Patients with type 2 diabetes mellitus present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to healthy subjects: a prospective cohort study.

AIM: To compare the kinetics of neutralizing antibodies (NΑbs) against SARS-CoV-2 after vaccination with the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with T2DM and healthy controls. METHODS: NAb levels after the BNT162b2 mRNA vaccine were compared between 50 patients with non-insulin treated T2DM and 50 age-, gender-, and BMI-matched healthy controls up to 3 months after the second dose. The median age of both groups was 70 years. RESULTS: On day 1, mean NAbs of the control and T2DM groups were 14.64% (standard error, SE = 2.30) and 14.04% (SE = 2.14), respectively (p value = 0.926). Three weeks later, the mean NAb values were 39.98% (SE = 3.53) in the control group and 40.97% (SE = 3.99) in participants with T2DM (p value = 0.698). One month after the second vaccination, mean NAb values increased to 87.13% (SE = 2.94) in the control group and 89.00% (SE = 2.18) in the T2DM group. Three months after the second vaccine dose, the mean inhibitory titers decreased to 83.49% (SE = 3.82) (control group) and 76.36% (SE = 3.33) (T2DM group). On all occasions, no significant difference was found between the two groups (all p values > 0.05). CONCLUSIONS: Patients with T2DM present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to that of healthy subjects.

Type 2 diabetes in children and adolescents: distinct characteristics and evidence-based management.

PURPOSE: Since the dramatic rise of obesity prevalence in childhood and adolescence has contributed to increased rates of type 2 diabetes (T2D) in youth, we sought to explore current evidence-based management options for pediatric T2D patients. METHODS: A comprehensive literature search was performed for studies of T2D in childhood and adolescence until September 2021. RESULTS: Special pathophysiological and diagnostic characteristics of T2D in this age are presented, while the main focus of the article is on management. Lifestyle interventions with healthy diet and exercise are of great importance for the treatment of T2D in children and adolescents. Metformin and insulin remain the traditional therapeutical means, while liraglutide recently gained indication for children older than 10 years both in USA and Europe. Data on the use, efficacy, safety and therapeutic considerations of other pharmacological treatments in children and adolescents with T2D are critically discussed. CONCLUSION: Although many new and promising therapeutic strategies have been introduced during recent years for the management of T2D in adults, available therapeutic options for the management of pediatric T2D remain limited.

Circulating levels of five proglucagon-derived peptides in response to intravenous or oral glucose or lipids and to a mixed-meal in subjects with normal weight, overweight, and obesity.

AIMS: Proglucagon-derived peptides (PGDPs) secreted by the gut and pancreas play a major role in metabolism. We measured concentrations of five PGDPs in response to per os (PO) or intravenous (IV) glucose or lipid intake and a mixed meal test (MMT) consumed by subjects with normal weight, overweight or obesity. MATERIALS AND METHODS: GLP-1, oxyntomodulin and glicentin (gut-secreted PGDPs) and glucagon and MPGF (pancreas-secreted PGDPs) were assessed in: (a) 32 subjects receiving PO or IV glucose, lipids or water over 6 h, (b) 33 subjects with normal weight, overweight or obesity who consumed a MMT. RESULTS: (a) GLP-1, oxyntomodulin, glicentin and glucagon levels increase more profoundly and persistently after lipids PO (2.5  g/kg) than glucose PO (2.5  g/kg) or IV lipids (Intralipid/Liposyn II 20% at 0.35 ml/kg/h and Intralipid/Liposyn II 20% at 0.83  ml/kg/h for 6 h) or IV glucose (10% glucose at 3.6 ml/kg/h for 6 h). Oxyntomodulin and glicentin increased more than GLP-1 in response to lipids PO. MPGF levels decrease in response to glucose PO or IV indicating a shift towards preferential production of gut-secreted peptides. (b) Fasting and postprandial areas under the curve (AUCs) after MMT of GLP-1, MPGF and glucagon levels correlated positively with BMI. The fasting levels of glucagon and MPGF were elevated in obesity and remained elevated after the MMT. CONCLUSION: Circulating levels of PGDPs are differentially regulated by body weight, the type of macronutrients administered and the respective route of administration. Mechanistic studies are needed to define the exact mechanisms underlying this regulation. CLINICAL TRIAL REGISTRATION: Study 1 has the NCT01520454 and the NCT04888325 number in ClinicalTrials.gov. Study 2 has the number NCT01495754 in ClinicalTrials.gov.

