Clinical Endocrinology (1992) 36, 535-536

Commentary

Post-prandial thermogenesis and insulin sensitivity in the polycystic ovary syndrome

Roy Taylor Human Diabetes and Metabolism Research Centre, Newcastle upon Tyne, UK

Metabolic abnormalities in the polycystic ovary syndrome (PCOS) have received close attention in the last decade. The sensitivity to insulin’s effects upon glucose metabolism is subnormal and modest hyperinsulinaemia prevails (Dunaif et al., 1989). The lack of sensitivity to insulin appears to be a primary defect, neither the obesity nor the hyperandrogen- ism being responsible (Chang et al., 1983; Dunaif et al., 1990). Hyperinsulinaemia acting directly on the ovary appears to cause increased androgen production (Barbieri el

a[., 1986; Stuart et al., 1987). The tendency to relatively greater abdominal deposition of fat (high waist/hip ratio) is likely to be a consequence of the high circulating androgen levels (Evans et a/., 1983).

However, the association of obesity with PCOS remains to be explained. Starting from the observation that insulin insensitivity tends to be associated with decreased rise in metabolic rate after a meal, Robinson and colleagues (1992) set out to test the hypothesis that the insulin insensitivity in PCOS could be related to decreased post-prandial energy expenditure and hence obesity. They measured rates of energy expenditure in the immediate post-prandial period by means of indirect calorimetry. This ‘post-prandial thermo- genesis’ was found to be significantly lower in both lean and obese PCOS subjects. They also observed a greater increase in plasma insulin levels occurred in the PCOS group to maintain a normal area under the plasma glucose curves. If the observed lower rates of post-prandial thermogenesis were to be extrapolated to calculate expected storage of surplus energy over one year, the lean and obese PCOS subjects would gain 0.5 and 1.9 kg of fat respectively. These conclusions deserve close inspection.

A genuine decrease in rates of post-prandial thermogene- sis at the same time as normal tissue uptake of substrate can be explained only on the basis of increased efficiency of storing energy. How could this relate to insulin insensitivity, especially as more insulin was secreted? There is no basis for postulating increased rates of glucose oxidation and hence proportionately less glucose going through the metabolically expensive process of glycogen synthesis and lipogenesis. The data from indirect calorimetry could readily be analysed to examine this. Postulation of differential insulin sensitivity in Correspondence: Dr Roy Taylor, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NEI 4LP UK.

different metabolic pathways or in liver and muscle could resolve the conundrum. Thus in normal subjects muscle blood flow will increase after eating (Walker et a/., 1990) and the tissue will take up glucose for storage as glycogen and subsequent release in Cori cycle activity. Storage in liver will also occur. If muscle is disproportionately insensitive to insulin, cardiac output will not be perturbed by increased flow through muscle, and a greater proportion of the ingested carbohydrate will be stored in liver both as glycogen and directly as triglyceride. The latter process may be more energy efficient, avoiding intermediate steps. It is interesting to note that using the euglycaemic hyperinsulinaemic clamp technique (which measures mainly insulin action in muscle) Dunaif et al. (1989) observed relatively greater insulin resistance in a PCOS group compared with controls than Robinson et al. (1992) who used the intravenous insulin tolerance test (which mainly measures rapid suppression of hepatic glucose output).

Attempts to hypothesize a rational basis for reconciling insulin resistance with metabolic super-efficiency should not obscure consideration of whether the conclusion of de- creased post-prandial thermogenesis in PCOS is generally correct. In the only other similar study, Segal and Dunaif (1989) found that PCOS subjects had slightly but non- significantly higher rates of post-prandial thermogenesis than obesity-matched controls. There are several differences between the two studies, but the most important is likely to be that the PCOS subjects in the latter study exhibited abnormal glucose tolerance associated with much more marked hyperinsulinaemia.

Controversy about post-prandial thermogenesis is not new, arguments having abounded in the field of obesity for over half a century (Jung et a[., 1979; Strang & McCluggage, 1931). There are some lessions to be learned. After a meal, increased energy expenditure continues for many hours, and measurement over only short periods may be misleading. Secondly, post-prandial thermogenesis is calculated by the subtraction of two very large numbers: post-prandial and resting energy expenditure. Both are subject to the potential pitfalls in employing indirect calorimetry (Cooper et al., 1991; Ferrannini, 1988). Use of the double labelled water technique (Prentice et al., 1986) would allow estimation of energy expenditure and hence metabolic efficiency over an adequate period of time. Although expensive, this is likely to resolve the controversy most efficiently. The gauntlet has been thrown down: Will it be picked up in an energy-sparing manner?

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536 R. Taylor Clinical Endocrinology (1992) 36

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