Universal Fasting Glucose Screening Before Gastric Emptying Scintigraphy and the High Prevalence of Undiagnosed Diabetes and Prediabetes.

The aim of this study was to assess the rates of undiagnosed diabetes mellitus (DM) and pre-DM in patients undergoing gastric emptying scintigraphy (GES). Diabetes is an epidemic in the United States, and the disease is associated with altered gut motility. As a result, we suspected that a significant number of patients referred for GES may have undiagnosed DM or pre-DM. Given that established procedure standards for GES require all patients to prepare with an 8-h fast, an opportunity is provided to measure the fasting blood glucose (FBG) in all individuals before they undergo the examination. Methods: The charts of patients undergoing GES were reviewed for a history of DM and correlated with FBG and GES results. FBG values, obtained by point-of-care testing, were categorized as normal, pre-DM, or DM. Results: Patients with known DM made up 23% of those referred for GES, and most (55%) had a normal FBG. In those without a history of DM, there were a significant number with undiagnosed pre-DM (12%) and DM (33%). Conclusion: Our study provides the first measure of the likely prevalence of undiagnosed DM and pre-DM and characterizes the different gastric emptying patterns among patients with normal FBG, likely undiagnosed pre-DM, likely undiagnosed DM, and known DM.

Disrupted pattern of rich-club organization in structural brain network from prediabetes to diabetes: A population-based study.

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.

The association of prediabetes and type 2 diabetes with hippocampal subfields volume: The Maastricht study.

AIMS/HYPOTHESIS: We investigated whether prediabetes, type 2 diabetes, and continuous measures of hyperglycemia are associated with tissue volume differences in specific subfields of the hippocampus. METHODS: We used cross-sectional data from 4,724 participants (58.7 ± 8.5 years, 51.5% women) of The Maastricht Study, a population-based prospective cohort. Glucose metabolism status was assessed with an oral glucose tolerance test, and defined as type 2 diabetes (n = 869), prediabetes (n = 671), or normal glucose metabolism (n = 3184). We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1w and FLAIR 3T MRI images. We used multiple linear regression and linear trend analysis, and adjusted for total intracranial volume, demographic, lifestyle, and cardiovascular risk factors. RESULTS: Type 2 diabetes was significantly associated with smaller volumes in the hippocampal subfield fimbria (standardized beta coefficient ± standard error (ß ± SE) = -0.195 ± 0.04, p-value < 0.001), the hippocampus proper, i.e. Cornu Ammonis (CA) 1, CA2/3, CA4, dentate gyrus, subiculum and presubiculum (ß ± SE < -0.105 ± 0.04, p-value < 0.006); as well as the hippocampal tail (ß ± SE = -0.162 ± 0.04, p-value < 0.001). Prediabetes showed no significant associations. However, linear trend analysis indicated a dose-response relation from normal glucose metabolism, to prediabetes, to type 2 diabetes. Multiple continuous measures of hyperglycemia were associated with smaller volumes of the subfields fimbria (ß ± SE < -0.010 ± 0.011, p-value < 0.001), dentate gyrus (ß ± SE < -0.013 ± 0.010, p-value < 0.002), CA3 (ß ± SE < -0.014 ± 0.011, p-value < 0.001), and tail (ß ± SE < -0.006 ± 0.012, p-value < 0.003). CONCLUSIONS/INTERPRETATION: Type 2 diabetes and measures of hyperglycemia are associated with hippocampal subfield atrophy, independently of lifestyle and cardiovascular risk factors. We found evidence for a dose-response relationship from normal glucose metabolism, to prediabetes, to type 2 diabetes. Prediabetes stages could give a window of opportunity for the early prevention of brain disease.

Pre-diabetes is associated with attenuation rather than volume of epicardial adipose tissue on computed tomography.

The volume of epicardial adipose tissue (EATV) is increased in type-2 diabetes (T2D), while its attenuation (EATA) appears to be decreased. Similar patterns have been suggested in pre-diabetes, but data is scarce. In both pre-diabetes and T2D, any independent role of EATV and EATA in disease development remains to be proven, a task complicated by their substantial co-variation with other anthropometrics, e.g. BMI, waist circumference, and abdominal visceral adipose tissue (VAT). EATV and EATA was quantified in computed tomography (CT) images in a population study (n = 1948) using an automatic technique. Data was available on BMI, waist circumference, abdominal visceral adipose tissue (VAT) area, insulin resistance (IR) and glucose tolerance, the latter ranging from normal (NGT), over pre-diabetes (impaired fasting glucose [IFG, n = 414] impaired glucose tolerance [IGT, n = 321] and their combination [CGI, n = 128]), to T2D. EATV was increased in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI, however not when adjusting for waist or VAT. EATA was reduced in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI and waist, however not when adjusting for VAT. Adjustment for other co-variates had little influence on the results. In conclusion, EATV is increased and EATA reduced in pre-diabetes, T2D and IR, however, significant co-variation with other anthropometrics, especially VAT, obscures their function in disease development. The current results do not exclude a pathophysiological role of epicardial fat, but future studies need to adjust for anthropometrics, or focus on the microenvironment within the pericardial sac.

Diagnostic performance of hypoechoic perinephric fat as a predictor of prediabetes and diabetes.

PURPOSE: To evaluate prevalence and predictive value of hypoechoic perinephric fat (HPF) in patients with prediabetes and diabetes compared to non-diabetics. METHODS: Of 240 patients with renal ultrasound and hemoglobin A1c (HbA1c) measurements, 114 patients had either prediabetes (HbA1c 5.7-6.4%) or diabetes (HbA1c ≥ 6.5%), and 126 patients did not. Two radiologists (blinded to diagnosis) reviewed images and discrepancies were resolved by a third. Inter-reader agreement was compared using free-marginal kappa and intraclass correlation coefficient. Fisher's exact test, Mann-Whitney test, multivariable logistic regression, and Spearman's rank correlation test with two-tailed p < 0.05 were used to determine statistical significance. RESULTS: HPF was exclusively identified in prediabetic and diabetic patients with a prevalence of 23% (vs 0%; p < 0.001). Identification of HPF had almost perfect inter-reader agreement (k = 0.94) and was statistically significant (p = 0.034) while controlling for body mass index (BMI) and estimated glomerular filtration rate in multivariable analysis. HPF had extremely high specificity and positive predictive value (100% for both) in patients with prediabetes and diabetes although it was not a sensitive finding (23% sensitivity). In patients with prediabetes and diabetes, those with HPF were statistically significantly more likely to have chronic kidney disease (CKD) (p = 0.003). There was no statistically significant difference in BMI, stages of CKD, and types of diabetes. CONCLUSION: Hypoechoic perirenal fat has almost perfect inter-reader agreement and is highly specific for and predictive of prediabetes and diabetes. Its presence may also help identify those with chronic kidney disease among prediabetic and diabetic patients.

Cardiometabolic predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots in patients at high cardiovascular risk: an 8-year prospective cohort study.

INTRODUCTION: Adiposity has a few phenotypes associated with various levels of risk for diabetes mellitus (DM), but their exact predictive value is not well understood. OBJECTIVES: We aimed to assess the predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots for long­term cardiometabolic risk. PATIENTS AND METHODS: A total of 150 patients with chronic coronary syndrome (CCS) scheduled for elective coronary angiography were enrolled and a comprehensive clinical and ultrasound assessment of adiposity was performed (2012-2013). Of them, 143 individuals were followed for 8 years for insulin resistance (IR) and / or DM development. RESULTS: At baseline, DM and prediabetes were found in 22% and 8% of the patients, respectively. It was established that 11.7% of the participants died during the follow­up. The rate of DM increased to 46% with a decrease in the prediabetes rate (3.5%). Significant correlations with the Homeostatic Model Assessment of Insulin Resistance and glycated hemoglobin were observed for major anthropometric and ultrasound variables. In the multivariable analysis, independent predictors of IR were preperitoneal fat thickness (PreFT) (per 10mm increase: odds ratio [OR], 1.63; 95% CI, 1.22-2.33; P = 0.003) and body surface area (per 0.1m2 increase: OR, 1.59; 95% CI, 1.11-2.39; P = 0.02). DM was independently predicted by the high­density lipoprotein cholesterol concentration (OR, 0.93; 95% CI, 0.87-0.97; P = 0.005) and body fat mass (OR, 1.09; 95% CI, 1.03-1.17; P = 0.003). CONCLUSIONS: A complex assessment of the adipose tissue in patients with CCS is a valuable method for improving metabolic risk stratification. Some anthropometric and ultrasound parameters, such as PreFT or body surface area, were associated with IR and DM development.

Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study.

A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m2, and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population.

Association between visceral adipose tissue volume, measured using computed tomography, and cardio-metabolic risk factors.

We evaluated the associations between metabolic parameters with visceral adipose tissue (VAT) volume in women with prediabetes or type 2 diabetes (T2DM), and we compared the VAT volume with the VAT area. We enrolled women aged > 20 years with prediabetes or T2DM, who underwent oral glucose tolerance test and whose VAT was evaluated using computed tomography (CT) at our institution between 2017 and 2019. All participants underwent unenhanced spiral CT with a 3-mm slice thickness from the level of the diaphragm to the level of the mid-thigh. The two VAT areas were defined as the free drawn area on the levels of the umbilicus and L2 vertebra. The VAT areas were also manually drawn from the level of the diaphragm to the level of the pelvic floor and were used to calculate the VAT volumes by summing all areas with a slice thickness of 3 mm after setting the attenuation values from -45 to -195 Hounsfield Unit. All metabolic characteristics, except blood pressure, were significantly correlated with the VAT volume. The VAT areas measured at the level of the L2 vertebra and umbilicus were correlated with serum triglyceride, high-density lipoprotein cholesterol, and Framingham steatosis index alone. Multivariable regression analyses revealed that the VAT volume was significantly associated with several metabolic parameters. In conclusion, in women with prediabetes and T2DM, the VAT volume acquired from CT-based calculation has more significant correlations with metabolic risk factors compared with the VAT area.

Associations of plasma 8-iso-prostaglandin F2αlevels with fasting blood glucose (FBG) and intra-abdominal fat (IAF) area in various Glycometabolism populations.

BACKGROUND: This study aimed to investigate the differences in oxidative stress (OS) levels represented by 8-iso-prostaglandin F2α (8-iso-PGF2α) and analyze its correlation with the intra-abdominal fat (IAF) area and the glycolipid index. METHODS: We recruited a total of 160 eligible subjects. According to the blood glucose levels and the T2DM duration, subjects were divided into three groups: Type 2 Diabetes (T2DM) group, Prediabetic group, and Normal glucose-tolerance (NC) group, containing 66, 41, 53 patients, respectively. T2DM groups were additionally divided into a new-onset T2DM group including 29 patients and a non-new-onset T2DM group including 37 patients. General clinical data and biochemical indicators were collected. Intra-abdominal fat (IAF) was measured by MRI. 8-iso-PGF2α was measured by ELISA. RESULTS: Compared with the NC group, levels of systolic blood pressure (SBP), waist-to-hip ratio (WHR), FBG, 2 h postprandial glycemia(2hPG), 2 h insulin (2 h INS), IAF area, HOMA-IR, and 8-iso-PGF2α increased, and high-density lipoprotein cholesterol (HDL-C) decreased in T2DM groups and Prediabetic group (P < 0.05). The 2 h INS level was the highest in the Prediabetic group; 2hPG, and IAF area were the highest in the new-onset T2DM group; WHR, FBG, HOMA-IR and 8-iso-PGF2α were the highest in the non-new-onset T2DM group. Multiple stepwise regression analysis identified IAF area and FBG as the strongest and independent determinant of 8-iso-PGF2α (P < 0.01). CONCLUSIONS: In various glycometabolism populations, 8-iso-PGF2α is significantly correlated with FBG and IAF, this suggests that high blood glucose and abdominal obesity can increase the damage related to the OS in vivo.

Pre-gestational diabetes: Maternal body mass index and gestational weight gain are associated with augmented umbilical venous flow, fetal liver perfusion, and thus birthweight.

OBJECTIVES: To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus. METHODS: In a longitudinal observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24-36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160). RESULTS: The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02). CONCLUSIONS: The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.

