Protocolo para el seguimiento del tratamiento farmacológico individualizado en pacientes con diabetes tipo 2. 2ª ed

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Of fat, β cells, and diabetes.

The molecular mechanisms linking diet, obesity, and type 2 diabetes are still poorly understood. In a recent paper, Ohtsubo et al. (2011) show that high lipid levels induce nuclear exclusion of Foxa2 and HNF1α in β cells, leading to impaired expression and glycosylation of proteins controlling glucose-stimulated insulin secretion.

Macronutrient composition of the diet and prospective weight change in participants of the EPIC-PANACEA study.

BACKGROUND The effect of the macronutrient composition of the usual diet on long term weight maintenance remains controversial. METHODS 373,803 subjects aged 25-70 years were recruited in 10 European countries (1992-2000) in the PANACEA project of the EPIC cohort. Diet was assessed at baseline using country-specific validated questionnaires and weight and height were measured at baseline and self-reported at follow-up in most centers. The association between weight change after 5 years of follow-up and the iso-energetic replacement of 5% of energy from one macronutrient by 5% of energy from another macronutrient was assessed using multivariate linear mixed-models. The risk of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to initial Body Mass Index. RESULTS A higher proportion of energy from fat at the expense of carbohydrates was not significantly associated with weight change after 5 years. However, a higher proportion of energy from protein at the expense of fat was positively associated with weight gain. A higher proportion of energy from protein at the expense of carbohydrates was also positively associated with weight gain, especially when carbohydrates were rich in fibre. The association between percentage of energy from protein and weight change was slightly stronger in overweight participants, former smokers, participants ≥60 years old, participants underreporting their energy intake and participants with a prudent dietary pattern. Compared to diets with no more than 14% of energy from protein, diets with more than 22% of energy from protein were associated with a 23-24% higher risk of becoming overweight or obese in normal weight and overweight subjects at baseline. CONCLUSION Our results show that participants consuming an amount of protein above the protein intake recommended by the American Diabetes Association may experience a higher risk of becoming overweight or obese during adult life.

The association between dietary energy density and type 2 diabetes in Europe: results from the EPIC-InterAct Study

BACKGROUND Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association between DED and risk of T2D in a large prospective study with heterogeneity of dietary intake. METHODOLOGY/PRINCIPAL FINDINGS A case-cohort study was nested within the European Prospective Investigation into Cancer (EPIC) study of 340,234 participants contributing 3.99 million person years of follow-up, identifying 12,403 incident diabetes cases and a random subcohort of 16,835 individuals from 8 European countries. DED was calculated as energy (kcal) from foods (except beverages) divided by the weight (gram) of foods estimated from dietary questionnaires. Prentice-weighted Cox proportional hazard regression models were fitted by country. Risk estimates were pooled by random effects meta-analysis and heterogeneity was evaluated. Estimated mean (sd) DED was 1.5 (0.3) kcal/g among cases and subcohort members, varying across countries (range 1.4-1.7 kcal/g). After adjustment for age, sex, smoking, physical activity, alcohol intake, energy intake from beverages and misreporting of dietary intake, no association was observed between DED and T2D (HR 1.02 (95% CI: 0.93-1.13), which was consistent across countries (I(2) = 2.9%). CONCLUSIONS/SIGNIFICANCE In this large European case-cohort study no association between DED of solid and semi-solid foods and risk of T2D was observed. However, despite the fact that there currently is no conclusive evidence for an association between DED and T2DM risk, choosing low energy dense foods should be promoted as they support current WHO recommendations to prevent chronic diseases.

Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.

BACKGROUND: Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficiency virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population. METHODS: We evaluated the contribution of 22 SNPs identified in genome-wide association studies and of longitudinally measured clinical factors to DM. We genotyped all 94 white participants in the Swiss HIV Cohort Study who developed DM from 1 January 1999 through 31 August 2009 and 550 participants without DM. Analyses were based on 6054 person-years of follow-up and 13,922 measurements of plasma glucose. RESULTS: The contribution to DM risk explained by SNPs (14% of DM variability) was larger than the contribution to DM risk explained by current or cumulative exposure to different antiretroviral therapy combinations (3% of DM variability). Participants with the most unfavorable genetic score (representing 12% and 19% of the study population, respectively, when applying 2 different genetic scores) had incidence rate ratios for DM of 3.80 (95% confidence interval [CI], 2.05-7.06) and 2.74 (95% CI, 1.53-4.88), respectively, compared with participants with a favorable genetic score. However, addition of genetic data to clinical risk factors that included body mass index only slightly improved DM prediction. CONCLUSIONS: In white HIV-infected persons treated with antiretroviral therapy, the DM effect of genetic variants was larger than the potential toxic effects of antiretroviral therapy. SNPs contributed significantly to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population.

Diabetic nephropathy: changes after diabetes surgery?

