Vitamin D and Insulin-Dependent Diabetes: A Systematic Review of Clinical Trials.

(1) Background: Vitamin D supplementation after type 1 diabetes mellitus (T1DM) onset has led to conflicting results on beta-cell preservation. Aim: This paper presents a systematic review to verify whether randomized prospective controlled trials (RCTs) demonstrate that improved vitamin D status confers protection on T1DM. (2) Methods: A systematic review was conducted up until 18 January 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, using keywords "vitamin D", "type 1 diabetes", and "children". (3) Results: Following the above-mentioned search process, 408 articles in PubMed and 791 in Embase met inclusion criteria. After removing duplicates, 471 articles remained. After exclusion criteria, 11 RCTs remained. Because of major heterogeneity in design and outcomes, no meta-analyses were conducted, allowing only for qualitative analyses. There was no strong evidence that vitamin D supplementation has lasting effects on beta-cell preservation or glycemic control in new-onset T1DM. (4) Conclusions: More rigorous, larger studies are needed to demonstrate whether vitamin D improves beta-cell preservation or glycemic control in new-onset T1DM. Because T1DM may cause osteopenia, it is advisable that patients with new onset T1DM have adequate vitamin D stores.

Comparison of the effects of monounsaturated fatty acids and polyunsaturated fatty acids on the lipotoxicity of islets.

Background: Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat saturated fatty acid (SFA)-induced cellular damage, however, their clinical effects on patients with metabolic diseases such as diabetes and hyperlipidemia are still controversial. Since comparative studies of the effects of these two types of unsaturated fatty acids (UFAs) are still limited. In this study, we aimed to compare the protective effects of various UFAs on pancreatic islets under the stress of SFA-induced metabolic disorder and lipotoxicity. Methods: Rat insulinoma cell line INS-1E were treated with palmitic acid (PA) with or without UFAs including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and oleic acid (OA) to determine cell viability, apoptosis, endoplasmic reticulum (ER) stress, and inflammatory. In vivo, male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 w. Then the lard in HFD was partially replaced with fish oil (FO) and olive oil (OO) at low or high proportions of energy (5% or 20%) to observe the ameliorative effects of the UFA supplement. Results: All UFAs significantly improved PA-induced cell viability impairment in INS-1E cells, and their alleviation on PA induced apoptosis, ER stress and inflammation were confirmed. Particularly, OA had better effects than EPA, DHA, and AA on attenuating cellular ER stress. In vivo, the diets with a low proportion of UFAs (5% of energy) had limited effects on HFD induced metabolic disorder, except for a slight improved intraperitoneal glucose tolerance in obese mice. However, when fed diets containing a high proportion of UFAs (20% of energy), both the FO and OO groups exhibited substantially improved glucose and lipid metabolism, such as decrease in total cholesterol (TC), low-density lipoprotein (LDL), fasting blood glucose (FBG), and fasting blood insulin (FBI)) and improvement of insulin sensitivity evidenced by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT). Unexpectedly, FO resulted in abnormal elevation of the liver function index aspartate aminotransferase (AST) in serum. Pathologically, OO attenuated HFD-induced compensatory hyperplasia of pancreatic islets, while this effect was not obvious in the FO group. Conclusions: Both MUFAs and PUFAs can effectively protect islet ß cells from SFA-induced cellular lipotoxicity. In particular, both OA in vitro and OO in vivo showed superior activities on protecting islets function and enhance insulin sensitivity, suggesting that MUFAs might have greater potential for nutritional intervention on diabetes.

Momordica charantia fruit reduces plasma fructosamine whereas stems and leaves increase plasma insulin in adult mildly diabetic obese Göttingen Minipigs.

BACKGROUND: Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs. METHODS: Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design. RESULTS: Bitter gourd fruit from the cultivars "Palee" and "Good healthy" reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 µmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars "Palee" (>3.9-fold) and "Good healthy" (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar "Bilai" increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs. CONCLUSIONS: Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.

Probiotics and synbiotics for glycemic control in diabetes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: The escalating prevalence of diabetes mellitus may benefit from add-on therapeutic approaches. Given the recognized need for an updated synthesis of the literature, this systematic review and meta-analysis aimed to synthesize and critically assess the available randomized controlled trials (RCTs) that investigate the efficacy of probiotics and synbiotics on glycemic control in patients with Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus. METHODS: Comprehensive searches were conducted on PubMed, Embase, CINAHL, Scopus, and Web of Science, focusing on adults with T1DM or T2DM. All comparators were deemed eligible. Primary outcomes included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and insulin levels. Only RCTs were included, and the Cochrane RoB2 tool assessed the risk of bias. Random-effect models facilitated data analysis, supplemented by sensitivity, subgroup analyses, and meta-regressions. RESULTS: A total of 537 records were screened, resulting in 41 RCTs for analysis, which comprises 2991 (54% females) patients with diabetes. The meta-analysis revealed statistically significant improvements in HbA1c (standardized mean difference (SMD) = -0.282, 95% CI: [-0.37, -0.19], p < 0.001), FPG (SMD = -0.175, 95% CI: [-0.26, -0.09], p < 0.001), and insulin levels (SMD = -0.273, 95% CI: [-0.35, -0.20], p < 0.001). A medium degree of heterogeneity between studies was found in HbA1c (I2 = 62.5%), FPG (I2 = 71.5%), and insulin levels (I2 = 66.4%) analyses. Subgroup analyses indicated that the efficacy varied based on the type of strains used and the country. Multispecies strains were particularly effective in improving HbA1c levels. CONCLUSION: The study findings suggest that probiotics and synbiotics may be effective as complementary therapies for managing diabetes. Additionally, the study underscores the need for further tailored research that considers variables such as strain types and geographical factors to deepen the understanding of the role of these interventions in diabetes care. REVIEW REGISTRATION NUMBER: PROSPERO (CRD42023396348).

Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is a significant geriatric syndrome (GS) prevalent in older adults and seriously affects patient prognosis and quality of life. We assessed the impact of the multicomponent intervention of health education, dietary advice, and exercise with oral nutritional supplementation (ONS) on nutritional status, body composition, physical functions, and quality of life. METHODS: This multicenter randomized clinical trial (RCT) was performed from April 2021 to April 2022. The intervention lasted for 12 weeks, and 99 older adults with malnutrition or at risk of malnutrition were enrolled in six nursing homes. All participants were randomly assigned to the control (health education plus standard diet plus exercise) or research (health education plus standard diet plus exercise plus ONS) group. The research group consumed ONS (244 kcal, 9.8g protein, and 9.6g fat per time) twice a day between meals. The primary outcomes were changes in the nutritional status and body composition from baseline to 12 weeks. The secondary outcomes were changes in physical function, quality of life and nutritional associated other blood markers. RESULTS: For primary outcomes, after 12 weeks, body weight increased similarly in both treatment arms (time × treatment effect, P > 0.05). There were no between-group differences in body mass index (BMI) or mini nutritional assessment tool-short form (MNA-SF) scores (time × treatment effects, P > 0.05). The MNA-SF score from 11.0 (10.5, 12.0) to 13.0 (11.0, 13.0) in the research group and from 11.0 (10.0, 12.0) to 12.0 (11.0, 13.0) in the control group (both P < 0.05). There were no between-group differences in the skeletal muscle mass index (SMI), fat-free mass index (FFMI), appendicular skeletal muscle mass (ASMM), fat mass (FAT), or leg muscle mass (LMM) (time × treatment effects, P > 0.05). Both groups showed similar and highly significant increases in SMI, FFMI, and LMM after (P < 0.05). The research group showed an increase in fat-free mass (FFM) and ASMM and a decrease in the percent of body fat (PBF) and waist circumference (WC) (P < 0.05). For secondary outcomes, There were no between-group differences in grip strength, short physical performance battery (SPPB), 6-min walking distance (6MWD), activities of daily living (ADL), instrumental activities of daily living (IADL), frailty status (FRAIL), mini-mental state examination (MMSE), Tinetti, geriatric depression scale-15 (GDS-15), or 12-item short form survey (SF-12) (time × treatment effects, P > 0.05). Although there was no significant difference, the 6MWD changed differentially between the two treatment arms during the study period in favor of the research group. Although not significant, SF-12 scores improved after 12 weeks in both groups. No between-group differences were observed in prealbumin (PRE), c-reactive protein (CRP), vitamin D (VIT-D), insulin-like growth factor 1 (IGF-1), alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), insulin, and adiponectin levels (time × treatment effects, P > 0.05). Insulin and adiponectin levels were significantly higher in the control group (P < 0.05). CONCLUSION: The twelve-week multicomponent intervention improved the nutritional status of older people in China at risk of malnutrition. ONS may enhance the effects of exercise on muscle mass. This clinical trial was registered (https://www. CLINICALTRIALS: gov). The trial number is ChiCTR2000040343.

Vitamin D3 mitigates type 2 diabetes induced by a high carbohydrate-high fat diet in rats: Role of the purinergic system.

