Diabetic Medicine

Aims  To establish a unified working diagnostic tool for the metabolic syndrome (MetS) that is convenient to use in clinical practice and that can be used world‐wide so that data from different countries can be compared. An additional aim was to highlight areas where more research into the MetS is needed.

Participants  The International Diabetes Federation (IDF) convened a workshop held 12–14 May 2004 in London, UK. The 21 participants included experts in the fields of diabetes, public health, epidemiology, lipidology, genetics, metabolism, nutrition and cardiology. There were participants from each of the five continents as well as from the World Health Organization (WHO) and the National Cholesterol Education Program—Third Adult Treatment Panel (ATP III). The workshop was sponsored by an educational grant from AstraZeneca Pharmaceuticals.

Consensus process  The consensus statement emerged following detailed discussions at the IDF workshop. After the workshop, a writing group produced a consensus statement which was reviewed and approved by all participants.

Conclusions  The IDF has produced a new set of criteria for use both epidemiologically and in clinical practice world‐wide with the aim of identifying people with the MetS to clarify the nature of the syndrome and to focus therapeutic strategies to reduce the long‐term risk of cardiovascular disease. Guidance is included on how to compensate for differences in waist circumference and in regional adipose tissue distribution between different populations. The IDF has also produced recommendations for additional criteria that should be included when studying the MetS for research purposes. Finally, the IDF has identified areas where more studies are currently needed; these include research into the aetiology of the syndrome.

Aim  To conduct a systematic literature review in order to estimate the prevalence and odds ratio of clinically relevant depression in adults with Type 2 diabetes compared with those without.

Methods  medline, embase and psycinfo databases were searched using MeSH terms and free text to identify relevant controlled studies. Published reference lists were also examined. Study selection and appraisal were conducted independently by two reviewers and a meta‐analysis was performed to synthesize and analyse the data.

Results  Ten controlled studies including a total of 51 331 people were published between January 1980 and May 2005. The prevalence of depression was significantly higher in patients with Type 2 diabetes compared with those without [17.6 vs. 9.8%, OR = 1.6, 95%, confidence interval (CI) 1.2–2.0]. However, in most studies, patients with diabetes differed from those without on variables known to be associated with an increased risk of depression. The prevalence of depression was higher in females with diabetes (23.8%) compared with males (12.8%); however, the odds ratio for depression in patients with Type 2 diabetes compared with those without was higher in males (OR = 1.9, 95% CI 1.7–2.1) than females (OR = 1.3, 95% CI 1.2–1.4). Failure to report potential confounders prevented a more rigorous meta‐analysis of risk.

Conclusion  We identified raised rates of depression in people with Type 2 diabetes, however, there is a need for well‐controlled and better‐reported studies to inform the development of effective treatments for depression in these patients.

The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r=0.61, p < 0.001) but not insulin resistance (r= −0.05, p >0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = −0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA) also correlated well with insulin resistance (r= −0.57, p < 0.001) but not insulin secretion (r= 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance.

Aims We set out to examine the evidence for an association between cognitive impairment or dementia and the presence of Type 2 diabetes mellitus (DM). We also sought evidence of potential mechanisms for such an association.

Methods A literature search of three databases was performed and the reference lists of the papers so identified were examined, using English language papers only.

Results We found evidence of cross‐sectional and prospective associations between Type 2 DM and cognitive impairment, probably both for memory and executive function. There is also evidence for an elevated risk of both vascular dementia and Alzheimer’s disease in Type 2 DM albeit with strong interaction of other factors such as hypertension, dyslipidaemia and apolipoprotein E phenotype. Both vascular and non‐vascular factors are likely to play a role in dementia in diabetes.

Conclusions Current classification structures for dementia may not be adequate in diabetes, where mixed pathogenesis is likely. Further research into the mechanisms of cognitive impairment in Type 2 DM may allow us to challenge the concept of dementia, at least in these patients, as an irremediable disease.

Diabet. Med. 16, 93–112 (1999)

Aims The aim was to develop an automated screening system to analyse digital colour retinal images for important features of non‐proliferative diabetic retinopathy (NPDR).

Methods High performance pre‐processing of the colour images was performed. Previously described automated image analysis systems were used to detect major landmarks of the retinal image (optic disc, blood vessels and fovea). Recursive region growing segmentation algorithms combined with the use of a new technique, termed a ‘Moat Operator’, were used to automatically detect features of NPDR. These features included haemorrhages and microaneurysms (HMA), which were treated as one group, and hard exudates as another group. Sensitivity and specificity data were calculated by comparison with an experienced fundoscopist.

