Oral Hypoglycemic Drugs Research Articles

Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.

A PKPD interaction between Momordica charantia and oral hypoglycemic drug –dapagliflozin in STZ induced hyperglycemic rats

Traditional medications obtained from the medicated herbal plants are used by about maximum percentage of world population for different chronic disease condition. Diabetes (Hyperglycemia- high blood sugar level) is a very important metabolic disorder in different developed, developing countries including India. It providing to very serious complications on health of human beings, especially in the rural and subruralareas. Hence, the research studies required to be subjected to pharmacodynamic and pharmacokinetic studies in order to determine effect of Momordica charantia herb on the hyperglycaemic patients who are taking the therapy with synthetic drugs. This study was to discover the influence of Momordica charantia on the pharmacokinetics and pharmacodynamics of Dapagliflozinand in rats. Results have proved the negative (decrease) effect of Momordica charantia on pharmacokinetics but positive (increase) effect on pharmacodynamics of Dapagliflozin.

Comparison Of Quality Of Sleep Between Diabetic And Non-Diabetic Population Using Pittsburgh Sleep Quality Index

Background: Sleep is an essential event that effects quality of life and hormonal balance in human body. The association between sleep and diabetes is bi-directional. Methods: This study was conducted with a case control design in the Department of Medicine of Combined Military Hospital Peshawar between June 2022 to November 2022. Results: . Mean age of study population was 51.1±12.94 years with 46% females and 54% males. Majority population was educated up to matriculation with BMI in normal (18.5-24.9 kg/m2) range. There was no statistical difference in demographic data amongst diabetic and control group . Avg HbA1c was 8.546% ± 1.57% in the diabetic group and 5.712% ± 0.49% in control group. As per PSQI questionnaire 47 (47%) participants were good sleeper across the study population, which included 17 out 50 (34%) individuals in the diabetic and 30 out of 50 (60%) in control group. This equated to statistically significant difference amongst two group with a p value 0.007. A statistically significant difference (p = 0.001) was also seen in PSQI score between diabetic and control groups (9.40 ± 5.82 vs 5.98 ± 4.85 respectively). Diabetics had 2.9 times odds (95% confidence interval 1.29-6.57, p = 0.01) of having bad quality sleep as compared to controls. In the diabetic group majority were males educated up to matriculate having medium adherence treated with both oral hypoglycemic drugs and insulin having 3 or more comorbid condition with hypertension being most prevalent single comorbid disease. Conclusion: By strict glycemic control in diabetics we can imove their quality of sleep Interventions to improve sleep hygiene can be suggested to patients by diabetes educators as part of diabetes self-management education programs.

Pharmacoecomonic study of oral antidiabetic drugs available in Indian pharmaceutical market

Background: Diabetes mellitus is a metabolic disorder requiring lifelong medication which further adds to comorbidity. Cost of the drug pays an important role in adherence and compliance to the treatment. There is a wide variation in prices of oral hypoglycemic drugs available in Indian pharmaceutical market. Aims and objectives of the study was planned to evaluate cost of oral antidiabetic drugs of various brands currently available in Indian market either as single drug or in combination. Methods: Cost of antidiabetic medications manufactured by various pharmaceutical companies in the same strength and dosage form was obtained from the price list provided by various pharmaceutical companies in current index of medical specialties December 2022-March2023. The cost ratio and percentage price variation for each formulation was calculated and analyzed. Results: Among single antidiabetic drugs, Tab. Metformin 500 mg shows highest percentage price variation (809%) and highest cost ratio (9.09). Among fixed dose combinations, Tab. Glibenclamide 5 mg + Tab. Metformin 500 mg shows highest percentage price variation 300.8% and highest cost ratio 4. Conclusions: Our study shows that there is high price variation for oral anti diabetics. It is important to bring awareness about wide variation in prices so that drug cost can be reduced and made affordable to common man which plays major role in compliance of patient.

