A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control.

AIMS/HYPOTHESIS: Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaemic control is still lacking. METHODS: Here we report a broad metabolomics study in a clinical setting, covering 2,178 metabolite measures in saliva, blood plasma and urine from 188 individuals with diabetes and 181 controls of Arab and Asian descent. Using multivariate linear regression we identified metabolites associated with diabetes and markers of acute, short-term and long-term glycaemic control. RESULTS: Ninety-four metabolite associations with diabetes were identified at a Bonferroni level of significance (p < 2.3 × 10(-5)), 16 of which have never been reported. Sixty-five of these diabetes-associated metabolites were associated with at least one marker of glycaemic control in the diabetes group. Using Gaussian graphical modelling, we constructed a metabolic network that links diabetes-associated metabolites from three biofluids across three different timescales of glycaemic control. CONCLUSIONS/INTERPRETATION: Our study reveals a complex network of biochemical dysregulation involving metabolites from different pathways of diabetes pathology, and provides a reference framework for future diabetes studies with metabolic endpoints.

An Evaluation of Inter- and Intraobserver Reliability of Cone-beam Computed Tomography- and Two Dimensional-based Interpretations of Maxillary Canine Impactions using a Panel of Orthodontically Trained Observers.

OBJECTIVES: To assess intra- and interobserver agreement when evaluating maxillary impacted canines using cone beam computed tomography (CBCT) and two-dimensional (2D) images through a panel of orthodontically trained observers. MATERIALS AND METHODS: An adult skull with permanent dentition was employed to perform 15 simulated maxillary canine impactions. Two sets of 2D and three-dimensional (3D) radiographic images were acquired. A panel of assessors including 11 PhD and MSc postgraduate orthodontic students evaluated maxillary impacted canines using a standard questionnaire with 11 categorical variables. Kappa (K) statistics as well as Krippendorff's alpha (α) coefficients were used for the analysis of reliability. RESULTS: A high level of intraobserver agreement was found for both the CBCT- and 2D-based interpretations. The 11 observers demonstrated a higher interobserver agreement for the CBCT-based interpretations than that of the 2D-based interpretations (α = 0.68 and 0.38 respectively). The employed 3D classifications canines was found to be reliable among observers on CBCT images for the labiopalatal position (K = 0.87), mesiodistal position, vertical position, labiopalatal inclination and mesiodistal inclination (α = 0.95, 0.83, 0.84 and 0.92 respectively). The 2D-based interpretations were not in agreement among the 11 observers, except for the mesiodistal position (α = 0.88) and mesiodistal inclination (α = 0.88). CONCLUSION: The intraobserver agreement was high for both the 2D- and the CBCT-based interpretations. The interobserver agreement for the CBCT-based interpretations was remarkably higher than that of the 2D-based interpretations. The utilized CBCT-based 3D classifications for the location and inclination of maxillary impacted canines were found reliable among observers.

Elevated HbA1c levels in individuals not diagnosed with type 2 diabetes in Qatar: a pilot study.

BACKGROUND: The prevalence of type 2 diabetes (T2D) in Qatar and the Middle East is one of the highest in the world. It is estimated that about one quarter of the individuals with tbl2D are undiagnosed. Elevated HbA1c levels are an indicator of tbl2D or a pre-diabetic state. In this study we set out to examine which factors, such as anthropometric and socio-demographic risk factors, are associated with elevated HbA1c levels in a population without tbl2D. METHODS: We examined 191 subjects with no record of tbl2D. Anthropometrics and HbA1c were measured. Socio-demographic (age, gender, ethnicity and educational level) and health information were assessed through questionnaires. Elevated HbA1c levels were defined as >6.0% (>42 mmol/mol). Individual risk factors were examined in relationship to having elevated HbA1c levels using logistic regression. RESULTS: Thirty-eight (20%) study participants had elevated HbA1c levels. Participants from South Asian and Filipino descent were more likely to present with elevated HbA1c levels than Arab participants (adjusted odds ratios (OR): 13.30 (95% confidence interval (CI): 4.24, 41.79), p < 0.001 for South Asian and 4.54 (95% CI: 1.04, 19.83), p = 0.04 for Filipinos). A body mass index of above 30 kg/m(2) was associated with elevated HbA1c levels (adjusted OR: 2.90 (95% CI: 1.29, 6.51), p = 0.01). Neither gender nor educational level was associated with elevated HbA1c levels. CONCLUSIONS: Elevated HbA1c levels in individuals not diagnosed with diabetes were most frequently found in the South Asian and Filipino immigrant population. Special attention should therefore be given to the early identification of tbl2D in these subjects.

Evaluation of the diagnostic accuracy of CBCT-based interpretations of maxillary impacted canines compared to those of conventional radiography: An in vitro study.

