Chemical and Nutritional Profiling of the Seaweed Dictyota dichotoma and Evaluation of Its Antioxidant, Antimicrobial and Hypoglycemic Potentials.

Seaweed has been known to possess beneficial effects forhuman health due to the presence of functional bioactive components. The n-butanol and ethyl acetate extracts of Dictyota dichotoma showed ash (31.78%), crude fat (18.93%), crude protein (14.5%), and carbohydrate (12.35%) contents. About 19 compounds were identified in the n-butanol extract, primarily undecane, cetylic acid, hexadecenoic acid, Z-11-, lageracetal, dodecane, and tridecane, whereas 25 compounds were identified in the ethyl acetate extract, mainly tetradecanoic, hexadecenoic acid, Z-11-, undecane, and myristic acid. FT-IR spectroscopy confirmed the presence of carboxylic acid, phenols, aromatics, ethers, amides, sulfonates, and ketones. Moreover, total phenolic contents (TPC) and total flavonoid contents (TFC) in ethyl acetate extract were 2.56 and 2.51 mg GAE/g and in n-butanol extract were 2.11 and 2.25 mg QE/g, respectively. Ethyl acetate and n-butanol extracts at a high concentration of 100 mg mL-1 showed 66.64 and 56.56 % inhibition of DPPH, respectively. Antimicrobial activity revealed that Candida albicans was the most susceptible microorganism, followed by Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, whereas Pseudomonas aeruginosa showed the least inhibition at all concentrations. The in vivo hypoglycemic study revealed that both extracts exhibited concentration-dependent hypoglycemic activities. In conclusion, this macroalgae exhibited antioxidant, antimicrobial, and hypoglycemic potentials.

Inhibition of α-Glycosidase by Lippia dulcis Trevir. (Verbenaceae) Preparations, Quantification of Verbascoside, and Study of Its Molecular Docking.

This study aimed to quantify verbascoside (VEB), perform molecular docking studies of VEB with the α-glucosidase (GL) of Bacillus stearothermophilus, and evaluate the inhibition of the enzyme by L. dulcis preparations. The substrate concentration and presence of reduced glutathione were evaluated for their effect on the in vitro inhibition of the GL enzyme. Assays were also performed in the presence and absence of simulated gastric fluid. The antidiabetic fractions 2 and 3 were the most inhibited GL, but their activity were significantly decreased in the presence of gastric fluid. Chromatographic analyses confirmed the predominant presence of VEB in the samples. The samples had VEB concentrations between 49.9 and 243.5 mg/g. Simulation of the molecular docking of VEB were consistent with its GL-inhibitory activity. It can conclude that the crude ethanol extract and fractions show inhibitory activity against the GL enzyme.

Effect of Dietary Fiber on the Level of Free Hypoglycemic Agents in Vitro.

We studied the effect of dietary fibers (DFs) on the levels of free hypoglycemic agents in vitro, i.e., glimepiride and the biguanides buformin and metformin. The levels of free buformin and free metformin were not affected by mixtures of DFs, i.e., cellulose, chitosan, pectin (PE), and glucomannan (GM), in fluids of pH 1.2 and 6.8 (similar to the pH of the stomach and intestines, respectively). However, the free biguanide level was significantly reduced by mixing with PE or sodium alginate (AL), in water. The free glimepiride level was reduced in the mixture of AL, PE, and GM (in a solution with a pH of 6.8). The changes in aqueous AL solution pH seemed to reflect the free metformin levels. Therefore, the effects of DFs on free drug levels were dependent on drug type, hypoglycemic agent, and mixing solution. In this study, the oral regimen concentrations of the drug and DFs were used. Based on these results, it is important to consider the interactions between hypoglycemic agents and DFs.

Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: Results of a phase 3, randomized controlled trial.

BACKGROUND: Dasiglucagon, a next-generation, ready-to-use aqueous glucagon analog formulation, has been developed to treat severe hypoglycemia in individuals with diabetes. OBJECTIVE: The aim of this trial was to evaluate the safety and efficacy of dasiglucagon in pediatric individuals with type 1 diabetes (T1DM). Participants were children and adolescents (6-17 years) with T1DM. METHODS: In this randomized double-blind trial, 42 participants were randomly allocated (2:1:1) to a single subcutaneous (SC) injection of dasiglucagon (0.6 mg), placebo, or reconstituted glucagon (GlucaGen; dosed per label) during insulin-induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery (first PG increase ≥20 mg/dL after treatment initiation without rescue intravenous glucose). The primary comparison was dasiglucagon vs. placebo; glucagon acted as a reference. RESULTS: The median time (95% confidence interval) to PG recovery following SC injection was 10 min (8-12) for dasiglucagon vs. 30 min (20 to -) for placebo (P < .001); the median time for glucagon was 10 min (8-12), which did not include the time taken to reconstitute the lyophilized powder. PG recovery was achieved in all participants in the dasiglucagon and glucagon groups within 20 min of dosing compared to 2 out of 11 patients (18%) with placebo. The most frequent adverse events were nausea and vomiting, as expected with glucagon treatment. CONCLUSIONS: Consistent with adult phase 3 trials, dasiglucagon rapidly and effectively restored PG levels following insulin-induced hypoglycemia in children and adolescents with T1DM, with an overall safety profile similar to glucagon.

Risk of metformin failure in the treatment of women with gestational diabetes.

OBJECTIVES: To estimate the metformin failure rate in women with gestational diabetes. METHODS: The study was designed as a retrospective cohort of women diagnosed with gestational diabetes by the 75 g 2 h oral glucose tolerance test. Women were placed into two groups: metformin success (107 patients not requiring insulin therapy) or metformin failure (15 patients requiring the addition of, or, transition to insulin). Primary outcome: rate of metformin failure. Secondary outcomes: maternal and neonatal factors. RESULTS: The failure rate of metformin was 15% (19/122 women) in the study. The failure group was more likely to have 3 abnormal values on a 2-h 75 g oral glucose tolerance test (37% (n=7/19) vs. 15% (n=15/103), p=0.02). Patients who failed had higher average fasting blood glucose levels on the glucose tolerance test as well as on pretreatment fasting finger stick values. Those who failed metformin were diagnosed with gestational diabetes and started on metformin earlier in gestation. CONCLUSIONS: Overall low rate of metformin failure in treatment of gestational diabetes.

The timing of initiation of pharmacotherapy for women with gestational diabetes mellitus.

BACKGROUND: The decision to initiate pharmacotherapy is integral in the care for pregnant women with gestational diabetes mellitus (GDM). We sought to compare pregnancy outcomes between two threshold percentages of elevated glucose values prior to initiation of pharmacotherapy for GDM. We hypothesized that a lower threshold at pharmacotherapy initiation will be associated with lower rates of adverse perinatal outcomes. METHODS: This was a retrospective cohort study of women with GDM delivering in a single tertiary care center. Pregnancy outcomes were compared using bivariable and multivariable analyses between women who started pharmacotherapy (insulin or oral hypoglycemic agent) after a failed trial of dietary modifications at two different ranges of elevated capillary blood glucose (CBG) values: Group 1 when 20-39% CBG values were above goal; Group 2 when ≥40% CBG values were above goal. The primary outcome was a composite GDM-associated neonatal adverse outcome that included: macrosomia, large for gestational age (LGA), shoulder dystocia, hypoglycemia, hyperbilirubinemia requiring phototherapy, respiratory distress syndrome, stillbirth, and neonatal demise. Secondary outcomes included cesarean delivery, preterm birth (< 37 weeks), neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). RESULTS: A total of 417 women were included in the study. In univariable analysis, the composite neonatal outcome was statistically significantly higher in Group 2 compared to Group 1 (47.9% vs. 31.4%, p = 0.001). In addition, rates of preterm birth (15.7% vs 7.4%, p = 0.011), NICU admission (11.7% vs 4.0%, p = 0.006), and LGA (21.2% vs 9.1% p = 0.001) were higher in Group 2. In contrast, higher rates of SGA were noted in Group 1 (8.0% vs. 2.9%, p = 0.019). There was no difference in cesarean section rates. These findings persisted in multivariable analysis after adjusting for confounding factors (composite neonatal outcome aOR = 0.50, 95%CI [0.31-0.78]). CONCLUSIONS: Initiation of pharmacotherapy for GDM when 20-39% of CBG values are above goal, compared to ≥40%, was associated with decreased rates of adverse neonatal outcomes attributable to GDM. This was accompanied by higher rates of SGA among women receiving pharmacotherapy at the lower threshold. Additional studies are required to identify the optimal threshold of abnormal CBG values to initiate pharmacotherapy for GDM.