Distribution patterns of intramyocellular and extramyocellular fat by magnetic resonance imaging in subjects with diabetes, prediabetes and normoglycaemic controls.

AIM: To evaluate the distribution of intramyocellular lipids (IMCLs) and extramyocellular lipids (EMCLs) as well as total fat content in abdominal skeletal muscle by magnetic resonance imaging (MRI) using a dedicated segmentation algorithm in subjects with type 2 diabetes (T2D), prediabetes and normoglycaemic controls. MATERIALS AND METHODS: Subjects from a population-based cohort were classified with T2D, prediabetes or as normoglycaemic controls. Total myosteatosis, IMCLs and EMCLs were quantified by multiecho Dixon MRI as proton-density fat-fraction (in %) in abdominal skeletal muscle. RESULTS: Among 337 included subjects (median age 56.0 [IQR: 49.0-64.0] years, 56.4% males, median body mass index [BMI]: 27.2 kg/m2 ), 129 (38.3%) were classified with an impaired glucose metabolism (T2D: 49 [14.5%]; prediabetes: 80 [23.7%]). IMCLs were significantly higher than EMCLs in subjects without obesity (5.7% [IQR: 4.8%-7.0%] vs. 4.1% [IQR: 2.7%-5.8%], P < .001), whereas the amounts of IMCLs and EMCLs were shown to be equal and significantly higher in subjects with obesity (both 6.7%, P < .001). Subjects with prediabetes and T2D had significantly higher amounts of IMCLs and EMCLs compared with normoglycaemic controls (P < .001). In univariable analysis, prediabetes and T2D were significantly associated with both IMCLs (prediabetes: ß: 0.76, 95% CI: 0.28-1.24, P = .002; T2D: ß: 1.56, 95% CI: 0.66-2.47, P < .001) and EMCLs (prediabetes: ß: 1.54, 95% CI: 0.56-2.51, P = .002; T2D: ß: 2.15, 95% CI: 1.33-2.96, P < .001). After adjustment for age and gender, the association of IMCLs with prediabetes attenuated (P = 0.06), whereas for T2D, both IMCLs and EMCLs remained significantly and positively associated (P < .02). CONCLUSION: There are significant differences in the amount and distribution ratio of IMCLs and EMCLs between subjects with T2D, prediabetes and normoglycaemic controls. Therefore, these patterns of intramuscular fat distribution by MRI might serve as imaging biomarkers in both normal and impaired glucose metabolism.

Tissue-specific glucose partitioning and fat content in prediabetes and type 2 diabetes: whole-body PET/MRI during hyperinsulinemia.

OBJECTIVE: To obtain direct quantifications of glucose turnover, volumes and fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated approach for whole-body imaging. DESIGN AND METHODS: Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI. RESULTS: Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in controls to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to control subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity assessed as glucose infusion rate correlated with liver MRglu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MRglu only in the same muscle group. CONCLUSIONS: This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.

Evaluation of the Systolic and Diastolic Right Ventricular Function: A Comparison Between Diabetes, Prediabetes and Normal Patients Without Coronary Artery Disease.

Diabetes mellitus is a well-known dangerous factor for cardiovascular disease with high rate of comorbidities. Patients suffering from this disease have represented more heart failures which is entangled with Ischemic heart disease or high blood pressure. Thus, depending on the recent scientific facts, diabetes mellitus as a separate factor which is independent from CAD, Arterial blood pressure or other factors, is claimed to culminate in advance heart failure. Previous studies have concentrated on the impacts of diabetes and prediabetes on the performance of the left ventricular which leaves right ventricular uncovered. Consequently, the aim of this article is to analyze and compare the systolic and diastolic function of the right ventricular in normal patients and the ones with diabetes and prediabetes without any coronary artery disease.

Universal haemoglobin A1c screening reveals high prevalence of dysglycaemia in patients undergoing total knee arthroplasty.

