Decreases in serum testosterone concentrations in aging men are associated with metabolic disorders. Testosterone has been reported to increase GLUT4-dependent glucose uptake in skeletal muscle cells and cardiomyocytes. However, studies on glucose uptake occurring in response to testosterone stimulation in adipocytes are currently not available. This study was designed to determine the effects of testosterone on glucose uptake in adipocytes. Glucose uptake was assessed with 2-[(3)H] deoxyglucose in 3T3-L1 adipocytes. GLUT4 translocation was evaluated in plasma membrane (PM) sheets and PM fractions by immunofluorescence and immunoblotting, respectively. Activation of GLUT4 translocation-related protein kinases, including Akt, AMPK, LKB1, CaMKI, CaMKII, and Cbl was followed by immunoblotting. Expression levels of androgen receptor (AR) mRNA and AR translocation to the PM were assessed by real-time RT-PCR and immunoblotting, respectively. The results showed that both high-dose (100 nM) testosterone and testosterone-BSA increased glucose uptake and GLUT4 translocation to the PM, independently of the intracellular AR. Testosterone and testosterone-BSA stimulated the phosphorylation of AMPK, LKB1, and CaMKII. The knockdown of LKB1 by siRNA attenuated testosterone- and testosterone-BSA-stimulated AMPK phosphorylation and glucose uptake. These results indicate that high-dose testosterone and testosterone-BSA increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes by inducing the LKB1/AMPK signaling pathway.

Recent studies have suggested that the inter-arm blood pressure difference (IAD) is associated with cardiovascular events and mortality. The aim of this study was to assess whether the IAD could be a marker for subclinical atherosclerosis in patients with type 2 diabetes who are at high risk of cardiovascular disease (CVD). In a cross-sectional retrospective study of 206 Japanese patients with type 2 diabetes aged 49-76 years, we examined the correlation of the IAD with the carotid intima-media thickness (IMT), ankle-brachial index (ABI) or cardio ankle vascular index (CAVI). The IAD was positively correlated with the maximum IMT (r=0.266, P<0.0001), mean IMT (r=0.209, P=0.00726) or CAVI (r=0.240, P=0.0005). The IAD was higher in patients with CVD than in those without (P=0.0020). A multiple linear regression analysis demonstrated that the IAD was an independent determinant of maximum IMT (β=0.169, P=0.0167), mean IMT (β=0.178, P=0.0153), ABI (β=-0.222, P=0.0033) or CAVI (β=0.213, P=0.0011) after adjusting for known risk factors. The area under the receiver operating characteristic curve (AUC) of the IAD as a predictor of subclinical atherosclerosis was similar to the AUC of the Framingham 10-year coronary heart disease risk score. In conclusion, the IAD could be a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

We investigated the impact of combined effect of body mass index and waist-to-height ratio on risk of diabetes. Overweight and abdominal obesity were defined as body mass index ≥23 kg/m2 and waist-to-height ratio ≥0.5, respectively. We divided participants into four groups according to presence of overweight and/or abdominal obesity. About 20% individuals with overweight did not complicated with an abdominal obesity. Among 3,737 participants, 286 participants had diabetes at baseline-examination. Adjusted odds ratios for prevalence of diabetes compared with non-overweight participants without abdominal obesity were as follow: 1.87 (95% confidence interval 1.09–3.14, p = 0.024) in non-overweight participants with abdominal obesity, 1.51 (0.87–2.55, p = 0.141) in overweight participants without abdominal obesity and 3.25 (2.37–4.52, p<0.001) in overweight participants with abdominal obesity. In the follow-up examination, 86 participants were diagnosed as diabetes among 2,263 participants. Adjusted odds ratios for incident diabetes were as follow: 2.59 (0.98–6.44, p = 0.056) in non-overweight participants with abdominal obesity, 1.65 (0.64–4.00, p = 0.288) in overweight participants without abdominal obesity and 2.77 (1.55–5.15, p<0.001) in overweight participants with abdominal obesity. Non-overweight individuals with abdominal obesity as well as overweight individuals with abdominal obesity was associated with diabetes compared with non-overweight individuals without abdominal obesity.

BackgroundHemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages.MethodsContinuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide.ResultsNine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment.ConclusionThese results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.

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Transient remission of NAFLD significantly decreased the risk of developing T2DM.

The aim of this study was to evaluate the reliability of self-reported home blood pressure (HBP) in patients with type 2 diabetes by comparing the self-reported values with HBP measurements stored in the memory of the blood pressure (BP) monitor. We also examined what factors affect the reliability of HBP measurements. A cross-sectional study was conducted in 280 patients with type 2 diabetes. Patients were requested to perform triplicate morning and evening measurements over a span of 2 weeks and to enter their HBP values into logbooks. Patients were not informed about the memory function of their BP monitoring devices. The concordance rate of HBP reporting was 78.6%. A total of 51.4% of patients (n=144) had >90% concordant data, and 15.7% of patients (n=44) had ⩽50% concordant data. In general, HBP values from the logbook were significantly lower and less variable than those from the stored memory (P<0.05). The most common type of incorrect data was selected data that were reported in the logbooks that were randomly selected from multiple readings by the HBP monitors (55.8%). The concordance rate of HBP reporting significantly correlated with hemoglobin A1c levels (β=-0.156; P=0.0149) and with smoking status (current vs. never, β=-0.165; P=0.0184). In conclusion, HBP measurements from the patients' logbooks were lower and less variable than those from the stored memory in the BP monitors of patients with type 2 diabetes, and the reliability of HBP reporting was affected by glycemic control and smoking status. Repeated instructions regarding HBP measurement to the patients or the use of stored BP measurements is recommended to ensure accurate HBP measurements in patients with type 2 diabetes.

Background: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. Methods: The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in 1 group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. Discussion: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.