Glycated haemoglobin (HbA1c) is currently the gold standard for glucose monitoring in patients with diabetes, and has been increasingly adopted as a criteria for diabetes diagnosis. However, conditions that determine alterations in haemoglobin metabolism can interfere with the reliability of HbA1c measurements. Glycated albumin and fructosamine (total glycated serum proteins) are alternative markers of glycaemia, which have been recognised to provide additional information to HbA1c or to provide a reliable measure when HbA1c is observed not to be dependable. Additionally, while HbA1c monitors the exposure to circulating glycaemia in the previous 3 months, glycated albumin and fructosamine represent exposure for a shorter period, which may be beneficial to monitor rapid metabolic alterations or changes in diabetes treatment. The present review further discusses the relative value of HbA1c, glycated albumin, and fructosamine, in prediabetes and diabetes diagnosis, evaluation of glucose variability, and complications risk prediction. Also, a novel molecular role for albumin is presented by which glycated albumin contributes to glucose intolerance development and thus to progression to diabetes, besides the role of glycated albumin as a pro-atherogenic factor.

Background: Exercise, when performed on a regular basis, is a well-accepted strategy to improve vascular function in patients with type 2 diabetes. However, the exercise intensity that yields maximal adaptations on structural and functional indices in patients with type 2 diabetes remains uncertain. Our objective was to analyze the impact of a 1-year randomized controlled trial of combined high-intensity interval training (HIIT) with resistance training (RT) vs. a combined moderate continuous training (MCT) with RT on structural and functional arterial indices in patients with type 2 diabetes. Methods: Patients with type 2 diabetes (n = 80) were randomized into an exercise intervention with three groups: control, combined HIIT with RT and combined MCT with RT. The 1-year intervention had 3 weekly exercise sessions. High-resolution ultrasonography of the common carotid artery and central and peripheral applanation tonometry were used to assess the changes in structural and functional arterial indices. Generalized estimating equations were used to model the corresponding outcomes. Results: After adjusting the models for sex, baseline moderate-to-vigorous physical activity, and mean arterial pressure changes, while using the intention-to-treat analysis, a significant interaction was observed on the carotid intima-media thickness (cIMT) for both the MCT (β = − 4.25, p < 0.01) and HIIT group (β = − 3.61, p < 0.01). However, only the HIIT observed favorable changes from baseline to 1-year on peripheral arterial stiffness indices such as carotid radial arterial pulse wave velocity (β = − 0.10, p = 0.044), carotid to distal posterior tibial artery pulse wave velocity (β = − 0.14, p < 0.01), and on the distensibility coefficient (β = − 0.00, p < 0.01). No effect was found for hemodynamic variables after the intervention. Conclusions: Following a 1-year intervention in patients with type 2 diabetes, both the MCT and HIIT group reduced their cIMT, whereas only the HIIT group improved their peripheral arterial stiffness indices and distensibility coefficient. Taken together, HIIT may be a meaningful tool to improve long-term vascular complications in type 2 diabetes. Trial registration clinicaltrials.gov ID: NCT03144505

We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N ^G-nitro-l-arginine methyl ester (l-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 ± 2.1% compared with control (from 287.3 ± 18.1 to 155.3 ± 10.1 mg glucose/kg, P < 0.05). Insulin sensitivity was restored to 321.7 ± 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal sodium nitroprusside (20 nmol · kg⁻¹ · min⁻¹), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor l-buthionine-[ S,R]-sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1%. Insulin sensitivity after l-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by l-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.

A mathematical model of calcium homeostasis is presented in which the controlling factors are the plasma concentrations of calcium, PTH, and calcitriol, and the effector organs are the parathyroids, bone, kidney, and intestine. Other factors can be added as the need arises. The model is aimed at simulating what happens in a single individual, but its parameters and variables were adjusted to the corresponding published average values. Simulations of published observations in humans undergoing the infusion of calcium or its chelators are presented. With a single exception, these simulations provided a good fit to the data. The response of the system to extrinsic perturbations was characterized by simulating chronic infusions of calcium, PTH, and calcitriol. Finally, the steady state response to perturbations in some of its parameters (the secretory mass of the parathyroids and the affinity and/or sensitivity of the calcium, PTH, and calcitriol receptors) and to renal failure were also investigated in an attempt to analyze the pathogenesis of clinical hypo- or hypercalcemias. In its present form the model cannot be used to base clinical decisions in individual cases. However, it requires modest computational resources, and clinicians with a modest mathematical background can manipulate it. It is a useful tool for the analysis of general mechanisms of the diseases of calcium metabolism and for the design of clinical experiments aimed at characterizing these diseases. The model can also be the core of future autoadaptive extensions to be used in individual patients.