Aim: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been demonstrated to improve glycemic control and reduce body weight and fat mass in type 2 diabetes mellitus (T2DM). Here, our aim was to investigate the effects of SGLT2i dapagliflozin-treatment on body muscle mass and muscle fat content in patients with T2DM.Methods: We prospectively recruited uncontrolled (hemoglobin A1c [HbA1c] > 7%) Japanese T2DM patients who had a body mass index (BMI) < 35 kg/m2. Patients were treated with dapagliflozin (5 mg/day) or non-SGLT2i medicines for six months to improve HbA1c. We investigated changes in body composition using bioelectrical impedance analysis and changes in psoas muscle mass using abdominal computed tomography (CT).Results: Subjects were 50 T2DM patients (72% male) with a mean age of 56.1 years, mean BMI of 27.1 kg/m2 and mean HbA1c of 7.9%. HbA1c, body weight, and BMI were significantly decreased in both treatment groups, and the HbA1c decrease was not significantly different between groups. Dapagliflozin treatment significantly decreased body weight and total fat mass without affecting skeletal muscle mass. The absolute change in soft lean mass and skeletal muscle mass was not significantly different between groups. Dapagliflozin treatment did not significantly decrease psoas muscle index, and the absolute change in this index was not significantly different between groups. Dapagliflozin therapy also produced a significant increase in CT radiation attenuation in the third lumbar paraspinal muscles compared with non-SGLT2i therapy.Conclusions: Treatment with dapagliflozin for six months significantly improved glycemic control and reduced body weight without reducing muscle mass in T2DM patients.

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Objective Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular events and decrease the body fat mass in patients with type 2 diabetes mellitus (T2DM). We examined whether or not the SGLT2-inhibitor dapagliflozin can improve the endothelial function associated with a reduction in abdominal fat mass. Methods We prospectively recruited patients with uncontrolled [hemoglobin A1c (HbA1c) >7.0%] T2DM who were not being treated by SGLT2 inhibitors. Patients were treated with add-on dapagliflozin (5 mg/day) or non-SGLT2 inhibitor medicines for 6 months to improve their HbA1c. We measured the peripheral microvascular endothelial function as assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and calculated the natural logarithmic transformed value of the RH-PAT index (LnRHI). We then investigated changes in the LnRHI and abdominal fat area using computed tomography (CT). Results The subjects were 54 patients with uncontrolled T2DM (72.2% men) with a mean HbA1c of 8.1%. The HbA1c was significantly decreased in both groups, with no significant difference between the groups. Dapagliflozin treatment, but not non-SGLT2 inhibitor treatment, significantly increased the LnRHI. The changes in the LnRHI were significantly greater in the dapagliflozin group than in the non-SGLT2 inhibitor group. Dapagliflozin treatment, but not non-SGLT2 inhibitor treatment, significantly decreased the abdominal visceral fat area, subcutaneous fat area (SFA), and total fat area (TFA) as assessed by CT and significantly increased the plasma adiponectin levels. The percentage changes in the LnRHI were significantly correlated with changes in the SFA, TFA, systolic blood pressure, and adiponectin. Conclusion Add-on treatment with dapagliflozin significantly improves the glycemic control and endothelial function associated with a reduction in the abdominal fat mass in patients with uncontrolled T2DM.

Aims. Glucagon-like peptide-1 (GLP-1) analog promotes insulin secretion by acting on pancreatic β-cells. This antihyperglycemic treatment for type 2 diabetes mellitus (DM) has attracted increased clinical attention not only for its antihyperglycemic action but also for its potential extrapancreatic effects. We investigated whether liraglutide, a GLP-1 analog, could enhance insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp in type 2 DM patients. Materials. We prospectively enrolled 31 uncontrolled type 2 DM patients who were hospitalized and equally managed by guided diet- and exercise-therapies and then introduced to either liraglutide- or intensive insulin-therapy for 4 weeks. Insulin sensitivity was assessed by the glucose infusion rate (GIR) using hyperinsulinemic-euglycemic clamp before and after the therapies. Results. Values of HbA1c, postprandial plasma glucose, and body mass index (BMI) were significantly decreased by hospitalized intensive insulin-therapy or liraglutide-therapy. GIR was significantly increased by liraglutide-therapy but not by insulin-therapy, indicating that liraglutide-therapy significantly enhanced insulin sensitivity. BMI decreased during liraglutide-therapy but was not significantly correlated with changes in GIR. Multivariate logistic regression analysis demonstrated that liraglutide-therapy significantly correlated with increased insulin sensitivity in uncontrolled DM patients. Conclusions. Liraglutide may exhibit favorable effects on diabetes control for type 2 DM patients by increasing insulin sensitivity as an extrapancreatic action. Clinical trial registration Unique Identifier is UMIN000015201.

BackgroundLarge randomized clinical trials of patients with type 2 diabetes mellitus (T2DM) and at high risk for cardiovascular disease revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduced renal events. However, the trials included small numbers of patients with moderate-to-severe chronic kidney disease (CKD). Therefore, the renoprotective effects of SGLT2 inhibitors remain unknown in T2DM patients complicated with impaired renal function. We examined if SGLT2 inhibitors conferred beneficial effects on kidney function in T2DM patients with CKD.MethodsWe retrospectively recruited T2DM patients who were newly treated with add-on of SGLT2 inhibitors and suffered from moderate-to-severe renal impairment with CKD stages 3b-4 (15 < estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2), at initiation of SGLT2 inhibitor therapy. We analyzed T2DM patients with moderate-to-severe renal impairment who continued to use SGLT2 inhibitors for at least 1 year. We investigated the effects of SGLT2 inhibitor therapy on 1-year changes in eGFR and urinary protein excretion before and after the treatment.ResultsWe analyzed 42 T2DM patients with median eGFR of 40.4 mL/min/1.73 m2. One-year SGLT2 inhibitor therapy lowered median hemoglobin A1c (HbA1c) levels from 7.6% to 7.5% (not significant). Body weight and blood pressure were significantly decreased, and hemoglobin was significantly increased. The median value of eGFR after 1 year of SGLT2 inhibitor therapy was 41.0 mL/min/1.73 m2, with no significant difference compared with baseline. The annual decline in eGFR improved significantly after SGLT2 inhibitor therapy (eGFR: (median), pre: -3.8, vs. post: 0.1 mL/min/1.73 m2 per year, P < 0.01). We also found a significant decrease in urinary protein excretion after SGLT2 inhibitor therapy (urinary protein-to-creatinine ratio: (median), pre: 0.36, vs. post: 0.23 g/g creatinine, n = 35, P < 0.01).ConclusionsThis study revealed the promising observations that add-on treatment with SGLT2 inhibitors exerted significant renoprotective effects, culminating in improvements in annual decline in eGFR and urinary protein excretion in T2DM patients with CKD stages 3b-4, but did not significantly reduce HbA1c. Further prospective clinical trials are warranted to fully elucidate the effects of SGLT2 inhibitors on glycemic control and renal function in T2DM patients with moderate-to-severe renal impairment.

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BackgroundSmoking cessation in newly diagnosed type 2 diabetes patients is reported to be associated with amelioration of metabolic parameters and blood pressure (BP), and the reduction of microalbuminuria. The aim of this study is to demonstrate changes in BP, pulse rate (PR), and microalbuminuria in already diagnosed diabetes patients who quit smoking.MethodsWe retrospectively evaluated diabetes outpatients who were habitual smokers, and who visited to our smoking cessation clinic. Patients were divided into two groups based on their smoking status at the termination of a 3-month smoking cessation program (smoking cessation group and smoking group), and analyzed systolic and diastolic BPs, PR, HbA1c, and body weight at the start date, and at 1, 3, 6, and 12 months thereafter. The urinary albumin-to-creatinine ratio was also measured at the start date and at 12 months.ResultsThirty-five patients met our criteria. Mean diabetes duration was 12 years. Eighteen patients (52%) quit smoking. Success or failure of smoking cessation depended on nicotine dependence rather than good or bad glycemic control. Both BP and PR decreased significantly after 1 month or later in the smoking cessation group without worsening HbA1c, while both parameters did not show any changes in the smoking group. Microalbuminuria was also ameliorated significantly at 12 months compared with that at the start date in the smoking cessation group (95.8 ± 92.9 mg/gCr vs. 75.5 ± 96.3 mg/gCr, P = 0.0059), while it did not show a significant change in the smoking group. (61.9 ± 43.5 mg/gCr vs. 97.7 ± 90.4 mg/gCr, P = 0.1039).ConclusionsSmoking cessation might cause a reduction in chronic kidney disease progression through ameliorating microalbuminuria without metabolic adverse effects in patients already diagnosed with diabetes mellitus.

Background and objectiveObesity is globally recognized as an important clinical problem and sodium-glucose co-transporter 2 (SGLT2) inhibitors are considered a suitable therapy for obese patients with type 2 diabetes mellitus (T2DM). We examined the clinical factors associated with initial decrease in body-fat percentage (Fat %) induced by SGLT2 inhibitors in patients with T2DM.MethodsWe retrospectively enrolled patients newly treated with SGLT2 inhibitors in addition to ongoing medications at Jinnouchi Hospital between April 2014 and December 2015. We examined the SGLT2 inhibitor-induced change in body composition by using a bioelectrical impedance analyzer (InBody770®) before SGLT2 inhibitor administration and after 4 weeks’ treatment.ResultsA total of 175 patients with T2DM were enrolled and we analyzed 148 patients. Add-on SGLT2 inhibitor treatment significantly reduced body weight (− 1.04 ± 1.18 kg, p < 0.01), total fat quantity (− 0.62 ± 1.19 kg, p < 0.01), and Fat % (− 0.4 ± 1.4%, p < 0.01). Pretreatment levels of glycated hemoglobin (HbA1c) [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.15–2.25, p < 0.01] and smoking (OR, 2.65; 95% CI, 1.14–6.15, p = 0.02) were significantly associated factors for greater fat-reduction defined as more than 0.4% (median) decrease in Fat % in multivariate logistic regression analysis. In receiver operator characteristic analysis, the cut-off value of pretreatment levels of HbA1c for a greater Fat % decrease was 7.7% (sensitivity 53% and specificity 69%, p < 0.01).ConclusionAdditional treatment with SGLT2 inhibitors effectively decreased Fat % in T2DM patients with high HbA1c levels before SGLT2 inhibitor administration. Our results suggest a greater initial response in Fat % reduction to SGLT2 inhibitor therapy in diabetic patients with pretreatment HbA1c levels ≥ 7.7%.