The Health Economics of Automated Insulin Delivery Systems and the Potential Use of Time in Range in Diabetes Modeling: A Narrative Review.

Intensive therapy with exogenous insulin is the treatment of choice for individuals living with type 1 diabetes (T1D) and some with type 2 diabetes, alongside regular glucose monitoring. The development of systems allowing (semi-)automated insulin delivery (AID), by connecting glucose sensors with insulin pumps and algorithms, has revolutionized insulin therapy. Indeed, AID systems have demonstrated a proven impact on overall glucose control, as indicated by effects on glycated hemoglobin (HbA1c), risk of severe hypoglycemia, and quality of life measures. An alternative endpoint for glucose control that has arisen from the use of sensor-based continuous glucose monitoring is the time in range (TIR) measure, which offers an indication of overall glucose control, while adding information on the quality of control with regard to blood glucose level stability. A review of literature on the health-economic value of AID systems was conducted, with a focus placed on the growing place of TIR as an endpoint in studies involving AID systems. Results showed that the majority of economic evaluations of AID systems focused on individuals with T1D and found AID systems to be cost-effective. Most studies incorporated HbA1c, rather than TIR, as a clinical endpoint to determine treatment effects on glucose control and subsequent quality-adjusted life year (QALY) gains. Likely reasons for the choice of HbA1c as the chosen endpoint is the use of this metric in most validated and established economic models, as well as the limited publicly available evidence on appropriate methodologies for TIR data incorporation within conventional economic evaluations. Future studies could include the novel TIR metric in health-economic evaluations as an additional measure of treatment effects and subsequent QALY gains, to facilitate a holistic representation of the impact of AID systems on glycemic control. This would provide decision makers with robust evidence to inform future recommendations for health care interventions.

Vitamin D supplementation modulates glycated hemoglobin (HBA1c) in diabetes mellitus.

Diabetes is a metabolic illness that increases protein glycosylation in hyperglycemic conditions, which can have an impact on almost every organ system in the body. The role of vitamin D in the etiology of diabetes under RAGE (receptor for advanced glycation end products) stress has recently received some attention on a global scale. Vitamin D's other skeletal benefits have generated a great deal of research. Vitamin D's function in the development of type 1 and type 2 diabetes is supported by the discovery of 1,25 (OH)2D3 and 1-Alpha-Hydroylase expression in immune cells, pancreatic beta cells, and several other organs besides the bone system. A lower HBA1c level, metabolic syndrome, and diabetes mellitus all seems to be associated with vitamin D insufficiency. Most of the cross-sectional and prospective observational studies that were used to gather human evidence revealed an inverse relationship between vitamin D level and the prevalence or incidence of elevated HBA1c in type 2 diabetes. Several trials have reported on the impact of vitamin D supplementation for glycemia or incidence of type 2 diabetes, with varying degrees of success. The current paper examines the available data for a relationship between vitamin D supplementation and HBA1c level in diabetes and discusses the biological plausibility of such a relationship.

Clinical Evaluation of a Novel, Patented Green Coffee Bean Extract (GCB70®), Enriched in 70% Chlorogenic Acid, in Overweight Individuals.

OBJECTIVE: Obesity and overweight are challenging health problems of the millennium that lead to diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis. Green coffee bean exhibited significant promise in healthy weight management, potentiating glucose-insulin sensitization and supporting liver health. The safety and efficacy of a novel, patented water-soluble green coffee bean extract (GCB70® enriched in 70% total chlorogenic acid and <1% caffeine) was investigated in 105 participants for 12 consecutive weeks. An institutional review board and Drugs Controller General (India) (DCGI) approvals were obtained, and the study was registered at ClinicalTrials.gov. METHOD: Body weight, body mass index (BMI), waist circumference, lipid profile, plasma leptin, glycosylated hemoglobin (HbA1c), and total blood chemistry were assessed over a period of 12 weeks of treatment. Safety was affirmed. RESULTS: GCB70 (500 mg BID) supplementation significantly reduced body weight (approximately 6%; p = 0.000**) in approximately 97% of the study population. About a 5.65% statistically significant reduction (p = 0.000**) in BMI was observed in 96% of the study volunteers. Waist circumference was significantly reduced by 6.77% and 6.62% in 98% of the male and female participants, respectively. Plasma leptin levels decreased by 13.6% in 99% of the study population as compared to the baseline value. Upon completion of 12 weeks' treatment, fasting glucose levels decreased by 13.05% (p = 0.000**) in 79% of the study population. There was a statistically significant decrease in HbA1c levels in both male and female participants (p = 0.000**), while 86.7% of the study participants showed a statistically significant decrease in thyroid-stimulating hormone (TSH) levels (p = 0.000**). The mean decrease in TSH levels on completion of the treatment was 14.07% in the study population as compared to baseline levels. Total blood chemistry analysis exhibited broad-spectrum safety. CONCLUSIONS: This investigation demonstrated that GCB70 is safe and efficacious in healthy weight management.

A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

BACKGROUND: As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. OBJECTIVE: This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. METHODS: This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. RESULTS: In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). CONCLUSIONS: Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

Correlation of Fasting Blood Sugar and Glycated Hemoglobin (HbA1c) With Thiamine Levels in Diabetic Patients.

Introduction It has been discovered that low levels of thiamine reserves in the body are related to diabetes mellitus (DM) because thiamine directly influences carbohydrate metabolism. Therefore, the purpose of this study was to assess several metabolic variables and blood thiamine levels in patients with type 1 and type 2 DM and compare them with those in a control group of healthy individuals. Methods This case-control study was conducted at multiple diabetic outpatient centers in Karachi. A total of 90 participants, who were divided into three groups, each containing 30 individuals, were chosen using a convenient non-probability sampling technique. Group A served as the control group and consisted of healthy, non-diabetic individuals. Groups B and C contained subjects with type 1 and type 2 DM, respectively. Descriptive analysis was reported as mean standard deviation, whereas gender and comorbidities were expressed as frequencies and percentages. The chi-square test and Pearson's correlation coefficient were used to determine the associations of the variables with type 1 DM, type 2 DM, and controls. Results The study results revealed statistically significant differences between controls, type 1 and type 2 DM, in the means of blood glucose levels and all lipid profiles, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), random blood sugar (RBS), serum thiamine, triglycerides (p < 0.001), high-density lipoprotein (HDL) (p = 0.014), and total cholesterol (p = 0.013). Furthermore, it was shown that among the control group, type 1 and type 2 DM, HbA1c, and FBS were insignificantly correlated with thiamine levels, whereas the HbA1c and FBS of the combined diabetic groups were significantly correlated with the thiamine level (r = 0.465, p < 0.001) and (r = 0.360, p = 0.005), respectively, where 'r' is the Pearson correlation coefficient. Additionally, HbA1c and FBS in the combined three groups were significantly correlated with the thiamine level (r = -0.626, p < 0.001) and (r = -0.561, p < 0.001), respectively. Conclusion This study concluded that patients with type 1 and type 2 DM had significantly higher levels of FBS, RBS, HbA1c, triglycerides, and total cholesterol than controls. Furthermore, both type 1 and type 2 DM patients' serum thiamine and HDL levels were observed to be considerably lower than those of controls. Additionally, among both types of DM and controls, there was a strong correlation between FBS and HbA1c. Therefore, we recommend that serum thiamine levels be routinely monitored in diabetic patients, and thiamine supplementation should be considered to avoid complications, especially vascular complications of DM.

Ayurveda approach in the treatment of type 2 diabetes mellitus - A case report.

Diabetes mellitus is a growing concern all over the world. There are no many published literature available documenting the effectiveness of Ayurveda intervention on diabetes mellitus. This report is about a case in which successful reversal of diabetes mellitus was achieved in a patient who reported with glycosylated Hb percentage (HbA1C) as high as 14.87%. The patient had classical symptoms of diabetes mellitus viz. excessive thirst, fatigue and frequent urination. His fasting blood glucose level was 346 mg/dl and post prandial glucose level of 511 mg/dl. Further more his HbA1C was as high as 14.87%, thus diagnosed with diabetes mellitus. Based on his specific clinical symptoms the patient was diagnosed with kaphaja prameha. Treatment was given according to classical Ayurveda intervention for kaphaja prameha. The patient responded well to the treatment. His HbA1C reduced to 6.05% in a span of eight months. The case report shows the effectiveness of Ayurvedic intervention in diabetes mellitus. It is limited in its scope as it is a case report, nevertheless this can be taken up as an information that may lead to new research and advances in the field of clinical practice in Ayurveda.