Characteristics and Early Hypoglycemic Medications of Patients at Risk of Progression to Type 2 Diabetes in Japan: A Retrospective Cohort Study of Health Checkup and Claims Data.

Medication therapy management by tracking patients with risk of progression to type 2 diabetes has not been investigated in Japan. We aimed to assess the characteristics of these patients and their early medications. Claims (n = 190507) and health checkup data (n = 106984) between April 2005 and March 2015 in Japan were selected. We selected patients aged ≥40 years with fasting plasma glucose levels of 100-125 mg/dL or glycated hemoglobin A1c values of 5.7-6.4%. The early-medication group comprised patients who received hypoglycemic medications within 6 months after their first clinic visit, while the no-medication group comprised patients who did not receive any hypoglycemic medications. Main outcome measures were characteristics and early hypoglycemic medications of patients at risk of progression to type 2 diabetes. Of 5676 individuals, hypoglycemic medications were initiated in 276 (5%). The early-medication group had a higher proportion of individuals with a body mass index ≥25 kg/m2 and current smokers and drinkers than the no-medication group. Approximately 83% of patients in the early-medication group were prescribed a single hypoglycemic medication, and since 2010, dipeptidyl peptidase-4 inhibitors were prescribed to one-third of these patients. In our population, early hypoglycemic medication was initiated within 6 months of the first clinic visit, indicating that initiation took place earlier than recommended by current guidelines. Early hypoglycemic medications, especially dipeptidyl peptidase-4 inhibitors with low risks of hypoglycemia, might be prescribed based on patient characteristics. Further epidemiological studies are needed to confirm the suitability of early hypoglycemic medication.

Effects of empagliflozin treatment on cardiac function and structure in patients with type 2 diabetes: a cardiac magnetic resonance study.

BACKGROUND: The effects of empagliflozin on cardiac structure and function are not known. AIMS: To examine the changes in cardiac structure and function following the addition of empagliflozin in patients with type 2 (T2D) diabetes using cardiac magnetic resonance (CMR) imaging. METHODS: Twenty patients attending a specialist diabetes service recommended for treatment with empagliflozin, and 8 control patients with T2D on stable glucose lowering therapy were recruited for cardiac imaging. Participants underwent CMR scans at baseline and 6 months. Inclusion criteria were established T2D, age < 75 years, estimated glomerular filtration rate ≥45 mL/min/1.73 m2 . RESULTS: 17 of 20 in the empagliflozin group, and all of 8 in the control group completed the study. Empagliflozin therapy was associated with reduction in left ventricular end diastolic volume 155 mL (137 mL, 174 mL) at baseline to 145 mL (125 mL, 165 mL) at 6 months, P < 0.01, compared with the control group 153 mL (128 mL, 179 mL) at baseline and 158 mL (128 mL, 190 mL), not significant. There were no differences in measures of left ventricular mass, ejection fraction, heart rate or markers of cardiac fibrosis at baseline and 6 months in either group. CONCLUSIONS: This is the first CMR study to examine the effects of empagliflozin on cardiac function and structure, showing evidence of reduced end diastolic volume. This is likely to reflect change in plasma volume, and may explain the reduced cardiovascular death and heart failure seen in the EMPA-REG OUTCOME trial.

Antidyslipidemic Effect of Ocimum sanctum Leaf Extract in Streptozotocin Induced Diabetic Rats.

The antidyslipidemic activity of Ocimum sanctum leaf extract was studied in streptozotocin induced diabetic rats. In this model, there was significant increase in plasma markers of diabetic-dyslipidemia following diminution of lipid metabolizing enzymes. Oral administration of leaf extract (500 mg/kg b.w.p.o.) for 15 days resulted in significant decrease in diabetogenic and dyslipidemia parameters; namely blood glucose, glycosylated hemoglobin, lipid peroxide, free fatty acids, small dense low density lipoprotein, lipid and protein components of plasma lipoproteins, adipose and liver. The regulation of lipids was accompanied by stimulation of postheparin lipolytic activity, reactivation of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase enzymes. The results of the present study demonstrated antidyslipidemic and antioxidant activities in leaf extract of O. sanctum which could be used in prevention of diabetic-dyslipidemia and related complications.

Velagliflozin, a once-daily, liquid, oral SGLT2 inhibitor, is effective as a stand-alone therapy for feline diabetes mellitus: the SENSATION study.

OBJECTIVE: To investigate safety and effectiveness of velagliflozin oral solution as sole therapy in naïve and previously insulin-treated diabetic cats. ANIMALS: 252 client-owned cats receiving ≥ 2 doses of velagliflozin; 214 (85%) naïve diabetics and 38 (15%) insulin-treated diabetics. PROCEDURES: Prospective, baseline-controlled, open-label clinical field trial. Cats received velagliflozin orally, once daily. Physical examinations and blood collections were performed days 0, 3, 7, 30, 60, 120, and 180. RESULTS: Data are median (range). Screening blood glucose (BG) was 436 mg/dL (272 to 676 mg/dL). On days 30, 60, 120, and 180, single BG after receiving velagliflozin was 153 mg/dL (62 to 480 mg/dL), 134 mg/dL (64 to 414 mg/dL), 128 mg/dL (55 to 461 mg/dL), and 125 mg/dL (77 to 384 mg/dL), respectively. Screening fructosamine was 538 µmol/L (375 to 794 µmol/L). On the same recheck days, fructosamine was 310 µmol/L (204 to 609 µmol/L), 286 µmol/L (175 to 531 µmol/L), 269 µmol/L (189 to 575 µmol/L), and 263 µmol/L (203 to 620 µmol/L). At day 180, 81% of 158 cats remaining had BG and/or fructosamine within reference ranges; 88.6% (124 of 140) and 87.7% (121 of 138) showed improvement in polyuria and polydipsia, respectively. Ketonuria developed in 35 cats (13.9%), including 18 (7.1%) that had ketoacidosis. Ketoacidosis was less common in naïve diabetic cats (11 of 214 [5.1%]) compared to insulin-treated diabetic cats (7 of 38 [18.4%]). At ketoacidosis diagnosis, 14 of 18 cats (77.8%) were euglycemic (ie, BG < 250 mg/dL). Most episodes of ketosis or ketoacidosis (30 of 35 [85.7%]) occurred within the first 14 days of treatment. Insulin-treated diabetic cats were less likely to complete the trial. No clinical hypoglycemia occurred. CLINICAL RELEVANCE: Velagliflozin improved glycemic parameters and clinical signs in diabetic cats. Velagliflozin provides an alternative to insulin as a stand-alone treatment of diabetic cats.

Antidyslipidemic and Antioxidant Activities of Hibiscus rosa sinensis Root Extract in Alloxan Induced Diabetic Rats.

The antidyslipidemic activity of Hibiscus rosa sinensis (Malvaceae) root extract has been studied in alloxan induced diabetic rats. In this model, oral administration of root extract (500 mg/kg bw. p.o.) for 15 days resulted in significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the root extract (50-500 µg) when tested for its antioxidant activity, inhibited the generation of super oxide anions and hydroxyl radicals, in both enzymic and non enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities in root extract of H. rosa sinensis which could be used in prevention of diabetic-dyslipidemia and related complications.

Sodium-Glucose Cotransporter-2 Inhibitor Prevents Stroke in Patients With Diabetes and Atrial Fibrillation.

