Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states.

Aims Analyze the relationship between obesity and influenza. Methods Basal hormone milieu, defective response of both innate and adaptive immune system and sedentariness are major determinants in the severity of influenza viral infection in obese patients. Being overweight not only increases the risk of infection and of complications for the single obese person, but a large prevalence of obese individuals within the population might increase the chance of appearance of more virulent viral strain, prolongs the virus shedding throughout the total population and eventually might increase overall mortality rate of an influenza pandemic. Results Waiting for the development of a vaccination against COVID-19, isolation of positive cases and social distancing are the primary interventions. Nonetheless, evidence from previous influenza pandemics suggests the following interventions aimed at improving immune response: (1) lose weight with a mild caloric restriction; (2) include AMPK activators and PPAR gamma activators in the drug treatment for obesity associated with diabetes; and (3) practice mild-to-moderate physical exercise. Conclusions Due to prolonged viral shedding, quarantine in obese subjects should likely be longer than normal weight individuals.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Amino acids have been shown to stimulate protein synthesis, inhibit proteolysis, and decrease whole-body and forearm glucose disposal. Using cultured hepatoma and myotube cells, we demonstrate that amino acids act as novel signaling elements in insulin target tissues. Exposure of cells to high physiologic concentrations of amino acids activates intermediates important in the initiation of protein synthesis, including p70 S6 kinase and PHAS-I, in synergy with insulin. This stimulatory effect is largely due to branched chain amino acids, particularly leucine, and can be reproduced by its transamination product, ketoisocaproic acid. Concurrently, amino acids inhibit early steps in insulin action critical for glucose transport and inhibition of gluconeogenesis, including decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2, decreased binding of grb 2 and the p85 subunit of phosphatidylinositol 3-kinase to IRS-1 and IRS-2, and a marked inhibition of insulin-stimulated phosphatidylinositol 3-kinase. Taken together, these data support the hypothesis that amino acids act as specific positive signals for maintenance of protein stores, while inhibiting other actions of insulin at multiple levels. This bidirectional modulation of insulin action indicates crosstalk between hormonal and nutritional signals and demonstrates a novel mechanism by which nutritional factors contribute to insulin resistance.

OBJECTIVESome obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk.RESEARCH DESIGN AND METHODSFifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m2; obese: ≥30 kg/m2) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5).RESULTSObese insulin-sensitive subjects represented 11% (95% CI 8.1–14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08–1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46–2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects.CONCLUSIONSIn contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study.

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

OBJECTIVE -Fatty liver may be involved in the pathogenesis of type 2 diabetes. Physical exercise is a tool to improve insulin sensitivity, but little is known about its effect on intrahepatic fat (IHF) content. The purpose of this study was to examine the association of habitual physical activity, insulin resistance, and adiponectin with IHF content.RESEARCH DESIGN AND METHODS -Participants were 191 (77 female and 114 male) apparently healthy, nonalcoholic individuals (aged 19 -62 years; BMI 17.0 -35.5 kg/m 2 ). IHF content was assessed in a quantitative fashion and noninvasively as a continuous variable by means of 1 H magnetic resonance spectroscopy (MRS), and habitual physical activity was assessed by means of a questionnaire. Fatty liver was defined as IHF content of Ͼ5% wet weight, and insulin sensitivity was estimated using the computer homeostasis model assessment (HOMA)-2 indexes.RESULTS -A reduced prevalence of fatty liver in the quartile of the most physically active individuals (25,11,25, and 2% in quartile 1, 2, 3, and 4, respectively; 2 ϭ 15.63; P ϭ 0.001) was found along with an inverse correlation between the physical activity index and the IHF content when plotted as continuous variables (Pearson's r ϭ Ϫ0.27; P Ͻ 0.000). This association was not attenuated when adjusted for age, sex, BMI, HOMA-2, and adiponectin (partial correlation r ϭ Ϫ0.25; P Ͻ 0.001).CONCLUSIONS -This study demonstrated that a higher level of habitual physical activity is associated with a lower IHF content and suggested that this relationship may be due to the effect of exercise per se. Diabetes Care 30:683-688, 2007A lanine aminotransferase and ␥-glutamyltransferase are associated with type 2 diabetes risk (1-3), and it is thought that the link is represented by the intrahepatic fat (IHF) content. Ectopic fat accumulation within the liver, in fact, has been reported in association with impairment of insulin-stimulated glucose metabolism, of suppression of endogenous glucose production, and of whole-body lipolysis in nondiabetic individuals with nonalcoholic fatty liver disease (NAFLD) (4,5). Additional results also demonstrated that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the IHF content, suggesting that hypoadiponectinemia may be involved in excessive hepatic fat accumulation (6).Physical exercise was found to be associated with a reduced risk of development of type 2 diabetes (7,8) and is a wellrecognized tool to improve insulin sensitivity at the level of the skeletal muscle (9). However, whether physical exercise may affect insulin sensitivity and diabetes risk via an effect on the IHF content and adiponectin remains unknown.The IHF content may be assessed as a continuous variable by means of 1 H magnetic resonance spectroscopy (MRS) (10), and recently this technique was found to be a sensitive, quantitative, and noninvasive method also when applied to a large population (11) without the need for the use of a more invasive approach such as liver biopsy. The ...

Mauri (2019) Minimallyinvasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group,

Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2 H2]glucose and 1 H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 Ϯ 0.6 and 3.2 Ϯ 0.8 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) similar to OFF (5.3 Ϯ 0.4 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) compared with NOR (8.5 Ϯ 0.5 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.001). Soleus IMCL content was increased in T1DM (112 Ϯ 15 AU), T2DM (108 Ϯ 10 AU) and OFF (82 Ϯ 13 AU) compared with NOR (52 Ϯ 7 AU, P Ͻ 0.05) and the result was inversely proportional to the MCR (R 2 ϭ 0.27, P Ͻ 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R 2 ϭ 0.57, P Ͻ 0.001). Fasting plasma adiponectin was reduced in T2DM (7 Ϯ 1 g/ml, P ϭ 0.01) and OFF (11 Ϯ 1 g/ml, P ϭ 0.03) but not in T1DM (25 Ϯ 6 g/ml), whose plasma level was increased with respect to both OFF (P ϭ 0.03) and NOR (16 Ϯ 2 g/ml, P ϭ 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear. intramyocellular triglyceride content; leptin; magnetic resonance spectroscopy