Effects of Tocotrienol-Rich Fraction Supplementation in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There are a large number of studies that have reported benefits of tocotrienol-rich fraction (TRF) in various populations with different health status. To date, no systematic reviews have examined randomized controlled trials (RCTs) on the effect of TRF supplementations specifically in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to examine the changes in HbA1c (glycated hemoglobin), blood pressure, and serum Hs-CRP (C-reactive protein high sensitivity) levels at post-TRF supplementation. Online databases including PubMed, Scopus, OVID Medline, and Cochrane Central Register of Controlled Trials were searched from inception until March 2023 for RCTs supplementing TRF in patients with T2DM. A total of 10 studies were included in the meta-analysis to estimate the pooled effect size. The Cochrane Risk-of-Bias (RoB) Assessment Tool was utilized to evaluate the RoB in individual studies. The meta-analysis revealed that TRF supplementation at a dosage of 250-400 mg significantly decreased HbA1c (-0.23, 95% CI: -0.44, -0.02, P < 0.05, n = 754), particularly where the intervention duration is less than 6 mo (-0.47%, 95% CI: -0.90, -0.05, P < 0.05, n = 126) and where duration of diabetes is less than 10 y (-0.37, 95% CI: -0.68, -0.07, P < 0.05, n = 83). There was no significant reduction in systolic and diastolic blood pressure and serum Hs-CRP (P > 0.05). The present meta-analysis demonstrated that supplementing with TRF in patients with T2DM decreased HbA1c but does not decrease systolic and diastolic blood pressure and serum Hs-CRP.

Efficacy of ozone therapy on visual evoked potentials in diabetic patients.

BACKGROUND: The involvement of the central nervous system is a frequent yet underestimated complication of diabetes mellitus. Visual evoked potentials (VEP) are a simple, sensitive, and noninvasive method for detecting early alterations in central optic pathways. The objective of this paralleled randomized controlled trial was to evaluate the impact of ozone therapy on visual pathways in diabetic patients. METHODS: Sixty patients with type 2 diabetes visiting clinics of Baqiyatallah university in Tehran (Iran) hospital were randomly assigned to two experimental groups: Group 1 (N = 30) undergoing a cycle of 20 sessions of systemic oxygen-ozone therapy in addition to standard therapy for metabolic control; Group 2 (N = 30)-serving as control-receiving only standard therapy against diabetes. The primary study endpoints were two VEP parameters; P100 wave latency and P100 amplitude at 3 months. Moreover, HbA1c levels were measured before the start of treatment and three months later as secondary study endpoint. RESULTS: All 60 patients completed the clinical trial. P100 latency significantly reduced at 3 months since baseline. No correlation was found between repeated measures of P100 wave latency and HbA1c (Pearson's r = 0.169, p = 0.291). There was no significant difference between baseline values and repeated measures of P100 wave amplitude over time in either group. No adverse effects were recorded. CONCLUSIONS: Ozone therapy improved the conduction of impulses in optic pathways of diabetic patients. The improved glycemic control following ozone therpay may not fully explain the reduction of P100 wave latency though; other mechanistic effects of ozone may be involved.

Treatment on Nature's lap: Use of herbal products in the management of hyperglycemia.

Diabetes mellitus (DM) is characterized by persistently elevated blood glucose concentration that lead to multisystem complications. There are about 400 medicinal plants cited to have a beneficial effect on DM. We must choose products wisely based on data derived from scientific studies. However, a major obstacle in the amalgamation of herbal medicine in modern medical practices is the lack of clinical data on its safety, efficacy and drug interaction. Trials of these herbal products often underreport the side effects and other crucial intervention steps deviating from the standards set by Consolidated Standards of Reporting Trials. Due to a lack of knowledge of the active compounds present in most herbal medicines, product standardization is difficult. Cost-effectiveness is another issue that needs to be kept in mind. In this mini-review, we focus on the anti-hyperglycemic effect of herbal products that are commonly used, along with the concerns stated above.

Self-monitoring of blood glucose two-weekly versus weekly in gestational diabetes on nutrition therapy: A randomized trial.

OBJECTIVE: To evaluate 4-point per day self-monitoring of blood glucose (SMBG) every 2 weeks compared with every week. METHODS: A total of 104 patients with lifestyle-controlled gestational diabetes (GDMA1) were randomized to 2-weekly or weekly 4-point per day (fasting on awakening and 2-h post-meals) SMBG. Primary outcome was the change in glycated hemoglobin (HbA1c) level from enrollment to 36 weeks of pregnancy across trial arms. The non-inferiority margin was an HbA1c increase of 0.2%. RESULTS: The mean difference for change in HbA1c from enrollment to 36 weeks was 0.003% (95% confidence interval [CI] -0.098% to +0.093%), within the 0.2% non-inferiority margin. The change in HbA1c level increased significantly within both trial arms-0.275% ± 0.241% (P < 0.001) in 2-weekly arm versus 0.277% ± 0.236% (P < 0.001) in the weekly arm. Participants randomized to 2-weekly SMBG were significantly less likely to receive anti-glycemic treatment-5/52 (9.6%) versus 14/50 (28.0%) (relative risk 0.34, 95% CI 0.13-0.88; P = 0.017). All secondary outcomes-maternal weight gain, preterm delivery, cesarean delivery, birthweight, and neonatal admission-were not significantly different. CONCLUSIONS: In GDMA1, 2-weekly is non-inferior to weekly SMBG on the change in HbA1c level. Two-weekly SMBG appeared to be adequate for monitoring women with GDMA1. CLINICAL TRIAL REGISTRATION: This study was registered in ISRCTN registry on March 25, 2022 with trial identification number: ISRCTN13404790 (https://doi.org/10.1186/ISRCTN13404790). The first participant was recruited on April 12, 2022.

The Impact of Providing Material Benefits to Improve Access to Food on Clinical Parameters, Dietary Intake, and Household Food Insecurity in People with Diabetes: A Systematic Review with Narrative Synthesis.

The high cost of healthy foods makes maintaining a healthy dietary pattern challenging, particularly among people with diabetes who are experiencing food insecurity. The objectives of this study were to: 1) review evidence on the impact of providing material benefits (e.g., food coupons/vouchers, free food, or financial subsidies/incentives) to improve access to food on clinical parameters, dietary intake, and household food insecurity in people with diabetes, and 2) review relevant economic evidence. Six databases were searched from inception to March 2023 for longitudinal studies with quantitative outcomes. Twenty-one studies were included in the primary review and 2 in the economic analysis. Risk of bias was high in 20 studies and moderate in 1 study. The number of randomized controlled trials and nonrandomized studies reporting statistically significant improvement, alongside Grading of Recommendations Assessment, Development, and Evaluation (GRADE) certainty of the evidence was: HbA1c: 1/6 and 4/12 (very low), systolic blood pressure: 0/3 and 1/8 (very low), diastolic blood pressure: 0/3 and 1/7 (very low), BMI: 0/5 and 2/8 (very low), body weight: 0/0 and 1/3 (very low), hypoglycemia: 1/2 and 1/2 (very low), daily intake of fruits and vegetables: 1/1 and 1/3 (very low), daily intake of whole grains: 0/0 and 0/2 (very low), overall diet quality: 2/2 and 1/1 (low), and household food insecurity: 2/3 and 0/0 (very low). The 2 studies included in the economic analysis showed no difference in Medicare spending from Supplemental Nutrition Assistance Program participation and cost-savings from medically tailored meals in an economic simulation. Overall, providing material benefits to improve access to food for people with diabetes may improve household food insecurity, fruit and vegetable intake, and overall diet quality, but effects on clinical parameters and whole grain intake are unclear. The certainty of evidence was very low to low by GRADE. PROSPERO (CRD42021212951).

Changes in Prediabetes Status Among Adults During a 6-Month Randomized Placebo-controlled Supplement Trial With Nutrition and Lifestyle Counselling and 6-Month Follow-up.

OBJECTIVES: In this work, we present an exploratory within-trial analysis of the changing prevalence of prediabetes in response to nutrition and lifestyle counselling provided as part of a randomized placebo-controlled supplement trial with follow-up. We aimed to identify factors associated with changing glycemia status. METHODS: Participants (n=401) in this clinical trial were adults with a body mass index (BMI) of ≥25 kg/m2 and prediabetes (defined by the American Diabetes Association as a fasting plasma glucose [FPG] of 5.6 to 6.9 mmol/L or a glycated hemoglobin [A1C] of 5.7% to 6.4%) within 6 months before trial entry. The trial consisted of a 6-month randomized intervention with 2 dietary supplements and/or placebo. At the same time, all participants received nutrition and lifestyle counselling. This was followed by a 6-month follow-up. Glycemia status was assessed at baseline and at 6 and 12 months. RESULTS: At baseline, 226 participants (56%) met a threshold for prediabetes, including 167 (42%) with elevated FPG and 155 (39%) with elevated A1C. After the 6-month intervention, the prevalence of prediabetes decreased to 46%, driven by a reduction in prevalence of elevated FPG to 29%. The prevalence of prediabetes then increased to 51% after follow-up. Risk of prediabetes was associated with older age (odds ratio [OR], 1.05; p<0.01), BMI (OR, 1.06; p<0.05), and male sex (OR, 1.81; p=0.01). Participants who reverted to normoglycemia had greater weight loss and lower baseline glycemia. CONCLUSIONS: Glycemia status can fluctuate over time and improvements can be gained from lifestyle interventions, with certain factors associated with a higher likelihood of reverting to normoglycemia.

