Chapter 2 — Carbohydrate Metabolism, Glucose and Diabetes

What is diabetes mellitus?

A clinical syndrome with chronically elevated blood glucose due to absolute or relative insulin deficiency.

What is the most basic laboratory test for diabetes diagnosis?

Blood glucose determination.

What fasting venous plasma glucose value indicates diabetes according to WHO 1999?

≥7.0 mmol/L.

What 2-hour venous plasma glucose value indicates diabetes after OGTT?

≥11.1 mmol/L.

What are the main types of diabetes mellitus?

Primary diabetes, secondary diabetes and gestational diabetes.

What are the two main forms of primary diabetes?

Type 1 and type 2 diabetes mellitus.

What characterizes type 1 diabetes mellitus?

Autoimmune beta-cell destruction, absolute insulin deficiency, severe hyperglycemia and risk of ketoacidosis.

What percentage of diabetes cases are type 1?

About 5–10%.

What characterizes type 2 diabetes mellitus?

Insulin resistance with relative insulin deficiency.

What percentage of diabetes cases are type 2?

About 80–90%.

Is ketoacidosis common in type 2 diabetes?

No, it is rare.

What is secondary diabetes?

Diabetes caused by another disease, condition or drug.

Name causes of secondary diabetes.

Pancreatic damage, Cushing disease, acromegaly, corticosteroids, beta-cell defects and genetic syndromes.

What is gestational diabetes?

Diabetes first diagnosed during pregnancy.

Which sample types can be used for glucose measurement?

Whole blood, plasma or serum; venous or capillary blood.

How does whole blood glucose compare with plasma/serum glucose?

Whole blood glucose is slightly lower.

How does venous glucose compare with capillary glucose?

Venous glucose is slightly lower.

Why must glucose sample type be standardized?

Because results differ between whole blood, serum/plasma, venous and capillary samples.

Why does glucose decrease in unprocessed blood?

Because blood cells continue glycolysis.

How can glycolysis be inhibited in glucose samples?

By using sodium fluoride or rapid separation of plasma/serum from cells.

Which two glucose methods are most common in clinical biochemistry?

Glucose oxidase method and hexokinase method.

What is the GOD-PAP glucose reaction idea?

Glucose is converted to H₂O₂, and H₂O₂ forms a colored dye.

What is the first GOD-PAP reaction?

Glucose + O₂ + H₂O → gluconic acid + H₂O₂.

Which enzyme catalyzes the first GOD-PAP reaction?

Glucose oxidase.

What is the second GOD-PAP reaction?

H₂O₂ reacts with phenol and 4-aminophenazone to form quinoneimine dye.

Which enzyme catalyzes the GOD-PAP color reaction?

Peroxidase.

What does the GOD-PAP spectrophotometer measure?

The absorbance of the red-violet quinoneimine dye.

What is the hidden idea of GOD-PAP?

More glucose produces more H₂O₂, more dye and higher absorbance.

What is the hexokinase method reaction idea?

Glucose is converted to glucose-6-phosphate, then NAD⁺ is reduced to NADH.

What is the first hexokinase reaction?

Glucose + ATP → glucose-6-phosphate + ADP.

Which enzyme catalyzes glucose phosphorylation in the hexokinase method?

Hexokinase.

What is the second hexokinase reaction?

Glucose-6-phosphate + NAD⁺ → gluconate-6-phosphate + NADH + H⁺.

Which enzyme catalyzes the second hexokinase reaction?

Glucose-6-phosphate dehydrogenase.

Why is NADH important in the hexokinase method?

NADH absorbs UV light around 340 nm.

What does the hexokinase method measure?

The increase in NADH absorbance.

Why is the hexokinase method called a UV test?

Because NADH is measured in the UV range.

What is deproteinisation?

Removal of proteins from a sample, often by precipitation.

Why is deproteinisation used in whole blood glucose analysis?

