Dietary potassium intake and risk of diabetes : a systematic review and meta-analysis of prospective studies

(1) Background: Dietary potassium intake is positively associated with reduction of cardiovascular risk. Several data are available on the relationship between dietary potassium intake, diabetes risk and glucose metabolism, but with inconsistent results. Therefore, we performed a meta-analysis of the prospective studies that explored the effect of dietary potassium intake on the risk of diabetes to overcome these limitations. (2) Methods: A random-effects dose–response meta-analysis was carried out for prospective studies. A potential non-linear relation was investigated using restricted cubic splines. (3) Results: A total of seven prospective studies met the inclusion criteria. Dose–response analysis detected a non-linear relationship between dietary potassium intake and diabetes risk, with significant inverse association starting from 2900 mg/day by questionnaire and between 2000 and 5000 mg/day by urinary excretion. There was high heterogeneity among studies, but no evidence of publication bias was found. (4) Conclusions: The results of this meta-analysis indicate that habitual dietary potassium consumption is associated with risk of diabetes by a non-linear dose–response relationship. The beneficial threshold found supports the campaigns in favour of an increase in dietary potassium intake to reduce the risk of morbidity and mortality. Further studies should be carried out to explore this topic

GSTB1-1 from Proteus mirabilis: a snapshot of an enzyme in the evolutionary pathway from a redox enzyme to a conjugating enzyme.

The native form of the bacterial glutathione transferase B1-1 (EC ) is characterized by one glutathione (GSH) molecule covalently linked to Cys-10. This peculiar disulfide, only found in the Beta and Omega class glutathione S-transferases (GSTs) but absent in all other GSTs, prompts questions about its role and how GSH can be activated and utilized in the reaction normally performed by GSTs. Stopped-flow and spectroscopic experiments suggest that, in the native enzyme (GSTB1-1ox), a second GSH molecule is present, albeit transiently, in the active site. This second GSH binds to the enzyme through a bimolecular interaction followed by a fast thiol-disulfide exchange with the covalently bound GSH. The apparent pK(a) of the non-covalently bound GSH is lowered from 9.0 to 6.4 +/- 0.2 in similar fashion to other GSTs. The reduced form of GSTB1-1 (GSTB1-1red) binds GSH 100-fold faster and also induces a more active deprotonation of the substrate with an apparent pK(a) of 5.2 +/- 0.1. Apparently, the absence of the mixed disulfide does not affect k(cat) and K(m) values in the GST conjugation activity, which is rate-limited by the chemical step both in GSTB1-1red and in GSTB1-1ox. However, GSTB1-1ox follows a steady-state random sequential mechanism whereas a rapid-equilibrium random sequential mechanism is adopted by GSTB1-1red. Remarkably, GSTB1-1ox and GSTB1-1red are equally able to catalyze a glutaredoxin-like catalysis using cysteine S-sulfate and hydroxyethyl disulfide as substrates. Cys-10 is an essential residue in this redox activity, and its replacement by alanine abolishes this enzymatic activity completely. It appears that GSTB1-1 behaves like an "intermediate enzyme" between the thiol-disulfide oxidoreductase and the GST superfamilies

Impact of a mediterranean dietary pattern and its components on cardiovascular risk factors, glucose control, and body weight in people with type 2 diabetes: A real-life study

This study evaluates the relation of a Mediterranean dietary pattern and its individual components with the cardiovascular risk factors profile, plasma glucose and body mass index (BMI) in people with type 2 diabetes. We studied 2568 participants at 57 diabetes clinics. Diet was assessed with the EPIC (European Prospective Investigation into Cancer and Nutrition) questionnaire, adherence to the Mediterranean diet was evaluated with the relative Mediterranean diet score (rMED). A high compared to a low score was associated with a better quality of diet and a greater adherence to the nutritional recommendations for diabetes. However, even in the group achieving a high score, only a small proportion of participants met the recommendations for fiber and saturated fat (respectively 17% and 30%). Nonetheless, a high score was associated with lower values of plasma lipids, blood pressure, glycated hemoglobin, and BMI. The relationship of the single food items components of the rMED score with the achievement of treatment targets for plasma lipids, blood pressure, glucose, and BMI were also explored. The study findings support the Mediterranean dietary model as a suitable model for type 2 diabetes and the concept that the beneficial health effects of the Mediterranean diet lie primarily in its synergy among various nutrients and foods rather than on any individual component

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (>= 4.7 mg/dL) and CVM (>= 5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p < 0.001) and CVM (1.31 [1.11-1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels

Role of continuous glucose monitoring in diabetic patients at high cardiovascular risk. an expert-based multidisciplinary delphi consensus