Interplay between baroreflex sensitivity, obesity and related cardiometabolic risk factors (Review).

The baroreflex represents a rapid negative feedback system implicated in blood pressure regulation, which aims to prevent blood pressure variations by regulating peripheral vascular tone and cardiac output. The aim of the present review was to highlight the association between baroreflex sensitivity (BRS) and obesity, including factors associated with obesity, such as metabolic syndrome, hypertension, cardiovascular disease and diabetes. For the present review, a literature search was conducted using the PubMed database until August 21, 2021. The searched terms included 'baroreflex', and other terms such as 'sensitivity', 'obesity', 'metabolic syndrome', 'hypertension', 'diabetes', 'gender', 'aging', 'children', 'adolescents', 'physical activity', 'bariatric surgery', 'autonomous nervous system' and 'cardiometabolic risk factors'. Obesity and its related metabolic disorders can influence baroreflex functionality and decrease BRS, mostly by potentiating sympathetic nervous system activity. Obesity induces inflammation, which can increase sympathetic system activity and lead to a higher incidence of cardiovascular events. Obesity also represents an important risk factor for hypertension through numerous mechanisms; in this setting, dysfunctional baroreceptors are not able to protect against constantly elevated blood pressure. Furthermore, diabetes mellitus and oxidative stress result in deterioration of BRS, whereas aging is also generally related to reduced cardiovagal BRS. Differences in BRS have also been observed between men and women, and overall cardiovagal BRS in healthy women is less intense compared with that in men. BRS appears lower in children with obesity compared with that in children of a healthy weight. Notably, physical exercise can increase BRS in both hypertensive and normotensive subjects, and BRS can also be significantly improved following bariatric surgery and weight loss. In conclusion, obesity and its related metabolic disorders may influence baroreflex functionality and decrease BRS, and baroreceptors cannot protect against the constantly elevated blood pressure in obesity. However, following bariatric surgery and weight loss, BRS can be significantly improved. The present review summarizes the role of obesity and related metabolic risk factors in BRS, providing details on possible mechanisms and shedding light on their interplay leading to autonomic neuropathy.

Eligibility and Awareness Regarding Metabolic Surgery in Patients With Type 2 Diabetes Mellitus in the Real-World Clinical Setting; Estimate of Possible Diabetes Remission.

Despite high-quality evidence highlighting metabolic surgery as an effective treatment option for type 2 diabetes mellitus (T2DM), the number of patients receiving bariatric surgery (BS) remains low. Since the introduction of the Diabetes Surgery Summit II (DSS-II) eligibility criteria, data on eligibility rates for BS in T2DM cohorts remain scarce. The aims of the present study were to examine in a real-world clinical setting: (i) what is the percentage of T2DM patients visiting diabetes outpatient clinics who meet the DSS-II eligibility criteria, (ii) how many of these have been informed about the option of BS, and (iii) what are the characteristics associated with eligibility and awareness of BS. Demographic, anthropometric, clinical and socioeconomic data were obtained for all patients with T2DM who were consecutively examined in the outpatient clinics of three large-volume university hospitals (n = 1167). A medical registry form was completed to screen for BS eligibility. Patients were considered eligible if the recommendation by DSS-II criteria was either to "consider" or "recommend" BS. Eligible patients were further inquired whether they had ever been informed about the option of BS by their physicians. The advanced DiaRem score (ADRS) was applied to eligible patients to assess their probability of achieving postoperative T2DM remission. A significant percentage of T2DM patients who are routinely assessed in outpatient clinics meet the DSS-II eligibility criteria (15.3%). Eligible patients are younger and more obese, have a shorter T2DM duration, worse glycaemic control and better renal function, compared to non-eligible ones. Among eligible patients, only 39.3% have been medically informed about the option of BS. Informed patients are younger and more severely obese than non-informed ones. A significant percentage of non-informed patients (35%) have an ADRS ≤10, indicating a considerable probability for T2DM remission after BS, and are thus deprived of this opportunity due to lack of appropriate medical counseling. Screening and awareness of BS remain an unmet need in current T2DM management. Future research should focus on intensifying screening for BS eligibility at every medical visit and promoting evidence-based clinical recommendations for patients expected to benefit the most.