BACKGROUND: Cone-beam computed tomography (CBCT) imaging has become widespread in diagnosing impacted teeth in the context of orthodontic treatment. However, the diagnostic accuracy of this 3D imaging tool has not been comprehensively evaluated yet. The objectives of this study were: (1) to investigate the diagnostic accuracy of employing CBCT imaging in the three-dimensional (3D) localization of maxillary impacted canines compared to the use of traditional two-dimensional (2D) imaging, and (2) to calculate sensitivity, specificity and diagnostic accuracy values for specific variables assessed in 3D and 2D. MATERIAL AND METHODS: An adult cadaver skull with permanent dentition was employed and 15 simulations of maxillary canine impactions were created. Two sets of 2D and 3D radiographic images were obtained. The two sets of images were evaluated by eleven postgraduate orthodontic students. Cochran's Q tests, Friedman's tests, and then McNemar's, McNemar-Bowker's and Wilcoxon tests were used to compare Observers' responses in 3D and 2D with the gold standard values. RESULTS: Insignificant differences were found between the CBCT-based interpretations and the gold standard (GS) concerning the labiopalatal position (P=0.34), labiopalatal and mesiodistal inclination (P=0.66 and P=0.194, respectively), whereas the mesiodistal and vertical positioning showed significant differences (P=0.002 and P<0.001, respectively). The percentages of agreement between the 2D- and 3D-based interpretations were acceptable in terms of labiopalatal and mesiodistal inclinations (71.5% and 77.5%, respectively). Remarkably higher values of sensitivity, specificity and diagnostic accuracy for the CBCT-based interpretations were observed. CONCLUSIONS: The diagnostic accuracy of CBCT outweighed that of 2D radiography in the labiopalatal localization of maxillary impacted canines, contact relationship with adjacent teeth and resorption diagnosis. 3D-based assessments and the gold standard had high percentages of agreement especially for the labiopalatal position evaluation and the proximity diagnosis.

Propionic acidemia and zinc deficiency presenting as necrolytic migratory erythema.

Necrolytic migratory erythema was first described in 1942 in a patient with pancreatic islet cell carcinoma. The disease can, however, have other etiologies including nutritional dermatoses. Here, we describe the clinicopathological picture of a 7-year-old female patient who presented with necrolytic migratory erythema which we believe is secondary to a rare combination of zinc deficiency and propionic acidemia.

1,5-Anhydroglucitol in saliva is a noninvasive marker of short-term glycemic control.

CONTEXT: In most ethnicities at least a quarter of all cases with diabetes is assumed to be undiagnosed. Screening for diabetes using saliva has been suggested as an effective approach to identify affected individuals. OBJECTIVE: The objective of the study was to identify a noninvasive metabolic marker of type 2 diabetes in saliva. DESIGN AND SETTING: In a case-control study of type 2 diabetes, we used a clinical metabolomics discovery study to screen for diabetes-relevant metabolic readouts in saliva, using blood and urine as a reference. With a combination of three metabolomics platforms based on nontargeted mass spectrometry, we examined 2178 metabolites in saliva, blood plasma, and urine samples from 188 subjects with type 2 diabetes and 181 controls of Arab and Asian ethnicities. RESULTS: We found a strong association of type 2 diabetes with 1,5-anhydroglucitol (1,5-AG) in saliva (P = 3.6 × 10(-13)). Levels of 1,5-AG in saliva highly correlated with 1,5-AG levels in blood and inversely correlated with blood glucose and glycosylated hemoglobin levels. These findings were robust across three different non-Caucasian ethnicities (Arabs, South Asians, and Filipinos), irrespective of body mass index, age, and gender. CONCLUSIONS: Clinical studies have already established 1,5-AG in blood as a reliable marker of short-term glycemic control. Our study suggests that 1,5-AG in saliva can be used in national screening programs for undiagnosed diabetes, which are of particular interest for Middle Eastern countries with young populations and exceptionally high diabetes rates.

Ethnic and gender differences in advanced glycation end products measured by skin auto-fluorescence.

Background Advanced glycation end products (AGEs) have been shown to be a predictor of cardiovascular risk in Caucasian subjects. In this study we examine whether the existing reference values are useable for non-Caucasian ethnicities. Furthermore, we assessed whether gender and smoking affect AGEs. Methods AGEs were determined by a non-invasive method of skin auto-fluorescence (AF). AF was measured in 200 Arabs, 99 South Asians, 35 Filipinos and 14 subjects of other/mixed ethnicity in the Qatar Metabolomics Study on Diabetes (QMDiab). Using multivariate linear regression analysis and adjusting for age and type 2 diabetes, we assessed whether ethnicity, gender and smoking were associated with AF. Results The mean AF was 2.27 arbitrary units (AU) (SD: 0.63). Arabs and Filipinos had a significant higher AF than the South Asian population (0.25 arbitrary units (AU) (95% CI: 0.11‒0.39), p = 0.001 and 0.34 (95% CI: 0.13‒0.55), p = 0.001 respectively). Also, AF was significantly higher in females (0.41 AU (95% CI: 0.29‒0.53), p < 0.001). AF associated with smoking (0.21 AU (95% CI: 0.01‒0.41), p = 0.04) and increased with the number of pack-years smoked (p = 0.02). Conclusions This study suggests that the existing reference values should take ethnicity, gender and smoking into account. Larger studies in specific ethnicities are necessary to create ethnic- and gender-specific reference values.