To examine the effect of various carbohydrates on the metabolic and hormonal response to exercise, 75 g glucose, fructose, or placebo were given to nine well-trained males (VO2 max 60 +/- 1 ml . kg-1 . min-1) 45 min before cycle ergometer exercise performed at 75% VO2 max for 30 min. After glucose ingestion, the rise in plasma glucose was 3-fold (P less than 0.005) in plasma insulin 2.5-fold (P less than 0.01) greater than after fructose. During exercise, after glucose administration plasma glucose fell from 5.3 +/- 0.3 to 2.5 +/- 0.2 mmol/l (P less than 0.001) and after fructose from 4.5 +/- 0.1 to 3.9 +/- 0.3 mmol/l (P less than 0.05). The fall in plasma glucose was closely related to the preexercise levels of plasma insulin (r = 0.82, P less than 0.001) and glucose (r = 0.81, P less than 0.001). Both glucose and fructose ingestion decreased the FFA levels by 40-50% (P less than 0.005) and during exercise they remained 30-40% lower after carbohydrate than placebo administration (P less than 0.02). This study suggests that glucose ingestion prior to exercise results in hypoglycemia during vigorous exercise, this rapid fall in plasma glucose is mediated, at least in part, by hyperinsulinemia, and fructose ingestion is associated with a modest rise in plasma insulin and does not result in hypoglycemia during exercise.

In order to examine the effect of short-acting insulin analogue on the exercise-induced hypoglycaemia in insulin-dependent diabetes mellitus (IDDM) patients we compared the glycaemic response of 40 min cycle ergometer exercise performed either shortly (40 min) or later (180 min) after a breakfast meal and subcutaneous injection of either short-acting insulin analogue [Lys(B28) Pro(B29)] or soluble human insulin (Humulin Regular) in ten IDDM patients with long duration of the disease. Both preparations had been used 1 month before respective studies. Changes in blood glucose, insulin and counterregulatory hormones were assayed. As compared to human insulin, after the analogue injection the peak insulin concentration came earlier, was 56% higher (p < 0.05) and disappeared faster, and the postprandial blood glucose response was lower (p < 0.05). In the analogue-treated patients the exercise-induced hypoglycaemia was 2.2-fold greater (p < 0.01) during the early exercise, but 46% less (p < 0.05) during late exercise as compared to the treatment with human insulin. Serum insulin or analogue concentration at the beginning of the exercise correlated closely with the fall in blood glucose during exercise (r = 0.74, p < 0.01; r = 0.73, p < 0.02, respectively). In the analogue-treated patients, fasting serum glucagon and adrenalin concentrations were higher than during human insulin therapy (p < 0.05) and remained so throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin is known to increase expression of the ob gene product leptin in adipose tissue of rodents. We determined whether insulin increases circulating leptin concentrations in humans, and whether this effect might be altered in patients with noninsulin-dependent diabetes mellitus (NIDDM). Plasma leptin concentrations were determined during an 8.5-h hyperinsulinaemic clamp (serum free insulin approximately 480 pmol/l) and during an 8.5-h infusion of physiological NaCl solution (saline) in eight normal subjects (age 51 +/- 3 years, BMI 26.3 +/- 0.6 kg/m2, fasting plasma glucose 5.6 +/- 0.2 mmol/l) and seven patients with NIDDM (age 54 +/- 2 years, 27.0 +/- 0.9 kg/m2, 11.1 +/- 0.8 mmol/l). Fasting serum insulin level correlated with plasma leptin (r = 0.72, p < 0.005), even after adjusting for the percentage of body fat (p < 0.005). During the insulin infusion, a significant increase in the plasma leptin concentration was observed after 6 h (37 +/- 14%; 5.2 +/- 0.8. vs 3.9 +/- 0.6 ng/ml, 6 vs 0 h, p < 0.05) in the normal subjects and after 8.5 h (38 +/- 11%; 7.1 +/- 1.0 vs 5.5 +/- 0.9 ng/ml, 8.5 vs 0 h, p < 0.05) in the patients with NIDDM. During the saline infusion, plasma leptin concentrations decreased significantly in the normal subjects by 11 +/- 1% (p < 0.005) and in the patients with NIDDM by 14 +/- 1% (p < 0.01) after 2 h. During the infusion of insulin as compared to saline, plasma leptin concentrations were 32 +/- 13 (p < 0.05), 53 +/- 14 (p < 0.001), 106 +/- 15 (p < 0.001) and 165 +/- 21 (p < 0.001) % higher at 2, 4, 6 and 8.5 h in the normal subjects, and 11 +/- 9 (p < 0.05), 27 +/- 10 (p < 0.05), 58 +/- 7 (p < 0.001) and 106 +/- 13 (p < 0.001) % higher in the patients with NIDDM, respectively. No differences were observed in plasma leptin concentrations between the normal subjects and patients with NIDDM, under any conditions. We conclude that prolonged exposure to insulin increases plasma leptin concentrations in humans implying a role for insulin in chronic but not acute regulation of plasma leptin concentrations. The decrease in plasma leptin concentrations during saline infusion was greater than that expected on the basis of change in serum insulin concentrations, suggesting that factors other than insulin also contribute to regulation of plasma leptin concentrations.

The effect of body composition on clearance of infused insulin was studied in 21 young normal weight (relative body weight 107 +/- 2%, of ideal mean +/- SEM) healthy subjects. In each subject, the per cent of body weight made up of muscle and fat tissue (% muscle and % fat) were determined. Clearance of insulin was estimated during infusion of insulin at the rate of 40 mU/m2/min under maintenance of normoglycaemia using the euglycaemic clamp technique. Steady-state plasma insulin levels (92.6 +/- 3.2 mU/litre) correlated negatively with % muscle (r = -0.60, P less than 0.01), and positively with % fat (r = 0.55, P less than 0.01). Clearance of insulin was directly related to % muscle (r = 0.60, P less than 0.01), and inversely related to % fat (r = -0.48, P less than 0.01). Steady-state plasma insulin levels or insulin clearance did not correlate with relative body weight. Multiple linear regression analysis revealed a significant multivariate correlation between the rate of insulin clearance versus % muscle and % fat (r = 0.62, P less than 0.02). The changes in % muscle and % fat could predict 37% of the observed interindividual variance of insulin clearance. These results indicate that insulin clearance depends on body composition and is higher in muscular than in adipose subjects. This difference may reflect either a greater distribution space of insulin in muscular as compared to adipose subjects or an influence of body composition on insulin catabolism.

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