INTRODUCTION: Diabetes mellitus is an established modifiable risk factor for periprosthetic joint infection (PJI). Haemoglobin A1c (HbA1c) is a glycaemic marker that correlates with diabetic complications and PJI. As diabetes and prediabetes are frequently asymptomatic, and there is increasing evidence to suggest a correlation between dysglycaemia and osteoarthritis, it is reasonable to provide HbA1c screening before total knee arthroplasty (TKA). The aim of the present study was to determine the prevalence of dysglycaemia in patients who underwent TKA and investigate whether HbA1c screening and optimisation of glycaemic control before TKA affects the incidence of PJI after TKA. METHODS: Patients who underwent primary TKA before and after routine HbA1c screening was introduced in our unit were reviewed. Prediabetes and diabetes were defined according to the American Diabetes Association. Patients with HbA1c ≥7.5% were referred to an endocrinologist for optimisation of glycaemic control before TKA. The incidence PJI, defined according to the Musculoskeletal Infection Society criteria, was recorded. RESULTS: A total of 729 patients (934 knees) had HbA1c screening before TKA. Of them, 17 (2.3%) and 184 (25.2%) patients had known prediabetes and diabetes, respectively, and 265 (36.4%) and 12 (1.6%) had undiagnosed prediabetes and diabetes, respectively. The incidence of PJI was significantly lower in all patients who received HbA1c screening compared with those who did not (0.2% vs 1.02%, P=0.027). CONCLUSION: Screening for HbA1c before TKA provides a cost-effective opportunity to identify undiagnosed dysglycaemia. Patients identified as having dysglycaemia receive modified treatment, significantly reducing the rate of PJI when compared with historical controls.

Normalized Indices Derived from Visceral Adipose Mass Assessed by Magnetic Resonance Imaging and Their Correlation with Markers for Insulin Resistance and Prediabetes.

Visceral adipose tissue (VAT) plays an important role in the pathogenesis of insulin resistance (IR), prediabetes and type 2 diabetes. However, VAT volume alone might not be the best marker for insulin resistance and prediabetes or diabetes, as a given VAT volume may impact differently on these metabolic traits based on body height, gender, age and ethnicity. In a cohort of 1295 subjects from the Tübingen Diabetes Family Study (TDFS) and in 9978 subjects from the UK Biobank (UKBB) undergoing magnetic resonance imaging for quantification of VAT volume, total adipose tissue (TAT) in the TDFS, total abdominal adipose tissue (TAAT) in the UKBB, and total lean tissue (TLT), VAT volume and several VAT-indices were investigated for their relationships with insulin resistance and glycemic traits. VAT-related indices were calculated by correcting for body height (VAT/m:VAT/body height; VAT/m2:VAT/(body height)2, and VAT/m3:VAT/(body height)3), TAT (%VAT), TLT (VAT/TLT) and weight (VAT/WEI), with closest equivalents used within the UKBB dataset. Prognostic values of VAT and VAT-related indices for insulin sensitivity, HbA1c levels and prediabetes/diabetes were analyzed for males and females. Males had higher VAT volume and VAT-related indices than females in both cohorts (p < 0.0001) and VAT volume has shown to be a stronger determinant for insulin sensitivity than anthropometric variables. Among the parameters uncorrected VAT and derived indices, VAT/m3 most strongly correlated negatively with insulin sensitivity and positively with HbA1c levels and prediabetes/diabetes in the TDFS (R2 = 0.375/0.305 for females/males for insulin sensitivity, 0.178/0.148 for HbA1c levels vs., e.g., 0..355/0.293 and 0.144/0.133 for VAT, respectively) and positively with HbA1c (R2 = 0.046/0.042) in the UKBB for females and males. Furthermore, VAT/m3 was found to be a significantly better determinant of insulin resistance or prediabetes than uncorrected VAT volume (p < 0.001/0.019 for females/males regarding insulin sensitivity, p < 0.001/< 0.001 for females/males regarding HbA1c).Evaluation of several indices derived from VAT volume identified VAT/m3 to correlate most strongly with insulin sensitivity and glucose metabolism. Thus, VAT/m3 appears to provide better indications of metabolic characteristics (insulin sensitivity and pre-diabetes/diabetes) than VAT volume alone.

Pre-Diabetes, but not Type 2 Diabetes, Is Related to Brain Amyloid in Late Middle-Age.

BACKGROUND: Type 2 diabetes is a dementia risk factor, but its relation to Alzheimer's disease (AD), the most common cause of dementia, is unclear. OBJECTIVE: Our primary objective was to examine the association of pre-diabetes and type 2 diabetes with brain amyloid-ß (Aß), the putative main culprit of AD. Our secondary objective was to examine the association of pre-diabetes and type 2 diabetes with neurodegeneration, cerebrovascular disease (CVD), and memory performance. METHODS: We conducted a cross-sectional study of 350 late middle-aged Hispanics without dementia in New York City. We classified diabetes status as normal glucose tolerance (NGT), pre-diabetes, and type 2 diabetes following American Diabetes Association criteria. Brain Aß was ascertained as global Aß standardized value uptake ratio using PET with 18F-Florbetaben. Neurodegeneration was operationalized as cortical thickness in regions affected by AD using MRI. CVD was operationalized as white matter hyperintensity volume (WMH) on MRI, and memory as performance with the selective reminding test (SRT). RESULTS: Mean age was 64.15±3.34 years, 72.00% were women, and 35.43% were APOEɛ4 carriers. Pre-diabetes, but not type 2 diabetes, was associated with higher Aß compared with NGT. Type 2 diabetes treatment was related to lower Aß. Type 2 diabetes was related to lower cortical thickness, higher WMH, and lower SRT score. CONCLUSION: Pre-diabetes, but not type 2 diabetes, is associated with higher brain Aß in late middle age, and this observation could be explained by the relation of diabetes treatment with lower brain Aß. Whether type 2 diabetes treatment lowers brain Aß requires further study.

Trends in Bone Mineral Density, Osteoporosis, and Osteopenia Among U.S. Adults With Prediabetes, 2005-2014.

OBJECTIVE: We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture. RESEARCH DESIGN AND METHODS: We collected and analyzed data from the U.S. National Health and Nutrition Examination Surveys during the period from 2005 to 2014. Femoral neck and lumbar spine BMD data were available for 5,310 adults with prediabetes and 5,162 adults with NGR >40 years old. RESULTS: A shift was observed toward a lower BMD and a higher prevalence of osteopenia/osteoporosis at the femoral neck and lumbar spine in U.S. adults >40 years old with prediabetes since 2005, especially in men <60 and women ≥60 years old. A shift toward a higher prevalence of osteopenia/osteoporosis at the femoral neck was also observed in adults >40 years old with NGR. Moreover, prediabetes was associated with a higher prevalence of hip fracture, although participants with prediabetes had higher BMD and a lower prevalence of osteopenia/osteoporosis at the femoral neck. CONCLUSIONS: There was a declining trend in BMD from 2005 to 2014 in U.S. adults >40 years old with prediabetes and NGR, and this trend was more significant in men <60 years old. Populations with prediabetes may be exposed to relatively higher BMD but a higher prevalence of fracture.

Renal and renal sinus fat volumes as quantified by magnetic resonance imaging in subjects with prediabetes, diabetes, and normal glucose tolerance.

