1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120–150 min after administration of 500 mg of the anti-lipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus.

2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 ± 0.02 versus 0.55 ± 0.05 mmol/1, P < 0.001) and blood glycerol (8 ± 1 versus 56 ± 8 μmol/l, P < 0.001) concentrations. The lipid oxidation rate was decreased (0.63 ± 0.05 versus 1.02 ± 0.08 mg min−1 kg−1, P < 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 ± 0.17 versus 1.22 ± 0.18 mg min−1 kg−1, P = 0.02). In addition, in the lipolysis-suppressed patients, there was a significant increase in serum cortisol (329 ± 47 versus 196 ± 43 nmol/l, P=0.03), serum growth hormone (5.44 ± 2.1 versus 0.6 ± 0.2 ng/ml, P=0.04), plasma glucagon (12 ± 2.5 versus 8.2 ± 2.0 ng min−1 ml−1, P = 0.005), plasma noradrenaline (1.82 ± 0.26 versus 1.39 ± 0.21 nmol/l, P=0.004) and adrenaline (0.32 ± 0.08 versus 0.20 ± 0.05 nmol/l, P=0.04) concentrations compared with control. Despite this marked hormonal response, there was no difference in hepatic glucose output, fasting blood glucose concentration or peripheral glucose disposal, although non-oxidative glucose disposal was less after acipimox (0.16 ± 0.16 versus 0.74 ± 0.20 mg min−1 kg−1, P=0.05).

3. We conclude that an acute decrease in fatty acid oxidation results in a switch to oxidation of glucose at the expense of glycogen stores, but apparently does not increase peripheral glucose uptake. Hepatic glucose output and fasting blood glucose concentration are maintained by an acute counter-regulatory response which presumably increases glycogen breakdown. Inhibitors of lipolysis and lipid oxidation are therefore more likely to lower fasting blood glucose concentration in the glycogen-depleted state.

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