Background Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA2DS2-VASc score is a well-established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016-December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA2DS2-VASc score in the propensity score-matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow-up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA2DS2-VASc score in the propensity score-matched population. The stroke rate was 3.4% (95% CI, 2.8-4.2) patient-years in SGLT2i users and 4.3% (95% CI, 4.0-4.6) in nonusers (P=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64-0.99]; P=0.043) after adjustment for the CHA2DS2-VASc score. Conclusions Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first-line treatment in patients with diabetes and AF.

Adherence to Hypoglycemic Agents in Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Aims This study aimed to elucidate the level and determinants of adherence to oral hypoglycemic agents (OHAs) among type 2 diabetes mellitus patients and to employ patient interview as a prediction tool for suboptimal adherence, for preventing and reducing complications. Methods In this analytical, cross-sectional study, 383 patients with type 2 diabetes mellitus were interviewed using an electronic, self-constructed, validated questionnaire. Patients were recruited from all Ministry of Health centers across Jeddah, through stratified random sampling. Univariate and multivariate logistic regression analyses were used to evaluate the significance of the results. Results Suboptimal levels of adherence were reported by 74.9% of the participants. Predictors of suboptimal adherence are as follows: younger age (P = 0.003), employment [odd ratio (OR), 1.7; 95% confidence interval (CI), 1.1-3.0], unavailability of reminder (OR, 1.9; 95% CI, 1.1-3.1), and non-commitment to appointments (OR, 6.1; 95% CI, 1.1-3.1). Conclusion The level of adherence to OHAs was found to be suboptimal. Encountering any of the predictors of suboptimal adherence while interviewing the patient should prompt extra vigilance in the approach. Furthermore, utilizing methods to augment adherence might be prudent.

In-vitro and in-vivo pharmacological screening of Iris Albican.

OBJECTIVE: To evaluate the anti-oxidant, enzyme inhibition, anti-pyretic, anti-inflammatory and anti-diabetic activities of Iris albicans. METHODS: Anti-oxidant assay was evaluated using DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging and ABTS (2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) inhibitory protocol while enzyme inhibitory assay was evaluated by lipoxygenase and cyclooxygenase-2 inhibitory protocol respectively. Antipyretic, anti-inflammatory and anti-diabetic potential was evaluated using brewer's yeast induced pyrexia, carrageenan induced paw edema and streptozocin induced diabetes protocols respectively. Serum biochemical parameters were monitored for the period of study. RESULTS: The anti-oxidant activity of chloroform fraction of Iris albicans showed the highest scavenging potential against DPPH and ABTS while the maximum inhibitory action recorded against lipo-oxygenase and cyclooxygenase-2 enzymes was shown by n-hexane and chloroform fractions respectively. The anti-pyretic potential of the crude methanolic extract showed dose dependent activity in reducing pyrexia, thereby when the dose was increased the anti-pyretic effect was also enhanced. The anti-inflammatory action of the crude methanolic extract administered at the dose of 300 mg/kg was significant at 1 h after its administration, which was found maintained up to 5 h. Similarly the anti-diabetic effect of the crude methanolic extract administered at the dose of 200 and 300 mg/kg was noted highly significant at day 6 and was found well maintained throughout the study time period up to 10 days. Significant (P < 0.001) improvement appeared in hemoglobin, protein, cholesterol, triglycerides, urea, creatinine, HDL and LDL of extract treated diabetic mice. CONCLUSION: From this data it could be concluded that Iris albicans have significant anti-oxidant, enzyme inhibition, ant-pyretic, anti-inflammatory and anti-diabetic potential.

Current status of diabetes treatment in Miyazaki Prefecture, Japan: Results of a questionnaire survey conducted in 2016 and 2020.

