Glucose

Regulation of Blood Glucose in Fasting State

• Fasting is the post absorptive state when no food is taken at all and sufficient energy is not available.
• Catabolic pathways predominate.
• Plasma levels of glucose, amino acids, TAG, fall
• Insulin secretion decreases
• Glucagon and epinephrine secretion increases.
• Liver in this state:-
  • Maintains normal blood glucose level.
  • Provides glucose to tissues by glycogenolysis and gluconeogenesis.
  • Synthesizes and distributes ketone bodies to peripheral tissues.
• Presence of glucose-6-phosphate in liver releases glucose from both glycogenolysis and gluconeogenesis
• Glycogen stores start getting depleted 5-6 hours into fasting and are completely depleted at the end of 10-18 hours.
• Increased gluconeogenesis using carbon skeleton from glucogenic amino acids, lactate from muscles, and glycerol from adipose tissue.
• Adipose tissue undergoes lipolysis and releases free fatty acids as an alternate source of energy.

Regulation of Blood Glucose in Fed State

• Fed state is the absorptive state, 2-4 hours after ingestion of a normal meal.
• Increased uptake of glucose
• Increased phosphorylation of glucose by glucokinase as glucokinase has low Km but in liver glucose concentration is high.
• After phosphorylation, G-6-P cannot come out of the cell and is thus utilized by glycolysis, glycogen synthesis and HMP shunt pathway.
• These are by: Increased insulin to glucagon ratio and activates the enzymes of these pathways.
• Insulin is an anabolic hormone.

Normal Blood Glucose Level

Normal random blood glucose level, fasting : 70 – 110 mg/dl

Normal random blood glucose level, post prandial: 80- 140mg/dl

Monitoring Test-

• Microalbumin Test-
  • Early indication of nephropathy in diabetics and hypertensives
  • Expressed as albumin creatinine ratio
  • Normal level:-
    • Male- <23 mg/g of Creatinine
    • Female- <32 mg/g of Creatinine
• Glycated Hemoglobin-
  • Gives glucose value over last 3 months as half-life of RBCs is around 120 days.
  • Glycation is irreversible, non-enzymatic addition of sugar to protein.
  • Interpretation-
    • 4-5.5% : Normal (<110 mg/dl of glucose)
    • 6%- Good glycemic control of DM (126mg/dl glucose)
    • 7%- adequate control
    • 8%- Inadequate control
    • 9% – Poor control
    • 1% reduction reduces incidence of complications by 30%
  • Advantages-
    • Fasting is not required
    • Not affected by acute factors
    • Gives report of last 3 months
    • Helps in prediction of complications
  • Disadvantages-
    • Not a good indicator in cases of thalassemia, sickle cell anemia and other hemolytic conditions.
• Lipid Profile
• Renal Function Tests

Diagnostic Test- OGTT

• Indications-
  • Patient has symptoms of DM, but inconclusive fasting blood sugar value.
  • Excessive weight gain during pregnancy
  • History of big baby(>4kg)
  • History of miscarriage
  • To rule out benign renal glucosuria
• Contraindications-
  • Confirmed DM
  • Follow up of DM
  • Acutely ill patients
• Procedure-
  • The patient who is scheduled for OGTT is instructed to consume high carbohydrate diet for at least 3 days prior to the test, and come after an overnight fast on the day of the test.
  • A fasting blood glucose sample is first drawn.
  • 75 grams of glucose [or 1.75 grams per kg of body weight in case of children ] dissolved in 250-300 ml of water is given orally.
  • After giving glucose, blood and urine specimens are collected at half hourly intervals for at least two hours in case of classical gtt.
  • As per current WHO recommendations, Mini GGT is conducted in which only fasting and 2 hour post glucose load sample of blood and urine is collected.
  • A graph is plotted with plasma glucose on the vertical axis, against time of collection on the horizontal axis called the Glucose Tolerance Curve
• Interpretation
  • In Normal Condition – After the glucose load, insulin is secreted from beta cells of pancreas. Utilization of glucose by the cells maintains the normal blood glucose level.
  • In Impaired Glucose Tolerance- Impairment in the secretion of insulin to maintain normal blood glucose. These patients have 2% risk progression to developing diabetes mellitus.
  • In Diabetes Mellitus- Insulin deficiency or resistance seen. After the glucose load it cannot be utilized, therefore, excretes in urine (renal threshold is 180 mg/dl). Fasting and 2 hours after glucose load values are >126 mg/ dl and >200 mg/dl.
  • In Increased Tolerance-
    • Increased ability of body to utilise glucose
    • Fasting blood glucose is lower than normal
    • Even after glucose load, only a small rise in blood glucose, no more than 100mg% is observed.
    • A flatter curve is obtained
    • No appearance of glucose in urine.
    • Appears in case of endocrine hypoactivity, such as
      • Hypothyroidism like myxedema and creatinine.
      • Hypoadrenalism like Addison’s disease
      • Hypopituitarism

• Diagnostic Criteria for DM-
  • Fasting plasma sugar more than 126 mg/dl on more than one occasion
  • 2-hour post load OGTT value is more than 200mg/dl even at one occasion
  • Random plasma sugar level is more than 200 mg/dl on more than one occasion
  • Diagnosis should be repeated and not based on single random test.