Glycemic variability in diagnosis of gestational diabetes as predictor of pharmacological treatment.

INTRODUCTION: To establish whether glycemic variability (GV) parameters used when gestational diabetes mellitus (GDM) has been diagnosed could help predict the probability that a patient will need pharmacological treatment, and to analyze the link of these parameters to the development of maternal-fetal complications. MATERIALS AND METHODS: A prospective study of 87 women with GDM who underwent retrospective continuous glucose monitoring (CGM) for six days between weeks 26 and 32 of gestation, following diagnosis. The mean glycemia levels and GV variables were analyzed together with their link to maternal-fetal complications, and the need for pharmacological treatment. ROC (receiver operating characteristic) curves were developed to determine validity to detect the need for pharmacological treatment. RESULTS: Patients with higher mean glycemia (p < 0.001) and continuous overlapping of net glycemic action in a period of n-hours (CONGAn) (p = 0.001) required pharmacological treatment. The ROC curves showed cut-off points of 98.81 mg/dL for mean glycemia, and 86.70 mg/dL for CONGAn, with 83.3% sensitivity and 67.8% specificity for both parameters. No relation between the GV parameters and development of maternal-fetal complications was observed. CONCLUSIONS: The use of CGM, once GDM is diagnosed, enables us to identify those patients who would benefit from closer monitoring during gestation, and facilitate a speedier take-up of pharmacological treatment. However, prospective studies involving a higher number of patients are needed, as well as a cost assessment for recommending the use of CGM following GDM diagnosis.

Cardiovascular Risk Factors in Transgender People after Gender-Affirming Hormone Therapy.

INTRODUCTION: In the last decade, healthcare for the transgender population has increased considerably in many countries thanks to depathologization movements and the easier accessibility of medical assistance. The age at which they request to start gender-affirming hormones (GAHs) is increasingly younger. The cardiovascular risk associated with hormonal treatment is a novel research field, and the published studies are heterogeneous and inconclusive. Our objective is to determine the metabolic impact of GAHs in the transgender people treated in our Gender Identity Treatment Unit. METHODS: We designed a pre-post study to analyze changes in anthropometric parameters (weight and body mass index), analytical determinations (fasting blood glucose, glycated hemoglobin, and lipoproteins), and blood pressure control in the transgender population treated with GAHs in Puerta del Mar University Hospital. These variables were collected before and one year after hormonal therapy. RESULTS: A total of 227 transgender people were recruited between 2017 and 2020, 97 (40.09%) transwomen and 136 (59.91%) transmen. The average age at which GAHs began was 18 years. Weight, body mass index, and blood pressure increased significantly in both genders. Transmen showed a more atherogenic lipid profile, with a decrease in cholesterol LDL (p < 0.001) and an increase in triglycerides (p < 0.001). The risk of developing prediabetes or diabetes did not increase one year after treatment, although non-specific alterations in carbohydrate metabolism were detected, such as an increase in glycated hemoglobin in transmen (p = 0.040) and fasting blood glucose in transwomen (p = 0.008). No thromboembolic processes or cardiovascular events were reported during the first year of treatment. CONCLUSION: In our setting, transgender people developed changes in their metabolic profiles in the first year after hormonal treatment. Both transmen and transwomen showed early alterations in lipid and carbohydrate metabolism, slight elevations in blood pressure, and a tendency to gain weight. This makes lifestyle interventions necessary from the beginning of GAHs.

Significance of Umbilical Cord Leptin Profile during Pregnancy in Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis.

BACKGROUND: The literature provides limited evidence of cord blood leptin levels in gestational diabetes mellitus (GDM), with contradictory and inconsistent results with respect to their possible implications for maternal, perinatal, and future complications. METHODS: MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched in order to investigate the state of evidence on the association of leptin profile in cord blood during perinatal complications in GDM. We critically assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed, and heterogeneity and publication bias were analyzed. RESULTS: sixteen primary-level studies were included, recruiting 573 GDM and 1118 control pregnant women. Cord blood leptin levels were significantly higher in GDM participants compared to controls (standardized mean difference [SMD] = 0.59, 95% confidence intervals (CI) = 0.37 to 0.80, p < 0.001). All subgroups also maintained significant differences stratified by continents (Asia: SMD = 0.91, 95% CI = 0.45 to 1.37, p < 0.001; Europe: SMD = 0.38, 95% CI = 0.20 to 0.56, p < 0.001), analysis technique (ELISA: SMD = 0.70, 95% CI = 0.44 to 0.97, p < 0.001; RIA: SMD = 0.30, 95% CI = 0.11 to 0.49, p = 0.002), and sample source (plasma: SMD = 0.71, 95% CI = 0.33 to 1.09, p < 0.001; serum: SMD = 0.55, 95% CI = 0.34 to 0.77, p < 0.001). CONCLUSION: Cord blood leptin levels were significantly higher in GDM compared to controls. Further research is needed to clarify its role as a predictive biomarker of subsequent metabolic diseases in mothers with GDM and offspring.

Significance of cell adhesion molecules profile during pregnancy in gestational diabetes mellitus. A systematic review and meta-analysis.

Endothelial dysfunction has been considered as a key etiological factor contributed to the development of vascular disease in diabetes mellitus. Serum level of endothelial cell adhesion molecules (AMs) were reported to be increased in GDM and pregnant women with normal glucose tolerance when compared with nonpregnant women. The literature provides limited evidence of endothelial dysfunction in GDM with heterogeneous and contradictory results respect to their possible involvement in maternal, perinatal and future complications. Our objective is to evaluate current evidence on the role of AMs in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Nineteen relevant studies were finally included, recruiting 765 GDM and 2368 control pregnant women. AMs levels were generally higher in GDM participants showing statistical significance maternal ICAM-1 levels (SMD = 0.58, 95% CI = 0.25 to 0.91; p = 0.001). Our meta-analysis did not detect significant differences in subgroups or in meta-regression analyses. Future studies are needed to establish the potential role of these biomarkers in GDM and its complications.

Autoimmune disorders in oral lichen planus: A systematic review and meta-analysis.

OBJECTIVES: The association of OLP with other autoimmune processes points to the possibility that OLP-affected patients are actually developing an autoimmune status that predisposes them to autoaggression against different targets. This systematic review and meta-analysis aim to evaluate the current evidence on the prevalence of autoimmune disorders in patients with OLP and their magnitude of association. METHODS: We searched PubMed, Embase, Web of Science, Scopus databases for the studies published before May 2021, with no limitation in regards to their publication date or language. We evaluated the quality of studies, carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses. RESULTS: Inclusion criteria were met by 153 studies (23,327 patients). Our results indicate the existence of high prevalence and a frequent association between OLP and some autoimmune disorders, especially in regards to thyroid disease (PP = 7.96%, 95% CI = 6.32-9.75; OR = 1.99, 95% CI = 1.60-2.49, p < 0.001) and diabetes mellitus (PP = 9.41%,95% CI = 8.16-10.74; OR = 1.64, 95% CI = 1.34-2.00, p < 0.001). CONCLUSIONS: Our study demonstrates the existence of a comorbidity between autoimmune thyroid diseases as well as between diabetes mellitus and OLP respectively. Quality of evidence should be upgraded on other autoimmune diseases (fibromyalgia, gastrointestinal disorders, rheumatic diseases, Sjogren's syndrome, lupus erythematosus, and dermatological diseases) for which the current data do not allow us to know whether they are really associated with OLP.

Higher daytime systolic BP, prepregnancy BMI and an elevated sFlt-1/PlGF ratio predict the development of hypertension in normotensive pregnant women.

BACKGROUND: The risk of hypertensive disorders of pregnancy (HDP) varies in women with gestational diabetes mellitus (GDM), depending on the degree of insulin resistance and is also influenced by obesity. The aim of this study was to evaluate clinical features, blood pressure (BP) profiles and inflammatory markers, to identify patients with an elevated risk of developing HDP. METHODS: A total of 146 normotensive pregnant women were studied. We analysed the relationships of BP profiles detected by ambulatory blood pressure monitoring (ABPM) with serum biomarkers and angiogenic factors and their association with the development of HDP. RESULTS: Fourteen (9.6%) women developed HDP, of which 11 had GDM and 8 had obesity. Women with HDP had higher values of 24-h and daytime systolic/diastolic BP (113/69 vs. 104/64; 115/72 vs. 106/66 mmHg, respectively; p <  0.05). Higher levels of leptin (10.97 ± 0.82 vs. 10.2 ± 1.11; p = 0.018) andmonocyte chemoattractant protein-1 (MCP-1) (5.24 ± 0.60 vs. 4.9 ± 0.55; p = 0.044) and a higher soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio (4.37 ± 2.2 vs. 2.2 ± 1.43; p = 0.003) were also observed in the HDP patients. Multivariate analysis showed that a higher sFlt-1/PlGF ratio was associated with an increased risk of developing HDP [OR = 2.02; IC 95%: 1.35-3.05]. Furthermore, higher daytime systolic BP [OR = 1.27; IC 95% 1.00-1.26] and prepregnancy body mass index (BMI) [OR = 1.14; IC 95%: 1.01-1.30] significantly increased the risk of developing HDP. CONCLUSIONS: Higher daytime systolic BP values, prepregnancy BMI and the sFlt-1/PlGF ratio are useful for identifying normotensive pregnant women with an increased risk of developing HDP.

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes.

Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.

Special Issue "The Prevention, Treatment, and Complications of Diabetes Mellitus".

Diabetes mellitus (DM) is a world health problem of global repercussion [...].

Unravelling the Inflammatory Processes in the Early Stages of Diabetic Nephropathy and the Potential Effect of (Ss)-DS-ONJ.

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic (Ss)-DS-ONJ is able to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of (Ss)-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation. The (Ss)-DS-ONJ treatment is able to inhibit the epithelial-to-mesenchymal transition (EMT) progression, but only when the IL18 levels are reduced by the treatment. These findings suggest that (Ss)-DS-ONJ could be a novel, and multifactorial treatment for DN.

A New Perspective on Huntington's Disease: How a Neurological Disorder Influences the Peripheral Tissues.

Huntington's disease (HD) is a neurodegenerative disorder caused by a toxic, aggregation-prone expansion of CAG repeats in the HTT gene with an age-dependent progression that leads to behavioral, cognitive and motor symptoms. Principally affecting the frontal cortex and the striatum, mHTT disrupts many cellular functions. In fact, increasing evidence shows that peripheral tissues are affected by neurodegenerative diseases. It establishes an active crosstalk between peripheral tissues and the brain in different neurodegenerative diseases. This review focuses on the current knowledge of peripheral tissue effects in HD animal and cell experimental models and identifies biomarkers and mechanisms involved or affected in the progression of the disease as new therapeutic or early diagnostic options. The particular changes in serum/plasma, blood cells such as lymphocytes, immune blood cells, the pancreas, the heart, the retina, the liver, the kidney and pericytes as a part of the blood-brain barrier are described. It is important to note that several changes in different mouse models of HD present differences between them and between the different ages analyzed. The understanding of the impact of peripheral organ inflammation in HD may open new avenues for the development of novel therapeutic targets.

Significance of Serum-Plasma Leptin Profile during Pregnancy in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM.

Adult kidney explants is a physiologic model for studying diabetic nephropathy.

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. In vitro approach using cell lines help to understand the mechanisms involves and allow the molecular and biochemical processes. Adult kidney (AK) explants remain an essential instrument for advancing our understanding of the molecular and cellular regulation of signalling pathways from an organotipic view with physiological system interaction integrated. AK explants from T1DM animal model (BB rat) are obtained by slicing central kidney area preserving the organ's cytoarchitecture and reproduce the classical events detected during the DN in an in vivo model such as inflammation, epithelial-mesenchymal transition (EMT) processes by the modulation of a-SMA and e-Cadherin among others which have been determined by qRT-PCR, western-blot and immunohistochemistry. In this regard, AK explants reproduce the signalling pathways involve in DN progression (proinflammatory NFkB and inflammasome complex). This work demonstrates AK explants is a physiological experimental approach for studying the development and progression of DN. Furthermore, the inflammatory processes in AK explants under a diabetic environment and/or BB rats could be modulated by potential treatments for DN.

IL-1ß Implications in Type 1 Diabetes Mellitus Progression: Systematic Review and Meta-Analysis.

During Type 1 Diabetes Mellitus (T1DM) progression, there is chronic and low-grade inflammation that could be related to the evolution of the disease. We carried out a systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers such as interleukin-1 beta (IL-1ß) is significantly different among patients with or without T1DM, in gender, management of the T1DM, detection in several biological fluids, study design, age range, and glycated hemoglobin. We searched PubMed, Embase, Web of Science, and Scopus databases, and 26 relevant studies (2186 with T1DM, 2047 controls) were included. We evaluated the studies' quality using the Newcastle−Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Compared with controls, IL-1ß determined by immunoassays (pooled standardized mean difference (SMD): 2.45, 95% CI = 1.73 to 3.17; p < 0.001) was significantly elevated in T1DM. The compared IL-1ß levels in patients <18 years (SMD = 2.81, 95% CI = 1.88−3.74) was significantly elevated. The hemoglobin-glycated (Hbg) levels in patients <18 years were compared (Hbg > 7: SMD = 5.43, 95% CI = 3.31−7.56; p = 0.001). Compared with the study design, IL-1ß evaluated by ELISA (pooled SMD = 3.29, 95% CI = 2.27 to 4.30, p < 0.001) was significantly elevated in T1DM patients. IL-1ß remained significantly higher in patients with a worse management of T1DM and in the early stage of T1DM. IL-1ß levels determine the inflammatory environment during T1DM.

Angiogenic Imbalance and Inflammatory Biomarkers in the Prediction of Hypertension as Well as Obstetric and Perinatal Complications in Women with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28−32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23−0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24−5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties.

sp2-Iminosugar glycolipids (sp2-IGLs) represent a consolidated family of glycoconjugate mimetics encompassing a monosaccharide-like glycone moiety with a pseudoamide-type nitrogen replacing the endocyclic oxygen atom of carbohydrates and an axially-oriented lipid chain anchored at the pseudoanomeric position. The combination of these structural features makes them promising candidates for the treatment of a variety of conditions, spanning from cancer and inflammatory disorders to parasite infections. The exacerbated anomeric effect associated to the putative sp2-hybridized N-atom imparts chemical and enzymatic stability to sp2-IGLs and warrants total α-anomeric stereoselectivity in the key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp2-IGLs by reporting the synthesis of α-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position. Structure-activity relationship studies in three different scenarios, namely cancer, Leishmaniasis and inflammation, convey that the therapeutic potential of the sp2-IGLs is highly dependent, not only on the length of the lipid chain (linear aliphatic C12 vs. C8), but also on the nature of the glycosidic atom (nitrogen vs. sulfur vs. selenium). The ensemble of results highlights the α-dodecylseleno-ONJ-glycoside as a promising multitarget drug candidate.

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity.

Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce reactive astrogliosis in an attempt to preserve the neuronal network and re-establish glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote reactive astrogliosis and increase susceptibility of neurons to stress-induced apoptosis. Such effects could be reversed by ORY1001 treatment both in vitro and in vivo, paving the way for a new therapeutic approach for Type 2 Diabetes Mellitus.

Specific model for the coordination of primary and hospital care for patients with diabetes mellitus. Evaluation of two-year results (2015-2017).

INTRODUCTION: Diabetes mellitus (DM) is one of the most prevalent chronicdiseases and has a significant health and social impact. Strict control of blood glucose levels and other risk factors for vascular disease (VD) reduces complications and mortality and is related to the quality of care received. Although care should be interdisciplinary, based on the coordination of primary care (PC) and hospital care (HC), little information is available on the effectiveness of the different existing intervention models. OBJECTIVE: To assess, in a population with DM from a healthcare area, the impact on health, quality of care, and effectiveness in the use of resources of a specific model of shared management of patients with DM (Instrument for Evaluation of Models of Chronic Care in Diabetes Mellitus; IEMAC-DM). PATIENTS AND METHODS: A quasi-experimental before-after intervention study in patients with DM in the Cádiz-San Fernando Healthcare Area (Andalusia, Spain) that allows for identifying the capacity of the program to improve the quality indicators both in the whole population with DM and in that referred to HC. For this, a working group consisting of healthcare professionals of different profiles and care levels was set up. An initial self-assessment was done using the IEMAC-DM tool and, after analysis of the preliminary results, improvement strategies were established and implemented. Finally, the clinical and resource management results were assessed before and two years after the implementation of the model. RESULTS: During the study period, no significant changes were seen in process indicators related to laboratory practices or examinations in the health area. The proportion of patients with acceptable metabolic control [glycosylated hemoglobin (HbA1c) level < 8%] was 49% in 2015 and 45% in 2017. The number of admissions related to acute myocardial infarction (AMI) and stroke remained constant, but there was an increase in the standardized ratio of major lower limb amputations (1.5 vs. 1.9). Of the 295 patients referred from PC to HC, the proportion of adequate referrals increased from 40% in 2015 to 76% in 2017 (P = .001). In the referred patients, a significant improvement was seen in the mean difference in glycosylated hemoglobin levels (HbA1c; 1.14 ± 1.73%; 95% CI: 0.73-1.55; P = .0001) and cholesterol (11.28 ± 40 mg/dL; 95% CI: 2.07-20.48; P = .012). CONCLUSIONS: This study shows that an intervention based on a chronicity care model adapted to patients with DM improves certain aspects related to the quality of care and the degree of metabolic control. Improving health outcomes will require long-term evaluation and, probably, other additional interventions.

Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (SS,1R)-1-docecylsulfiny-5N,6O-oxomethylidenenojirimycin ((Ss)-DS-ONJ), a member of the sp2-iminosugar glycolipid (sp2-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (Ss)-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of (SS)-DS-ONJ in microglia. (SS)-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR.

Validation of an Automated Screening System for Diabetic Retinopathy Operating under Real Clinical Conditions.

BACKGROUND: Retinopathy is the most common microvascular complication of diabetes mellitus. It is the leading cause of blindness among working-aged people in developed countries. The use of telemedicine in the screening system has enabled the application of large-scale population-based programs for early retinopathy detection in diabetic patients. However, the need to support ophthalmologists with other trained personnel remains a barrier to broadening its implementation. METHODS: Automatic diagnosis of diabetic retinopathy was carried out through the analysis of retinal photographs using the 2iRetinex software. We compared the categorical diagnoses of absence/presence of retinopathy issued by family physicians (PCP) with the same categories provided by the algorithm (ALG). The agreed diagnosis of three specialist ophthalmologists is used as the reference standard (OPH). RESULTS: There were 653 of 3520 patients diagnosed with diabetic retinopathy (DR). Diabetic retinopathy threatening to vision (STDR) was found in 82 patients (2.3%). Diagnostic sensitivity for STDR was 94% (ALG) and 95% (PCP). No patient with proliferating or severe DR was misdiagnosed in both strategies. The k-value of the agreement between the ALG and OPH was 0.5462, while between PCP and OPH was 0.5251 (p = 0.4291). CONCLUSIONS: The diagnostic capacity of 2iRetinex operating under normal clinical conditions is comparable to screening physicians.