AIMS/INTRODUCTION: The Japanese diabetes treatment guidelines do not specify the first choice of hypoglycemic agents, unlike those of Western countries. Furthermore, the current situation in diabetes treatment is that the choice of hypoglycemic agents is determined by each physician. Therefore, we aimed to determine the current situation in Miyazaki Prefecture, Japan, in this context. For this, we carried out a questionnaire survey among physicians twice regarding the target value of glycated hemoglobin and the choice of hypoglycemic agents in various cases. MATERIALS AND METHODS: We administered an unsigned questionnaire to physicians in Miyazaki Prefecture, Japan, in July 2016 and March 2020. We divided responses into those of diabetologists and those of non-diabetologists, and analyzed each response. We then compared the results between both years. RESULTS: In total, 18 diabetologists and 142 non-diabetologists responded in 2016, and 21 diabetologists and 134 non-diabetologists responded in 2020. Many diabetologists chose biguanide as the first-line drug for obese type 2 diabetes patients. In addition, the rate of choice of sodium-glucose cotransporter 2 inhibitor (SGLT2i) among physicians almost increased in 2020. Some non-diabetologists, and even a few diabetologists, inappropriately chose SGLT2i and biguanide for patients with severe renal dysfunction. CONCLUSIONS: Because SGLT2i became available in 2016 and a few years have passed, both diabetologists and non-diabetologists seemed to refrain from prescribing SGLT2i. However, with the emergence of various lines of firm evidence regarding the use of SGLT2i, physicians started to prescribe it. However, some diabetologists and non-diabetologists chose hypoglycemic agents inadequately; therefore, there is a need for novel and precise information.

An Insulin Receptor-Binding Multifunctional Protein from Tamarindus indica L. Presents a Hypoglycemic Effect in a Diet-Induced Type 2 Diabetes-Preclinical Study.

The objectives of this study were to evaluate the hypoglycemic effect of the trypsin inhibitor isolated from tamarind seeds (TTI) in an experimental model of T2DM and the in silico interaction between the conformational models of TTI 56/287 and the insulin receptor (IR). After inducing T2DM, 15 male Wistar rats were randomly allocated in three groups (n = 5): 1-T2DM group without treatment; 2-T2DM group treated with adequate diet; and 3-T2DM treated with TTI (25 mg/kg), for 10 days. Insulinemia and fasting glucose were analyzed, and the HOMA-IR and HOMA-ß were calculated. The group of animals treated with TTI presented both lower fasting glucose concentrations (p = 0.0031) and lower HOMA-IR indexes (p = 0.0432), along with higher HOMA-ß indexes (p = 0.0052), than the animals in the other groups. The in silico analyses showed that there was an interaction between TTIp 56/287 and IR with interaction potential energy (IPE) of -1591.54 kJ mol-1 (±234.90), being lower than that presented by insulin and IR: -894.98 kJ mol-1 (±32.16). In addition, the presence of amino acids, type of binding and place of interaction other than insulin were identified. This study revealed the hypoglycemic effect of a bioactive molecule of protein origin from Tamarind seeds in a preclinical model of T2DM. Furthermore, the in silico analysis allowed the prediction of its binding in the IR, raising a new perspective for explaining TTI's action on the glycemic response.

Dry eye disease in patients with type II diabetes mellitus: A retrospective, population-based cohort study in Taiwan.

Purpose: To investigate the risk and protective factors of dry eye disease (DED) in patients with type II diabetes mellitus (DM). Design: A retrospective cohort study using Chang- Gung research database collecting data from 2005 to 2020. Methods: Patients with type II DM were included, and those with previous ocular diseases were excluded. Ten thousand twenty nine developed DED (DED group), and 142,491 didn't (non-DED group). The possible risk and protective factors were compared and analyzed using the logistic regression model. Results: A majority of the DED group were female with significantly higher initial and average glycated hemoglobin levels, and higher incidence of diabetic neuropathy and retinopathy. In conditional logistic regression model, advanced age was a risk factor. After adjusting for sex, age, and DM duration; average glycated hemoglobin level, diabetic neuropathy, retinopathy, and nephropathy with eGFR 30 ~ 59 and intravitreal injection, vitrectomy, pan-retinal photocoagulation, and cataract surgery were contributing factors of DED. Considering antihyperglycemic agents, DPP4 inhibitor, SGLT2 inhibitor, GLP-1 agonist, and insulin monotherapy and dual medications combining any two of the aforementioned agents were protective factors against DED compared with metformin alone. In the monotherapy group, SLGT2 inhibitor had the lowest odds ratio, followed by GLP1 agonist, DPP4 inhibitor, and insulin. Conclusions: DED in patients with DM is associated with female sex, advanced age, poor diabetic control, microvascular complications and receiving ocular procedures. GLP-1 agonist, SGLT-2 inhibitor, DPP4 inhibitor, and insulin are superior to metformin alone in preventing DM-related DED. A prospective randomized control trial is warranted to clarify our results.

