Increased Intake of Both Caffeine and Non-Caffeine Coffee Components Is Associated with Reduced NAFLD Severity in Subjects with Type 2 Diabetes.

Coffee may protect against non-alcoholic fatty liver disease (NAFLD), but the roles of the caffeine and non-caffeine components are unclear. Coffee intake by 156 overweight subjects (87% with Type-2-Diabetes, T2D) was assessed via a questionnaire, with 98 subjects (all T2D) also providing a 24 h urine sample for quantification of coffee metabolites by LC-MS/MS. NAFLD was characterized by the fatty liver index (FLI) and by Fibroscan assessment of fibrosis.

Leveraging the future of diagnosis and management of diabetes: From old indexes to new technologies.

Background: Diabetes is a heterogeneous and multifactorial disease. However, glycemia and glycated hemoglobin have been the focus of diabetes diagnosis and management for the last decades. As diabetes management goes far beyond glucose control, it has become clear that assessment of other biochemical parameters gives a much wider view of the metabolic state of each individual, enabling a precision medicine approach.

Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

Aims/hypothesis: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven.

Methods: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet.

Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.

Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored.

S-Nitrosoglutathione Reverts Dietary Sucrose-Induced Insulin Resistance.

The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase in insulin sensitivity from the fast to the postprandial status. Hepatic regulation of glucose metabolism is crucial and has been shown to be modulated by glutathione (GSH) and nitric oxide (NO). However, knowledge of the metabolic action of GSH and NO in glucose homeostasis remains incomplete.

Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia.

Type 2 diabetes (T2D) heterogeneity is a major determinant of complications risk and treatment response. Using cluster analysis, we aimed to stratify glycemia within metabolic multidimensionality and extract pathophysiological insights out of metabolic profiling. We performed a cluster analysis to stratify 974 subjects (PREVADIAB2 cohort) with normoglycemia, prediabetes, or non-treated diabetes.

How Inflammation Impinges on NAFLD: A Role for Kupffer Cells.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most prevalent cause of liver disease worldwide and afflicts adults and children as currently associated with obesity and insulin resistance. Even though lately some advances have been made to elucidate the mechanism and causes of the disease much remains unknown about NAFLD. The aim of this paper is to discuss the present knowledge regarding the pathogenesis of the disease aiming at the initial steps of NAFLD development, when inflammation impinges on fat liver deposition.

Acute glucagon induces postprandial peripheral insulin resistance.

Glucagon levels are often moderately elevated in diabetes. It is known that glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn is associated with decreased postprandial insulin sensitivity. Given that cAMP pathway controls GSH levels we tested whether insulin sensitivity decreases after intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated whether glucagon promotes insulin resistance through decreasing hepatic GSH levels.

Risk of postprandial insulin resistance: the liver/vagus rapport.

Ingestion of a meal is the greatest challenge faced by glucose homeostasis. The surge of nutrients has to be disposed quickly, as high concentrations in the bloodstream may have pathophysiological effects, and also properly, as misplaced reserves may induce problems in affected tissues. Thus, loss of the ability to adequately dispose of ingested nutrients can be expected to lead to glucose intolerance, and favor the development of pathologies.

Effects of CPAP on nitrate and norepinephrine levels in severe and mild-moderate sleep apnea.

Background: Reduced plasma nitrate (NO(x)) levels and increased urinary norepinephrine (U-NE) levels have been described in severe obstructive sleep apnea (OSA), and are reverted by continuous positive airway pressure (CPAP). The effect of CPAP on these biomarkers in mild-moderate OSA is not well understood. The aim of this study was to compare NO(x) and U-NE levels and blood pressure (BP) between male patients with mild-moderate and severe OSA and determine the impact of 1 month of CPAP therapy on these parameters.

Postprandial but not fasting insulin resistance is an early identifier of dysmetabolism in overweight subjects.

The dynamic response to insulin is highly potentiated after meal ingestion, and this meal-induced insulin sensitization (MIS) in healthy subjects is dependent on cholinergic mechanisms. The main objective of this study was to test the hypothesis that the reduced response to insulin observed in moderately overweight subjects, in comparison with control lean subjects, is due to MIS impairment and not to a reduction in the direct hypoglycemic action of insulin. Both lean and overweight male subjects were recruited.

Meal-induced insulin sensitization and its parasympathetic regulation in humans.

In animal studies, the whole-body glucose disposal effect of insulin is low in the fasted state or after atropine infusion, but doubles after a meal, consistent with the hepatic insulin-sensitizing substance (HISS) hypothesis. We tested how a standardized test meal and atropine affected the dynamic response to insulin in humans. Insulin sensitivity was assessed in healthy male subjects (aged 28.

A new technique to assess insulin sensitivity in humans: the rapid insulin sensitivity test (RIST).

The objective of this study was to develop a Rapid Insulin Sensitivity Test (RIST) in humans, a test already used in animal studies. Insulin sensitivity was assessed using a rapid modified euglycemic clamp, the RIST. In this test, glucose disposition was determined after an intravenous (i.

In vitro nitrosation of insulin A- and B-chains.

The physiological roles of insulin and nitric oxide (NO) have been recently recognized by several studies. A diversity of chemical modifications of insulin is reported both in vivo and in vitro. S-nitrosation, the covalent linkage of NO to cysteine free thiol is recognized as an important post-translational regulation in many proteins.

Hepatic-dependent and -independent insulin actions are impaired in the obese Zucker rat model.

Objective: Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity.

Carvedilol's actions are largely mediated by endogenous nitric oxide.

Carvedilol's adrenergic antagonism does not fully explain its therapeutic actions. We therefore tested the hypothesis that its action is associated with an increase in NO synthesis. Wistar rats (male, 9 weeks, n = 10) anesthetized with sodium pentobarbital were used.

Carvedilol action is dependent on endogenous production of nitric oxide.

Background: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO).