The effect of bolus advisors on glycaemic parameters in adults with diabetes on intensive insulin therapy: A systematic review with meta-analysis.

AIM: To conduct a systematic review with meta-analysis to provide a comprehensive synthesis of randomized controlled trials (RCTs) and prospective cohort studies investigating the effects of currently available bolus advisors on glycaemic parameters in adults with diabetes. MATERIALS AND METHODS: An electronic search of PubMed, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov was conducted in December 2022. The risk of bias was assessed using the revised Cochrane Risk of Bias tool. (Standardized) mean difference (MD) was selected to determine the difference in continuous outcomes between the groups. A random-effects model meta-analysis and meta-regression were performed. This systematic review was registered on PROSPERO (CRD42022374588). RESULTS: A total of 18 RCTs involving 1645 adults (50% females) with a median glycated haemoglobin (HbA1c) concentration of 8.45% (7.95%-9.30%) were included. The majority of participants had type 1 diabetes (N = 1510, 92%) and were on multiple daily injections (N = 1173, 71%). Twelve of the 18 trials had low risk of bias. The meta-analysis of 10 studies with available data on HbA1c showed that the use of a bolus advisor modestly reduced HbA1c compared to standard treatment (MD -011%, 95% confidence interval -0.22 to -0.01; I2 = 0%). This effect was accompanied by small improvements in low blood glucose index and treatment satisfaction, but not with reductions in hypoglycaemic events or changes in other secondary outcomes. CONCLUSION: Use of a bolus advisor is associated with slightly better glucose control and treatment satisfaction in people with diabetes on intensive insulin treatment. Future studies should investigate whether personalizing bolus advisors using artificial intelligence technology can enhance these effects.

Addition of Dulaglutide or Empagliflozin to Standard-of-Care Treatment: Effect on Liver Steatosis in Patients With Type 2 Diabetes Mellitus.

Background Patients with liver steatosis and diabetes mellitus can benefit from medications like glucagon-like peptide 1 receptor agonists or sodium-glucose co-transporter 2 inhibitors, as far as both hyperglycemia and fatty liver are concerned. Studies comparing members of both these families have not yet been published. We aimed to compare the effects of Empagliflozin and Dulaglutide, focusing primarily on liver steatosis. Methodology This prospective, observational, controlled study enrolled 78 patients from two centers in Athens, Greece. Adults with type 2 diabetes mellitus (DM2) and nonalcoholic fatty liver disease were assigned to one of three groups and received either Empagliflozin or Dulaglutide or any other medical treatment deemed appropriate by their physician. The primary endpoint was the reduction in liver fat fraction, assessed using magnetic resonance imaging-proton density fat fraction. Additionally, we evaluated the proportion of patients achieving a relative reduction above 30% of their initial liver fat concentration. Results The Empagliflozin group exhibited a reduction in liver fat fraction. Furthermore, the percentage of patients with a relative reduction of liver steatosis, >30%, was significantly larger in this group, compared to the Dulaglutide and Control groups. Significant body weight reduction was observed in all three groups, but no improvement in fibrosis assessing scores was noted. Conclusions Empagliflozin is effective in improving liver steatosis, while Dulaglutide does not exhibit a similar effect. Larger studies, comparing these or related agents, are necessary, to further assess benefits in patients with DM2 and nonalcoholic fatty liver.

At any Level of Adiposity, Relatively Elevated Leptin Concentrations Are Associated With Decreased Insulin Sensitivity.

CONTEXT: The impact of obesity on glucose homeostasis has high interindividual variability, which may be partially explained by different adipokine concentrations. Leptin regulates energy balance and metabolism, and although its plasma levels are proportional to fat mass, they vary significantly across individuals with the same level of adiposity. OBJECTIVE: We tested whether glucose homeostasis differs in subjects with similar degrees of adiposity but different leptin levels. METHODS: We analyzed 1290 healthy adults from the Relationship Between Insulin Sensitivity and Cardiovascular Disease study cohort (30-60 years; male/female, 577/713; body mass index [BMI], 25 ± 3 kg/m2) characterized for body composition and metabolic variables with a 75-g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp, ß-cell function, and lipidomics. RESULTS: Individuals were divided into relatively high and low leptin (RHL and RLL) if they were above or below the sex-specific leptin-fat mass (%) regression. Despite similar glucose tolerance, RHL showed markedly higher fasting and oral glucose tolerance test insulin concentration (+30% and +29%, respectively; P < .0001) and secretion (+17% and +11%, respectively; P < .0001). Regardless of BMI, RHL individuals had lower whole-body (-17-23%, P < .0001) and adipose tissue insulin sensitivity (-24%, P < .0001) compared with RLL. Notably, lean RHL individuals showed similar insulin sensitivity and ß-cell function to RLL individuals with overweight/obesity. CONCLUSION: Subjects with leptin levels that are inappropriately elevated for their fat mass show whole-body/adipose tissue insulin resistance and hyperinsulinemia, regardless of BMI.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 µSiemens) and estimated glomerular filtration rate (eGFR). RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Glycemia is associated with subclinical atherosclerosis through renal function in nondiabetic apparently healthy adults: a mediation analysis.

The causative associations between glycemia and early alterations in renal and vascular function remain unclear. To examine the interplay among glycemia, renal function, and markers of subclinical atherosclerosis in apparently healthy subjects. Nondiabetic (30-60 years old) individuals (n = 205) without chronic kidney disease or cardiovascular disease were consecutively recruited from a cardiovascular prevention clinic. All subjects underwent arterial stiffness assessment by measuring the carotid-femoral pulse wave velocity (cfPWV). Glomerular filtration rate (GFR) was estimated by CKD-EPI equation. Study procedures were identical in the two visits (median follow-up 66 months). We employed structural equation modeling (SEM) analysis to investigate the directionality of associations. Baseline fasting plasma glucose (FPG) was independently and inversely associated with GFR (p = 0.008). GFR was significantly associated with cfPWV (p < 0.001) at baseline. By SEM analysis decreasing baseline GFR directly correlated with increasing cfPWV (p = 0.003) whereas FPG correlated with cfPWV indirectly through GFR (mediation) (P = 0.032). FPG did not mediate the effect of GFR on cfPWV (P = 0.768). SEM analysis of longitudinal data revealed bidirectional correlations between changes in FPG and GFR (P < 0.001). Alterations in GFR were directly related to changes in cfPWV (p < 0.001) whereas FPG only indirectly correlated with cfPWV through GFR changes (P = 0.002). In apparently healthy nondiabetic subjects, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status. These findings provide the first clinical evidence supporting the directionality between kidney function and glycemia in nondiabetic subjects leading to vascular dysfunction. In apparently healthy nondiabetic subjects, without cardiovascular disease or chronic kidney disease, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status.

Diabetes and COVID-19; A Bidirectional Interplay.

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection.

AIMS: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after COVID-19 infection. METHODS AND RESULTS: In a case-control prospective study, we included 70 patients 4 months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID-19 patients had similar CFR and FMD as hypertensives (2.48 ± 0.41 vs. 2.58 ± 0.88, P = 0.562, and 5.86 ± 2.82% vs. 5.80 ± 2.07%, P = 0.872, respectively) but lower values than controls (3.42 ± 0.65, P = 0.0135, and 9.06 ± 2.11%, P = 0.002, respectively). Compared to controls, both COVID-19 and hypertensives had greater PBR5-25 (2.07 ± 0.15 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid-femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/s, P = 0.036) and impaired left and right ventricular GLS (-19.50 ± 2.56% vs. -19.23 ± 2.67%, P = 0.864 vs. -21.98 ± 1.51%, P = 0.020 and -16.99 ± 3.17% vs. -18.63 ± 3.20%, P = 0.002 vs. -20.51 ± 2.28%, P < 0.001). MDA and thrombomodulin were higher in COVID-19 patients than both hypertensives and controls (10.67 ± 0.32 vs 1.76 ± 0.03, P = 0.003 vs. 1.01 ± 0.05 nmol/L, P = 0.001 and 3716.63 ± 188.36 vs. 3114.46 ± 179.18 pg/mL, P = 0.017 vs. 2590.02 ± 156.51 pg/mL, P < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers. CONCLUSIONS: SARS-CoV-2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection.

Early and late endocrine complications of COVID-19.

