RESUMEN
OBJECTIVE: To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS: EMPA treatment resulted in a placebo-corrected absolute change of -1.8% (95% CI -3.4, -0.2; P = 0.02) and relative change in LFC of -22% (-36, -7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS: EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Adiposidad/efectos de los fármacos , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hígado/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Método Doble Ciego , Regulación hacia Abajo/efectos de los fármacos , Femenino , Alemania , Humanos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Placebos , Pérdida de Peso/efectos de los fármacosRESUMEN
OBJECTIVE: To test whether cognitive function is impaired in early states of diabetes and to identify possible risk factors for cognitive impairment. METHODS: A cross-sectional analysis within the German Diabetes Study included patients with type 1 or type 2 diabetes within the first year after diagnosis or five years after study inclusion and metabolically healthy individuals. Participants underwent comprehensive metabolic phenotyping and testing of different domains of cognitive function. Linear regression models were used to compare cognition test outcomes and to test associations between cognitive function and possible influencing factors within the groups. RESULTS: In participants with recently diagnosed diabetes, verbal memory was poorer in patients with type 2 diabetes (P = 0.029), but not in type 1 diabetes (P = 0.156), when compared to healthy individuals. Five years after diagnosis, type 2 diabetes patients also showed lower verbal memory than those with type 1 diabetes (P = 0.012). In addition to crystallized intelligence, a higher body mass index among individuals with recently diagnosed type 2 diabetes and male sex among individuals with recently diagnosed type 1 diabetes were associated with impaired verbal memory (all P < 0.05). CONCLUSION: Verbal memory is impaired in individuals with recently diagnosed type 2 diabetes and likely associated with higher body mass. This trial is registered with the trial registration number NCT01055093.