specific, screening tests.
• The tests often rely on enzymes like glucose oxidase, incorporated into diagnostic strips.
• Proximal tubular cells usually re-absorb most glucose from the glomerular filtrate; glycosuria occurs when plasma and glomerular filtrate concentrations surpass the tubular reabsorptive capacity.
• Glycosuria can occur when plasma and glomerular filtrate concentrations exceed approximately 10mmol/L, overwhelming normal tubular re-absorption.
• Reduced glomerular filtration rate may prevent glycosuria despite plasma glucose concentrations above 10mmol/L.
• A diagnosis of diabetes mellitus should not rely solely on glycosuria; however, some diabetic patients use glycosuria testing to monitor their therapy.

Blood Glucose

• Glucose testing reagent strips can measure blood glucose concentrations.
• Strips can be assessed visually or through a portable glucose meter; the reaction often involves enzymatic determination of glucose, such as glucose oxidase.
• Meters should undergo regular checks by laboratory staff.
• Insulin doses can adjusted more accurately based on blood glucose measurements, despite the discomfort of skin punctures to obtain the sample.
• Blood glucose testing is useful for detecting hypoglycemia.
• Urinary glucose testing serves as an alternative for those averse to blood testing, though it cannot detect hypoglycemia and depends on the renal glucose threshold.

Glycated Hemoglobin

• Glycated hemoglobin (HbA1c) is expressed as a percentage of total blood hemoglobin concentration.
• HbA1c provides a retrospective assessment of mean plasma glucose concentration over the prior 6–8 weeks.
• A higher percentage indicates poorer diabetic or glycemic management.
• Glycated hemoglobin forms through non-enzymatic glycation.
• Glycation is determined by mean plasma glucose concentrations and the lifespan of red blood cells.
• Patients with hemolytic disease may show falsely low HbA1c values.
• Blood HbA1c measurement serves as an adjunct, not a replacement, for serial plasma glucose estimations, which are needed to reveal potentially dangerous short-term swings.
• HbA1c does not detect hypoglycemic episodes.
• Intervention trials in type 1 and 2 diabetes show that optimizing glycemic control to about 7% reduces the risk of microvascular diabetic complications with HbA1c monitoring.
• Measuring HbA1c has been used for the diagnosis of Diabetes Mellitus.

Urinary Albumin Determination & Diabetic Nephropathy

• Microalbuminuria, characterized by small amounts of albumin in the urine, is one of the earliest signs of diabetic renal dysfunction.
• Microalbuminuria: If untreate, it can lead to overt albuminuria or proteinuria (exceeding 300 mg/day), impaired renal function, and ultimately end-stage renal failure.

Microalbuminuria

• Microalbuminuria is defined as urinary albumin excretion of 30–300 mg/day or 20–200 µg/min.
• Normoalbuminuria is defined by an albumin concentration less than 30 mg/day or less than 20 µg/min.
• A random urine sample or timed overnight collection can measure urinary albumin excretion.
• A urinary albumin:creatinine ratio (ACR) can be measured to avoid timed urine collection, with normal values below 2.5 g/mol in males and 3.5 g/mol in females.
• Confirm an abnormal ACR value in two out of three urine samples, absent other causes of proteinuria.
• Urinary albumin excretion is associated with increased vascular permeability and a higher risk of cardiovascular disease.

Treating Microalbuminuria

• Glycemic control optimization and hypertension treatment can slow the progression of microalbuminuria.
• A blood pressure target below 140/80 mmHg is recommended for type 2 diabetes, or 135/75 mmHg or lower if microalbuminuria is present.
• Blood pressure targets are typically more aggressive in type 1 diabetes due to higher lifetime risks of overt nephropathy.
• Angiotensin–converting enzyme (ACE) inhibitors like lisinopril can reduce albumin excretion in type 1 diabetic patients with microalbuminuria; similar effects were observed with enalapril in type 2 diabetes.
• ACE inhibitors have renal protective benefits beyond their blood pressure-lowering effects.

Fructosamine

• Plasma fructosamine concentrations can be used to assess glucose control over a shorter period than HbA1c (approximately 2–4 weeks), but the assay has methodological limitations.
• Fructosamine reflects glucose bound to plasma proteins, predominantly albumin, which has a plasma half-life of about 20 days.
• Fructosamine assays can be helpful in pregnancy and when hemoglobin variants, such as HbS or HbC, interfere with HbA1c assays.

Acute Metabolic Complications of Diabetes Mellitus

• Hyperglycemia
• Diabetic ketoacidosis
• Hyper-osmolal non-ketotic coma
• Lactic acidosis

Measurements to Detect Complications

• Assess acid-base balance during complication management.
• Assess kidney function via electrolytes, urea, and creatinine.
• Evaluate cardiovascular risks through lipid profiles.
• Check Cardiac markers, if indicated.