A novel test for IGT utilizing metabolite markers of glucose tolerance.

The oral glucose tolerance test (OGTT) is the only method to diagnose patients having impaired glucose tolerance (IGT), but its use has diminished considerably in recent years. Metabolomic profiling studies have identified a number of metabolites whose fasting levels are associated with dysglycemia and type 2 diabetes. These metabolites may serve as the basis of an alternative test for IGT. Using the stable isotope dilution technique, quantitative assays were developed for 23 candidate biomarker metabolites. These metabolites were measured in fasting plasma samples taken just prior to an OGTT from 1623 nondiabetic subjects: 955 from the Relationship between Insulin Sensitivity and Cardiovascular Disease Study (RISC Study; 11.7% IGT) and 668 subjects from the Diabetes Mellitus and Vascular Health Initiative (DMVhi) cohort from the DEXLIFE project (11.8% IGT). The associations between metabolites, anthropometric, and metabolic parameters and 2hPG values were assessed by Pearson correlation coefficients and Random Forest classification analysis to rank variables for their ability to distinguish IGT from normal glucose tolerance (NGT). Multivariate logistic regression models for estimating risk of IGT were developed and evaluated using AUCs calculated from the corresponding ROC curves. A model based on the fasting plasma levels of glucose, α-hydroxybutyric acid, ß-hydroxybutyric acid, 4-methyl-2-oxopentanoic acid, linoleoylglycerophosphocholine, oleic acid, serine and vitamin B5 was optimized in the RISC cohort (AUC = 0.82) and validated in the DMVhi cohort (AUC = 0.83). A novel, all-metabolite-based test is shown to be a discriminate marker of IGT. It requires only a single fasted blood draw and may serve as a more convenient surrogate for the OGTT or as a means of identifying subjects likely to be IGT.

A novel fasting blood test for insulin resistance and prediabetes.

BACKGROUND: Insulin resistance (IR) can precede the dysglycemic states of prediabetes and type 2 diabetes mellitus (T2DM) by a number of years and is an early marker of risk for metabolic and cardiovascular disease. There is an unmet need for a simple method to measure IR that can be used for routine screening, prospective study, risk assessment, and therapeutic monitoring. We have reported several metabolites whose fasting plasma levels correlated with insulin sensitivity. These metabolites were used in the development of a novel test for IR and prediabetes. METHODS: Data from the Relationship between Insulin Sensitivity and Cardiovascular Disease Study were used in an iterative process of algorithm development to define the best combination of metabolites for predicting the M value derived from the hyperinsulinemic euglycemic clamp, the gold standard measure of IR. Subjects were divided into a training set and a test set for algorithm development and validation. The resulting calculated M score, M(Q), was utilized to predict IR and the risk of progressing from normal glucose tolerance to impaired glucose tolerance (IGT) over a 3 year period. RESULTS: M(Q) correlated with actual M values, with an r value of 0.66. In addition, the test detects IR and predicts 3 year IGT progression with areas under the curve of 0.79 and 0.70, respectively, outperforming other simple measures such as fasting insulin, fasting glucose, homeostatic model assessment of IR, or body mass index. CONCLUSIONS: The result, Quantose(TM), is a simple test for IR based on a single fasting blood sample and may have value as an early indicator of risk for the development of prediabetes and T2DM.

Mortality and predictors of death in a cohort of patients presenting to an eating disorders service.

OBJECTIVE: The main aim was to investigate mortality across the spectrum of eating disorders presenting to a specialized service for adults in the UK. A secondary aim was to explore whether any clinical and demographic factors may be associated with increased risk. METHOD: We conducted a "tracing" study of 1,892 patients assessed by the Service between 1992 and 2004. We used the Office of National Statistics to identify all deaths recorded up to August 2007. We also compared deceased patients with matched controls in terms of a number of clinical and demographic variables at initial presentation to the service. RESULTS: Anorexia nervosa had a ten-fold increased risk of early death, but there was also evidence of increased risk in other groups of patients, including eating disorder not otherwise specified. A number of clinical factors predicted increased mortality risk, especially very low body mass index and the presence of alcohol misuse. DISCUSSION: The study confirms previous evidence of a markedly increased mortality risk for anorexia nervosa, but also suggests that the risk is not confined to this eating disorder and that greater attention needs to be focused on wider psychiatric comorbidity.

Males assessed by a specialized adult eating disorders service: Patterns over time and comparisons with females.

OBJECTIVE: In view of previous inconsistencies and the limited literature on males with eating disorders, we aimed to examine changes in presentation rates over time and any differences between males and females. METHOD: In a cohort of 2,554 new patients assessed by a specialized service for adults over a 21-year period, we examined rates by gender over time. We also carried out a detailed comparison of selected clinical and demographic variables on a series of 65 males and females matched by diagnosis and date of assessment. RESULTS: Approximately 5% of patients were male and there was no evidence of a change in presentation rate by gender over time. Males were more likely to be diagnosed as not having a clinical eating disorder and less likely to abuse laxatives, but otherwise there was little difference in clinical presentation. CONCLUSION: Eating disorders continue to present predominantly in females and the proportion of males remains broadly stable.

Clinical application of 1,5-anhydroglucitol measurements in patients with hepatocyte nuclear factor-1alpha maturity-onset diabetes of the young.