Introduction: Obesity, as a central piece inside metabolic syndrome, is associated with early chronic kidney disease (CKD). In addition, several observational, cross sectional, and longitudinal studies have demonstrated that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of CKD including diabetic nephropathy. This implies that when obesity is reversed, many CKD risk factors and CKD itself could be favorably influenced. So all measures aimed at weight loss are recommended to minimize risks from obesityrelated conditions and generate improvements in the metabolic profile. Recent evidence shows that bariatric surgery (BS) can revert or improve proteinuria and CKD in morbidly obese patients. Objectives and methods: The present review is aimed to provide the evidence regarding the beneficial effects of weight loss after BS in different stages of CKD including kidney transplant recipients, with an special focus on the beneficial effect in reducing or improving proteinuria and renal failure. Furthermore, this updated systematic review of the literature analyzes potential adverse effects that BS could induce not only on renal function but also on morbidity and mortality risk in perioperative and postoperative period. Conclusions: Results from the different case reports, meta analysis as well as systematic review of clinical trials show that obesity treatment by way of lifestyle changes, pharmacotherapies and BS can reduce proteinuria and help to prevent loss of renal function. Also BS may reduce complications, and allow obese patients with end-stage renal disease to undergo kidney transplantation with good results.

Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and what else?

The proline-specific dipeptidyl aminopeptidase IV (DPP IV, DPP-4, CD26), widely expressed in mammalians, releases X-Pro/Ala dipeptides from the N-terminus of peptides. DPP IV is responsible of the degradation of the incretin peptide hormones regulating blood glucose levels. Several families of DPP IV inhibitors have been synthesized and evaluated. Their positive effects on the degradation of the incretins and the control of blood glucose levels have been demonstrated in biological models and in clinical trials. Presently, several DPP IV inhibitors, the "gliptins", are approved for type 2 diabetes or are under clinical evaluation. However, the gliptins may also be of therapeutic interest for other diseases beyond the inhibition of incretin degradation. In this Perspective, the biological functions and potential substrates of DPP IV enzymes are reviewed and the characteristics of the DPP IV inhibitors are discussed in view of type 2 diabetes and further therapeutic interest.

Recommendations of the GARIN group for managing non-critically ill patients with diabetes or stress hyperglycaemia and artificial nutrition.

BACKGROUND & AIMS By means of this update, the GARIN working group aims to define its position regarding the treatment of patients with diabetes or stress hyperglycaemia and artificial nutrition. In this area there are many aspects of uncertainty, especially in non-critically ill patients. METHODS Bibliographical review, and specific questions in advance were discussed and answered at a meeting in the form of conclusions. RESULTS We propose a definition of stress hyperglycaemia. The indications and access routes for artificial nutrition are no different in patients with diabetes/stress hyperglycaemia than in non-diabetics. The objective must be to keep pre-prandial blood glucose levels between 100 and 140 mg/dl and post-prandial levels between 140 and 180 mg/dl. Hyperglycemia can be prevented through systematic monitoring of capillary glycaemias and adequately calculate energy-protein needs. We recommend using enteral formulas designed for patients with diabetes (high monounsaturated fat) to facilitate metabolic control. The best drug treatment for treating hyperglycaemia/diabetes in hospitalised patients is insulin and we make recommendations for adapt the theoretical insulin action to the nutrition infusion regimen. We also addressed recommendations for future investigation. CONCLUSIONS This recommendations about artificial nutrition in patients with diabetes or stress hyperglycaemia can add value to clinical work.

In vivo assessment of antiretroviral therapy-associated side effects

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus.

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gut microbiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gut microbiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gut microbiota is dependent on the type of birth. With effect from this point, gut microbiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gut microbiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases.

Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet.

C57BL/6J mice were fed a high-fat, carbohydrate-free diet (HFD) for 9 mo. Approximately 50% of the mice became obese and diabetic (ObD), approximately 10% lean and diabetic (LD), approximately 10% lean and nondiabetic (LnD), and approximately 30% displayed intermediate phenotype. All of the HFD mice were insulin resistant. In the fasted state, whole body glucose clearance was reduced in ObD mice, unchanged in the LD mice, and increased in the LnD mice compared with the normal-chow mice. Because fasted ObD mice were hyperinsulinemic and the lean mice slightly insulinopenic, there was no correlation between insulin levels and increased glucose utilization. In vivo, tissue glucose uptake assessed by 2-[(14)C]deoxyglucose accumulation was reduced in most muscles in the ObD mice but increased in the LnD mice compared with the values of the control mice. In the LD mice, the glucose uptake rates were reduced in extensor digitorum longus (EDL) and total hindlimb but increased in soleus, diaphragm, and heart. When assessed in vitro, glucose utilization rates in the absence and presence of insulin were similar in diaphragm, soleus, and EDL muscles isolated from all groups of mice. Thus, in genetically homogenous mice, HFD feeding lead to different metabolic adaptations. Whereas all of the mice became insulin resistant, this was associated, in obese mice, with decreased glucose clearance and hyperinsulinemia and, in lean mice, with increased glucose clearance in the presence of mild insulinopenia. Therefore, increased glucose clearance in lean mice could not be explained by increased insulin level, indicating that other in vivo mechanisms are triggered to control muscle glucose utilization. These adaptive mechanisms could participate in the protection against development of obesity.

