Sleep quality and sex-related factors in adult patients with immune-mediated diabetes: a large cross-sectional study

AimTo analyze sleep quality and its relationships with clinical and biochemical features in a large cohort of adults with autoimmune diabetes.MethodsWe administered to 553 patients with autoimmune diabetes the questionnaires: Pittsburgh Sleep Quality Index (PSQI), diabetes distress scale, diabetes-related quality of life and diabetes treatment satisfaction questionnaire. We excluded patients with missing HbA1c +/- 4 months from PSQI administration or incorrect PSQI compilation (n = 110).ResultsAltered sleep quality was recorded in 142/443 subjects (32%), insufficient total sleep time in 177/443 (40%). The altered sleep quality group had higher HbA1c (median 56 mmol/mol [interquartile range-IQR 49-62] vs 59 [IQR 52-68]; P < 0.001), higher average HbA1c in the previous 36 months (59 mmol/mol [IQR 54-68] vs 56 [IQR 51-62]; P < 0.001), and more individuals with HbA1c > 53 mmol/mol (74.6% vs 62.8%; P = 0.014). Diabetes duration (P = 0.63), type of insulin delivery (P = 0.48) and glucose monitoring (P = 0.35) were uninfluential. Patients with altered sleep quality showed higher prevalence of autoimmune (42 vs 28%; P = 0.005) and mental diseases (12 vs 4%; P = 0.002); there were greater emotional distress, and lower quality of life and treatment satisfaction (P < 0.001 for all), irrespective of sex. Men with altered sleep quality had higher HbA1c and prevalence of autoimmune diseases. Women showed greater prevalence of psychiatric disorders. Average HbA1c of the previous 36 months, autoimmune or psychiatric disorders were independent predictive factors for altered sleep quality.ConclusionOne-third of the patients with autoimmune diabetes showed altered sleep quality, which associates with worse glycemic control, and autoimmune and mental disorders, with sex-specific differences

Pharmacokinetics and pharmacogenetics of SSRIs during pregnancy : An observational study

Background: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. Methods: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses. Results: Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway. Conclusions: Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn

A simple index of lipid overaccumulation is a good marker of liver steatosis

<p>Abstract</p> <p>Background</p> <p>Liver steatosis is often found in association with common cardiometabolic disorders, conditions that may all occur in a shared context of abdominal obesity and dyslipidemia. An algorithm for identifying liver steatosis is the fatty liver index (FLI). The lipid accumulation product (LAP) is an index formulated in a representative sample of the US population to identify cardiometabolic disorders. Because FLI and LAP share two components, namely waist circumference and fasting triglycerides, we evaluated the ability of LAP to identify liver steatosis in the same study population from the Northern Italian town where FLI was initially developed.</p> <p>Methods</p> <p>We studied 588 individuals (59% males) aged 21 to 79 years. Liver steatosis was detected by ultrasonography and coded ordinally as none, intermediate and severe. 44% of the individuals had liver steatosis. Using proportional-odds ordinal logistic regression, we evaluated the ability of log-transformed LAP (lnLAP) to identify liver steatosis. We considered the benefits to our model of including terms for sex, age, suspected liver disease and ethanol intake. We calculated the 3-level probability of liver steatosis according to lnLAP and sex, providing tables and nomograms for risk assessment.</p> <p>Results</p> <p>An ordinal proportional-odds model consisting of lnLAP and sex offered a reasonably accurate identification of liver steatosis. The odds of more severe <it>vs. </it>less severe steatosis increased for increasing values of lnLAP (odds ratio [OR] = 4.28, 95%CI 3.28 to 5.58 for each log-unit increment) and was more likely among males (OR = 1.88, 95%CI 1.31 to 2.69).</p> <p>Conclusion</p> <p>In a study sample of adults from Northern Italy, the simple calculation of LAP was a reasonably accurate approach to recognizing individuals with ultrasonographic liver steatosis. LAP may help primary care physicians to select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. A more thorough assessment of LAP's potential for identifying liver steatosis will require its cross-evaluation in external populations.</p

Diabetes and liver disease: an ominous association

Diabetes mellitus and advanced liver disease are associated with each other more frequently than expected by chance, and such an association carries a significant risk of morbidity and mortality. A metabolic pathway leading to advanced liver disease via fatty liver and steatohepatitis has been demonstrated, further supporting the possibility that cirrhosis may be a late complication of diabetes. In addition, an interaction between hepatitis C virus (HCV) and insulin resistance increases the overall prevalence of associated diseases, through largely unidentified mechanisms. Extensive prospective monitoring of non-alcoholic fatty liver disease cases, analysis of insulin signaling in HCV-infected patients using molecular biology techniques, and intervention studies, will help to clarify the mechanisms of action of the possible clinical strategies, the predictive value of biochemical, histological, and clinical markers, and the effectiveness of treatments availabl

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Abstract. -A paradox exists in the relationship between nutrition and cancer. Excessive dietary intake of nutrients and decreased physical activity represent two modifiable factors responsible for cancer development, namely for cancers of the gastrointestinal (GI) tract, and the present epidemics of obesity and diabetes is likely to increase the incidence of GI and metabolically-derived liver in the next few years. At the same time, in subjects diagnosed with cancer, malnutrition represents a risk factor of poor outcome following surgical resection, as well as of increased toxicity following chemo-and radiotherapy. Any effort should be made to modify the current trend of obesity for cancer prevention, as well as to provide enteral or parenteral nutritional support in cancer patients, to cope with nutritional needs and prevent cancer-related cachexia

Approcci nutrizionali nella steatoepatite non alcolica

La steatosi epatica non alcolica (Nonalcoholic fatty Liver Disease, NAFLD), manifestazione epatica della sindrome metabolica, strettamente associata ad obesit\ue0 e diabete, \ue8 patologia epatica che riconosce come meccanismo patogenetico l\u2019insulino-resistenza, sia a livello dell\u2019intero organismo, sia pi\uf9 specificamente epatica. La steatosi, definita per un accumulo di trigliceridi nel fegato superiore al 5-10% del suo peso, \ue8 variamente associata a fibrosi e necroinfiammazione, realizzando il quadro della steatoepatite non-alcolica (Non-Alcoholic Steatohepatitis, NASH), la fibrosi e la cirrosi. Attraverso questa via metabolica una percentuale non irrilevanti di pazienti giunge all\u2019insufficienza epatica terminale; circa il 10-15% dei soggetti in lista di trapianto di fegato nella varie strutture potrebbero essere giunti ad una insufficienza epatica terminale attraverso questo via. Il riconoscimento di questa patologia come problema importante di salute ha condotto a verificare la possibilit\ue0 che, accanto agli effetti negativi dell\u2019eccesso ponderale, la progressione della patologia potesse essere sostenuta da errati comportamenti alimentari e/o dalla sedentariet\ue0. Per quanto riguarda l\u2019apporto alimentare, i soggetti con NAFLD si caratterizzano per un eccessivo apporto di grassi saturi e sopratutto di carboidrati raffinati, che vengono convertiti a trigliceridi all\u2019interno del fegato. Una serie di studi condotti da un gruppo di ricerca finlandese ha estesamente dimostrato l\u2019esistenza di fattori genetici che possono condizionare gradi diversi di steatosi in presenza di simile eccesso ponderale, un effetto diretto di una dieta sperimentale ricca di grassi sul contenuto in trigliceridi del fegato, sul quadro di insulino-resistenza globale ed epatica, ed infine sul profilo biochimico

Il monitoraggio AIFA dei nuovi farmaci per il trattamento del diabete

Gli incretino-mimetici (exenatide) e gli inibitori della dipeptidil-peptidasi (DDP-4) (sitagliptin e vildagliptin) sono nuovi farmaci, attualmente disponibili in Italia, sviluppati per il controllo della glicemia in pazienti con diabete tipo 2. Un sistema di monitoraggio \ue8 stato attivato dall\u2019AIFA per valutare i reali vantaggi in termini di efficacia e di sicurezza di questi farmaci altamente innovativi. L\u2019analisi dei dati raccolti dal monitoraggio ha sostanzialmente confermato ci\uf2 che \ue8 emerso dagli studi pre-registrativi. L\u2019exenatide si \ue8 dimostrata in grado di migliorare il compenso metabolico e di indurre un calo ponderale in soggetti con diabete tipo 2. E\u2019 risultato essere un farmaco sicuro con effetti collaterali di lieve entit\ue0 principalmente a carico dell\u2019apparato gatro-intestinale e tendenti a scomparire con il protrarsi della terapia. L\u2019ipoglicemia \ue8 risultata un evento molto raro, osservato quando l\u2019exenatide era usata in terapia di associazione con sulfaniluree. Gli inibitori della DDP-4 hanno dimostrato una riduzione significativa dell\u2019Hb-glicata (lievemente inferiore rispetto all\u2019exenatide) ed un effetto complessivamente neutro sul peso corporeo. Si sono dimostrati farmaci ben tollerati, anche in soggetti in et\ue0 avanzata, con bassissimo rischio di ipoglicemia. Dato anche l\u2019alto costo saranno necessari ulteriori approfondimenti per definire meglio la tipologia del paziente che pu\uf2 usufruire di questi farmaci e i possibili effetti di queste molecole sui fattori di rischio cardiovascolare e sulle complicanze micro- e macro-angiopatiche. Interessante sar\ue0 confermare in vivo le capacit\ue0 rigenerative e proliferative di queste molecole sulla beta-cellula

Insulin resistance in nonalcoholic fatty liver disease

Abstract: Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. NAFLD is considered the hepatic component of the metabolic syndrome and insulin resistance represents its pathophysiological hallmark. Insulin resistance in NAFLD is characterized by reduced whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanism(s) underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Liver fat is highly correlated with all the components of the metabolic syndrome, independent of obesity, and NAFLD may increase the risk of type 2 diabetes and atherosclerosis. Overproduction of glucose, very low-density lipoproteins, C-reactive protein and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease. The reason(s) why some patients will develop NASH are poorly understood. Circulating free fatty acids may be cytotoxic by inducing lipid peroxidation and hepatocyte apoptosis. Insulin resistance is often associated with chronic low-grade inflammation, and numerous mediators released from immune cells and adipocytes may contribute liver damage and liver disease progression. Understanding the molecular mediators of liver injury would promote the development of mechanism-based therapeutic interventions. This article briefly summarizes the recent advances in our understanding of the relationship between NAFLD/NASH, insulin resistance and the metabolic syndrome