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Background: Experience of stroke is associated with an increased risk for diabetes and metabolic syndrome, yet few interventions exist that have been tailored to the population's unique needs., Purpose: To examine adherence and efficacy of the Diabetes Prevention Program Group Lifestyle Balance program (DPP-GLB) modified for individuals post stroke (GLB-CVA) using a randomized controlled trial., Methods: Adults (18-85 years of age), >12 months post stroke, and body mass index ≥25 kg/m2 were included in this study. Sixty-five individuals were assigned to either the GLB-CVA intervention or a 6-month wait-list control. Participants completed the 12-month GLB-CVA intervention, with attendance and assessment of weight, anthropometric, biomarker, functional, and patient reported outcome data collected at baseline, 3, 6, and 12 months., Results: High attendance (90%) and dietary and activity tracking (71%) suggest high adherence to the 12-month GLB-CVA. Six-month randomized controlled trial data indicate significant weight loss (p = .005) in the GLB-CVA group (7.4 ± 13.6 lbs, 3.65%) compared with the wait-list control (0.1 ± 10.1 lbs, 0%), and improvements in arm circumference (p = .04), high-density lipoprotein (HDL) cholesterol (p = .028), 8-year diabetes risk (p = .011), and pain interference (p < .001). Combined 12-month data showed participants lost 10.1 ± 16.8 lbs (4.88%) and improved waist circumference (p = .001), HbA1c (3.6%), diastolic blood pressure (p < .001), pain (p = .001), social participation (p = .025), and eating practices (p = .01) and habits (p < .001)., Conclusions: Engagement in the GLB-CVA can result in weight loss and improved health for individuals who are overweight or obese following stroke. Future efforts should examine effectiveness in real-world settings and focus on knowledge translation efforts., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The aim of the present study was to recalibrate the effectiveness of Indian Diabetes Risk Score (IDRS) and Community-Based Assessment Checklist (CBAC) by opportunistic screening of Diabetes Mellitus (DM) and Hypertension (HT) among the people attending health centres, and estimating the risk of fatal and non-fatal Cardio-Vascular Diseases (CVDs) among them using WHO/ISH charts., Methods: All the people aged ≥ 30 years attending the health centers were screened for DM and HT. Weight, height, waist circumference, and hip circumferences were measured, and BMI and Waist-Hip Ratio (WHR) were calculated. Risk categorization of all participants was done using IDRS, CBAC, and WHO/ISH risk prediction charts. Individuals diagnosed with DM or HT were started on treatment. The data was recorded using Epicollect5 and was analyzed using SPSS v.23 and MedCalc v.19.8. ROC curves were plotted for DM and HT with the IDRS, CBAC score, and anthropometric parameters. Sensitivity (SN), specificity (SP), Positive Predictive Value (PPV), Negative Predictive Value (NPV), Accuracy and Youden's index were calculated for different cut-offs of IDRS and CBAC scores., Results: A total of 942 participants were included for the screening, out of them, 9.2% (95% CI: 7.45-11.31) were diagnosed with DM for the first time. Hypertension was detected among 25.7% (95% CI: 22.9-28.5) of the participants. A total of 447 (47.3%) participants were found with IDRS score ≥ 60, and 276 (29.3%) with CBAC score > 4. As much as 26.1% were at moderate to higher risk (≥ 10%) of developing CVDs. Area Under the Curve (AUC) for IDRS in predicting DM was 0.64 (0.58-0.70), with 67.1% SN and 55.2% SP (Youden's Index 0.22). While the AUC for CBAC was 0.59 (0.53-0.65). For hypertension both the AUCs were 0.66 (0.62-0.71) and 0.63 (0.59-0.67), respectively., Conclusions: IDRS was found to have the maximum AUC and sensitivity thereby demonstrating its usefulness as compared to other tools for screening of both diabetes and hypertension. It thus has the potential to expose the hidden NCD iceberg. Hence, we propose IDRS as a useful tool in screening of Diabetes and Hypertension in rural India., (© 2022. The Author(s).)

Free fatty acid receptor 1 (FFAR1) is a G-protein coupled receptor with prominent expression on pancreatic beta cells, bones, intestinal cells as well as the nerve cells. This receptor mediates a multitude of functions in the body including release of incretins, secretion of insulin as well as sensation of pain. Since FFAR1 causes secretion of insulin and regulates glucose metabolism, efforts were made to unfold its structure followed by discovering agonists for the receptor and the utilization of these agonists in the therapy of type 2 diabetes mellitus. Development of such functional FFAR1 agonists is a necessity because the currently available therapy for type 2 diabetes mellitus has numerous drawbacks, of which, the major one is hypoglycemia. Since the most prominent effect of the FFAR1 agonists is on glucose concentration in the body, so the major research is focused on treating type 2 diabetes mellitus, though the agonists could benefit other metabolic disorders and neurological disorders as well. The agonists developed so far had one major limitation, i.e., hepatotoxicity. Although, the only agonist that could reach phase 3 clinical trials was TAK-875 developed by Takeda Pharmaceuticals but it was also withdrawn due to toxic effects on the liver. Thus, there are numerous agonists for the varied binding sites of the receptor but no drug available yet. There does seem to be a ray of hope in the drugs that target FFAR1 but a lot more efforts towards drug discovery would result in the successful management of type 2 diabetes mellitus., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Glycoproteomics deals with glycoproteins that are formed by post-translational modification when sugars (like fucose and sialic acid) are attached to protein. Glycosylation of proteins influences function, but whether glycosylation is altered by diet is unknown., Objective: To evaluate the effect of consuming a diet based on the Dietary Guidelines for Americans on circulating glycoproteins that have previously been associated with cardiometabolic diseases., Design: Forty-four women, with one or more metabolic syndrome characteristics, completed an 8-week randomized controlled feeding intervention (n = 22) consuming a diet based on the Dietary Guidelines for Americans (DGA 2010); the remaining consumed a 'typical American diet' (TAD, n = 22). Fasting serum samples were obtained at week0 (baseline) and week8 (post-intervention); 17 serum proteins were chosen for targeted analyses. Protein standards and serum samples were analyzed in a UHPLC-MS protocol to determine peptide concentration and their glycan (fucosylation or sialylation) profiles. Data at baseline were used in correlational analyses; change in proteins and glycans following intervention were used in non-parametric analyses., Results: At baseline, women with more metabolic syndrome characteristics had more fucosylation (total di-fucosylated proteins: p = 0.045) compared to women with a lesser number of metabolic syndrome characteristics. Dietary refined grain intake was associated with increased total fucosylation (ρ = - 0.530, p < 0.001) and reduced total sialylation (ρ = 0.311, p = 0.042). After the 8-week intervention, there was higher sialylation following the DGA diet (Total di-sialylated protein p = 0.018, poly-sialylated orosomucoid p = 0.012) compared to the TAD diet., Conclusions: Based on this study, glycosylation of proteins is likely affected by dietary patterns; higher sialylation was associated with a healthier diet pattern. Altered glycosylation is associated with several diseases, particularly cancer and type 2 diabetes, and this study raises the possibility that diet may influence disease state by altering glycosylation., Clinical Trial Registration: NCT02298725 at clinicaltrials.gov; https://clinicaltrials.gov/ct2/show/NCT02298725 ., (© 2021. The Author(s).)

Long noncoding RNAs (lncRNAs) are increasingly implicated in the pathology of diabetic complications. Here, we examined the role of lncRNAs in monocyte dysfunction and inflammation associated with human type 2 diabetes mellitus (T2D). RNA sequencing analysis of CD14+ monocytes from patients with T2D versus healthy controls revealed downregulation of antiinflammatory and antiproliferative genes, along with several lncRNAs, including a potentially novel divergent lncRNA diabetes regulated antiinflammatory RNA (DRAIR) and its nearby gene CPEB2. High glucose and palmitic acid downregulated DRAIR in cultured CD14+ monocytes, whereas antiinflammatory cytokines and monocyte-to-macrophage differentiation upregulated DRAIR via KLF4 transcription factor. DRAIR overexpression increased antiinflammatory and macrophage differentiation genes but inhibited proinflammatory genes. Conversely, DRAIR knockdown attenuated antiinflammatory genes, promoted inflammatory responses, and inhibited phagocytosis. DRAIR regulated target gene expression through interaction with chromatin, as well as inhibition of the repressive epigenetic mark H3K9me2 and its corresponding methyltransferase G9a. Mouse orthologous Drair and Cpeb2 were also downregulated in peritoneal macrophages from T2D db/db mice, and Drair knockdown in nondiabetic mice enhanced proinflammatory genes in macrophages. Thus, DRAIR modulates the inflammatory phenotype of monocytes/macrophages via epigenetic mechanisms, and its downregulation in T2D may promote chronic inflammation. Augmentation of endogenous lncRNAs like DRAIR could serve as novel antiinflammatory therapies for diabetic complications.