Hidratos de carbono: actualización de su papel en la diabetes mellitus y la enfermedad metabólica.

BACKGROUND: There is a prevalence of diabetes mellitus (DM), unknown DM and stress hyperglycemia among hospital patients, and the nutritional treatment is a key part of care, where carbohydrates (CH) intake is a controversial issue. There is also a discussion on the increase of prevalence for DM, obesity and metabolic disease with refined CH or sugar. OBJECTIVES: This review examines the recommendations from different scientific societies about the percentage of CH in the total calorie intake of the diabetic patient, the CH value in the glycemic index and glycemic load, the new CH included in enteral formulae and the association of refined CH with the high prevalence of DM and metabolic disease. METHODS: Systematic review of literature using the electronic scientific databases Pubmed, Science Direct, Scielo, Scopus and Medline. CONCLUSIONS: Scientific societies are flexible about the CH intake in the diet of diabetic patients, suggesting to customize it according to each metabolic profile. Using the glycemic index and glycemic load can provide an extra benefit in the postprandial glycemic control. The new diabetes-specific enteral formulae, with fructooligosaccharides, resistant maltodextrins and fructose-free show efficacy in improving the glycemic control, although more controlled and long-term studies are needed. There is still some controversy about the links between sugar intake and DM, obesity and metabolic disease, although this relationship would be more linked to an increase of the total calorie intake than to a specific nutrient. .

Estudio y prevalencia de la diabetes mellitus postrasplante; análisis en un grupo de pacientes trasplantados renales.

INTRODUCTION: The onset of post-transplant diabetes mellitus (PTDM) among kidney recipients is associated with an increased risk of graft failure and high rates of morbidity and mortality. Minimize the risk of PTDM is a priority for improving long-term survival rates. Aims. This study aims to assess the prevalence of PTDM in a renal transplant patient population, to identify risk factors and assess the graft and patient survival. METHODS: The sample consisted of 112 renal transplant patients , 69 men and 43 women , renal transplant , who attended for five years post-transplant consultation. Were analyzed as potential risk factors for PTDM : age , sex, body mass index (BMI ) , obesity , VHC , hypertension, dyslipidemia , total cholesterol (TC) , serum triglyceride and immunosuppressive therapy ( cyclosporine , tacrolimus , mycophenolate mofetil and sirolimus ), also the prevalence of acute rejection episodes was evaluated. RESULTS: The prevalence of PTDM was 24.2 %, compared with 85 patients (75.8%) with standard glucose (PGN) . PTDM patients showed a higher BMI , a higher percentage of overweight , dyslipidemia , total cholesterol levels , triglycerides and performed a greater percentage of patients with PDMPT including Mycophenolate mofetil was administered. CONCLUSIONS: There is a high incidence of PTDM in kidney recipients , the importance of weight control and strict adherence to all identified risk factors , as well as in minimizing the doses of immunosuppressive therapies to prevent the onset of PTDM.

Potential of education-based insulin therapy for achievement of good metabolic control: a real-life experience.

Diabet. Med. 28, 539-542 (2011) ABSTRACT: Aims  Achievement of good metabolic control in Type 1 diabetes is a difficult task in routine diabetes care. Education-based flexible intensified insulin therapy has the potential to meet the therapeutic targets while limiting the risk for severe hypoglycaemia. We evaluated the metabolic control and the rate of severe hypoglycaemia in real-life clinical practice in a centre using flexible intensified insulin therapy as standard of care since 1990. Methods  Patients followed for Type 1 diabetes (n = 206) or those with other causes of absolute insulin deficiency (n = 17) in our outpatient clinic were analysed in a cross-sectional study. Mean age (± standard deviation) was 48.9 ± 15.7 years, with diabetes duration of 21.4 ± 14.4 years. Outcome measures were HbA(1c) and frequency of severe hypoglycaemia. Results  Median HbA(1c) was 7.1% (54 mmol/mol) [interquartile range 6.6-7.8 (51-62 mmol/mol)]; a good or acceptable metabolic control with HbA(1c) < 7.0% (53 mmol/mol) or 7.5% (58 mmol/mol) was reached in 43.5 and 64.6% of the patients, respectively. The frequency of severe hypoglycaemic episodes was 15 per 100 patient years: 72.3% of the patients did not experience any such episodes during the past 5 years. Conclusions  Good or acceptable metabolic control is achievable in the majority of patients with Type 1 diabetes or other causes of absolute insulin deficiency in routine diabetes care while limiting the risk for severe hypoglycaemia.