The role of amputative and non-amputative foot deformities severity in the risk for diabetic ulceration classification systems building: a cross-sectional and case-control pilot investigation.

INTRODUCTION: Foot deformities and amputations are parameters that have been studied as risk factors for diabetic foot ulceration (DFU). However, inclusion of "foot deformities" and "amputations" in a single, broad variable and with reference to the severity of these deformities, may better characterize subjects who are prone to develop DFU. METHODS: The objective of the study was the examination of amputative and non-amputative foot deformities severity as risk factor for DFU in relation with the other established risk factors. A cross-sectional and case-control study was conducted from October 2005 to November 2016. One hundred and thirty-four subjects with type 1 and 2 diabetes, with and without active foot ulcers, participated. A structured quantitative interview guide was used. Univariate logistic regression analysis for the literature's established risk factors was performed, as well as for two versions of the "amputative and non-amputative foot deformities severity" variable. Subsequently, multivariate logistic regression analysis (MLRA) for three models and receiver operating characteristic (ROC) curve analysis were carried out. RESULTS: From the MLRA, only PAD (peripheral arterial disease) was significant (OR 3.56, 95% CI 1.17-10.82, P=0.025 and OR 3.33, 95% CI 1.02-10.08, P=0.033). Concerning the ROC curve analysis of the models, the one with the three categories amputative and non-amputative foot deformities severity variable, had the greatest area under the ROC curve (0.763, P<0.001). CONCLUSION: A united variable for lower extremity amputations and other foot deformities with reference to their severity, could be more helpful to the clinicians in identifying patients with diabetes at risk for foot ulceration.

Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Narrative Review.

Postprandial hypertriglyceridaemia, defined as an increase in plasma triglyceride-containing lipoproteins following a fat meal, is a potential risk predictor of atherosclerotic cardiovascular disease and other chronic diseases. Several non-modifiable factors (genetics, age, sex and menopausal status) and lifestyle factors (diet, physical activity, smoking status, obesity, alcohol and medication use) may influence postprandial hypertriglyceridaemia. This narrative review considers the studies published over the last decade that evaluated postprandial hypertriglyceridaemia. Additionally, the genetic determinants of postprandial plasma triglyceride levels, the types of meals for studying postprandial triglyceride response, and underlying conditions (e.g. familial dyslipidaemias, diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver and chronic kidney disease) that are associated with postprandial hypertriglyceridaemia are reviewed; therapeutic aspects are also considered.

Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Main Text.

Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile. An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed. Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL). Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.

Associations between Adiponectin Gene Variability, Proinflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

BACKGROUND: Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications. OBJECTIVE: To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM. METHODS: Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry. RESULTS: Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299. CONCLUSION: Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects.

OBJECTIVE: The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. METHODS: Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. RESULTS: In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. CONCLUSIONS: Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.

Follistatins in glucose regulation in healthy and obese individuals.