OBJECTIVE: 1,5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in a lowered plasma concentration. As a low renal threshold for glucose has been described in hepatocyte nuclear factor-1alpha (HNF-1alpha) maturity-onset diabetes of the young (MODY), the 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in patients with HNF-1alpha MODY and in type 2 diabetic subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1alpha MODY. RESEARCH DESIGN AND METHODS: We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 type 2 diabetic patients and 47 nondiabetic control subjects. The 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). Receiver operating characteristic (ROC) curve analysis was used to evaluate 1,5-AG as a screening marker for HNF-1alpha MODY. RESULTS: The mean 1,5-AG plasma concentration in diabetic HNF-1alpha mutation carriers was 5.9 microg/ml, and it was lower than that in type 2 diabetic patients (11.0 microg/ml, P = 0.003) and in nondiabetic control subjects (23.9 microg/ml, P < 0.00005). The ROC curve analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1alpha MODY at the criterion of <6.5 microg/ml in patients with an A1C level between 6.5 and 9.0%. CONCLUSIONS: 1,5-AG may be a useful biomarker for differential diagnosis of patients with HNF-1alpha MODY with a specific range of A1C, although this requires further investigation. However, the clinical use of this particle in diabetic HNF-1alpha mutation carriers for metabolic control has substantial limitations.

Clinical and socio-demographic characteristics of university students referred to an eating disorders service.

This study describes the socio-demographic characteristics and eating disorders symptomatology of university students assessed by a specialised NHS eating disorders service in the UK over a 4-year period. Information was gathered on past treatment history, source of referral, details of university and course of study, whether the patient was still open to the service or discharged, and if the patient had dropped out of contact from services. The study also describes the diagnosis of the assessed patients as well as the results of the Eating Disorders Inventory (EDI), Rosenberg Self-Esteem Scale (RSES) and Revised Symptom Check List 90 (SCL-90-R) questionnaires. The study shows that the university students attending an eating disorder service often suffer from severe conditions, which are generally well-established before they start their university studies. The study discusses the implication of those results in service delivery and future service development.

Season of birth and eating disorders: patterns across diagnoses in a specialized eating disorders service.

OBJECTIVE: In view of inconsistent findings from previous studies, the aim was to investigate possible seasonal variation in month of birth in patients with anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified. METHOD: We examined the month of birth in a cohort of 1,305 adult patients with a DSM-IV eating disorder diagnosis at first presentation to a specialized eating disorders service. RESULTS: When compared to general population data, we found no evidence of significant variation in month or season of birth in anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified. CONCLUSION: The authors question whether people who develop eating disorders differ from the general population in their season of birth. Caution is expressed about further speculation regarding the etiological significance of season of birth in eating disorders.

1,5-anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes.

OBJECTIVE: Postprandial hyperglycemia is often inadequately assessed in diabetes management. Serum 1,5-anhydroglucitol (1,5-AG) drops as serum glucose rises above the renal threshold for glucose and has been proposed as a marker for postprandial hyperglycemia. The objective of this study is to demonstrate the relationship between 1,5-AG and postprandial hyperglycemia, as assessed by the continuous glucose monitoring system (CGMS) in suboptimally controlled patients with diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 or type 2 diabetes and an HbA(1c) (A1C) between 6.5 and 8% with stable glycemic control were recruited from two sites. A CGMS monitor was worn for two consecutive 72-h periods. Mean glucose, mean postmeal maximum glucose (MPMG), and area under the curve for glucose above 180 mg/dl (AUC-180), were compared with 1,5-AG, fructosamine (FA), and A1C at baseline, day 4, and day 7. RESULTS: 1,5-AG varied considerably between patients (6.5 +/- 3.2 mug/ml [means +/- SD]) despite similar A1C (7.3 +/- 0.5%). Mean 1,5-AG (r = -0.45, P = 0.006) correlated with AUC-180 more robustly than A1C (r = 0.33, P = 0.057) or FA (r = 0.38, P = 0.88). MPMG correlated more strongly with 1,5-AG (r = -0.54, P = 0.004) than with A1C (r = 0.40, P = 0.03) or FA (r = 0.32, P = 0.07). CONCLUSIONS: 1,5-AG reflects glycemic excursions, often in the postprandial state, more robustly than A1C or FA. 1,5-AG may be useful as a complementary marker to A1C to assess glycemic control in moderately controlled patients with diabetes.

Cluster analysis of key diagnostic variables from two independent samples of eating-disorder patients: evidence for a consistent pattern.

INTRODUCTION: The optimal classification of eating disorders has been a matter of considerable debate. The present paper tackles this issue using cluster analysis with large independent samples of eating-disorder patients. METHOD: Two samples of adult female patients from Sweden (n = 631) and England (n = 472) were classified on the basis of 10 key clinical variables of primary significance for diagnosing eating disorders. A separate series of cluster analyses were conducted on each sample. RESULTS: Results suggested that a three-cluster solution was optimal in both samples. The first cluster ('generalized eating disorder') was characterized by high levels of eating-disorder psychopathology on all variables except weight and menstrual functioning. The second cluster ('anorexics') was typified by low weight, amenorrhoea and the absence of binge eating, and seemed to correspond to the clinical picture of anorexia nervosa. The third cluster ('overeaters') was characterized by high weight and moderate levels of binge eating and compensatory behaviour. CONCLUSIONS: Results suggest that patients presenting to eating-disorder services in different countries have clinical features that fall into very similar patterns. These patterns resemble, but are not identical to, existing diagnostic categories.