Impact of Clinical Pharmacist in Collaboration with Physicians in Minimizing Drug Therapy Problems among Hypertension and Diabetes Mellitus

It is estimated that one in six people worldwide, or nearly one billion, are affected by high blood pressure(1).7.6 million deaths per annum worldwide(1). Globally, an estimated 462 million individuals are affected by type 2 diabetes, corresponding to 6.28% of the world's population(2). More than 1 million deaths were attributed to this condition in 2017 alone, ranking it as the ninth leading cause of mortality(2). The clinical pharmacist’s role is to assess the status of the patient's health problems and determine whether the prescribed medications are optimally meeting the patient's needs and goals of care(3). To study the impact of Clinical pharmacists in collaboration with Physicians in minimizing drug-therapy problems among Hypertension and Type 2 Diabetes Mellitus. A Prospective interventional study was carried out at Sangareddy District Government Hospital for a period of 6 months. A structured proforma was designed to collect patient data. Descriptive analysis was analyzed using MS Excel 2019 MSO to describe demographics, Drug-Related problems, Clinical pharmacist -Physician Intervention, Antihypertensive Drugs, and oral hypoglycemic drug usage. Out of 133 study individuals, the majority of subjects had a Sub-therapeutic goal (44%), followed by an Inappropriate Drug[41%]. The majority of patients had at least one DRP(82%). The most common Intervention performed was the addition of appropriate drugs(31%), followed by cessation of drugs(30%). Our study concludes that the collaboration of Clinical Pharmacists with Physicians can assist in identifying and preventing drug-related problems through interventions and their expertise in pharmacotherapy can assist in providing rational drug therapy.

Stability-Indicating Densitometric Analysis of Evogliptin Tartrate in Bulk and Tablet Dosage Form.

Evogliptin tartrate is a novel dipeptidyl peptidase (DPP-4) inhibitor very recently introduced into the market as an oral hypoglycemic drug. The literature review has revealed no reports of stability-indicating analytical methods so far for evogliptin tartrate. So, the goal of this study was to develop and validate a stability indicating HPTLC method for evogliptin tartrate in bulk and tablet dosage form. For the study pre-coated plates of silica gel 60F254 were utilized as stationary phase and acetonitrile: water: formic acid (30:8:2; v/v/v) was used as a developing system. The densitometric scanning was performed at 270 nm and the method was validated as per ICH guidelines for accuracy, precision, LOD and LOQ. Evogliptin was subjected to forced degradation studies and was exposed to various stress conditions like acid/base hydrolysis, oxidation, thermal stress, and UV light. The developed method furnished compact spots of evogliptin (Rf 0.62 ± 0.05) and was linear in the concentration range of 1-5 µg/spot. The lowest detection and quantitation values were found to be 0.331 and 1.003 µg/spot respectively and % recovery was found to be 101.09. The low RSD values (below 2%) for intra-day (% RSD 1.86) and inter-day (% RSD 1.43) precision studies demonstrated the preciseness of the developed method. All the validation parameters were found to be within the acceptable range prescribed by ICH guidelines indicating that the developed method was accurate, precise, selective, and reproducible. A total of five degradation products were resolved under various stress conditions. The proposed method has a promising application commercially for identification, routine quantitative determination, and monitoring of stability of the evogliptin tartrate in bulk and tablet dosage forms to guarantee its safety, efficacy, and quality. Moreover, the developed method will also help in formulation development and in determining the appropriate storage conditions.

MODY6 with NEUROD1 Mutation an Unusual Presentation in Adolescent: A Case Report

MODY( Maturity onset diabetes of young) is a rare monogenic type of diabetes and which comprises 1-5 % of all diabetes cases [1]. It is often misdiagnosed as either type 1 or type 2 diabetes mellitus in children and adolescents due to common clinical signs and symptoms. With the availability of genetic testing, an increasing number of cases of MODY are being reported. We are reporting a case of 15 years old male child who presented with hyperglycemia without metabolic acidosis. He started on standard insulin regimen in view of suspected type1 diabetes. Later he was detected with NEUROD1 mutation, which is associated with MODY6, and the child was put on oral hypoglycemic drug, Metformin. At present the child is not on medication and is euglycemic. NEUROD1 is one of the least reported mutations in MODY6, only 5-6 cases are reported from India, and we report the youngest case.

