scholarly journals Effects of Sodium-Glucose Cotransporter 2 Inhibition on Glucose Metabolism, Liver Function, Ascites, and Hemodynamics in a Mouse Model of Nonalcoholic Steatohepatitis and Type 2 Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Koichi Yabiku ◽  
Keiko Nakamoto ◽  
Maho Tsubakimoto
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Heart Rate ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Mouse Model ◽  
Nonalcoholic Steatohepatitis ◽  
Blood Glucose Monitoring ◽  
Sodium Glucose Cotransporter

Many blood glucose-lowering drugs cannot be used once patients with type 2 diabetes (T2D) and nonalcoholic fatty liver disease develop nonalcoholic steatohepatitis (NASH). Therefore, such patients often require insulin treatment. We aimed to determine the effect of sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin monotherapy on glucose metabolism in a mouse model of NASH/T2D, with a focus on its diuretic effects. To imitate ascites and to determine its severity by imaging, meglumine sodium amidotrizoate (MSA) was infused into the abdominal cavities of mice. The reduction in ascites induced by dapagliflozin was compared with that induced by furosemide using microcomputed tomography. The effects of each drug on hemodynamics were also compared. A dapagliflozin-related improvement in glucose tolerance was achieved in mice fed a high-fat diet (HFD) or an HFD + methionine-and-choline-deficient diet (MCDD). In dapagliflozin-treated NASH mice, hypoglycemia was not identified during 24-hour casual blood glucose monitoring. In the dapagliflozin and furosemide-treated groups, the time taken for the resolution of artificial ascites was significantly shorter than in the untreated group, and there were no significant differences between these groups. Furosemide significantly reduced the blood pressure and significantly increased the heart rate of the mice. Dapagliflozin caused a mild decrease in systolic, but not diastolic blood pressure, and the heart rate and circulating catecholamine and renin-aldosterone concentrations were unaffected. Dapagliflozin treatment improved glycemic control in the NASH mice versus untreated mice. Thus, dapagliflozin had a prompt diuretic effect but did not adversely affect the hemodynamics of mice with NASH and T2D. Therefore, it may be useful for the treatment of patients with both T2D and liver cirrhosis.

scholarly journals Different Responses of Muscle Sympathetic Nerve Activity to Dapagliflozin Between Patients With Type 2 Diabetes With and Without Heart Failure

2021 ◽  
Author(s):  
Takuto Hamaoka ◽  
Hisayoshi Murai ◽  
Tadayuki Hirai ◽  
Hiroyuki Sugimoto ◽  
Yusuke Mukai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Brain Natriuretic Peptide ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Sodium Glucose Cotransporter

Background Sodium‐glucose cotransporter 2 inhibitors improve cardiovascular outcomes in patients with diabetes with and without heart failure (HF). However, their influence on sympathetic nerve activity (SNA) remains unclear. The purpose of this study was to evaluate the effect of sodium‐glucose cotransporter 2 inhibitors on SNA and compare the responses of SNA to sodium‐glucose cotransporter 2 inhibitors in patients with type 2 diabetes with and without HF. Methods and Results Eighteen patients with type 2 diabetes, 10 with HF (65.4±3.68 years) and 8 without HF (63.3±3.62 years), were included. Muscle SNA (MSNA), heart rate, and blood pressure were recorded before and 12 weeks after administration of dapagliflozin (5 mg/day). Sympathetic and cardiovagal baroreflex sensitivity were simultaneously calculated. Brain natriuretic peptide level increased significantly at baseline in patients with HF than those without HF, while MSNA, blood pressure, and hemoglobin A1c did not differ between the 2 groups. Fasting blood glucose and homeostatic model assessment of insulin resistance did not change in either group after administering dapagliflozin. MSNA decreased significantly in both groups. However, the reduction in MSNA was significantly higher in patients with HF than patients with non‐HF (−20.2±3.46 versus −9.38±3.65 bursts/100 heartbeats; P =0.049), which was concordant with the decrease in brain natriuretic peptide. Conclusions Dapagliflozin significantly decreased MSNA in patients with type 2 diabetes regardless of its blood glucose‐lowering effect. Moreover, the reduction in MSNA was more prominent in patients with HF than in patients with non‐HF. These results indicate that the cardioprotective effects of sodium‐glucose cotransporter 2 inhibitors may, in part, be attributed to improved SNA.

scholarly journals A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome with diabetes and the choices of the appropriate hypoglycemic drugs: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhiying Liu ◽  
Sai Wang ◽  
Ruixiao Zhang ◽  
Cui Wang ◽  
Jingru Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Gitelman Syndrome ◽  
Blood Glucose Monitoring ◽  
Oral Glucose ◽  
Compound Heterozygous ◽  
Slc12a3 Gene

Abstract Background Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. It is universally known that both hypokalemia and hypomagnesemia can influence insulin secretion and insulin resistance, but the exact mechanisms require further study. We identified a novel deletion variant of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. Case presentation A 55-year-old diabetic female patient was hospitalized for evaluation because of paroxysmal general weakness and numbness of extremities for one year. We suspected that she was suffering from GS by initial estimation. Direct Sanger sequencing was used to analyze the causative gene SLC12A3 of GS. Oral glucose tolerance test (OGTT) was carried out to assess the glucose metabolism and insulin resistance status. Genetic analysis revealed that she was a compound heterozygote for a recurrent missense mutation c.179C > T and a novel deletion c.1740delC in SLC12A3, thus her diagnosis of GS was confirmed. The patient was treated with potassium chloride (3.0 g/d) and magnesium chloride (element magnesium 350 mg/d) on the basis of initial treatment of diabetes with hypoglycemic drug (Repaglinide, 3.0 mg/day). However, she developed frequent hypoglycemia after one week. OGTT showed that her glucose metabolism and insulin resistance much improved after potassium and magnesium supplemental therapy. Then we changed the hypoglycemic agent to a dipeptidyl peptidase-4 (DPP-4) inhibitor (Trajenta 5 mg/d), since then her blood glucose level remained normal during two-year of follow-up. Conclusion We have identified a novel deletion of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. We suggested that attention need to be paid to blood glucose monitoring in GS patients, especially when hypokalemia and hypomagnesemia are corrected. Besides, the insufficient blood volume and serum electrolyte disturbance should also be taken into consideration in the selecting hypoglycemic drugs for GS patients.

941-P: Frequency of Blood Glucose Monitoring in Relation to Medical Cost and Glycemic Control in Hospitalized Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 941-P
Author(s):  
LEI ZHANG ◽  
YAN GU ◽  
YUXIU YANG ◽  
NA WANG ◽  
WEIGUO GAO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycemic Control ◽  
Medical Cost ◽  
Glucose Monitoring ◽  
Hospitalized Patients ◽  
Blood Glucose Monitoring

scholarly journals Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

AbstractDiabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = − 0.10%, 95% CI [− 0.17, − 0.03], body weight (MD = − 4.57 kg, 95% CI [− 4.74, − 4.39], systolic blood pressure (MD = − 4.77 mmHg, 95% CI [− 5.39, − 4.16]), diastolic blood pressure (MD = − 2.07 mmHg, 95% CI [− 2.74, − 1.40], and fasting plasma glucose (MD = − 0.55 mmol/L, 95% CI [− 0.69, − 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

scholarly journals Effects of Vildagliptin and Metformin on Blood Pressure and Heart Rate Responses to Small Intestinal Glucose in Type 2 Diabetes

Diabetes Care ◽  
2017 ◽  
Vol 40 (5) ◽  
pp. 702-705 ◽  
Author(s):  
Tongzhi Wu ◽  
Laurence G. Trahair ◽  
Tanya J. Little ◽  
Michelle J. Bound ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Heart Rate ◽  
Small Intestinal

scholarly journals The association of six-minutes walking test (6MWT) with cardiovascular disease risk among older women with type 2 diabetes mellitus in a rural primary health care: a pilot observational study

2020 ◽  
Vol 3 (1) ◽  
pp. 34
Author(s):  
Rakhmat Ari Wibowo ◽  
Arum Tri Wahyuningsih ◽  
Rio Jati Kusuma ◽  
Wahyu Pamungkasih ◽  
Denny Agustiningsih
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Heart Rate ◽  
Older Women ◽  
Walking Test ◽  
Primary Health ◽  
Ascvd Risk

The recent systematic review found that cardiovascular events contributed to approximately half of all deaths among patients with type 2 diabetes mellitus (T2DM). Several studies suggested that the six-minutes walking test (6MWT) could be a valuable prognostic tool for predicting cardiovascular disease (CVD) events in particular diseases. However, less is known concerning the role of 6MWT in predicting CVD events among patients with T2DM. Thus, this pilot observational study aimed to test the feasibility of conducting the 6MWT and to examine the association of measures collected during 6MWT with ASCVD risk estimator parameters for predicting CVD events among T2DM patients. Fourteen older women with T2DM in a rural primary health care were enrolled in this cross-sectional study. Blood pressure measurement, heart rate measurement, and blood sampling for HDL, LDL, and total cholesterol measurements were carried out during rest. Both heart rate and distance were measured at the end of the following 6MWT. Feasibility data were collected. Recruitment rate and measurement completion rate were 85.7% and 40% respectively. No adverse events during the 6MWT were reported. Patient’s heart rate at the end of 6MWT was correlated with diastolic blood pressure (r=0.5 p=0.48). Multivariate analyses suggested that every one-meter increase in distance of 6MWT, there is a decrease in diastolic blood pressure of -0.9 mmHg (p=0.01; 95% CI= -1.6 to -0.2). In conclusion, 6MWT is a feasible simple test which could provide a valuable prediction of ASCVD risk among older women with T2DM. Thus, this test should be considered to be conducted as a part of routine examination. Cohort study with a larger sample could be suggested to establish the usefulness of the 6MWT in predicting CVD risk.

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