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Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary volumetric reduction, but its maintenance could be due to loss of visceral fat mass. Structured ultrasound (US) imaging of abdominal adipose tissue ("eco-obesity") is a recently described methodology used to measure 5 consecutive layers of abdominal fat, not assessable by DEXA or CT scan: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om) and right perirenal (RK). PP, Om and RK are predictors of metabolic syndrome (MS) with defined cut-off points. To assess the effect of SLGT2i on every fat depot we enrolled 29 patients with type 2 Diabetes (HbA1c 6.5-9%) and Obesity (IMC > 30 kg/m 2 ) in an open-label, randomized, phase IV trial (EudraCT: 2019-000979-16): the Omendapa trial. Diabetes was diagnosed < 12 months before randomization and all patients were treatment naïve. 14 patients were treated with metformin alone (cohort A) and 15 were treated with metformin + dapaglifozin (cohort B). Anthropometric measures and laboratory tests for glucose, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP and microalbuminuria (MAL) were done at baseline, 3rd and 6th months. At 6th month, weight loss was -5.5 ± 5.2 kg (5.7% from initial weight) in cohort A and -8.4 ± 4.4 kg (8.6%) in cohort B. Abdominal circumference showed a -2.7 ± 3.1 cm and -5.4 ± 2.5 cm reduction, respectively (p = 0.011). Both Metformin alone (-19.4 ± 20.1 mm; -21.7%) or combined with Dapaglifozin (-20.5 ± 19.4 mm; -21.8%) induced significant Om fat reduction. 13.3% of cohort A patients and 21.4% of cohort's B reached Om thickness below the cut-off for MS criteria. RK fat loss was significantly greater in cohort B group compared to cohort A, at both kidneys. Only in the Met + Dapa group, we observed correlations between Om fat with leptin/CRP/MAL and RK fat with HOMA-IR. US is a useful clinical tool to assess ectopic fat depots. Both Metformin and Dapaglifozin induce fat loss in layers involved with MS but combined treatment is particularly effective in perirenal fat layer reduction. Perirenal fat should be considered as a potential target for cardiovascular dapaglifozin beneficial effects., (© 2024. The Author(s).)

Introduction: Ultrasonography (US) in patients with obesity allows us to measure different layers of abdominal fat (superficial subcutaneous, deep subcutaneous, preperitoneal, omental, and perirenal), not assessable by DEXA or CT scan. Omental and perirenal fat depots are considered predictors of metabolic complications. Liraglutide is particularly effective in reducing weight in patients with insulin-resistance, but its direct impact on each abdominal fat layer is unknown., Methods: We measured, at the L4 level, all 5 abdominal fat depots in 860 patients with obesity (72.8% women, mean age 56.6 ± 1.5 years, BMI 34.4 ± 4.7 kg/m2, body fat 47 ± 2%, abdominal circumference 105.8 ± 3 cm), before and after 6 months of liraglutide treatment. Laboratory tests for glucose, insulin, and lipid profile were routinely done. T-student was used to compare intraindividual differences., Results: Weight loss was 7.5 ± 2.8 kg (7.96% from baseline), with no differences by sex/age/BMI. Greater loss was observed in patients with higher dosages and NAFLD. All US-measured fat layers showed a significant reduction (p &lt; 0.05) at 6th months. Preperitoneal fat showed a -26 ± 5.5% reduction and 46% of the patients went below metabolic syndrome (MS) risk cut-off values. Omental fat was reduced by -17.8 ± 5% (67% of the patients below MS risk) and perirenal fat by -22.4 ± 4.4% (56% of the patients below MS). Both omental and perirenal fat reduction correlated with total and LDL cholesterol. Higher perirenal fat reduction (-28%) was seen among patients with obesity and hypertension. Perirenal fat also correlated with blood pressure reduction., Conclusion: Liraglutide induces greater fat loss in the layers involved with MS. However, the maximal reduction is seen at perirenal fat, which has been recently related with hypertension and could play an important role in modulating kidney's expansion and intraglomerular pressure. US is a reproducible clinical tool to assess pathologic fat depots in patients living with obesity., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: Abdominal fat ultrasound (US) is a simple clinical tool that may allow measures of fat depots not visible using common dual-energy X-ray absorptiometry (DEXA) or computerized tomography (CT) imaging. The aim of this study was to validate the technique, give measures of superficial and profound subcutaneous , preperitoneal , omental and perirenal (retroperitoneal) fat and correlate them with MS markers., Methods: Sequential US measures of these five abdominal fat layers were done at 397 adults. Blood pressure (BP), body mass index (BMI), waist, body fat %, HOMA-IR index (homeostatic model assessment of insulin resistance), lipid profile and leptin were recorded. Metabolic syndrome (MS) was defined according to Cholesterol education programme adult treatment panel III (ATPIII) criteria., Results: Subcutaneous and omental fat were increased among people with obesity, whereas preperitoneal and perirenal fat did not show any difference according to BMI or waist. Women showed thicker subcutaneous fat (both superficial and profound), whereas men had bigger omental fat. Both postmenopausal and diabetic patients had changes in omental fat only, whereas patients with fatty liver showed thicker preperitoneal and perirenal fat, as well. MS patients showed both thicker perirenal and omental fat. A cut-off of 54 mm in male (M)/34 mm in female (F) of omental fat and 22.5 mm (M)/12.5 mm (F) of perirenal fat could be predictive of later MS onset., Conclusions: US is a valid method to measure all different abdominal fat depots. Omental and perirenal fat measures may classify patients at risk for MS. Preperitoneal fat depot may also correlate with fatty liver disease., Competing Interests: All the authors have declared no having any conflict of interest and send the form to the corresponding author., (© 2020 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Objective Growth hormone (GH) was shown to stimulate proliferation, migration and survival of neural cells in animal models. GH deficiency (GHD) was reported following traumatic brain lesions; however, there are not available data in spinal cord injury (SCI) patients. The aim of the study was to evaluate (1) the frequency of GHD in chronic SCI population; (2) the efficacy/safety of GH replacement in patients with SCI and suboptimal GH secretion. Design and methods Nineteen consecutive patients with chronic thoracic complete SCI (AIS-A) were studied. Patients with low GH secretion were randomized in a double-blind, placebo-controlled study to receive either subcutaneous placebo injections or GH combined with physical therapy, for 6 months. Baseline cranial MRI, AIS motor and sensory scale, quality of life (spinal cord impact measurement) and modified Ashworth spasticity scale, quantitative sensory testing and neurophysiological exploration were assessed at baseline, 1, 3 and 6 months following treatment. Results Thirteen had GH deficiency. Seven received GH, five placebo and one dropped out. Both groups were similar according to clinical and demographical data at baseline, except for greater GH deficiency in the GH treatment group. At 6th month, patients treated with GH showed a significant improvement in SCIM-III score and in electrical perception threshold up to the 5th level below SCI, on both sides compared to baseline. Conclusions GHD seems to be frequent in traumatic SCI and GH replacement is safe without side effects. GH combined with physical therapy can improve quality of life of SCI patients and, strikingly, the sensory perception below lesion level.

Background: The validity of anthropometric indexes in ascertaining the body composition (BC) in morbidly obese (MO) subjects has been questioned. Our objective was to evaluate, in MO subjects, whether bioelectrical impedance analysis (BIA) of BC is more closely associated with the metabolic syndrome (MS) and insulin resistance (IR) than are classic anthropometric measurements. The setting was a university hospital., Methods: The association between anthropometric (body mass index, waist circumference [WC]) and BIA (total fat mass [FM] [percentage of FM], truncal FM, android FM) estimates of BC, MS, and IR was evaluated in 784 white MO subjects (212 men and 572 women). BIA estimates were calculated using equations specific for MO subjects developed by our own group and validated against dual energy x-ray absorptiometry., Results: The prevalence of the MS and IR was 78.6% and 88.6%, respectively. The body mass index was greater in women with the MS (P <.001) or IR (P <.001), and the WC was larger in subjects of both genders with the MS or IR (P <.001). Moreover, the WC correlated significantly with all the MS components (P <.05). In contrast, the percentage of FM, truncal FM, and android FM were significantly associated with the MS only in women. Stepwise logistic regression analysis demonstrated the WC as the only significant predictor of the MS or IR (both P <.001). Furthermore, receiver operating curve analysis showed WC was the most accurate BC parameter for the identification of subjects with the MS (area under the curve, WC = .681, P <.001) or IR (area under the curve, WC = .753, P <.001)., Conclusion: In MO subjects, the BIA-derived indexes of total and central adiposity were not better predictors of the MS or IR than were traditional anthropometric measurements., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: Validated equations for body composition analysis using bioelectrical impedance (BIA) in morbidly obese (MO) subjects are scarce. Thus, our aim was todevelop new equations from physical and BIA parameters to estimate whole-body and segmental body composition inMO subjects, with dual-energy X-ray absorptiometry(DXA) as the reference method., Methods: A cross-sectional study on 159 Caucasian MO subjects (female 78%, age 43.5 ± 11.8 years, BMI 45.6 ± 4.9 kg/m2) divided in two groups was conducted: model building cohort (n = 110) and model validation cohort (n 0 49). Stepwise regression analysis was used to develop specific fat free mass (FFM) and fat mass (FM) equations., Results: Gender, body weight, and height2/impedance accounted, respectively, for 89.4% (p < 0.001) and 89.3% (p < 0.001) of the variability of DXA-total FFM in the two cohorts. Using the new equation, the mean difference between the DXA-FFM and BIA-FFM estimates was +0.180 kg (95% CI: -0.34 to +0.7 kg, p 0 NS), and the resulting limits of agreement were +6.76 and −6.40 kg. Similarly, good estimates of DXA truncal-, android-, and gynoid-FM from anthropometric and BIA parameters could be obtained from weight, height2/impedance, and waist and hip circumferences (respectively, R2 adjusted: 0.657, 0.776, and 0.770; p < 0.001)., Conclusions: The new equations derived from physical and BIA parameters provide accurate estimates of body composition in MO subjects.

Aim: Considering the poor long-term success of current dietary and pharmacological interventions, we aimed to evaluate the potential effect of sodium tungstate in the treatment of grade I and II obesity (ClinicalTrials.gov identifier: NCT00555074)., Methods: Prospective, randomized, placebo-controlled, double-blind, proof-of-concept study was carried out. Following a 2-week lead-in period, 30 obese (body mass index, BMI 30.0-39.9 kg/m(2)), non-diabetic subjects were randomized to receive either sodium tungstate (100 mg bid) or placebo for 6 weeks. The primary study endpoint was the absolute change in body weight relative to the time of randomization., Results: Treatment with sodium tungstate [-0.135 ± 0.268 kg (95% CI -0.686 to +0.416 kg)] was not associated with a significant weight loss compared to placebo [-0.063 ± 0.277 kg (95% CI -0.632 to +0.507 kg)] (p = 0.854). Likewise, treatment with sodium tungstate was not associated with significant changes in fat mass (DEXA), resting energy expenditure (indirect calorimetry) or caloric consumption (3-day food records)., Conclusion: Our data do not support sodium tungstate as a pharmacological agent in the treatment of human obesity., (© 2010 Blackwell Publishing Ltd.)

Twenty patients were randomized to receive either 2.5 mg isradipine twice daily or 20 mg nifedipine retard once daily for 6 months. After 2 weeks of placebo wash-out, evaluations were carried out every 4 weeks. These evaluations included assessment of blood pressure, lipid profile, hemoglobin A1 sigma glucagon, C peptide, and insulin requirements. Both isradipine and nifedipine retard lowered systolic and diastolic blood pressures to normal values (P < .001). However, isradipine was accompanied by a decrease in heart rate (P < .005). Neither drug modified hemoglobin A1c or the glycemic profile. The endogenous insulin-secretion response decreased in both treatment groups (P < .05). In conclusion, isradipine and nifedipine retard are efficacious in the treatment of hypertension in patients with type II diabetes mellitus, and neither treatment produces modification of metabolic control.

Guanfacine, a central alpha-adrenoreceptor agonist, may increase growth hormone (GH) secretion. We have investigated the effect of guanfacine upon plasma GH levels in 16 hypertensive non-insulin-dependent diabetic (NIDD) patients. Guanfacine (1 to 2 mg/day/os) was administered for six months, and GH measured in basal plasma samples before and after treatment with this drug. Our results show an increase in GH plasma levels after guanfacine administration (2.88 +/- 2.05 ng/ml (X +/-SD) before, and 4.37 +/- 1.80 ng/ml (X +/- SD) after treatment). Since it is believed that GH levels plays a role in the course of diabetic retinopathy, caution should be taken with guanfacine antihypertensive treatment in patients affected with diabetes mellitus.

We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity.

Although restoration of normoglycemia in non-insulin-dependent diabetic subjects improves insulin release evoked by several secretagogues, conflicting data were reported concerning the effect of intensive insulin therapy on the first-phase response of the B-cell to an intravenous glucose challenge. In the present study, 14 non-insulin-dependent diabetics underwent an intravenous glucose test performed before and after 20 h of glycemic normalization. Before insulin treatment, glucose failed, as a rule, to provoke an early positive secretory response. On the contrary, a paradoxical inhibition of insulin release was observed in most patients. This phenomenon was reproducible when a second test was performed 120 min after the first one. The paradoxical inhibition was not observed any more after glycemic normalization. As judged from the paired difference (delta) between the early increment in insulin release before and after insulin treatment, normoglycemia resulted in an improved secretory response (delta greater than 5.0 microU/ml) in seven patients, whilst the first-phase response remained little affected (delta less than 3.0 microU/ml) in the other seven subjects. These findings suggest that an impaired first-phase response to glucose does not always represent an irreversible primary defect of the pancreatic B-cell in diabetic subjects.

Ophthalmic evolution was studied for 2 years in 17 patients with insulin-dependent diabetes mellitus and background diabetic retinopathy. Nine patients were treated with triflusal, a new platelet antiaggregant drug, and the eight remaining patients, with similar clinical and biological characteristics, were considered the control group. At the end of the study the ophthalmic evolution was different in the two groups. In the control group the degree of fluorescein leakage and the number of microaneurysms increased, while in the triflusal-treated group both parameters were reduced. There were no differences in visual acuity and computerised perimetry between the groups. Our results suggest that platelet antiaggregant therapy can be useful in the treatment of background diabetic retinopathy.

Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity.

The acute effect of glibenclamide, a hypoglycemic sulfonylurea, upon transglutaminase activity was investigated in 6 type II diabetic patients by perfusing 1 mg glibenclamide during 1 h. Blood samples were drawn 0, 10, 20, 30, 60 min during and 30 and 60 min after perfusion to determine insulin, glucose and transglutaminase activity. No significant modifications in plasma insulin, plasma glucose and transglutaminase activity in red cells was induced by glibenclamide perfusion. Nevertheless, glibenclamide induced a significant decrease (p less than 0.005) in transglutaminase activity after 20 min of perfusion (629.83 +/- 53.08 and 521.18 +/- 43.92, mean +/- SE, at 0 and 20 min). No correlation was observed between glucose or insulin plasma levels and transglutaminase activity.