Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes.

AIMS: Anti-insulin antibodies in insulin-treated diabetes can derange glycaemia, but are under-recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making. METHODS: Forty people with insulin-treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad-specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation. RESULTS: Twenty-seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate. CONCLUSIONS: Anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice.

Effects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes.

BACKGROUND: Improvement in vascular endothelial function is widley cited as a beneficial effect of hormone replacement therapy (HRT). Women with type 2 diabetes (T2DM) are at increased cardiovascular risk and have impaired endothelial function. Any benefits of HRT on endothelial function in this group are of particular interest. OBJECTIVES: We assessed effects on vascular function of oral 17beta oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with T2DM. DESIGN: Double-blind, randomised, placebo-controlled trial. ASSESSMENTS: Twenty-eight women had pulse wave velocity (PWV) and adhesion molecules VCAM-1 and ICAM-1 assessed before and after three months' treatment. Twenty-four women also had gluteal fat biopsy for assessment of resistance vessel function (using wire myography). RESULTS: HRT did not affect PWV, VCAM-1, ICAM-1 or carbachol response. Effects of L-NAME and indomethacin on carbachol sensitivity were similar in both groups. CONCLUSIONS: This HRT preparation had no detectable effect on these measures of endothelial function in women with T2DM.

Clinical impact of the new criteria for the diagnosis of diabetes mellitus.

In 1997 the American Diabetes Association lowered the threshold for diagnosis of diabetes from a fasting plasma glucose concentration of 7.8 mmol/l to 7.0 mmol/l and advised that the oral glucose tolerance test no longer be used in routine clinical practice. In 1999 the World Health Organization endorsed the reduction in fasting plasma glucose threshold but recommended retaining the oral glucose tolerance test for anyone with impaired fasting glucose (6.1 mmol/l-6.9 mmol/l). This Review discusses the impact of these changes on the prevalence of diabetes and examines the implications for individuals and specific high-risk groups. The phenotype of those diagnosed with diabetes and the predictive value for the development of complications according to the different criteria are compared. It is clear that these changes in diagnostic criteria have major importance both for individuals and for resource planning at a national level.