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Background: Insulin-like growth factor binding protein-1 (IGFBP-1) is a hepatically synthesised protein which can be used as a marker of insulin resistance. We hypothesised that the fall in serum IGFBP-1 at 2 h following a glucose load (ΔIGFBP-10-2h) would be a more robust measure of hepatic insulin resistance than a fasting level alone., Methods: All subjects had a standard 75 g oral GTT including IGFBP-1 and insulin measurement to enable calculation of ΔIGFBP-10-2h, ΔInsulin0-2h, and insulin sensitivity indices. At a second visit, subjects had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in order to determine the insulin sensitivity index, Si., Results: Twenty-two individuals had normal glucose tolerance (NGT) and 9 impaired fasting glucose (IFG). ΔIGFBP-10-2h correlated with Si in total subjects (r = 0.49, p = 0.005) and NGT subjects (r = 0.50, p = 0.02) but not in IFG subjects (r = 0.43, p = 0.24). ΔInsulin0-2h/ΔIGFBP-10-2h correlated significantly with Si in total subjects (r = -0.68, p < 0.001) and in NGT subjects (r = -0.57, p = 0.005). Multivariate analysis was fitted using different models while keeping other explanatory variables constant. The fasting IGFBP-1 model was a better predictor of Si (β = 0.431, p < 0.0001) than the ΔInsulin0-2h/ΔIGFBP10-2h model (β = -0.185, p = 0.004)., Conclusions: The dynamic indices ΔIGFBP-10-2h and ΔInsulin0-2h/ΔIGFBP-10-2h appear suitable markers of (hepatic) insulin resistance with potential clinical utility.

Background: Insulin resistance is associated with an increased risk of cardiovascular disease and diabetes. It can be assessed using complex reference techniques, such as clamp or frequently sampled intravenous glucose tolerance test (FSIVGTT). Therefore, simple indices derived from fasting insulin and glucose concentrations have been proposed. The aim of this study is to assess fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) as a simple index of insulin sensitivity compared with other simple indices and FSIVGTT., Methods: Fasting serum IGFBP-1, fasting plasma insulin (FPI), homeostasis model assessment (HOMA-IR), quantitative insulin check index (QUICKI), fasting glucose to insulin ratio (FGIR), Raynaud and insulin glycaemic index (ISI-gly) were correlated with FSIVGTT (Si) in 22 subjects with normal glucose tolerance (NGT) and nine with impaired fasting glucose (IFG)., Results: In NGT individuals, IGFBP-1 correlated more strongly with Si than did any other index both before (r = 0.76) and after (r = 0.79) natural logarithm (ln) transformation. In subjects with IFG, IGFBP-1 was weakly correlated with Si before and after ln-transformation (r = 0.55, r = 0.56, respectively), but ISI-gly was the index most strongly correlated with Si (r = 0.77, r = 0.85, respectively)., Conclusions: In subjects with NGT, fasting serum IGFBP-1 could be used as a simple reliable marker of insulin sensitivity. For more accurate estimation of insulin sensitivity in normal subjects and those with IFG, ln-transformation is preferred over raw data.

Insulin resistance is a common condition, recognized to be a central feature of the metabolic syndrome, and strongly associated with an increased risk of cardiovascular disease and diabetes. The quantitative assessment of insulin sensitivity is not used for routine clinical purposes, but the emerging importance of insulin resistance has led to its wider application to research studies that have examined its pathogenesis, aetiology and consequences. The gold standard method for the determination of insulin sensitivity is the euglycaemic hyperinsulinaemic clamp from which indices of insulin sensitivity can be derived. The clamp technique is both expensive and complex to undertake and has prompted the use of surrogate methods, notably the insulin tolerance test and frequently sampled intravenous glucose tolerance test. Indices may be derived from these methods and correlate well with those derived from clamp studies. Indices can also be derived from measurements made during a standard oral glucose tolerance test and from one-off fasting specimens (e.g. homeostasis model assessment and quantitative insulin sensitivity check index). These indices lend themselves for use in large population studies where a relatively simple, inexpensive assessment is necessary. However, these tests all suffer from important limitations, including poor precision. Insulin resistance is increasingly being assessed in clinical situations, where relatively simple markers are required. Insulin-like growth factor binding protein-1 is an emerging marker which may be useful in this context.

We describe the case of a 69-year-old man with a history of muscular symptoms dating back to his childhood; McArdle's disease (glycogen-storage disease V) was diagnosed following an episode of myositis in which a statin and physical exertion appear to have been precipitating factors. This case demonstrates that the ischaemic lactate-ammonia test still has a place in screening patients with symptoms suggestive of McArdle's disease and emphasizes the importance of carrying out glycogen phosphorylase histochemistry on the skeletal muscle biopsy to confirm the diagnosis. In patients who develop a raised plasma creatine kinase level or muscular symptoms during lipid-lowering therapy, the clinician should be alert to the possibility of an underlying myopathy.

We describe a patient with a 6-year history of pancreatic malabsorption following surgical subtotal pancreatectomy. She presented at 33 weeks of pregnancy with night blindness as a result of vitamin A deficiency. She had had two successful pregnancies 9 and 8 years previously, giving birth to a healthy baby boy on each occasion. We suggest that patients with long-term malabsorption due to intestinal or pancreatic disease should have vitamin A status checked prior to and during pregnancy so that prompt supplementation can be commenced if necessary. The possibility that vitamin A deficiency may be contributing to anaemia present in pregnancy should also be considered.

The ischaemic lactate-ammonia test is widely used for investigating patients with muscle pain and fatigue. It involves measuring plasma lactate and ammonia produced as a result of forearm exercise under ischaemic conditions in a fasted subject. Its clinical use is to screen patients with muscle complaints for disorders of carbohydrate metabolism, in particular to identify those in whom further investigation may provide useful diagnostic information. There is a wide variety of methods described, reflecting attempts to optimize the response and hence the diagnostic value of the test. Although it is often considered a general screening test for metabolic muscle disease, the situations in which it is useful are specific. Here we review the use of the test and present the results of an audit of its use in our departments.

A rapid vacuum-driven procedure, using pre-treated Sep-Pak C18 cartridges, has been developed for the simultaneous extraction of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) from plasma. Non-specific interference was removed by fractional elution with an aqueous methanol/trifluoroacetic acid (TFA) mixture. AVP and ANP were coeluted under positive pressure with a methanol/TFA mixture and the eluates air-dried before measurement using separate radioimmunoassays. Assay ranges for AVP and ANP were 0.12-29.5 pmol/L and 0.65-162 pmol/L, respectively, with mean recoveries (standard deviation in parentheses) for AVP of 96.4% (5.5%) at a level of 11.8 pmol/L and for ANP of 94.8% (5.9%) at a level of 32.4 pmol/L. The extraction and assay procedures were validated by observing the changes in plasma AVP and ANP concentrations in normal subjects at different stages of hydration and in elderly patients during treatment for congestive cardiac failure.