Background: Continuous glucose monitoring (CGM) shows in more detail the glycaemic pattern of diabetic subjects and provides several new parameters (“glucometrics”) to assess patients’ glycaemia and consensually guide treatment. A better control of glucose levels might result in improvement of clinical outcome and reduce disease complications. This study aimed to gather an expert consensus on the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk or with heart disease. Methods: A list of 22 statements concerning type of patients who can benefit from CGM, prognostic impact of CGM in diabetic patients with heart disease, CGM use during acute cardiovascular events and educational issues of CGM were developed. Using a two-round Delphi methodology, the survey was distributed online to 42 Italian experts (21 diabetologists and 21 cardiologists) who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement. Results: Forty experts (95%) answered the survey. Every statement achieved a positive consensus. In particular, the panel expressed the feeling that CGM can be prognostically relevant for every diabetic patient (70%) and that is clinically useful also in the management of those with type 2 diabetes not treated with insulin (87.5%). The assessment of time in range (TIR), glycaemic variability (GV) and hypoglycaemic/hyperglycaemic episodes were considered relevant in the management of diabetic patients with heart disease (92.5% for TIR, 95% for GV, 97.5% for time spent in hypoglycaemia) and can improve the prognosis of those with ischaemic heart disease (100% for hypoglycaemia, 90% for hyperglycaemia) or with heart failure (87.5% for hypoglycaemia, 85% for TIR, 87.5% for GV). The experts retained that CGM can be used and can impact the short- and long-term prognosis during an acute cardiovascular event. Lastly, CGM has a recognized educational role for diabetic subjects. Conclusions: According to this Delphi consensus, the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk is promising and deserves dedicated studies to confirm the experts’ feeling

Le complicanze micro e macroangiopatiche del diabete mellito tipo 2

Le complicanze del diabete mellito tipo 2, sia micro che macroangiopatiche, hanno un notevole impatto socio-ecomonico, riducendo notevolmente l’aspettativa e la qualità di vita dei pazienti diabetici: la patologia macrovascolare è infatti la più frequente causa di morte nella popolazione diabetica, mentre la nefropatia e la retinopatia diabetica sono le più frequente cause di insufficienza renale terminale e di cecità rispettivamente. Le evidenze scientifiche dimostrano che i programmi di screening ed il trattamento di queste patologie riducono significativamente la mortalità e la morbilità nei pazienti diabetici. Da qui nasce l’esigenza di una maggiore attenzione alla ricerca di marcatori sempre più precoci di malattia, che potrebbero permettere l’individuazione di soggetti a maggior rischio di sviluppare le complicanze del diabete, nei quali l’applicazione di appropriati interventi potrebbero prevenire o ritardare la progressione a stadi più avanzati della malattia È per questo motivo che la mia attività di ricerca svolta durante questo ciclo di dottorato si è soffermata su tre aspetti specifici delle complicanze croniche del diabete: 1) lo studio di un indice utile come marcatore precoce della nefropatia diabetica e predittore di sviluppo e progressione del danno renale 2) lo studio delle subfrazioni lipoproteriche come nuovi fattori di rischio di aterosclerosi subclinica a livello carotideo (ispessimento medio-intimale e placche carotidee) 3) la valutazione comparativa di due trattamenti ipoglicemizzanti orali sulla mortalità cardiovascolare Per quanto riguarda la predizione della nefropatia diabetica, il mio studio, prospettico osservazionale, ha dimostrato che l’indice di resistenza renale, una semplice misura dell’emodinamica intrarenale misurata attraverso l’ecodoppler delle arterie renali, è un marcatore di nefropatia diabetica largamente utilizzabile nella pratica clinica, capace di predire lo sviluppo e la progressione della malattia renale anche nei soggetti normoalbuminurici, quindi in una fase precocissima della malattia in cui tali soggetti sarebbero identificati, secondo le attuali conoscenze, come esenti da danno renale. Per quanto riguarda invece il secondo punto, questo studio ha permesso di dimostrare che la concentrazione e le dimensioni delle diverse particelle lipoproteiche hanno un ruolo importante come fattori di rischio cardiovascolare, aggiuntivo rispetto al profilo lipidico classico. In particolare indica che esistono possibili differenze nei determinanti lipoproteici dell’IMT e della comparsa (e/o peggioramento) delle placche: la concentrazione di particelle LDL potrebbe essere più strettamente correlate all’IMT, mentre la concentrazione delle VLDL piccole e delle LDL grandi potrebbero essere più legate alla formazione di placche. La relazione tra il numero di placche e le LDL larghe piuttosto che con le LDL totali o piccole suggerisce che le particelle LDL grandi, e non solo le piccole, possono essere implicate nell’evoluzione del processo aterosclerotico e nella malattia cardiovascolare. Il secondo aspetto studiato della malattia cardiovascolare è tutt’ora in corso di valutazione con uno studio di intervento multicentrico randomizzato che si propone di valutare nei pazienti diabetici l’effetto di due differenti strategie terapeutiche (associazione metformina + sulfoniluree vs metformina + tiazolidinedioni), largamente utilizzate nella pratica clinica, su mortalità e morbidità cardiovascolare, nonché compenso glicemico, effetti collaterali, rapporto costo/efficacia. Questo studio è di grande interesse ed attualità perché permetterà di rispondere a importanti domande che si pongono sulla efficacia dei farmaci ipoglicemizzanti nella prevenzione della malattia cardiovascolare, domande a cui non è stata data una chiara risposta dai trials finora condotti, così come sottolineato dalle maggiori società scientifiche nazionali ed internazionali