Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity.

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/m2) 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.

Effect of Liraglutide in Different Abdominal Fat Layers Measured by Ultrasound: The Importance of Perirenal Fat Reduction.

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 < 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.

Ultrasound measures of abdominal fat layers correlate with metabolic syndrome features in patients with obesity.

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.

Effect of cross-sex hormone treatment on cardiovascular risk factors in transsexual individuals. Experience in a specialized unit in Catalonia.

BACKGROUND AND AIMS: Since the onset of cross hormone therapy (CHT) in transsexual individuals, there has been concern about possible chronic side effects. Our objective was to assess baseline differences in lipid profile in individuals with gender identity disorder in relation to prior CHT, and changes in the lipid profile and other cardiovascular (CV) risk factors after 24 months of treatment. METHODS: Retrospective longitudinal study including all individuals assisted for the first time in the Gender Identity Unit of Catalonia from 2006 to 2010. Socio-demographical, anthropometric and laboratory data were collected. RESULTS: We evaluated 247 transsexuals, 150 male to female (MtF: 60.7%) and 97 female to male (FtM; 39.3%). At baseline, FtM transsexuals were younger and had started prior CHT less often than MtF (13.4% vs. 64.7%; p<0.001). During follow up, in MtF weight and BMI increased significantly, as well as systolic and diastolic blood pressure, though these latter remained within normal range. No significant differences in lipid profile were observed. FtM transsexuals also presented an increase in weight and BMI, without differences in blood pressure. A general worsening in lipid profile was observed in this group, with increased total cholesterol (166.0 ± 35.1 vs. 175.6 ± 38.2mg/dL; p=0.001), triglycerides (70.6 ± 30.7 vs. 102.3 ± 68.5 mg/dL; p<0.001) and LDL cholesterol (103.8 ± 28.7 vs. 112.8 ± 30.3 mg/dL; p=.013) and decreased HDL cholesterol (52.2 ± 12.2 vs. 45.4 ± 13.8 mg/dL; p=0.001), even though final levels were all within normal range. CONCLUSION: There is no detectable increase in CV risk factors in MtF transsexuals who were treated with currently prescribed estrogenic compounds, while a slight worsening in lipid profile takes place in the FtM group, though within normal limits.

Postpartum metabolic control in a cohort of women with type 1 diabetes.

BACKGROUND AND OBJECTIVE: Pregnancy in women with type 1 diabetes (T1D) involves greater risks as compared to non-diabetic women, but less information is available about blood glucose and weight control after delivery. Our aim was to evaluate the postpartum metabolic profile (blood glucose and weight control) of women with T1D and the factors related to those metabolic outcomes. METHODS: A retrospective, observational study of 36 women with T1D during pregnancy and for up to one year after delivery. RESULTS: Fifty percent of patients attended a preconceptional planning program (PPP), and 44.4% of women were treated with continuous subcutaneous insulin infusion. Mean preconceptional HbA1c and body mass index (BMI) were 7.2±1.2% and 23.8±5.0 respectively. In the total cohort, blood glucose control significantly worsened one year after delivery (HbA1c: 7.2±1.2 vs 7.6±1.2%, P<0.001). Lower preconceptional HbA1c values were found in patients who attended PPP (6.6±0.5 vs. 7.8±1.4%; P=0.02), and were maintained for one year after delivery. No differences were found in body mass index (BMI) from the pregestational period to one year after delivery in any of two groups (No PPP 22.5±4.6 vs 23.2±4.8, P=0.078; PPP 25.4±3.4 vs 25.5±3.4 kg/m(2), P=0.947). Preconceptional HbA1c was shown to be the most important determinant of metabolic control (ß=0.962, p<0.001) and weight one year after delivery (ß=0.524, p=0.025) and weight gain during pregnancy (ß=0.633, p=0.004). CONCLUSIONS: Pregnant women with T1D return to prepregnancy body weight one year after delivery, especially those with lower HbA1c levels and BMI before pregnancy. However, blood glucose control deteriorates after delivery, suggesting the need for changes in clinical practice after delivery.

Gastrointestinal hormones and weight loss response after Roux-en-Y gastric bypass.