Vanadium(IV)-diamine complex with hypoglycemic activity and a reduction in testicular atrophy.

The insulin enhancing activity, histological analysis and, testicular degeneration by a VIVO-complex containing the 2,2'-(ethane-1,2-diylbis(azanediyl))diethanolate ligand, VOIV(C6H14N2O2-κ2N,κ2O), abbreviated VIVO(BHED), were investigated in diabetic male Wistar rats. The complex was administered by oral gavage of freshly prepared solutions of vanadium complex. Biological studies demonstrated that the vanadium complex normalized the elevated glucose levels in male Wistar rats with streptozotocin-induced diabetes and these compounds also avoided common responses in diabetic animals such as weight loss and reduction in the size of the epididymis, prostate, testis and seminal gland. The 51V NMR and EPR studies showed the formation of VIVO(BHED) and the oxidation product [VVO2BHED]- with two possible decomposition pathways. In summary, these studies demonstrate that the VIVO(BHED) complex or its decomposition products show similar effects as insulin in decreasing elevated blood glucose levels.

Hypertension in diabetes care: emerging roles of recent hypoglycemic agents.

Patients with type 2 diabetes (T2D) frequently have multiple cardiovascular, metabolic, and renal comorbidities, such as hypertension, dyslipidemia, hyperuricemia, chronic kidney disease, and heart failure. Accordingly, this patient population often requires polypharmacy, which is associated with an increased risk of drug-drug interactions, poor adherence, and even adverse outcomes. Accumulating evidence on newer hypoglycemic agents, such as glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, has highlighted the marked improvements in cardiovascular and renal outcomes associated with the off-target benefits for relevant comorbidities, including hypertension. These classes of hypoglycemic agents are unique, as they achieve consistently modest but significant reductions in systolic and diastolic blood pressure (BP), an effect that has not been targeted and observed with conventional hypoglycemic agents. In addition to this BP-lowering effect, these agents also have multifaceted beneficial impacts on other cardiometabolic and renal parameters, which appear to be helpful for providing an important comprehensive therapeutic approach to improve the prognosis in patients with T2D. The clinical advantages of these agents may reduce the dose and number of concomitant medications used to treat T2D and related comorbidities. These positive spillover effects may also enhance the clinical use of agents to achieve better diabetes care. As a consequence, the clinical significance of these hypoglycemic agents now extends beyond their hypoglycemic effects, thereby providing a new-normal strategy to use in an evidence-based, patient-centric approach to diabetes care.

Skipping breakfast, late-night eating and current smoking are associated with medication adherence in Japanese patients with diabetes.

AIMS: Little is known about the relationship between medication adherence for oral hypoglycemic agents (OHAs) and glycemic control after adjusting healthy adherer effect in large scale study. Thus, adjusting for health-related behaviors, we investigated the clinical variables associated with medication adherence and the relationship between medication adherence and glycemic control using a large claims database. METHODS: Analyzed were 8805 patients with diabetes whose medication records for OHA were available for at least 1year. Medication adherence was evaluated by the proportion of days covered (PDC). Multivariate logistic regression model was used to identify clinical variables significantly associated with non-adherence. Multiple regression analysis evaluated the relationship between PDC and HbA1c after adjusting for health-related behaviors. RESULTS: Mean PDC was 80.1% and 32.8% of patients were non-adherence. Logistic analysis indicated that older age and taking concomitant medications were significantly associated with adherence while skipping breakfast (odds ratio 0.66 [95% CI 0.57-0.76]), late-night eating (0.86 [0.75-0.98]), and current smoking (0.89 [0.80-0.99]) were significantly associated with non-adherence. CONCLUSIONS: Skipping breakfast, late-night eating and current smoking were significantly associated with medication adherence, suggesting that clinicians pay attention to those health-related behaviors to achieve good medication adherence.