Elías Delgado

Adiponectin, hepatocellular dysfunction and insulin sensitivity

objective  Insulin resistance plays a major aetiological role in the development of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin resistance and liver damage, we wished to study whether low circulating adiponectin would be associated with higher serum concentrations of liver enzymes in healthy subjects.

Population-Based Incidence of Type 2 Diabetes in Northern Spain: The Asturias Study

OBJECTIVE—The aim of this study was to define the incidence of type 2 diabetes in a low-risk Caucasian population in northern Spain and its association with various risk factors. RESEARCH DESIGN AND METHODS—The Asturias Study is a prospective, population-based survey of diabetes and cardiovascular risk factors. The baseline examination was carried out during 1998–1999 when 1,034 individuals, aged 30–75 years, were randomly selected to determine the prevalence of type 2 diabetes and pre-diabetes in the Principality of Asturias (northern Spain). In 2004–2005, these same subjects were invited for a follow-up examination; 700 participated. This study includes only those individuals who did not have diabetes at baseline. We used the World Health Organization 1999 criteria to classify glucose metabolism at both baseline and follow-up. RESULTS—The incidence of diabetes adjusted for the age and sex structure of Asturias was 10.8 cases/1,000 person-years (95% CI 8.1–14.8). The incidence rates were 5 cases/1,000 person-years in individuals with normoglycemia, 21 cases/1,000 person-years in individuals with isolated impaired glucose tolerance (IGT), 34.7 cases/1,000 person-years in individuals with isolated impaired fasting glucose (IFG), and 95.2 cases/1,000 person-years in individuals with combined IFG-IGT. Stepwise multiple logistic regression analysis showed that, together with fasting plasma glucose (FPG) and 2-h plasma glucose, which were the strongest predictors of diabetes, triglycerides and BMI were also independently associated with progression to diabetes. CONCLUSIONS—In this 6-year prospective population-based study, we found an incidence of type 2 diabetes of 10.8 cases/1,000 person-years. Both FPG and 2-h plasma glucose were strongly predictive of diabetes, and their effect was additive.

Vitamin D deficiency in Spain: a population-based cohort study

Background:Vitamin D deficiency is common worldwide. No homogenous reference values have yet been established and no studies of values have been conducted in Spain involving a large number of participants.Objective:To study the population concentrations of vitamin D in a representative sample of the Spanish population.Subjects/Methods:The study involved two cohorts from Spain, the Asturias study and the Pizarra study, which are two prospective, population-based studies involving 2260 participants. In 1262 subjects (age: 20–83 years) we studied 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), calcium, phosphorus and creatinine.Results:The median population values of 25-hydroxyvitamin D and iPTH were 22.46 ng/ml and 42.29 pg/ml, respectively. The values of 25-hydroxyvitamin D were significantly higher in summer and correlated with age (β=−0.05±0.01, P<0.0001), creatinine (β=6.42±1.17, P<0.0001) and iPTH (−0.07±0.01, P<0.0001), but not with calcium, phosphorus or sex. The increase in iPTH with age was seen whatever the values of 25-hydroxyvitamin D, and was greater in the older persons. The concentration of iPTH rose continuously with effect from 25-hydroxyvitamin D values below ≈30 ng/ml. Values above ≈35 ng/ml were associated with a significantly lower concentration of iPTH.Conclusions:One-third (33.9%) of the Spanish population may be at risk for Vitamin D deficiency. The 25-hydroxyvitamin D values above 30 ng/ml can safely discard ‘hyper PTH’. The increase in iPTH concentration is greater in older persons for similar values of 25-hydroxyvitamin D.

Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

Aims  To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO‐1985 and 1999 and ADA‐1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes.

Prevalence and outcome of newly detected diabetes in patients who undergo percutaneous coronary intervention

AIMS The beneficial effect of specific measures in patients with newly detected diabetes during percutaneous coronary intervention (PCI) has been poorly studied. Here, we determined the prevalence of newly detected diabetes in a cohort of patients who underwent PCI and analysed their clinical outcome. METHODS AND RESULTS A prospective study included patients without previous diagnosis of diabetes that were referred for PCI between November 2005 and May 2006. Major cardiac events were registered after admission and during 12 months of follow-up, and oral glucose tolerance was tested at 15 days after hospital discharge. Six hundred and sixty-two consecutive patients were referred to our hospital for PCI. The distribution of the glycometabolic state of the entire population was (95% CI): known diabetes 28.8% (25.2-32.6), newly detected diabetes 16.2% (13.1-19.8), impaired glucose tolerance 24.5% (20.8-28.5), impaired fasting glucose 1% (0.4-2.4), and normal glucose regulation 29.5% (25.5-33.7). In a multivariable analysis, the presence of newly detected diabetes was not an independent predictor of cardiac events after 1 year of follow-up. CONCLUSION The prevalence of diabetes in patients who underwent PCI was very high (45%), 35% of which was patients with newly detected diabetes. In our series newly detected diabetes was not an independent predictor of outcome at 12 months. Nevertheless, this finding requires independent confirmation in other series to draw general conclusions on the whole spectrum of percutaneous interventions.

Epidemiología de la diabetes tipo 2 en España

La diabetes mellitus es una de las enfermedades con mayor impacto sociosanitario, no solo por su alta prevalencia, sino tambien por sus complicaciones cronicas y su elevada tasa de mortalidad. La forma mas exacta de estimar la prevalencia de DM es la practica de un test de tolerancia oral a la glucosa. En Espana, la prevalencia de DM se estima en un 6,2% para grupos de edad 30-65 anos, y en un 10% para 30-89 anos. La proporcion de DM conocida frente a la ignorada oscila entre 1/3 y 2/3 del total. Los factores de riesgo de DM mas importantes son la edad, la obesidad y la historia familiar de DM. La incidencia de DM2 se estima en 8/1.000 habitantes ano. La prevalencia de las distintas complicaciones cronicas varia en funcion del tipo de DM, tiempo de evolucion y grado de control metabolico, estimandose globalmente en la siguiente: neuropatia 25%, retinopatia 32% y nefropatia 23%. La DM es una de las principales causas de mortalidad en Espana, ocupando el tercer lugar en mujeres y el septimo en varones.

Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

OBJECTIVE Increased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance. DESIGN We performed both cross-sectional and longitudinal (diet-induced weight loss) studies. METHODS Circulating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (S(I), Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19). RESULTS Circulating calprotectin was significantly increased in IGT-T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin with S(I) was independent of BMI and age. In fact, S(I) together with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR. CONCLUSION These findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

Iodine intake in the adult population. Di@bet.es study

BACKGROUND & AIMS To date no nation-wide study has yet been undertaken in Spain to estimate the iodine deficiency. The aim was to evaluate iodine intake and its conditioning factors in a representative sample of the whole adult population. METHODS The Di@bet.es Study is a national, cross-sectional, population-based survey conducted in 2009-2010 in Spain. RESULTS The median urinary iodine (UI) was 117.2 μg/L. Iodized salt (IS) was consumed by 43.9% of the population. The median UI in those who consumed IS and in those who did not consume IS was 131.1 and 110.8 μg/L respectively (p<0.0001). The likelihood of having UI levels above 100 μg/L was significantly associated with the intake of IS (OR=1.47) and milk at least once a day (OR=1.22). Within each individual autonomous communities, the median UI levels in those who consumed IS correlated significantly with the median levels of those who did not consume IS (r=0.76, p=0.001). CONCLUSIONS Though strictly speaking, Spain should be considered within the category of a country having an adequate iodine intake, the current value is too close to the cut point and does not guarantee that those groups with a greater need for iodine will have the required intake of iodine.

Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity

OBJECTIVE Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations. RESEARCH DESIGN AND METHODS Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort. RESULTS In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss. CONCLUSIONS These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.

Comparison of Basal-Bolus and Premixed Insulin Regimens in Hospitalized Patients With Type 2 Diabetes.

OBJECTIVE Premixed insulin is a commonly prescribed formulation for the outpatient management of patients with type 2 diabetes. The safety and efficacy of premixed insulin formulations in the hospital setting is not known. RESEARCH DESIGN AND METHODS In a prospective, open-label trial, we randomized general medicine and surgery patients to receive a basal-bolus regimen with glargine once daily and glulisine before meals (n = 33) or premixed human insulin (30% regular insulin and 70% NPH insulin) twice daily (n = 39). Major outcomes included differences in daily blood glucose (BG) levels and frequency of hypoglycemic events (<70 mg/dL) between treatment groups. RESULTS At the first prespecified interim analysis, the study was stopped early because of an increased frequency of hypoglycemia >50% in patients treated with premixed human insulin. A total of 64% of patients treated with premixed insulin experienced one or more episodes of hypoglycemia compared with 24% in the basal-bolus group (P < 0.001). There were no differences in mean daily BG level after the first day of insulin treatment (175 ± 32 vs. 179 ± 43 mg/dL, P = 0.64) between groups. A BG target between 80 and 180 mg/dL before meals was achieved in 55.9% of BG readings in the basal-bolus group and 54.3% of BG readings in the premixed insulin group (P = 0.23). There was no difference in the length of hospital stay or mortality between treatment groups. CONCLUSIONS Inpatient treatment with premixed human insulin resulted in similar glycemic control but in significantly higher frequency of hypoglycemia compared with treatment with basal-bolus insulin regimen in hospitalized patients with diabetes.