BACKGROUND: Mechanisms underlying variable weight loss (WL) response after Roux-en-Y gastric bypass (RYGB) are poorly understood. The objective of this study was to compare gastrointestinal hormonal responses to meal intake, and fasting plasma concentrations of surrogate markers of enterocyte mass and bile acid effect between patients with failed (F-WL) or successful WL (S-WL) after RYGB. METHODS: Cross-sectional study including 30 nondiabetic patients, evaluated at≥24 months after RYGB. Cases (F-WL; n = 10) and controls (S-WL; n = 20) were selected based on percent of excess WL (%EWL)<50% or≥50% from 12 months onwards after surgery. Groups were matched for gender, age, presurgical BMI, and length of follow up. Glucagon-like peptide 1 (GLP-1), peptide YY (PYY), GLP-2, and ghrelin responses to a meal challenge, and fasting plasma concentrations of citrulline and serum fibroblast growth factor 19 (FGF-19) were compared. RESULTS: F-WL patients presented lesser suppression of ghrelin (incremental area under the curve [iAUC]: F-WL -12490±6530 versus S-WL -31196±4536 pg×mL(-1)×min; P<.01), and lesser increase in the GLP-1 (iAUC: F-WL 3354±737 versus S-WL 5629±542 pmol×L(-1)×min; P = .02) but not in the PYY and GLP-2, response to meal intake. Citrulline concentrations were significantly correlated with time after surgery (rho = .537; P<.01). However, citrulline was higher in S-WL compared to F-WL patients (P<.05). Serum FGF-19 concentration was similar between groups. CONCLUSION: Although limited by the cross-sectional design, our data suggest a role of some gastrointestinal hormones as mediators of successful weight loss but argues against larger enterocyte mass after BS as determinant of failed weight loss after RYGB.

Transitory beneficial effects of professional continuous glucose monitoring on the metabolic control of patients with type 1 diabetes.

BACKGROUND: The benefit of professional continuous glucose monitoring (PCGM) in the metabolic control of patients with type 1 diabetes mellitus (T1DM) is uncertain. SUBJECTS AND METHODS: This was a retrospective study of all consecutive T1DM patients who underwent a 6-day PCGM in our Diabetes Unit over the course of 17 months. According to the indication, two groups were arbitrarily defined: "hyperglycemic" and "hypoglycemic." Data from medical files and sensor reports were reviewed. Glycated hemoglobin (HbA1c) was evaluated 2-4 weeks prior to PCGM, as well as 3-5 and 12 months after PCGM. In the hypoglycemic group, the number of self-reported mild hypoglycemic episodes (as defined by the American Diabetes Association) was collected. RESULTS: Of the 67 patients reviewed, 43 were in the hyperglycemic group, and 24 were in the hypoglycemic group. In the hyperglycemic group, the HbA1c level dropped at 3-5 months post-intervention from 8.45 ± 0.72% to 8.04 ± 0.9%, with the decline being statistically significant (-0.4%; P = 0.001) and positively correlated with the initial HbA1c value (0.366; P=0.016). One year after the PCGM study, the HbA1c level tended to return to the initial values: 8.20 ± 1.05% (-0.24%; P = 0.081). In the hypoglycemic group, HbA1c did not change either 3-5 or 12 months after PCGM, although the percentage of patients in whom the number of mild hypoglycemic episodes was significantly reduced was 86% (P=0.001). CONCLUSIONS: Although a transient phenomenon, PCGM can be useful in the short term in improving metabolic and clinical profile of suboptimally controlled T1DM subjects, including those with repeated hypoglycemia.

Assessment of use of specific features of subcutaneous insulin infusion systems and their relationship to metabolic control in patients with type 1 diabetes.

BACKGROUND AND OBJECTIVE: Patients with type 1 diabetes (T1DM) treated with continuous subcutaneous insulin infusion (CSII) have available several specific features of these devices. The aim of this study was to evaluate the relationship between real use of them and the degree of glycemic control in patients using this therapy. PATIENTS AND METHODS: Forty-four T1DM patients on CSII therapy with or without real-time continuous glucose monitoring (CGM) were included. Data from 14 consecutive days were retrospectively collected using the therapy management software CareLink Personal/Pro(®) and HbA1c measurement performed at that period. The relationship between the frequency of usie of specific features of insulin pumps (non-sensor augmented or sensor-augmented) and glycemic control was analyzed. RESULTS: Mean HbA1c in the group was 7.5 ± .8%. Mean daily number of boluses administered was 5.1 ± 1.8, with 75.4% of them being bolus wizards (BW). Daily number of boluses was significantly greater in patients with HbA1c <7.5% than in those with HbA1c>7.5% (5.3 ± 1.6 vs. 4.3 ± 1.6, P=.056). There was a trend to greater use of BW in patients with better control (82.8 ± 21.4% vs. 69.9 ± 29.1%, P=.106). HbA1c was lower in patients using CGM (n=8) as compared to those not using sensor-augmented pumps (7.6 ± .8 vs 7.1 ± .7, P=.067), but the difference was not statistically significant. CONCLUSIONS: More frequent use of BW appears to be associated to better metabolic control in patients with T1DM using pump therapy. In standard clinical practice, augmentation of insulin pump with CGM may be associated to improved glycemic control.