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Coronary circulation plays an essential role in delivering oxygen and metabolic substrates to satisfy the considerable energy demand of the heart. This article reviews the history that led to the current understanding of coronary physiology, beginning with William Harvey's revolutionary discovery of systemic blood circulation in the 17th century, and extending through the 20th century when the major mechanisms regulating coronary blood flow (CBF) were elucidated: extravascular compressive forces, metabolic control, pressure-flow autoregulation, and neural pathways. Pivotal research studies providing evidence for each of these mechanisms are described, along with their clinical correlates. The authors describe the major role played by researchers in the 19th century, who formulated basic principles of hemodynamics, such as Poiseuille's law, which provided the conceptual foundation for experimental studies of CBF regulation. Targeted research studies in coronary physiology began in earnest around the turn of the 20th century. Despite reliance on crude experimental techniques, the pioneers in coronary physiology made groundbreaking discoveries upon which our current knowledge is predicated. Further advances in coronary physiology were facilitated by technological developments, including methods to measure phasic CBF and its regional distribution, and by biochemical discoveries, including endothelial vasoactive molecules and adrenergic receptor subtypes. The authors recognize the invaluable contribution made by basic scientists toward the understanding of CBF regulation, and the enormous impact that this fundamental information has had on improving clinical diagnosis, decision-making, and patient care. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a prevalent chronic disease in patients who die of COVID-19. The aim of this study was to investigate the clinical and metabolic characteristics of diabetic patients with COVID-19 during the pre-vaccination phase. A retrospective cohort study was conducted from February 2020 to February 2021 to examine the clinical and metabolic profiles of unvaccinated diabetic patients affected by COVID-19. Data were collected from claim databases, hospital discharge records, and clinical records within a healthcare district located in northeastern Italy with a population of 936,000. Potential prognostic indicators including sex, age, Body Mass Index (BMI), duration and type of diabetes, metabolic control, and the use of antidiabetic, antihypertensive, lipid-lowering, and antiplatelet therapies were investigated. For hospitalized patients, additional variables were recorded, such as length of hospital stay, blood pressure at admission, comorbidities, D-dimer levels, blood glucose (BG), in-hospital insulin and corticosteroid therapies, requirement for mechanical ventilation (i.e., orotracheal or tracheostomy), admission to the Intensive Care Unit (ICU), and mortality. Diabetic patients hospitalized for COVID-19 with a poorer prognosis were characterized by advanced age, longer diabetes duration, hypertension, higher usage of sulfonylureas, and lower usage of dietotherapy alone, metformin, Glucagon-Like Peptide-1 Receptor agonists (GLP1-Ra), and Renin-Angiotensin-Aldosterone System inhibitors (RAAS-i). Considering the potential for COVID-19 to become endemic, special care should be taken in managing older diabetic patients' treatments. • Use of RAAS-i prior to COVID-19 was found to be associated with the best outcomes. • Dietotherapy alone, metformin, and GLP1-Ra were related to fewer hospitalizations. • Use of sulfonylureas and in-hospital corticosteroids were related to poor prognosis. • The COVID-19 endemic phase demands cautious therapy for older diabetic patients. [ABSTRACT FROM AUTHOR]

The study aim was to evaluate the effects of public lockdown during the covid-19 pandemic on glucose and metabolic parameters as well as body weight control in type 2 diabetic patients. This study was conducted in two outpatient Diabetes Clinics and analyzed data available in database of Diabetes Clinic. Data related to a year before covid-19 pandemic and a year during covid-19 pandemic was collected from the database and analyzed. Patients with type 2 diabetes included in the analysis if they had referred to Diabetes Clinics both before and during covid-19 pandemic. Demographic information and data about metabolic status were collected from the records of previous outpatient Clinic visits and compared Finally 9440 patients with mean age of 61.08 ± 11.62 referred to Diabetes Clinics in both the year before and the year of the corona pandemic. Mean FBS and HbA1c in diabetes patients reduced significantly from 155.37 ± 62.93 and 7.97 ± 1.74 before pandemic, respectively to 138.77 ± 45.39 and 7.54 ± 1.34, respectively during covid-19 outbreak. During covid-19 pandemic, all metabolic parameters including glycemic and lipid profile (except for triglyceride) and BMI (body mass index) reduced significantly statistically, but, these changes were not clinically significant. However, triglyceride level increased statistically significantly but again it was not significant clinically. During COVID-19 lockdown, glycemic and metabolic control of diabetes patients have improved significantly except for triglycerides. • During covid-19 lockdown, glycemic control of diabetes patients improved significantly. • During lockdown lipid profile except for triglyceride improved significantly. • During lockdown BMI reduced significantly. • All metabolic improvement were statistically significant but not clinically. • This metabolic improvement indicates improved self-care. [ABSTRACT FROM AUTHOR]

Recent research has strengthened the notion that microbes allocate their biosynthetic capacity to maximize the growth rate, λ. Yet many microbes can grow substantially faster after laboratory evolution. Chure and Cremer advance a resource-allocation model, which they derive from first principles, that offers resolution to this conundrum. [ABSTRACT FROM AUTHOR]

Aims: This study was carried out to investigate fear levels, treatment compliance, and metabolic control of type II Diabetes Mellitus patients during the COVID-19 pandemic.Methods: The study employed a single-center, observational design and was conducted between January and April 2021. The study consisted of 303 patients who attended the internal medicine outpatient clinic of a university hospital in Turkey. For data collection, the Patient Identification Form, COVID-19 Fear Scale, and the Type II Diabetes Treatment Compliance Scale were used. The study complied with the Helsinki Declaration criteria. IBM SPSS v25.0 statistics package program was used for data analysis.Results: The mean age of the patients was 45.8 ± 7.5 years, the mean duration of illness was 8.2 ± 3.6 years. Moreover, 40.6% of patients presented with poor levels of treatment compliance. In addition, the mean FCV-19S score of the patients was 29.1 ± 3.05. It was noticeable that those with high mean scores of FCV-19S had poor compliance with treatment and metabolic control during the pandemic (p < 0.05).Practice Implications: Fear of COVID-19 negatively affects treatment compliance and metabolic control of type II diabetes patients. The patients avoided attending their regular follow-ups at the hospital due to fear of contracting COVID-19. In order to reduce the fear of COVID-19 it is paramount to maintain optimum metabolic control and treatment compliance. [ABSTRACT FROM AUTHOR]

Background and Aims: Coronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD.Methods and Results: This was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131-3.136]), C-reactive protein (1.046 [1.020-1.073]), blood pressure >140/90 mmHg (2.686 [1.506-4.791]), fibrates (2.032 [1.160-3.562]), calcium channel blockers (2.082 [1.158-3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240-4.721]), heart failure (2.139 [1.032-4.433]), LDL-C >70 mg/dL (4.594 [1.401-15.069]), and diuretics (3.328 [1.677-6.605]) were associated with cardiovascular mortality.Conclusions: The composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%. [ABSTRACT FROM AUTHOR]

Background There remains a limited understanding of the metabolic perturbations, beyond phenylalanine (Phe) metabolism, that contribute to phenotypic variability in phenylketonuria (PKU). Objectives This study aimed to characterize changes in the PKU plasma metabolome following a 5-d metabolic camp intervention and to compare PKU profiles with those of matched healthy controls. Methods In 28 females (aged 12–57 y), fasting plasma samples were collected on the first (day 1) and final (day 5) days of camp to measure metabolic control and to complete untargeted metabolomic profiling. Three-day dietary records were collected to assess changes in dietary adherence and composition. Univariate (Wilcoxon signed-rank and Mann–Whitney U test) and multivariate (random forest, hierarchical clustering) analyses were performed to identify clinical and metabolic features that were associated with the intervention and disease state. Results Relative to healthy controls, Phe catabolites, ketones, and carnitine- and glycine-conjugated fatty acids were elevated in females with PKU at baseline, whereas fatty acylcholine metabolites were substantially lower. After the camp intervention, plasma Phe concentrations decreased [median change: –173 µmol/L (IQR: –325, –28 µmol/L)] and 70% of PKU participants demonstrated improved dietary adherence by decreasing Phe intake and/or increasing medical food consumption. This was accompanied by a shift in abundance for 223 metabolites (q  < 0.05). Compounds associated with the metabolism of Phe, fatty acids, and choline contributed most to profile differences between camp days 1 and 5. Conclusions In females with PKU, untargeted metabolomics identified prominent perturbations in amino acid and lipid metabolites associated with bioenergetic impairment and oxidative stress. Choline-conjugated lipids could have fundamental roles in these pathways and they have not been previously evaluated in PKU. A short-term camp intervention was effective for improving or fully normalizing the abundance of the identified discriminatory metabolites. [ABSTRACT FROM AUTHOR]

Periodontitis has been defined as the Sixth complication of Diabetes Mellitus. Since both diabetes mellitus and periodontitis have a high prevalence in the general population, the Italian Society of Diabetology, the Italian Society of Periodontology and Implantology and the Italian Association of Clinical Diabetologists revised the present scientific literature in the present consensus report. A bi-directional interaction was demonstrated: Patients affected by type 1 and type 2 diabetes have a higher prevalence of periodontitis than the general population, due to several metabolic factors (e.g. chronic hyperglycemia, autoimmunity, dietary and life-style factors); similarly, periodontitis predisposes to type 2 diabetes mellitus mainly via the increase of systemic cytokines release. Conversely, improvement of metabolic control of diabetic patients delay the progression of periodontitis as well as periodontitis treatment reduces glycosylated hemoglobin levels in blood. Due to the bi-directional causal interaction between periodontitis and diabetes mellitus, a strict collaboration among dentists and diabetologists is required and strongly recommended. The inter-societies consensus proposes specific flow-diagrams to improve the treatment of patients and management of the general population regarding the issue of periodontitis and diabetes. [ABSTRACT FROM AUTHOR]

• Type 1 diabetes alone develops earlier than one combined with thyroid disease. • Levothyroxine treatment improves glycaemic control in type 1 diabetes. • APS3 patients develop microalbuminuria earlier than type 1 diabetes alone. The primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. We retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. Patients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16–30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). We found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16–30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones. [ABSTRACT FROM AUTHOR]

Aim: This study used a randomized controlled trial design and was carried out to examine the effect of education on diabetes self-management and self-efficacy in patients with type 2 diabetes.Methods: The study was carried out between July 2016-March 2017. Data were collected using information form, Diabetes Self-Management Questionnaire (DSMQ), self-efficacy scale for patients with type 2 diabetes (DSS).The individuals in the experimental group were given education. Both groups were reminded about the control time of their metabolic values on the phone in the 3rd and 6th months.Results: The average age of the individuals was 59.91 ± 8.93 (n = 78), 62.8% (n = 49) were female, 92.3% (n = 72), were married, 42.3% (n = 33) were high school graduates and their diabetes duration was 7.05 ± 3.9. There was a statistically significant difference in the 6th month metabolic values in the experimental group compared to the control group. When diabetes self-management and self-efficacy were examined, a statistically significant difference was found in the experimental group compared to the control group at 3rd and 6th months (p < 0.05, p < 0.01).Conclusion: In this study, a significant increase in diabetes self-management and self-efficacy and a significant decrease in metabolic values were observed as a result of education and phone reminders given to individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To determine the incidence rates of cardiovascular disease (CVD) and assess the effect of metabolic risk factor management on the development of CVD in patients with diabetes.Methods: We studied 733 patients with diabetes without prior CVD in the Shanghai Taopu community health service center. Success in managing CVD risk factors was evaluated as follows: (1) glucose control (haemoglobin A1c [HbA1c] <7.0% in patients aged <65years and <8.0% in patients aged ≥65years), (2) blood pressure control (<140/90mmHg), and (3) lipid control (high-density lipoprotein cholesterol ≥1.0mmol/L in men and ≥1.3mmol/L in women, and triglycerides <1.7mmol/L).Results: During a median 8.0-year follow-up, 206 CVD incident cases were identified. Each 1% increment in HbA1c, 10mmHg increment in systolic blood pressure (SBP), and 1mmol/L increment in triglycerides during follow-up significantly increased the risk of CVD by 17%, 37%, and 14%, respectively. Compared to those who did not, patients who met the blood pressure and glucose control goals during follow-up had a 64% and a 29% decreased risk of CVD, respectively. The multivariable-adjusted hazard ratios of CVD were 1.00, 1.78 (95% confidence interval [CI] 1.10-2.87), and 2.51 (95% CI 1.54-4.07) among patients who attained three, two, and one/none of the CVD factor control goals (HbA1c, blood pressure, and lipid) during follow-up, respectively.Conclusions: Average levels of HbA1c, SBP, and triglycerides during follow-up were positively associated with the risk of CVD, and treatment targeting multiple factors can significantly reduce CVD risk. [ABSTRACT FROM AUTHOR]

• Diabetic patients face higher Herpes Zoster hospitalization rates in Piedmont, Italy (2010–2019). • Key risk factors for hospitalization are age > 65, obesity, and poor glycaemic control. • Diabetes increases recurrent HZ hospitalizations and severe complications risk. This study explores the association between Herpes Zoster (HZ) hospitalizations and diabetes in Piedmont, Italy from 2010 to 2019. Focusing on the burden of HZ hospitalizations in diabetic and non-diabetic groups, it aims to identify risk factors in diabetics to enhance prevention strategies. In a two-phase study, we first compared age-standardized HZ hospitalization rates between diabetic and non-diabetic individuals from 2010 to 2019. We then examined hospitalization risk factors for HZ within a diabetic patient cohort managed by regional diabetes clinics. Of 3,423 HZ hospitalizations in 2010–2019, 17.9 % (613 cases) were diabetic patients, who exhibited higher hospitalization rates (15.9 to 6.0 per 100,000) compared to non-diabetese individuals. Among diabetics subjects risk factors for HZ hospitalization included age over 65, obesity (BMI > 30), and poor glycemic control (HbA1c > 8.0 %). These patients had a 40 % increased rehospitalization risk and a 25 % higher risk of severe complications, such as stroke and myocardial infarction, post-HZ. Diabetes markedly increases HZ hospitalization rates, rehospitalization, and complication risks. These findings underscore the need for preventive strategies, especially improved glycemic control among high-risk diabetic patients, to inform public health policies and clinical practices aimed at mitigating HZ's impact on this population. [ABSTRACT FROM AUTHOR]

Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects. To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals. We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs). Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents : studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents : Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term. Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely. [ABSTRACT FROM AUTHOR]

