Reduced Number of Remaining or Healthy Teeth in Patients with Type 2 Diabetes Mellitus: A Cross-sectional Study Assessed by Dentists or Dental Hygienists in Japan.

Objective This study assessed the relationships between oral health (number of remaining and healthy teeth and periodontal disease) and type 2 diabetes mellitus (T2DM) to contribute to improved patient care. Patients We conducted a cross-sectional cohort study of consecutive patients being regularly treated for chronic diseases (T2DM, hypertension, and dyslipidemia). A dentist or dental hygienist accurately evaluated the oral environment. Patients with fewer than 20 teeth were classified as having reduced remaining teeth (RRT). Results A total of 267 patients were enrolled, including 153 patients (57%) with T2DM and 114 without (43%). Patients with T2DM had 3 fewer remaining teeth on average than those without DM [median: 22 (interquartile range (IQR): 11-27) vs. median: 25 (IQR: 17.3-28), p=0.02]. In addition, patients with T2DM had 4 fewer healthy teeth on average than those without DM [median: 8 (IQR: 2.8-15) vs. median: 12 (IQR: 6-16), p=0.02]. The frequency of RRT was higher in the T2DM group (n=63; 41%) than in the non-DM group (n=31; 27%, p=0.02). Multivariable logistic regression for the presence of RRT in the T2DM group found that age [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.03-1.13; p<0.01] and regular dental consultations (OR, 0.28; 95% CI, 0.10-0.76; p=0.01) were independently and significantly associated. Conclusion The number of remaining or healthy teeth was significantly lower in patients with T2DM than in those without T2DM in current Japanese clinical practice. Regular dental consultation is recommended to preserve remaining teeth in patients with T2DM.

Potential Identification of Type 2 Diabetes with Elevated Insulin Clearance.

BACKGROUND: Decreased blood insulin concentrations resulting from reduced pancreatic ß-cell insulin secretion and elevated insulin clearance (IC) could be involved in impaired glucose metabolism in diabetes. Recently, we reported a patient with type 2 diabetes mellitus (T2DM) who had decreased blood insulin concentrations and elevated IC. METHODS: For this study, we recruited patients with newly diagnosed, treatment-naïve T2DM and measured the metabolic clearance rate of insulin (MCRI) determined by a hyperinsulinemic-euglycemic clamp examination. We defined elevated IC as an MCRI of more than 700 ml/min/m2. Using this tentative cutoff, we identified patients with T2DM with elevated IC and investigated their clinical characteristics. RESULTS: We enrolled 101 patients in this study; 78.2% were men. Patients had a mean age of 54.1 years, a median body-mass index (BMI) of 25.1 kg/m2 (interquartile range [IQR], 22.9 to 28.4 kg/m2), a median hemoglobin A1c of 10.0% (IQR, 8.0 to 12.3%), and a median MCRI of 655 ml/min/m2 (IQR, 562 to 810 ml/min/m2). Our case definition for elevated IC was met by 44 patients whose median MCRI was 842 ml/min/m2 (IQR, 747 to 975 ml/min/m2) compared with those without elevated IC (570 ml/min/m2; IQR, 500 to 628 ml/min/m2). On the basis of this division, fasting blood glucose and insulin levels were 178 mg/dl (IQR, 140 to 218 mg/dl) and 4.2 mU/l (IQR, 2.7 to 5.5 mU/l), respectively, in patients with elevated IC compared with 146 mg/dl (IQR, 128 to 188 mg/dl) and 9.6 mU/l (IQR, 6.6 to 14.9 mU/l), respectively, in patients without elevated IC. The BMI of patients with elevated IC was 22.9 kg/m2 (IQR, 20.7 to 24.2 kg/m2) compared with 27.3 kg/m2 (IQR, 25.2 to 29.4 kg/m2) in patients who did not have elevated IC. There were no clinically significant differences in renal or hepatic function test results. CONCLUSIONS: Our data suggest that there is a group of patients with T2DM with elevated IC, and that they are nonobese and have decreased blood insulin concentrations. If confirmed, this novel form of T2DM could affect the treatment of such patients. (UMIN Clinical Trials Registry number, UMIN000032014.)

