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.

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