Modern understanding of latent autoimmune diabetes in adults

Latent autoimmune diabetes in adults (LADA) according to various sources is from 4 to 12% of all cases of type 2 diabetes mellitus (T2DM). Its uniqueness lies in the simultaneous combination of autoantibodies to β-cells (characteristic of T1DM) and the possibility of treatment with oral hypoglycemic drugs (characteristic of T2DM) for at least 6 months. This is based on the pathogenesis common for T1DM and T2DM — the presence of an autoimmune reaction with the simultaneous involvement of adaptive and innate immunity, as well as, to a lesser extent, insulin resistance and a number of components of the metabolic syndrome. LADA has more in common with T1DM — the same stages in the development of the disease, from genetic predisposition to the undoubted development of insulin dependence, the difference lies in the duration of each of the periods and the age of manifestation. LADA is characterized by an older age of manifestation of 30–35 years and a slower rate of destruction of β-cells. This article presents data on the diagnosis, progress of LADA, its similarities and differences with other types of DM, and immunological features. The article also analyzes the modern approach to the treatment of patients with LADA and promising methods of treatment. The search for information was processing in published sources attached to the search engines PubMed, Google Scholar, Scopus, Web of Science, eLibrary.ru over the past 10 years. The following medical subject headings were used: latent autoimmune diabetes in adults, diabetes mellitus type 1 and 2, immunology, pancreas, genetic, treatment in various combinations using OR and AND logical operators.

Fabrication and characterization of coated microneedle patches based on PEGDA for transdermal administration of metformin.

Type 2 diabetes is one of the major challenges that the world is facing today. However, metformin (MET) as most type 2 diabetics' first-line oral hypoglycemic drug may cause serious side effects such as gastrointestinal irritation and nausea which reduce the patients' medication compliance. Therefore, the aim of the study was to design a safe and effective self-treatment device for the delivery of MET. Here, a kind of coated microneedle (MN) patches based on poly(ethylene glycol)diacrylate (PEGDA) were prepared by a two-step casting method and photopolymerization process for transdermal administration of MET. The needles wrapped with drug-loaded hyaluronic acid (HA) coating showed promising mechanical properties and drug delivery ability that allowed them to penetrate the skin barrier for rapid drug delivery, and they had no skin irritancy. The in vivo experiment of type 2 diabetic rats showed a satisfying hypoglycemic effect of the coated MN patches. The study shows that the prepared MN patches will be a potential method for the treatment of type 2 diabetes in the future.

Analysis of Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Case-Control Study

The incidence of DM (Diabetes mellitus) is rising all over the world. Inadequate glycemic control in patients having type 2 DM presents a higher risk of developing associated complications. This study was conducted to analyse the information on the management of diabetes in standard clinical practice. The study provides description of clinical profile of subjects with DM2 (Type 2 diabetes mellitus) under treatment with insulin and oral hypoglycemic drugs. A total of 500 patients diagnosed with DM2, and equal number of age and gender matched controls participated in the study. Clinical data including previous medical history of diabetes, medication taken for treatment, comorbidities, pre-prandial and post-prandial plasma glucose, and glycosylated haemoglobin (HbA1c) levels were collected. It was observed that among all participants 59.4% were obese and 30.6% were overweight. It was also found that 57.4% patients were suffering from hypertension while 56% were suffering from hyperlipidemia. Patient’s data about family history revealed that 62.2% patients had both or either of the two parents suffering from diabetes. The mean fasting and random plasma glucose levels were found to be 178.6mg/dL and 245.4mg/dL respectively. Moreover, only 8% patients achieved glycemic goals and had HbA1c levels under normal limits. The study reveals that lack of awareness and poor self-care can increase the risk of comorbidities associated with type 2 DM. This study provides a basis for further investigations on quality of life of diabetic patients in various regions of Pakistan.

Analysis of Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Case-Control Study

The incidence of DM (Diabetes mellitus) is rising all over the world. Inadequate glycemic control in patients having type 2 DM presents a higher risk of developing associated complications. This study was conducted to analyse the information on the management of diabetes in standard clinical practice. The study provides description of clinical profile of subjects with DM2 (Type 2 diabetes mellitus) under treatment with insulin and oral hypoglycemic drugs. A total of 500 patients diagnosed with DM2, and equal number of age and gender matched controls participated in the study. Clinical data including previous medical history of diabetes, medication taken for treatment, comorbidities, pre-prandial and post-prandial plasma glucose, and glycosylated haemoglobin (HbA1c) levels were collected. It was observed that among all participants 59.4% were obese and 30.6% were overweight. It was also found that 57.4% patients were suffering from hypertension while 56% were suffering from hyperlipidemia. Patient’s data about family history revealed that 62.2% patients had both or either of the two parents suffering from diabetes. The mean fasting and random plasma glucose levels were found to be 178.6mg/dL and 245.4mg/dL respectively. Moreover, only 8% patients achieved glycemic goals and had HbA1c levels under normal limits. The study reveals that lack of awareness and poor self-care can increase the risk of comorbidities associated with type 2 DM. This study provides a basis for further investigations on quality of life of diabetic patients in various regions of Pakistan.

