Extracellular volume fraction of the pancreas predicts glucose intolerance in patients undergoing major pancreatic surgeries.

PURPOSE: Pancreatic T1 value and extracellular volume fraction (ECV) are potential imaging biomarkers for pancreatic exocrine and endocrine function. This study aims to evaluate the ability of native T1 value and ECV of the pancreas in predicting postoperative new-onset diabetes (NODM) and worsened glucose tolerance in patients undergoing major pancreatic surgeries. METHODS: This retrospective study involved 73 patients who underwent 3 T pancreatic MRI with pre- and postcontrast T1 mapping before major pancreatic surgeries. Patients were divided into non-diabetic, pre-diabetic and diabetic groups based on their glycated hemoglobin (HbA1c) value. Preoperative native T1 value and ECV of the pancreas were compared among the three groups. The correlation of pancreatic T1 value and ECV with HbA1c was assessed by linear regression analysis, and the ability of pancreatic T1 value and ECV for predicting postoperative NODM and worsened glucose tolerance was assessed using Cox Proportional hazards regression analysis. RESULTS: Native pancreatic T1 value and ECV were both significantly higher in diabetic patients compared to pre-diabetic/non-diabetic patients, and ECV was also significantly higher in pre-diabetic patients compared to non-diabetic patients (all p < 0.05). Both native pancreatic T1 value and ECV showed positive correlation with preoperative HbA1c value (r = 0.50 and 0.55, respectively, both p < 0.001). ECV > 30.7% was the only independent predictor for NODM (HR = 5.687, 95% CI: 1.557, 13.468, p = 0.012) and worsened glucose tolerance (HR = 6.783, 95% CI:, 1.753, 15.842, p = 0.010) after surgery. CONCLUSIONS: Pancreatic ECV predicts the risk of postoperative NODM and worsened glucose tolerance in patients undergoing major pancreatic surgeries.

Comparison of pancreatic fat content measured by different methods employing MR mDixon sequence.

OBJECTIVE: To compare the reliability of different methods for measuring fat content of pancreas by MR modified Dixon(mDixon) Sequence and accurately evaluate pancreatic fat in as simple a way as possible. METHODS: This is a retrospective study, 64 patients were included in this study who underwent abdominal MR scan that contained the mDixon sequence from June 2019 to May 2020(Included 7 patients with type 2 diabetes and 4 patients with impaired glucose tolerance (IGT), they were admitted to hospital through the obesity clinic set up by endocrine department, all of them were initially diagnosed and untreated). All of the 64 patients were scanned in 3.0T MR (Philips Ingenia II) due to their condition, 10-34 slice pancreas images were obtained, which were different from each other. Three different methods of measurement were employed by two observers using Philips Intellispace Portal software: (1) All images (whole-pancreas) measurement, the whole-pancreatic fat fraction (wPFF) was calculated by software. (2) Interval slices measurement, that is half-pancreatic slices fat fraction (hPFF) measured in the same way, fat fraction obtained by the interlayer assay was calculated. (3) As usual, the fat content of pancreatic head, body and tail fat was measured respectively, and in order to improve credibility, we also measured head、 body and tail in every layer, and its average value was taken. The elapsed time of the above different measurement methods was recorded. Intra-group correlation coefficient (ICC) was used to analyze the consistency of the measured data within and between observers. T-tests and Friedman tests were applied to compare the difference of measured values among groups. RESULTS: No matter in normal person or diabetic or IGT, hPFF has shown good stability (ICChPFF = 0.988), and there was no significant difference compared with wPFF. But the average fat percentage composition of head, body and tail were significantly different from wPFF and hPFF (P < 0.01). At the same time, compared with normal person, pancreatic fat content in IGT and diabetic patients showed progressive significance(P<0.05). CONCLUSION: The distribution of pancreatic fat is not uniform, the method of measuring half pancreas by interlayer data collection can reflect the fat content of the entire pancreas, this suggests that measuring 50% of the pancreas is sufficient, this method effectively saves time and effort without affecting the results, which may have a better clinical application prospect.

Lifestyle Intervention Improves Prothrombotic Coagulation Profile in Individuals at High Risk for Type 2 Diabetes.

CONTEXT: Patients with obesity and insulin resistance are at higher risk for arterial and venous thrombosis due to a prothrombotic state. OBJECTIVE: The present study addressed whether this is reversible by lifestyle intervention and elucidated potential underlying associations. METHODS: A total of 100 individuals with impaired glucose tolerance or impaired fasting plasma glucose participated in a 1-year lifestyle intervention, including precise metabolic phenotyping and MRS-based determination of liver fat content as well as a comprehensive analysis of coagulation parameters before and after this intervention. RESULTS: During the lifestyle intervention, significant reductions in coagulation factor activities (II, VII, VIII, IX, XI, and XII) were observed. Accordingly, prothrombin time (PT%) and activated partial thromboplastin time (aPTT) were slightly decreased and prolonged, respectively. Moreover, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and also protein C and protein S decreased. Fibrinogen, antithrombin, D-dimer, and FXIII remained unchanged. Searching for potential regulators, especially weight loss, but also liver fat reduction, improved insulin sensitivity, and decreased low-grade inflammation were linked to favorable changes in hemostasis parameters. Independent of weight loss, liver fat reduction (FII, protein C, protein S, PAI-1, vWF), improved insulin sensitivity (protein S, PAI-1), and reduced low-grade inflammation (PT%, aPTT, FVIII/IX/XI/XII, vWF) were identified as single potential regulators. CONCLUSION: Lifestyle intervention is able to improve a prothrombotic state in individuals at high risk for type 2 diabetes. Besides body weight, liver fat content, insulin sensitivity, and systemic low-grade inflammation are potential mechanisms for improvements in hemostasis and could represent future therapeutic targets.

Evaluation of glucose tolerance and effect of dietary management on increased visceral fat in a patient with Werner syndrome.

Werner syndrome (WS), a type of progeria, is a hereditary condition caused by a mutation in the WRN gene. A 62-year-old Japanese woman was diagnosed with WS at the age of 32 and has been visiting the hospital for follow-up since the last 30 years. The patient developed diabetes at the age of 46, and at the age of 60, her body mass index increased from 20.1 to 22.7 kg/m2 owing to her unhealthy eating habits; her visceral fat area at the age of 61 was 233 cm2. With dietary control, her body weight, including the visceral fat and subcutaneous fat, decreased at the age of 62, and her insulin secretion, obesity, and fatty liver improved. We conducted the oral glucose challenge test four times, including at the prediabetic stage, to evaluate the insulin-secretion ability. The patient's insulin resistance gradually increased for more than 14 years, and her insulin secretion ability began to decrease 14 years after her diabetes diagnosis. Despite a remarkable decrease in body weight and fat mass with dietary management, the psoas muscle index did not decrease significantly in proportion to the body weight or fat mass. However, muscle mass monitoring is important for preventing the progression of sarcopenia. Hence, gradual reduction of visceral fat and weight by dietary management may be useful in treating diabetes in patients with WS, particularly in those whose visceral fat is significantly increased.

High-Performance Liquid Chromatography-Mass Spectrometry-Based Lipid Metabolite Profiling of Acromegaly.

CONTEXT: Metabolic disorders, especially dysregulated lipid metabolism, increase the risk of cardiovascular mortality in acromegaly. Previous studies measuring plasma macromolecular lipids have yielded conflicting results. PURPOSE: To explore the plasma lipid metabolite profiles by metabolomics analysis and identify potential metabolites associated with cardiac function in acromegaly. METHODS: Plasma was obtained from 80 newly diagnosed, untreated patients with acromegaly and 80 healthy controls. Echocardiography was performed. Based on the results of an oral glucose tolerance test (OGTT), patients were categorized into 2 groups: normal glucose tolerance (NGT, n = 28) and impaired glucose tolerance or diabetes mellitus (IGT/DM, n = 52). High-performance liquid chromatography-mass spectrometry (HPLC-MS)-based metabolomics analysis was conducted. Data were processed by principal components analysis (PCA), orthogonal partial least square-discriminant analysis (OPLS-DA), and MetaboAnalyst 4.0. Associations between metabolic substances and cardiovascular parameters were also explored. RESULTS: Metabolomics uncovered a distinct metabolic pattern between acromegaly and healthy controls, and perturbed pathways mainly include glycerophospholipid metabolism, sphingolipid metabolism, as well as linoleic acid metabolism. Collective analysis showed that phosphatidylethanolamine (PE) (22:6/16:0) was positively correlated with LV mass, while lysophosphatidylcholine (LysoPC) (16:0) was positively correlated with fractional shortening (FS) and left ventricle ejection fraction (LVEF). CONCLUSION: Patients with acromegaly have distinct lipid metabolite profiling, while PE (22:6/16:0) and LysoPC (16:0) are correlated with cardiac structure and function, which may contribute to the risk of cardiovascular complications.

Fat redistribution and accumulation of visceral adipose tissue predicts type 2 diabetes risk in middle-aged black South African women: a 13-year longitudinal study.

BACKGROUND: Cross-sectional studies in South Africa (SA) have shown that black SA women, despite being more insulin resistant, have less visceral adipose tissue (VAT) and more subcutaneous adipose tissue (SAT) than white women. This study aimed to investigate whether baseline and/or change in body fat and its distribution predict type 2 diabetes (T2D) risk in middle-aged black SA women, 13 years later. METHODS: We studied 142 black SA women who are the caregivers of the Birth-to-Twenty plus cohort, and who had normal glucose tolerance (NGT) at baseline. At baseline and follow-up, fasting blood samples, basic anthropometry and dual-energy X-ray absorptiometry-derived body composition were measured. At follow-up, an oral glucose tolerance test was completed. The WHO diabetes diagnostic criteria were used to define NGT, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), impaired glucose metabolism (IGM) and T2D. RESULTS: At follow-up, 64% of participants remained NGT, whereas 25% developed IGM, and 11% developed T2D. The IGM and the T2D groups were combined for statistical analyses. At baseline, trunk fat mass (FM), VAT but not SAT (measures of central FM) were higher in the IGM/T2D group than the NGT group (p < 0.0001). In contrast, the IGM/T2D group had lower leg %FM at baseline than the NGT group (p < 0.0001). Baseline trunk FM (Odds ratio per 1 kg increase (95% confidence interval, 1.95 (1.43-2.67))), and VAT (OR per 10 cm2 increase, 1.25 (1.10-1.42)), and the change in VAT (1.12 (1.03-1.23)) were associated with greater odds of developing IGM/T2D, whereas baseline leg FM (OR per 1 kg increase, 0.55 (0.41-0.73)) were associated with reduced IGM/T2D risk at follow-up (p < 0.05). CONCLUSIONS: Relative fat redistribution, with VAT accumulation, predicted the development of IGM/T2D 13 years before its onset. Prevention of central obesity is a key factor to reduce the risk of developing T2D among middle-aged urban black SA women.

Evaluation of plaque characteristics in coronary artery patients with impaired glucose tolerance through optical coherence tomography.

OBJECTIVE: With the adoption of optical coherence tomography (OCT), this study targets the impacts on plaque characteristics brought about by impaired glucose tolerance (IGT) in patients with coronary artery disease. METHODS: For this study, 150 patients with coronary artery disease were recruited. Regarding glycosylated hemoglobin (HbAlc), the patients were sectioned into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) groups. Coronary angiography (CAG) and OCT were conducted for 150 patients. RESULTS: There were 186 plaques discovered in 150 patients (37, 40, 44, and 65 in the NGT, IFG, IGT, and DM groups, respectively). Compared to the NGT group, the lipid core size, which is presented as the average angle of the lipid arc, was markedly larger in the IFG,IGT and DM groups ( 135.7 ± 32.7 Ê, 161.2 ± 55.7 Ê, 162.5 ± 55.8 Ê, and 170.2 ± 59.7 Ê, respectively, all P values< 0.05). Meanwhile, the fibrous cap over the lipid core in the NGT group was remarkably thicker than that in the IFG, IGT, and DM groups (115.7 ± 47.7 µm vs. 77.7 ± 23.5 µm, 75.1 ± 23.2 µm, 71.2 ± 22.1 µm, all P values<0.05). CONCLUSION: Coronary plaques in coronary artery patients with NDT are more stable than in those with IGT and DM.

Evaluation of plaque characteristics in coronary artery patients with impaired glucose tolerance through optical coherence tomography

SUMMARY OBJECTIVE With the adoption of optical coherence tomography (OCT), this study targets the impacts on plaque characteristics brought about by impaired glucose tolerance (IGT) in patients with coronary artery disease. METHODS For this study, 150 patients with coronary artery disease were recruited. Regarding glycosylated hemoglobin (HbAlc), the patients were sectioned into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) groups. Coronary angiography (CAG) and OCT were conducted for 150 patients. RESULTS There were 186 plaques discovered in 150 patients (37, 40, 44, and 65 in the NGT, IFG, IGT, and DM groups, respectively). Compared to the NGT group, the lipid core size, which is presented as the average angle of the lipid arc, was markedly larger in the IFG,IGT and DM groups ( 135.7 ± 32.7 Ê, 161.2 ± 55.7 Ê, 162.5 ± 55.8 Ê, and 170.2 ± 59.7 Ê, respectively, all P values< 0.05). Meanwhile, the fibrous cap over the lipid core in the NGT group was remarkably thicker than that in the IFG, IGT, and DM groups (115.7 ± 47.7 μm vs. 77.7 ± 23.5 μm, 75.1 ± 23.2 µm, 71.2 ± 22.1 µm, all P values<0.05). CONCLUSION Coronary plaques in coronary artery patients with NDT are more stable than in those with IGT and DM.

RESUMO OBJETIVO Com a adoção da tomografia de coerência óptica (OCT), o presente estudo visa as características dos impactos na placa trazidos pela tolerância diminuída à glicose (IGT) em pacientes com doença na artéria coronária. MÉTODOS Cento e cinquenta doentes com doença arterial coronária foram recrutados para este estudo. De acordo com a hemoglobina glicosilada (HbAlc), os pacientes foram divididos em grupos: tolerância normal à glicose (NGT), diminuição da glicemia de jejum (IFG), diminuição da tolerância à glicose (IGT) e diabetes mellitus (DM). Angiografia coronária (CAG) e OCT foram conduzidas para 150 doentes. RESULTADOS Existem 186 placas descobertas em 150 doentes (37, 40, 44 e 65 nos grupos NGT, IFG, IGT e DM, respectivamente). Em relação ao grupo NGT, o tamanho do núcleo lipídico, que é apresentado como o ângulo médio do arco lipídico, foi significativamente maior nos grupos IFG, IGT e DM (135,7 ± 32,7 Ê, 161,2 ± 55,7 Ê, 162,5 ± 55,8 Ê, e 170,2 ± 59,7 Ê, separadamente, os valores de P<0,05). Entretanto, a tampa sobre o núcleo de lipídios fibrosos no grupo NGT estava bem mais grossa do que nos grupos IFG, IGT e DM (115,7 ± 47,7μm vs. 77,7 ± 23,5 μm, 75,1 ± 23,2 µm, 71,2 ± 22,1 µm, todos os valores de P<0,05). CONCLUSÃO Placas coronárias na artéria coronária de pacientes com NDT são mais estáveis do que em doentes com IGT e DM.

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. METHODS: One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. RESULTS: There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance (P<0.001, P<0.001, P<0.001), impaired glucose tolerance (P=0.004, P<0.001, P=0.002), and type 2 diabetes mellitus (P<0.001, P<0.001, P<0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density (r=-0.187, P=0.03; r=-0.229 P=0.01), corneal nerve fiber length (r=-0.228, P=0.009; r=-0.285; P=0.001), and corneal nerve branch density (r=-0.187, P=0.033; r=-0.229, P=0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. CONCLUSIONS: Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke.

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance.

PURPOSE: Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). METHODS: A total of 28 healthy men (body mass index = 20.7-30.0 kg·m, age = 40-55 yr) and 16 men with DGT (body mass index = 23.8-33.5 kg·m, age = 43-53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by H-MRS. RESULTS: At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = -42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (-5%) and PAT (-6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. CONCLUSION: Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC.

A novel imaging platform for non-invasive screening of abnormal glucose tolerance.

Optical measurement of skin auto-fluorescence (SAF), most likely emanating from accumulated advanced glycation end-products (AGEs), has been proposed for the noninvasive diagnosis of glucose intolerance in clinical settings. Here, we developed a novel imaging system with transmission geometry for SAF measurement and compared its diagnostic performance in a Korean population.

Relevance of plasma obestatin and early arteriosclerosis in patients with type 2 diabetes mellitus.

We investigated the correlation between obestatin and metabolic parameters and carotid intima-media thickness (IMT) in plasma of patients with type 2 diabetes mellitus (T2DM). We collected 103 patients aged from 60 to 83 years (69.26 ± 5.83 years) form January, 2007 to May, 2009. All patients were divided into normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM according to the oral glucose tolerance test (OGTT). We found that higher levels of fasting insulin (Fins), fasting blood glucose, 2 h OGTT glucose, homeostasis model assessment of insulin resistance (HOMA-IR), low density lipoprotein cholesterol, glycated haemoglobin, and C-reactive protein (CRP), as well as lower obestatin level and higher intima-media thickness level (IMT), existed in T2DM group compared with NGT group and IGT group (P < 0.01). Also, obestatin level was independently associated with HOMA-IR and CRP, while IMT level was independently associated with HOMA-IR, triglyceride, Fins, and obestatin (P < 0.01), based on stepwise multiple regression analysis. Therefore, we deduced that the low level of plasma obestatin might be related to early arteriosclerosis in patients with T2DM via increasing IMT level, and elevated plasma obestatin levels might protect T2DM patients against carotid atherosclerosis to some extent.

Cardiac diastolic evaluation in pregnant women with abnormal glucose tolerance: an opportunity to detect the early and subclinical alterations and prevent cardiovascular diseases.

OBJECTIVES: of this study were to assess diastolic function in pregnant women with abnormal glucose tolerance (AGT), compared with normal glucose tolerance (NGT) women, and to evaluate the insulin resistance status and its association with Doppler-echocardiographic indexes. Echocardiograms of 108 consecutive Caucasian women with singleton pregnancies were performed. Insulin resistance status was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). All the studied women showed normal diastolic patterns. Patients with AGT (50.9%), as compared with NGT women, had higher HOMA-IR (1.70 ± 1.30 versus 1.01 ± 0.81, P = 0.003), lower QUICKI (0.36 ± 0.005 versus 0.40 ± 0.06, P = 0.004), higher lateral mitral annulus late diastolic velocity (13.6 ± 4.9 versus 11.9 ± 4.9, P = 0.03), and higher A-wave velocity, the wave responsible for the active atrial contraction component (75.2 ± 14.2 versus 67.7 ± 16.2, P = 0.01). At multivariate regression analysis HOMA-IR was the only parameter associated with A-wave velocity. In conclusion, women with AGT had an increased subclinical diastolic active participation, which is associated with higher levels of insulin resistance. For the increased risk of deterioration of cardiac diastolic function, earlier and more seriously than normal pregnancy, AGT women may have a careful followup to detect the early signs of cardiac alteration and to prevent cardiovascular diseases.

Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus.

