It is not everyday that Piscatrix comes across some ‘pure’ biochemistry as she scours the journals for articles of interest to the readership. Imagine therefore my excitement on discovering newly minted additions to the already complex lipid biochemical pathways. Coined a ‘high maintenance’ protein, the lipase maturation factor, or LMF1, is essential for the transport of lipoprotein lipase to the capillary endothelium where it releases free fatty acids from the triglycerides of VLDL and chylomicrons (Nat Genet 2007;39:1483–7). Hypertriglyceridaemia has long been associated with high carbohydrate diets, obesity, insulin resistance and diabetes. While it is a feature of familial combined hyperlipidaemia, precious few causative gene defects in the structural proteins of the lipid-processing pathway have been found. This has now changed with the identification of the lmf1 gene. The initial research was undertaken in a murine mouse strain with combined lipase deficiency. These mice survived only a few days after birth due to the haemodynamic consequences of trying to ‘transport butter through their bloodstream’, with triglyceride concentrations 100-fold increased. Genetic detective work identified the lmf1 gene – a single mutation resulted in a truncated, inactive protein. The human corollary was identified among a cohort with severe hypertriglyceridaemia. The patient typically had triglyceride concentrations of greater than 32 mmol/L and had had repeated episodes of pancreatitis. He had a markedly compromised response in LPL activity after heparin injection. The identification of an important candidate gene for hypertriglyceridaemia is an important milestone in the understanding the genetic basis of hyperlipidaemia – the lipid metabolic pathways have got even more complicated.

Hyperglycaemia and hypertriglyceridaemia often co-exist, as referenced in the article above. A recent review of the evidence provides compelling proof that hyperglycaemia in hospitalized patients is strongly associated with adverse outcome (J R Soc Med 2007;100:503–7). The evidence is strongest for patients admitted with myocardial infarction, acute coronary syndrome or thrombotic strokes. According to the authors, who conducted the literature review, it would appear to be independent of previously existing diabetes. Indeed, it would appear that patients with hyperglycaemia without a previous diagnosis of diabetes had a poorer outcome than those patients with established diabetes.

The outcome could be improved if therapeutic lowering of glucose with insulin was attempted. There are, however, problems in defining not only hyperglycaemia, but also for the type of fluid – whole blood or plasma – in which the measurement is undertaken.

Certainly, there was no consensus in the 12 studies examined and little correlation with the cut-off recommended by the World Health Organization for the diagnosis of diabetes. There may be some headway to be made on comparative data, according to an article in the March issue of Annals (Ann Clin Biochem 2008;45:140–8). This study confirms what many of us in the laboratory see on a daily basis – that hyperglycaemia is common in the hospital population. However with increasing provision of ward-based testing and fewer measurements made in the laboratory, it may be more difficult to undertake what the authors recommend which is further long-term standardized studies particularly to evaluate the benefits of therapeutic lowering of glucose.

Unfortunately, another recent criminal case in the UK highlights how the lowering of blood glucose in elderly, vulnerable patients was not undertaken for therapeutic purposes.

One of our own – Vincent Marks – has had a long-standing interest in insulin-related crimes and an excerpt of his recent book (Insulin Murders. London: RSM Press, 2007) describes the case of the American thought to have murdered at least 11 family members. The culprit's career spanned 20 years until he was convicted in 1968. What is of interest to scientists is that while there was good evidence of low blood sugars in his victims, no one had fully explored the availability of the radioimmunoassay for insulin that had been developed in 1960 by Yalow and Berson. A rather primitive immunohistological technique was used to support the prosecution case – evidence that would not have stood up to scrutiny today. As the recent criminal case highlights, it is an indictment on society and health professionals in particular that insulin assays are still required for forensic purposes.

Finally, the genetic determinants of freckles and flame hair have been tracked down among the Icelandic population (Nat Genet 2007;39:1443–52). Pigmentation is subject to substantial geographic stratification, and skin tone in particular reflects a history of adaptation to latitude-dependent concentrations of ultraviolet radiation.