PURPOSE: We hypothesize that MRI-based renal compartment volumes, particularly renal sinus fat as locally and potentially independently acting perivascular fat tissue, increase with glucose intolerance. We therefore analyze the distribution of renal volumes in individuals with normal glucose levels and prediabetic and diabetic individuals and investigate potential associations with other typical cardiometabolic biomarkers. MATERIAL AND METHODS: The sample comprised N = 366 participants who were either normoglycemic (N = 230), had prediabetes (N = 87) or diabetes (N = 49), as determined by Oral Glucose Tolerance Test. Other covariates were obtained by standardized measurements and interviews. Whole-body MR measurements were performed on a 3 Tesla scanner. For assessment of the kidneys, a coronal T1w dual-echo Dixon and a coronal T2w single shot fast spin echo sequence were employed. Stepwise semi-automated segmentation of the kidneys on the Dixon-sequences was based on thresholding and geometric assumptions generating volumes for the kidneys and sinus fat. Inter- and intra-reader variability were determined on a subset of 40 subjects. Associations between glycemic status and renal volumes were evaluated by linear regression models, adjusted for other potential confounding variables. Furthermore, the association of renal volumes with visceral adipose tissue was assessed by linear regression models and Pearson's correlation coefficient. RESULTS: Renal volume, renal sinus volume and renal sinus fat increased gradually from normoglycemic controls to individuals with prediabetes to individuals with diabetes (renal volume: 280.3±64.7 ml vs 303.7±67.4 ml vs 320.6±77.7ml, respectively, p < 0.001). After adjustment for age and sex, prediabetes and diabetes were significantly associated to increased renal volume, sinus volume (e.g. ßPrediabetes = 10.1, 95% CI: [6.5, 13.7]; p<0.01, ßDiabetes = 11.86, 95% CI: [7.2, 16.5]; p<0.01) and sinus fat (e.g. ßPrediabetes = 7.13, 95% CI: [4.5, 9.8]; p<0.001, ßDiabetes = 7.34, 95% CI: [4.0, 10.7]; p<0.001). Associations attenuated after adjustment for additional confounders were only significant for prediabetes and sinus volume (ß = 4.0 95% CI [0.4, 7.6]; p<0.05). Hypertension was significantly associated with increased sinus volume (ß = 3.7, 95% CI: [0.4, 7.0; p<0.05]) and absolute sinus fat volume (ß = 3.0, 95% CI: [0.7, 5.3]; p<0.05). GFR and all renal volumes were significantly associated as well as urine creatinine levels and renal sinus volume (ß = 1.6, 95% CI: [0.1, 2.9]; p<0.05). CONCLUSION: Renal volume and particularly renal sinus fat volume already increases significantly in prediabetic subjects and is significantly associated with VAT. This shows, that renal sinus fat is a perivascular adipose tissue, which early undergoes changes in the development of metabolic disease. Our findings underpin that renal sinus fat is a link between metabolic disease and associated chronic kidney disease, making it a potential imaging biomarker when assessing perivascular adipose tissue.

The Association between HbA1c Levels, Olfactory Memory and Cognition in Normal, Pre-Diabetic and Diabetic Persons.

BACKGROUND AND AIM: Recent data have shown that olfactory dysfunction is strongly related to Alzheimer's Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes. METHODS: We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT). RESULTS: We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction. CONCLUSION: To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline.

Carotid intima-media thickness values are significantly higher in patients with prediabetes compared to normal glucose metabolism.

Carotid intima-media thickness (C-IMT) increases in patients with adult type-2 diabetes mellitus (DM) and is used for early detection of macrovascular complications. We aimed to investigate the change of C-IMT in prediabetes and type-2 DM patients compared to subjects with normal glucose metabolism (NGM).A total of 180 individuals (60 subjects with NGM, 60 patients with prediabetes and 60 patients with type-2 DM) were included in this study. Routine laboratory and micro-macrovascular involvement were investigated. Urine albumin-creatinine ratio (ACR) was measured for urinary albuminuria detection. In addition to routine laboratory examination, right-left common and internal C-IMT (CC-IMT and IC-IMT) were measured.Systolic and diastolic blood pressure values were found to be higher in prediabetes and type-2 DM groups than NGM group. The prevalence of nephropathy and presence of CAD were higher in type-2 DM groups than prediabetes. Glucose, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, blood urea nitrogen, creatinine, high sensitive C reactive protein (hs-CRP) levels and urinary ACR were significantly higher in patients within prediabetes and type-2 DM groups than NGM group. Glucose, HbA1c and hs-CRP levels were found to be higher in type-2 DM groups than prediabetes. Estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol level was found to be lower in patients within prediabetes and type-2 DM groups than NGM group. Right-left-mean CC-IMT and IC-IMT values were found to be higher in prediabetes and type-2 DM groups than NGM group. Left IC-IMT, left CC-IMT, and mean IC-IMT values were found to be higher in type-2 DM patients compared to prediabetes. LDL and HDL cholesterols, HbA1c, and hs-CRP levels were independently associated with IC-IMT and CC-IMT.C-IMT values were significantly higher in impaired glucose metabolism compared to NGM. C-IMT measurement may be used as part of routine screening of macrovascular complication in patients with prediabetes and newly diagnosed type-2 DM.