Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1–12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8–4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.

TCF7L2 is the susceptibility gene for Type 2 diabetes (T2D) with the largest effect on disease risk that has been discovered to date. However, the mechanisms by which TCF7L2 contributes to the disease remain largely elusive. In addition, epigenetic mechanisms, such as changes in DNA methylation patterns, might have a role in the pathophysiology of T2D. This study aimed to investigate the differences in terms of DNA methylation profile of TCF7L2 promoter gene between type 2 diabetic patients and age- and Body Mass Index (BMI)- matched controls. We included 93 type 2 diabetic patients that were recently diagnosed for T2D and exclusively on diet (without any pharmacological treatment). DNA was extracted from whole blood and DNA methylation was assessed using the Sequenom EpiTYPER system. Type 2 diabetic patients were more insulin resistant than their matched controls (mean HOMA IR 2.6 vs 1.8 in controls, P<0.001) and had a poorer beta-cell function (mean HOMA B 75.7 vs. 113.6 in controls, P<0.001). Results showed that 59% of the CpGs analyzed in TCF7L2 promoter had significant differences between type 2 diabetic patients and matched controls. In addition, fasting glucose, HOMA-B, HOMA-IR, total cholesterol and LDL-cholesterol correlated with methylation in specific CpG sites of TCF7L2 promoter. After adjustment by age, BMI, gender, physical inactivity, waist circumference, smoking status and diabetes status uniquely fasting glucose, total cholesterol and LDL-cholesterol remained significant. Taken together, newly diagnosed, drug-naïve type 2 diabetic patients display specific epigenetic changes at the TCF7L2 promoter as compared to age- and BMI-matched controls. Methylation in TCF7L2 promoter is further correlated with fasting glucose in peripheral blood DNA, which sheds new light on the role of epigenetic regulation of TCF7L2 in T2D.

Close ties have been made among certain nutrients, obesity, type 2 diabetes and circadian clocks. Among nutrients, taurine has been documented as being effective against obesity and type 2 diabetes. However, the impact of taurine on circadian clocks has not been elucidated. We investigated whether taurine can modulate or correct disturbances in daily rhythms caused by a high-fat diet in mice. Male C57BL/6 mice were divided in four groups: control (C), control + taurine (C+T), high-fat diet (HFD) and HFD + taurine (HFD+T). They were administered 2% taurine in their drinking water for 10 weeks. Mice were euthanized at 6:00, 12:00, 18:00, and 24:00. HFD mice increased body weight, visceral fat and food intake, as well as higher levels of glucose, insulin and leptin, throughout the 24 h. Taurine prevented increments in food intake, body weight and visceral fat, improved glucose tolerance and insulin sensitivity and reduced disturbances in the 24 h patterns of plasma insulin and leptin. HFD downregulated the expression of clock genes Rev-erbα, Bmal1, and Per1 in pancreatic islets. Taurine normalized the gene and protein expression of PER1 in beta-cells, which suggests that it could be beneficial for the correction of daily rhythms and the amelioration of obesity and diabetes.

Prediabetes and old age are both high risk factors for developing Type 2 Diabetes (T2D), while obesity is one of the most important factors triggering the disease. Nutritional interventions are the most effective tool for preventing T2D, as they improve different biochemical and anthropometric outcomes and growth-promoting/inhibiting gut microbiota populations. However, to date there are no specific dietary recommendations to stop the development of T2D in elderly groups, for whom hypocaloric diets and other commonly used weight-loss programs could be considered dangerous. The objective of our study, thus, was to understand the impact of dietary patterns on T2D risk as related to gut microbiota profile in obese and non-obese elderly prediabetic subjects. A cross-sectional study was performed in 182 subjects ≥65 years old with prediabetes, divided into obese (OB) or non-obese (NOB) subgroups, and their risk of developing T2D was measured according to FINDRISK score and biochemical parameters. Also, clusters into different dietary patterns in each group by PCA analysis was related with gut microbiota, which was analyzed from stool samples by qPCR. The creation of clusters was used to re-evaluate T2D risk. OB was at higher risk of developing T2D and showed worse metabolic outcomes. Unhealthier and healthier dietary pattern clusters were observed for both OB (OB-6 and OB-5 respectively) and NOB (NOB-2 and NOB-3 respectively) groups. Results obtained from the gut microbiota showed that only Prevotella was higher in NOB, but when comparisons were made between clusters, a clear relation with dietary pattern was observed; showing in healthier dietary clusters a decrease in Prevotella, an increase of Faecalibacterium prausnitzii and an increase in lactic acid bacteria. T2D risk was greater in the obese group between unhealthier dietary clusters. No difference between healthier dietary clusters was observed. A healthy dietary pattern and the growth-promoting beneficial and growth-inhibiting disadvantageous gut microbiota populations linked to it provide protection against the development of T2D in an obese population with advanced age and preDM.

This study aimed to observe if quinoa could produce a benefit on postprandial glycemia that would result in less progression to type 2 diabetes (T2D). A cross-over design pilot clinical study with a nutritional intervention for 8 weeks was performed: 4 weeks on a regular diet (RD) and 4 weeks on a quinoa diet (QD). Nine subjects aged ≥65 years with prediabetes were monitored during the first 4 weeks of RD with daily dietary records and FreeStyle Libre^®. Subsequently, participants started the QD, where quinoa and 100% quinoa-based products replaced foods rich in complex carbohydrates that they had consumed in the first 4 weeks of RD. The glycemic measurements recorded by the sensors were considered as functions of time, and the effects of nutrients consumed at the intended time period were analyzed by means of a function-on-scalar regression (fosr) model. With QD participants, decreased body weight (−1.6 kg, p = 0.008), BMI (−0.6 kg/m²p = 0.004) and waist circumference (−1.5 cm, p = 0.015) were observed. Nutrients intake changed during QD, namely, decreased carbohydrates (p = 0.004) and increased lipids (p = 0.004) and some amino acids (p < 0.05). The fosr model showed a reduction in postprandial glycemia in QD despite intrapersonal differences thanks to the joint action of different nutrients and the suppression of others consumed on a regular diet. We conclude that in an old age and high T2D-risk population, a diet rich in quinoa reduces postprandial glycemia and could be a promising T2D-preventive strategy.

We studied the contribution of the constitutive and the regulated pathways to the total secretion of islet amyloid polypeptide (IAPP) in human pancreatic islets after prolonged culture at either 5.5 or 24.4 m M glucose. In islets cultured in low concentrations of glucose, the secretion of IAPP in response to glucose was unaffected by brefeldin A (BFA) and completely blocked by ethyleneglycoltetraacetic acid. In islets cultured in high glucose concentrations, it was strongly inhibited by both agents. BFA had no effect on the glucose-induced insulin secretion. The determination of the islet peptide contents and the mRNA levels revealed a several-fold increase in the IAPP/insulin molar ratio of islets cultured in high glucose concentrations. Thus, prolonged exposure of human islets to high concentrations of glucose results in an increase in the synthesis of IAPP with respect to insulin. As a result, the release of IAPP through a mechanism sensitive to BFA is favored. These data support the hypothesis that IAPP and insulin are regulated in a noncoordinated way in human pancreatic islets.