Carbohydrates, proteins and lipids share common metabolic pathways which may play important roles in the regulation of glucose metabolism. For the purpose of synthesis of energy-rich equivalents, catabolism of carbohydrates, lipids and several amino acids converge to yield acetyl coenzyme A (CoA) which will subsequently be oxidized in the tricarboxylic acid cycle. Other amino acids are converted to intermediate substrates of the same cycle. Oxidation of acetyl CoA is coupled to the synthesis of ATP and is therefore determined essentially by the rate of ADP formation from ATP or, in other words, by energy expenditure. Since acetyl CoA oxidation is pulled by the rate of ATP hydrolysis and cannot be pushed by substrate provision, excessive synthesis of acetyl CoA from one of the macro nutrients may subsequently interfere with the catabolism of other nutrients. Thus, from a theoretical point of view, an excess supply of lipids or amino acids may possibly interfere with glucose utilisation (Fig. 1). Most amino acids, the glycerol molecules released during hydrolysis of triglycerides and the lactate/pyruvate produced by non-oxidative glycolysis may also be reconverted to glucose in the gluconeogenic pathway. This is known to occur essentially in liver and kidney cells and it is currently estimated that it contributes to 30–60% of overall fasting glucose production (1–3). Obesity is characterized by various degrees of whole body insulin resistance and hyperinsulinemia. Noninsulin dependent diabetes mellitus (NIDDM) is encountered with increased frequency in obese patients, indicating that this condition confers an increased risk for this disease (4). Alterations in the metabolism of lipids and proteins are also encountered in obese patients, due to changes in substrate intake and body composition. In particular, obese patients display increased rates of lipid oxidation and enhanced concentrations of free fatty acids in their blood. Tracer studies demonstrate that they have increased rates of glycerol and free fatty acid turnover, indicating increased lipolysis (5–7). Obese patients also have elevated protein turnover rates (8). This increased availability of lipid and amino acid substrates may possibly exert important effects on glucose metabolism which could contribute to insulin resistance. At the skeletal muscle and adipose cell level where insulin stimulates glucose oxidation, increased oxidation rates of other macro nutrients, driven by their increased blood concentrations, may interfere with glucose oxidation and hence its utilisation. At the level of the liver and kidneys, enhanced provision of glucose precursors may stimulate glucose synthesis and increase hepatic glucose production. The blood glucose concentration is controlled by the balance between the systemic delivery of glucose on the one hand, and glucose utilisation on the other. The former results from glycogenolysis and gluconeogenesis in liver and kidney cells, while the latter corresponds to glucose oxidation, which occurs at a constant rate in insulin-insensitive tissues (e.g. brain, kidney, medullae, etc.) and at variable rates according to insulin concentrations in insulinsensitive tissues (e.g. skeletal muscle, adipose cells, etc.), and glucose storage as glycogen. Insulin regulates blood glucose concentrations by modulating both glucose production and glucose utilisation.