Research Progress of α-glucosidase Inhibitors of Medicinal and Edible Homologous Plants and Their use in the Treatment of Diabetes

Diabetes is one of the common diseases in modern society, which cannot be cured. It has a significant impact on the lives of patients. Type II diabetes patients mainly rely on oral hypoglycemic drugs and insulin injection to maintain blood sugar balance. While traditional hypoglycemic medications such as insulin, biguanides, and sulfonylureas may reduce blood glucose for a brief period of time, it often has some side effects and can lead to body dependence. Therefore, as a safe and economical natural hypoglycemic plant polysaccharide, it has received more and more attention. Natural active ingredients with glucosidase inhibitory activity from plants will become potential resources for research and treatment of type II diabetes. A large number of medicinal and food homologous plants have been identified as an important source of glucosidase inhibitors, and have received widespread attention. This article focuses on homologous medicinal and edible plant species and their application in diabetes treatment, here, we reviewed functional components with glucosidase inhibitory activity in homologous medicinal and edible plants and their state of research. In this paper, we hope to provide a theoretical benchmark for the development of drugs for type II diabetes from natural plants.

Fungal Metabolites: A Potential Source of Antidiabetic Agents with Particular Reference to PTP1B Inhibitors.

Diabetes is a growing health concern worldwide because it affects people of all age groups and increases the risk of other diseases such as renal impairment and neural and cardiovascular disorders. Oral hypoglycemic drugs mainly control diabetes; however, their associated side effects limit their use in patients with other complications. PTP1B is a viable drug target to explore new antidiabetic drugs. PTP1B acts as a negative regulator of the insulin-signaling pathway, and therefore, PTP1B inhibitors display antihyperglycemic activity. Several classes of compounds from natural and synthetic sources act as PTP1B inhibitors. Fungi are comprehensive in their diversity and recognized as a valuable source for therapeutically active molecules. In recent years, researchers have reported diverse classes of fungal secondary metabolites as potent PTP1B inhibitors. Some metabolites such as 6-O-methylalaternin, fumosorinone A, nordivaricatic acid, and the divarinyl divarate showed good activity and can be taken forward as a lead to develop novel PTP1B inhibitors and antidiabetic drugs. Therefore, the present review focuses on the fungal metabolites identified in the last five years possessing PTP1B inhibitory activity. A total of 128 metabolites are reviewed. Their fungal species and source, chemical structure, and activity in terms of IC50 are highlighted.

Cavernosal abscess and primary scrotal calcinosis in the diabetic patient: A case report and review of literature

Abstract A cavernosal abscess is a rare urological condition to occur. It is classified as primary and secondary. The primary is mostly idiopathic, whereas the secondary is associated with some precipitating factors. Most of the cases were diagnosed clinically. In some cases, imaging such as an ultrasound of the local region or magnetic resonance imaging may be required. Cavernosal abscesses can be treated using a minimally invasive procedure such as image-guided drainage or incision and drainage along with systemic antibiotics. A 52-year-old uncircumscribed uncontrolled diabetic patient presented with a complaint of swelling in the penile region for the 1-week duration. He also complains of pain in the penile region for a 5-day duration. He is a known case of type 2 diabetes on oral hypoglycemic drugs for the past 2 years. Clinical examination confirmed the diagnosis of cavernosal abscess. The patient underwent circumcision with incision and drainage of abscess under higher antibiotic coverage (vancomycin and metronidazole). The patient underwent local excision of primary scrotal calcinosis after 1 month. The patient is followed up for more than 2 years without any evidence of recurrence or impotence. The cavernosal abscess is one of the rare urological conditions, which needs immediate surgical intervention to reduce future complications such as erectile dysfunction and recurrent abscess. Uncontrolled diabetes has a high chance of developing cavernosal abscesses even without precipitating factors.