This study evaluated the effect of vitamin D3 (VIT D3) supplementation on the enzymatic activities and density of ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5-nucleotidase (E-5'-NT), adenosine deaminase (ADA), as well as the density of P2 × 7R, P2Y12R, A1R, A2AR receptors, IL-1ß, and oxidative parameters in type 2 diabetic rats. Forty male Wistar rats were fed a high carbohydrate-high fat diet (HCHFD) and received an intraperitoneal injection containing a single dose of streptozotocin (STZ, 35 mg/kg). Animals were divided into four groups: 1) control; 2) control/VIT D3 12 µg/kg; 3) diabetic; and 4) diabetic/VIT D3 12 µg/kg. Results show that VIT D3 reduced blood glucose, ATP hydrolysis, ADA activity, P2Y12R density (platelets), as well as ATP, ADP, and AMP hydrolysis and ADA activity (synaptosomes). Moreover, VIT D3 increased insulin levels and AMP hydrolysis (platelets) and improved antioxidant defense. Therefore, we suggest that VIT D3 treatment modulates hyperglycemia-induced changes via purinergic enzymes and receptor expression, consequently attenuating insulin homeostasis dysregulation in the diabetic state.

Comprehensive management of children and adolescents with type 1 diabetes mellitus through personalized physical exercise and education using an mHealth system: The Diactive-1 study protocol.

Introduction: The use of new technologies presents an opportunity to promote physical activity, especially among young people with type 1 diabetes (T1DM), who tend to be less active compared to their healthy counterparts. The aim of this study is to investigate the impact of a personalized resistance exercise program, facilitated by the Diactive-1 App, on insulin requirements among children and adolescents diagnosed with T1DM. Methods and analysis: A minimum of 52 children and adolescents aged 8-18 years, who were diagnosed with T1DM at least 6 months ago, will be randomly assigned to either a group engaging in an individualized resistance exercise program at least 3 times per week over a 24-week period or a waiting-list control group. The primary outcome will be the daily insulin dose requirement. The secondary outcomes will include glycemic control, cardiometabolic profile, body composition, vascular function, physical fitness, 24-hour movement behaviors, diet, and psychological parameters. The usability of the app will also be assessed. Ethics and dissemination: Ethical approval to conduct this study has been granted by the University Hospital of Navarra Research Board (PI_2020/140). Parents or legal guardians of minors participating in the study will provide written consent, while children and adolescents will sign an assent form to indicate their voluntary agreement. The trial's main findings will be shared through conference presentations, peer-reviewed publications, and communication directly with participating families. This study aims to offer valuable insights into the holistic management of children and adolescents with T1DM by utilizing personalized exercise interventions through an mHealth system. Trial registration: NCT06048757.

Vitamin D intervention as a curative measure for glucose intolerance in obese children and adolescents: a systematic review on randomized control trials.

Vitamin D deficiency is associated with obesity and its associated metabolic disorders, as specified in many epidemiological studies. The assertion that vitamin D can mitigate insulin insensitivity in obese children and adolescents lacks adequate empirical substantiation. Thus, the study utilized some clinical trials on vitamin D interventions to examine the impact of vitamin D supplementation on insulin resistance in obese children and adolescents. The literature was extracted by applying the PRISMA method through electronic databases such as Scopus, Science Direct, Medline, the Cochrane Library, and PubMed from 2012 to 2022. All the articles were in English, and the inclusion criteria for each article were based on the study design and the anthropometric and biochemical parameters of the subjects. A total of 572 research articles were acquired, out of which only seven closely adhered to the inclusion criteria of the study. The studies in this systematic review are based on randomized control trials. The age range of the children in this study spans from 2 to 19 years, and the follow-up period ranges from 3 to 12 months. The range of daily vitamin D doses provided varied from 2000 to 10,000 IU. The results indicate that four randomized controlled trials have demonstrated a positive impact on glycemic parameters, such as insulin levels, fasting blood sugar, and insulin resistance, in the subjects following vitamin D treatment. However, the three trials did not provide sufficient evidence to support a statistically significant effect. CONCLUSION: The present review highlights that a significant proportion of the studies incorporated in the analysis demonstrate that the administration of vitamin D may be a preventive measure in ameliorating insulin resistance among pediatric patients with obesity, but it is advisable to implement a prolonged intervention with a substantial sample size and perform micro-level analysis at the gene level to evaluate the impact of vitamin D treatment. WHAT IS KNOWN: • Childhood obesity and its associated metabolic disorder is a concerned global problem. • Several studies showed an association of vitamin D deficiency with adiposity- induced metabolicdisorders which are still controversial. This study focused on finding interlink between vitamin Dsupplementation with obesity induced insulin resistance in children and adolescents. WHAT IS NEW: • This study supports that high dosage of Vitamin D in long term may be protective against insulinresistance in obese paediatric individuals. • A new factor is also reported in the study that vitamin D may alter the composition of gut microbiotawhich represents a compelling approach to the therapeutic management of obesity and diabetes.

Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk.

Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p < 0.05) by a decline in food intake (p < 0.01), organ-to-liver ratio (p < 0.001), adiposity index (p < 0.01), and a rise in body temperature and brain serotonin level (p < 0.001). Dxt demonstrated anti-obesity effects by multiple mechanisms including interaction with hypothalamic GABAA channels and anti-inflammatory and free radical scavenging effects, improving the brain serotonin levels, and increasing insulin release from the pancreatic ß-cells.

A high-fat diet supplemented with medium-chain triglycerides ameliorates hepatic steatosis by reducing ceramide and diacylglycerol accumulation in mice.

Non-alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium-chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin-resistant mice. To achieve that, we fed C57BL/6 male mice a high-fat diet (HFD) for 12 weeks to induce obesity and hepatic steatosis, after which obese mice were assigned randomly either to remain on the HFD or to transition to an HFD supplemented with MCTs (HFD + MCTs) or a low-fat diet (LFD) for 6 weeks as another dietary intervention model. Another group of mice was kept on an LFD throughout the study and used as a lean control group. Obese mice that transitioned to HFD + MCTs exhibited improvement in glucose and insulin tolerance tests, and the latter improvement was independent of changes in adiposity when compared with HFD-fed mice. Additionally, supplementation with MCTs significantly reduced hepatic steatosis, improved liver enzymes and decreased hepatic expression of inflammation-related genes to levels similar to those observed in obese mice transitioned to an LFD. Importantly, HFD + MCTs markedly lowered hepatic ceramide and diacylglycerol content and prevented protein kinase C-ε translocation to the plasma membrane. Our study demonstrated that supplementation with MCTs formulated mainly from C8 and C10 effectively ameliorated NAFLD in obese mice.

Adding L-carnitine to antagonist ovarian stimulation doesn't improve the outcomes of IVF/ ICSI cycle in patients with polycystic ovarian syndrome: a double-blind randomized clinical trial.

OBJECTIVE: To investigate the effect of L-carnitine supplementation during the controlled ovarian stimulation (COS) cycle with antagonist protocol in patients with polycystic ovary syndrome (PCOS) diagnosis undergoing IVF/ICSI treatment. METHODS AND MATERIALS: This was a double-blind clinical trial study including 110 patients with PCOS attended to Royan Institute between March 2020 and February 2023. At the beginning of the COS cycle, the eligible patients were allocated into two groups randomly according to the coding list of the drugs prepared by the statistical consultant. In the experimental group, patients received 3 tablets daily (L-carnitine 1000 mg) from the second day of menstruation of the previous cycle until the puncture day in the cases of freeze-all embryos (6 weeks) or until the day of the pregnancy test (8 weeks) in fresh embryo transfer cycle. In the control group, patients received 3 placebo tablets for the same period of time. Weight assessment and fasting blood sugar and insulin tests, as well as serum lipid profile were also measured at the baseline and ovum pick-up day. The results of the COS cycle as well as the implantation and pregnancy rates were compared between groups. RESULTS: Finally, 45 cases in L-carnitine group versus 47 cases in the placebo group were completed study per protocol. Data analysis showed that the two groups were homogeneous in terms of demographic characteristics and baseline laboratory tests and severity of PCOS. There is no statistically significant difference in terms of the oocyte recovery ratio and oocyte maturity rate, and the number and quality of embryos, as well as the rates of the fertilization, chemical and clinical pregnancy between groups. However, the means of weight (P < 0.001) and serum levels of fasting blood sugar (P = 0.021), fasting insulin (P = 0.004), triglyceride (P < 0.001) and cholesterol (P < 0.001), LDL (P < 0.001) have significantly decreased in women after consuming L-carnitine supplementation. CONCLUSION: The oral intake of L-carnitine during COS in PCOS women for 6 weeks had no effect on COS and pregnancy outcomes. However, taking this supplement for 6 weeks has been associated with weight loss and improved lipid profile and serum glucose. TRIAL REGISTRATION: The study was registered in the Clinicaltrials.gov site on December 17, 2020 (NCT04672720).

