AK

chemistry unit 2 note glucose metabolism

Normal Physiology of Glucose Metabolism

  • Blood glucose testing is the single most-performed analysis in clinical chemistry; reflects cellular energy status.
  • Glucose = simple monosaccharide; chemical formula C6H{12}O_6.
  • Digestion/absorption
    • Dietary carbohydrates → monosaccharides absorbed in small intestine.
    • Liver converts non-glucose monosaccharides (galactose, fructose) → glucose.
  • Intracellular metabolic fates (dictated by cell needs & insulin)
    • Glycolysis → ATP (anaerobic & aerobic pathways).
    • Glycogenesis → glycogen storage (mainly liver & skeletal muscle; ≈10 % of liver weight).
    • Lipogenesis → conversion to fatty acids → adipose storage.
    • Protein synthesis → carbon skeletons for amino acids.
  • Key anabolic pathway terms
    • Glycogenesis – excess glucose → glycogen (liver, muscle).
    • Gluconeogenesis – lactate/amino acids → glucose; stimulated by glucagon, cortisol, thyroxine (T4).

Endocrine & Counter-Regulatory Hormones

  • Pancreas = mixed gland; endocrine portion = Islets of Langerhans.
    • β-cells → insulin (post-prandial hypoglycemic hormone).
    • α-cells → glucagon (fasting hyperglycemic hormone).
  • Insulin actions
    • Increases membrane glucose transporters → cellular uptake.
    • Promotes glycogenesis, lipogenesis, protein synthesis.
  • Glucagon actions
    • Opposes insulin; stimulates hepatic glycogenolysis & gluconeogenesis → ↑blood glucose.
  • Additional insulin antagonists: cortisol, growth hormone, epinephrine, thyroxine → maintain euglycemia during fasting/stress.

Post-Prandial & Fasting Balance

  • Carbohydrate-rich meal → plasma glucose spike → returns to baseline within 1.5–2 h with normal insulin response.
  • Single hormone lowers glucose (insulin); multiple raise it (counter-regulators) → imbalance leads to dysglycemia.

Definitions of Dysglycemia

  • Hyperglycemia
    • ↑blood glucose due to ↓/absent insulin, ↑glycogenolysis, or excess counter-hormones.
    • Principal clinical disorder: Diabetes Mellitus (DM).
  • Hypoglycemia
    • Blood glucose < 3.0\text{ mmol/L}.
    • Causes: iatrogenic insulin overdose, glycogen storage disease, insulinoma, islet-cell hyperplasia.
    • Life-threatening to CNS & cardiac tissue → symptoms: nausea, vomiting, tremor, seizures, coma.

Epidemiology (Canada)

  • >3 million diagnosed diabetics (8.9 % of population); prevalence rising 3.3 %/year.
  • 6.1 % exhibit pre-diabetes (high risk for Type 2 DM).

Clinical Classes of Diabetes

  1. Type 1 DM (T1DM)
    • Autoimmune β-cell destruction → absolute insulin deficiency.
    • Usually childhood onset; HLA-DR/DQ genes (6p21) linked; comorbid with celiac disease.
    • Lack of insulin → lipolysis → ketone bodies → diabetic ketoacidosis (DKA) → metabolic acidosis.
  2. Type 2 DM (T2DM)
    • Insulin resistance + progressive β-cell secretory defect.
    • Historically >40 y but rising in children/adolescents.
    • Risk factors: obesity (BMI >85th percentile in <18 y), family history, ethnicity, acanthosis nigricans, hypertension, gestational exposure.
    • Hyperglycemia complications similar to T1DM; ketoacidosis rarer.
  3. Gestational DM (GDM)
    • Glucose intolerance first recognized in pregnancy (usually 24–28 weeks).
    • Placental hormones → insulin resistance; maternal insulin demand ×3.
    • Untreated GDM harms fetus (macrosomia, neonatal hypoglycemia) though not teratogenic like pre-existing DM.
  4. Other specific causes: genetic β-cell defects, exocrine pancreatic disease (CF), drug/chemical induced (transplant immunosuppression, antiretrovirals), endocrine hyperfunction, traumatic brain injury, febrile illness.

Cardinal Signs & Symptoms of Diabetes

  • Polyuria, polydipsia, polyphagia, sudden weight loss, hyperglycemia (>renal threshold 10\text{ mmol/L}) → glucosuria, ketonemia/ketonuria during acute decompensation.

Laboratory Diagnosis & Monitoring

Core Tests

  • Fasting Plasma Glucose (FPG)
  • Oral Glucose Tolerance Test (OGTT)
  • Random Plasma Glucose
  • HbA1c (glycated hemoglobin)
  • Ketone determination (blood/urine)

Glycated Hemoglobin (HbA1c)

  • Non-enzymatic attachment of glucose to N-terminal valine of β-chain.
  • Reflects time-averaged glycemia over preceding ≈120 days (RBC lifespan).
  • Sample: EDTA whole blood; analysed via automated chemistry, HPLC, ion-exchange, or electrophoresis.
  • Diagnostic & therapeutic target:
    • ADA treatment goal <7 % (≤6.5 % preferable per CDA).
    • Test ≥2×/year if stable; quarterly if therapy changes/poor control.

OGTT Protocols

  • Standard adult: 75 g glucose load after ≥8 h fast; measure fasting & 2 h post-dose.
  • Paediatrics: 1.75\,\text{g kg}^{-1} up to 75 g.
  • GDM screening: 50 g (non-fasting) → 1 h plasma; if abnormal, confirm with 75 g OGTT (fasting + 1 h + 2 h).
  • WHO/CDA diagnostic cut-offs (mmol/L):
    • FPG ≥7.0 or 2 h ≥11.1 → diabetes.
    • IFG: FPG 6.1–6.9.
    • IGT: 2 h 7.8–11.0.
    • GDM confirmatory: FPG ≥5.3, 1 h ≥10.6, 2 h ≥9.0.

Reference & Critical Values (mmol/L)

  • Fasting 3.3–6.0; Random 3.3–11.0.
  • Critical (alert) ≤2.5 or ≥25.0 → immediate notification.
  • CSF glucose ≈ \tfrac{2}{3} of synchronous plasma (2.22–3.9 adult).
  • HbA1c reference (non-diabetic) 5.3–7.5 %.

Specimen Collection & Handling

Blood Matrices

  • Capillary (finger-stick): approximates arterial glucose; ~5 mg/dL (0.3 mmol/L) higher than venous fasting.
  • Venous whole blood, plasma, serum acceptable.
  • Tube selection
    • Grey-top (NaF/K-oxalate): inhibits glycolysis → stable for delayed testing.
    • Gold SST / Light-green PST: centrifuge within 2 h (gel barrier separates cells).
  • Fasting definition: no caloric intake 8–12 h; only water/approved meds.

Specimen Types & Use

  • Random: screening; no prep.
  • Post-Cibum (PC) 1–2 h after meal: occasionally monitor GDM.
  • Fasting: diagnosis, monitoring.
  • GDM screen: 50 g load anytime; 1 h plasma.
  • OGTT/GTT: fasting + timed draws (commonly 2 h).
  • Conversion factor: 1\text{ mmol/L}\approx18\text{ mg/dL}.

Point-of-Care Testing (POCT) – Glucometers

  • Provide intensive self-monitoring → ↓microvascular complications.
  • Specimen: capillary whole blood.
  • Strip chemistry
    • Glucose oxidase converts glucose → gluconic acid + H2O2.
    • Peroxidase + chromogenic indicator → colour proportional to glucose.
    • Reflectance/electrochemical meters read signal.
  • Quality Control
    • Manufacturer QC solutions (high & low) run per schedule; meter flags non-blood matrix.
    • Check strip expiry, lot integrity; follow IFU.
  • Lab vs POCT: laboratory hexokinase/glucose oxidase assays = higher accuracy, fewer interferences (e.g., maltose, galactose).

Laboratory Analytical Methods

  • Qualitative (historic): Benedict’s copper-reduction (colour change).
  • Quantitative
    • Glucose Oxidase-Peroxidase (colourimetric; suitable for CSF, limited in urine unless pre-treated).
    • Hexokinase/G-6-PD (NADPH absorbance at 340 nm); reference method, minimal interference; ideal for plasma, urine, other fluids.

Ketone Body Analysis

  • Increased when cells cannot utilize glucose (insulin lack) → fat catabolism.
  • Ketones: 3-β-hydroxybutyrate (78 %), acetoacetate (20 %), acetone (2 %).
  • Clinical contexts: DKA, starvation, prolonged vomiting.
  • Definitions
    • Ketonemia (blood), Ketonuria (urine).
  • Testing
    • Urine reagent strip with sodium nitroprusside → purple if positive (detects acetoacetate primarily).

Urinalysis in Glycemic Assessment

  • Glucosuria when plasma >10\text{ mmol/L} (renal threshold).
  • Fresh sample preferred; room-temp loss can reach 40 % in 24 h.
  • Refrigeration or preservatives required for delayed analysis.

Critical Thinking, Safety & Patient Care

  • Recognize adverse reactions to oral glucose drinks: nausea, diaphoresis, light-headedness; typically transient.
  • Allergy consideration (corn, tapioca) – arrange alternative solution.
  • Pregnancy: glucose drinks safe; remain in clinic to ensure timed draws.
  • Ethical/QA Imperatives
    • Accurate reporting of critical values → immediate clinician notification.
    • Maintain QC/QA logs for POCT & laboratory instruments.
    • Respect copyright/use limitations of learning material (Anderson College ©2022).

Integration & Real-World Relevance

  • Tight glycemic control demonstrated (DCCT/UKPDS) to reduce microvascular disease; underpins self-monitoring & HbA1c targets.
  • Insulin resistance central to metabolic syndrome → cardiovascular risk; early detection (pre-diabetes) allows lifestyle/pharmacologic intervention (e.g., metformin in post-GDM women).
  • POCT empowers patient autonomy, yet laboratory confirmation remains gold standard for diagnosis & legal documentation.

Quick Reference Cheat-Sheet

  • Diabetic Dx
    • FPG ≥7.0 OR 2 h OGTT ≥11.1 OR Random ≥11.1 + symptoms OR HbA1c ≥6.5 % (lab standardized).
  • Hypoglycemic Panic ≤2.5\text{ mmol/L}; Hyperglycemic Panic ≥25.0.
  • OGTT adult dose: 75 g; paediatric: 1.75\text{ g kg}^{-1} (max 75 g).
  • HbA1c monitoring: stable = biannual; unstable/change = quarterly.
  • Conversion \text{mg/dL} = mmol/L ×18.