Pharmaceutical targeting of the cannabinoid type 1 receptor impacts the crosstalk between immune cells and islets to reduce insulitis in humans.

AIMS/HYPOTHESIS: Insulitis, a hallmark of inflammation preceding autoimmune type 1 diabetes, leads to the eventual loss of functional beta cells. However, functional beta cells can persist even in the face of continuous insulitis. Despite advances in immunosuppressive treatments, maintaining functional beta cells to prevent insulitis progression and hyperglycaemia remains a challenge. The cannabinoid type 1 receptor (CB1R), present in immune cells and beta cells, regulates inflammation and beta cell function. Here, we pioneer an ex vivo model mirroring human insulitis to investigate the role of CB1R in this process. METHODS: CD4+ T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) from male and female individuals at the onset of type 1 diabetes and from non-diabetic individuals, RNA was extracted and mRNA expression was analysed by real-time PCR. Single beta cell expression from donors with type 1 diabetes was obtained from data mining. Patient-derived human islets from male and female cadaveric donors were 3D-cultured in solubilised extracellular matrix gel in co-culture with the same donor PBMCs, and incubated with cytokines (IL-1ß, TNF-α, IFN-γ) for 24-48 h in the presence of vehicle or increasing concentrations of the CB1R blocker JD-5037. Expression of CNR1 (encoding for CB1R) was ablated using CRISPR/Cas9 technology. Viability, intracellular stress and signalling were assayed by live-cell probing and real-time PCR. The islet function measured as glucose-stimulated insulin secretion was determined in a perifusion system. Infiltration of immune cells into the islets was monitored by microscopy. Non-obese diabetic mice aged 7 weeks were treated for 1 week with JD-5037, then euthanised. Profiling of immune cells infiltrated in the islets was performed by flow cytometry. RESULTS: CNR1 expression was upregulated in circulating CD4+ T cells from individuals at type 1 diabetes onset (6.9-fold higher vs healthy individuals) and in sorted islet beta cells from donors with type 1 diabetes (3.6-fold higher vs healthy counterparts). The peripherally restricted CB1R inverse agonist JD-5037 arrested the initiation of insulitis in humans and mice. Mechanistically, CB1R blockade prevented islet NO production and ameliorated the ATF6 arm of the unfolded protein response. Consequently, cyto/chemokine expression decreased in human islets, leading to sustained islet cell viability and function. CONCLUSIONS/INTERPRETATION: These results suggest that CB1R could be an interesting target for type 1 diabetes while highlighting the regulatory mechanisms of insulitis. Moreover, these findings may apply to type 2 diabetes where islet inflammation is also a pathophysiological factor. DATA AVAILABILITY: Transcriptomic analysis of sorted human beta cells are from Gene Expression Omnibus database, accession no. GSE121863, available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM3448161 .

Identification of risk factors for suffering fear of hypoglycemia in type 1 Diabetes Mellitus patients.

Hypoglycemia is one of the main burdens for type I Diabetes Mellitus (DM I) patients. The consequences of hypoglycemia can be quite unpleasant due to the variety of disagreeable physical and psychological symptoms it triggers. The patient's previous experience with hypoglycemia episodes will condition his psychological reaction to future episodes, promoting behavioral modifications that associate with poor glycemic control and worse prognosis, and even with developing psychological disorders, leading to fear of hypoglycemia (FH). To be able to provide tailored prevention and treatment of patients with FH it is necessary to identify the risk factors in DM I patients. We developed and validated the FH-15 scale, a novel instrument to assess FH, which showed good concurrent and predictive validity in DM I patients. In this work we aim to identify the risk factors for suffering FH by detecting DM I patients with FH using the FH-15 scale and then analyzing the association of clinical and sociodemographic variables. We found that age, needing help to resolve an episode of hypoglycemia, and a perceived lack of social support are risk factors for suffering FH.

Factors determining weight gain in adults and relation with glucose tolerance.

