Productos finales de glicación avanzada (AGEs) y su importancia en enfermedades crónicas relacionadas con la nutrición / Advanced glycation end products (AGEs) and its importance in chronic diseases related to nutrition

Maillard reaction occurs when reducing sugars react in a non-enzymatic way with amino groups from proteins, lipids and nucleic acids. Products of this reaction are known as Advanced Glycation End Products (AGEs). These products are formed from endogenous sources (within the body) and exogenously (produced in food preparation, as well as those supported in their formation by tobacco smoke). In the food industry this reaction is known as “browning” and is directly related to cooking time of these, affecting its color and flavor. After food preparation and the formation of exogenous AGEs, these are absorbed in the digestive tract and are part of the pool of total body AGEs. AGEs alter structure and function of molecules and increase oxidative stress in biological systems. AGEs generally refers to non-reactive terminal products as CML (3,4-Ne carboxymethyl-lysine), but alsoincludes intermediate or precursor of AGEs as 3DG (3-deoxyglucosone), or MGO (methyl -glyoxal) and its derivatives. Glycation corresponds to a non-enzymatic glycosylation. This process contributes to protein post-translational modification. This process causes quantitative and qualitative changes in the extracellular matrix components which can affect cell adhesion, growth, and others. The process of protein glycation has been associated with development mechanisms of various diseases and complications such as retinopathy, nephropathy and neuropathy associated with diabetes, macrovascular disease, Alzheimer’s disease, cataracts, and aging.

Cetoacidosis diabética: Casuística 2008-2012, epidemiología y fisiopatología / Treatment of diabetic ketoacidosis using 2009 American Diabetes Association guidelines

Background: During 2009, new guidelines for the treatment of diabetic ketoacidosis were published by the American Diabetes Association. Aim: To assess the impact of new treatment guidelines on the evolution of patients treated for diabetic ketoacidosis (KAD). Patients and Methods: Anonymous data was obtained from computational medical records of patients treated for KAD at our institution two years before (“Traditional Protocol”) and TWO years after (“ADA-2009 Protocol”) the publication of the 2009 American Diabetes Association (ADA) KAD guidelines. Results: Twenty three patients aged 36.5 ± 15.1 years were treated with the traditional method and 23 patients aged 44.4 ± 21.1 years were treated following 2009 ADA guidelines. Among patients treated with the traditional protocol and treated following ADA 2009 guidelines, the diabetes type 1/type 2 ratio was18/5 and 19/16 respectively (p = NS), the glycosylated hemoglobin on admission was 12.6 ± 2.5 and 14.3 ± 2.7% respectively (p = 0.03), minimal blood pH was 7.15 ± 0.14 and 7.19 ± 0.09 respectively (p = NS), bicarbonate was required in seven and no patient respectively (p = 0.01), hypokalemia < 3.5 mEq/L occurred in 78.2 and 48.5% of patients (p = 0.03), the lapse until resolution was 28.7 ± 28.0 and 28.8 ± 20.6 hours (p = NS). Only one patient, treated following ADA 2009 guidelines, died. Conclusions: Introduction of the ADA-2009 protocol for the treatment of KAD resulted in decrease in the use of intravenous bicarbonate and a reduction in the incidence of hypokalemia. There was no impact neither in the lapse until resolution or lethality.

La hipótesis de Pedersen no es suficiente: Otros nutrientes además de la glucosaexplicarían la macrosomía fetal enpacientes diabéticas gestacionales consobrepeso y buen control glicémico / Nutrients other than glucose might explain fetal overgrowth in gestationaldiabetic pregnancies

