Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis

GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control

Serum homocysteine levels in men with and without erectile dysfunction: A systematic review and meta-analysis

Objectives. Elevated levels of serum homocysteine (Hcy) have been associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). This meta-analysis was aimed to assess serum Hcy levels in subjects with ED compared to controls in order to clarify the role of Hcy in the pathogenesis of ED. Methods. Medline, Embase, and the Cochrane Library were searched for publications investigating the possible association between ED and Hcy. Results were restricted by language, but no time restriction was applied. Standardized mean difference (SMD) was obtained by random effect models. Results. A total of 9 studies were included in the analysis with a total of 1320 subjects (489 subjects with ED; 831 subjects without ED). Pooled estimate was in favor of increased Hcy in subjects with ED with a SMD of 1.00, 95% CI 0.65-1.35, p < 0.0001. Subgroup analysis based on prevalence of diabetes showed significantly higher SMD in subjects without diabetes (1.34 (95% CI 1.08-1.60)) compared to subjects with diabetes (0.68 (95% CI 0.39-0.97), p < 0 0025 versus subgroup w/o diabetes). Conclusions. Results from our meta-analysis suggest that increased levels of serum Hcy are more often observed in subjects with ED; however, increase in Hcy is less evident in diabetic compared to nondiabetic subjects

Efficacy and safety of flash glucose monitoring in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis

INTRODUCTION: Flash glucose monitoring (FGM) is a factory-calibrated sensor-based technology for the measurement of interstitial glucose. We performed a systematic review and meta-analysis to assess its efficacy and safety in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched in July 2019. Twelve studies with a follow-up longer than 8 weeks, evaluating 2173 patients on prandial insulin, multiple daily insulin injections or continuous subcutaneous insulin infusion were included. The following data were extracted: HbA1c, time in range, time above 180 mg/dL, time below 70 mg/dL, frequency of hypoglycemic events, number of self-monitoring of blood glucose (SMBG) measurements, total daily insulin dose, patient-reported outcomes, adverse events, and discontinuation rate. A comparison with SMBG was conducted. RESULTS: FGM use was associated with a reduction in HbA1c (-0.26% (-3 mmol/mol); p=0.002) from baseline to the last available follow-up, which correlated with HbA1c levels at baseline (-0.4% (-4 mmol/mol) for each 1.0% (11 mmol/mol) of HbA1c above 7.2% (55 mmol/mol)). Also, a decrease in time below 70 mg/dL was found (-0.60 hours/day; p=0.04). Favorable findings in patient-reported outcomes and no device-related serious adverse events were reported. When compared with SMBG, FGM was characterized by no statistically different change in HbA1c (p=0.09), with lower number of SMBG measurements per day (-3.76 n/day; p<0.001) and risk of discontinuation (relative risk=0.42; p=0.001). A limited number of studies, with a heterogeneous design and usually with a short-term follow-up and without specific training, were found. CONCLUSIONS: The present review provides evidence for the use of FGM as an effective strategy for the management of diabetes

Postprandial glucose and HbA1c are associated with severity of obstructive sleep apnoea in non-diabetic obese subjects

Introduction: Obstructive sleep apnoea (OSA) is an underdiagnosed condition frequently associated with glycaemic control impairment in patients with type 2 diabetes. Aim: To assess the relationship between glycometabolic parameters and OSA in obese non-diabetic subjects. Methods: Ninety consecutive subjects (mean age 44.9 ± 12 years, mean BMI 42.1 ± 9 kg/m2) underwent polysomnography and a 2-h oral glucose tolerance test (OGTT). Results: OSA was identified in 75% of subjects, with a higher prevalence of males compared to the group of subjects without OSA (62% vs 32%, p = 0.02). Patients with OSA had comparable BMI (42.8 kg/m2 vs 39.4 kg/m2), a higher average HbA1c (5.8% vs 5.4%, p < 0.001), plasma glucose at 120 min during OGTT (2 h-PG; 123 mg/dl vs 97 mg/dl, p = 0.009) and diastolic blood pressure (81.1 mmHg vs 76.2 mmHg, p = 0.046) than obese subjects without OSA. HbA1c and 2 h-PG were found to be correlated with the apnoea-hypopnoea index (AHI; r = 0.35 and r = 0.42, respectively) and with percent of sleep time with oxyhaemoglobin saturation < 90% (ST90; r = 0.44 and r = 0.39, respectively). Further, in a linear regression model, ST90 and AHI were found to be the main determinants of 2 h-PG (β = 0.81, p < 0.01 and β = 0.75, p = 0.02, respectively) after controlling for age, sex, waist circumference, physical activity, and C-reactive protein. Similarly, ST90 and AHI persisted as independent determinants of HbA1c (β = 0.01, p = 0.01 and β = 0.01, p = 0.01, respectively). Conclusion: Beyond the traditional clinical parameters, the presence of a normal-high value of 2 h-PG and HbA1c should raise suspicion of the presence of OSA in obese subjects

Urine Proteome Analysis May Allow Noninvasive Differential Diagnosis of Diabetic Nephropathy

AbstractObjective: Chronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy (DN) in over one third of cases. We interrogated urine proteomic profiles generated by SELDI-TOF/MS with the aim to isolate a set of biomarkers able to reliably identify biopsy-proven DN and to establish a stringent correlation with the different patterns of renal injury. Research design and methods: Ten mug urine proteins from 190 subjects [20 healthy subjects (HS), 20 normoalbuminuric (NAD) and 18 microalbuminuric (MICRO) diabetic patients, and 132 patients with biopsy-proven nephropathy (65 DN, 10 diabetics with non-diabetic CKD (nd-CKD) and 57 non-diabetic patients with CKD)] were run by CM10 ProteinChip array and analysed by supervised learning methods (CART analysis). Results: The classification model correctly identified 75% NAD, 87.5% MICRO and 87.5% DN when applied to a blinded testing set. Most importantly, it was able to reliably differentiate DN from nd-CKD in both diabetic and non-diabetic patients. Among the best predictors of the classification model, we identified and validated 2 proteins, ubiquitin and ss2-microglobulin. Conclusions: Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis

Polyphenol intake and cardiovascular risk factors in a population with\ua0type 2 diabetes: The TOSCA.IT study.

Summary Background The role of polyphenol intake on cardiovascular risk factors is little explored, particularly in people with diabetes. Aim: To evaluate the association between the intake of total polyphenols and polyphenol classes with the major cardiovascular risk factors in a population with type 2 diabetes. Methods Dietary habits were investigated in 2573 males and females participants of the TOSCA.IT study. The European Prospective Investigation on Cancer and Nutrition (EPIC) questionnaire was used to assess dietary habits. In all participants, among others, we assessed anthropometry, plasma lipids, blood pressure, C-reactive protein and HbA1c following a standard protocol. The USDA and Phenol-Explorer databases were used to estimate the polyphenol content of the habitual diet. Results Average intake of polyphenols was 683.3 \ub1 5.8 mg/day. Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%, respectively). After adjusting for potential confounders, people with the highest intake of energy-adjusted polyphenols (upper tertile) had a more favorable cardiovascular risk factors profile as compared to people with the lowest intake (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9 mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs 148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs 134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was 1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the analysis was conducted separately for flavonoids or phenolic acids, the two main classes of polyphenols consumed in this population. Conclusions Polyphenol intake is associated with a more favorable cardiovascular risk factors profile, independent of major confounders. These findings support the consumption of foods and beverages rich in different classes of polyphenols particularly in people with diabetes. Clinical trial http://www.clinicaltrials.gov; Study ID number: NCT00700856

Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons

Decreased renal function in overweight and obese prepubertal children

BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity