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.

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.

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.

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.

Angiotensin blockade in diabetic patients decreases insulin resistance-associated low-grade inflammation.

BACKGROUND: Insulin-resistant states, such as metabolic syndrome and diabetes mellitus type 2 (DM2), have been associated with chronic low-grade systemic inflammation. Elevated levels of interleukin-6 (IL-6), monocyte chemoattractant protein (MCP-1) and C-reactive protein (hs-CRP), are found in patients with type 2 diabetes with and without complications. Angiotensin II (Ang II), a potent vasopressor, seems to regulate also the expression of the above inflammatory mediators acting as proinflammatory cytokine. In this study, we examined the effects of candesartan, an angiotensin receptror blocker, in the chronic low-grade inflammation observed in DM 2. MATERIALS AND METHODS: Seventeen patients with DM2 of <5years duration were recruited for the study. Patients received 4mg of candesartan, an angiotensin receptor blocker, for 6months. Blood levels of IL-6, MCP-1, hs-CRP and other inflammatory indices were measured before and at the end of candesartan administration. RESULTS: At the end of treatment with candesartan, IL-6 levels decreased significantly (P<0·05). Serum levels of MCP-1 and hs-CRP showed a trend for significant decrease with treatment (P<0·08 and P<0·09, respectively). Statistically significant correlations were found between hs-CRP and MCP-1 (r=0·623, P< 0·05), IL-6 and MCP-1 (r=0·703, P<0·05) and TRT and MCP-1 (r=0·752, P<0·05), before but not at the end of candesartan administration. CONCLUSIONS: Candesartan could decrease the low-grade inflammation of type 2 DM as shown by the decrease of inflammatory mediators. Thus, angiotensin receptor blockers could be useful for treating patients with DM2 not only for their antihypertensive capacity but also for their anti-inflammatory actions.

Screening for the high-risk foot of ulceration: tests of somatic and autonomic nerve function.

Diabetic foot ulcers affect almost 5% of the patients with diabetes and carry a huge physical, emotional, and financial burden. Almost 80% of amputations in patients with diabetes are preceded by a foot ulcer. The need for simple screening methods for prevention of foot ulcers and amputations is indisputable. Simple tests such as monofilament, tuning fork, vibration perception threshold determination, ankle reflexes, and pinprick sensation alone or in combination have been studied prospectively and can be used for identification of patients at risk. Newer tests examining sudomotor dysfunction and skin dryness have been introduced in recent years. In cross-sectional studies sudomotor dysfunction assessed by either sympathetic skin response or NEUROPAD™ (Miro Verbandstoffe GmbH, Wiehl-Drabenderhöhe, Germany) testing has been consistently associated with foot ulceration. In addition, NEUROPAD™ testing is simple, reproducible, and widely available and has a high sensitivity for the diagnosis of clinical or subclinical diabetic polyneuropathy. Prospective studies are required to establish whether sudomotor dysfunction can predict foot ulcers and if simple methods assessing sudomotor dysfunction (eg, NEUROPAD™ testing) can be included in the screening tests for the prevention of this complication.

Evaluation of three methods for retrospective correction of vignetting on medical microscopy images utilizing two open source software tools.

Correction of vignetting on images obtained by a digital camera mounted on a microscope is essential before applying image analysis. The aim of this study is to evaluate three methods for retrospective correction of vignetting on medical microscopy images and compare them with a prospective correction method. One digital image from four different tissues was used and a vignetting effect was applied on each of these images. The resulted vignetted image was replicated four times and in each replica a different method for vignetting correction was applied with fiji and gimp software tools. The highest peak signal-to-noise ratio from the comparison of each method to the original image was obtained from the prospective method in all tissues. The morphological filtering method provided the highest peak signal-to-noise ratio value amongst the retrospective methods. The prospective method is suggested as the method of choice for correction of vignetting and if it is not applicable, then the morphological filtering may be suggested as the retrospective alternative method.

ß2-Microglobulin, pulse pressure and metabolic alterations in hemodialysis patients.

