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.

Changes in urinary glucose concentration and body weight in patients treated with the selective SGLT2 inhibitor luseogliflozin.

AIMS: We investigated the effects of the SGLT2 inhibitor luseogliflozin on blood and urinary glucose and body weight. METHODS: Luseogliflozin 2.5 mg was administered once daily for 24 weeks to 30 outpatients with type 2 diabetes. Urinary glucose concentration, continuous glucose monitoring values, HbA1c, fasting glucose, and body weight were evaluated. Correlations with urinary glucose, subcutaneous/visceral fat mass, insulin, EPA/AA ratio, plasma free fatty acids, ghrelin, blood ketones, plasma 1,5-anhydro-D-glucitol were evaluated. RESULTS: Urinary glucose significantly increased from 11.1 ± 11.8 g at Week -4 to 84.5 ± 46.8 g at Week 24. HbA1c significantly declined from 7.88 ± 0.88% to 7.36 ± 1.13% at Week 24. Mean blood glucose significantly decreased from 149.6 ± 41.8 to 131.6 ± 31.1 mg/dL at Week 24. Subcutaneous and visceral fat mass was also significantly decreased, as were AST and ALT (P < 0.01). Blood urea nitrogen was significantly increased, and urate significantly decreased from 5.04 ± 1.07 to 4.53 ± 0.94 mg/dL. The homeostasis model assessment ratio remained significantly improved throughout the treatment period. Acyl ghrelin levels remained constant but des-acyl ghrelin increased significantly. CONCLUSIONS: Luseogliflozin monotherapy resulted in an improvement in blood glucose, a decrease in body weight, and decreased insulin resistance. Luseogliflozin appears to be an effective therapy for obese diabetics.

A Non-obese, Treatment-Naive Japanese Diabetic Patient With Elevated Insulin Clearance and Hyperglycemia Under Enhanced Insulin Sensitivity and Increased Insulin Secretion: Elevated Insulin Clearance as Type 2 Japanese Diabetes Mellitus (T2JDM).

Diabetes mellitus is a heterogeneous and complex metabolic disorder characterized by hyperglycemia secondary to either resistance to insulin actions on the liver and peripheral tissues, insufficient insulin secretion from pancreatic ß-cells, or both. An integrated balance between blood insulin levels and whole-body insulin sensitivity could theoretically provide the clinical effectiveness of insulin action. Peripheral blood insulin concentrations might be determined by the capacity of endogenous pancreatic ß-cell insulin secretion and the degree of the whole body insulin clearance. Here, we report a non-obese normoinsulinemic Japanese diabetic patient with elevated insulin clearance assessed by a hyperinsulinemic-euglycemic clamp examination and increased insulin secretion measured by daily urinary excretion of C-peptide immunoreactivity. We propose this unique pathogenic condition of diabetes with normoinsulinemia and elevated insulin clearance as "type 2 Japanese diabetes mellitus (T2JDM)."

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.

Type 2 Diabetes Remission and Substantial Body Weight Reduction Achieved with Metformin and a Sodium-Glucose Cotransporter 2 Inhibitor.

The overall goal in the treatment of type 2 diabetes mellitus (T2DM) is remission. However, the effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) on remission of T2DM are unknown. We herein report a case involving an overweight 43-year-old man who completely recovered from T2DM after SGLT2i therapy (dapagliflozin at 5 mg/day). In the pretreatment period, he had a body mass index (BMI) of 26.0 kg/m2, hemoglobin A1c (HbA1c) concentration of 10.3%, advanced insulin resistance, pancreatic ß-cell dysfunction, and fatty liver. Eighteen months after comprehensive therapy, including the administration of an SGLT2i and metformin, his BMI had decreased to 21.3 kg/m2 and his glycemic control was almost normal (HbA1c of 5.3%) despite discontinuation of all hypoglycemic medications. This report is the first to propose the usefulness of the combination therapy of SGLT2i and metformin for achieving normal body weight and remission of newly diagnosed T2DM in a real-world clinical situation.

Cognitive function in post-cardiac intensive care: patient characteristics and impact of multidisciplinary cardiac rehabilitation.

New/worsening cognitive and physical impairments following critical care pose significant problems. Multidisciplinary cardiac rehabilitation (CR) can improve physical function after cardiac intensive care (CIC). This observational study aimed to evaluate cognitive function in patients participating in multidisciplinary CR and to identify correlates of impaired cognitive function after CIC. We analyzed 111 consecutive patients admitted to our comprehensive care ward at least 7 days after CIC and assessed factors associated with cognitive function using the Functional Independence Measure (FIM). Patients were stratified into two groups based on the median FIM-Cognitive scores: impaired (n = 56) and preserved cognition (n = 55) groups. Multiple logistic regression analysis identified age [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.00-1.13; p = 0.042], Mini-Nutrition Assessment-Short Form (MNA-SF; OR 0.73; 95% CI 0.56-0.95; p = 0.017), and FIM-Physical scores (OR: 0.94; 95% CI 0.90-0.99; p = 0.012) as significant and independent factors associated with impaired cognition. The median length of hospital stay was 28 (interquartile range: 18, 43) days. The FIM-Cognitive and FIM-Physical scores significantly increased from admission to discharge [32.0 (27.0, 35.0) vs. 34.0 (29.0, 35.0) points; p < 0.001; 67.0 (53.0, 75.0) vs. 85.0 (73.5, 89.0) points; p < 0.001, respectively]. On subgroup analysis within the impaired cognition group, increased FIM-Cognitive scores positively and significantly correlated with increased FIM-Physical scores (ρ = 0.450; p = 0.001). Multiple linear regression analysis identified atrial fibrillation (AF; ß = - 0.29; p = 0.016), ln(glycated hemoglobin; HbA1c) (ß = 0.29; p = 0.018), and ln(high-sensitivity C-reactive protein; hs-CRP) (ß = - 0.26; p = 0.034) as significant and independent factors correlated with increased FIM-Cognitive scores. In conclusion, advanced age, low MNA-SF score, and FIM-Physical score were independent factors associated with impaired cognition in post-CIC patients. Multidisciplinary CR improved both physical and cognitive functions, and AF, HbA1c, and hs-CRP were independent factors correlated with increased FIM-Cognitive score.

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.

One quarter of total myocardial infarctions are silent manifestation in patients with type 2 diabetes mellitus.

BACKGROUND: Silent events with newly developed Q waves in electrocardiogram (ECG) [silent myocardial infarction (MI)] in diabetic patients is reported to be independently associated with an increased risk of fatal MI. However, the incidence rate of silent MI in diabetic patients has yet to be clarified. We sought to determine the incidence rate of first symptomatic MI and silent MI in diabetic patients. METHODS: We conducted a prospective cohort study on patients enrolled in the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial which was started in 2002. It is a randomized controlled trial to examine the efficacy of low-dose aspirin therapy for the primary prevention of atherosclerotic events in type 2 diabetic patients. No patients had Q waves in their ECG before entry to the JPAD trial. We followed-up 1825 patients until July 2015 after completion of the JPAD trial in 2008. The median follow-up period was 10.3 years. We collected 1648 patients' ECGs to identify patients with silent MI. RESULTS: Symptomatic MI occurred in 65 patients and silent MI occurred in 22 patients. The incidence rate of symptomatic MI was 4.26 per 1000 patient-years and 1.44 for silent MI in diabetic patients. Thus, 25% of total MIs were silent. Cause-specific Cox proportional hazard model indicated that age (hazard ratio 1.06, 95% confidence interval; 1.03-1.10, p=0.0004) and long history of diabetes (1.00, 1.01-1.07, p=0.01) were independently associated with symptomatic MI, but these were not associated with silent MI. CONCLUSIONS: We demonstrated that incidence rate of first silent MI and that proportion of silent MI to all MIs was 25% in diabetic patients without a history of atherosclerotic events. Diabetic patients frequently need ECG screening for detection of silent MI.

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study.

AIMS: To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target. MATERIALS AND METHODS: This exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group. RESULTS: Data were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28-0.82; P = 0.007). CONCLUSIONS: This post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy.

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 Molar Ratio of N-terminal pro-B-type Natriuretic Peptide/B-type Natriuretic Peptide for Heart Failure-related Events in Stable Outpatients with Cardiovascular Risk Factors.

Objective B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) should be secreted from cardiomyocytes in response to increased myocardial wall stress in a molar ratio of 1.00; however, the calculated molar blood levels of NT-proBNP are often greater than those of BNP in routine clinical practice. The purpose of this study was to investigate the hypothesis that the molar ratio of NT-proBNP/BNP provides useful clinical information in stable outpatients with cardiovascular risk factors. Methods We measured both the BNP and NT-proBNP levels simultaneously in 551 consecutive, stable outpatients with at least one cardiovascular risk factor and then calculated the molar ratio of NT-proBNP/BNP. All patients were prospectively followed-up for the occurrence of heart failure (HF)-related events. Results Of those patients, 38 patients had an HF-related event. A multivariate Cox hazards analysis showed that the log (molar ratio of NT-proBNP/BNP) was an independent predictor of future HF-related events (p=0.039). A Kaplan-Meier analysis showed a significantly higher probability of HF-related events in patients with a higher molar ratio of NT-proBNP/BNP (≥1.70) (p<0.001). The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for the molar ratio of NT-proBNP/BNP to predict HF-related events was 0.75 (p<0.001). The AUC of the ROC curve analysis with the molar ratio of NT-proBNP/BNP for the prediction of HF-related events was not significantly greater than that of BNP or NT-proBNP. Conclusion The molar ratio of NT-proBNP/BNP may be a significant prognostic factor for HF-related events.