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Studies on thyroid function in obesity yielded inconsistent results; high thyroid-stimulating hormone (TSH) levels were generally shown; high free triiodothyronine (fT)-3 or fT4 levels were described in some, but not in other studies. After weight loss, TSH and thyroid hormones have been described to either increase or decrease. Our aim was to describe TSH, fT3, and fT4 in obese subjects with normal thyroid function before and after durable and significant weight loss, obtained through laparoscopic gastric banding (LAGB), in comparison with nonobese subjects. TSH, fT3, fT4, and fT3/fT4 ratio (an index of D1 and D2 deiodinase activity), were evaluated in 99 healthy controls and in 258 obese subjects, at baseline and 6 months, 1 year, and 2 years after LAGB, together with indexes of glucose (glucose, insulin, homeostasis model assessment of insulin resistance index) and lipid (triglycerides, total and high-density lipoprotein–cholesterol) metabolism, and anthropometric measures (BMI and waist circumference). Under basal conditions, TSH, fT3, and fT4 were all in the normal range, but higher in obese than in nonobese subjects, and fT3/fT4 ratio was normal; with weight loss, fT3 and fT3/fT4 ratio decreased in obese subjects, while fT4 increased and TSH remained steady; all values were again within the normal range. Albumin and cholesterol levels remained steady, while triglycerides, insulin, and homeostasis model assessment of insulin resistance decreased, and high-density lipoprotein–cholesterol increased. These changes, however, do not modify TSH, letting us to hypothesize that the changes are due to a decrease of D1 and D2 deiodinase activities. [ABSTRACT FROM AUTHOR]

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment. [ABSTRACT FROM AUTHOR]

Metabolic disorders such as obesity and type 2 diabetes (T2D) are considered the major risk factors for the development of cardiovascular diseases (CVD). Although the pathological mechanisms underlying the mutual development of obesity and T2D are difficult to define, a better understanding of the molecular aspects is of utmost importance to identify novel therapeutic targets. Recently, a class of non-coding RNAs, called microRNAs (miRNAs), are emerging as key modulators of metabolic abnormalities. There is increasing evidence supporting the role of intra- and extracellular miRNAs as determinants of the crosstalk between adipose tissues, liver, skeletal muscle and other organs, triggering the paracrine communication among different tissues. miRNAs may be considered as risk factors for CVD due to their correlation with cardiovascular events, and in particular, may be related to the most prominent risk factors. In this review, we describe the associations observed between miRNAs expression levels and the most common cardiovascular risk factors. Furthermore, we sought to depict the molecular aspect of the interplay between obesity and diabetes, investigating the role of microRNAs in the interorgan crosstalk. Finally, we discussed the fascinating hypothesis of the loss of protective factors, such as antioxidant defense systems regulated by such miRNAs. [ABSTRACT FROM AUTHOR]

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many diseases, few studies have investigated salivary miRNAs and their role in pregnancy or neonatal outcomes. In this study, we sought to investigate the associations between salivary miRNAs of pregnant women with oral diseases and their effects on neonatal outcomes. Eleven (n = 11) salivary miRNAs from a cohort of pregnant women with oral diseases (n = 32; oral health, H; gingivitis, G; and periodontitis, P) were detected using a previous profiling analysis with an FDR < 0.20 and a fold change (FC) < 0.5 or FC > 2 for the most highly expressed miRNAs. Spearman correlations were performed for 11 salivary microRNAs associated with oral-derived inflammation, which could affect neonatal outcomes during pregnancies at risk for cardiometabolic disease (CMD), defined by the presence of a high pregestational BMI. In addition, ROC curves demonstrated the diagnostic accuracy of the markers used. Upregulation of miR-423-5p expression and a decrease in miR-27b-3p expression were detected in the P-group (p < 0.05), and ROC analysis revealed the diagnostic accuracy of miR-423-5p for discriminating oral diseases, such as gingivitis versus periodontitis (P vs. G, AUC = 0.78, p < 0.05), and for discriminating it from the healthy oral cavity (P vs. H, AUC = 0.9, p < 0.01). In addition, miR-27b-3p and miR-622 were also able to discriminate the healthy group from the P-group (AUC = 0.8, p < 0.05; AUC = 0.8, p < 0.05). miR-483-5p was able to discriminate between the G-group (AUC = 0.9, p < 0.01) and the P-group (AUC = 0.8, p < 0.05). These data support the role of salivary miRNAs as early biomarkers for neonatal outcomes in pregnant women with periodontal disease at high risk for CMD and suggest that there is cross-talk between salivary miRNAs and subclinical systemic inflammation. [ABSTRACT FROM AUTHOR]

Focuses on the intranasal calcitonin administration. Presence of hypercalcaemia on the subjects studied; Falls in plasma concentrations of ionized calcium value; Side effects with intravenous administration of calcitonin.

A letter to the editor is presented in response to the article "Limited Recovery of β-Cell Function After Gastric Bypass Despite Clinical Diabetes Remission" by R. Dutia and colleagues, published in the 2014 issue.

With bariatric restrictive procedures a major issue is represented by search of clinical outcome predictors; non-surgical and psychological factors play a role in bariatric surgery long term-results. In this study we evaluated a set of predictors of short-term and long-term clinical outcome including psychiatric and psychological variables. 172 consecutive patients undergoing laparoscopic adjustable gastric banding (LAGB) with a minimum 12 months follow-up; were studied; before surgery they were administered the NIMH Diagnostic Interview Schedule (Version III-R, DIS III-R), and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (Version 2.0, SCID-II). After surgery, patients were scheduled for visits at fortnight intervals up to two months, at monthly intervals up to one year, at three-monthly intervals for 2 years; compliance with diet, rules, physical exercise, plus integrated compliance (sum of scores), and percentage of attendance at scheduled visits were recorded; patients were contacted again at 36 and at 48 months. BMI, compliance, percentage of attendance at scheduled visits (positively), and narcissitic personality (negatively) were associated with weight loss at 12, 24 (and 36 months); percentage of attendance was associated at 48 months. At stepwise regression analysis, BMI and integrated compliance predicted weight loss at 12, 24, and 36 months, while percentage of attendance at scheduled visits predicted weight loss at 48 months; narcissistic personality predicted weight loss only at 12 months. We conclude that narcissistic personality and adherence to scheduled visits, as well as compliance to recommended rules, predicts success of LAGB, at least during the first 4 years. [ABSTRACT FROM AUTHOR]

Obesity and elevated liver enzymes are risk factors for the development of type 2 diabetes (T2D). Bariatric surgery-weight loss has been shown to restore normal glucose tolerance in T2D. In a cohort of 159 consecutive morbid obese patients (60%NGT; 22%IGT; 18%T2D; age 41±1y, BMI 44.4±0.4 kg/m²) we measured liver enzymes (AST and ALT), oral glucose tolerance (GT) and fat mass before and after LAGB. At baseline 44% of the subjects (N=70, 49F/21M) had high liver enzymes (HLE) (defined as AST/ALT=30 U/l). Among HLE subjects, 21% had T2D and 24% had IGT; in subjects with normal liver enzymes (NLE, n=89, 83F/6M) 15% had T2D and 20% had IGT. Compared with NLE, HLE patients had reduced insulin sensitivity (both peripheral=OGIS, 6.3±0.2 vs 7.0±0.1 ml/min.kg, p<0.005 and hepatic=QUICKI, 307±3 vs 316±3 p=0.02), independently of glucose tolerance status. In a multiple regression model, insulin sensitivity (OGIS) correlated independently with both ALT (partial r=-0.21, p=0.01) and waist (partial r=-0.26, p=0.001), after accounting for age/gender/BMI. 1 year after LAGB, mean weight loss was 21±1 kg, BMI was 36.6±0.4 kg/m² and waist circumference decreased by 15.2±0.8 cm. Overall, after LAGB we observed: a) significant and stable weight loss; b) decrease in liver enzymes (ALT from 36±2 to 23±1 mU/l; 30% of subjects went from HLE to NLE, 52% remained NLE, 18% still had HLE); c) improved glucose tolerance (79%NGT, 13%IGT, 8%T2D); d) improved peripheral (+29±) and hepatic (+11%) insulin sensitivity (IS). Subjects with both HLE and NLE similarly improved their IS; after 1y. ΔIS was strongly correlated with ΔBMI (r=-0.48, p<0.0001). Conclusions: a large proportion of morbidly obese subjects have increased liver enzymes which are associated with higher insulin resistance and increased waist circumference. LAGB weight loss improved glucose tolerance and significantly reduced circulating liver enzymes. [ABSTRACT FROM AUTHOR]

Bariatric surgery is effective in inducing significant and durable weight loss in severely obese patients (BMI>35 kg/m2), and in improving glucose metabolism. Our aim was to compare restrictive (LAGB, laparoscopic gastric banding) and malabsorptive approaches (BIBP, biliary intestinal by-pass) on loss of fat-free mass (FFM), fat mass (FM), and on improvement of glucose, insulin, and HOMA. Body composition (bio-impedance analysis, BIA), blood glucose, and insulin were measured under basal conditions and I year after surgery in consecutive patients undergoing LAGB (n=45), BIBP (n=18), and in control patients (receiving diet treatment, n=29). BMI and FM decrease was greater with BIBP (14.6±1.01 kg/m2 and 32.2±2.78 kg) than in LAGB (7.2±0.46 kg/ m2 and vs 14.9±1.11 kg) and in control patients (-0.7±0.30 kg/m2 and -1.55±0.75 kg); in contrast, FFM loss was not significantly different with the two approaches (LAGB 4.7±0.69 kg vs BIBP 6.3±1.29 kg), greater than in controls (-0.73±0.60 kg). Blood glucose and insulin decrease was greater with BIBP (40.9±10.47 mg/dl and 20.4±4.69 µU/ml) than LAGB (16.9±2.17 mg/dl and 16.7±0.93 µU/ml) and in controls (10.5±2.74 mg/dl and 5.8±0.89 µU/ml); HOMA decrease was similar with LAGB and BIBP. BG, insulin, and HOMA decrease significantly correlated with FM decrease, not FFM. We conclude that decrease of BMI, of FM, of insulin, and glucose are greater with malabsorptive approaches than with restrictive approaches, while loss of FFM is similar, and of low entity, with different approaches. Improvement of glucose metabolism is proportional to decrease of fat mass, not of fat-free mass. [ABSTRACT FROM AUTHOR]

Editorial. Focuses on the increase awareness in European Society for Clinical Investigation (ESCI) by the European Journal of Clinical Investigation (EJCI). Link between EJCI and ESCI; Background of ESCI; Assessment on the Annual Scientific Meetings of ESCI.

The aim of this retrospective study was to evaluate risk factors for 3-years mortality after hospital discharge in all inpatients admitted to a general hospital in Milano, Italy. A total of 2580 consecutive patients admitted to Ospedale San Paolo, July 1 to December 31, 2012, for several classes of diseases (internal medicine, cancer, infectious diseases, trauma and surgery, pneumonia, and heart diseases) were studied. Age, total disease, type of admission, length of admission, age-adjusted Charlson index, prognostic nutritional index (PNI), and full blood count were evaluated. Univariate Cox models were used to evaluate the association between variables and death. Of the 2580 consecutive patients (age 66.8 ± 19.36 years, mean ± SD), 920 died within 3 years after discharge. At univariate analysis, all investigated variables, except sex and lymphocytes, were associated with patient death. Stepwise regression analyses revealed that the age-adjusted Charlson index or age plus total diseases, type of admission, number of admissions, and PNI were significant risk factors in the whole sample and in some classes of disease. Results were superimposable when considering death from date of admission instead of date of discharge, meaning that in-hospital death was not relevant to the total death count (115 out of 902). Seriousness of baseline conditions represents the major risk factor for mortality in most classes of disease, and possibly influences other predictors, such as type of admission and length of stay. This suggests that the current model of hospital admission might be improved, for instance, through comprehensive care at home, instead of hospital admission, or before admission. [ABSTRACT FROM AUTHOR]

Aims: Bariatric surgeries induce profound weight loss (decrease in body mass index, BMI), through a decrease in fat mass (FM) and to a much lesser degree of fat-free mass (FFM). Some reports indicate that the weight which is lost after gastric bypass (RYGB) and sleeve gastrectomy (SG) is at least partially regained 2 years after surgery. Here we compare changes in BMI and body composition induced by four bariatric procedures in a 5 years follow-up study. Methods: We analyzed retrospectively modifications in BMI, FM and FFM obtained through Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), biliopancreatic diversion (BPD) and a long common limb revisional biliopancreatic diversion (reduction of the gastric pouch and long common limb; BPD + LCL−R). Patients were evaluated at baseline and yearly for 5 years. Of the whole cohort of 565 patients, a subset of 180 patients had all yearly evaluations, while the remaining had incomplete evaluations. Setting University Hospital. Results: In a total of 180 patients evaluated yearly for 5 years, decrease in BMI and FM up to 2 years was more rapid with RYGB and SG than BPD and BPD + LCL−R; with RYGB and SG both BMI and FM slightly increased in the years 3–5. At 5 years, the differences were not significant. When analysing the differences between 2 and 5 years, BPD + LCL−R showed a somewhat greater effect on BMI and FM than RYGB, BPD and SG. Superimposable results were obtained when the whole cohort of 565 patients with incomplete evaluation was considered. Conclusions: All surgeries were highly effective in reducing BMI and fat mass at around 2 years; with RYGB and SG both BMI and FM slightly increased in the years 3–5, while BPD and BPD + LCL−R showed a slight further decreases in the same time interval. [ABSTRACT FROM AUTHOR]

Background: Information about the renin–angiotensin–aldosterone system (RAAS) in obese individuals before and after bariatric surgery is scarce. Aim of this study was to analyze the RAAS in severely obese subjects, in relation to anthropometric and metabolic variables, with special reference to glucose tolerance. Methods: 239 subjects were evaluated at baseline, and 181 one year after bariatric surgery [laparoscopic gastric banding (LAGB)]. Results: At baseline, renin (plasma renin activity, PRA) was increased from normal to glucose tolerance and more in diabetes, also correlating with ferritin. After LAGB, the decrease of PRA and aldosterone was significant in hypertensive, but not in normotensive subjects, and correlatied with decrease of ferritin. PRA and glucose levels were predictive of persistent hypertension 1 year after LAGB. Conclusions: These data support the role of RAAS in the pathophysiology of glucose homeostasis, and in the regulation of blood pressure in obesity. Ferritin, as a proxy of subclinical inflammation, could be another factor contributing to the cross-talk between RAAS and glucose metabolism. [ABSTRACT FROM AUTHOR]

Liver and heart disease are major causes of death worldwide. It is known that metabolic alteration causing type 2 diabetes (T2D) and Nonalcoholic fatty liver (NAFLD) coupled with a derangement in lipid homeostasis, may exacerbate hepatic and cardiovascular diseases. Some pharmacological treatments can mitigate organ dysfunctions but the important side effects limit their efficacy leading often to deterioration of the tissues. It needs to develop new personalized treatment approaches and recent progresses of engineered RNA molecules are becoming increasingly viable as alternative treatments. This review outlines the current use of antisense oligonucleotides (ASOs), RNA interference (RNAi) and RNA genome editing as treatment for rare metabolic disorders. However, the potential for small non-coding RNAs to serve as therapeutic agents for liver and heart diseases is yet to be fully explored. Although miRNAs are recognized as biomarkers for many diseases, they are also capable of serving as drugs for medical intervention; several clinical trials are testing miRNAs as therapeutics for type 2 diabetes, nonalcoholic fatty liver as well as cardiac diseases. Recent advances in RNA-based therapeutics may potentially facilitate a novel application of miRNAs as agents and as druggable targets. In this work, we sought to summarize the advancement and advantages of miRNA selective therapy when compared to conventional drugs. In particular, we sought to emphasise druggable miRNAs, over ASOs or other RNA therapeutics or conventional drugs. Finally, we sought to address research questions related to efficacy, side-effects, and range of use of RNA therapeutics. Additionally, we covered hurdles and examined recent advances in the use of miRNA-based RNA therapy in metabolic disorders such as diabetes, liver, and heart diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.Methods: Duodenal tissues were collected from aged (21.2 ± 1.3 years, 19.5 ± 3.1 kg, n = 39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated.Results: Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 ± 6.93%) and was correlated with AC (r = 0.60, p < 0.001), weight (r = 0.38, p = 0.02), leptin (r = 0.63, p < 0.001), adiponectin (r = − 0.32, p < 0.05), and triglyceride (r = 0.41, p = 0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 µm2, p = 0.02).Conclusions: Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition. [ABSTRACT FROM AUTHOR]

An increased prevalence of female sexual dysfunction (FSD) has been reported in women with diabetes mellitus (DM). Our aim was to evaluate correlates (psychological, cardiovascular, and neurophysiologic) of FSD in DM women without chronic diabetic complications. Female Sexual Function Index (FSFI), Beck Depression Inventory (BDI), Michigan Diabetic Neuropathy Index (DNI), and the symptoms of diabetic neuropathy (SDN) questionnaires, metabolic variables, endothelial vascular function (flow-mediated dilation, FMD), echocardiography, and electromyography were studied. 109 pre-menopausal women (18–50 years) [48 with DM (14 type 1 DM, 34 type 2 DM, duration 12.6 ± 1.91 years), and 61 healthy women] received the above questionnaires; physical activity, smoking habits, parity, BMI, waist circumference, HOMA-IR index, fibrinogen, cholesterol (total, HDL, LDL), triglycerides, HbA1c, high-sensitivity C-reactive protein, total testosterone, and estradiol were measured; echocardiography, assessment of intima-media thickness (IMT), FMD, ECG (heart rate and Qtc, indexes of sympathetic activity), and electromyography were performed. FSFI total score and score for arousal, lubrication, and orgasm domains were lower in DM women than in controls ( P < 0.05); DM women had higher BDI, Doppler A wave peak velocity, DNI, and SDN score ( P < 0.001 to P < 0.04). Doppler E wave peak velocity, peroneal, posterior tibial and sural nerves conduction velocity and amplitude were lower in diabetic women than in controls ( P < 0.05 to P < 0.001). FSFI score was positively correlated with physical activity, Doppler E wave peak velocity, and peroneal nerve amplitude and negatively with BDI, parity, IMT, SDN, and HbA1c ( P < 0.05 to P < 0.001). At stepwise regression, SDN score (negatively) and Doppler E wave peak velocity (positively) predicted FSFI score ( r = 507, P < 0.001). In conclusion, cardiovascular and neurological impairments are associated with FSD in diabetic women. Follow-up studies are required to evaluate sexual dysfunction as a risk factor for future cardiovascular or neurological events. [ABSTRACT FROM AUTHOR]