CONTEXT: Excess visceral fat is associated with chronic systemic inflammation and cardiovascular complications. Pioglitazone has been reported to variably influence visceral fat volume; however, its effect on metabolic activity of the visceral fat remains uncharacterized. OBJECTIVE: The aim of this study was to assess the effects of pioglitazone on glucose metabolism of fat tissue by using (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography imaging. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET and computed tomography imaging were performed in 56 patients with impaired glucose tolerance or type 2 diabetes mellitus; lipid and glycemic profiles and inflammatory biomarkers were obtained in all patients. These patients were randomized to treatment with either pioglitazone or glimepiride for 16 weeks. MAIN OUTCOME MEASURES: The metabolic activity of the visceral fat tissues as assessed by FDG uptake was expressed as a target-to-background ratio (TBR) of blood-normalized standardized uptake value. RESULTS: The study was completed in 32 pioglitazone-treated and 21 glimepiride-treated patients (40 men and 13 women; mean age, 67.7 ± 8.1 y; body mass index, 25.0 ± 3.6 kg/m(2); glycated hemoglobin, 6.78 ± 0.70%). Both treatments were well-tolerated and comparably improved glycemic control. At baseline, visceral fat exhibited a higher TBR value than subcutaneous fat (0.55 ± 0.14 vs 0.30 ± 0.07, P < .001). Pioglitazone, but not glimepiride, significantly decreased the visceral fat volume (130.5 ± 53.0 to 122.1 ± 51.0 cm(2), P = .013) and TBR values (0.57 ± 0.16 to 0.50 ± 0.11, P = .007). Neither pioglitazone nor glimepiride treatment showed any effect on the volume or TBR values of subcutaneous fat. After 16 weeks of treatment with pioglitazone, reduction in visceral fat TBR was correlated to the increase in high-density lipoprotein cholesterol levels. CONCLUSIONS: Our study indicated that pioglitazone decreased the visceral fat volume and its metabolic activity in patients with impaired glucose tolerance or type 2 diabetes mellitus. The beneficial effects of pioglitazone on visceral fat may be independent of its glucose-lowering effect.

Abdominal visceral fat measurement using dual-energy X-ray: association with cardiometabolic risk factors.

OBJECTIVE: To examine the association between cardiometabolic risk factors and visceral adipose tissue (VAT) measurements using a dual-energy X-ray absorptiometry (DXA) based approach. DESIGN AND METHODS: An analysis of cross-sectional relationships between DXA VAT measured using CoreScan (GE Healthcare) and cardiometabolic indicators was conducted on a sample of 939 subjects (541 females and 398 males; average age, 56 years; average BMI, 26 kg/m2) who had previously undergone a total body DXA scan as well as measurements of key cardiometabolic risk factors. RESULTS: Sex-specific, age-adjusted multivariable regression analysis showed that for both men and women, DXA VAT was significantly associated with increased odds of hypertension, impaired fasting glucose, metabolic syndrome, and type 2 diabetes (P < 0.001). After additional model adjustment for BMI and waist circumference, the odds ratio (per SD change in VAT) for type 2 diabetes was 2.07 for women and 2.25 for men. Similarly, the odds ratio for metabolic syndrome for women was 3.46 and for men was 1.75. CONCLUSIONS: VAT measured using DXA showed a significant association with cardiometabolic risk factors and disease. These relationships persist after statistical adjustment for age, BMI, and waist circumference. DXA VAT may provide a new accessible option for quantifying VAT-related cardiometabolic risk.

Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging.

We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent serial (15)O-water positron emission tomography scans (age at first scan, 69.6 ± 7.5 years) and oral glucose tolerance tests 12 years earlier (age at first oral glucose tolerance test, 57.2 ± 11.1 years). Using voxel-based analysis, we compared changes in rCBF over an 8-year period between 15 participants with IGT in midlife and 49 with NGT. Significant differences were observed in longitudinal change in rCBF between the IGT and NGT groups. The predominant pattern was greater rCBF decline in the IGT group in the frontal, parietal, and temporal cortices. Some brain regions in the frontal and temporal cortices also showed greater longitudinal increments in rCBF in the IGT group. Our findings suggest that IGT in midlife is associated with subsequent longitudinal changes in brain function during aging even in cognitively normal older individuals.