AIMS: It has been suggested recently that follistatin (FST) and its homologous protein, follistatin-like 3 (FSTL3), may be a therapeutic target in the treatment of type 2 diabetes because of their glucose-regulatory effects in rodents. MATERIALS AND METHODS: We investigated this hypothesis in humans by studying the physiology of a possible glycaemia-follistatin feedback loop, that is, whether glucose, but not lipid intake (oral or intravenous), can regulate circulating FST and FSTL3 in healthy humans (n = 32), whether the levels of follistatins change in response to various types of bariatric operation in morbidly obese individuals, with or without type 2 diabetes (n = 41), and whether such changes are associated prospectively with improvement of glucose homeostasis/insulin sensitivity. RESULTS: In healthy individuals, circulating FST decreases after intravenous or oral glucose intake compared to controls, indicating the presence of a negative feedback mechanism. In morbid obesity, insulin resistance, glycaemia, circulating FST and FSTL3 are all reduced (by 22%-33%) after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. Importantly, the changes in circulating FST 3 months after bariatric surgery are associated prospectively with the changes in glucose, insulin, HOMA-IR and HbA1c observed 6 months postoperatively in individuals with and without type 2 diabetes. CONCLUSIONS: Our findings provide evidence of an important role of FST in glucose homeostasis in healthy individuals as well as in severely obese individuals with insulin resistance and type 2 diabetes. Our data extend recent results from animal studies to humans and support the need for further evaluation of FST inactivation strategies for targeting hyperglycaemia and insulin resistance.

Pain management of chronic wounds: Diabetic ulcers and beyond.

Patients who suffer from ulcers often experience pain of sufficient severity to reduce their quality of life. The aim of this review article is to collect, analyze and qualitatively resynthesize information regarding the definition and prevalence of ulcer pain, the pathophysiology of such pain, its assessment, and the optimal systemic and topical treatments. Early identification and prompt treatment are key to pain management. Further management should focus on appropriate dressing as much as on pain medication. The goal is to provide maximum relief with minimum side-effects.

Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a Short-term Follow-up Analysis.

PURPOSE: We aimed to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on postprandial glucose and lipid metabolism in addition to weight loss and fasting metabolic profile, in non-diabetic patients undergoing bariatric surgery. METHODS: Seventy-one patients were consecutively recruited and studied preoperatively, 3 and 6 months after surgery. Of these, 28 underwent RYGB (7 males, age 38 ± 9 years, BMI 46.9 ± 5.0 kg/m2), and 43 SG (9 males, age 38 ± 9 years, BMI 50.2 ± 7.0 kg/m2). A semi-liquid mixed meal was consumed, and blood samples were taken before, and every 30 min after meal ingestion up to 180 min postprandially, for measurement of glucose, insulin, and lipids. The overall postprandial response was assessed as area under the concentration-time curve (AUC). RESULTS: Baseline metabolic parameters were similar between RYGB and SG. Both groups experienced comparable weight loss, and a similar improvement in fasting glucose, insulin, and insulin resistance. Total and LDL cholesterol levels were lower at 6 months after RYGB compared to SG, while there was no difference in HDL cholesterol or triglycerides. Glucose AUC was lower after RYGB compared to SG at both 3 (p = 0.008) and 6 months (p = 0.016), without any difference in postprandial insulin response. Triglyceride AUC was also lower in RYGB vs. SG at 3 and 6 months (p ≤ 0.001). CONCLUSIONS: RYGB is superior to SG in improving postprandial glycaemia and lipaemia and cholesterol profile 6 months postoperatively in non-diabetic, severely obese patients. These findings imply procedure-specific effects, such as the malabsorptive nature of RYGB, and less likely a different incretin postoperative response.

Hypertension in patients with type 2 diabetes mellitus: Targets and management.

Two-thirds of patients with type 2 diabetes mellitus (T2DM) have arterial hypertension. Hypertension increases the incidence of both micro- and macrovascular complications in these patients, while the co-existence of these two major risk factors leads to a four-fold increased risk for cardiovascular disease (CVD) compared with normotensive non-diabetic controls. The aim of this article is to comprehensively review the literature and present updated information on targets for blood pressure (BP) and on the management of hypertension in patients with T2DM. A BP target of <140/90 mmHg applies to most patients, but individualization is always important. All classes of antihypertensive drugs can be used in the management of hypertension in patients with T2DM, as long as they are effective and safe and after taking co-morbidities into account. Angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are the ideal choice for initial or early treatment of hypertension in patients with T2DM and albuminuria. Combination of two or more drugs seems to be inevitable as most of these patients demonstrate resistant hypertension. The combination of ACE inhibitors with ARBs should be avoided. Thiazide and thiazide-like diuretics might be beneficial, alone or in a fixed-dose combination with ACE inhibitors or ARBs. Calcium channel blockers (CCBs) constitute an ideal option as a second- or third-line agent. Beta-blockers are not considered as first-line antihypertensive agents, except for those patients with heart failure or previous myocardial infarction. The addition of mineralocorticoid receptor antagonists to a triple-drug therapy seems the next ideal step. Gender-specific characteristics regarding BP, T2DM and CVD should be taken into consideration, even if different recommendations do not exist yet.

Effects of Newer Antidiabetic Drugs on Endothelial Function and Arterial Stiffness: A Systematic Review and Meta-Analysis.

BACKGROUND: Newer antidiabetic drugs, i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert distinct cardiovascular effects. We sought to explore their impact on vascular function. METHODS: Published literature was systematically searched up to January 2018 for clinical studies assessing the effects of DPP-4 inhibitors, GLP-1 RAs, and SGLT-2 inhibitors on endothelial function and arterial stiffness, assessed by flow-mediated dilation (FMD) of the brachial artery and pulse wave velocity (PWV), respectively. For each eligible study, we used the mean difference (MD) with 95% confidence intervals (CIs) for FMD and PWV. The pooled MD for FMD and PWV were calculated by using a random-effect model. The presence of heterogeneity among studies was evaluated by the I 2 statistic. RESULTS: A total of 26 eligible studies (n = 668 patients) were included in the present meta-analysis. Among newer antidiabetic drugs, only SGLT-2 inhibitors significantly improved FMD (pooled MD 1.14%, 95% CI: 0.18 to 1.73, p = 0.016), but not DPP-4 inhibitors (pooled MD = 0.86%, 95% CI: -0.15 to 1.86, p = 0.095) or GLP-1 RA (pooled MD = 2.37%, 95% CI: -0.51 to 5.25, p = 0.107). Both GLP-1 RA (pooled MD = -1.97, 95% CI: -2.65 to -1.30, p < 0.001) and, to a lesser extent, DPP-4 inhibitors (pooled MD = -0.18, 95% CI: -0.30 to -0.07, p = 0.002) significantly decreased PWV. CONCLUSIONS: Newer antidiabetic drugs differentially affect endothelial function and arterial stiffness, as assessed by FMD and PWV, respectively. These findings could explain the distinct effects of these drugs on cardiovascular risk of patients with type 2 diabetes.

The Real-Life Effectiveness and Care Patterns of Type 2 Diabetes Management in Greece.

AIM: To investigate the prevalence of hypoglycaemia during sulfonylurea (SU) treatment of type 2 diabetes mellitus (T2DM) in Greece and its influence on glycaemic control, treatment adherence and quality of life (QoL). PATIENTS AND METHODS: This was a retrospective cross-sectional study. We included 383 T2DM patients ≥30 years old on treatment with SU in monotherapy or in combination with metformin for at least 6 months. Patients were requested to fill in retrospective questionnaires on hypoglycaemia experience, adherence, weight gain and lifestyle/behavioural factors along with QoL (EQ-5D-3L), treatment satisfaction (TSQM), and fear of hypoglycaemia (HFS-II Worry scale). RESULTS: HbA1c<7% was found in 161 (42.0%) patients. In total, 165 (43.1%) patients reported hypoglycaemic symptoms during the previous 6 months: 41.6% (67/161) of those with HbA1c <7% and 44.1% (98/222) of those with HbA1c ≥7%. Glycaemic control was achieved by 43.1% (94/218) of patients without hypoglycaemia and 50.0% (41/82), 36.8% (25/68) and 6.7% (1/15) of patients with mild, moderate or severe hypoglycaemia, respectively (p=0.013). In multivariate analysis, both occurrence (none vs. mild/moderate/severe) and severity (none vs. mild vs. moderate vs. severe) of hypoglycaemia were significantly associated with impaired global treatment satisfaction (p=0.002 and p<0.0001 respectively) and HFS-II Worry scale scores (both p<0.0001), while lower QoL (EQ-5D (UK) Index) was related to hypoglycaemia severity (p=0.024) only. Finally, treatment adherence was associated with increased (none/mild vs. moderate/severe) hypoglycaemia severity in univariate analysis (p=0.019). CONCLUSION: A high prevalence of patient treated with SU reported hypoglycaemia in Greek healthcare settings with negative effects on treatment satisfaction, patient worry and adherence. Severity of hypoglycaemic symptoms was associated with reduced glycaemic control.

Association of matrix γ-carboxyglutamic acid protein levels with insulin resistance and Lp(a) in diabetes: A cross-sectional study.

AIMS: The risk of cardiovascular disease (CVD) and mortality is increased in patients with chronic kidney disease (CKD), with a background role of vascular calcification in the development of CVD also reported. Studies have demonstrated that high lipoprotein(a) (Lp(a)) levels accelerate the development of atherosclerolsis and are potentially involved in the vascular calcification. Matrix Gla Protein (MGP) seems to play an important role in vascular calcification. The aim of the study was to examine the potential association of MGP concentrations with Lp(a) and insulin resistance. METHODS: The study involved 100patients divided in four groups: 25 with both CKD stage 4 and Type2 Diabetes (DM) (Group-A), 25 with CKD4 without DM (Group-B), 25 non uremic patients with DM (Group-C) and 25 healthy subjects (Group-D). Serum glucose, Lp(a), MGP, plasma HBA1c and insulin were measured in all patients. Insulin resistance was estimated by the homeostasis model assessment equation (HOMA-IR). RESULTS: A significant positive linear association between MGP and Lp(a) levels (r=0.272, p=0.006) was noted, as well as between MGP and HOMA-IR levels (r=0.308, p=0.002). However, no significant linear association between Lp(a) and HOMA-IR levels was recorded. A similar positive association between MGP and insulin levels (r=0.204, p=0.042) was also found. CONCLUSION: This study concluded that diabetes coexisting with renal disease leads to extreme vascular calcification expressed by elevated MGP levels, resulting in higher frequency of cardiovascular disease in comparison to CKD patients without diabetes. The detected Lp(a) and MGP association in CKD4 patients may also represent the key to the complicated mechanism of their coexisting accelerated atherosclerosis and vascular calcification.

Subclinical atherosclerosis in Systemic Lupus Erythematosus: Comparable risk with Diabetes Mellitus and Rheumatoid Arthritis.

OBJECTIVE: Although a high risk of subclinical atherosclerosis has been reported in Systemic Lupus Erythematosus (SLE), it is not adequately compared with that observed in other rheumatic and non-rheumatic high-cardiovascular (CVD) risk diseases, such as Rheumatoid Arthritis (RA) and Diabetes Mellitus (DM). Our objective was to evaluate the relative risk (RR) of subclinical atherosclerosis in SLE, RA and DM patients compared to healthy controls, and examine potential associations with traditional and disease-related CVD risk factors in SLE. METHODS: We examined for atherosclerotic plaques 460 individuals (92% female) without CVD history, using carotid and femoral artery ultrasound: 115 SLE patients and matched 1:1 for age and gender RA, DM, and control subjects. Multivariate models were used to determine relative risk estimates for the number of atherosclerotic plaques in patient groups versus controls, and associations of plaques with traditional CVD and disease-related factors in SLE. RESULTS: A nearly two-fold higher number of atherosclerotic plaques in the carotid and femoral arteries was detected in each of SLE, RA and DM groups compared to controls, after adjusting for the effect of traditional CVD risk factors (RR=1.80, 95% CI 1.05-3.08, p=0.033, RR=1.90 (1.11-3.26), p=0.019, RR=1.93 (1.14-3.28), p=0.015, respectively). In SLE patients, the number of atherosclerotic plaques was associated with age (p<0.001), smoking (p=0.016), hypertension (p=0.029), and cumulative corticosteroid dose (p=0.007). CONCLUSION: The relative risk of subclinical atherosclerosis in SLE was comparable to that found in RA and DM, indicating that SLE patients merit a similar diligence in CVD risk assessment and management measures.