Gestational Diabetes Mellitus pregnancy by pregnancy. early, late and nonrecurrent GDM

Aims: To assess the GDM recurrence rate in a cohort of pregnant women with prior GDM, to compare two consecutive pregnancies complicated by GDM, to compare women with nonrecurrent and recurrent GDM and to stratify the latter in women with early and late recurrent GDM.Methods: Retrospective study including 113 women with GDM in an index pregnancy (G1), at least a postindex pregnancy (G2) and normal glucose tolerance in between. The GDM recurrence rate was assessed, and maternal and neonatal outcomes and pancreatic beta cell function of the index pregnancy were compared with those of the postindex pregnancy (G1 vs. G2). Women with nonrecurrent GDM were compared with those with recurrent GDM.Results: The GDM recurrence rate was 83.2% and the minimum prevalence of early recurrent GDM was 43,4%. The pregravid BMI of women with recurrent GDM increased between the two pregnancies (27.3 +/- 5.98 vs. 28.1 +/- 6.19 kg/m(2), p < 0.05). Women with recurrent GDM had a higher prepregnancy BMI than those with nonrecurrent GDM either at the index (27.3 +/- 5.98 vs. 23.1 +/- 4.78 kg/m(2), p < 0.05) or the postindex pregnancy (27 +/- 6vs.24 +/- 4,4 kg/m2, p < 0.05).Conclusions: GDM shows a high recurrence rate in our cohort of slightly overweight women, with an early GDM minimum prevalence of 43.4%

Screening of postpartum diabetes in women with gestational diabetes: high-risk subgroups and areas for improvements-the strong observational study

AIMS: To assess the proportion of women with gestational diabetes (GDM) by performing postpartum Oral Glucose Tolerance Test (OGTT) and to identify GDM phenotypes at high-risk of postpartum dysglycemia (PPD).METHODS: Observational, retrospective, multicenter study involving consecutive GDM women. Recursive partitioning (RECPAM) analysis was used to identify distinct and homogeneous subgroups of women at different PPD risk.RESULTS: From a sample of 2,736 women, OGTT was performed in 941 (34.4%) women, of whom 217 (23.0%) developed PPD. Insulin-treated women having family history of diabetes represented the subgroup with the highest PPD risk (OR 5.57, 95% CI 3.60-8.63) compared to the reference class (women on diet with pre-pregnancy BMI<=28.1kg/m2). Insulin-treated women without family diabetes history and women on diet with pre-pregnancy BMI>28.1kg/m2 showed a two-fold PPD risk. Previous GDM and socioeconomic status represent additional predictors. Fasting more than post-prandial glycemia plays a predictive role, with values of 81-87mg/dl (4.5-4.8mmol/l) (lower than the current diagnostic GDM threshold) being associated with PPD risk.CONCLUSIONS: Increasing compliance to postpartum OGTT to prevent/delay PPD is a priority. Easily available characteristics identify subgroups of women more likely to benefit from preventive strategies. Fasting BG values during pregnancy lower than those usually considered deserve attention

Effetti clinici e placentari dell'iperglicemia in gravidanza in donne con diabete mellito

