The hyperinsulinaemic‒euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects

2000 ◽  
Vol 98 (4) ◽  
pp. 367 ◽  
Author(s):  
Mattias SOOP ◽  
Jonas NYGREN ◽  
Kerstin BRISMAR ◽  
Anders THORELL ◽  
Olle LJUNGQVIST
2000 ◽  
Vol 98 (4) ◽  
pp. 367-374 ◽  
Author(s):  
Mattias SOOP ◽  
Jonas NYGREN ◽  
Kerstin BRISMAR ◽  
Anders THORELL ◽  
Olle LJUNGQVIST

To examine the reproducibility of the hyperinsulinaemic–euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects {age 50 (25, 59) years [median (range)], body mass index 23.1 (20.8, 25.5) kg·m-2} were investigated with three 2 h hyperinsulinaemic (60 µmol·l-1)–euglycaemic (4.5 mmol·l-1) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11.02) and 6.63 (4.42, 10.3) mg·kg-1·min-1, with a median intra-individual coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P < 0.05). This increase was correlated inversely with the GIR between 1 and 2 h (r = -0.82; P < 0.05), and directly with age (r = 0.86; P < 0.05). Carbohydrate oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6,6-2H2]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic–euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.


1992 ◽  
Vol 55 (4) ◽  
pp. 851-856 ◽  
Author(s):  
J E Swanson ◽  
D C Laine ◽  
W Thomas ◽  
J P Bantle

1984 ◽  
Vol 105 (4) ◽  
pp. 515-520 ◽  
Author(s):  
G. C. Viberti ◽  
P. D. Home ◽  
R. W. Bilous ◽  
K. G. M. M. Alberti ◽  
N. Dalton ◽  
...  

Abstract. The metabolic and hormonal response to moderately severe exercise 2 h after breakfast was assessed in 8 insulin-dependent diabetics during conventional insulin injection therapy and after 3 weeks of continuous sc insulin infusion. Blood glucose fell from 12.1 to 4.4 mmol/l on injection therapy; this was accompanied by a significant rise (P < 0.05) in free insulin to 57 mU/l. On infusion therapy plasma glucose fell and stabilised at 3.6 mmol/l from pre-exercise levels of 7.1 mmol/l, while free insulin level was unchanged at the end of the exercise period (31 mU/l). The fall in blood glucose on injection therapy was accompanied by an exaggerated growth hormone response to exercise that was normalised by 3 weeks of infusion therapy. Basal and post-prandial levels of intermediary metabolites, catecholamines and glucagon were comparable on the two insulin regimens. Responses during exercise were generally similar and no different from those of normal subjects, with the exception of plasma NEFA levels which became abnormally suppressed. Good metabolic control of diabetes is thus accompanied by nearly normal hormonal and metabolic response to moderately severe exercise.


1986 ◽  
Vol 113 (4) ◽  
pp. 559-563 ◽  
Author(s):  
O. Schmitz ◽  
J. Arnfred ◽  
O. Hother Nielsen ◽  
H. Beck-Nielsen ◽  
H. Ørskov

Abstract. To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45 mU/kg · min or in identical amounts in pulses of 1½ to 2¼ min followed by intervals of 10½ to 9¾ min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270–294 min: 8.7 ± 0.7 vs 6.8 ± 0.9 ml/kg · min, P < 0.01, and 330–354 min: 8.9 ± 0.5 vs 7.4 ± 0.9 ml/kg · min, P <0.05). The superior efficacy of pulsatile insulin delivery on glucose uptake was not consistently found until after 210 min of insulin administration. In both infusion protocols, endogenous glucose production as estimated by the [3-3H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion.


1986 ◽  
Vol 18 (02) ◽  
pp. 129-133 ◽  
Author(s):  
P. Hale ◽  
E. Black ◽  
M. Nattrass

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