Results The algorithm for exudate recognition was applied to 30 retinal images of which 21 contained exudates and nine were without pathology. The sensitivity and specificity for exudate detection were 88.5% and 99.7%, respectively, when compared with the ophthalmologist. HMA were present in 14 retinal images. The algorithm achieved a sensitivity of 77.5% and specificity of 88.7% for detection of HMA.

Conclusions Fully automated computer algorithms were able to detect hard exudates and HMA. This paper presents encouraging results in automatic identification of important features of NPDR.

Diabet. Med. 19, 105–112 (2002)

Aim To determine the relationship of birth weight to later glucose and insulin metabolism.

Methods Systematic review of the published literature. Data sources were Medline and Embase. Included studies were papers reporting the relationship of birth weight with a measure of glucose or insulin metabolism after 1 year of age, including the prevalence of Type 2 diabetes mellitus (DM). Three reviewers abstracted information from each paper according to specified criteria.

Results Forty‐eight papers fulfilled the criteria for inclusion, mostly of adults in developed countries. Most studies reported an inverse relationship between birth weight and fasting plasma glucose concentrations (15 of 25 papers), fasting plasma insulin concentrations (20 of 26), plasma glucose concentrations 2 h after a glucose load (20 of 25), the prevalence of Type 2 DM (13 of 16), measures of insulin resistance (17 of 22), and measures of insulin secretion (16 of 24). The predominance of these inverse relationships and the demonstration in a minority of studies of other directions of the relationships could not generally be explained by differences between studies in the sex, age, or current size of the subjects. However, the relationship of birth weight with insulin secretion was inconsistent in studies of adults.

Conclusions The published literature shows that, generally, people who were light at birth have an adverse profile of later glucose and insulin metabolism. This is related to higher insulin resistance, but the relationship to insulin secretion in adults is less clear.

Diabet. Med. 20, 339–348 (2003)

Background  The last two decades have witnessed unprecedented technological progress in the development of continuous glucose sensors, resulting in the first generation of commercial glucose monitors. This has fuelled the development of prototypes of a closed‐loop system based on the combination of a continuous monitor, a control algorithm, and an insulin pump.

Method  A review of electromechanical closed‐loop approaches is presented. This is followed by a review of existing prototypes and associated glucose sensors. A literature review was undertaken from 1960 to 2004.

Results  Two main approaches exist. The extracorporeal s.c.–s.c. approach employs subcutaneous glucose monitoring and subcutaneous insulin delivery. The implantable i.v.–i.p. approach adopts intravenous sampling and intraperitoneal insulin delivery. Feasibility of both solutions has been demonstrated in small‐scale laboratory studies using either the classical proportional–integral–derivative controller or a model predictive controller. Performance in the home setting has yet to be demonstrated.

Conclusions  The glucose monitor remains the main limiting factor in the development of a commercially viable closed‐loop system, as presently available monitors fail to demonstrate satisfactory characteristics in terms of reliability and/or accuracy. Regulatory issues are the second limiting factor. Closed‐loop systems are likely to be used first by health‐care professionals in controlled environments such as intensive care units.

Type 1 diabetes mellitus in adults may present in a manner similar to that of Type 2 diabetes but with a late development of insulin dependency. We studied 65 patients who presented with ‘adult‐onset’ diabetes after the age of 30 years. Of these patients, 19 required insulin therapy. The insulin‐treated patients were significantly younger, their onset of diabetes was at an earlier age, and their postprandial serum C‐peptide levels were lower than those of the non‐insulin‐treated group. Moreover, the insulin‐treated subjects had a higher mean concentration of antibodies to glutamic acid decarboxylase (GAD) (66.8 ± 10.2 units) than the patients who did not require insulin (9.9 ± 1.9 units) (p < 0.001) and their frequency of anti‐GAD positivity was 73.7% versus 4.3% (p < 0.001). Thus, among patients attending a diabetes clinic, the majority (73.7%) of subjects who presented with diabetes after 30 years of age and who subsequently required therapy with insulin, actually have the islet cell lesion of Type 1 diabetes which progresses at a slower tempo than in children. We conclude that testing for anti‐GAD in adult‐onset non‐obese diabetic patients should be a routine procedure in order to detect latent insulin‐dependency at the earliest possible stage, since this assay can assist in the correct classification of diabetes, and more appropriate therapy.