M. R. Bernal-Lopez

Progression from High Insulin Resistance to Type 2 Diabetes Does Not Entail Additional Visceral Adipose Tissue Inflammation

Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.

HbA1c in adults without known diabetes from southern Europe. Impact of the new diagnostic criteria in clinical practice

Diabet. Med. 28, 1319–1322 (2011)

Effects of a long-term lifestyle intervention program with Mediterranean diet and exercise for the management of patients with metabolic syndrome in a primary care setting.

BACKGROUND The impact of a lifestyle intervention (LSI) program for the long-term management of subjects with metabolic syndrome in a primary care setting is not known. METHODS This 3-year prospective controlled trial randomized adult subjects with metabolic syndrome to receive intensive LSI or to usual care in a community health centre in Malaga, Spain. LSI subjects received instruction on Mediterranean diet and a regular aerobic exercise program by their primary care professionals. Primary outcome included changes from baseline on different components of metabolic syndrome (abdominal circumference, blood pressure, HDL-cholesterol, fasting plasma glucose and triglycerides). RESULTS Among the 2,492 subjects screened, 601 subjects with metabolic syndrome (24.1%) were randomized to LSI (n = 298) or to usual care (n = 303); of them, a 77% and a 58%, respectively, completed the study. At the end of the study period, LSI resulted in significant differences vs. usual care in abdominal circumference (-0.4 ± 6 cm vs. + 2.1 ± 6.7 cm, p < 0.001), systolic blood pressure (-5.5 ± 15 mmHg vs. -0.6 ± 19 mmHg, p = 0.004), diastolic blood pressure (-4.6 ± 10 mmHg vs. -0.2 ± 13 mmHg, p < 0.001) and HDL-cholesterol (+4 ± 12 mg/dL vs. + 2 ± 12 mg/dL, p = 0.05); however, there were no differences in fasting plasma glucose and triglyceride concentration (-4 ± 35 mg/dl vs. -1 ± 32 mg/dl, p = 0.43 and -0.4 ± 83 mg/dl vs. +6 ± 113 mg/dl, p = 0.28). CONCLUSION Intensive LSI counseling provided by primary care professionals resulted in significant improvements in abdominal circumference, blood pressure and HDL-cholesterol but had limited effects on glucose and triglyceride levels in patients with metabolic syndrome.

National trends in diabetes mellitus hospitalization in Spain 1997–2010: Analysis of over 5.4 millions of admissions

AIMS To analyze national trends in the rates of hospitalizations (all-cause and by principal discharge diagnosis) in total diabetic population of Spain. METHODS We carried out a nation-wide population-based study of all diabetic patients hospitalized between 1997 and 2010. All-cause hospitalizations, hospitalizations by principal discharge diagnosis, mean age, Charlson Comorbidity Index, readmission rates and length of hospital stay were examined. Annual rates adjusted for age and sex were analyzed and trends were calculated. RESULTS Over 14-years-period, all-cause hospitalizations of diabetic patients increased significantly, with an average annual percentage change of 2.5 (95%CI: 1.5-3.5; Ptrend < 0.01). The greatest increase was observed in heart failure (5.4; 95%CI: 4.8-6.0; Ptrend < 0.001), followed by neoplasms (4.9; 95%CI: 3.6-5.8; Ptrend < 0.001), pneumonia (2.7; 95%CI: 2.0-4.0; Ptrend < 0.001), stroke (2.4; 95%CI: 1.6-3.4; Ptrend < 0.001), chronic obstructive pulmonary disease (2.0; 95%CI: 1.4-3.4; Ptrend < 0.001) and coronary artery disease (1.6; 95%CI: 1.1-2.3; Ptrend < 0.01). The adjusted number of all-cause hospitalizations of patients with diabetes per 100,000 inhabitants increased 2.6-fold. The increase in hospitalizations was significantly higher among patients ≥75 years old. Males experienced a greater increase in all-cause, neoplasm, heart failure, chronic obstructive pulmonary disease, and pneumonia hospitalizations (p < 0.01 for all). Hospitalized diabetic patients were progressively older and had more comorbidities, higher readmission rates and shorter hospital stays (p < 0.05 for all). CONCLUSIONS Hospitalizations of diabetic patients more than doubled in Spain during the study period. Heart failure and neoplasms experienced the greatest annual increases and remained the principal causes of hospitalization, probably associated with advanced age and comorbidities of hospitalized diabetics. Coronary and cerebrovascular diseases experienced a lower annual increase, suggesting an improvement in cardiovascular care in diabetes in Spain.

HbA1c for diabetes diagnosis. Are we ready

153 IU ⁄ l (normal range 28–100) and 273 IU ⁄ l (normal range 13–60), respectively. Together, these findings were consistent with fulminant Type 1 diabetes. The patient had a heterozygous HLA DRB1*0403 ⁄ *1302, HLA DQB1 *0302 ⁄ *0604 genotype. It has been reported that fulminant Type 1 diabetes is associated with viral infections such as human herpes virus 6, herpes simplex virus, coxsakie B virus, mumps and encephalomyocarditis virus [1]. However, to the best of our knowledge, this is the first report of fulminant Type 1 diabetes associated with acute hepatitis A. Although the mechanism of hepatitis A virus-induced B-cell destruction is unknown, pancreatic involvement during acute hepatitis A has been reported [2] and is thought to be attributable to an immune response, rather than to a direct cytotoxic effect as in the case of hepatocellular injury with acute hepatitis A [3]. In addition, hepatitis A virus is associated with immune-associated diseases, including autoimmune hepatitis, immune thrombocytopenic purpura, cryoglobulinaemia and vasculitis [4]. Tanaka et al. reported a histopathological examination of fulminant Type 1 diabetes where CD8 lymphocytes had infiltrated into both the endocrine and exocrine pancreas [5]. In addition, it has been suggested that cellular immunoreactivity to pancreatic B-cell antigens may be unregulated in fulminant Type 1 diabetes, at least after the onset of overt diabetes [6]. Taken together, hepatitis A viral infection may trigger the destruction of pancreatic B-cells in susceptible individuals through the activation of host immune reaction, finally resulting in fulminant Type 1 diabetes. Furthermore, three patients with diabetic ketoacidosis have been reported within 2– 3 weeks of acute hepatitis A, although the C-peptide levels were not measured [7]. Therefore, patients with acute hepatitis A should be studied to better understand the aetiology and pathogenesis of fulminant Type 1 diabetes. The patient has given written informed consent to the genetic studies and to publication of this case.

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m2) was 38.15 ± 4.7 vs. 34.18 ± 4.5 (p < 0.02), and body weight (kg) was 98.5 ± 13.1 vs. 88.28 ± 12.2 (p < 0.03). All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex (p < 0.001), left posterior cingulate (p < 0.001), and right posterior cingulate (p < 0.03); decreased connectivity between the left superior frontal gyrus and the right temporal cortex (p < 0.01); decreased connectivity between the prefrontal cortex and the somatosensory cortex (p < 0.025); and decreased connectivity between the left and right posterior cingulate (p < 0.04). Results were considered significant at a voxel-wise threshold of p ≤ 0.05, and a cluster-level family-wise error correction for multiple comparisons of p ≤ 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity (the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex) may be modified by a weight loss program including a Mediterranean diet and physical exercise.

Characterization of lipid profile by nuclear magnetic resonance spectroscopy (1H NMR) of metabolically healthy obese women after weight loss with Mediterranean diet and physical exercise

Abstract Obesity is associated with an atherogenic lipid profile. No data exists on lipoprotein particle profiles in metabolically healthy obese (MHO) individuals. Our aim is to characterize lipoprotein size, particle, and subclass concentrations in MHO women after 3 months of weight loss through dietary restriction and physical exercise. A total of 115 nondiabetic women (aged 35–55 years) with a body mass index (BMI) of 30 to 40 kg/m2 and ⩽1 of the following criteria: blood pressure ⩽135/85 mm Hg, fasting plasma glucose ⩽100 mg/dL, HDL-cholesterol ⩽50 mg/dL, and triglycerides ⩽150 mg/dL were included. After 3 months of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5% to <10%, and ≥10%. Lipoprotein size, particle, and subclass concentrations were measured using 1H NMR. The final sample, after dropouts, comprised 104 women (age: 44.4 ± 3.7 years, BMI: 36.3 ± 4.7 kg/m2), of whom 47 (45.2%), 27 (26%), and 30 (28.8%) lost <5%, ≥5% to <10%, and ≥10% of baseline body weight, respectively. All participants experienced significant weight loss and decreases in BMI. The lipid profiles showed an increase in small, medium, and large very low density lipoprotein (VLDL) particles in all groups of study with the exception of small VLDL particles in women with ≥10% of weight loss, in which it decreased. The number of VLDL particles decreased in women who had ≥10% weight loss. On the other hand, we detected a decrease in all low density lipoprotein (cLDL) and high density lipoprotein (cHDL) concentrations. These results indicate that intensive lifestyle modification alters lipid profiles. In particular, it decreases small LDL and HDL particle numbers and does not increase medium or large HDL particles numbers.