BACKGROUND/AIM: Pulse pressure (PP) is a result of arterial stiffness seen in dialysis patients, but may be a consequence of fluid overload. We examined the role of ß(2)-microglobulin (ß(2)M) in PP in relation to metabolic alterations in patients on different hemodialysis (HD) modalities. METHODS: We studied 76 hemodialyzed patients on regular HD (n = 34), predilution bagged hemodiafiltration (n = 19) and online predilution hemodiafiltration (n = 23). ß(2)M levels were measured by radioimmunoassay, and the clearance of ß(2)M was assessed by Kt/V for ß(2)M. Arterial stiffness was measured as carotid-femoral pulse wave velocity, and PP was derived. Insulin levels were measured using immunoradioassay, and insulin resistance was calculated using homeostasis model assessment insulin resistance (HOMA-IR). Serum bicarbonate levels were measured using a blood gas analyzer, and percent sodium removal was calculated. RESULTS: ß(2)M levels predict increased PP (p = 0.02) adjusting for age, HD modalities, HD duration, HOMA-IR and percent sodium removal. ß(2)M was positively associated with HOMA-IR (r = 0.306, p = 0.007). Serum bicarbonate levels and carotid-femoral pulse wave velocity were inversely associated (r = -0.719, p = 0.001). CONCLUSIONS: ß(2)M levels were positively associated with PP, which was influenced mainly by dialysis modality fluid and sodium balance and less by arterial stiffness. ß(2)M levels were positively associated with insulin resistance. Uremic acidosis may contribute to arterial stiffness.

The impact of metabolic syndrome on left ventricular myocardial performance.

BACKGROUND: Metabolic syndrome (MetS) is common and is associated with increased cardiovascular morbidity and mortality. Recent prospective studies suggested that MetS is associated with increased risk of heart failure. In the present cross-sectional study, we examined the association between left ventricular myocardial performance with MetS. MATERIALS AND METHODS: A total of 550 non-diabetic subjects, 275 without MetS and 275 with MetS, matched for gender, age and body mass index and free of clinically apparent macrovascular disease were studied. MetS was diagnosed using the NCEP-ATP III criteria. Left ventricular myocardial performance was assessed using the Tei index. RESULTS: Both men and women with MetS had higher values of the Tei index, indicating worse myocardial performance, in comparison with those without MetS (p < 0.001). Participants with a cluster of more components of the MetS had higher Tei index values than those with fewer components of the MetS. In addition, among normotensive subjects, those with MetS had significantly higher Tei index values than subjects without MetS. Multivariate linear regression analysis, after adjustment for age and body mass index, demonstrated that MetS status and from the individual components of the MetS, high fasting blood glucose levels, higher blood pressure, low high density lipoprotein levels and high waist circumference were associated with worse myocardial performance. CONCLUSION: MetS is associated with subclinical myocardial dysfunction in both men and women. Strategies to reduce the cardiovascular burden and the risk of heart failure associated with MetS should aim at prevention of the MetS and its related conditions.

Heart rate variability in advanced chronic kidney disease with or without diabetes: midterm effects of the initiation of chronic haemodialysis therapy.

BACKGROUND: Previous studies in different clinical settings have established heart rate variability (HRV) as a significant independent risk factor for higher mortality and cardiac death. The aim of this study was to examine the effect of chronic haemodialysis therapy on time- and frequency-domain parameters of HRV in diabetic and non-diabetic patients with chronic kidney disease (CKD). METHODS: We studied 25 patients with stage 4 CKD and type 2 diabetes mellitus (CKD4+DM), 25 patients with stage 4 CKD without diabetes (CKD4), 25 patients with type 2 diabetes mellitus (DM) and 25 healthy subjects (HS). The study was performed in two phases. In the first phase, a 24-h Holter electrocardiographic (ECG) monitoring was performed in all subjects. The patients with stage 4 CKD were followed up until they progressed to stage 5, and in the second phase of the study, they underwent a 24-h Holter ECG monitoring after completion of 3 months of conventional haemodialysis treatment. RESULTS: In the first phase of the study, a reduction in cardiac sympathetic activity in CKD4 patients (significantly lower SDNN, SDANN/5 min, SD and VLF vs. HS) and worse autonomic function in CKD4+DM patients (significantly lower SDNN, SDANN/5 min, SD, VLF and LF/HF) vs. HS, DM and CKD4 was observed. After 3 months of dialysis therapy, the patients with CKD+DM showed a significant improvement only in the time-domain parameter SDANN/5 min, while the time-domain parameters SDNN, SDANN/5 min and SD were improved in CKD patients without diabetes. Frequency-domain parameters of HRV remained unchanged in both groups. CONCLUSIONS: CKD is associated with worse cardiac autonomic function. Haemodialysis therapy for 3 months improves some indices of HRV, and this effect is more pronounced in non-diabetic subjects. Our findings suggest that the improvement of HRV after the initiation of chronic dialysis therapy can ameliorate clinical outcomes and survival in patients with end-stage renal disease.