To remove proteins and cellular material that may interfere.

What does a glucometer measure?

Glucose in capillary whole blood using dry reagents on a strip or cuvette.

What are two principles of glucometer measurement?

Reflectance photometry or electrochemistry.

What is glucosuria?

Presence of glucose in urine.

Why does glucosuria occur?

Blood glucose exceeds renal tubular reabsorption capacity.

What is the renal threshold for glucose?

The blood glucose level above which glucose appears in urine, roughly 9–11 mmol/L.

What is renal glucosuria?

Glucosuria despite normal blood glucose due to reduced tubular glucose reabsorption.

How is urine glucose usually detected?

By dry chemistry test strips using glucose oxidase.

What are ketone bodies detected in urine by?

Reaction of acetoacetate and acetone with sodium nitroprusside.

Which ketone body is not detected by sodium nitroprusside?

Beta-hydroxybutyrate.

What does glucose plus ketone bodies in diabetic urine indicate?

Poor diabetes control and need for more intensive treatment.

Can ketones appear without diabetes?

Yes, during fasting.

What type of method are urine test strips?

Semiquantitative.

Why are urine test strips semiquantitative?

The color intensity is compared with a reference scale, giving approximate concentration ranges.

What is OGTT?

Oral glucose tolerance test.

When is OGTT especially useful?

When fasting glucose is near or slightly above the upper reference limit.

How much glucose is given in adult OGTT?

75 g glucose dissolved in 250–300 mL water.

How long should the patient fast before OGTT?

12–14 hours.

How much carbohydrate should be eaten before OGTT?

At least 150 g per day for 3 days.

When is blood usually drawn after glucose intake in OGTT?

After 120 minutes.

What fasting glucose is normal in OGTT criteria?

What 2-hour glucose is normal in OGTT criteria?

What is impaired fasting glycemia?

Fasting glucose ≥6.1 and <7.0 mmol/L with 2-hour glucose <7.8 mmol/L.

What is impaired glucose tolerance?

Fasting glucose <7.0 mmol/L and 2-hour glucose ≥7.8 mmol/L.

What is HbA1c?

Glycated hemoglobin formed by non-enzymatic glucose binding to hemoglobin A.

Why does HbA1c reflect long-term glycemic control?

Because glycation is irreversible and erythrocytes live about 120 days.

What period does HbA1c mainly reflect?

The previous 2–3 months.

What is the normal HbA1c reference range?

About 4.0–6.0%.

What HbA1c value is diagnostic for diabetes according to ADA 2012?

≥6.5%.

What is the treatment goal for HbA1c in established diabetes?

Below 7.0%.

When can HbA1c be falsely low?

Hemolytic anemia or recent significant blood loss.

When can HbA1c be falsely high?

Iron-deficiency anemia.

What is fructosamine?

Glycated serum proteins, mainly glycated albumin.

What time period does fructosamine reflect?

Previous 2–3 weeks.

Why can fructosamine change faster than HbA1c?

Albumin has a shorter half-life than erythrocytes.

What is microalbuminuria?

Urinary albumin excretion of 30–300 mg/24 h.

Why is microalbuminuria important in diabetes?

It is an early marker of diabetic nephropathy.

Why may routine urine strips miss microalbuminuria?

Their detection limit is too high for low albumin increases.

What samples can be used for microalbuminuria?

24-hour urine, overnight urine, short timed urine or first morning urine albumin/creatinine ratio.

Why are repeated microalbuminuria measurements recommended?

Because intraindividual variation is high.

What is C-peptide?

A peptide released in equimolar amounts with endogenous insulin from proinsulin.

Why is C-peptide useful?

It reflects endogenous insulin production.

Why is C-peptide better than insulin in insulin-treated patients?

It is not affected by injected insulin.

What are indications for C-peptide measurement?

Diabetes evaluation, insulinoma, post-pancreatectomy monitoring and beta-cell transplant assessment.