The Impact of Medical Nutritional Therapy on the Efficacy of Premix Insulin in Glycemic Control in Patients with Type 2 Diabetes.

Background: Medical nutritional therapy (MNT) is a key component in the treatment of Diabetes mellitus (DM). MNT is completely individual and should be present in the treatment of diabetes from the very beginning, continuously with pharmacological therapy, taking into account lifestyle, dietary habits and the type of antidiabetic therapy. Mistakes that are made when planning the diet are the absence of individual adjustment of the diet, which means that the number and time of meals, as well as the amount of UH per meal, is not adjusted to the patients' oral or insulin therapy according to their pharmacokinetics and pharmacodynamics. Objective: This study investigated the effect of MNT with reduced carbohydrate content (MNT M-ADA) on the efficacy of human and analogue premix insulin in patients with T2DM. Methods: Subjects were randomized into two groups (human and analog premix insulins), and then each group into two subgroups of 30 subjects each. One subgroup each on therapy with human and analog biphasic insulins was educated about MNT and learned to count UH, and then they applied MNT M-ADA for 24 weeks, unlike the other two subgroups. In this review, we present only the subgroup analysis on human and analog premix insulins that applied MNT M-ADA (200 g UH/day). Efficacy outcomes in the analysis of these subgroups were estimated changes in each subgroup from baseline to end point (week 24) and differences between subgroups at the end of the study in levels of glycated hemoglobin (HbA1c), self-measured glucose values (SMBG) and frequency of hypoglycemia. Results: Both subgroups of subjects with MNT M-ADA improved glycemic control, which was assessed by improvements in HBA1C, SMBG levels, without an increase in the frequency of hypoglycemia, but at the end of the study there was no statistically significant difference in the mentioned parameters between the subgroups. Conclusion: The effectiveness of MNT M-ADA in people with T2DM did not depend on the type of insulin, both insulin regimens are effective if the amount of ingested UH is taken into account.

Evaluation of Sida cordifolia and Sida rhombifolia extracts in a rat model of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Sida cordifolia and Sida rhombifolia are regarded as useful herbs as they have been shown to be effective, inexpensive and harmless in the prevention of diabetes, and are recognized as valuable therapeutic substances. OBJECTIVES: The purpose of this study was to assess the effect of S. cordifolia and S. rhombifolia in the treatment of diabetic nephropathy using a rat model. MATERIAL AND METHODS: Extracts of S. cordifolia and S. rhombifolia were obtained using the Soxhlet method. The hydroalcoholic extract solvent was used in the following proportions: 70:30, 50:50 and 80:20. The 80:20 hydroalcoholic extract was observed to be the most potent. The inhibitory effects of the extract were determined using the α-amylase assay. The most potent extract also underwent total flavonoid, phenolic and free radical scavenging tests, and was incorporated into an animal study. Diabetes was induced in rats by administering nicotinamide (NAD; 230 mg/kg) and streptozotocin (STZ; 65 mg/kg) intraperitoneally. In addition to a standard control of pioglitazone, the rats received extract dosages of 100 mg/kg/day or 200 mg/kg/day. Body weight, blood glucose, glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), serum albumin, serum creatinine, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance were assessed at various time points. The animals also underwent histopathological examination to observe alterations induced by the treatment. RESULTS: Sida cordifolia was the most successful in lowering blood glucose and HbA1c levels. Renal function indices and antioxidant enzyme levels were regained in a dose-dependent manner. Furthermore, S. cordifolia (200 mg/kg/day) extract, similar to pioglitazone, inhibited the production of advanced glycation byproducts by the kidney. CONCLUSIONS: The effects of various S. cordifolia and S. rhombifolia extracts on rats with diabetic nephropathy were observed. Sida cordifolia may be further explored for the treatment of diabetic nephropathy and, due to its diverse nature, may be utilized for the treatment of a wide range of diseases, as it provided more significant findings.

Effect of vitamin E intake on glycemic control and insulin resistance in diabetic patients: an updated systematic review and meta-analysis of randomized controlled trials.

Since a 2014 meta-analysis, several randomized controlled trials (RCTs) evaluating the effect of vitamin E intake on glycemic indices and insulin resistance in adults with diabetes have reached inconsistent conclusions. Therefore, we updated the previous meta-analysis to summarize the current evidence in this regard. Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched to identify relevant studies published up to September 30, 2021, using relevant keywords. Random-effects models were used to obtain overall mean difference (MD) comparing vitamin E intake with a control group. In total, 38 RCTs with a total sample size of 2171 diabetic patients (1110 in vitamin E groups and 1061 in control groups) were included. Combining the results from 28 RCTs on fasting blood glucose, 32 RCTs on HbA1c, 13 RCTs on fasting insulin, and 9 studies on homeostatic model assessment for insulin resistance (HOMA-IR) showed a summary MD of -3.35 mg/dL (95% CI: -8.10 to 1.40, P = 0.16), -0.21% (95% CI: -0.33 to -0.09, P = 0.001), -1.05 µIU/mL (95% CI: -1.53 to -0.58, P < 0.001), and -0.44 (95% CI: -0.82 to -0.05, P = 0.02), respectively. This indicates a significant lowering effect of vitamin E on HbA1c, fasting insulin and HOMA-IR, while no significant effect on fasting blood glucose in diabetic patients. However, in subgroup analyses, we found that vitamin E intake significantly reduced fasting blood glucose in studies with an intervention duration of < 10 weeks. In conclusion, vitamin E intake has a beneficial role in improving HbA1c and insulin resistance in a population with diabetes. Moreover, short-term interventions with vitamin E have resulted in lower fasting blood glucose in these patients. This meta-analysis was registered in PROSPERO with code CRD42022343118.

A beneficial cardiometabolic health profile associated with dietary supplement use: A cross-sectional study.

As a follow-up to an earlier study demonstrating healthier cardiometabolic profiles among long-term multiple dietary supplement (LTMDS) users, we examined if cardiometabolic health benefits associated with LTMDS use persisted with aging. The study is based on LTMDS users from North America and 2007-2010 NHANES participants who were used for comparison to the LTMDS users. NHANES subjects were classified as non-dietary supplement (NS) users, single supplement/single purpose supplement (SS) users, multivitamin/mineral supplement (MVMS) users, and multiple dietary supplement (MDS) users. Supplement groups were compared for total, HDL and LDL cholesterol; triglycerides; glucose; insulin; CRP and HbA1c ≥ 6.5%, adjusting for age, sex, income, education, BMI, history of CVD, and medications for hypercholesterolemia and diabetes. Geometric mean (95% confidence interval) LDL cholesterol was significantly lower (P < 0.05) for all supplement groups (SS: 110 (104-117) mg/dL; MVMS: 113 (107-119) mg/dL; MDS: 115 (111-118) mg/dL; LTMDS: 112 (105, 119) mg/dL) compared with the NS users (122 (118-126) mg/dL). Compared with the NS group, MDS users had significantly (P < 0.05) lower mean total cholesterol (198 (194-201) vs 201 (197, 206) mg/dL), MDS and LTMDS users higher mean HDL cholesterol (54.2 (53.3-55.1) and 60.0 (57.4, 62.7) mg/dL vs 52.0 (50.8-53.3) mg/dL), LTMDS users lower fasting glucose (100 (98-103) vs 105 (103-106) mg/dL), SS and MDS users lower insulin (8.4 (7.4-9.6) and 9.1 (8.3-9.9) vs 10.2 (9.4-11.1) µIU/mL), and MDS users lower CRP (% ≥ 1.5 mg/L, 50.8 (47.9-53.6) vs 57.0 (52.4-61.6) %). These findings add to the evidence that use of dietary supplements may provide cardiometabolic health benefits.

Effect of zinc supplementation on blood glucose level in different age groups of diabetes type 2.