Associations of plasma glucose levels and traits of metabolic syndrome with carotid intima media thickness in nondiabetic elderly subjects: are they mediated by insulin resistance?

BACKGROUND: The independent role of insulin resistance (IR) and high fasting blood glucose (FBG) levels within the normal range on vascular diseases is still under debate. This study was designed to explore whether IR, FBG levels, and the traits of metabolic syndrome are associated with increased carotid intima media thickness (IMT), the early marker of subclinical atherosclerosis, independently of each other in nondiabetic elderly subjects. METHODS: Blood analytes and anthropometric measurements were obtained. Carotid IMT was measured by ultrasonography; metabolic syndrome was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. IR was assessed through homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: At total of 207 subjects aged 68.2±3.6 years were enrolled. Subjects with increased carotid IMT (50.7%) were older (P=0.001), had a higher prevalence of metabolic syndrome (P<0.0001) and all its traits, impaired fasting glucose (IFG) (P<0.0001), and values of HOMA-IR (P<0.0001) than normal subjects. Increased carotid IMT significantly correlated with metabolic syndrome, its traits, IFG, and HOMA-IR. When multivariable regression models were constructed, central obesity [B=0.392; 95% confidence interval (CI) 0.280-0.505; P<0.0001], high-density lipoprotein cholesterol (HDL-C) (B=-0.007; 95% CI -0.013-0.000; P=0.042], hypertension (B=0.475; 95% CI 0.363-0.587; P<0.0001), and IFG (B=0.230; 95% CI 0.092-0.367; P=0.001) were found to be the independent determinants of increased carotid IMT independently of HOMA-IR, but not FBG (B=0.013; 95% CI 0.000-0.026; P=0.050) and HOMA-IR itself. CONCLUSIONS: Our results suggest that hypertension, low HDL-C, and central obesity are independently associated with increased carotid IMT in nondiabetic elderly subjects. These associations seem to be not affected by IR. The associations of FBG levels within the normal range and IR with carotid IMT should be investigated further.

Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

CONTEXT: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. METHODS: 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. RESULTS: Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. CONCLUSIONS: Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

VO(dmpp)2 normalizes pre-diabetic parameters as assessed by in vivo magnetic resonance imaging and spectroscopy.

Type 2 diabetes mellitus has been associated with obesity, metabolic syndrome, cardiovascular diseases and cancer. Attempts have been made for early diagnosis and finding effective drugs to prevent severe consequences and ameliorate the symptoms of this disorder. In this work, the pharmacological properties of VO(dmpp)(2), [bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxovanadium(IV)], were in vivo evaluated. For 4 weeks fatty Zucker rats were subjected to a daily dose of VO(dmpp)(2) (44 µmol/kg) and their metabolic profile was followed by assessing different biological parameters at established time points: body weight, subcutaneous fat width and hepatic triglyceride content determined by magnetic resonance imaging and spectroscopy, respectively. A glucose tolerance test was performed at the end of the experiment. After treatment, treated obese rats presented a weight significantly lower than the non-treated obese animals (359.0±11.1 vs. 433.5±6.2g, P<0.05), a thinner subcutaneous fat width, and a statistically significant decrease in hepatic triglyceride content (5.41±0.59 vs. 21.03±1.40%, P<0.0005). Additionally, the glucose intolerant profile of fatty Zucker rats was completely reversed in treated animals (102.3±2.1 vs. 172.4±1.3 mg/100 mL; P<0.0005). These results reinforce the therapeutic action of VO(dmpp)(2) which shows particular effects on lipid metabolism.

Effects of insulin on brain glucose metabolism in impaired glucose tolerance.

OBJECTIVE: Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS: We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [(18)F]fluorodeoxyglucose (for brain glucose metabolism) and [(15)O]H(2)O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS: The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS: We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance.