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.

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.

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.

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.

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.

Cost-Effectiveness of Dapagliflozin as Add-On to Metformin for the Treatment of Type 2 Diabetes Mellitus in Greece.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that has been spread worldwide over the past three decades and associated with increased morbidity and mortality resulting in considerable socioeconomic implications for national healthcare systems. Effective management of disease is highly needed ensuring patients receive the best possible care within the available budget. The objective of this study was to evaluate the long-term cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, compared with a sulfonylurea (SU) or a dipeptidyl-peptidase-4 inhibitor (DPP-4i), when added to metformin, in T2DM patients inadequately controlled on metformin alone in Greece. METHODS: The published and validated Cardiff diabetes model, a lifetime micro-simulation model, was adapted to a Greek healthcare setting to determine the incidence of micro- and macro-vascular complications and diabetes-specific and all-cause mortality. Clinical, cost, and utility data were retrieved from literature and assigned to model parameters to calculate total quality-adjusted life-years (QALYs) and total costs as well as incremental cost-effectiveness ratios (ICERs). The analysis was conducted from the perspective of a third-party payer in Greece. Uncertainty surrounding important model parameters was explored with univariate and probabilistic sensitivity analyses (PSA). RESULTS: Over a patient's lifetime, dapagliflozin was associated with 0.48 and 0.04 incremental QALYs compared with SU and DPP-4i, respectively, at additional costs of €5142 and €756, respectively. The corresponding ICERs were €10,623 and €17,695 per QALY gained versus the treatment with SU and DPP-4i, respectively. Results were robust across various univariate and scenario analyses. At the defined willingness-to-pay threshold of €34,000 per QALY gained, PSA estimated that treatment with dapagliflozin had a 100 % and 79.7 % probability of being cost-effective relative to the SU and DPP-4i treatments. CONCLUSIONS: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment alternative for patients with T2DM whose metformin regimen does not provide sufficient glycemic control in a Greek healthcare setting.

Anti-TNFα treatment for recalcitrant ulcerative necrobiosis lipoidica diabeticorum: A case report and review of the literature.

INTRODUCTION: Necrobiosis lipoidica diabeticorum (NLD) is a rare degenerative connective tissue disorder associated with diabetes mellitus, which usually presents with red papules or plaques with raised edges and occasional ulceration. Ulcerating NLD is notoriously difficult to treat. We present a young patient with ulcerative NLD who was successfully treated with the anti-TNFα agent infliximab. Case presentation is followed by a review of therapeutic TNFα blockade in NLD. CASE PRESENTATION: A 17-year old woman with type 1 diabetes since the age of 8, presented with a long-standing and extensively ulcerated and infected NLD lesion on her left shin. After achieving better glycemic control and treating her for infection of the wound, several NLD treatments failed to help, including corticosteroids and hyperbaric oxygen. She was treated successfully with 4 monthly sessions of 5mg/kg body weight intravenous infliximab, achieving complete resolution of ulceration. DISCUSSION: A multitude of available treatments have been suggested for NLD over the past decades, based on two axes, one through wound healing and the other through immunosuppression. Anti-TNFα agents are relatively new drugs that brought a revolution in chronic inflammatory diseases and have been on the rise as novel potential treatments for NLD. Three out of the five available anti-TNFα agents have been safely tested so far, both topically and systematically, with mostly favorable results. CONCLUSION: Intravenous infliximab was successful in the treatment of recalcitrant ulcerating NLD in our patient. Taken together with an increasing number of similar reports revealing a pathogenetic role of TNFα in NLD, we suggest that anti-TNFα agents are promising drugs in the management of this condition.

Study of postprandial lipaemia in type 2 diabetes mellitus: exenatide versus liraglutide.

Therapeutic approaches based on the actions of the incretin hormone GLP-1 have been widely established in the management of T2DM. Nevertheless, much less research has been aimed at elucidating the role of GLP-1 in lipid metabolism and in particular postprandial dyslipidemia. Exenatide and liraglutide are two GLP-1 receptor agonists which are currently available as subcutaneously administered treatment for T2DM but their chronic effects on postprandial lipaemia have not been well investigated. The aim of this study is to examine the effect of treatment with either liraglutide or exenatide for two weeks on postprandial lipaemia in obese subjects with T2DM. This study was a single-center, two-armed, randomized, controlled 2-week prospective intervention trial in 20 subjects with T2DM. Patients were randomized to receive either liraglutide or exenatide treatment and underwent a standardized meal tolerance test early in the morning after 10 h fast at baseline (visit 1, beginning of treatment) and after a two-week treatment period (visit 2). Exenatide and liraglutide both appear to be equally effective in lowering postprandial lipaemia after the first administration and after a two-week treatment. The mechanisms which lead to this phenomenon, which seem to be independent of gastric emptying, are yet to be studied.

The spatial QRS-T angle: implications in clinical practice.

The ventricular gradient (VG) as a concept was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. The contemporary spatial QRS-T angle is based on the concept of the VG and defined as its mathematical and physiological integral. Its current major clinical use is to assess the cardiac primary repolarization abnormalities in 3-dimensional spatial vectorial plans which are normally untraced in the presence of secondary electrophysiological activity in a 2-dimensional routine electrocardiogram (ECG). Currently the calculation of the spatial QRS-T angle can be easily computed on the basis of a classical ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local heterogeneity of the myocardial ventricular action potention duration. Recent population-based studies suggest that the spatial QRS-T angle is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary cardiovascular prevention efforts and should be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial QRS-T angle. The main focus is its role in ECG assessment of dispersion of repolarization, a key factor in arrythmogeneity.

The association of the 174G>C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus.

AIMS: To evaluate the association of 174G>C polymorphism on interleukin-6 (IL-6) gene with diabetic nephropathy in patients with type 2 diabetes. METHODS: A total of 393 Greek subjects with type 2 diabetes (mean age 66.5±10.0years, men n=203, women n=190) were examined. Diabetic nephropathy was defined as presence of microalbuminuria and/or proteinuria. The IL-6 174G>C polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme digestion. High sensitivity C-reactive protein was assayed by particle-enhanced immunonephelometry. RESULTS: The genotype distribution (%) was GG: 49.1, GC: 26.8 and CC: 24.1, with no gender difference. The CC homozygotes had lower albumin excretion (mg/24h) in comparison with the GC genotype [CC: 8.9 (4.0-20.9) vs GC: 21.95 (9.1-53.35), P=0.004]. Participants with the GC genotype tended to have more frequently nephropathy than those with the GG or the CC genotype [GC: 44.55% vs GG: 35.1% and CC: 28.3%, P=0.07)]. The CC homozygotes in comparison with GC heterozygotes had lower odds to have nephropathy (odds ratio: 0.51, 95% confidence intervals=0.28-0.91, P=0.02), even after adjustment for sex, age, duration of diabetes, body mass index, smoking, hypertension, lipids and glycated hemoglobin, (P=0.01). CONCLUSION: In type 2 diabetes states, CC homozygotes have lower albumin excretion and are protected from nephropathy in comparison with GC genotypes.

Cigarette Smoking Is Associated with Prolongation of the QTc Interval Duration in Patients with Type 2 Diabetes Mellitus.

Aims. Aim of the study was to evaluate the effect of smoking on autonomic nervous system (ANS) activity and QTc interval duration in patients with Type 2 diabetes mellitus (T2DM). Methods. A total of 70 patients with T2DM (35 chronic smokers, 35 nonsmokers) treated with oral antidiabetic medications underwent continuous ECG Holter monitoring for 24 hours and analysis of time- and frequency-domain measures of heart rate variability (HRV). HRV over short time was also assessed using the deep breathing test. In addition, baroreflex sensitivity (BRS) was evaluated using the spontaneous sequence method. The mean QTc interval was measured from the 24-hour ECG recordings. Results. Smokers had lower body mass index (BMI) and exhibited higher 24-hour mean heart rate. There was no difference regarding all measures of ANS activity between the two groups. Smokers showed increased mean QTc duration during the 24 hours (439.25 ± 26.95 versus 425.05 ± 23.03 ms, P = 0.021) as well as in both day (439.14 ± 24.31 ms, P = 0.042) and night periods (440.91 ± 32.30 versus 425.51 ± 24.98 ms, P = 0.033). The association between smoking status and mean QTc interval persisted after adjusting for BMI. Conclusions. Cigarette smoking is associated with prolongation of the QTc interval in patients with T2DM by a mechanism independent of ANS dysfunction.

Screening for HbA1c-defined prediabetes and diabetes in an at-risk greek population: performance comparison of random capillary glucose, the ADA diabetes risk test and skin fluorescence spectroscopy.

BACKGROUND: We examined the accuracy of random capillary glucose (RCG) and two noninvasive screening methods, the ADA diabetes risk test (DRT) and skin fluorescence spectroscopy (SFS) as measured by Scout DS for detecting HbA1c-defined dysglycemia or type 2 diabetes in an at-risk cohort. METHODS: Subjects were recruited at two clinical sites for a single non-fasting visit. Each subject had measurements of height, weight and waist circumference. A diabetes score was calculated from skin fluorescence measured on the left forearm. A finger prick was done to measure RCG and HbA1c (A1C). Health questionnaires were completed for the DRT. Increasing dysglycemia was defined as A1C ≥ 5.7% (39 mmol/mol) or ≥ 6.0% (42 mmol/mol). Type 2 diabetes was defined as A1C ≥ 6.5% (47.5 mmol/mol). RESULTS: 398 of 409 subjects had complete data for analysis with means for age, body mass index, and waist of 52 years, 27 kg/m(2) and 90 cm. 51% were male. Prevalence of A1C ≥ 5.7%, ≥ 6.0% and ≥ 6.5% were 54%, 34% and 12%, respectively. Areas under the curve (AUC) for detection of increasing levels dysglycemia or diabetes for RCG were 63%, 66% and 72%, for the ADA DRT the AUCs were 75%, 76% and 81% and for SFS the AUCs were 82%, 84% and 90%, respectively. For each level of dysglycemia or diabetes, the SFS AUC was significantly higher than RCG or the ADA DRT. CONCLUSIONS: The noninvasive skin fluorescence spectroscopy measurement outperformed both RCG and the ADA DRT for detection of A1C-defined dysglycemia or diabetes in an at-risk cohort.

Improvement in cardiovascular indices after Roux-en-Y gastric bypass or sleeve gastrectomy for morbid obesity.

BACKGROUND: Morbidly obese patients display cardiac abnormalities which are partially reversed after weight loss. The aim of the present study was to assess the potential difference in cardiovascular disease indices between patients who underwent either gastric bypass surgery or sleeve gastrectomy. METHODS: Thirty-seven morbidly obese patients who underwent either Roux-en-Y gastric bypass (RYGB) (n = 14) or SG (n = 23) were examined before, 3 and 6 months after surgery. Indices of cardiac autonomic nervous system activity were evaluated, namely baroreflex sensitivity (BRS) and heart rate variability (HRV). A complete echocardiographic study was performed in a subgroup of 17 patients (RYGB 8, SG 9) preoperatively and 6 months after surgery, evaluating epicardial fat thickness, aortic distensibility, left ventricular (LV) Tei index, left atrium diameter, ejection fraction, and LV mass. RESULTS: All subjects experienced significant (p < 0.001) and similar weight loss independently of the type of operation. BRS and HRV indices improved significantly and to the same degree after surgery in both groups. In the echocardiographic study, all parameters improved significantly at 6 months in comparison with the baseline values. In addition, the RYGB group displayed significantly greater reduction in epicardial fat thickness (p = 0.007) and also tended to have a better LV performance as expressed by the lower values of the Tei index (p = 0.06) compared to the SG group 6 months after surgery. CONCLUSIONS: Both RYGB and SG exert comparable effects on weight loss and improvement of cardiovascular parameters. RYGB displays a more beneficial influence on epicardial fat thickness and left ventricular performance than SG.

The effect of alpha antagonists on pupil dynamics: implications for the diagnosis of intraoperative floppy iris syndrome.

PURPOSE: To assess pupil dynamics quantitatively in relation to the use of α1-adrenoceptor antagonists, which contribute to the features of intraoperative floppy iris syndrome, using a new, hand-held, digital pupillometer. DESIGN: Prospective case-control study. METHODS: We studied 15 and 25 patients administered tamsulosin and alfuzosin, respectively, as well as 25 control patients. Resting pupil diameter and subsequent contraction, latency, constriction velocity, and dilation velocity were recorded using an electronic pupillometer. All pupil measurements were performed before and after pharmacologic dilation. RESULTS: In predilation pupillary measurements, we detected a significant decrease in maximum pupillary diameter by 0.50±0.19 mm (P=.011) and in the mean percentage of diameter reduction after stimulation (5.23±2.42%, P=.035) in the tamsulosin group. Alfuzosin also induced a significant decrease in maximum pupillary diameter (0.49±0.17 mm, P=.005). Constriction velocity was significantly reduced by 0.70±0.20 m/s (P=.001) in the tamsulosin group and by 0.54±0.18 m/s (P=.004) in the alfuzosin group. In terms of postdilation measurements, maximum and minimum pupil diameters were reduced significantly only in the tamsulosin group (by 1.09±0.31 mm [P=.001] and by 0.89±0.36 mm [P=.016], respectively). CONCLUSIONS: We describe a reliable, accurate, and rapid method to acquire quantitative pupil measurements and identify the tendency for intraoperative floppy iris syndrome before cataract surgery after the use of alfuzosin and tamsulosin. This investigation also analyzed the similarities and differences induced by the 2 drugs in predilation and postdilation pupil dynamics, demonstrating that tamsulosin is more potent than alfuzosin in inducing intraoperative floppy iris syndrome.

Type 2 diabetes mellitus is associated with obesity, smoking and low socioeconomic status in large and representative samples of rural, urban, and suburban adult Greek populations.

OBJECTIVE: In this cross-sectional epidemiologic study we examined the association between type 2 diabetes mellitus and demographic, clinical, and socioeconomic parameters in large rural, urban and suburban populations of adult Greeks. DESIGN: Of the total target adult population (≥19 years, n=14233) in nine selected geographical regions covering rural, suburban, and urban areas of Greece, 10,647 subjects were included in the study. Data were collected by physicians who interviewed subjects at their homes between 1996 and 1999. RESULTS: A total of 8740 subjects participated (response rate 82.1%). Among participants there were 360 subjects with type 2 diabetes. Multivariate logistic regression analysis after adjustment for factors associated with type 2 DM in univariate analyses including occupation, education level, place of residence, and number of persons living together demonstrated that advancing age, obesity-but not overweight status-and smoking in the past were associated with higher odds of type 2 diabetes. Moreover, low socioeconomic status was associated with type 2 diabetes independently of the effects of age, obesity, and smoking. CONCLUSIONS: In large representative rural, urban, and suburban populations of adult Greeks, type 2 Diabetes was associated with advancing age, obesity, exposure to smoke, and low socioeconomic status.