Background: Studies on humans have revealed the beneficial effects of zinc (Zn) supplementation in patients with type-2 diabetes. Aim: The present study was designed to investigate the effects of zinc supplementation on blood glucose level in type-2 diabetic patients and determine the interaction between age and zinc supplementation on type-2 diabetic patients. Methods: A randomized placebo-control trial conducted in Bashir Hospital of Sialkot, Allama Iqbal Memorial Hospital Sialkot and Civil Hospital of Daska, Sialkot. 144 diabetic patients were selected including an expected drop-out rate of 20%. All the participants were randomly divided into Group 1 (Treatment group with intervention given Zn tablets 20 mg/day) and Group 2 (control group with placebo effect). Each group was further divided into 2 age categories Category 1 (30-50 years of age) and Category 2 (51-70 Years of age). Demographic data, Anthropometric measurements, 24-h dietary recall, serum blood glucose analysis, HbA1C, and serum zinc levels were recorded at the beginning (0 day) and end of the study (60 days). Results: Final fasting serum glucose levels were significantly lowered in group 1 with (p < 0.05) as compared to group 2, but interestingly, results were significant (p < 0.05) in the older age group (51-70 years) as compared to their younger age counterparts (30-50 years) of group2. A similar trend was also found in the HbA1c, serum Zn levels and BMI of the participants. Conclusion: Results implied the possible phenomenon of better response to Zn supplementation among aged patients as compared to younger counterparts, which may suggest higher Zn demands with advanced age.

Diabetic Neuropathy: A Repercussion of Vitamin D Deficiency.

Diabetes mellitus is a crucial health issue worldwide. The worldwide ubiquity is 8.8% among adults, which is predicted to rise to 10.4% by 2040. Diabetic neuropathy is a long-term complication associated with the diabetes mellitus condition, which primarily targets Schwann cells, peripheral axons and cell bodies (perikarya) in DRG (dorsal root ganglia). It can be accompanied by different factors such as metabolic factors such as insulin resistance, hypertension, obesity, low HDL level, and hypertriglyceridemia. The etiology of DPN is multifactorial. It is caused by hyperglycemia, micro-angiopathy, HbA1c, duration of diabetes, smoking status, high-density lipoprotein cholesterol and hypertension. Also, increased glucose conditions decrease vitamin D levels. Vitamin D, which is involved in neurotrophins such as NGF (nerve growth factor) and NCH (neuronal calcium homeostasis), plays a neuroprotective role in peripheral nerves. Depletionleads to vitamin D deficiency which further develops peripheral neuropathy in diabetic patients. Accumulation of AGEs (advanced glycation end product) plays a significant role in the pathogenesis of sensory neuronal damage. It contributes to microangiopathy and endoneurial vascular dysfunction in peripheral nerves. With vitamin D supplementation, the neuropathy pain scores were improved.

Antidiabetic Potential of Commonly Available Fruit Plants in Bangladesh: Updates on Prospective Phytochemicals and Their Reported MoAs.

Diabetes mellitus is a life-threatening disorder affecting people of all ages and adversely disrupts their daily functions. Despite the availability of numerous synthetic-antidiabetic medications and insulin, the demand for the development of novel antidiabetic medications is increasing due to the adverse effects and growth of resistance to commercial drugs in the long-term usage. Hence, antidiabetic phytochemicals isolated from fruit plants can be a very nifty option to develop life-saving novel antidiabetic therapeutics, employing several pathways and MoAs (mechanism of actions). This review focuses on the antidiabetic potential of commonly available Bangladeshi fruits and other plant parts, such as seeds, fruit peals, leaves, and roots, along with isolated phytochemicals from these phytosources based on lab findings and mechanism of actions. Several fruits, such as orange, lemon, amla, tamarind, and others, can produce remarkable antidiabetic actions and can be dietary alternatives to antidiabetic therapies. Besides, isolated phytochemicals from these plants, such as swertisin, quercetin, rutin, naringenin, and other prospective phytochemicals, also demonstrated their candidacy for further exploration to be established as antidiabetic leads. Thus, it can be considered that fruits are one of the most valuable gifts of plants packed with a wide spectrum of bioactive phytochemicals and are widely consumed as dietary items and medicinal therapies in different civilizations and cultures. This review will provide a better understanding of diabetes management by consuming fruits and other plant parts as well as deliver innovative hints for the researchers to develop novel drugs from these plant parts and/or their phytochemicals.