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Objective: We investigated prevalence and predictors of glucose metabolism disorders (GMDs) among People Living with HIV (PLWH) on efavirenz- and atazanavir/ritonavir-based combination antiretroviral therapy (cART). Methods: This cross-sectional study involved adult PLWH on efavirenz- (n = 240) and atazanavir/ritonavir-based (n = 111) cART. The prevalence of GMDs was determined by fasting serum glucose, insulin, and homeostasis model assessment. A logistic regression model was used to determine predictors. Results: The overall prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0–32.6%] s, with 31.1% (75/240) [95% CI 25.4–37.5%] for efavirenz-based and 19.8% (22/111) [95% CI 12.9–28.5%)] for atazanavir/ritonavir-based cART group. The prevalence of impaired fasting glycemia was significantly higher (p = 0.026) in the efavirenz- [(15.4%) (37/240); 95%CI (11.1–20.6%)] than atazanavir/ritonavir-based [(7.2%) (8/111), (95%CI (3.2–13.7%)] cART. However, no significant difference was observed in the prevalence of diabetes mellitus and insulin resistance between the two regimens. Age ≥46 years old and specific type of ARV contained in cART, such as TDF, were independent predictors of GMD in both groups. Whereas the male gender and BMI category were predictors of GMDs among EFV-based cART group, AZT- and ABC- containing regimens and triglyceride levels were predictors in the ATV/r-based group. Conclusions: GMDs were highly prevalent among adults on EFV- than ATV/r-based cARTs. Age ≥46 years and TDF-containing cARTs are common predictors in both regimens. Close monitoring for impaired fasting glucose during long-term EFV-based cART is recommended for early diagnosis of type-2 diabetes and management. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study is to investigate whether type of depressive symptoms (i.e. cognitive-affective or somatic) is related to a patient-perceived need for professional psychological care in individuals with diabetes. Methods: In total 2266 participants were recruited as part of the screening procedure for a multi-center randomized controlled trial on the treatment of depressive symptoms among individuals with diabetes. Individuals were invited to complete Beck Depression Inventory-II (BDI-II). Patients with elevated depressive symptoms (BDI-II ≥14) were interviewed about their psychological care need. Based on their care needs patients were categorized into: unmet need, no need, met need and unclear need. These groups were compared on type of depressive symptoms, as categorized into cognitive-affective symptoms and somatic symptoms. Results: 568 eligible individuals had elevated depressive symptoms, of whom 519 were reached. Among these depressed individuals, 19.7% (102 of 519) had an unmet need for psychological care. Participants with an unmet need were younger (p<0.001) and had higher total depression scores compared to the group with no need (p<0.001). They also scored higher on cognitive-affective symptoms (p<0.001), whereas somatic symptoms did not significantly differ (p = 0.232). Logistic regression revealed that cognitive-affective symptoms predicted an unmet need (p = 0.001). However, overall predictive capacity of type of depressive symptoms on care needs was weak. Conclusions: Cognitive-affective symptoms of depression—but not somatic symptoms—were associated with an unmet need for psychological care among depressed individuals with diabetes. Future research is needed to reveal better predictors explaining the discrepancy between distress and low care needs in order to optimize screening procedures. [ABSTRACT FROM AUTHOR]

Background: Serum amyloid A (SAA), a potent inflammatory mediator, and Janus kinase 2 (JAK2), an intracellular signaling kinase, are increased by diabetes. The aims were to elucidate: 1) a JAK2-mediated pathway for increased SAA in the kidneys of diabetic mice; 2) a JAK2-SAA pathway for inflammation in podocytes. Methods: Akita diabetic mice (129S6) with podocyte JAK2 overexpression and angiotensin II infusion (4 weeks) were given a JAK1,2 inhibitor (LY03103801, 3 mg/kg/day orally for the last two weeks). Kidneys were immunostained for SAA isoform 3 (SAA3). SAA3 knockout and control mouse podocytes were exposed to advanced glycation end products (AGE) or exogenous SAA with JAK2 inhibition (Tyrphostin AG 490, 50μM). JAK2 activity (phosphorylation, Western blot, 1 hour) and mRNA for SAA3 and associated inflammatory genes (Cxcl5, Ccl2, and Ccl5) were measured by RT-PCR (20 hours). Results: SAA3 protein was present throughout the diabetic kidney, and podocyte JAK2 overexpression increased tubulointerstitial SAA3 compared to wild type diabetic controls, 43% versus 14% (p = 0.007); JAK1,2 inhibition attenuated the increase in SAA3 to 15% (p = 0.003). Urine albumin-to-creatinine ratio (r = 0.49, p = 0.03), mesangial index (r = 0.64, p = 0.001), and glomerulosclerosis score (r = 0.51, p = 0.02) were associated with SAA3 immunostaining scores across mouse groups. Exposing podocytes to AGE or exogenous SAA increased JAK2 activity within one hour and mRNA for associated inflammatory genes after 20 hours. JAK2 inhibition reduced SAA3 mRNA expression in podocytes exposed to AGE or SAA. SAA3 knockout podocytes had >85% lower AGE-induced inflammatory genes. Conclusion: JAK1,2 inhibition reduced SAA and histological features of DKD in podocyte JAK2-overexpressing mice. In podocytes exposed to a diabetes-like condition, JAK2 inhibition reduced expression of SAA, while SAA knockout blocked expression of associated pro-inflammatory mediators. SAA may promote JAK2-dependent inflammation in the diabetic kidney. [ABSTRACT FROM AUTHOR]

Altered systemic redox status is often observed in lung cancer. However, detailed information on factors other, than smoking, which influence this perturbation is rather scarce. Elevated oxidative stress has been linked with disturbances in glucose metabolism before, but such associations have not been investigated in lung cancer. The aim of this study was to evaluate the relationship between systemic parameters of glucose metabolism and redox status in lung cancer patients (LC). Biochemical variables related to circulating glucose, i.e. glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. β-hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as well as redox status i.e. total antioxidant status (TAS) and total oxidant status (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA-IR and the oxidative stress index (OSI) were calculated. LC patients had an altered redox status and glucose metabolism compared to CS. Positive correlations in LC were observed between TOS, OSI and circulating glucose as well as FA, while TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC, NEFAs and BHB positively correlated with OSI. Smoking status additionally stratified the observed relationships. In conclusion, we found that parameters related to circulating glucose or non-enzymatic glycation were correlated with oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking seem to influence these correlations. However, the detailed mechanism of this relationship requires further research, in particular as regards the surprising positive correlation between NEFAs and TAS. [ABSTRACT FROM AUTHOR]

Introduction: Macrophagic myofasciitis (MMF) is an emerging condition with highly specific myopathological alterations. A peculiar spatial pattern of a cerebral glucose hypometabolism involving occipito-temporal cortex and cerebellum have been reported in patients with MMF; however, the full pattern is not systematically present in routine interpretation of scans, and with varying degrees of severity depending on the cognitive profile of patients. Aim was to generate and evaluate a support vector machine (SVM) procedure to classify patients between healthy or MMF 18F-FDG brain profiles. Methods: 18F-FDG PET brain images of 119 patients with MMF and 64 healthy subjects were retrospectively analyzed. The whole-population was divided into two groups; a training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy subjects). Dimensionality reduction was performed using a t-map from statistical parametric mapping (SPM) and a SVM with a linear kernel was trained on the training set. To evaluate the performance of the SVM classifier, values of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were calculated. Results: The SPM12 analysis on the training set exhibited the already reported hypometabolism pattern involving occipito-temporal and fronto-parietal cortices, limbic system and cerebellum. The SVM procedure, based on the t-test mask generated from the training set, correctly classified MMF patients of the testing set with following Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%. Conclusion: We developed an original and individual approach including a SVM to classify patients between healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning algorithms are promising for computer-aided diagnosis but will need further validation in prospective cohorts. [ABSTRACT FROM AUTHOR]

Diabetes mellitus accelerates atherosclerosis that causes most cardiovascular events. Several metabolic pathways are considered to contribute to the development of atherosclerosis, but comprehensive metabolic alterations to atherosclerotic arterial cells remain unknown. The present study investigated metabolic changes and their relationship to vascular histopathological changes in the atherosclerotic arteries of rabbits with alloxan-induced diabetes. Diabetic atherosclerosis was induced in rabbit ilio-femoral arteries by injecting alloxan (100 mg/kg), injuring the arteries using a balloon, and feeding with a 0.5% cholesterol diet. We histologically assessed the atherosclerotic lesion development, cellular content, pimonidazole positive-hypoxic area, the nuclear localization of hypoxia-inducible factor-1α, and apoptosis. We evaluated comprehensive arterial metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using 18F-fluorodeoxyglucose and pimonidazole. Plaque burden, macrophage content, and hypoxic areas were more prevalent in arteries with diabetic, than non-diabetic atherosclerosis. Metabolomic analyses highlighted 12 metabolites that were significantly altered between diabetic and non-diabetic atherosclerosis. A half of them were associated with glycolysis metabolites, and their levels were decreased in diabetic atherosclerosis. The uptake of glucose evaluated as 18F-fluorodeoxyglucose in atherosclerotic lesions increased according to increased macrophage content or hypoxic areas in non-diabetic, but not diabetic rabbits. Despite profound hypoxic areas, the nuclear localization of hypoxia-inducible factor-1α decreased and the number of apoptotic cells increased in diabetic atherosclerotic lesions. Altered glycolysis metabolism and an impaired response to hypoxia in atherosclerotic lesions under conditions of insulin-dependent diabetes might be involved in the development of diabetic atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: The associations between dysglycemia and mortality in septic patients with and without diabetes are yet to be confirmed. Our aim was to analyze the association of diabetes and sepsis mortality, and to examine how dysglycemia (hyperglycemia, hypoglycemia and glucose variability) affects in-hospital mortality of patients with suspected sepsis in emergency department (ED) and intensive care units. Methods: Clinically suspected septic patients admitted to ED were included, and stratified into subgroups according to in-hospital mortality and the presence of diabetes. We analyzed patients’ demographics, comorbidities, clinical and laboratory parameters, admission glucose levels and severity of sepsis. Odds ratio of mortality was assessed after adjusting for possible confounders. The correlations of admission glucose and CoV (blood glucose coefficients of variation) and mortality in diabetes and non-diabetes were also tested. Results: Diabetes was present in 58.3% of the patients. Diabetic patients were older, more likely to have end-stage renal disease and undergoing hemodialysis, but had fewer malignancies, less sepsis severity (lower Mortality in Emergency Department Sepsis Score), less steroid usage in emergency department, and lower in-hospital mortality rate (aOR:0.83, 95% CI 0.65–0.99, p = 0.044). Hyperglycemia at admission (glucose≥200 mg/dL) was associated with higher risks of in-hospital mortality among the non-diabetes patients (OR:1.83 vs. diabetes, 95% CI 1.20–2.80, p = 0.005) with the same elevated glucose levels at admission. In addition, CoV>30% resulted in higher risk of death as well (aOR:1.88 vs. CoV between 10 and 30, 95%CI 1.24–2.86 p = 0.003). Conclusions: This study indicates that while diabetes mellitus seems to be a protective factor in sepsis patients, hyper- or hypoglycemia status on admission, and increased blood glucose variation during hospital stays, were independently associated with increased odds ratio of mortality. [ABSTRACT FROM AUTHOR]

Background: Atypical antipsychotics such as olanzapine cause metabolic side effects leading to obesity and insulin resistance. The underlying mechanisms remain elusive. In this study we investigated the effects of chronic treatment of olanzapine on the fatty acid composition of plasma in mice. Methods: Twenty 8-week female Balb/c mice were randomly assigned to two groups: the OLA group and the control group. After treatment with olanzapine (10 mg/kg/day) or vehicle intraperitoneally for 8 weeks, fasting glucose, insulin levels and oral glucose tolerance test were determined. Effects on plasma fatty acid profile and plasma indices of D5 desaturase, D6 desaturase and SCD1 activity were also investigated. Results: Chronic administration of olanzapine significantly elevated fasting glucose and insulin levels, impaired glucose tolerance, but did not increase body weight. Total saturated fatty acids and n-6 polyunsaturated fatty acids were significantly increased and total monounsaturated fatty acids were significantly decreased, while total n-3 polyunsaturated fatty acids showed no prominent changes. Chronic olanzapine treatment significantly up-regulated D6 desaturase activity while down-regulating D5 desaturase activity. Palmitic acid (C16:0), dihomo-γ-linolenic acid (C20:3n-6) and D6 desaturase were associated with an increase probability of insulin resistance, whereas nervonic acid (C24:1) and SCD1 were significantly associated with a lower insulin resistance probability. Conclusions: All results indicated that such drug-induced effects on fatty acid profile in plasma were relevant for the metabolic adverse effects associated with olanzapine and possibly other antipsychotics. Further studies are needed to investigate geneticand other mechanisms to explain how plasma fatty acids regulate glucose metabolism and affect the risk of insulin resistance. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal glucose metabolism is an independent risk factor for poor outcome following acute ischemic stroke. However, the relationship between initial hemoglobin A1c level and functional outcome (defined by modified Rankin Scale scores) following small-artery occlusion, a subtype of ischemic stroke, is unknown. The aim of the present study was to evaluate this association among patients diagnosed with small-artery occlusion. Materials and Methods: Data on 793 patients diagnosed with small-artery occlusion from October 25, 2012 to June 30, 2015 were collected from the stroke registry of the Department of Neurorehabilitation of HuanHu Hospital. Hemoglobin A1c values at admission were classified into three groups according to tertiles (<5.9,5.9to<6.7, and≥6.7). We used receiver operating characteristics curves to investigate the predictive value of hemoglobin A1c and examined the relationship between hemoglobin A1c levels at admission and modified Rankin Scale scores using univariate and multivariate analyses. Results: The area under the curve was 0.570 (95%CI, 0.509–0.631; P = 0.023). Patients in the highest HbA1c stratification (≥6.7) had a significantly higher risk of an unfavorable outcome than patients in the lowest stratification (<5.9; adjusted odds ratio, 2.099; 95%CI, 1.160–3.798; P = 0.014). However, a significant association was not seen in the middle stratification (5.9 to <6.7; P = 0.115). Conclusions: Elevated hemoglobin A1c level on admission was adversely associated with functional outcomes 3 months after stroke onset among patients presenting with small-artery occlusion. [ABSTRACT FROM AUTHOR]

Background and Aim: Recent studies revealed a link between hypovitaminosis D3 and the risk for hyperglycemia. Further mechanistic and interventional investigations suggested a common reason for both conditions rather than a causal relationship. Exposure to sunlight is the most relevant source of vitamin D3 (25(OH)D), whereas adipose tissue is able to store relevant amounts of the lipophilic vitamin. Since running/bicycling leads to increased out-door time and alters physiological response mechanisms, it can be hypothesized that the correlation between hypovitaminosis D3 and hyperglycemia might be disturbed in outdoor athletes. Methods: 47 elderly marathoners/bicyclists and 47 age/sex matched controls were studied in a longitudinal setting at baseline and after three years. HbA1c as a surrogate for (pre-)diabetic states was quantified via HPLC, 25(OH)D levels were measured by means of chemiluminescent assays. Physical performance was assessed by ergometry. Results: When adjusted for seasonal variations, 25(OH)D was significantly higher in athletes than in controls. 25(OH)D levels inversely correlated with triglycerides in both groups, whereas only in controls an association between high BMI or low physical performance with hypovitaminosis D3 had been found. Likewise, the presence of hypovitaminosis D3 at baseline successfully predicted hyperglycemia at the follow up examinations within the control group (AUC = 0.85, 95% CI [0.74, 0.96], p < .001, statistically independent from BMI), but not in athletes. Conclusion: Our data suggest that mechanisms of HbA1c elevation might differ between athletes and controls. Thus, intense physical activity must be taken into account as a potential pre-analytic confounder when it is aimed to predict metabolic risk by vitamin D3 levels. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. Methods: Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. Results: The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. Conclusions: Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods: In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results: HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions: HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution. [ABSTRACT FROM AUTHOR]

Little is known about the associations between long-term weight change and the natural history of impaired fasting glucose (IFG) in young adults. We investigated the association between long-term body mass index (BMI) change and the risk of IFG using data of 24,930 20- to 40-year-old participants from the Vorarlberg Health Monitoring and Promotion Program (VHM&PP) cohort. Poisson models were applied to estimate the 10-year risk for new development of IFG (≥5.6 mmol/L), and persistence of IFG. Over 10 years, most men (68.2%) and women (70.0%) stayed within their initial BMI category. The risk for incident IFG was highest for men and women with persisting obesity (37.4% and 24.1%) and lowest with persisting normal weight (15.7% and 9.3%). Men transitioning from normal to overweight increased their risk of incident IFG by factor 1.45 (95%-CI: 1.31, 1.62), women by 1.70 (95%-CI: 1.50, 1.93), whereas transitioning from overweight to normal weight decreased the risk in men by 0.69 (95%-CI: 0.53, 0.90) and 0.94 (95%-CI: 0.66, 1.33) in women. Relative risks for men and women transitioning from obesity to overweight were 0.58 and 0.44, respectively. In conclusion, 10 year weight increase was associated with an increased IFG risk, weight decrease with a decreased risk of IFG in young adults. [ABSTRACT FROM AUTHOR]

Objective: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a metabolite produced endogenously from dietary sources of furan fatty acids. The richest source of furan fatty acids in human diet is fish. CMPF was recently shown to be elevated in fasting plasma in individuals with gestational diabetes and type 2 diabetes, and mechanistically high level of CMPF was linked to β cell dysfunction. Here we aimed to study the association between plasma CMPF level and glucose metabolism in persons with impaired glucose metabolism. Methods: Plasma CMPF concentration was measured from plasma samples of the study participants in an earlier controlled dietary intervention. All of them had impaired glucose metabolism and two other characteristics of the metabolic syndrome. Altogether 106 men and women were randomized into three groups for 12 weeks with different fish consumption (either three fatty fish meals per week, habitual fish consumption or maximum of one fish meal per week). Associations between concentration of CMPF and various glucose metabolism parameters at an oral glucose tolerance test at baseline and at the end of the study were studied. Results: Fasting plasma CMPF concentration was significantly increased after a 12-week consumption of fatty fish three times per week, but the concentration remained much lower compared to concentrations reported in diabetic patients. Increases of plasma CMPF concentrations mostly due to increased fish consumption were not associated with impaired glucose metabolism in this study. Instead, elevated plasma CMPF concentration was associated with decreased 2-hour insulin concentration in OGTT. Conclusions: Moderately elevated concentration of CMPF in plasma resulting from increased intake of fish is not harmful to glucose metabolism. Further studies are needed to fully explore the role of CMPF in the pathogenesis of impaired glucose metabolism. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Aims: Visceral adipose tissue measured by CT or MRI is strongly associated with an adverse metabolic risk profile. We assessed whether similar associations can be found with ultrasonography, by quantifying the strength of the relationship between different measures of obesity and indices of glucose metabolism in a population at high risk of type 2 diabetes. Methods: A cross-sectional analysis of 1342 participants of the ADDITION-PRO study. We measured visceral adipose tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and body fat percentage by bioelectrical impedance. Indices of glucose metabolism were derived from a three point oral glucose tolerance test. Linear regression of obesity measures on indices of glucose metabolism was performed. Results: Mean age was 66.2 years, BMI 26.9kg/m2, subcutaneous adipose tissue 2.5cm and visceral adipose tissue 8.0cm. All measures of obesity were positively associated with indicators of glycaemia and inversely associated with indicators of insulin sensitivity. Associations were of equivalent magnitude except for subcutaneous adipose tissue and the visceral/subcutaneous adipose tissue ratio, which showed weaker associations. One standard deviation difference in BMI, visceral adipose tissue, waist circumference, waist/height ratio and body fat percentage corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher 2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin sensitivity, 20% lower Gutt’s index of insulin sensitivity, and 100 unit higher Stumvoll’s index of beta-cell function. After adjustment for waist circumference visceral adipose tissue was still significantly associated with glucose intolerance and insulin resistance, whereas there was a trend towards inverse or no associations with subcutaneous adipose tissue. After adjustment, a 1cm increase in visceral adipose tissue was associated with ~5% lower insulin sensitivity (p≤0.0004) and ~0.18mmol/l higher 2-hr glucose (p≤0.001). Conclusion: Visceral and subcutaneous adipose tissue assessed by ultrasonography are significantly associated with glucose metabolism, even after adjustment for other measures of obesity. [ABSTRACT FROM AUTHOR]

Background: Health-economic models of diabetes are complex since the disease is chronic, progressive and there are many diabetic complications. External validation of these models helps building trust and satisfies demands from decision makers. We evaluated the external validity of the IHE Cohort Model of Type 2 Diabetes; the impact of using alternative macrovascular risk equations; and compared the results to those from microsimulation models. Methods: The external validity of the model was analysed from 12 clinical trials and observational studies by comparing 167 predicted microvascular, macrovascular and mortality outcomes to the observed study outcomes. Concordance was examined using visual inspection of scatterplots and regression-based analysis, where an intercept of 0 and a slope of 1 indicate perfect concordance. Additional subgroup analyses were conducted on ‘dependent’ vs. ‘independent’ endpoints and microvascular vs. macrovascular vs. mortality endpoints. Results: Visual inspection indicates that the model predicts outcomes well. The UKPDS-OM1 equations showed almost perfect concordance with observed values (slope 0.996), whereas Swedish NDR (0.952) and UKPDS-OM2 (0.899) had a slight tendency to underestimate. The R2 values were uniformly high (>0.96). There were no major differences between ‘dependent’ and ‘independent’ outcomes, nor for microvascular and mortality outcomes. Macrovascular outcomes tended to be underestimated, most so for UKPDS-OM2 and least so for NDR risk equations. Conclusions: External validation indicates that the IHE Cohort Model of Type 2 Diabetes has predictive accuracy in line with microsimulation models, indicating that the trade-off in accuracy using cohort simulation might not be that large. While the choice of risk equations was seen to matter, each were associated with generally reasonable results, indicating that the choice must reflect the specifics of the application. The largest variation was observed for macrovascular outcomes. There, NDR performed best for relatively recent and well-treated patients, while UKPDS-OM1 performed best for the older UKPDS cohort. [ABSTRACT FROM AUTHOR]

Rationale: Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion. Objective: To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D), and in combination with metformin (M) and metformin plus low-dose rosiglitazone (MR), in diverse women with midlife weight gain (defined as >20lbs since the twenties), normal glucose tolerance, and hyperinsulinemia. Participants: 46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers. Methods: A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization. Main Outcome Measure: Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS) measures, leptin, and adiponectin. Results: Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p’s.049, .002, and.032). HOMA–IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p’s = .054, .013). Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001) Study medications were well tolerated. Conclusions: These findings suggest that EMPOWIR’s easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]