Background: Metabolic Syndrome (MetS) is a cardio-metabolic cluster that increases the risk of type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Whilst it affects 35% of the American adult population, its pathogenesis remains to be elucidated. Both insulin resistance and increased inflammation appear to be pivotal mechanisms. The NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome, an intracellular multi-protein complex, is crucial in the activation of Caspase 1, resulting in an increase in both IL-1and IL-18. In this preliminary report we examined the relationship between metabolites from our exploratory metabolomics studies with the NLRP3 inflammasome activity in the adipose tissue of patients with nascent MetS., Patient and Methods: This study comprised patients with nascent MetS matched with controls. All patients in this study had normal renal and hepatic function. Metabolites were analyzed from frozen early morning urine samples and correlated with adipose tissue Caspase 1, interleukin-1, and interleukin-18 density., Results: Caspase 1, a marker of NLRP3 inflammasome activity, was significantly elevated in patients with nascent MetS compared to controls. Isoleucine, GABA, Carnitine and PC34: 2 were also significantly increased in patients with MetS. Caspase1 correlated positively with Isoleucine, GABA, Carnitine, and PC34:2., Conclusion: We make the novel observation that the NLRP3 inflammasome activity is correlated with certain metabolites (Isoleucine, GABA, Carnitine and PC34:2) and hypothesize that they could trigger increased NLRP3 Inflammasome activity in MetS. However, these preliminary ,hypothesis generating novel findings need confirmation in larger studies of the metabolome and inflammasome., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by any of the authors., (Published by Elsevier Inc.)

Background and Aims: Dyslipidemia is a common problem in diabetic patients that predisposes to premature ASCVD. Dyslipidemia in Type 2 diabetes (T2DM) is very common and is characterized by hypertriglyceridemia (HTG) with decreased levels of high-density lipoprotein (HDL)-cholesterol., Methods: Recommendations for lipid testing in diabetics from the Canadian, European and American guidelines will be discussed in this mini-review., Results: It is crucial to obtain appropriate lipid testing in patients with TG > 2.3 mmol/L and or LDL-C< 1.8 mmol/L. We also discuss the utility of the different measures of calculated LDL-C and their pitfalls., Conclusion: In conclusion, we propose obtaining a non-HDL-C (preferred) or direct -LDL-C or apo B level to manage diabetic patients with dyslipidemia and optimize care. Also in some patients with a strong FH of premature ASCVD and have few or no risk factors, Lp (a) can be assayed to optimize statin therapy., Competing Interests: Declaration of competing interest I.Jialal and S. Devaraj: No commercial or similar relationships to products or companies mentioned in or related to the subject matter of the article being submitted., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Fueled by perceptions regarding Indian dietary patterns and premixed insulin's claim to fame of providing dual fasting and post-prandial control, there was a greater inclination towards using premixed insulins in clinical practice until the last decade. However, the advent of insulin glargine 100 U/mL (Gla-100) opened up a new dimension in insulin therapy landscape in India. The data from the last 5 years reveal that Gla-100 has gained more traction among Indian clinical practitioners. Basis evidences that have emerged from various clinical studies, this present review elaborates on certain key issues which have helped Gla-100 carve its own niche and effected a progressive shift in insulin prescription pattern in India., (© Journal of the Association of Physicians of India 2011.)

(E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1-27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α-amylase and α-glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14-17, 19, and 21-25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC 50 values ranging (IC 50  = 13.02 ± 0.04-46.90 ± 0.05 µM) and (IC 50  = 13.09 ± 0.08-46.44 ± 0.24 µM) in comparison to standard acarbose (IC 50  = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α-amylase and α-glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α-amylase and α-glucosidase inhibitors 5, 7, 9, 15, 24, and 27, suggested non-competitive and competitive types of inhibition mechanism for α-amylase and α-glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H-<, <-<, and <-H etc., against the corresponding targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The optimal diet to improve glycemia in patients with type 2 diabetes remains unclear. Low carbohydrate, high fat (LCHF) diets can improve glycemic control, but have not been investigated in real-world settings., Research Design and Methods: We investigated effects of the LCHF diet compared with usual care in a community-based cohort of patients with type 2 diabetes by performing a retrospective study of 49 patients who followed the LCHF diet for ≥3 months, and compared glycemic outcomes with age-matched and body mass index (BMI)-matched controls who received usual care (n=75). The primary outcome was change in A1C from baseline to the end of follow-up., Results: Compared with the usual care group, the LCHF group showed a significantly greater reduction in A1C (-1.29% (95% CI -1.75 to -0.82; p<0.001)) and body weight (-12.8 kg (95% CI -14.7 to -10.8; p<0.001) at the end of follow-up after adjusting for age, sex, baseline A1C, BMI, baseline insulin dose. Of the patients initially taking insulin therapy in the LCHF group, 100% discontinued it or had a reduction in dose, compared with 23.1% in the usual care group (p<0.001). The LCHF group also had significantly greater reduction in fasting plasma glucose (-43.5 vs -8.5 mg/mL; p=0.03) compared with usual care., Conclusions: In a community-based cohort of type 2 diabetes, the LCHF diet was associated with superior A1C reduction, greater weight loss and significantly more patients discontinuing or reducing antihyperglycemic therapies suggesting that the LCHF diet may be a metabolically favorable option in the dietary management of type 2 diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Aims: The present study aimed to compare the clinical characteristics of patients with fibrocalculous pancreatic diabetes (FCPD) and those with type 2 diabetes mellitus (T2DM) to identify the characteristics distinctive of FCPD., Methods: A total of 133 patients with FCPD were compared with 665 patients with T2DM matched for duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular and macrovascular complications in both groups., Results: The mean duration of diabetes was 4.42 ± 5.65 years in the FCPD group and 4.51 ± 3.88 years in the T2DM group. FCPD participants were significantly younger at diagnosis and leaner than patients with T2DM. The FCPD group had higher fasting and postprandial glucose and HbA1c levels than the T2DM group. The FCPD group had significantly lower triglyceride, total cholesterol, low-density lipoprotein cholesterol, serum total calcium, hemoglobin, and serum creatinine values than the T2DM group. The prevalence of coronary artery disease, stroke, and retinopathy was significantly higher in the T2DM patients while the prevalence of distal symmetric polyneuropathy was significantly lower. On multivariate logistic regression analysis, duration of diabetes and HbA1c (OR = 1.17, P = 0 0.04) in FCPD patients and age (OR = 1.04, P < 0 0.001), duration of diabetes (OR = 1.17, P < 0 0.001) and HbA1c (OR = 1.28, P < 0.001) in T2DM patients were associated with microvascular complications., Conclusions: There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM. Timely diagnosis may have implications in the follow-up and management of patients., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective- Macrophages play key roles in inflammation and diabetic vascular complications. Emerging evidence implicates long noncoding RNAs in inflammation, but their role in macrophage dysfunction associated with inflammatory diabetic complications is unclear and was therefore investigated in this study. Approach and Results- RNA-sequencing and real-time quantitative PCR demonstrated that a long noncoding RNA Dnm3os (dynamin 3 opposite strand) is upregulated in bone marrow-derived macrophages from type 2 diabetic db/db mice, diet-induced insulin-resistant mice, and diabetic ApoE -/- mice, as well as in monocytes from type 2 diabetic patients relative to controls. Diabetic conditions (high glucose and palmitic acid) induced Dnm3os in mouse and human macrophages. Promoter reporter analysis and chromatin immunoprecipitation assays demonstrated that diabetic conditions induce Dnm3os via NF-κB activation. RNA fluorescence in situ hybridization and real-time quantitative PCRs of subcellular fractions demonstrated nuclear localization and chromatin enrichment of Dnm3os in macrophages. Stable overexpression of Dnm3os in macrophages altered global histone modifications and upregulated inflammation and immune response genes and phagocytosis. Conversely, RNAi-mediated knockdown of Dnm3os attenuated these responses. RNA pull-down assays with macrophage nuclear lysates identified nucleolin and ILF-2 (interleukin enhancer-binding factor 2) as protein binding partners of Dnm3os, which was further confirmed by RNA fluorescence in situ hybridization immunofluorescence. Furthermore, nucleolin levels were decreased in diabetic conditions, and its knockdown enhanced Dnm3os-induced inflammatory gene expression and histone H3K9-acetylation at their promoters. Conclusions- These results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications.

Angiotensin converting enzyme 2 (ACE2) and neprilysin (NEP) are metalloproteases that are highly expressed in the renal proximal tubules. ACE2 and NEP generate renoprotective angiotensin (1-7) from angiotensin II and angiotensin I, respectively, and therefore could have a major role in chronic kidney disease (CKD). Recent data demonstrated increased urinary ACE2 in patients with diabetes with CKD and kidney transplants. We tested the hypothesis that urinary ACE2, NEP, and a disintegrin and metalloproteinase 17 (ADAM17) are increased and could be risk predictors of CKD in patients with diabetes. ACE2, NEP, and ADAM17 were investigated in 20 nondiabetics (ND) and 40 patients with diabetes with normoalbuminuria (Dnormo), microalbuminuria (Dmicro), and macroalbuminuria (Dmacro) using ELISA, Western blot, and fluorogenic and mass spectrometric-based enzyme assays. Logistic regression model was applied to predict the risk prediction. Receiver operating characteristic curves were drawn, and prediction accuracies were calculated to explore the effectiveness of ACE2 and NEP in predicting diabetes and CKD. Results demonstrated that there is no evidence of urinary ACE2 and ADAM17 in ND subjects, but both enzymes were increased in patients with diabetes, including Dnormo. Although there was no detectable plasma ACE2 activity, there was evidence of urinary and plasma NEP in all the subjects, and urinary NEP was significantly increased in Dmicro patients. NEP and ACE2 showed significant correlations with metabolic and renal characteristics. In summary, urinary ACE2, NEP, and ADAM17 are increased in patients with diabetes and could be used as early biomarkers to predict the incidence or progression of CKD at early stages among individuals with type 2 diabetes.

Objective: When glucose records from self blood glucose monitoring (SBGM) do not reflect estimated average glucose from glycosylated hemoglobin (HgBA1) or when patients' clinical symptoms are not explained by their SBGM records, clinical management of diabetes becomes a challenge. Our objective was to determine the magnitude of differences in glucose values reported by SBGM versus those documented by continuous glucose monitoring (CGM)., Methods: The CGM was conducted by a clinical diabetes educator (CDE)/registered nurse by the clinic protocol, using the Medtronic iPRO2 ™ system. Patients continued SBGM and managed their diabetes without any change. Data from 4 full days were obtained, and relevant clinical information was recorded. De-identified data sets were provided to the investigators., Results: Data from 61 patients, 27 with type 1 diabetes (T1DM) and 34 with T2DM were analyzed. The lowest, highest, and average glucose recorded by SBGM were compared to the corresponding values from CGM. The lowest glucose values reported by SBGM were approximately 25 mg/dL higher in both T1DM ( P = .0232) and T2DM ( P = .0003). The highest glucose values by SBGM were approximately 30 mg/dL lower in T1DM ( P = .0005) and 55 mg/dL lower in T2DM ( P<.0001). HgBA1c correlated with the highest and average glucose by SBGM and CGM. The lowest glucose values were seen most frequently during sleep and before breakfast; the highest were seen during the evening and postprandially., Conclusion: SBGM accurately estimates the average glucose but underestimates glucose excursions. CGM uncovers glucose patterns that common SBGM patterns cannot., Abbreviations: CDE = certified diabetes educator; CGM = continuous glucose monitoring; HgBA1c = glycosylated hemoglobin; MAD = mean absolute difference; SBGM = self blood glucose monitoring; T1DM = type 1 diabetes; T2DM = type 2 diabetes.

Piperazine Sulfonamide analogs (1-19) have been synthesized, characterized by different spectroscopic techniques and evaluated for α-amylase Inhibition. Analogs 1-19 exhibited a varying degree of α-amylase inhibitory activity with IC 50 values ranging in between 1.571 ± 0.05 to 3.98 ± 0.397 μM when compared with the standard acarbose (IC 50  = 1.353 ± 0.232 μM). Compound 1, 2, 3 and 7 showed significant inhibitory effects with IC 50 value 2.348 ± 0.444, 2.064 ± 0.04, 1.571 ± 0.05 and 2.118 ± 0.204 μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Described since long as a member of the nuclear receptor superfamily, peroxisome proliferator-activated receptors (PPARs) regulate the gene expression of proteins involved in glucose and lipid metabolism. PPARs indeed regulate several physiologic processes, including lipid homeostasis, adipogenesis, inflammation, and wound healing. PPARs bind natural or synthetic PPAR ligands can function as cellular sensors to regulate the gene transcription. Dyslipidemia, and type 2 diabetes mellitus (T2DM) with insulin resistance are treated using agonists of PPARα and PPARγ, respectively. The PPARγ is a key regulator of insulin sensitization and glucose metabolism, and therefore is considered as an imperative pharmacological target to combat diabetic metabolic disease and insulin resistance. Of note, currently available PPARγ full agonists like rosiglitazone display serious adverse effects such as fluid retention/oedema, weight gain, and increased incidence of cardiovascular events. On the other hand, PPARγ partial agonists are being suggested to devoid or having less incidence of these undesirable events, and are under developmental stages. Current research is on the way for the development of novel PPARγ partial agonists with enhanced therapeutic efficacy and reduced adverse effects. This review sheds lights on the current status of development of PPARγ partial agonists, for the management of T2DM, having comparatively less or no adverse effects to that of PPARγ full agonists., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To evaluate the feasibility and health improvements from a Zumba® intervention in overweight/obese women., Methods: Twenty-eight (14 type 2 diabetic and 14 non-diabetic) over-weight/obese women (BMI: 37.3±1.5 kg/m(2)) 50.8±1.8 y of age, completed a 16-week intervention attending Zumba® dance classes 3 days/week, 60 minutes/class. We measured aerobic fitness, body weight, body fat %, and motivation to exercise before and after the study., Results: Intrinsic motivation to exercise (p < .05) and aerobic fitness (1.01 ± 0.40 mL/kg/min, p < .05) improved, and the participants lost body weight (-1.05 ± 0.55kg, p < .05) and body fat% (-1.2 ± 0.6%, p < .01)., Conclusion: The Zumba® intervention improved health and physical fitness in women.

The mechanisms by which macrophages mediate the enhanced inflammation associated with diabetes complications are not completely understood. We used RNA sequencing to profile the transcriptome of bone marrow macrophages isolated from diabetic db/db mice and identified 1,648 differentially expressed genes compared with control db/+ mice. Data analyses revealed that diabetes promoted a proinflammatory, profibrotic, and dysfunctional alternatively activated macrophage phenotype possibly via transcription factors involved in macrophage function. Notably, diabetes altered levels of several long noncoding RNAs (lncRNAs). Because the role of lncRNAs in diabetes complications is unknown, we further characterized the function of lncRNA E330013P06, which was upregulated in macrophages from db/db and diet-induced insulin-resistant type 2 diabetic (T2D) mice, but not from type 1 diabetic mice. It was also upregulated in monocytes from T2D patients. E330013P06 was also increased along with inflammatory genes in mouse macrophages treated with high glucose and palmitic acid. E330013P06 overexpression in macrophages induced inflammatory genes, enhanced responses to inflammatory signals, and increased foam cell formation. In contrast, small interfering RNA-mediated E330013P06 gene silencing inhibited inflammatory genes induced by the diabetic stimuli. These results define the diabetic macrophage transcriptome and novel functional roles for lncRNAs in macrophages that could lead to lncRNA-based therapies for inflammatory diabetes complications., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Individuals with type 2 diabetes have a myriad of metabolic aberrations including increased inflammation, increasing their cardiovascular risk. Toll-like receptors (TLRs) and their ligands play a key role in insulin resistance and atherosclerosis. However, there is a paucity of data examining the expression and activity of TLRs in type 2 diabetes. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression, their ligands, and signaling in monocytes of recently diagnosed type 2 diabetic patients., Research Design and Methods: TLR mRNA, protein expression, TLR ligands, and TLR signaling were measured in freshly isolated monocytes from healthy human control subjects (n = 23) and type 2 diabetic subjects (n = 23) using real-time RT-PCR, Western blot, and flow cytometric assays., Results: Type 2 diabetic subjects had significantly increased TLR2, TLR4 mRNA, and protein in monocytes compared with control subjects (P < 0.05). Increased TLR2 and TLR4 expression correlated with BMI, homeostasis model assessment-insulin resistance (HOMA-IR), glucose, A1C, N(epsilon)-(carboxymethyl) lysine (CML), and free fatty acid (FFA). Ligands of TLR2 and TLR4, namely, HSP60, HSP70, HMGB1, endotoxin, and hyaluronan levels, were elevated in type 2 diabetic subjects and positively correlated with TLR2 and TLR4. Type 2 diabetic subjects showed increased MyD88, phosphorylated IRAK-1, Trif, TICAM-1, IRF-3, and NF-kappaB p65 expression in monocytes compared with control subjects. Furthermore, TLR-MyD88-NF-kappaB signaling resulted in elevated levels of cytokines (P < 0.05), but increased interleukin (IL)-1beta, interferon (IFN)-gamma, and endotoxin were not significant when adjusted for BMI., Conclusions: In this comprehensive study, we make the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.

Background: There are numerous reports of abnormal glucose metabolism, including increased rates of type 2 diabetes mellitus, in psychiatric patients. It remains unclear, however, whether there is an intrinsic relationship between abnormal glucose metabolism and particular psychiatric disorders, because the relationship is complicated by treatment with psychotropic medications that promote weight gain and hyperglycemia. This study aimed to clarify this relationship., Methods: The medical records of 243 inpatients, aged 50-74 years, with diagnoses of major depression, bipolar I disorder, schizoaffective disorder, schizophrenia, and dementia were reviewed. Psychiatric and type 2 diabetes mellitus diagnoses, medications, body mass index (BMI), age, gender, and race were recorded. Diabetes rates were compared to age, race, and gender-matched rates in the US general population., Results: Rates of type 2 diabetes mellitus were: schizoaffective (50%) > bipolar I (26%) > major depression (18%) = dementia (18%) > schizophrenia (13%) (p < 0.006). Diabetic patients had a higher mean BMI (p = 0.01), but not a significantly higher use of psychotropic medications previously reported to be associated with new-onset type 2 diabetes (e.g., phenothiazines, clozapine, olanzapine). Logistic regression revealed that psychiatric diagnosis and BMI were the only significant and independent predictors of diabetes diagnosis. Compared to national norms, diabetes rates were significantly elevated only in bipolar I affective and schizoaffective patients., Limitations: This study was a retrospective chart review of older, hospitalized patients., Conclusions: This is the first published study to show an increased prevalence of type 2 diabetes mellitus among psychiatric patients with particular psychiatric illnesses independent of the effects of age, race, gender, medication, and body mass. This finding, which requires replication in a larger scale, prospective study, suggests an intrinsic relationship between abnormal glucose metabolism and bipolar I affective and schizoaffective disorders.

Objective: Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. alpha-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses. The aim of the study was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator inhibitor-1 (PAI-1), and soluble P-selectin (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects., Research Design and Methods: The volunteers comprised type 2 diabetic patients with (n=23) and without (n=24) MVCs and matched control subjects (n=25). Plasma levels of PAI-1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase., Results: Both diabetic groups had significantly increased levels of PAI-1 compared with control subjects (P < 0.025), whereas only type 2 diabetic patients with MVCs had significantly elevated levels of sP-selectin compared with control subjects. AT supplementation significantly lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P=0.005)., Conclusions: Thus, AT therapy decreases markers of thrombosis in diabetic patients and control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.

Background: Oxidation of low-density lipoprotein (LDL) is a crucial step in atherogenesis. There is an urgent need for direct measures of in vivo oxidative stress. Autoantibodies against oxidized low-density lipoprotein (Ab against Ox-LDL) are a direct measure of oxidative stress and predict cardiovascular disease. Our aim was to evaluate an ELISA for Ab against Ox-LDL in Type 2 diabetes, a condition with increased oxidative stress., Methods: Ab against Ox-LDL were measured by ELISA and expressed as a ratio of Ox-LDL to native LDL (N-LDL). Samples were obtained from 45 Type 2 diabetic patients and 25 matched controls before and after supplementation with alpha tocopherol (AT, 1200 IU/day)., Results: The assay had good precision. While there was no interference with bilirubin and hemolysis, triglycerides 500 mg/dl increased antibody titer, which was abrogated by airfuging. Compared to controls, significantly increased titers of Ab against Ox-LDL were found in diabetics (diabetes mellitus Type 2) with macrovascular disease (DM2-MV), but not without macrovascular disease (DM2) (DM2: 1.32+/-0.33; DM2-MV: 1.48+/-0.44 vs. controls, 1.21+/-0.28; p<0.05). AT supplementation significantly decreased titers of Ab against Ox-LDL in both diabetic groups (p<0.01)., Conclusion: This assay may serve as a future test for the assessment of cardiovascular risk especially in patients with increased oxidative stress.