Since 1964, the hypothesis of Pedersen has been used to explain fetal macrosomia observed in gestational diabetes mellitus (GDM), by a mechanism involving maternal hyperglycemia - fetal hyperglycemia - fetal hyperinsulinemia. However,since the 1980-89 decade, it is known that pregnant women with pre-gestationaloverweight not suffering from GDM still have a higher frequency of fetal macrosomia. Furthermore, pregnant women with GDM, despite being subjected to optimalglycemic control, still show unacceptably high frequencies of fetal macrosomia, aphenomenon that is concentrated in pregnancies with overweight or obesity priorto pregnancy. If glucose is not the single nutrient responsible for fetal macrosomiain pregnant women with gestational diabetes that undergo strict glycemic control,other nutrients may cause excessive fetal growth in pre-pregnancy overweightmothers. In this review, we propose that triglycerides (TG) could be responsible forthis accelerated fetal growth. If this hypothesis is validated in animal models andclinical studies, then normal and pathological ranges of TG should be defined, andmonitoring of triglyceride levels during pregnancy should be advised as a possiblenew alternative, besides a good glycemic control, for the management of fetal macrosomia in GDM women with overweight prior to pregnancy.

Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna / Mitochondrial DNA heteroplasmy of the m.3243A>G mutation in maternally inherited diabetes and deafness

Maternally Inherited Diabetes and Deafness (MIDD) is caused by mutations in mitochondrial DNA (mtDNA), mainly m.3243A>G. Severity, onset and clinical phenotype of MIDD patients are partially determined by the proportion ofmutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification ofMIDD allows a corred treatment with insulin avoiding drugs that may interfere with mitochondrial electrón chain transpon. We estimated the degree of heteroplasmy ofthe mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a femóle adult patient. For this purpose, PCR producís were inserted in a vector creatingplasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to créate a calibration curve used to interpólate heteroplasmy percentages with qPCR threshold cycles. The proportions of m.3243A>G heteroplasmy were 62% (muscle), 14% (saliva), 6% (blood leukocytes) and 3% in hair root. Quantitative analysis of heteroplasmy showed marked variations in different tissues (highest in muscle and lowest in blood). Given the relatively high heteroplasmy found in saliva, this type of biológical sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Bases fisiopatológicas para una clasificación de la neuropatía diabética / A new physiopathological classification of diabetic neuropathy

Nowadays, Diabetic Neuropathy (DN) is considered the most common cause of peripheral neuropathy in clinical practice. It can affect sensitive, motor or autonomic nerve fibers, with symmetric, asymmetric, acute or chronic presentations. Due to this variability, with multiple physiopathologic mechanisms involved, a complex clinical classification has been used until recently. The aim of this review is to present a new classification of diabetic neuropathy, based on its physiopathology. It is divided in metabolic microvascular and hypoxic, autoimmune and inflammatory, compressive, secondary to complications ofdiabetes and related to treatment. It must be understood that DN is notjust a functional disease, but a complication of diabetes with molecular and pathological substrates caused by hyperglycemia. Therefore, normalization of blood glucose is a fundamental step towards the successful prevention and treatment of DN.

Fisiopatología de la retinopatía y nefropatía diabéticas / Pathophysiology of diabetic retinopathy and nephropathy

Despite the availability of multiple therapeutic approaches, diabetes mellitus with chronic hyperglycemia remains as the main cause of new cases of blindness and chronic renal failure in the western hemisphere. We herein review the molecular mechanisms by which chronic hyperglycemia causes retinopathy and nephropathy in type I and type 2 diabetic patients. Diabetic retinopathy develops silently along years or decades, producing symptoms only in its very ¡ate stages. Its slow development starts with the activation of aldose reducíase, shortly followed by the destruction of the retinal pericyte cells, and ends in sudden blindness when vitreous hemorrhage ensues. Nephropathy, on the other hand, centers its pathophysiology in the mesangial cell, that starts as a modified smooth-muscle cell, and turns itself into a myo-fibroblast, produces such amounts of cytoplasm and extracellular protein that strangulates the glomerular capillaries and causes renal failure. After a detailed review of the molecular mechanisms of the aforementioned complications, we conclude that, apart from directing our attention to the emerging medications that are being developed to block these molecular pathways, we should never abandon the struggle for improving the glycemic control of our diabetic patients.