Whipple disease.

Whipple disease (WD) is a rare disease caused by Tropheryma whipplei. The classic profile of the patient is that of a middle-aged man presenting with fever, chronic diarrhea, and arthralgias. Extragastrointestinal manifestations are not rare. A high degree of clinical suspicion for the disease is needed in atypical cases. Trimethoprim-sulfamethoxazole is the treatment of choice. We present two patients with WD. The first presented with melena and generalized hyperpigmentation. The second had depression for two years before the typical symptoms. Both hyperpigmentation and long-lasting depression without the typical manifestations of the disease are rare. Histologic examination of tissue biopsies was diagnostic for WD. Both patients were treated successfully with trimethoprim-sulfamethoxazole.

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.

Association between asymptomatic median mononeuropathy and diabetic polyneuropathy severity in patients with diabetes mellitus.

BACKGROUND: Asymptomatic median mononeuropathy (AMM) and diabetic polyneuropathy (DPN) often coexist and can be difficult to distinguish electrophysiologically. Moreover, the potential association between AMM and DPN has not been extensively evaluated. OBJECTIVE: We investigated the relation between AMM and DPN severity in consecutive diabetic patients. METHODS: The non-dominant limb was studied electrophysiologically in 100 consecutive diabetic patients with no symptoms of carpal tunnel syndrome on the non-dominant side. AMM was diagnosed based on previously validated electrophysiological criteria. DPN severity was graded according to the Michigan diabetic neuropathy score. RESULTS: AMM was discovered in 28% of the study population (Adjusted Wald 95% CI: 20%-37%). It was more common in women, displayed a tendency of being more common in patients over 50 years old and correlated with the severity of DPN and the number of abnormal nerves on nerve conduction studies. It was present in 18.1% of patients without evidence of DPN. No correlation was found with the duration and type of diabetes. In multivariate logistic regression models increasing severity of DPN was independently associated with the presence AMM (Wald test=10.557, df=3, p=0.014). Patients with DPN stage III and IV had a five-fold (OR=5.06, 95% CI=1.49-17.19) and a four-fold (OR=4.50, 95% CI=1.15-17.65) respectively increased likelihood to present with AMM in comparison to DPN stage I (reference group). CONCLUSIONS: Our results confirmed the high incidence of AMM in diabetic patients. AMM was present in a significant number of patients in the absence of DPN and the likelihood of AMM detection increased with increasing severity of DPN.

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.

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.

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.

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.

Metabolic syndrome is not associated with reduction in aortic distensibility in subjects with type 2 diabetes mellitus.

BACKGROUND: Aortic distensibility (AD) is a marker of the elastic properties of the aorta. Reduction of AD occurs early in subjects with type 2 diabetes mellitus (T2DM) and it is associated with subclinical generalized atherosclerosis. Metabolic syndrome (MetS) is common in subjects with T2DM and predicts cardiovascular morbidity and mortality. This study examined the potential relationship between MetS and AD in a cohort of subjects with T2DM. METHODS AND RESULTS: A total of 210 subjects with T2DM were studied. MetS was diagnosed using the NCEP/ATP-III criteria. AD was assessed non-invasively by ultrasonography. The prevalence of MetS was 64.8%. AD was not significantly different between subjects with and without MetS (1.80 +/- 0.54 vs. 1.84 +/- 0.53 10-6 dyn-1 cm2, p = 0.55). Univariate linear regression analysis showed that AD was associated positively with male sex (p = 0.02) as well as glomerular filtration rate (p < 0.001), and negatively with age (p = 0.04), history of hypertension (p = 0.001), as well as duration of diabetes (p < 0.001). After multivariate adjustment, AD was associated independently and significantly only with age (p = 0.02), duration of diabetes p < 0.001), and history of hypertension (p = 0.004); no significant relationship was found with MetS status, the sum of the components of the MetS or the individual components-besides hypertension-of the MetS. CONCLUSION: In subjects with T2DM, MetS status per se is not associated with reduction of AD. In addition, it was shown that besides ageing, duration of glycemia was a strong predictor of AD. From the components of the MetS only hypertension was associated with reduction of the elastic properties of the aorta.