Association Between Diabetic Control And Anti-Diabetic Medication Adherence Using 8-Point Morisky Medication Adherence Scale In Local Population Of Khyber Pakhtunkhwa

Abstract:
 Background: Drug adherence to medications in diabetes is very necessary for strict glycemic control. Many factors in diabetics are associated with low adherence to drugs resulting in complications.
 Methods: This research was conducted as an observational study with cross-sectional study design. It was scheduled between July 2022 to December 2022 in medical outpatient department of Combined Military Hospital, Peshawar
 Results: 115 individuals were inducted over a period of 6 months from medical OPD ex Combined Military Hospital Peshawar. Five patients failed to follow-up with research team resulting in a total of 110 participants included in results. Average age across the study sample was 50.25 ± 11.97 years with 58 (52.73%) males and 52 (47.27%) females. Most participant in our study sample were educated up to matriculation with BMI <25kg/m2.
 Average duration of diabetes across the sample was 6.1 ± 3.69 years. In treatment options, 53 (48.18%) individuals were only managed with oral therapy, 16 (14.55%) on insulin only while 41 (37.27%) were prescribed with both oral hypoglycemic drugs and insulin. Most common comorbid across study population was hypertension, seen in 59 (53.94%) diabetic patients, followed by cataract in 41 (37.47%) and IHD in 33 (30%) patients.
 In all 110 individuals, only 29 (26.36%) individuals had good glycemic control i.e., HbA1c <7% with average glycosylated hemoglobin percentage measuring 8.29% ± 1.59%. As per MMAS-8 score, 25 (22.73%) patients reported good adherence, 31 (28.18%) patients reported fair adherence while rest 54 (49.09%) were found to have bad adherence. Average MMAS-8 score was 5.17.
 Conclusion: There is a correlation between medication adherence as measured by MMAS-8 score with control of diabetes as measured by HbA1c score in the range of 1.824% across the range of MMAS-8 score from 0-8. Sleep quality, BMI and multiple comorbid conditions were also linked with raised HbA1c.
 Key words: Drug adherence, Morisky Medication Adherence Scale, Diabetes, Non-diabetes, diabetic medications

Direct medical cost and medications for patient of diabetes retinopathy in Beijing, China, 2016–2018

AimsMedications and costs of drug for diabetic retinopathy in outpatient in China have not been evaluated. The purpose of this study was to evaluate the hypoglycemic drugs and medical costs of diabetic retinopathy patients in the Beijing medical insurance system, analyze the characteristics of outpatient treatment, and investigate the changes in the quantity and cost of hypoglycemic drugs from 2016 to 2018. MethodsThis is a retrospective observational study, including diabetic patients with outpatient records in Beijing medical insurance from 2016 to 2018. Data on oral hypoglycemic drugs, insulin and non-hypoglycemic drugs, complications, treatment strategies, and annual medical costs were recorded. ResultsA total of 2,853,036 diabetic patients in Beijing medical insurance were enrolled in this study. 4.19 %–4.67 % of patients were diagnosed with retinopathy. Patients with retinopathy have more diabetic complications (1.65 ± 0.71 vs 0.18 ± 0.44. p < .0001), and use more drugs (5.11 ± 2.60 vs 3.85 ± 2.34, p < .0001), the annual total drug cost is also higher (¥ 13,836 ± 11,244 vs ¥ 10,030 ± 9375, p < .0001). The numbers of medication in retinopathy patients increased (5.11 ± 2.60 vs 4.95 ± 2.57, p < .0001), and the annual total drug cost (¥13,836 ± 11,244 vs ¥15,642 ± 13,344, p < .0001) decreased in 2018 compared with 2016. ConclusionsPatients with retinopathy were associated with more complications. Compared with patients without retinopathy, the number of medications and total medical costs were significantly increased. From 2016 to 2018, there was an increase in the number of medication treatments for patients with retinopathy, but a decrease in cost.

Optimization of Potential Nanoemulgels for Boosting Transdermal Glimepiride Delivery and Upgrading Its Anti-Diabetic Activity.

Transdermal drug delivery has been widely adopted as a plausible alternative to the oral route of administration, especially for drugs with poor systemic bioavailability. The objective of this study was to design and validate a nanoemulsion (NE) system for transdermal administration of the oral hypoglycemic drug glimepiride (GM). The NEs were prepared using peppermint/bergamot oils as the oil phase and tween 80/transcutol P as the surfactant/co-surfactant mixture (Smix). The formulations were characterized using various parameters such as globule size, zeta potential, surface morphology, in vitro drug release, drug-excipient compatibility studies, and thermodynamic stability. The optimized NE formulation was then incorporated into different gel bases and examined for gel strength, pH, viscosity, and spreadability. The selected drug-loaded nanoemulgel formulation was then screened for ex vivo permeation, skin irritation, and in vivo pharmacokinetics. Characterization studies revealed the spherical shape of NE droplets with an average size of ~80 nm and a zeta potential of -11.8 mV, which indicated good electrokinetic stability of NE. In vitro release studies revealed enhanced drug release from the NE formulation compared to the plain drug. GM-loaded nanoemulgel showed a 7-fold increment in drug transdermal flux compared to plain drug gel. In addition, the GM-loaded nanoemulgel formulation did not elicit any signs of inflammation and/or irritation on the applied skin, suggesting its safety. Most importantly, the in vivo pharmacokinetic study emphasized the potential of nanoemulgel formulation to potentiate the systemic bioavailability of GM, as manifested by a 10-fold rise in the relative bioavailability compared to control gel. Collectively, transdermal NE-based GM gel might represent a promising alternative to oral therapy in the management of diabetes.

Biobioequivalence of Immediate Release-Glibenclamide Five mg Tablets A Comparative Study in Healthy Volunteers

Glibenclamide is a sulfonylurea oral hypoglycemic drug, which has long been in clinical use for diabetes mellitus.

Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58–0.90 respectively OR = 2.24, 95% CI 1.60–3.13).We found significant correlation for change in ECAC volume with diabetes (β = 0.46, 95% CI 0.03–0.89) and baseline ECAC volume (β = 0.81, 95% CI 0.73–0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48–3.16), age (OR = 2.00, 95% CI 1.19–3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20–11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (β = 0.92, 95% CI 1.59–7.02), use of oral hypoglycemic drugs (β = 0.86, 95% CI 0.12–1.59) and baseline ICAC volume (β = 0.71, 95% CI 0.55–0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.

Dapagliflozin inhibits the activity of lateral habenula to alleviate diabetes mellitus-induced depressive-like behavior

The prevalence of depression in diabetes mellitus (DM) patients is very high, and it severely impacts the prognosis and quality of life of these patients. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new type of oral hypoglycemic drugs, have been shown to alleviate depressive symptoms in DM patients; however, the mechanism underlying this effect is not well understood. The lateral habenula (LHb) plays an important role in the pathogenesis of depression expresses SGLT2, suggesting that the LHb may mediate antidepressant effects of SGLT2 inhibitors. The current study aimed to investigate the involvement of the LHb in the antidepressant effects of the SGLT2 inhibitor dapagliflozin. Chemogenetic methods were used to manipulate the activity of LHb neurons. Behavioral tests, Western blotting, immunohistochemistry, and neurotransmitter assays were used to determine the effects of dapagliflozin on the behavior of DM rats, AMP-activated protein kinase (AMPK) pathway and c-Fos expression in the LHb and 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the dorsal raphe nucleus (DRN). We found that DM rats demonstrated depressive-like behavior, increased c-Fos expression, and decreased AMPK pathway activity in the LHb. Inhibition of LHb neurons alleviated the depressive-like behavior of DM rats. Both systemic and local LHb administration of dapagliflozin alleviated the depressive-like behavior and reversed the changes of the AMPK pathway and c-Fos expression in the LHb of DM rats. Dapagliflozin, when microinjected into the LHb, also increased 5-HIAA /5-HT in the DRN. These results suggest that dapagliflozin directly acts on the LHb to alleviate DM-induced depressive-like behavior and that the underlying mechanism involves activating the AMPK signaling pathway, leading to the inhibition of LHb neuronal activity, which in turn increases serotonergic activity in the DRN. These results will help develop new strategies for the treatment of DM-induced depression.