OBJECTIVE: Modifications in lifestyle, diet and certain clinical events are major contributors for the high prevalence of obesity. The aim of this study was to assess factors associated with weight gain in a population of Spanish adults. DESIGN: The study was undertaken in two population-based cohorts from the north and the south of Spain (baseline and after 6 years). The Asturias Study, in the north, included 1034 persons aged 30-75 years, of whom 701 were reassessed. The Pizarra Study, in the south, included 1226 persons aged 18-65 years, of whom 783 were re-evaluated. Both studies involved a nutritional questionnaire, a physical examination and an oral glucose tolerance test (OGTT). RESULTS: During the follow-up, 32.3% of the participants lost weight, 34.5% gained fewer than 4 kg and 33.2% gained more than 4 kg. Weight gain was greater in persons younger than 50 years and in those with an initial body mass index below 30. Weight gain was associated with a greater incidence of type 2 diabetes mellitus (T2DM) and abnormal glucose tolerance, whereas weight loss in persons with these disorders was associated with a normal OGTT 6 years later. Persons who took less exercise and those who reported a higher daily calorie intake experienced greater weight gain. CONCLUSION: The longitudinal changes in weight affect the development of T2DM and abnormal glucose tolerance. The weight is a dynamic phenomenon affected by several social customs.

Efficacy and safety of basal insulin degludec 100 IU/mL versus glargine 300 IU/mL for type 1 diabetes: The single-center INEOX randomized controlled trial.

AIMS: To compare efficacy and safety of degludec 100 IU/mL (Deg-100) and glargine 300 IU/mL (Gla-300) in adults with type 1 diabetes. METHODS: Open-label, single-center, randomized, parallel-group, 24-week trial in adults with type 1 diabetes, on basal-bolus insulin therapy, HbA1c ≤ 10%, using self-monitoring blood glucose. Participants were randomized 1:1 to a basal-bolus insulin regimen with Deg-100 (N = 129) or Gla-300 (N = 131). Primary efficacy endpoint: mean change in HbA1c from baseline to week-24. Main safety outcome: incidence rate of hypoglycemia during the study. Quality of life (DQOL) and satisfaction with diabetes treatment (DTSQ) were assessed. RESULTS: At week 24, after adjusting for baseline HbA1c, the decrease in HbA1c did not differ between groups: Deg-100 (-0.07 ± 0.7%) and Gla-300 (-0.16 ± 0.77%) (P = 0.320). There were no significant differences between groups in HbA1c, nocturnal hypoglycemia, severe hypoglycemia, DQOL, or DTSQ scores. The incidence rates of hypoglycemia < 3.9 mmol/L (Deg-100: 115.24 events/person-year vs Gla-300: 99.01 events/person-year, p < 0.001); and < 3.0 mmol/L (Deg-100: 41.17 events/person-year vs Gla-300: 34.29 events/person-year, p < 0.001) were different between groups. CONCLUSIONS: Deg-100 and Gla-300 have similar metabolic efficacy, incidence ratio of nocturnal and severe hypoglycemia, DQOL and DTSQ scores. Differences in the incidence rate of hypoglycemia < 3.9 mmol/L and < 3.0 mmol/L should be confirmed.

Internet-based Cognitive-behavioral therapy (CBT) for depressive symptomatology in individuals with type 1 diabetes (WEB_TDDI1 study): A randomized controlled trial protocol.

BACKGROUND: Professionals need adequate tools to help patients with diabetes and depression. Although web programs integrating cognitive-behavioral therapy with diabetes education have shown good results, no similar approach has been performed as yet in Spain. The objective is to develop an Internet-based program for the treatment of mild-moderate depressive symptomatology in individuals with type 1 diabetes (WEB_TDDI1 study) based on Cognitive-behavioral therapy (CBT) and assess its results. METHODS: A 2-arm randomized controlled trial will be conducted. Adults with type 1 diabetes and mild-moderate depressive symptoms will be screened to participate in the study and randomly assigned to either the treatment group (TG) that will use a Web-based application for a specific 9-week intervention in depression and type 1 diabetes or the control group (CG) that will be on the waiting list during that time. RESULTS: Data on the primary variable (depressive symptoms) and secondary variables (treatment-related distress, anxiety, fear of hypoglycemia, quality of life, treatment adherence, coping strategies and glycemic control) will be collected from the TG at the beginning/baseline, at the end of treatment and at 3, 6 and 12 months after treatment. The CG will be assessed at the beginning and at the end of the TG intervention. On completion of the program by the TG, the treatment will then be carried out in the CG. CONCLUSIONS: The new web application developed is expected to be effective for the treatment of mild-moderate depressive symptoms in adults with type 1 diabetes, reducing depressive symptoms and improving the rest of the analyzed variables. TRIAL REGISTRATION: Registry: NCT03473704 (March 21, 2018); ClinicalTrials.gov.

Development and Validation of the Depression Inventory for Type 1 Diabetes (DID-1).

People with type 1 diabetes (T1D) are more likely to have depression than the general population and their prognosis is worse. Unfortunately, the characteristics of persons with T1D lead to inadequate screening for depression in this population. To aid in the detection of depression in this population, this study was undertaken to develop a depressive symptoms assessment instrument specific to patients with T1D and to examine its psychometric properties. A total of 207 people with T1D participated in this study. The reliability of the new scale was assessed using Cronbach's alpha and the Spearman-Brown split-half coefficient. The Depression Inventory for type 1 Diabetes (DID-1), composed of 45 items on a Likert scale (1-7), shows high internal and temporal consistency, as well as adequate concurrent, convergent and discriminant validity. Factor analysis identified 7 factors (Symptoms of depression, Diminished interest, Hopelessness and dissatisfaction, Guilt, Fear, frustration and irritability, Defenselessness, and Interference in daily life) that explained 61.612% of the total variability. The cut-off score for diagnosis was set at 155 points. It was concluded that the DID-1 scale is a reliable, valid and useful tool for the assessment of depressive symptoms, eliminating the bias of other nonspecific diabetes scales.

[Depression in type 1 diabetes mellitus and associated factors]. / Depresión en la diabetes mellitus tipo 1 y factores asociados.

BACKGROUND AND OBJECTIVE: In recent years, there has been an increased interest in depression and diabetes risk factors. Our objectives were 1) Study the variables associated with the presence of depression in patients with type 1 diabetes mellitus (DM1), 2) to analyze potential risk factors for depression in these patients, and 3) to study a possible explanatory model of depression scores in these patients. PATIENTS AND METHODS: 207 patients with DM1. We evaluated sociodemographic and biomedical variables by means of a structured interview. We assessed psychological variables by means of the Scale for Depression in Type 1 Diabetes (EDDI-1) and the Spanish version of Diabetes Quality of Life (Es DQOL). RESULTS: Prevalence of depression was 21,7%. Variables associated with risk of depression in this sample were to be female; be unemployed; smoking; having complications of diabetes or other physical conditions; not perceiving family support or support from friends or colleagues in relation to diabetes; having a high number of weekly hyperglycemia; and a poor quality of life. A model based on previous research was obtained. This model explains a high percentage of the variability in the scores of patients in the EDDI-1. CONCLUSIONS: These results provide an empirical support to the knowledge of the risk factors associated with depression in patients with DM1. Glycemic control and quality of life have an important effect on the scores of depression in these patients, providing information for their treatment.

Development and Preliminary Validation of a New Type 1 Diabetes Adjustment Scale (DAS-1).

BACKGROUND: This study focuses on the development and validation of a new Type 1 Diabetes Adjustment Scale (DAS-1). METHOD: A total of 204 participants aged 15-65 with type 1 diabetes completed the self-report measures of the DAS-1, which includes clinical and psychological variables. RESULTS: Robust confirmatory factor analysis detected a unidimensional structure of the item scores. The omega coefficient was 0.91 and test-retest reliability was 0.87. Classifying subjects as in a Positive or Negative mood state, ROC analysis yielded an optimal cut-off of 50 for the DAS-1 scores, with a clinical accuracy of AUC = 0.85. The DAS-1 demonstrated evidence of good reliability and acceptable construct validity. CONCLUSION: The DAS-1 demonstrated good clinical utility, good sensitivity and adequate specificity. Clinical and theoretical implications of these results are discussed.

Unilateral renal agenesis and abrupt onset diabetes: an unfrequent form of MODY type diabetes. / Agenesia renal unilateral y diabetes de inicio brusco: una forma infrecuente de diabetes tipo MODY.

INTRODUCTION: MODY diabetes encompasses heterogeneous group of monogenic forms of diabetes with low prevalence. It is not easily diagnosed because of the increase in obesity and family history of diabetes in the general population. PATIENTS AND METHODS: We present a clinical case with cardinal symptoms, diabetes,renal insufficiency with no acidosis and with a family history of diabetes and renal agenesis. RESULTS: Distinguishing MODY diabetes from DM1 and DM2 is very important to ensure optimal treatment, and because the risk of complications depends on each genetic defect. A proper diagnosis needs a detailed medical history. DISCUSSION: An earlier identification of family members at risk and a correct and individualised treatment could be possible. Many of these patients can be managed successfully in monotherapy without insulin therapy.

Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes.

INTRODUCTION: Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results. OBJECTIVE: To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2α) in children with T1DM. MATERIALS AND METHODS: A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. - Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2α. RESULTS: There were no statistically significant differences in urinary 8-iso-PGF2α levels (142±37 vs. 172±61pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2α and HbA1c levels (r=0.53), MBG (r=0.72), standard deviation (r=0.49), and MAGE (r=0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2α excretion were found in the 1st phase. CONCLUSIONS: A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health.

Effect of the combination of the variants -75G/A APOA1 and Trp64Arg ADRB3 on the risk of type 2 diabetes (DM2).

OBJECTIVE: Numerous genes have been associated with the risk for type 2 diabetes mellitus (DM2). In an attempt to understand how specific variants of different genes interact and intervene in the molecular and physiological mechanisms of disorders such as diabetes or insulin resistance, the search for gene-gene interactions is constantly growing. We searched for a possible interaction between two polymorphisms (Trp64Arg of ADRB3 gene and -75G/A of APOA1gene) and the risk for DM2 in a population from southern Spain. DESIGN AND METHODS: A cross-sectional study in southern Spain of 1020 people, aged 18-65 years. All persons underwent a clinical, anthropometrical and biochemical evaluation, including an oral glucose tolerance test (OGTT). Insulin resistance was measured by homeostasis model of assessment (HOMA). The polymorphisms -75G/A of APOA1 and Trp64Arg of ADRB3 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR, respectively. RESULTS: The genotype frequencies of the -75G/A polymorphism of the APOA1 gene were 62.7% GG, 25.7% GA and 11.6% AA, whereas for the Trp64Arg polymorphism of the ADRB3 gene, they were 87.5% Trp/Trp, 11.7% Trp/Arg and 0.8% Arg/Arg. Subjects with both gene variants had a greater odds ratio (OR) of having DM2 [OR = 5.5; 95% confidence interval (CI) = 1.2-23.5] than persons with one or none of the variants, after adjusting for age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSIONS: Joint association of allele -75A (APOA1) and allele Arg64 (ADRB3) increase the risk of DM2 in a population from southern Spain.

Comparison of the Effects of Goat Dairy and Cow Dairy Based Breakfasts on Satiety, Appetite Hormones, and Metabolic Profile.

The satiating effects of cow dairy have been thoroughly investigated; however, the effects of goat dairy on appetite have not been reported so far. Our study investigates the satiating effect of two breakfasts based on goat or cow dairy and their association with appetite related hormones and metabolic profile. Healthy adults consumed two breakfasts based on goat (G-Breakfast) or cow (C-Breakfast) dairy products. Blood samples were taken and VAS tests were performed at different time points. Blood metabolites were measured and Combined Satiety Index (CSI) and areas under the curves (AUC) were calculated. Desire to eat rating was significantly lower (breakfast & time interaction p < 0.01) and hunger rating tended to be lower (breakfast & time interaction p = 0.06) after the G-breakfast. None of the blood parameters studied were different between breakfasts; however, AUCGLP-1 was inversely associated with the AUChunger and AUCdesire-to-eat after the G-Breakfast, whereas triglyceride levels were directly associated with AUCCSI after the C-Breakfast. Our results suggest a slightly higher satiating effect of goat dairy when compared to cow dairy products, and pointed to a potential association of GLP-1 and triglyceride levels with the mechanisms by which dairy products might affect satiety after the G-Breakfast and C-Breakfast, respectively.

Comparison between a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study.

BACKGROUND AND OBJECTIVE: Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL). METHODS: A total of 45 patients with long-term diabetes and mean HbA1c values of 8.6±1.8% (70.5±15.4mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data. RESULTS: After the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p<0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p<0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p<0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p<0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p<0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9±0.7 vs. 7±0.6% [63±5.5 vs. 53±4.5mmol/mol]; p<0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p<0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7±0.6% [53±4.5mmol/mol] vs. MDI/G 7.6±0.9% [59.6±7.7mmol/mol]; p<0.03). CONCLUSIONS: Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes.

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in andalusian tertiary care hospitals.

INTRODUCTION: In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). OBJECTIVE: To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. METHOD: A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48 hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. RESULTS: 288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1 IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40 IU/day and 40-80 IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). CONCLUSIONS: Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged.

Night-time sleep duration and the incidence of obesity and type 2 diabetes. Findings from the prospective Pizarra study.

BACKGROUND: Several recent studies have related short sleep duration with different health problems, though the results related with the risk of obesity and type 2 diabetes (T2D) are far from conclusive. The aim of this study was to investigate the association between night-time sleep duration and the incidence of obesity and T2D in a prospective study with a follow-up of 11 years. MATERIAL AND METHODS: The study comprised 1145 people evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. At the three study points, subjects without known diabetes mellitus (KDM) were given an oral glucose tolerance test (OGTT). Anthropometric and biochemical variables were measured. The subjects were asked about their number of hours of night-time sleep. RESULTS: After adjustment, the OR of becoming obese was significantly higher in subjects who slept ≤ 7 hours per night, at both the 6-year follow-up (OR = 1.99; 95% CI = 1.12-3.55) and the 11-year follow-up (OR = 2.73; 95% CI = 1.47-5.04). The incidence of T2D at the 6-year follow-up in subjects without T2D at baseline was higher in those who slept ≤ 7 hours per night (OR = 1.96; 95% CI = 1.10-3.50). However, this association was not independent of obesity, weight gain or abnormal glucose regulation at baseline. At the 11-year follow-up however there was no association between night-time sleep duration and the incidence of T2D. CONCLUSIONS: The incidence of obesity over the 11-year follow-up increased in subjects with fewer hours of night-time sleep. The incidence of T2D according to the hours of night-time sleep depended on obesity and the carbohydrate metabolism phenotype.

Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?

Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 µM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk.

Modifications of the homeostasis model assessment of insulin resistance index with age.

The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, and an oral glucose tolerance test in subjects without diabetes. In the Di@bet.es study overall, an increase occurred in blood glucose until the age of 50, after which it remained stable (data adjusted for gender, body mass index, abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p < 0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra study, the HOMA-IR was significantly lower after 6-year follow-up in the whole study population. Subjects with a HOMA-IR level higher than the 75th percentile at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2-3.9; p = 0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not increase HOMA-IR levels, changes that might be related to higher rates of obesity and AGR in older subjects. The HOMA-IR was associated with an increased risk of developing type 2 diabetes 6 years later.

White rice consumption and risk of type 2 diabetes.

BACKGROUND & AIM: Recent studies suggest that white rice consumption increases risk of diabetes. AIM: to assess the association between white rice intake and the incidence of diabetes in a population from Southern Spain. METHODS: A population-based cohort study was undertaken in Pizarra, Spain. At baseline and follow-up, participants underwent an interview and a standardized clinical examination which included an oral glucose tolerance test in those subjects without known diabetes. Incidence and odds ratio (OR) for diabetes were calculated. Multivariate analysis was performed using stepwise logistical regression. RESULTS: Thirty eight percent of subjects reported rice consumption 2-3 times a week, 58.5% once or less a week, and 3.6% no rice consumption. In subjects who reported rice intake 2-3 times a week, incidence of diabetes after 6 years follow-up was 12.0%, and in those who reported once or less a week, 20.2% (p = 0.04, non adjusted). Subjects who ate rice frequently had lower risk to develop diabetes 6 years later (OR = 0.43, p = 0.04; adjusted for age, sex, obesity, and presence of impaired fasting glucose and/or impaired glucose tolerance at baseline). CONCLUSIONS: A negative association was found between white rice intake in the way it is consumed in Southern Spain, and the 6 years incidence of diabetes.

[Validation of the FINDRISC (FINnish Diabetes RIsk SCore) for prediction of the risk of type 2 diabetes in a population of southern Spain. Pizarra Study]. / Validación del FINDRISC (FINnish Diabetes Risk SCore) para la predicción del riesgo de diabetes tipo 2 en una población del sur de España. Estudio Pizarra.

BACKGROUND AND OBJECTIVE: The aim of this study was to validate the ability of the Finnish Diabetes Risk Score (FINDRISC) to predict the risk of DM2 in a population of south-eastern Spain (Pizarra Study). SUBJECTS AND METHODS: The Pizarra Study is a population-based prospective study developed in the town of Pizarra (Málaga). The first phase of the study was conducted in 1997-1998, including 1051 individuals aged 18-65 years randomly selected from the municipal census of the town. In 2003-2004 the subjects participating in the first study were reassessed. 824 individuals completed the second phase of the study (78.4%). All participants without known diabetes underwent an oral glucose tolerance test both at baseline and follow-up. We evaluated the ability of the FINDRISC to detect undiagnosed DM2 (first phase: cross-sectional study) and in predicting the incidence of DM2 (second phase: cohort study). RESULTS: The test showed good results both to detect undiagnosed DM2 (ROC-AUC 0.74) and to predict incident DM2 (ROC-AUC 0.75). The best prediction of risk of incident DM2 was found in those subjects with fasting glucose >100mg/dl and a FINDRISC ≥9 (OR: 19.37; 95%IC: 8,86-42,34; P<.0001). CONCLUSIONS: The results of our study show that FINDRISC can be a useful tool to detect subjects at high risk of diabetes in this population.