• Dried blood spot home monitoring is associated with increased biochemical control. • Monitoring frequency is positively correlated with biochemical control. • Younger patients' BCAA levels are more sensitive to increased monitoring. • Number of hospitalizations decreases throughout the life of the patient. Branched-chain amino acid (BCAA) concentrations must be tracked and maintained within an optimal range to minimize disease phenotypes in patients with maple syrup urine disease (MSUD). In 2014, the Hospital for Sick Children (SickKids) implemented a dried blood spot (DBS) home monitoring system, allowing patients to track BCAA concentrations without the inconvenience of having to travel to the hospital. We conducted a retrospective chart review study (n = 15) to assess the impacts of DBS monitoring implementation on biochemical control. Furthermore, we explored relationships among various MSUD patient parameters, including monitoring frequency, age, biochemical control, and hospitalizations. There was a 35% increase in the proportion of LEU concentrations that met recommended targets post-DBS monitoring implementation. Monitoring frequency was positively associated with better biochemical control in the newborn period (r = 0.68, p = 0.046). Frequency of hospital visits decreased steadily throughout life. DBS monitoring has resulted in a sharp increase in monitoring frequency, which is further correlated with biochemical control. Younger patients are more likely to visit the hospital and respond better to increased monitoring efforts. We recommend that DBS monitoring be adopted by other centers more broadly to improve metabolic control in MSUD patients. [ABSTRACT FROM AUTHOR]

Metabolons are dynamic associations of enzymes catalyzing consecutive reactions within a given pathway. Association results in enzyme stabilization and increased metabolic efficiency. Metabolons may use cytoskeletal elements, membranes and membrane proteins as scaffolds. The effects of glucose withdrawal on a putative glycolytic metabolon/F-actin system were evaluated in three Saccharomyces cerevisiae strains: a WT and two different obligate fermentative (OxPhos-deficient) strains, which obtained most ATP from glycolysis. Carbon source withdrawal led to inhibition of fermentation, decrease in ATP concentration and dissociation of glycolytic enzymes from F-actin. Depending on the strain, inactivation/reactivation transitions of fermentation took place in seconds. In addition, when ATP was very low, green fluorescent protein-labeled F-actin reorganized from highly dynamic patches to large, non-motile actin bodies containing proteins and enzymes. Glucose addition restored fermentation and cytoskeleton dynamics, suggesting that in addition to ATP concentration, at least in one of the tested strains, metabolon assembly/disassembly is a factor in the control of the rate of fermentation. Image 1 [ABSTRACT FROM AUTHOR]

Determine the correlation of quality of life (QoL) and the impact on the metabolic control of patients with type 2 diabetes mellitus (T2DM). An observational study was conducted at the outpatient consulting service in a specialized hospital in Santo Domingo, DR. We used a non-probabilistic, convenience sampling strategy, and the World Health Organization Quality of Life (WHOQOL-BREF) short form questionnaire was applied. The patients presented lower impact in QoL domains was: pain ( x ¯ = 29.07, SD = 3.04) and negative feelings ( x ¯ = 28.70, SD = 3.33). We found there is a negative correlation between the psychological domains and the fasting glycemia (r ho = −0.192, p < 0.05), also between the summary of all domains of QoL and metabolic control, HbA1C (r ho = −0.205, p < 0.05), and fasting glycaemia (r ho = −0.214, p < 0.05). There was a significant difference in the physical domains F (1, 131) = 9.73, p = 0.002, η2 = 0.069, indicating that men (M = 14.81) have a higher physical QoL than women (M = 13.72). Given the evidence of the impact of metabolic control and the different domains to QoL, it is necessary to consider these aspects in the treatment plan of patients with diabetes, to ensure adequate management and control of future complications. [ABSTRACT FROM AUTHOR]

Since they lack insulin-producing β -cells, patients with type 1 diabetes mellitus (T1DM) need to supply their body with insulin from external sources to manage their blood glucose (BG) concentration and mitigate the long-term effects of chronically increased BG levels. The common way of dosing insulin in T1DM is basal bolus therapy. In this method, patients continuously supply their body with a small amount of insulin that is meant for keeping their BG level more or less constant in case no large disturbances occur. Bolus insulin (which makes up roughly 30–60% of the total insulin amount) on the other hand is used to counterbalance such disturbances. The biggest perturbation of BG is caused by meals that can lead to large postprandial glucose excursions. By far, the most common approach to determine bolus insulin requirements in T1DM is known as Advanced Carbohydrate Counting (ACC). In ACC the bolus insulin amount is determined proportional to the estimated carbohydrate content of the ingested meal. Even though this semi-heuristic approach has proven very valuable in daily practice, its use is not without pitfalls. In this paper we discuss the background, implicit assumptions and limitations of ACC from an engineering perspective and show how concepts from the fields of data-based modeling and control have been successfully used to facilitate the computation of bolus insulin requirements. [ABSTRACT FROM AUTHOR]

Background: The benefits and risks of continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) in patients with Type 1 diabetes mellitus (T1DM) who fast during Ramadan are not known.Methods: Systematic review and meta-analysis of observational studies conducted in PubMed, Embase (Ovid), and the Cochrane Library. Quality of included studies was assessed using the ROBINS-I tool for risk of bias assessment and analyses were performed using RevMan version 5.1.Results: From 709 records, 306 full text studies were assessed. After exclusions, the final analysis included a total of 9 studies. Heterogeneity for outcomes was I2 = 0%. There was no significant difference for the change in glycemic control (HbA1c) between CSII and MDI (P > 0.05). There was no change in weight or the lipid profile in patients with T1DM on MDI during Ramadan. There were insufficient data to assess the impact on glucose profiles and the incidence of hypoglycemia or diabetic ketoacidosis (DKA) in patients on CSII or MDI during Ramadan.Conclusions: Studies assessing the effect of CSII or MDI in patients with T1DM who fast during Ramadan are limited to observational studies and show no difference in the change in HbA1c, weight or lipids during Ramadan. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effectiveness of a comprehensive care program to achieve and maintain goals in patients with type 2 diabetes.Methods: The CAIPaDi program includes 9 interventions delivered in 7 h. It seeks to achieve metabolic goals, identify and resolve barriers that would make implementation difficult, and provide self-efficacy and empowerment to patients by identifying personal profiles to establish individualized strategies. The program consists of a 4 intervention visits (1, 2, 3, and 4 months) and two follow up visits (12 and 24 months). Outcomes are compared between every visit. Main outcome was the attainment of the USA National Committee for Quality Assurance treatment goals.Results: 1104 patients completed the first 4 visits, 545 the 12 month evaluation, and 218 the 24 month evaluation. After the conclusion of the four monthly sessions, 80.6% had HbA1c <7%, 72.1% had BP <130/80 mmHg and 71.6% had LDL- cholesterol <100 mg/dl. After twelve months, the percentage of goals achieved were 65.9%, 67.7% and 43.3% respectively (p < 0.001). For the 2-year evaluation the percentages were 61.0%, 70.6%, and 40.8% respectively (p < 0.001). All patients had renal, eye, foot and dental evaluations. Empowerment and quality of life showed significant changes; anxiety and depression scores remained low at annual follow-ups.Conclusions: The CAIPaDI program results in sustained improvement and maintenance of treatment goals. [ABSTRACT FROM AUTHOR]

Secretagogin (SCGN) is a calcium sensor protein enriched in neuroendocrine cells in general and pancreatic β-cells in particular. SCGN regulates insulin secretion through several Ca2+-dependent interactions. Recent studies implicate SCGN in the β-cell physiology and extracellular insulin function, making it an intriguing candidate in diabetes research. Here, we propose a conjoining theme of diversified SCGN function in diabetes pathology. In our opinion, SCGN is an attractive therapeutic candidate ascribed by its role in β-cell maintenance and neuronal functions and in the efficacy of insulin. To scrutinize the therapeutic prospects of SCGN, we abridge putative diabetes-related properties of SCGN and put forth strategies to determine the precise role of SCGN in the pathogenesis/preclusion of diabetes. Highlights Secretagogin (SCGN) is a calcium sensor protein with the highest expression in pancreatic β-cells to regulate insulin expression and secretion. Diabetic patients have reduced SCGN levels. In mice, lack of SCGN causes glucose intolerance and pancreatic β-cell depletion, while exogenous injection impedes these symptoms. Several brain regions express SCGN for an unidentified purpose. In the hypothalamus, SCGN regulates CRH release to manifest stress response and activate HPA axis of systemic metabolic control. A consolidated understanding of diverse SCGN expression/function is lacking. We present a comprehensive view of current knowledge in the field and discuss future directions to resolve the opacity in perplexing diabetes nexus and imminent therapeutic prospects. [ABSTRACT FROM AUTHOR]

Abstract The present study evaluated the effect of age on glucose tolerance and cardiac function and assessed the relationship between metabolic control and cardiac function and performance. Thirty-four healthy women aged 40 to 81 years were divided into two age groups: younger (≤50 years of age, N = 19) and older (≥60 years of age, N = 15). Participants performed an oral glucose tolerance test and a graded cardiopulmonary exercise test with non-invasive haemodynamic measurements. Compared to younger, older women demonstrated significantly higher 2-hour glucose (4.67 ± 1.01 vs 6.08 ± 1.54 mmol/l, P < 0.01), but lower peak exercise O 2 consumption (1.96 ± 0.44 vs 1.38 ± 0.26 l/min, P < 0.01) and cardiac power output (4.06 ± 0.76 vs 3.35 ± 0.73 W, P = 0.01). When data from all study participants were combined, there was a significant negative relationship between 2-hour glucose and peak cardiac power (r = −0.39, P = 0.02), and peak O 2 consumption (r = −0.40, P = 0.02). The strength of these relationships was affected by age, with moderate negative relationship identified between 2-hour glucose and peak cardiac power output in younger compared to older participants (r = −0.38, P = 0.11 vs. r = −0.09, P = 0.75). Metabolic control and cardiac function decline with age. The lack of relationship between glucose control and cardiac power may suggest that metabolic control does not influence cardiac function and performance in older women. Highlights • Age is the major risk factor for development of cardiovascular and metabolic diseases. • Cardiac function and glucose control decline with age. • Cardiac function is not associated with glucose control in older women. [ABSTRACT FROM AUTHOR]

To unveil what controls mitochondrial ROS detoxification, the NADPH supply and GSH/GSSG recycling for oxidative stress management were analyzed in cancer and non-cancer mitochondria. Therefore, proteomic and kinetomic analyses were carried out of the mitochondrial (i) NADPH producing and (ii) GSH/GSSG recycling enzymes associated to oxidative stress management. The protein contents of the eight enzymes analyzed were similar or even higher in AS-30D rat hepatoma mitochondria (HepM) than in rat liver (RLM) and rat heart (RHM) mitochondria, suggesting that the NADPH/GSH/ROS pathway was fully functional in cancer mitochondria. The Vmax values of IDH-2 were much greater than those of GDH, TH and ME, suggesting that IDH-2 is the predominant NADPH producer in the three mitochondrial types; in fact, the GDH reverse reaction was favored. The Vmax values of GR and GPx were lower in HepM than in RLM, suggesting that the oxidative stress management is compromised in cancer mitochondria. The Km values of IDH-2, GR and GPx were all similar among the different mitochondrial types. Kinetic modeling revealed that the oxidative stress management was mainly controlled by GR, GPx and IDH. Modeling and experimentation also revealed that, due to their higher IDH-2 activity and lower GPx activity presumably by acetylation, HepM (i) showed higher steady-state NADPH levels; (ii) required greater peroxide concentrations to achieve reliable steady-state fluxes and metabolite concentration; and (iii) endured higher peroxide concentrations without collapsing their GSH/GSSG ratios. Then, to specifically prompt lower GSH/GSSG ratios under oxidative stress thus compromising cancer mitochondria functioning, GPx should be re-activated. [ABSTRACT FROM AUTHOR]

Aims: To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treatment of diabetes.Methods: APBSCT was performed in 23 patients. Control group comprised 8 non-APBSCT patients in whom after diagnosis insulin therapy was initiated. Fasting plasma glucose, glycated hemoglobin, fasting and postprandial C-peptide were assessed in all subjects and continuous glucose monitoring was performed at 6th, 12th, 24th, 36th, 48th month after transplantation. The APBSCT group was observed for 72 months.Results: Six months after the procedure, 22 of 23 transplant patients remained insulin-free, but after 6 years, there was only one APBSCT insulin-free patient. Good glycemic control was observed in all patients throughout the observation period, although fasting plasma glucose in control group was significantly higher in comparison with the both transplanted groups up to the 36th month. HbA1c values were significantly lower in the insulin-free group only at the 24th and 36th month. Fasting and postprandial C-peptide concentrations were higher in APBSCT group as compared with control group. The most serious adverse event was a fatal case of Pseudomonas aeruginosa sepsis.Conclusions: The effectiveness of APBSCT as a treatment for newly diagnosed DM1 seems to be limited in time. The metabolic control of APBSCT patients is similar to conventionally treated patients. The lower fasting plasma glucose and higher C-peptide achieved with APBSCT seem to not exceed the risks associated with the procedure. [ABSTRACT FROM AUTHOR]

Muscle stem cells or satellite cells are crucial for muscle maintenance and repair. These cells are mitotically quiescent and uniformly express the transcription factor Pax7, intermittently entering the cell cycle to give rise to daughter myogenic precursors cells and fuse with neighboring myofibers or self-renew, replenishing the stem cell pool in adult skeletal muscle. Pivotal roles of muscle stem cells in muscle repair have been uncovered, but it still remains unclear how muscle stem cell self-renewal is molecularly regulated and how muscle stem cells maintain muscle tissue homeostasis. Defects in muscle stem cell regulation to maintain/return to quiescence and self-renew are observed in degenerative conditions such as aging and neuromuscular disease. Recent works has suggested the existence of metabolic regulation and mitochondrial alterations in muscle stem cells, influencing the self-renewal commitment and function. Here I present a brief overview of recent understanding of how metabolic reprogramming governs self-renewal commitment, which is essential for conservation of muscle satellite cell pools throughout life, as well as the implications for regenerative medicine. [ABSTRACT FROM AUTHOR]

Aims: To compare type 2 diabetes (T2D) patients included in a Diabetes Integrated Management (DIM) program with those followed in Diabetes Specialized Care (DSC), investigating differences in general characteristics, changes in clinical outcomes, and factors related with the inclusion in the DIM program.Methods: T2D patients living in the ASLTO3 district and included into the DIM program, a shared disease management between general practitioners and diabetes specialists, from 2008 to 2014 were compared with T2D patients living in the same district and in charge of the local DSC. Demographic, anthropometric and clinical data for both groups of patients were obtained from the electronic records of DSC.Results: 1326 DIM patients were compared with 3494 DSC patients. A higher proportion of females was observed among DIM patients than among DSC patients. DIM patients were older, more frequently in therapy with diet only or with oral hypoglycemic, and had HbA1c and creatinine lower than DSC patients. The analyses of changes in clinical parameters during the study period showed a good and statistically significant improvement of most parameters, independently of the inclusion in DIM or DSC, with the exception of creatinine level.Conclusions: Integrated Management is an efficient and effective way to achieve good long-term clinical outcomes for patients with diabetes. [ABSTRACT FROM AUTHOR]

Background and aims Limited data is available on the factors influencing the lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. We aimed at assessing the influences of metabolic control and ApoE genotypes on lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. Methods Children, adolescents and young adults with type 1 diabetes from our nationwide cohort attending the annual check-up were prospectively included. Data on metabolic control and expanded lipid profiles were collected, and ApoE genotyping performed. Test for homoscedasticity of continuous variables was followed by ANOVA and Welch's ANOVA tests, and Chi-square test was used for categorical variables with Kruskal-Wallis test as a control. Results 467 patients were included in the data analysis: 226 female (48.4%), mean age 14.71 ± 5.09 years and diabetes duration 6.74 ± 4.54 years. Mean HbA1c was 61 ± 5 mmoL/mol (7.71 ± 1.22%), with no gender-related differences. Females had higher mean total cholesterol ( p  < 0.001), LDL-C ( p  = 0.005), HDL-C ( p  < 0.001), non-HDL-C ( p  = 0.003), and ApoB levels ( p  < 0.001). 26.3% of participants had LDL-C levels above the type 1 diabetes LDL-C-goal of 2.6 mmoL/L, and 19.5% had elevated/borderline-elevated lipoprotein(a) (Lp(a)). HbA1c levels were positively related to higher levels of LDL-C ( p  = 0.0070) and Lp(a) ( p  = 0.0020). Participants with ApoE4(e3/e4) allele had higher levels of LDL-C ( p  = 0.010), independently of HbA1c. Conclusions Females and subjects with suboptimal metabolic control had more adverse lipid profiles. ApoE4(e3/e4) alleles were associated with significantly higher LDL-C levels, independently of HbA1c. [ABSTRACT FROM AUTHOR]

Aims: To study the impact of a novel comprehensive eLearning approach in delivering diabetes related education program that includes knowledge and sets of practices to the school personnel in Kuwait to enable them to provide a supportive environment for students with diabetes.Methods: The program was designed with three components namely; knowledge, skills and recommendations. The diabetes knowledge was delivered through an interactive eLearning program, the effectiveness of which was assessed using diabetes knowledge questionnaires which were deployed pre- and post-course delivery. Additionally, the participants' knowledge retention and confidence in caring for a student with diabetes were evaluated at 6 or 12 months post-intervention.Results: A total of 124 public schools' personnel participated in the program. Post e-Learning delivery, diabetes knowledge increased significantly from baseline (p < 0.0001) and knowledge was retained over 6 and 12 months. Average of overall confidence scores in caring for students with diabetes was 61.86% in all items of care.Conclusions: Offering eLearning diabetes education for school personnel increases their knowledge which can be retained for up to 12 months and imparts confidence in caring for students with diabetes. This novel approach of delivering diabetes education will help school personnel in managing students with diabetes. [ABSTRACT FROM AUTHOR]

Background and Aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII).Methods and Results: Questionnaires investigating the organisation of diabetes care centres, individuals' clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. <58 mmol/mol for age <18 years and <53 mmol/mol for age >18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis.Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia.Clinical Trial Registration Number: NCT 02620917 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Aims: Evidence from randomised trials analysing effects of depression treatment on glycaemic control in group comparisons is inconsistent. The aim of this study was to test if the reduction of depressive symptoms would explain improved glycaemic control irrespective of treatment groups.Methods: The DIAMOS study tested effects of cognitive-behavioural therapy (CBT) versus usual care on depressive symptoms in a 12-month prospective trial; HbA1c was a secondary outcome. Since the results suggested superiority of CBT for improving depressive symptoms, but not HbA1c, we conducted this secondary analysis to test if reduction of depressive symptoms could explain improved glycaemic control when assessed irrespective of treatment group affiliation. Reduction of depressive symptoms was assessed using baseline-to-follow-up changes in the Center for Epidemiologic Studies Depression Scale (CES-D). We used multiple regression analyses, adjusting for baseline HbA1c and depression, group affiliation and covariates, to assess associations between reduction of depressive symptoms and follow-up HbA1c.Results: 181 participants provided eligible data. Depressive symptoms decreased between baseline and follow-up by averagely -5.1±11.8 CES-D points. Greater reduction of depressive symptoms predicted greater improvement of HbA1c at follow-up, while adjusting for baseline HbA1c and covariates (Beta=-0.24, P=0.004). Additionally, patients with greater reduction of depressive symptoms were more likely to reach in-target HbA1c (<7.5%) at follow-up (adjusted OR=1.04, 95% CI 1.01-1.08, P=0.023).Conclusions: The findings suggest that reduction of depressive symptoms can explain improved glycaemic control. Behavioural treatments might aim to improve both affective and glycaemic outcomes. [ABSTRACT FROM AUTHOR]

Objective To determine if symptoms of depression and anxiety are differentially associated with clinical diabetes measures and self-management behaviours in individuals with Type 2 diabetes, and whether these associations vary by patient sex. Research design and methods A cross-sectional analysis using data from 2035 adults with Type 2 diabetes in the Nord-Trøndelag Health Study. Multivariate logistic regression was used to explore associations between symptoms of depression and anxiety and waist girth, HDL cholesterol, systolic blood pressure, triglycerides, c-reactive protein, glycemic control, diet adherence, exercise, glucose monitoring, foot checks for ulcers, and the subjective patient experience. Analyses were stratified by sex. Results Depression was associated with a lower likelihood of avoiding saturated fats (OR = 0.20 [95% CI: 0.06, 0.68]) and increased odds of physical inactivity (OR = 1.69 [95% CI: 1.37, 2.72]). Anxiety was associated with increased odds of eating vegetables (OR = 1.66 [95% CI: 1.02, 2.73]), and an over two-fold increase of feeling that having diabetes is difficult. In women, anxiety was associated with elevated c-reactive protein levels (OR = 1.57 [95% CI: 1.05, 2.34]). In men, depressive symptoms were associated with elevated HbA1c (OR = 5.00 [95% CI: 1.15, 8.23). Conclusions Symptoms of depression and anxiety were differentially associated with some key diabetes-related measures. Our results suggest sex-specific differences with respect to two important clinical outcomes (i.e., anxiety and CRP in women and depression and glycemic control in men). These findings should alert practitioners to the importance of detection and management of psychological symptoms in individuals with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction Emerging adults (EA) with disordered eating behaviors (DEBs) and Type 1 diabetes (T1D) are at increased risk for severe complications of T1D, and these behaviors have been reported in EA women with T1D. Few studies, though, have included men. This study assessed the prevalence of DEB in both EA men and women with T1D. Methods DEB was measured with the diabetes-specific Diabetes Eating Problem Survey–Revised (DEPS-R); scores of 20 or greater indicate need for further evaluation for DEB. Results A total of 27 women and 33 men (age range = 21 ± 2.5 years) completed the DEPS-R; 27% of women and 18% of men had scores of 20 or greater ( p = .23). Hemoglobin A1c level was significantly higher in subjects with elevated DEPS-R scores (10.4 ± 2.1% vs. 7.8 ± 1.3%; p < .001), and DEPS-R scores correlated with increased body mass index values ( r = 0.27, p < .05). Discussion Clinicians should assess for DEB in both male and female emerging adults with T1D, especially overweight patients with poor glycemic control. [ABSTRACT FROM AUTHOR]

Aims To determine an association between hs-CRP and metabolic control/diabetic chronic vascular complications (DCVCCxs) in the patients with type 2 diabetes (DM). In addition, the possibility of using hs-CRP levels to predict risk of DCVCCxs will also be validated. Methods This cohort study randomly enrolled 608 patients with DM during the 2007–2008 study period. We also recorded basic laboratory findings at baseline and at one year, to include fasting plasma glucose, HbA1c, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and hs-CRP. Results Logistic regressions of odds ratios between hs-CRP and DCVCCxs (coronary arterial disease, cerebrovascular disease, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy ) showed significant correlations, except for cerebrovascular disease, as follows 0.2 (0.11–0.38), 0.09 (0.01–0.77), 0.06 (0.02–0.16), 0.31 (0.12–0.82), and 0.17 (0.07–0.43), respectively. Linear regression for changes in hs-CRP were significantly correlated with HbA1c (r = 0.38), fasting plasma glucose (r = 0.40), triglyceride (r = 0.20), low-density lipoprotein cholesterol (r = 0.12), and high-density lipoprotein cholesterol (r = −0.12). No correlation was found for total cholesterol (r = 0.06). Based on receiver operating characteristic (ROC) analysis, the cut-off points for hs-CRP levels for prediction of DCVCCxs were 2.89, 2.25, 2.10, 2.25, and 2.82 mg/L, for coronary arterial disease, cerebrovascular disease, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy, respectively. Conclusions Our data showed that DCVCCxs were associated with hs-CRP in patients with DM. The cut-off point for hs-CRP can be used to predict association with DCVCCxs. Well-controlled metabolic components in diabetic patients, especially HbA1c, fasting plasma glucose, and triglyceride may reduce the level of hs-CRP. [ABSTRACT FROM AUTHOR]

Biochemical monitoring of treatment in infants with classic congenital adrenal hyperplasia (CAH) is not yet well defined. The aim of this study was to perform a cluster analysis of the urinary steroid metabolome for treatment monitoring of infants with classic salt-wasting CAH. We analyzed spot urine samples obtained from 60 young children ≤ 4 years of age (29 females) with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone by targeted gas chromatography-mass spectrometry (GC-MS). Patients were classified into different groups according to their metabolic patterns (metabotypes) using unsupervised k-means clustering algorithms. Three metabotypes could be discovered. Metabotype #1 (N = 15 (25%)) showed high concentrations of androgen and 17-hydroxyprogesterone (17OHP) precursor steroids, metabotype #2 (N = 28 (47%)) revealed balanced metabolic control, and metabotype #3 (N = 17; 28%) demonstrated severe adrenal suppression with low concentrations of androgen and 17OHP precursor steroids. Daily hydrocortisone doses and urinary concentrations of cortisol and cortisone metabolites did not differ between all three metabotypes. Metabotype #2 had highest daily dose of fludrocortisone (p = 0.006). Receiver operating characteristic curve analysis showed that 11-ketopregnanetriol (area under the curve [AUC] 0.967) and pregnanetriol (AUC 0.936) were most suitable of separating metabotype #1 from #2. For separation between metabotypes #2 vs. #3, the 11-oxygenated androgen metabolite 11-hydroxyandrosterone (AUC 0.983) and the ratio of 11-hydroxyandrosterone to tetrahydrocortisone (AUC 0.970) were most suitable. In conclusion, GC-MS-based urinary steroid metabotyping is a new method to help monitor the treatment of infants with CAH. This method allows classification of under-, over- and adequately treated young children. • GC-MS-based urinary steroid metabotyping in treated young children with CAH is presented. • Three unique metabotypes could be discovered. • The identification of these different metabolic patterns allows for a truly personalized diagnostic and therapeutic approach. [ABSTRACT FROM AUTHOR]

Although the papers of Kacser and Burns (1973) and Heinrich and Rapoport (1974a,b) are commonly taken as the birth of metabolic control analysis, many of the ideas in them are foreshadowed in earlier papers, from 1956 onwards, when Kacser first argued for taking a systemic view of genetics and biochemistry. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of an intensive lifestyle intervention on metabolic control in patients with type 2 diabetes.Methods: 199 patients recently diagnosed with type 2 diabetes, with lack of metabolic control and overweight/obesity, were randomly assigned to intensive lifestyle intervention or collaborative educational program alone, with 6 months of follow-up. Intervention included 150min of physical activity a week to reduce body weight by 7%. Both groups received 16 sessions on behavior modification over the course of the 6 months. Measurements were taken at baseline, 3 and 6 months. Results were analyzed and compared.Results: Significant weight loss was achieved by both groups, with greater loss in the intervention group. Those with lower baseline A1c appeared to benefit more from the educational program than intensive intervention over time.Conclusions: Both interventions produced positive if modest changes in metabolic control. These results suggest that, for weight loss and control of A1c, an intensive intervention may be more effective.Practice Implications: The current study demonstrates the value of a systematic application of behavior modification and self-care techniques in the treatment of type 2 diabetes. It demonstrates the importance of intensive, all-inclusive treatment, and of attention to individual concerns. [ABSTRACT FROM AUTHOR]

Aims To evaluate how HbA1c in adolescents with type 1 diabetes affects microvascular complications in young adults. Methods All individuals registered in the Swedish paediatric diabetes quality registry (SWEDIABKIDS) 13–18 years of age, and as adults registered in the Swedish National Diabetes Registry (NDR) in both the years 2011 and 2012 were included, in total 4250 individuals. Results Of the individuals with mean HbA1c > 78 mmol/mol in SWEDIABKIDS 83.4% had retinopathy, 15.8% had microalbuminuria and 4.9% had macroalbuminuria in NDR. The logistic regression analysis showed that the OR to develop macroalbuminuria as a young adult was significantly higher in the group with mean HbA1c > 78 mmol/mol in SWEDIABKIDS (p < 0.05). Among the patients with mean HbA1c above 78 mmol/mol in both registries there was a significantly higher proportion that had retinopathy, microalbuminuria (p < 0.001) and/or macroalbuminuria (p < 0.01) compared to the group with HbA1c below 57 mmol/mol in both registries. Only 6.5% of the persons in this study were over 30 years of age. Conclusions Paediatric diabetes teams working with teenagers must be aware of the impact of good metabolic control during adolescence, and should intensify the care during this vulnerable period of life to reduce the risk of microvascular complications in young adults. [ABSTRACT FROM AUTHOR]

Aims: Diabetes education is a major subject in achieving optimal glycemic control. Effective empowerment approach can be beneficial for improving patients' health. The aim of this study was to evaluate the effect of empowerment model on indicators of metabolic control in patients with type 2 diabetes.Methods: a randomized controlled trial of 103 patients with type 2 diabetes were randomly assigned to either the intervention (empowerment approach training) or the control group (conventional training) 2014. Empowerment approach training were performed for the experimental group for eight weeks. Data collection tool included demographic information form and indicators of metabolic control checklist. Analysis was performed by one-way analysis of variance, chi-square test, paired t-test, independent t-test and multiple linear regression.Results: Before the intervention, two groups were homogeneous in terms of demographic variables, glycosylated hemoglobin (HbA1C), and other indicators of metabolic control. After the intervention, average HbA1C and other metabolic indicators except for LDL showed significant differences in the experimental group compared to the control group.Conclusion: study results indicated the positive effects of applying the empowerment model on the metabolic control indicators. Therefore, applying this model is recommended to nurses and the relevant authorities in order to improve clinical outcomes in diabetic patients. [ABSTRACT FROM AUTHOR]

Aims: Dementia and type 2 diabetes (T2D) are two major phenomena in older people. To compare anti-hyperglycemic therapy and diabetes-related comorbidities between elderly T2D patients with or without comorbid dementia.Methods: 215,932 type 2 diabetes patients aged ≥ 40 years (median [Q1;Q3]: 70.4 [61.2;77.7] years) from the standardized, multicenter German/Austrian diabetes patient registry, DPV, were studied. To identify patients with comorbid dementia, the registry was searched by ICD-10 codes, DSM-IV/-5 codes, respective search terms and/or disease-specific medication. For group comparisons, multiple hierarchic regression modeling with adjustments for age, sex, and duration of diabetes was applied.Results: 3.1% (n=6770; 57% females) of the eligible T2D patients had clinically recognized comorbid dementia. After adjustment for demographics, severe hypoglycemia (insulin group: 14.8 ± 0.6 vs. 10.4 ± 0.2 events per 100 patient-years, p<0.001), hypoglycemia with coma (insulin group: 7.6 ± 0.4 vs. 3.9 ± 0.1 events per 100 patient-years, p<0.001), depression (9.9 vs. 4.7%, p<0.001), hypertension (74.7 vs. 72.2%, p<0.001), stroke (25.3 vs. 6.5%, p<0.001), diabetic foot syndrome (6.0 vs. 5.2%, p=0.004), and microalbuminuria (34.7 vs. 32.2%, p<0.001) were more common in dementia patients compared to T2D without dementia. Moreover, patients with dementia received insulin therapy more frequently (59.3 vs. 54.7%, p<0.001), but metabolic control (7.7 ± 0.1 vs. 7.7 ± 0.1%) was comparable to T2D without dementia.Conclusions: In T2D with dementia, higher rates of hypoglycemia and other diabetes-related comorbidities were observed. Hence, the risks of a glucocentric and intense diabetes management with insulin and a focus on tight glycemic control without considering other factors may outweigh the benefits in elderly T2D patients with comorbid dementia. [ABSTRACT FROM AUTHOR]

Background After ingestion of phosphatidylcholine, l -carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk. Methods A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease. Results Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9 μmol/L; p < 0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980 μmol/L; p = 0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43 μmol/L; p = 0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho: −0.281; p < 0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8 μmol/L; p = 0.045). Conclusions Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease. [ABSTRACT FROM AUTHOR]

Summary Objective This study sought to evaluate the associations between metabolic control and each DSM-5 (Diagnostic and Statistical Manual, fifth edition) symptom of depression among young women and men with early-onset long-duration type 1 diabetes. Methods The data of 202 18–21-year-old patients with type 1 diabetes from a population-based, nationwide survey (40.1% male) with a mean age of 19.4 (standard deviation 0.9) years, a mean HbA1c level of 8.3% (1.6%) (i.e., 67 [17.5] mmol/mol), and a mean diabetes duration of 15.7 (1.0) years were included. The German version of the Patient Health Questionnaire (PHQ-9) was used to assess depression symptoms. For each PHQ-9 depressive symptom, the mean HbA1c values of screening-positive and screening-negative patients were compared via t -test. The associations between HbA1c levels and depressive symptoms were analyzed using multiple linear regression analyses and stepwise adjustments for individual, socioeconomic and health-related covariates. Results Exactly 43.0% and 33.3% of female and male participants reported at least one depressive symptom, and 5.0% and 2.5% met the DSM-5 criteria for major depressive syndrome. HbA1c levels increased with psychomotor agitation/retardation (women), overeating/poor appetite (men/women), lethargy (men), and sleep difficulty (men). Overeating/poor appetite, lethargy, and total PHQ-9 score (per score increase by one) were associated with increased HbA1c levels of 1.10, 0.96 and 0.09 units (%), respectively. Conclusions The associations between depressive symptoms and HbA1c levels vary by symptom and sex. Differentiating the symptoms of depression and targeted interventions might help to improve metabolic outcomes in young adults with early-onset type 1 diabetes and depression. [ABSTRACT FROM AUTHOR]

Aims To describe the diabetic population receiving primary care from the Tshwane district public health services and to assess the quality of care of members of this population, their level of disease control and the extent of their complications. Methods A cluster-randomised trial was conducted in 12 primary care clinics in Tshwane district. A total of 599 diabetic patients attending these clinics for review were consecutively interviewed and clinically examined. Data on the care received was also obtained from their clinical records for the previous 12 months. Patients randomised to the active arm of the study were screened for complications. Results The mean age was 58 years and 80.5% had a body mass index (BMI) ≥25 kg/m 2 . Sixty-eight percent of patients were female. Acceptable glycaemic control and LDL-cholesterol were found for only 27% and 33% of patients, respectively (HbA1c < 7%; LDL < 2.5 mmol/l). Despite more than 79% of patients reporting to be hypertensive, 68% of patients had a systolic blood pressure above 130 mmHg and 64% had a diastolic blood pressure above 80 mmHg. Evaluating patient records of the preceding year, screening for eye complications was only reported in 8.2%, feet complications in 6.5%, kidney complications in 21.4% and cardiovascular complications in 7.8%. The screening prevalences found were 29% for retinopathy, 22% for maculopathy, 5% for neuropathy (neurothesiometer), 7% for nephropathy (eGFR stages 3–5), 17% for possible infarction (Rose questionnaire) and 36% for severe erectile dysfunction (SHIM questionnaire). Conclusion Diabetes care and screening for complications at primary care level in the Tshwane district were found to be sub-optimal. Measures should be taken to address this. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the impact of gluten free diet (GFD) on growth, metabolic control and quality of life in children and adolescents with type 1 diabetes (T1D) and celiac disease (CD).Methods: A systematic search was performed including studies published in the last 15 years. PICOS framework was used in the selection process and evidence was assessed using the GRADE system.Results: Overall, studies comparing youth with T1D + CD on GFD to those with T1D only, showed no significant differences in growth parameters, HbA1c, number of episodes of hypoglycemia, total daily insulin doses. Studies assessing the effect of GFD introduction showed stable BMI and HbA1c. Only two studies assessed QoL of life, which was not different between T1D + CD vs T1D only youth, as well as pre- and post-CD diagnosis and introduction of GFD.Conclusion: This systematic review, including only studies of moderate-high evidence quality level and reporting data on objectively assessed adherence to GFD, highlights that adherence to GFD in youth with T1D + CD leads to regular growth, stable BMI, without any negative effect on HbA1c and insulin requirements. Although assessed in few studies, lipid profile and QoL improved with the introduction of GFD. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to analyse the evolution of the metabolic control, cardiovascular risk factors and chronic complications in a Type 2 Diabetes (T2D) population in a healthcare area of Barcelona.Methods: We carried out a comparative study of T2D patients (20.457) between 2012 and 2016 (data recorded in the "Electronic Clinical-Station in Primary Care") concerning: age, gender, body mass index (BMI), arterial blood pressure (BP), HbA1c, LDL-Cholesterol, smoking, heart failure (HF), micro and macrovascular complications.Results: Average HbA1c was 6.9 % in 2012 and 7 % in 2016 (Non significant differences)(NS). In 2012, 57.9 % of patients presented proper glycaemic control, 42.8 % LDL-Cholesterol < 100 mg/dL and 76.9 % BP < 140/90 while in 2016 it was 61.2 % (NS), 59.2 % (p = 0.001) and 82.9 % (p = 0.016) respectively. No changes were found in BMI or active smoking. Significant increases were found in the prevalence of microvascular complications, HF and peripheral vasculopathy (PV). Patients with vascular diseases (PVD) and adequate metabolic control increased from 57.5 % to 62.7 % (p = 0.006). Albuminuria > 30 mg/g were more frequent among PVD.Conclusions: Between 2012 and 2016 it was observed that, amongst our study population, glycaemic control was steady and cholesterol and BP levels were improved, while there was a significant increase of diabetic complications, HF and PV. [ABSTRACT FROM AUTHOR]

Cold storage of fruits and vegetables is essentially a respiring and metabolic network flow and control process for which the further study of metabolic control rules are needed in order to improve the shelf-life of these living food products. This study used Hami melon as a test subject to study the respiratory metabolic network and flux control of fruits and vegetables during their storage. Hami melon was stored at different temperatures (0, 5, 10, 15, 20, 25, 30, 35, 40, 45 °C), in order to obtain the metabolic flux of the following pathways: Embden–Meyerh of pathway (EMP), pentose phosphate pathway (PPP), sucrose synthesis pathway (SSP) and TCA cycle (TCA). The quantity and activities of primary enzymes (enzymatic expression variate) were measured during storage. In addition, we got the control coefficients of synthesis flux to sucrose and metabolic flux to lactate. The results showed that sucrose had a higher synthesis flux at the temperatures of 5 °C and 45 °C, and lactate had a higher metabolic flux at the temperature of 5 °C. The study on flux control coefficients indicated that sucrose phosphate synthase (SPS, FCC = 0.424) produced a larger impact on sucrose flux control in the sucrose synthesis pathway. Lactic dehydrogenase (LDH, FCC = 0.143), triosephosphate isomerase (TPI, FCC = 0.136) and pyruvate kinase (PK, FCC = 0.136) had a large control effect on lactate flux, while glucose-6-phosphate dehydrogenase (G6PDH, FCC = −0.246) had a negative control function. These findings will enable future detailed investigation of metabolic mechanism of fruits and research of new preservatives. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes. Methods: Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7–18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA. Results: Mean HbA1c level was higher in the least physically active groups (PA0: 8.8%±1.5 (72±16mmol/mol)) than in the most physically active groups (PA4: 7.7%±1.0 (60±11mmol/mol)) (p <0.001). An inverse dose–response association was found between PA and HbA1c (β: −0.30, 95% CI: −0.34 to −0.26, p <0.001). This association was found in both sexes and all age groups, apart from girls aged 7–10 years. Multiple regression analysis revealed that the relationship remained significant (β: −0.21, 95% CI: −0.25 to −0.18, p <0.001) when adjusted for possible confounding factors. Conclusions: Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Diets where carbohydrate has been partially exchanged for protein have shown beneficial changes in persons with type 2 diabetes but no studies have enrolled people with albuminuria. We aim to determine if a high protein to carbohydrate ratio (HPD) in an energy reduced diet has a beneficial effect on metabolic control and cardiovascular risk factors without negatively affecting renal function. Method and results: Adult, overweight participants with type 2 diabetes, with albuminuria (30–600 mg/24 h or an albumin-to-creatinine ratio of 3.0–60 mg/mmol), and estimated GFR of >40 ml/min/1.73 m2 were enrolled. Participants were randomized to an HPD or an SPD. Protein:fat:carbohydrate ratio was 30:30:40% of energy for the HPD and 20:30:50% for the SPD. Main outcomes were renal function, weight loss, blood pressure, serum lipids and glycaemic control. We recruited 76 volunteers and 45 (35 men and 10 women) finished. There were no overall changes in renal function at 12 months and no significant differences in weight loss between groups (9.7 ± 2.9 kg and 6.6 ± 1.4 kg HPD and SPD group respectively; p = 0.32). Fasting blood glucose decreased significantly with no treatment effect. The decrease in HbA1c differed between treatments at 6 months (HPD −0.9 vs. SPD −0.3%; p = 0.039) but not at 12 months. HDL increased significantly with no treatment effects. There were no changes in LDL or blood pressure overall but DBP was lower in the HPD group (p = 0.024) at 12 months. Conclusion: Weight loss improved overall metabolic control in this group of well controlled participants with type 2 diabetes regardless of diet composition. [Copyright &y& Elsevier]

Abstract: To investigate a possible role of the nitrogen-PTS (PTSNtr) in controlling carbon metabolism, we determined the growth of Escherichia coli LJ110 and of isogenic derivatives, mutated in components of the PTSNtr, on different carbon sources. The PTSNtr is a set of proteins homologous to the PEP-dependent phosphotransferase system (C-PTS) that transfers a phosphate group from PEP over EINtr (encoded by ptsP) and NPr (encoded by ptsO) to EIIANtr (encoded by ptsN). Strains deleted in ptsN were characterized by a high acetate production coupled to slow growth on glycolytic substrates. The ΔptsP and the ΔptsO strain showed the same behavior as the parent strain. As the phosphorylation level of EIIANtr in these mutants differed significantly from that of the parent strain, phosphorylation of EIIANtr obviously is not important for its function. During growth in minimal medium with defined carbon sources, EIIANtr was always completely phosphorylated in LJ110. Significant amounts of dephosphorylated EIIANtr were only visible in strains lacking EINtr or NPr. mRNA expression studies on glucose revealed a downregulation of genes encoding TCA cycle enzymes when EIIANtr was absent. 13C-flux analyses confirmed higher fluxes towards acetate and lower fluxes in the TCA cycle in the ptsN mutants but additionally hinted to a slightly but significantly increased flux through the pyruvate dehydrogenase complex (PDH). During growth on succinate the ΔptsN strain accumulated mutations in rpoS, while no rpoS mutants were observed for the ΔptsN-O strain. This hints to an additional function of NPr during growth with succinate. [Copyright &y& Elsevier]

Abstract: Recent clinical trials have changed the management paradigm for diabetic macular edema (DME). There is an urgent need to identify the most effective ways of preventing retinopathy or intervening at an early, asymptomatic stage in order to preserve vision. The rise in the incidence of diabetes is a serious public health concern. Grading and screening programmes help to identify sight threatening diabetic retinopathy in the community early and facilitate timely referral to an ophthalmologist. Systemic therapies for DME target the key modifiable risk factors: metabolic and blood pressure control. There may also be a role for modification of the renin-angiotensin system and for lipid lowering agents. Improved glycemic and blood pressure control remain the most effective ways of reducing morbidity from DME. Fenofibrate also has beneficial effects, but the mechanism for this remains unclear. Multiple new treatments are in the pipeline, and these are expected to change our approach to DME for the first time in 30 years. [Copyright &y& Elsevier]

Abstract: Background: Especially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD. Methods: Based on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated. Results: PD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02). After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD. Conclusion: Clear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care. [Copyright &y& Elsevier]

Objectives: To analyze the association between adherence to physical activity guideline recommendations and metabolic control in patients with type 1 diabetes (DM1). Methods: An observational, cross-sectional study was conducted in 130 adult DM1 patients from Spain with a mean age of 33.9±11.5 years and disease duration of 16.5±9.5 years. We analyzed several clinical, anthropometric and laboratory variables together with information obtained from the Minnesota Leisure Time Physical Activity Questionnaire. Results: Evaluated patients reported an average of 850.6±493.2min of physical activity per week, being classified as light (567.4±425.4min/week), moderate (169.9±212.1min/week) and intense activities (120.6±184.2). Patients who dedicated more time to intense physical activity were younger, had university studies and were males more often than those who spent none or less time on intense physical activity. We observed no differences in HbA1c levels in relation to time dedicated to moderate physical activities. However, patients who dedicated more than 150min to intense physical activity per week had lower levels of HbA1c (HbA1c: 7.2±1.0% versus 7.8±1.1% versus 8.0±1.0% in more than 149min, between 0 and 149min or 0min of intense physical activity per week, respectively). Conclusion: Performing more than 150min of intense physical activity a week is associated with better metabolic control in type 1 Spanish patients. No positive impact in metabolic control was observed in relation to the time spent in moderate physical activity. [ABSTRACT FROM AUTHOR]