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Recent evidence has linked circadian rhythm dysregulation to an increased risk of metabolic disorders. This study explores a potential association between variation in genes regulating the endogenous circadian timing system (clock genes) and the risk of type 2 diabetes (T2D) in a sample of Greek elderly people.Variants within and upstream or downstream of PPARA, PPARD, CLOCK/TMEM165, PER1, PER2 and PER3 genes were genotyped in 716 individuals with T2D (A) and 569 normoglycemic controls (B), and allele frequencies were compared between the groups in a case control study design.Samples were genotyped on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. To avoid the possibility of subjects with prediabetes being included in the control group, people with HbA1c5.7% and fasting glucose100 mg/dl comprised group C (n = 393), for whom a separate analysis was performed (secondary analysis).A protective role against T2D was identified for 14 variants in the PPARA gene. The rs7291444, rs36125344, rs6008384 in PKDREJ, located upstream of PPARA, and rs2859389 in UTS2, located upstream of PER3, demonstrated a protective role against T2D in both analyses. In contrast, rs6744132, located between HES6 and PER2, was positively correlated with T2D risk. Only in the secondary analysis, rs2278637 in VAMP2, located downstream of PER1, and rs11943456 in CLOCK/TMEM165 were found to confer protection against T2D. In a recessive model analysis of all groups, PPARD variants exhibited a protective role against disease.Our findings suggest a possible implication of clock genes in T2D susceptibility. Further studies are needed to clarify the mechanisms that connect circadian rhythm dysfunction and T2D pathogenesis.

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence and a significant burden of long-term complications. Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) are a novel treatment option for T2DM, exerting optimal effects on glucose control and weight loss, and pleiotropic actions. Pharmacogenetics, a promising research field of precision medicine, investigates how gene variations can affect individual response to drug therapy, assuming that the diverse genetic architecture of patients with T2DM could be partly associated with the considerable inter-individual variability in the therapeutic response to GLP-1 RAs. This review aims to summarize current evidence related to T2DM risk variants, affecting the incretin pathway, focus on the pharmacogenetics of the GLP-1 RA liraglutide, and discuss their potential clinical implications in the management of this complex disorder. Methods: A literature search was performed using electronic biomedical databases, and the findings of key studies are summarized and discussed in this narrative review. Results: Available evidence suggests the involvement of genetic polymorphisms in GLP-1 Rgene in variation in glycemic response, metabolic parameters and gastric emptying in people treated with liraglutide. Polymorphisms in CNR1, CTRB1/2, TMEM114 and CHST3 loci were also shown to be implicated in the disturbance of the incretin homeostasis in T2DM. These findings warrant further investigation by future studies. Conclusion: Robust findings from pharmacogenetic studies might be used to identify good responders to liraglutide treatment, in terms of both glycemic and weight control, thus reinforcing the patient-centered approach of T2DM management.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering agents which have changed the landscape of diabetes therapy, due to their remarkable cardiorenal protective properties. The attack of severe acute respiratory syndrome coronavirus 2 on the heart and kidneys shares similarities with diabetes; therefore, the notion that SGLT2i might have a role in the future management of Coronavirus Disease 2019 (COVID-19) is based on a solid pathophysiological hypothesis. SGLT2i have been proved to decrease the expression of proinflammatory cytokines, ameliorate oxidative stress and reduce sympathetic activity, thus resulting in downregulation of both systemic and adipose tissue inflammation. On the other hand, they have been linked to an increased risk of euglycemic diabetic ketoacidosis. Therefore, the efficacy and safety of SGLT2i in COVID-19 are still debatable and remain to be clarified by ongoing randomized trials, to assess whether the benefits of treatment with these drugs outweigh the potential risks.

Emerging data are linking coronavirus disease 2019 (COVID‐19) with an increased risk of developing new‐onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID‐19‐induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium‐glucose co‐transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium‐dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID‐19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID‐19 outweigh potential risks, particularly with respect to drug‐induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

The prevalence of gestational diabetes mellitus (GDM) has been following an increasing trend during the past few years, with available epidemiological data suggesting that it affects approximately ...

A hypocaloric diet, based on Orthodox fasting (OF) was followed by 29 overweight adults. A low-calorie, 16/8, time restricted eating (TRE) pattern was followed by 16 age- and weight-matched participants. Anthropometric, lipid, glycaemic and inflammation markers were assessed at baseline, at the end of the intervention (7 weeks from baseline) and 6 weeks after the cessation of diets (13 weeks from baseline). There was a trend of weight loss in both groups, which was evident at week 7 (TRE: -2.1 ± 1.0; OF: -2.0 ± 0.5 kg

Background Hyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose-lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns. Aim To present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk-benefit balance of such an approach in the era of cardiovascular outcomes trials. Methods PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. Results There is no robust evidence to suggest the use of metformin, thiazolidinediones, sulfonylureas and sodium-glucose co-transporter-2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase-4 inhibitors in inpatients with type 2 diabetes is supported by a few, well-designed, randomized controlled trials. These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose-lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase-4 inhibitors are co-administered with insulin, in individuals with mild to moderate hyperglycaemia and a stable clinical condition. Conclusion The administration of dipeptidyl peptidase-4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.

A number of studies have investigated primary and secondary prevention strategies for type 1 diabetes (T1D), since early interventions might improve long-term outcomes through the amelioration of immune processes and the preservation of beta-cell mass. Primary prevention trials focus on genetically at-risk individuals prior to the appearance of autoimmunity, whereas secondary prevention trials aim to halt the progression of complete beta-cell destruction in subjects with established islet autoimmunity (IA). Different approaches have been tested so far, focusing on both pharmaceutical (insulin and monoclonal antibodies) and non-pharmaceutical (vitamin D, omega-3 fatty acids, probiotics, and nicotinamide) interventions, as well as on environmental factors that are believed to trigger autoimmunity in T1D (cow's milk, gluten, and bovine insulin). Albeit certain strategies have displayed efficacy in reducing IA development rates, most efforts have been unsuccessful in preventing the onset of the disease in high-risk individuals. Moreover, significant heterogeneity in study designs, included populations, and explored outcomes renders the interpretation of study results challenging. The aim of this narrative review is to present and critically evaluate primary and secondary prevention strategies for T1D, seeking to fill existing knowledge gaps and providing insight into future directions.

Introduction Despite the progress made in the treatment of heart failure with reduced ejection fraction (HFrEF) in recent years, the prognosis of the disease remains poor, with ventricular arrhythmias (VA) contributing significantly to increased mortality. Areas covered A recently published post hoc analysis of the DAPA-HF trial evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin versus placebo on the incidence of VA, resuscitated cardiac arrest, or sudden death among people with HFrEF. During a median follow-up of 18.2 months, the composite primary outcome occurred in 140 (5.9%) people who received dapagliflozin compared to 175 (7.4%) participants in the placebo arm (hazard ratio 0.79; 95 confidence interval 0.63-0.99, P=0.037). Animal studies suggest that SGLT2i could ameliorate the deleterious effects of myocardial injury, through various mechanisms, including reduced sympathetic activity, improved oxidative stress, tissue oxygenation, autophagy, heart energy metabolism, and promotion of cardiac remodeling. Expert opinion Taken together, the above findings indicate a place for SGLT2i in future trials investigating novel treatments to improve survival in patients with acute cardiovascular episodes. This is primarily applicable for acute decompensated HF; however, their use could also be evaluated in other conditions that induce VA, such as acute coronary syndromes.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a promising therapeutic option for hyperglycemia and its complications. However, metformin remains the first-line pharmacological treatment in most algorithms for type 2 diabetes (T2D). Although metformin is generally believed to exert positive effects on cardiovascular (CV) outcomes, relevant data are mainly observational and potentially overinterpreted. Yet, it exerts numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities. CV outcome trials have demonstrated cardiorenal protection with SGLT2i among people at high CV risk and mostly on concomitant metformin therapy. However, post hoc analyses of these trials suggest that the cardiorenal effects of gliflozins are independent of background treatment and consistent across the full spectrum of CV risk. Considering the importance of addressing hyperglycemia as a means of preventing diabetic complications and significant knowledge gaps, particularly regarding the cost-effectiveness of SGLT2i in drug-naive populations with T2D, the position of metformin in the management of people with diabetes at low CV risk remains solid for the moment. On the other hand, available evidence-despite its limitations-suggests that specific groups of people with T2D, particularly those with heart failure and kidney disease, could probably benefit more from treatment with SGLT2i. This narrative mini-review aims to discuss whether current evidence justifies the use of SGLT2i as the first-line treatment for T2D.

The exact mechanisms mediating the metabolic effects of Orthodox fasting remain unclear. Plasma adiponectin, biochemical and anthropometrical data were evaluated in 55 Orthodox fasters (OF) and 42 time-restricted eating controls (all women, mean age 47.8 years) at three time points: baseline, end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). In the OF group, there was an increase in adiponectin values at 12 weeks compared with baseline (9815.99 vs 8983.52 mg/ml, p = 0.02) and a reduction in body fat mass between baseline and 12 weeks (35.44 vs 32.17%, p = 0.004) and between 7 and 12 weeks (35.33 vs 32.17%, p = 0.003). In the same group, an inverse correlation between adiponectin and waist circumference values was observed over the entire study period. Our results provide novel evidence that Orthodox fasting has favourable metabolic effects related to improved adiponectin concentrations.

Sotagliflozin is a dual sodium-glucose co-transporter (SGLT) 2 inhibitor, manifesting a 20-fold higher inhibitory activity for SGLT2 than for SGLT1. Differences in SGLT2 over SGLT1 selectivity of the available agents have been proposed to relate to variability in efficacy and safety characteristics. In contrast to other SGLT2 inhibitors, the cardiorenal effects of sotagliflozin in type 2 diabetes had not been explored until recently, when the results of SOLOIST-WHF (focusing on heart failure [HF] outcomes) and SCORED (focusing on renal outcomes) were published. In SOLOIST-WHF, sotagliflozin reduced the risk of the primary composite outcome of cardiovascular (CV) death and hospitalizations and urgent visits for HF. The findings showed that the risk reduction was consistent in people with reduced but also in those with preserved ejection fraction (EF). In SCORED, sotagliflozin significantly reduced the primary end point of CV deaths, hospitalizations for HF, and urgent visits for HF. A reduction in glycated hemoglobin was evident even in participants with estimated glomerular filtration rate values below 30 mL/min/1.73 m2. SCORED is also the first trial to illustrate the benefits of the class across the full range of albuminuria. Moreover, the endpoint of stroke was significantly reduced by 34% in the sotagliflozin compared with the placebo group. The findings of the two studies provide novel insights into the clinical utility of SGLT2 inhibitors, particularly with respect to the early initiation in stable HF, the benefits in HF with preserved EF, the glucose-lowering efficacy in people with severe renal impairment and their potential to improve atherosclerotic vascular disease, including stroke, outcomes.

“Two roads diverged in a yellow wood,And sorry I could not travel both”Robert Frost in the “Road Not Taken”According to the most recent ADA/EASD consensus report on the management of hyperglycemia ...

The provocative idea that type 2 diabetes (T2D) may be a surgically treated disorder is based on accumulating evidence suggesting impressive remission rates of obesity and diabetes following bariatric surgery interventions. According to the "anti-incretin" theory, ingestion of food in the gastrointestinal (GI) tract, apart from activating the well-described incretin effect, also results in the parallel stimulation of a series of negative feedback mechanisms (anti-incretin effect). The primary goal of these regulations is to counteract the effects of incretins and other postprandial glucose-lowering adaptive mechanisms. Disruption of the equilibrium between incretins and anti-incretins could be an additional pathway leading to the development of insulin resistance and hyperglycemia. This theory provides an alternative theoretical framework to explain the mechanisms behind the optimal effects of metabolic surgery on T2D and underlines the importance of the GI tract in the homeostatic regulation of energy balance in humans. The anti-incretin concept is currently based on a limited amount of evidence and certainly requires further validation by additional studies. The aim of the present review is to discuss and critically evaluate recent evidence on the anti-incretin theory, providing an insight into current state and future perspectives.

People with diabetes, particularly those being insulin treated, have been for many years considered ineligible for diving, because of the high risk of adverse events. Blood glucose levels tend to decline during diving, probably because of changes in insulin requirements and resistance, due to increased physical activity and effects of hyperbaric environment on glucose tolerance. Strict adherence to safety protocols, in conjunction with optimal physical status, lack of diabetic complications (especially impaired awareness of hypoglycaemia) and satisfactory baseline glycaemic control, seem to minimise the risk of complications during diving. The integration of modern technology into diabetes management, providing potential for underwater continuous glucose monitoring, can be useful in optimising metabolic control before, during and after diving. Despite the significant progress been made on safety issues, there is still a need to implement the relevant recommendations into divers' everyday practice. Existing evidence is mainly derived from small studies and there is a wide heterogeneity in terms of study designs and explored outcomes, rendering the extraction of definitive conclusions challenging. The aim of this review is to present and critically evaluate available evidence, use of technology, and gaps in existing knowledge that deserve further evaluation by future studies.

Monogenic Diabetes is relatively rare, representing only 1-2% of total diabetes cases; nevertheless, it is often misdiagnosed primarily as type 1 diabetes, leading to unnecessary insulin therapy and delayed recognition of affected family members. In the present article, we describe a case of a young, male patient who presented with hyperglycemia in the absence of ketosis and following genetic testing; he proved to harbor the loss-of-function p.Arg1353His (c.4058G>A) mutation in the ABCC8 gene, inherited from his mother. This mutation has been previously described in patients with Congenital Hyperinsulinism. Furthermore, different mutations in the ABCC8 gene have been linked with MODY 12, type 2, and gestational diabetes; however, to the best of our knowledge, this is the first report that associates this specific mutation with diabetes phenotype. ABCC8-related diabetes is characterized by remarkable heterogeneity in terms of clinical presentation and therapeutic approach. Early diagnosis and individualized treatment are essential to achieving metabolic targets and avoiding long-term diabetes complications.

Exposure to high altitude activates several complex and adaptive mechanisms aiming to protect human homeostasis from extreme environmental conditions, such as hypoxia and low temperatures. Short-term exposure is followed by transient hyperglycemia, mainly triggered by the activation of the sympathetic system, whereas long-term exposure results in lower plasma glucose concentrations, mediated by improved insulin sensitivity and augmented peripheral glucose disposal. An inverse relationship between altitude, diabetes, and obesity has been well documented. This is the result of genetic and physiological adaptations principally to hypoxia that favorably affect glucose metabolism; however, the contribution of financial, dietary, and other life-style parameters may also be important. According to existing evidence, people with diabetes are capable of undertaking demanding physical challenges even at extreme altitudes. Still, a number of issues should be taken into account, including the increased physical activity leading to changes in insulin demands and resistance, the performance of measurement systems under extreme weather conditions and the potential deterioration of metabolic control during climbing expeditions. The aim of this review is to present available evidence in the field in a comprehensive way, beginning from the physiology of glucose homeostasis adaptation mechanisms to high altitudes and ending to what real life experience has taught us.

OBJECTIVES: Christian Orthodox fasting (COF), a periodical vegetarian subset of the Mediterranean diet, has been proven to exert beneficial effects on human health. Athonian fasting is a pescetarian COF variation, where red meat is strictly restricted throughout the year. Previous studies have examined the COF nutritional synthesis and health effects in general population fasters (GF) and Athonian monks (AM), separately. The aim of this study is to comparatively evaluate the characteristics and effects of this nutritional advocacy between the two populations. METHODS: The study included 43 male GFs (20-45 y of age) and 57 age-matched male AMs following COF. Dietary intake data were collected in both groups during a restrictive (RD) and a nonrestrictive (NRD) day. Nutritional, cardiometabolic, and anthropometric parameters were compared between the two cohorts. RESULTS: AM presented lower daily total caloric intake for both RD (1362.42 ± 84.52 versus 1575.47 ± 285.96 kcal, P < 0.001) and NRD (1571.55 ± 81.07 versus 2137.80 ± 470.84 kcal, P < 0.001) than GF.They also demonstrated lower body mass index (23.77 ± 3.91 versus 28.92 ± 4.50 kg/m2, P

Irisin has been recently identified as an adipomyokine produced during physical activity and involved in the browning of adipose tissue. Despite the emerging evidence suggesting an inverse relationship between irisin plasma concentrations and adverse metabolic outcomes, the exact impact of diet on irisin levels remains obscure. Thus, we aimed to assess the effects of two dietary patterns, Christian Orthodox fasting (OF) and 16:8 time-restricted eating (TRE), on circulating irisin levels among overweight, metabolically healthy, adults. Plasma irisin, glucose and lipid parameters, calcium homeostasis, and anthropometry were evaluated in 29 Orthodox fasters and 14 age and body mass index (BMI)-matched TRE controls (mean age and BMI, 48.8 years and 28.7 kg/m2, respectively) at three, distinct time points—before the implementation of the energy-restricted diets (baseline), at the end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). Repeated measures analysis was applied to assess differences between the two groups and the effect of several indices on irisin levels at all three time points. At 12 weeks, the OF group manifested higher irisin concentrations compared with both its baseline values (64.3 ± 54.4 vs. 43.6 ± 42.2 ng/mL, p = 0.01) and those of the TRE group at the same time point (64.3 ± 54.4 vs. 44.2 ± 26.6 ng/mL, p = 0.04). Glycemic, lipid, and anthropometric parameters were not found to correlate with irisin levels. In contrast, parathyroid hormone (PTH) concentrations at 12 weeks correlated with irisin concentrations (p = 0.04), indicating that lower values of irisin are expected for higher PTH measurements. The findings of this pilot study suggest favorable long-term effects of OF on irisin levels. The interplay between irisin, PTH, and diet warrants further investigation.

Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored approach in its management is becoming increasingly evident. There is emerging evidence that irregular immune responses contribute to the development of hyperglycemia in T2D and, inversely, that insulin resistance is a component of the pathogenesis of autoimmune diabetes. Nevertheless, it has not yet been fully elucidated to what extent the presence of conventional autoimmune markers, such as autoantibodies, in subjects with T2D might affect the natural history of the disease and particularly each response to various treatments. The challenge for future research in the field is the discovery of novel genetic, molecular, or phenotypical indicators that would enable the characterization of specific subpopulations of people with T2D who would benefit most from the addition of immunomodulatory therapies to standard glucose-lowering treatment. This narrative review aims to discuss the plausible mechanisms through which the immune system might be implicated in the development of metabolic disturbances in T2D and obesity and explore a potential role of immunotherapy in the future management of the disorder and its complications.

For seven weeks, 37 overweight adults followed a hypocaloric diet based on Orthodox Fasting (OF). A hypocaloric, time restricted eating (TRE) plan (eating between 08:00 to 16:00 h, water fasting from 16:00 to 08:00 h) was followed by 23 Body Mass Index (BMI)-matched participants. Anthropometric, glycaemic and inflammation markers and serum lipids were assessed before and after the diets. Both OF and TRE groups demonstrated reductions in BMI (28.54 ± 5.45 vs 27.20 ± 5.10 kg/m2, p

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti‐inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel‐treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2‐arm, multicenter, open‐label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow‐up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex‐adjusted hazard ratio [HR], 0.468; 95% CI, 0.252–0.870; P =0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex‐adjusted HR, 0.38; 95% CI, 0.15–0.98; P =0.046) and improved the ankle‐brachial index and pain‐free walking distance values ( P =0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex‐adjusted HR, 1.080; 95% CI, 0.579–2.015; P =0.809). Conclusions Adjunctive cilostazol to clopidogrel‐treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02983214.

Background Latent Autoimmune Diabetes in Adults (LADA) is characterised by pathophysiological and clinical heterogeneity. Hence, the optimal treatment strategy for this type of diabetes remains a clinical challenge. Aim To discuss the potential of a modern therapeutic approach for LADA in the context of the novel findings of cardiovascular outcomes trials and stress the controversies surrounding LADA and the barriers in the effective management of people with this type of diabetes. Methods We performed a literature search in major biomedical databases in order to retrieve relevant literature. The results of key studies, along with the authors' clinical experience and perspective, are summarised and discussed in this narrative, mini review article. Results Insulin remains the primary treatment choice in individuals with low C-peptide levels. Although cardiovascular outcomes trials have mainly recruited participants with type 2 diabetes, recent data suggest that the cardiorenal protective properties of the new therapies are even present in people without diabetes and thus, the extrapolation of their results on LADA individuals sounds reasonable. Therefore, sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists should be considered for the management of people with preserved insulin production being at high cardiovascular risk. The risk of diabetic ketoacidosis with SGLT2is requires increased vigilance by treating physicians. Conclusions Individualisation, preservation of beta-cell mass and function and cardiorenal protection are the new challenges in LADA therapy.

Older people (those aged 65 years or more) with diabetes comprise a heterogenous group of patients with special needs and features; this is particularly true for those aged 75 years or more. It is important that individualized glycemic targets be adopted in this population, after considering life expectancy, presence of diabetic complications and other comorbidities. In general, less rigorous targets and avoidance of overtreatment seems to be a reasonable strategy in daily clinical settings. There is a paucity of data regarding the efficacy and safety of various hypoglycemic agents, especially for those aged over 75. The evidence suggests that sulfonylureas and insulin regimens should be used with caution due to a high risk of hypoglycemia. Dipeptidyl peptidase-4 inhibitors are a good choice for the management of diabetes in older age groups, although a warning against the use of specific agents in people with heart failure is valid. There are insufficient data to decide whether the cardiorenal protective properties of sodium-glucose co-transporter 2 inhibitors outweigh the risks associated with these drugs. The use of glucagon-like peptide-1 receptor agonists by older patients is supported not only by their good safety and efficacy profiles, but also by their potential to improve glucose-independent outcomes, through their pleiotropic actions. The aim of this narrative review is to summarize the evidence on glycemic targets and optimal therapeutic approaches for older patients with type 2 diabetes and discuss the risk-benefit balance of various therapeutic approaches in this group.

Previous research has demonstrated an association between genetic variation in the CTRB1/2 gene and response to incretin therapies. We aimed to evaluate the role of CTRB1/2 rs7202877 (T>G) polymorphism in glycemic response to liraglutide among Greek people with T2D. 116 adults with T2D (51% female, mean BMI 35.4±6.4 kg/m2, mean age 68.3±10.9 years), who had been on treatment with liraglutide for at least 6 months were genotyped for the rs7202877 polymorphism, using real-time PCR. Responders met at least one of the following criteria: i) achievement of good glycemic control defined as HbA1c level of Disclosure A. Kyriakidou: None. A.V. Kyriazou: Research Support; Self; Novo Nordisk A/S. T. Koufakis: None. Y. Vasilopoulos: None. I. Avramidis: None. S. Baltagiannis: None. E. Manthou: None. D.G. Goulis: None. P. Zebekakis: None. K. Kotsa: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Menarini Group. Other Relationship; Self; Novo Nordisk Inc. Funding Novo Nordisk (91220)

Previous studies have demonstrated an association between gene polymorphisms and weight loss response to GLP-1 RA therapy. We aimed to evaluate the role of rs7202877 (T>G) polymorphism in CTRB1/2 gene in weight loss response to liraglutide among Greek people with T2D. 116 adults with T2D (51% female, mean BMI 35.4±6.4 kg/m2, mean age 68.3±10.9 years), who had been on treatment with liraglutide for at least 6 months were genotyped for the rs7202877 polymorphism, using real-time PCR. Responders were defined as subjects who lost 3% or more of their baseline weight, whereas non-responders those who lost less than 3% of their initial weight after 3 or 6 months of liraglutide administration. 77 (66%) individuals were classified as responders and 39 (34%) as non-responders. 97 (84%) patients were homozygous for the wild type rs7202877 T allele (TT) and 19 (16%) patients carried one polymorphic G allele (TG). The probability of being weight loss responder was increased by 12%, when carrying the G allele; however, the result did not achieve significance (OR:1.12, 95% 0.4, 3.2, P=0.84). In the response group, weight was reduced by 5.9 kg (95% CI: -6.9, -4.9, P Disclosure A.V. Kyriazou: Research Support; Self; Novo Nordisk A/S. A. Kyriakidou: None. T. Koufakis: None. Y. Vasilopoulos: None. I. Avramidis: None. S. Baltagiannis: None. E. Manthou: None. D.G. Goulis: None. P. Zebekakis: None. K. Kotsa: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Menarini Group. Other Relationship; Self; Novo Nordisk Inc. Funding Novo Nordisk (91220)

Background Strict glycaemic control early in the treatment process has been shown to reduce the occurrence of micro- and macro- vascular complications of diabetes in the long-term. Thus, treatment guidelines advise early intensification of treatment to achieve glycaemic control goals. However, evidence in Greece suggests that, despite guideline recommendations, glycaemic control among patients with T2DM remains challenging. This study presents the demographic and clinical characteristics of patients with T2DM in Greece using data from an electronic registry designed specifically for this treatment category and investigates the factors that are independently associated with glycaemic control. Methods This is a multi-center, observational, cross-sectional study to investigate epidemiological and clinical factors affecting glycaemic control among patients with T2DM in Greece. Data was collected via a web-based disease registry, the Diabetes Registry, which operated from January 1st to December 31st, 2017. Five large specialized diabetes centers operating in Greek hospitals participated in the study. Results Data for 1141 patients were retrieved (aged 63.02 ± 12.65 years, 56.9% male). Glycaemic control (Hb1Ac Conclusion Inadequate lipid control, family history of diabetes and presence of obesity (ΒΜΙ ≥ 30 kg/m2) were associated with poor glycaemic control among study sample, whereas use of injectable antidiabetic agents was less likely to be associated with poor glycaemic control. These findings indicate how complex optimal glycaemic control is, highlighting the need for tailored interventions in high-risk subpopulations with T2DM.

The exact changes in physiology of individuals undergoing metabolic surgery are still under investigation. According to the foregut hypothesis, surgical bypass of certain parts of the gastrointestinal (GI) tract leads to the downregulation of biological factors that are secreted by the upper GI system, and compete against incretin actions (anti-incretins). Those molecules have a negative effect on insulin secretion, action, and sensitivity. Various biological factors have been hypothesized to exert anti-incretin properties, including dopamine, ghrelin, enterostatin, and oxyntomodulin. Disruption of the balance between incretins and anti-incretins could be considered as a pathway leading to the development of obesity and insulin resistance.

Absence of adequate maternal vitamin D supplementation and decreased maternal ultraviolet exposure during pregnancy are key determinants for the manifestation of neonatal hypovitaminosis D at birth. These parameters may vary, according to country-specific dietary patterns, health policies and sunshine exposure. We aimed to investigate differences in calcium metabolism and anthropometric profiles according to neonatal vitamin D status at birth, in a sunny region of Northern Greece. A secondary aim was to identify maternal parameters as risk factors for developing neonatal vitamin D deficiency at birth. A total of 129 mother-neonate pairs were included in the study and classified into three groups, according to neonatal 25-hydroxy-D [25(OH)D)] concentrations at birth [deficiency (30 nmol/l), insufficiency (30-50 nmol/l) and sufficiency (50 nmol/l)]. Neonatal biochemical and anthropometric profiles and maternal demographic, social, dietary and biochemical profiles were comparatively evaluated between the three groups. Univariate and multivariate logistic regression was performed to identify independent associations of maternal factors with neonatal vitamin D status. Vitamin D deficient-neonates manifested higher parathyroid hormone (7.20 ± 2.60 vs 5.50 ± 1.50 pg/ml, p = 0.01) and lower corrected calcium (10.70 ± 0.70 vs 11.30 ± 1.30 mg/dl, p = 0.02) concentrations compared with vitamin d-insufficient neonates. Mothers of vitamin D deficient and insufficient neonates had a lower total of 25(OH)D (31.7 ± 19.2 and 36.5 ± 22.3 vs 53.3 ± 39.0 nmol/l, p 0.01) and 25(OH)D

Orthodox fasting (OF) is deeply integrated in the dietary behavior of the Orthodox population, adopted as the predominant nutritional pattern by a large proportion of Orthodox Christians for prolonged periods annually. OF could be characterized as a periodical vegetarian advocacy, demonstrating several common characteristics with the typical Mediterranean diet and incorporating the majority of its cardioprotective and health-promoting mechanisms, including calorie restriction and reduced intake of dietary cholesterol and fatty acids. These features are translated into optimal effects on human health, particularly with respect to plasma lipid concentrations. However, studies having determined the impact of OF on specific populations, such as patients with chronic diseases, including diabetes and cardiovascular disorders, are currently lacking. In addition, dietary limitations of specific vitamins (D and B12) and minerals (mainly calcium) should be considered by health-care practitioners before suggesting this nutritional pattern, at least until robust evidence on this topic become available.

Previous studies have reported inconclusive results regarding the effects of Orthodox religious fasting (OF) on common cardiovascular risk factors, including arterial hypertension and diabetes. Contrariwise, an optimal effect on dyslipidemia has been demonstrated and significant reductions in total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) concentrations, in Orthodox populations without comorbidities, have been consistently reported. This favorable effect on lipid homeostasis is probably facilitated by a broad lifestyle modification related to OF, extended beyond dietary habits. However, several clinical issues require further clarification by future trials including the efficacy and safety of OF in specific groups of patients with dyslipidemia, mainly those with cardiovascular disease and diabetes, the effects of OF on high-density lipoprotein-cholesterol (HDL-C), the dietary limitations of specific vitamins and minerals during fasting, as well as the optimal duration of this dietary intervention. The present article aims to discuss, whether there is a strong enough theoretical background, to currently support the implementation of OF as a medical nutrition therapy for dyslipidemia in the daily clinical setting, with a discourse on available evidence and future research agenda.

We aimed to evaluate sex differences in changes of lipid profiles in a cohort of metabolically healthy adults following Orthodox fasting (OF), as well as to assess a potential role of vitamin D status in mediating these variations. 45 individuals (24 premenopausal females, 53.3 %) with mean age 48.3 ± 9.1 years and mean Body Mass Index 28.7 ± 5.8 kg/m2 were prospectively followed for 12 weeks. Anthropometry, dietary and biochemical data regarding serum lipids, and vitamin D status were collected at baseline, 7 weeks after the implementation of OF, and 5 weeks after fasters returned to their standard dietary habits (12 weeks from baseline). According to 25-hydroxy-vitamin D [25(OH)D] measurements, participants were divided into two groups: those with concentrations above and below the median of values. Females with 25(OH)D concentrations below the median manifested a non-significant reduction by approximately 15 % in total and low-density lipoprotein cholesterol during the fasting period, followed by a significant increase 5 weeks after OF cessation (170.7 vs. 197.5 and 99.6 vs. 121.0 mg/dl respectively, p