Body Muscle-to-Fat Ratio, Rather Than Fat-to-Muscle Ratio, Significantly Correlates With Measured Insulin Resistance in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Insulin resistance (IR) assessment is important in treating type 2 diabetes mellitus (T2DM). We thus compared body muscle-to-fat ratio (BMFR) and fat-to-muscle ratio (FMR) values against M/I values as clinical index of IR. METHODS: Subject included 118 untreated T2DM patients. Hyperinsulinemic-euglycemic clamp examination was performed to calculate the M/I as index of IR. Body composition was measured by impedance analysis using InBody770. RESULTS: Simple linear regression analyses confirmed correlations between M/I and BMFR (B: 0.756 (P < 0.01), coefficients of determination (R2): 0.572, mean absolute error (MAE): 3.19, and root mean squared error (RMSE): 4.14), and between M/I and FMR (B: -0.601 (P < 0.01), R2: 0.362, MAE: 3.97, and RMSE: 5.05). Against the M/I values, BMFR also showed better goodness-of-fit than did FMR. In comparing correlation coefficients, the BMFR absolute B value was significantly larger than that of FMR (P = 0.027). CONCLUSIONS: BMFR is more useful than FMR in quantifying IR in patients with T2DM because the correlation between BMFR and the insulin sensitivity index M/I is significantly greater than that between FMR and M/I.

Initial Acute Decline in Estimated Glomerular Filtration Rate After Sodium-Glucose Cotransporter-2 Inhibitor in Patients With Chronic Kidney Disease.

BACKGROUND: Renal function deterioration accompanied by an acute decrease in estimated glomerular filtration rate (eGFR) was observed early after starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy. It is unclear how much and how frequently the initial acute decline in eGFR (IAD-eGFR) would occur after SGLT2i administration, and the effects of IAD-eGFR on subsequent renal function are unknown in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD). METHODS: We retrospectively recruited T2DM patients with CKD (stage 3b; 30 ≤ eGFR < 45 mL/min/1.73 m2) and who were newly treated with add-on SGLT2i. We further investigated the effects of SGLT2i therapy on eGFR early after starting treatment (1 - 3 months) and after 6 months of treatment. We examined the factors associated with a large IAD-eGFR (≥ 10%) using logistic regression analyses. RESULTS: Eighty-seven patients (male, 74.7%; mean age, 69.8 years; median hemoglobin A1c, 7.3%; mean eGFR, 37.8 mL/min/1.73 m2) were analyzed. The mean minimum eGFR early after SGLT2i administration was 34.9 mL/min/1.73 m2, which was significantly lower than before treatment (mean, -7.7%). Seventy patients (80.5%) had IAD-eGFR, and 36 patients (41.4%) had a large IAD-eGFR (≥ 10%). Overall, the mean eGFR was 38.2 at 6 months after starting SGLT2i administration. In patients with a large IAD-eGFR (≥ 10%), the eGFR decreased by 72.2% at 6 months to 35.5 mL/min/1.73 m2, showing a significant decline from the pretreatment value. In patients without a large IAD-eGFR, eGFR increased by 66.7% at 6 months to 40.0 mL/min/1.73 m2. Multiple logistic regression analysis showed that patients with a large IAD-eGFR had a significant association with a high estimated daily salt intake. CONCLUSIONS: SGLT2i treatment frequently induced a significant decrease in eGFR early after starting therapy, but eGFR tended to recover after 6 months in T2DM patients with CKD stage 3b. A large IAD-eGFR (≥ 10%) caused by SGLT2i may lead to subsequent deterioration in renal function, and it was significantly associated with a higher estimated daily salt intake. These results suggest that a more effective renoprotective therapeutic strategy using SGLT2i may be implemented by avoiding the occurrence of a large IAD-eGFR. Further prospective studies are warranted.

Characteristics of nephropathy in severely obese Japanese patients complicated with type 2 diabetes mellitus: a cross-sectional cohort study.

PURPOSE: We aimed to investigate the characteristics of kidney disease in severely obese Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study of severely obese patients (body mass index ≥35 kg/m2) with T2DM treated at Jinnouchi Hospital, Kumamoto, Japan. RESULTS: A total of 3128 T2DM patients visited the hospital during the survey period, of whom 55 patients (1.7%) were severely obese and 50 patients were enrolled. In terms of diabetic nephropathy (DN), twenty-five patients were stage 1 (non-DN, 50.0%), sixteen were stage 2 (32.0%), five were stage 3 (10.0%), and four were stage 4 (8.0%). There were significant differences in the presence of urinary occult blood (P = 0.01) and history of cardiovascular disease (CVD) (P = 0.04) between patients with DN (stages 2-4) and those without DN (stage 1). The presence of urinary occult blood (odds ratio [OR], 4.96; 95% confidence interval, 1.32-18.6; P = 0.02) was significantly associated with the presence of DN according to multivariate logistic regression analysis with forced inclusion of age, sex, and CVD history. CONCLUSIONS: Urinary occult blood may be a significant independent factor associated with the presence of nephropathy in severely obese Japanese patients with T2DM. The presence of urinary occult blood could thus be an important pathogenic factor in obesity-related nephropathy in patients with T2DM.

Elevation of the renal threshold for glucose is associated with insulin resistance and higher glycated hemoglobin levels.

AIMS/INTRODUCTION: The renal threshold for glucose (RTg) corresponds to a blood glucose level of ~180 mg/dL; however, in hospitals, patients are often encountered who are hyperglycemic, but urine glucose test strip-negative, who remain negative for urine glucose even at blood glucose concentrations >180 mg/dL, implying a high RTg value. In this study, we aimed to identify factors determining high RTg in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: We estimated RTg (eRTg) using urinalysis data from 67 type 2 diabetes mellitus patients for whom the glucose infusion rate (GIR) was determined by hyperinsulinemic-euglycemic clamp. After allocating patients to two groups according to their baseline eRTg (<180 mg/dL or ≥180 mg/dL), we identified the factors affecting eRTg using simple and multiple linear regression analyses. RESULTS: GIR, glycated hemoglobin (HbA1c), insulin use and dyslipidemia differed significantly between the groups. In simple regression analysis, GIR, HbA1c, body muscle-to-fat ratio and insulin use were significantly correlated with eRTg; and in multiple regression analysis, GIR and HbA1c remained independent negative and positive determinants, respectively, with the contribution of GIR being substantial. In receiver operating characteristic curve analysis, when GIR <5.7 was used as the insulin resistance threshold, the cut-off value of eRTg was 189 mg/dL (P = 0.0001). Furthermore, in receiver operating characteristic analysis using eRTg ≥189 mg/dL, the cut-off value for HbA1c was 8.0% (P = 0.0006). CONCLUSIONS: High eRTg is associated with low GIR and high HbA1c, with GIR making a substantial contribution.

Body muscle-to-fat ratio gender-specific cut-off values for impaired insulin sensitivity in patients with treatment-naïve type 2 diabetes mellitus.

PURPOSE: We previously reported that the body muscle-to-fat ratio (BMFR), measured using bioelectrical impedance, significantly correlated with whole-body insulin sensitivity. We examined BMFR gender-specific cut-off values for impaired insulin sensitivity in treatment-naïve type 2 diabetes mellitus (T2DM) patients. METHODS: Subjects included 101 untreated T2DM patients (male, 66; female, 35). We performed a hyperinsulinemic-euglycemic clamp examination to measure the steady-state glucose infusion rate (M value) as an indicator of whole-body insulin resistance. We defined the M value divided by the steady-state serum insulin value as the M/I value. We defined the existence of insulin resistance using an M/I ratio <9.0. The optimal cut-off value for BMFR was calculated by receiver operating characteristics (ROC) analysis. RESULTS: The cut-off value of the BMFR for insulin resistance was 2.75 (area under the curve [AUC] = 0.83, sensitivity 75%, and specificity 76%, P < 0.001) for males and 1.65 (AUC = 0.87, sensitivity 84%, and specificity 81%, P < 0.001) for females. Simple linear regression analysis showed that BMFR was significantly correlated with the M/I value in both genders (males, B = 0.77, P< 0.01; females, B = 0.83, P< 0.01). CONCLUSIONS: BMFR cut-off values for impaired insulin sensitivity in treatment-naïve T2DM patients were 2.75 for males and 1.65 for females.

Renoprotective Effects of Additional SGLT2 inhibitor Therapy in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3b-4: A Real World Report From A Japanese Specialized Diabetes Care Center.

BACKGROUND: Large 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: This 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.

Clinical usefulness of the body muscle-to-fat ratio for screening obstructive sleep apnea syndrome in patients with inadequately controlled type 2 diabetes mellitus.

AIMS: To investigate whether body composition measures can be used for screening obstructive sleep apnea syndrome (OSAS) in patients with type 2 diabetes mellitus (T2DM) suspected of having OSAS. METHODS: Subjects were 186 hospital inpatients with inadequately controlled T2DM. We measured the respiratory disturbance index (RDI) as an indicator of OSAS using a sheet-type breath detection monitor, defining OSAS as an RDI ≥ 19 events/hour. Elementary body composition was measured by bioelectrical impedance analysis using InBody770. RESULTS: Simple logistic regression analysis identified body weight, body mass index (BMI), waist circumference, total body fat mass, body fat percentage, and body muscle-to-fat ratio (BMFR) as significantly associated with OSAS. The Nagelkerke R2 test showed that the BMFR was the most suitable measure for screening OSAS. Multivariate logistic regression analysis demonstrated that BMFR was significantly and independently associated with OSAS. In receiver operating characteristic curve analysis, the area under the BMFR curve was 0.70 (P < 0.001), indicating that BMFR was significantly predictive of OSAS. Furthermore, BMFR was the most suitable measure for screening OSAS in a sub-group analysis of non-obese patients with relatively low BMI (<27.5 kg/m2). CONCLUSIONS: In patients with T2DM, the BMFR is useful for screening OSAS in daily clinical practice.

Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus.

AIMS: We examined dapagliflozin-induced changes in liver fat accumulation. METHODS: We prospectively recruited Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM) [hemoglobin A1c (HbA1c) >7.0%]. Dapagliflozin (5 mg/day) or non-sodium glucose cotransporter 2 inhibitors (SGLT2i) was added to the patients' treatment regimen for 6 months. Changes in liver fat accumulation were assessed by the liver-to-spleen (L/S) attenuation ratio using abdominal computed tomography (CT). RESULTS: This study enrolled 55 Japanese T2DM patients. The L/S ratio significantly increased in the dapagliflozin group compared with the non-SGLT2i group. Abdominal subcutaneous fat area (SFA), visceral fat area, total fat area assessed by abdominal CT, aspartate aminotransferase, alanine aminotransferase (ALT), and γ-glutamyl transpeptidase decreased significantly only in the dapagliflozin group. Changes in the L/S ratio showed a significant negative relationship with changes in abdominal SFA, ALT, and non-esterified fatty acid. In sub-group analyses of non-insulin users, hepatic insulin extraction was assessed by the plasma C-peptide-to-insulin ratio, which was significantly increased in the dapagliflozin group but not in the non-SGLT2i group. CONCLUSION: In patients with inadequately controlled T2DM, additional dapagliflozin-treatment significantly reduced the liver fat accumulation associated with a decrease in abdominal SFA.

Impact of Dapagliflozin Therapy on Renal Protection and Kidney Morphology in Patients With Uncontrolled Type 2 Diabetes Mellitus.

BACKGROUND: We examined whether the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin can improve urine albumin-to-creatinine ratio (UACR) associated with a reduction in body weight or body fat in patients with type 2 diabetes mellitus (T2DM). METHODS: We prospectively recruited T2DM patients having inadequate glycemic control (hemoglobin A1c (HbA1c) > 7.0%) not on SGLT2i therapy. We treated the patients with add-on dapagliflozin treatment or intensification of non-SGLT2 inhibitor therapies for 6 months. We measured UACR, urine N-acetyl-ß-glucosaminidase (uNAG), and body composition including total body fat mass (TBFM) as assessed by bioelectrical impedance analysis. We also investigated changes in length and radiation attenuation properties of the kidneys and abdominal fat area using computed tomography. RESULTS: We enrolled 62 patients with a mean HbA1c of 8.0%. The HbA1c and fasting blood glucose were significantly decreased in both the dapagliflozin-group and non-SGLT2i-group, with no significant difference between the two groups. Dapagliflozin treatment, but not non-SGLT2i treatment, significantly decreased UACR and uNAG. The changes in UACR and uNAG were significantly greater in the dapagliflozin group compared with the non-SGLT2i group. Dapagliflozin treatment, but not non-SGLT2i treatment, significantly decreased the body weight, TBFM, and abdominal fat area and significantly increased kidney length and radiation attenuation. The percentage change in UACR was significantly correlated with changes in TBFM, but not with body weight. By multivariate logistic regression analysis, dapagliflozin treatment was significantly associated with the improvement of UACR. CONCLUSIONS: Add-on treatment with dapagliflozin exhibited significant renoprotective effects, with improvement of UACR and uNAG and increased kidney length and radiation attenuation in patients with uncontrolled T2DM.

Smoking Cessation Ameliorates Microalbuminuria With Reduction of Blood Pressure and Pulse Rate in Patients With Already Diagnosed Diabetes Mellitus.

BACKGROUND: Smoking 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. METHODS: We 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. RESULTS: Thirty-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). CONCLUSIONS: Smoking cessation might cause a reduction in chronic kidney disease progression through ameliorating microalbuminuria without metabolic adverse effects in patients already diagnosed with diabetes mellitus.

The SGLT2 Inhibitor Dapagliflozin Significantly Improves the Peripheral Microvascular Endothelial Function in Patients with Uncontrolled Type 2 Diabetes Mellitus.

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.

Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus.

AIMS: Obesity and ectopic fat accumulation are important conditions of type 2 diabetes mellitus (T2DM). Our aim was to determine whether bioelectrical impedance body composition analysis combined with blood test results could estimate liver ectopic fat accumulation in patients with treatment-naïve T2DM. METHODS: Subjects were 119 untreated T2DM patients. Computed tomography scans were performed to calculate the liver to spleen attenuation ratio (L/S ratio) as a measure of liver fat accumulation, with excess liver fat accumulation defined as an L/S ratio <1.0. Elementary body composition was measured by bioelectrical impedance analysis using InBody770. RESULTS: The Nagelkerke R2 test showed that the muscle mass/fat mass ratio (muscle/fat ratio) was the most suitable variable among anthropometric factors and body component indexes for estimating liver fat accumulation. The muscle/fat ratio was significantly correlated with the L/S ratio (ρ = 0.4386, P < 0.0001). Multivariable logistic regression analysis showed that the muscle/fat ratio (odds ratio 0.40, 95% confidence interval 0.22-0.73, P < 0.01) and alanine aminotransferase (odds ratio 1.06, 95% confidence interval 1.02-1.10, P < 0.01) were independently and significantly associated with liver fat accumulation. In receiver operating characteristic curve analysis, the cutoff value of the muscle/fat ratio for excess liver fat accumulation was 2.34. CONCLUSION: In patients with treatment-naïve T2DM, the muscle/fat ratio and ALT are useful for estimating the presence of excess liver fat accumulation in daily clinical practice.

Dapagliflozin Reduces Fat Mass without Affecting Muscle Mass in Type 2 Diabetes.

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.

Clinical Factors Associated with Initial Decrease in Body-Fat Percentage Induced by Add-on Sodium-Glucose Co-transporter 2 Inhibitors in Patient with Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE: Obesity 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. METHODS: We 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. RESULTS: A 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). CONCLUSION: Additional 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%.

Correlation of body muscle/fat ratio with insulin sensitivity using hyperinsulinemic-euglycemic clamp in treatment-naïve type 2 diabetes mellitus.

AIMS: Fat deposition and obesity are crucial pathological components of diabetes mellitus (DM). In clinical practice, assessment of insulin resistance is important. We hypothesized that body muscle and fat composition might be a key factor for insulin resistance in patients with type 2 DM. METHODS: Subjects included 61 untreated DM patients. Hyperinsulinemic-euglycemic clamp examination was performed to calculate the M/I value as the insulin resistance reference indicator. Elementary body composition was measured by impedance analysis using InBody770. RESULTS: Simple regression analysis showed that total muscle quantity/total fat quantity ratio (muscle/fat) was significantly correlated with M/I value (B=0.806, P<0.001). The regression equation was M/I value=3.6934×(muscle/fat ratio)+0.0347 (R(2)=0.6503, P<0.001). Multivariate logistic regression analysis showed that muscle/fat ratio was independently and significantly associated with insulin resistance, defined by M/I value <9 (odds ratio, 0.89; 95% confidence interval, 0.80-0.99, P=0.04). With receiver operating curve analysis, the cutoff value of muscle/fat ratio for insulin resistance was 2.40 and area under the curve was 0.87 (sensitivity 91% and specificity 76%, P<0.001), indicating that muscle/fat ratio was significantly effective for predicting insulin resistance in treatment-naïve DM. The result could provide a possible estimation of the M/I value using the regression equation M/I value=2.5438×(muscle/fat ratio)+48.6194×QUICKI-13.6522 (R(2)=0.7012). CONCLUSION: In treatment-naïve DM, the muscle/fat ratio, assessed by InBody770 is clinically useful for evaluating the presence of insulin resistance in daily clinical practice.

A pilot study of ezetimibe vs. atorvastatin for improving peripheral microvascular endothelial function in stable patients with type 2 diabetes mellitus.

BACKGROUND: Elevated cholesterol in type 2 diabetes mellitus (DM) can cause endothelial dysfunction. An effective clinical therapy to improve endothelial dysfunction remains to be established. Different cardiovascular actions between treatments for the inhibition of cholesterol absorption and the suppression of cholesterol synthesis for achieving improvement in endothelial function are unknown in DM. METHODS: Stable patients with type 2 DM and mildly elevated low-density lipoprotein cholesterol were enrolled. We evaluated peripheral microvascular endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT) examination and calculated a natural logarithmic transformed value for the RH-PAT index (LnRHI). We randomly assigned 33 patients to each monotherapy: cholesterol synthesis suppression using atorvastatin (5 mg/day, n=16) or cholesterol absorption inhibition using ezetimibe (10 mg/day, n=17). Patients were prospectively followed for 6 months. Serum lipids and LnRHI were repeatedly examined before and after each therapy. RESULTS: LDL significantly decreased in both groups, but the percent changes of LDL showed a greater decrease in the atorvastatin group compared with the ezetimibe group (-34.5±7.8% vs. -21.9±9.6%, p<0.01). Serum levels of non-esterified free fatty acids (NEFA) significantly decreased in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 561.1±236.8 to 429.7±195.9, p<0.01; atorvastatin group: 538.8±319.5 to 520.2±227.3, p=0.75). The percent decrease in NEFA was significantly greater in the ezetimibe group compared with the atorvastatin group (-19.9±27.4% vs. 11.3±44.1%, p<0.05). LnRHI showed a significant increase in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 0.471±0.157 to 0.678±0.187, p<0.01; atorvastatin group: 0.552±0.084 to 0.558±0.202, p=0.64). The percent changes in LnRHI were significantly greater in the ezetimibe group compared with the atorvastatin group (63.3±89.2% vs. 7.4±41.2%, p<0.05). CONCLUSIONS: In patients with type 2 DM, ezetimibe monotherapy significantly reduced LDL and NEFA, and improved peripheral microvascular endothelial dysfunction. Ezetimibe could potentially exhibit beneficial effects on lipid disorders and microvascular endothelial dysfunction in DM.

Liraglutide, a glucagon-like peptide-1 analog, increased insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp examination in patients with uncontrolled type 2 diabetes mellitus.

AIMS: Glucagon-like peptide-1 (GLP-1) analog promotes insulin secretion by acting on pancreatic ß-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.

[Determination of residual pesticides in processed foods manufactured from livestock foods and seafoods using ion trap GC/MS].

A simultaneous method using iontrap gas chromatography/mass spectrometry (GC/MS) was developed for the determination of pesticide residues in four processed foods (frozen Chinese dumpling, eel kabayaki, corned beef and retort curry). Pesticide residues were extracted from samples with ethyl acetate-cyclohexane (1:1) in the presence of anhydrous sodium sulfate. The extract was concentrated and the residue was dissolved in n-hexane. The lipids in the extract were removed by acetonitrile-n-hexane partitioning, following which the acetonitrile layer was cleaned up using a C(18) mini-cartridge column and a graphite carbon/PSA silica (GCB/PSA) mini-cartridge column. The limits of quantification of compounds in 4 processed foods were below 0.01 microg/g. The recoveries of 292 compounds spiked at 0.1 microg/g in 4 kinds of processed foods, and 210 to 262 pesticides showed acceptable recoveries of 70-120% with low repeatability (15%) and intermediate precision (<20%) only at the 0.1 microg/g spiked level. This method is expected to be useful for multi-residue analysis of pesticide residues in processed foods manufactured using livestock and seafoods as the main raw materials.