Hypoglycaemia in Clinical Diabetes

Table 7.2 Studies of antecedent hypoglycaemia (AH) in non-diabetic humansReferences No. of subjectsMethod of induction,nadir BG (mmol/l) andduration of AHInterval before testhypoglycaemiaTest hypo: methodand BG nadir(mmol/l)Effect of AH on subsequent responsesto hypoglycaemiaHeller and Cryer(1991)Widom and Simonson(1992)9 Clamp (3.0) 2 h 18 h Clamp (2.8) Reduced symptoms and CR responses10 Clamp (2.2–2.8) 1 h 4 consecutive dailyhyposStepped clamp(2.2)Veneman et al. (1993) 10 iv. infusion (2.2–2.5) 2 h 7 h Stepped clamp(2.3)Mellman et al. (1994) 9 Clamp (3.2) 2 h 1.5 h Stepped clamp(2.8)Elevated BG thresholds for symptomsand CR responsesNocturnal hypo: BG thresholds forsymptoms and CR responseselevatedElevated BG thresholds for symptomsand CR responsesRobinson et al. (1995) 10 Clamp (3.0) 2 h 24 h and 6 days Clamp (2.5) Reduced adrenaline and sweating at 6daysPeters et al. (1995) 10 iv. bolus injection ofinsulin (< 28)< 15 min4 consecutive dailyhyposiv. bolus (< 28)X4No effect on symptoms or CRresponsesGeorge et al. (1995) 8 Clamp (2.9) 2 h 2 and 5 days Clamp (2.5) Physiological responses still reducedafter 1 weekDavis et al. (1997) 8 Stepped clamp (2.9) 2 h < 24 h Clamp (2.9) Magnitude of reduced CR responserelated to depth of AHDavis et al. (2000a) 31 Clamp (2.9) 2 h (n = 15);30 min (n = 16); 5 min(n = 10)24 h Clamp (2.9) Reduced CR responses in all studies.Symptom scores unaffected byshort duration hypoglycaemiaDavis et al. (2000b) 16 Clamp (2.9) 2 h 24 h Exercise (90 min) Blunting of CR responses to exercise.Attenuated metabolic responses(reduced endogenous glucoseproduction)Fruehwald-Schulteset al. (2000)30 Stepped clamp (2.6) 2.5 h 18–24 h Clamp (3.1) Auditory-evoked brain potentials andshort-term memory less affectedBG = blood glucose; AH = antecedent hypoglycaemia; CR = counterregulatory (hormonal); iv = intravenous