Endocrine system plays a vital role in controlling human homeostasis. Understanding the possible effects of COVID-19 on endocrine glands is crucial to prevent and manage endocrine disorders before and during hospitalization in COVID-19-infected patients as well as to follow them up properly upon recovery. Many endocrine glands such as pancreas, hypothalamus and pituitary, thyroid, adrenal glands, testes, and ovaries have been found to express angiotensin-converting enzyme 2 receptors, the main binding site of the virus. Since the pandemic outbreak, various publications focus on the aggravation of preexisting endocrine diseases by COVID-19 infection or the adverse prognosis of the disease in endocrine patients. However, data on endocrine disorders both during the phase of the infection (early complications) and upon recovery (late complications) are scarce. The aim of this review is to identify and discuss early and late endocrine complications of COVID-19. The majority of the available data refer to glucose dysregulation and its reciprocal effect on COVID-19 infection with the main interest focusing on the presentation of new onset of diabetes mellitus. Thyroid dysfunction with low triiodothyronine, low thyroid stimulating hormone, or subacute thyroiditis has been reported. Adrenal dysregulation and impaired spermatogenesis in affected men have been also reported. Complications of other endocrine glands are still not clear. Considering the recent onset of COVID-19 infection, the available follow-up data are limited, and therefore, long-term studies are required to evaluate certain effects of COVID-19 on the endocrine glands.

The Predictive Low Glucose Management System in Prevention of Clinically Significant Hypoglycemia in Type 1 Diabetes. A Preliminary Study Identifying the Most Common Events Leading Up to Hypoglycemia During Insulin Pump Therapy.

BACKGROUND/AIM: Prevention of hypoglycemia remains a major challenge in diabetic management, despite the introduction of modern insulin pumps in daily clinical practice. The Low Glucose Suspend (LGS) and the newer Predictive Low Glucose Management (PLGM) systems incorporated in the Medtronic insulin pumps have shown promising results in prevention of hypoglycemia. Our aim was to evaluate the effect of the 2 systems relative to the frequency of clinically significant hypoglycemia in Type 1 diabetes (T1DM). In addition, we investigated the events preceding clinically significant hypoglycemia episodes. METHODS: A cross-sectional study was conducted in 30 T1DM patients using the MiniMed 640G vs. 30 using the MiniMed Veo sensor-augmented insulin pump. All data was recorded during patients' normal daily activity and living conditions. The patients were matched for age and duration of diabetes. RESULTS: PLGM use was associated with lower incidence of clinically significant hypoglycemia (1.9±1.4 vs. 3.6±1.9 episodes per week), along with reduced exposure to hypoglycemia. The data indicated that both pump systems are effective in preventing severe hypoglycemic episodes. In both groups the most common events preceding hypoglycemic episodes included adjustment of hyperglycemia, basal rate increase and miscalculation of carbohydrates. CONCLUSIONS: The results indicated that the use of the Minimed 640G pump system can help reduce the frequency of clinically significant hypoglycemia. Management of hyperglycemia must be addressed in diabetes education programs in order to encourage proper adjustment of high blood glucose levels. Future studies would be useful in exploring the details of the events preceding hypoglycemia episodes in insulin pump users.

Significant reduction in the visits to the emergency room department during the COVID-19 pandemic in a tertiary hospital in Greece: Indirect victims of the pandemic?

ABSTRACT: COVID-19 pandemic caused a major crisis, affecting and straining health care systems, including some very advanced ones. The pandemic may have also indirectly affected access to health care for patients with other conditions, not related to COVID-19, even in countries not overwhelmed by an outbreak.We analyzed and compared visits to the emergency room (ER) department during the same calendar period of 2019 and 2020 (from March 1 to March 31 of each year) in our hospital, a medium size, tertiary center, located in the center of Athens, which is not a referral center for COVID-19.Total ER visits were reduced by 42.3% and the number of those requiring hospitalization by 34.8%. This reduction was driven by lower numbers of visits for low risk, non-specific symptoms and causes. However, there was a significant decrease in admissions for cardiovascular symptoms and complications (chest pain of cardiac origin, acute coronary syndromes, and stroke) by 39.7% and for suspected or confirmed GI hemorrhage by 54.7%. Importantly, number of ER visits for infections remained unchanged, as well as the number of patients that required hospitalization for infection management; only few patients were diagnosed with COVID-19.During the initial period of the pandemic and lock-down in Greece, there was a major decrease in the patients visiting ER department, including decrease in the numbers of admissions for cardiovascular symptoms and complications. These observations may have implications for the management of non-COVID-19 diseases during the pandemic.

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data.

OBJECTIVES: To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. METHODS: Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. PARTICIPANTS: Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. INTERVENTION: Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. RESULTS: One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. CONCLUSIONS: ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes. REGISTRATION: - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.

Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study cohort.

BACKGROUND/AIMS: Uncertainty still exists on the earliest beta-cell defects at the bases of the type 2 diabetes. We assume that this depends on the inaccurate distinction between fasting and post-load glucose homeostasis and aim at providing a description of major beta-cell functions across the full physiologic spectrum of each condition. METHODS: In 1320 non-diabetic individuals we performed an OGTT with insulin secretion modeling and a euglycemic insulin clamp, coupled in subgroups to glucose tracers and IVGTT; 1038 subjects underwent another OGTT after 3.5 years. Post-load glucose homeostasis was defined as mean plasma glucose above fasting levels (δOGTT). The analysis was performed by two-way ANCOVA. RESULTS: Fasting plasma glucose (FPG) and δOGTT were weakly related variables (stß = 0.12) as were their changes over time (r = -0.08). Disruption of FPG control was associated with an isolated and progressive decline (approaching 60%) of the sensitivity of the beta-cell to glucose values within the normal fasting range. Disruption of post-load glucose control was characterized by a progressive decline (approaching 60%) of the slope of the full beta-cell vs glucose dose-response curve and an early minor (30%) decline of potentiation. The acute dynamic beta-cell responses, neither per se nor in relation to the degree of insulin resistance appeared to play a relevant role in disruption of fasting or post-load homeostasis. Follow-up data qualitatively and quantitatively confirmed the results of the cross-sectional analysis. CONCLUSION: In normal subjects fasting and post-load glucose homeostasis are largely independent, and their disruption is sustained by different and specific beta-cell defects.

Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review.

Here, we review insulin management options and strategies in nonpregnant adult patients with type 1 diabetes mellitus (T1DM). Most patients with T1DM should follow a regimen of multiple daily injections of basal/bolus insulin, but those not meeting individual glycemic targets or those with frequent or severe hypoglycemia or pronounced dawn phenomenon should consider continuous subcutaneous insulin infusion. The latter treatment modality could also be an alternative based on patient preferences and availability of reimbursement. Continuous glucose monitoring may improve glycemic control irrespective of treatment regimen. A glycemic target of glycated hemoglobin < 7% (53 mmol/mol) is appropriate for most nonpregnant adults. Basal insulin analogues with a reduced peak profile and an extended duration of action with lower intraindividual variability relative to neutral protamine Hagedorn insulin are preferred. The clinical advantages of basal analogues compared with older basal insulins include reduced injection burden, better efficacy, lower risk of hypoglycemic episodes (especially nocturnal), and reduced weight gain. For prandial glycemic control, any rapid-acting prandial analogue (aspart, glulisine, lispro) is preferred over regular human insulin. Faster-acting insulin aspart is a relatively new option with the advantage of better postprandial glucose coverage. Frequent blood glucose measurements along with patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity is paramount, as is education on the management of blood glucose under different circumstances.Plain Language Summary: Plain language summary is available for this article.

A Pilot Study About the Dysfunction of Adipose Tissue in Male, Sleep Apneic Patients in Relation to Psychological Symptoms.

Introduction: Obstructive sleep apnea (OSA) and its cardiometabolic alterations are closely associated with visceral obesity. Patients with OSA frequently present with symptoms of depression and anxiety. Although these subjective symptoms of OSA are the result of complex biological dysregulation, it remains unclear if they have a direct effect on the dysfunction of adipose tissue. Methods: In a pilot, prospective, randomized study, we evaluated 10 recently diagnosed male patients with severe OSA by full polysomnography (PSG) and 4 male non-apneic subjects matched for age and body mass index (BMI) with abdomen adipose tissue biopsies. Subjects with diabetes/prediabetes and cardiovascular and psychiatric diseases and who are current smokers were excluded. All patients underwent anthropometric measurements and completed the following questionnaires: Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Fasting venous blood samples were collected on the day after PSG, between 8:00 and 9:00 a.m., after an overnight fast. Fat biopsies were performed at the same time periods and adipose tissue samples of 300 mg were obtained from abdominal fat. Fat cell size, extent of fibrosis, vascularity, leukocyte common antigen inflammatory infiltration, and tissue macrophage accumulation were microscopically evaluated. Results: The mean age of the group was 47.4 ± 13.8 years, with mean BMI of 35.8 ± 4.8 kg/m2 and mean apnea-hypopnea index of 79.4 ± 46.1 events per hour of sleep (severe OSA). HADS-A and HADS-D scores were 5.8 ± 2.3 (3.0-8.0) and 4.7 ± 2.3 (2.0-8.0), respectively. HADS-A score correlated positively with macrophage accumulation in fat biopsy (r = 0.82, p = 0.047), whereas ESS, FSS, and HADS-D did not. Severity of fibrosis correlated largely with waist circumference (r = -0.66, p = 0.038) and neck circumference (r = -0.790, p = 0.006). Respiratory events correlated negatively with the extent of vascularization of adipose tissue (r = -0.614, p = 0.05). Conclusions: In the preliminary results of our pilot study, we assessed that the symptoms of anxiety mainly contribute to macrophage accumulation, whereas the increased number of respiratory events reduces the extent of vascularization in visceral fat in OSA. Based on this observation, further larger studies are required to verify if anxious OSA patients are more vulnerable to the metabolic manifestations of the syndrome.

High level of clinical inertia in insulin initiation in type 2 diabetes across Central and South-Eastern Europe: insights from SITIP study.

AIMS: Little is known regarding initiation of insulin therapy in type 2 diabetes (T2D) in Central and South-Eastern European countries. Therefore, we conducted a survey to characterise the prescribing practices of specialist diabetes healthcare professionals in this region and assessed factors that influence clinical decision-making regarding insulin initiation in T2D. METHODS: A cross-sectional survey sampled 211 specialist diabetes healthcare prescribers from five Central and South-Eastern European countries (Bulgaria, Croatia, Greece, Hungary, and Slovenia). A structured questionnaire was developed which surveyed current clinical practices and influencing factors, barriers to insulin initiation, and combination therapy prescribing preferences. RESULT: Only 9.4% (20 of out of 211 respondents) of healthcare professionals would initiate insulin therapy in T2D patients at the recommended HbA1c threshold of 7-7.9% [53-63 mmol/mol]. Large regional differences were evident in insulin initiation thresholds (≥ 9.0% [≥ 75 mmol/mol]: Bulgaria 80.8% vs. Slovenia 13.3%). Psychological distress was recorded as the major barrier to insulin initiation. Health insurance regulations were ranked more important than personal clinical experience and clinical guidelines in clinical decision-making. Information from peers was more influential than manufacturer information, clinical experience, and continuous medical education, respectively, for insulin initiation. CONCLUSIONS: Despite large regional variation, there is widespread delay of insulin initiation from specialist diabetes healthcare professionals in Central and South-Eastern Europe.

In-hospital dynamics of glucose, blood pressure and temperature predict outcome in patients with acute ischaemic stroke.

INTRODUCTION: We aimed to assess alterations in glucose, blood pressure and temperature in acute ischaemic stroke and investigate their association with early all-cause mortality and functional outcome. PATIENTS AND METHODS: We studied all consecutive acute ischaemic stroke patients admitted in 2001-2010 to the Acute Stroke Unit, at Alexandra University Hospital, in Athens. Serial measurements were performed in the first seven days post-stroke and different parameters have been estimated: mean daily values, variability, subject-specific baseline levels and rate of change in serial measurements. Cox-proportional-hazards-model analysis and logistic-regression analysis were applied to investigate the association between these parameters and all-cause mortality and functional outcome after adjustment for known confounders of stroke outcome. RESULTS: In 1271 patients (mean age 72.3 ± 11.2 years), after adjusting for confounders, baseline glucose levels (HR: 1.005, 95%CI: 1.001-1.01; p = 0.017), variability of systolic BP (SBP) as estimated by standard deviation (HR: 1.028, 95%CI: 1.01-1.048; p = 0.005), the baseline temperature (HR: 2.758, 95%CI: 2.067-3.68; p < 0.001) and the rate of temperature change (HR: 1.841, 95%CI: 1.616-2.908; p < 0.001) were independently associated with all-cause mortality within three months. Poor functional outcome was associated with subject-specific baseline values of temperature (OR: 1.743; 95%CI: 1.076-2.825; p = 0.024), the rate of SBP (OR: 1.159; 95% CI: 1.047-1.280; p = 0.004) and temperature change (OR: 1.402; 95% CI: 1.061-1.853; p = 0.018). DISCUSSION: The main strength of our study is that we analysed simultaneously three parameters and we used four different variables for each parameter of interest. CONCLUSION: Baseline glucose levels, variability of SBP and baseline temperature and its rate of change are independent predictors of all-cause mortality. Baseline values of temperature and the rate of changes in SBP and temperature are independent predictors of poor functional outcome.

Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort.

OBJECTIVE: To study whether the shape of the oral glucose tolerance test (OGTT)-glucose curve is a stable trait over time; it is associated with differences in insulin sensitivity, ß-cell function and risk of impaired fasting glucose (IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort. METHODS: OGTT-glucose curve shape was classified as monophasic, biphasic, triphasic and anomalous in 915 individuals. Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI) and ß-cell function were assessed at baseline and 3years apart. RESULTS: The OGTT-glucose curve had the same baseline shape after 3years in 540 people (59%; κ=0.115; p<0.0001). Seventy percent of the participants presented with monophasic OGTT-glucose curve shape at baseline and after 3years (percent positive agreement 0.74). Baseline monophasic shape was associated with significant increased risk of IFG (OR 1.514; 95% CI 1.084-2.116; p=0.015); biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310-0.936) and triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228-1.066; P=0.043) after 3years. Increased risks of IFG (OR 1.509; 95% CI 1.008-2.260; p=0.05) and IGT (OR 1.947; 95% CI 1.085-3.494; p=0.02) were found in people who kept stable monophasic morphology over time and in switchers from biphasic to monophasic shape (OR of IGT=3.085; 95% CI 1.377-6.912; p=0.001). CONCLUSION: After 3years follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes were associated with different OGIS and ß-cell function; persistence over time of the monophasic shape and switch from biphasic to monophasic shape with increased risk of impaired glucose metabolism.

The effect of hypohydration on endothelial function in young healthy adults.

PURPOSE: Hypohydration has been suggested as a predisposing factor for several pathologies including cardiovascular diseases (CVD). While CVD are the leading cause of death worldwide, no study has investigated whether acute hypohydration affects endothelial function and cardiovascular function. METHODS: Ten young, healthy males participated in this crossover study (age: 24.3 ± 2.3 year; weight: 80.8 ± 5.3 kg; BMI: 24.3 ± 0.4 kg m-2). Each subject completed two measurements of endothelial function by flow-mediated dilation (FMD) in euhydrated and hypohydrated state separated by 24 h. Following baseline assessment of hydration status and FMD, the subjects completed 100 min of low-intensity intermittent walking exercise to achieve hypohydration of -2 % of individual body mass. For the rest of the day, a standardized, low water content diet was provided. The following morning, hydration markers and endothelial function were recorded. RESULTS: Hypohydration by -1.9 ± 0.1 % of body mass resulted in decreased plasma volume by -3.5 ± 1.8 % and increased plasma osmolality by 9 ± 2 mmol kg-1 (P < 0.001). FMD as a response to hypohydration decreased by -26.8 ± 3.9 % (P < 0.05). CONCLUSION: The data suggested that a small degree of hypohydration induced by moderate exercise and fluid restriction significantly impaired endothelial function.

Type 2 Diabetes Mellitus and the Elderly: An Update on Drugs Used to Treat Glycaemia.

Type 2 Diabetes Mellitus (T2DM) and its complications are more prevalent in the elderly. As the general population worldwide is ageing, effective and safe treatment of older T2DM patients is becoming more important in clinical practice. Elderly T2DM patients should be carefully evaluated for functional, mental, geriatric and medical disorders before the initiation of antidiabetic drug therapy and regularly monitored thereafter. Treatment strategy and goals should be individualized based on patient comorbidities and drug pharmacokinetic and pharmacodynamic properties. This narrative review discusses the use of antidiabetic drugs in the elderly T2DM population.