Nelle donne diabetiche la placenta presenta delle alterazioni strutturali e funzionali potenzialmente correlabili a una disregolazione del sistema insulina/IGF che possono essere responsabili di un alterato trasporto di nutrienti al feto e di un aumentata crescita fetale. In queste donne la valutazione del sistema insulina/IGF placentare può fornire importanti informazioni sui meccanismi delle complicanze fetali/neonatali e materne e sulle patologie dell età evolutiva dei bambini nati da madre diabetica. Scopo dello studio è stato quello di valutare l effetto del compenso glicemico sulla placenta in termini di espressione di IR e IGF-1R e di valutare la fosforilazione recettoriale e la trasmissione del segnale intracellulare. Sono state studiate: 40 pazienti con gravidanza fisiologica, 20 pazienti con diabete gestazionale (GDM), 20 pazienti con diabete mellito tipo 1 (DMT1). Le pazienti con DMT1 hanno mostrato: una minore fosforilazione di AKT (0.6±0.1 UD) rispetto agli altri due gruppi (1.7±0.2 UD nel gruppo delle gravidanze fisiologiche; 1.9±0.6 UD nel gruppo GDM). Il dato permane anche se correggiamo i valori per la glicemia peri-parto. La deficitaria fosforilazione di AKT (e quindi una meno efficace attivazione della via metabolica), potrebbe essere implicata nella maggiore frequenza di macrosomia/LGA registrata nei neonati da madri con DMT1 (50%). Una simile tendenza è stata trovata quando, indipendentemente dalla diagnosi, le pazienti sono state divise in base alla presenza o meno della macrosomia: nelle placente delle donne con macrosomia la fosforilazione di AKT è risultata deficitaria rispetto alle placente delle donne senza macrosomia. Le pazienti con DMT1 hanno inoltre mostrato una maggiore fosforilazione di IGF-IR (3.6±0.6 UD) rispetto agli altri due gruppi (1.8±0.2 UD nel gruppo delle gravidanze fisiologiche; 2.9±0.8 UD nel gruppo GDM). Tale differenza significativa, però, scompare se correggiamo i valori per la glicemia peri-parto. Quindi tale maggiore fosforilazione potrebbe essere verosimilmente legata agli aumentati livelli di glicemia in acuto che si verificano nel periodo subito prima del parto. Ciò potrebbe significare che la fosforilazione di IGF-IR (rispetto a quella di IR) sia implicata nel determinismo di alcuni outcome neonatali sfavorevoli legati al periodo peri-parto (come ad esempio l ipoglicemia neonatale o la prematurità). Dall analisi di regressione lineare è emerso che l emoglobina glicata media del II e III trimestre correla positivamente con l espressione di AKT. Il peggiore compenso metabolico nelle fasi centrali della gravidanza potrebbe, quindi, condizionare la trasduzione del segnale intracellulare a valle del recettore insulinico. E inoltre emerso che il peso della placenta non correla con l espressione di IR, IGF-IR, ERK, AKT e con la loro fosforilazione nella placenta al momento del parto. Pertanto, potrebbero coesistere altri fattori in grado di influenzare la crescita della placenta. Tuttavia non si può escludere anche un ruolo di IR e IGF-IR dal momento che lo studio è stato effettuato a termine di gravidanza, mentre è possibile che tali recettori siano coinvolti in epoca gestazionale differente da quella finale. In letteratura è riportato che IR, IGF-IR e i loro ligandi sono importanti per la crescita placentare e fetale, ma i dati nelle donne diabetiche sono scarsi. Questo è il primo studio in cui vengono messi in relazione gli esiti sfavorevoli della gravidanza con l espressione e la fosforilazione di fattori di crescita a livello placentare

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer’s disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment

Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies

Influence of the Mediterranean and Ketogenic Diets on cognitive status and decline:a narrative review

Abstract Alzheimer’s disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders

Efficacy of flash glucose monitoring in pregnant women with poorly controlled pregestational diabetes (flashmom): a randomized pilot study

Background and Aims Good glycemic control is crucial to reduce the risk of adverse pregnancy outcomes. Our aim was to evaluate the efficacy of Flash Glucose Monitoring (FGM) on glucose control in women with pregestational diabetes. Methods and Results Forty women with inadequately controlled type 1 (T1D, n=34) and type 2 (T2D, n=6) diabetes at conception were randomly assigned to two arms: the Flash Glucose group (FG, n=21) using FGM, and the control group (CG, n=19) using self-monitoring of blood glucose (SMBG). Glycated hemoglobin (HbA1c, %), time in (TIR), below (TBR) and above (TAR) range, glucose variability as well as the occurrence of maternal and neonatal adverse outcomes, were evaluated. HbA1c decreased significantly (p<0.01) and similarly (-0.65±0.7 vs. -0.67±0.8 for FG and CG, respectively; p=0.89) in both groups during pregnancy. HbA1c reduction was positively associated with the number of daily FGM scans (p<0.01). TBR (12.1±2.0% vs. 19.6±3.9%, p=0.04) and the mean of the daily serum glucose difference (MODD) index (59.1±5.4 vs. 77.7±4.6, p=0.02) were significantly lower in FG at second trimester. The rates of perinatal adverse outcomes were not different in the two studied groups. Conclusions In women with pregestational diabetes, FGM and SMBG had similar efficacy on glucose control during pregnancy. FGM showed additional advantages in terms of TBR and glucose variability. Achievement of good metabolic results depended on the adequate use of glucose sensor

Attività fisica nella gravidanza di donne con diabete

Il diabete gestazionale (GDM) è il più diffuso disordine metabolico in corso di gravidanza e, se non tempestivamente diagnosticato e correttamentetrattato è potenzialmente dannoso sia per la madre che per il feto