Med‎ > ‎B-Enm‎ > ‎1-Endocrine‎ > ‎Diabetes‎ > ‎


    Hypoglycaemia Treatment Algorithm

    see pdf attachment


    • as per UK Hypoglycaemia Study defined hypoglycaemic event as 20min or more with BG<3.0mM/L[54mg/dL], reflecting duration and BG levels at which cognitive fx deteriorates in physiological studies
      • Donnelly LA, Morris AD, Frier BM, et al. Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study. Diabet Med 2005;22:749-755. [Medline]
      • UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50:1140-1147. [Medline]
      • Deary IJ. Effects of hypoglycaemia on cognitive function. In: Frier BM, Fisher BM, eds. Hypoglycaemia and diabetes: clinical and physiological aspects. London: Edward Arnold, 1993:80-92.
      • Evans ML, Pernet A, Lomas J, Jones J, Amiel SA. Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery. Diabetes Care 2000;23:893-897. [Abstract] [pdf]
        • 8 healthy volunteers, 1 x hyperinsulinaemic [vs 1 x euglycaemic] clamp to dcr PG rapidly to 2.65 for 90mins; Results: immediate impairm of cognitive fx; counterreg hormone responses (Adr, NA, Glucagon, cortisol, GH) and symptomatic awareness after 20min after onset of hypoglycaemia; during recovery, 4-choice reaction time remained abnl even after resolution of symptomatic awareness
        • symptoms questionnaire [scale 1-7: absent - max.]: (A: 7 autonomic symptoms:) •sweating, •warmth, •palpitations, •tingling, •anxiety, •trembling, •hunger, (B: 8 neuroglycopenic symptoms:) •blurred vision, •tiredness/drowsiness, •confusion, •weakness, •headache, •difficulty in speaking, •dizziness, •irritability;
        • cognitive fx tests: 1) 4-choice reaction time, 2) Stroop word subtest, 3) color-word subtest, 4) trail-making B test;

    Practice Guideline

    • ENDO: JCEM
    • Whipple's triad:
      1. symptoms/signs
        • adrenergic: palpitations, tremor, arousal/anxiety
        • cholinergic: sweating, hunger, paraesthesias
        • neuroglycopenic: behavioural changes, fatigue, confusion, seizure, loss of consciousness
      2. P-Glu<3.0mM/L=55mg/dL [cf. unequivocally nml P-Glu>3.9mM/L=70mg/dL]
        • NB: symptom threshold may be lower with recurrent hypoglycaemia or extended fasting, after exercise or sleep
        • NB: beware false-positives: e.g. without inhibitors of glycolysis, or delayed separation of plasma/serum from formed elements, esp. with erythrocytosis, leukocytosis, thrombocytosis
      3. resolution of symptoms/signs with P-Glu normalization
    • Evaluation strategy in non-diabetic adults:
      • first consider :
        1. drugs
        2. critical illness
        3. hormone deficiencies
        4. non-islet cell tumours
      • if neg: accidental/surreptitious/malicious hyperinsulinism or endogenous hyperinsulinism
      • if suspected endogenous: measure during episode of hypoglycaemia (*ref. values assume no intercurr illness/renal insuff), if needed provoked by up-to-72h fast (2/3 <24h, vast majority<48h) or mixed meal test over 5h with a meal most likely to cause hypo; NB: NEVER use oGTT)
        • glucose < 3.0mM/L=55ng/dL* (rise by >=1.4mM/L=25mg/dL after 1.0mg iv glucagon indicate mediation by insulin/insulin-like growth factor);
        • insulin (>=18pM/L=3.0mcU/mL* in endogenous hyperinsulinism, although may occas. be false-neg);
        • C-peptide (>=0.2nM/L=0.6ng/mL* in endogenous hyperinsulinism);
        • proinsulin (>=5.0pM/L* in endogenous hyperinsulinism);
        • beta-hydroxybutyrate (<=2.7mM/L indicates mediation by insulin/insulin-like growth factor; NB: rising levels indicate a negative fast!);
        • circulating oral hypoglycaemic agents (need to exclude before insulinoma localisation);
        • insulin antibodies (any time) (need to exclude before insulinoma localisation);

    Table 1. Causes of hypoglycemia in adults:

    • Ill or medicated individual
      • Drugs
        • Insulin or insulin secretagogue
        • Alcohol
        • Antihyperglycaemic agents
        • Others (Table 2)--according to quality of evidence:
          • moderate: Cibenzoline, Gatifloxacin, Pentamidine, Quinine, Indomethacin, Glucagon (during endoscopy)
          • low: Chloroquineoxaline sulfonamide, Artesunate/Artemisin/Artemether, IGF-I, Lithium, [Dextro-]Propoxyphene
          • very low (but >25 cases reported): ACEI, ARA, beta-blockers, levofloxacin, mifepristone, disopyramide, Trimethoprim-Sulfamethoxazole, Heparin, 6-Mercaptopurin
      • Critical illnesses
        • Hepatic, renal, or cardiac failure
        • Sepsis (including malaria)
        • Inanition
      • Hormone deficiency
        • Cortisol [, GH]
        • Glucagon and epinephrine (in insulin deficient diabetes mellitus)
      • Nonislet cell tumor hypoglycaemia=NICTH (usu. large mesenchymal tumours, causing overproduction of [incompletely processed] IGF-II (NB: may be nml IGF-II level, but hi pro-IGF-II/IGF-II ratio, and usu. hi IGF-II/IGF-I ratio due to suppressed GH secretion and therefore low IGF-I), also reported hi IGF-I)
    • Seemingly well individual
      • Endogenous hyperinsulinism
        • Insulinoma (usu. fasting hypoglycaemia, but may also be postprandial; incidence 1/250k pt-yrs; <10%malignant/multiple/MEN-I; often <1.0cm; CT/MRI detection ~ 70/85%; somatostatin receptor scintigraphy=SRS: ~50[-80]% sens.; endoscopic pancr US +-FNA: up to 90% sens. in some centres; selective pancreatic arterial calcium injection with >2[-5]fold icr in hepatic venous insulin levels regionalizes insulinoma with hi sens. and Ix of choice for functional β-cell disorders; ?role of PET); intraop. pancr US: almost invariably localizes tu.)
        • Functional β-cell disorders (nesidioblastosis) [treatment: dietary, medical: alpha-glucosidase inhibitor, diazoxide, octreotide, or steroids, growth hormone, else partial pancreatectomy]
          • Noninsulinoma pancreatogenous hypoglycemia=NIPHS (usu. postprandial due to diffuse islet hypertrophy/-plasia; confirmation: selective arterial calcium stimulation test)
          • Post gastric bypass hypoglycemia (usu. postprandial, usu. many mths after surgery)
        • Insulin autoimmune hypoglycemia
          • Antibody to insulin [rare, usu. Jap/Kor: Insulin binds to antibody, and released later in unregulated fashion, causing lo Glu]
          • Antibody to insulin receptor (due to agonist properties; NB: usu hi Insulin levels due to dcrd clearance, but appropriately suppressed C-peptide levels; often female African-American with autoimmune diseases)
        • Insulin secretagogue
        • Other
      • Accidental, surreptitious, or malicious hypoglycemia

    Hypoglycaemia: Overview

    • Symptoms if <=3.9mM/L (i.e. <="4") (Cox(1993)DiabetesCare: Perceived symptoms in the recognition of hypoglycemia.)
    • autonomic response: pallor, palpitations, sweating, shaking/trembling, hunger
    • neuroglycopaenic response: feeling light-headed, confusion, altered behaviour, paraesthesia, drowsiness, coma
    GI of foods used for treating hypoglycaemia
    • Lucozade 95±10, Cornflakes 81±3, Mars bar 65±3, Digestive biscuits 59±2, Coca Cola 58±5, Honey 55±5, Orange juice 50±4, Milk chocolate 43±3, Full-fat milk 27±4, Multi-grain bread 43, Ryvita 74 (?), [Jan Watson, J Diabetes Nursing 2008]
    Recommended treatment
    • 20-30g of hi GI carbohydrate food: 3-5 glucose tablets, 50mL Lucozade, glass of ordinary cola or fruit juice, or proprietary glucose gel
    Consider 'Hypo boxes'


    • Grade 1 hypoglycaemia: transitory symptoms not affecting normal activity
    • G2: temporarily incapacitated but patient able to control symptoms without help
    • G3: incapacitated and required assistance to control symptoms without help
    • G4: required medical attention or glucagon injection
    • Src: eg;

    Hypobox (FGH)

    • BG<4, unconscious:
      • 20mL 20%  or {1mg   + 10mg   
      • 20mL [BNF: 50mL] 20% Dextrose IV [=4g[10g] Dextrose], or
      • glucagon 1mg IM [+Metoclopramide 10mg PO/IM/IV: before low GI food], provided no prior alcohol
    • BG<4, losing consciousness:
      • Glycogel massaged into cheek, followed by food;
      • if no effect after 5 min: as above
    • BG<4, conscious:
      •  120 / 200 / 200 
        4 / 4
      • 120mL Lucozade original (1/2 tea cup); or:
      • 200mL fruit juice , 200mL Coca Cola (non-diet), 4 jelly babies , 4 dextrose tablets ;
      • recheck BM after 5mins: if <5: repeat Lucozade
      • 2 / 2
      • 2 digestive biscuits ; or: 2 slices granary/wholemeal bread


    Systematic: Hypoglycaemia

    Principle: imbalance between lo P-Glu and Insulin/Insulin-like factors and lack of counterregulation
    1-Nee: confusion, seizure, coma; Phenytoin, Li can cause hypos
    2-Rsp: after steroid withdrawal: icrd insulin sensitivity in DM
    3-Crc: ? hypo-associated arrhythmias (? due to icrd QTc); ACEI, ARA: can cause hypos?; severe heart failure
    4-Dig: severe hepatic failure; gastric bypass (via nesidioblastosis); insulinoma, NIPHS;
    5-Ugo: severe renal failure;
    6-Msk: after steroid withdrawal
    7-Ski: after steroid withdrawal
    8-Psy: confusion; surreptitious hypoglycaemia;
    9-Inf: sepsis;
    A-Hae: hi RBC/WBC/Plt: "Pseudohypo"; Ins/InsRec-Ab;
    B-Enm: hi Insulin; lo Glucose; Cort-def, Glucagon-def, GH-def; prolonged fasting/inanition;
    C-Tum: Insulinoma, NICTH=non-islet cell tumour hypoglycaemia: IGF-II (lo GH, lo IGF-I)
    D-Xtn: insulin, antihyperglycaemics, Quinine, Lithium, ACEI, ARA
    E-Fam: [InsReceptor variants]
    Andreas Jostel,
    21 Mar 2009, 18:50