Black soybean seed coat polyphenols have different effects on glucose and lipid metabolism in growing and young adult mice.

Black soybean contains flavan-3-ols and cyanidin 3-O-glucoside in its seed coat. Polyphenol-rich black soybean seed coat extract (BE) possesses various health benefits, such as antioxidant, anti-obesity, and anti-hyperglycemic effects. However, these functions have been evaluated mainly in the growing stage of animals, and there is no comparison data for different life stages. In this present study, we compared the effect of BE in growing (5-week old) and young adult (22-week old) ICR male mice. These mice were given an AIN 93M diet containing 2.0% BE for 4 weeks. BE did not affect body weight gain in both growing and young adult mice, but it suppressed mesenteric and subcutaneous white adipose tissue weights and decreased the cell size. BE also significantly suppressed plasma free-fatty acid levels. The effect of both BE and life stages were observed in the protein expression of adipogenesis-related transcription factors; in particular, BE suppressed the expression of C/EBPα and PPARγ. No significant change was observed in lipolysis and lipogenesis factors in the white adipose tissue and liver. Alternatively, BE showed low glucose tolerance without affecting plasma insulin levels after glucose loading in young adult mice, as seen from the results of the oral glucose tolerance test. However, plasma glucose and insulin levels remained unchanged at the end of the experimental period. In conclusion, these results strongly suggest that the health-beneficial effects of BE may alter in mice at different life stages.

The effects of EGCG supplementation on pancreatic islet α and ß cells distribution in adult male mice.

Tea and tea products are widely used as the most popular beverage in the world. EGCG is the most abundant bioactive tea polyphenol in green tea, which has positive effects on the prevention and treatment of diabetes. However, the impact of EGCG exposure on glucose homeostasis and islets in adult mice have not been reported. In this study, we studied glucose homeostasis and the morphological and molecular changes of pancreatic islet α and ß cells in adult male mice after 60 d of exposure to 1 and 10 mg/kg/day EGCG by drinking water. Glucose homeostasis was not affected in both EGCG groups. The expression of pancreatic duodenal homebox1 (Pdx1) in ß cells was upregulated, which might be related to increased insulin level, ß cell mass and ß cell proliferation in 10 mg/kg/day EGCG group. The expression of aristaless-related homeobox (Arx) in α cells did not change significantly, which corresponded with the unchanged α-cell mass. The significant reduction of musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) positive α-cells might be associated with decreased glucagon level in both EGCG groups. These results suggest that EGCG supplementation dose-dependent increases ß cell mass of adult mice and affects the levels of serum insulin and glucagon. Our results show that regular tea drinking in healthy people may have the possibility of preventing diabetes.

Ayurveda for a Type 1 Diabetes Patient with Peripheral Arterial Occlusive Disease: A Case Report.

INTRODUCTION: The effect of Ayurvedic therapy in type 2 diabetes (T2D) is well documented. For people with type 1 diabetes (T1D), there is little evidence on the applicability of Ayurvedic therapy. This case illustrates the course of Ayurvedic treatment in a person with T1D accompanied by peripheral arterial occlusive disease (PAOD). CASE PRESENTATION: The patient had insulin-dependent T1D since the age of 6 years. At 39 years of age, he developed progressive bilateral PAOD of the femoral arteries. He presented claudication symptoms at a walking distance of 150 m. Ten surgical interventions for recanalization have been performed. The PAOD put heavy psychological strains on the patient. He developed moderate depression with anxiety and complained of tinnitus and sleep disturbances. Through an initial outpatient Ayurvedic treatment mainly focused on dietary, lifestyle changes and phytotherapeutics, and a subsequent 6-week inpatient Ayurvedic treatment in India, a weight reduction of 12 kg, a reduction in insulin requirement to 65% of baseline, as well as a walking performance without restriction at a medium load could be achieved. The depression and inner tension retreated, and one-sided tinnitus and existing sleep disturbances dissolved completely. The lasting effect was still perceptible 5 months after the inpatient stay. CONCLUSIONS: For this person with T1D with PAOD, outpatient and inpatient Ayurvedic therapy could generate a significant improvement of his situation. The case demonstrates that people with T1D can benefit from using individualized Ayurvedic therapy. This case motivates to invest in Ayurvedic research for people with T1D and complications.Die Wirkung der ayurvedischen Therapie bei Typ-2-Diabetes (T2D) ist gut dokumentiert. Für Menschen mit Typ-1-Diabetes (T1D) gibt es kaum Belege für die Anwendbarkeit der ayurvedischen Therapie. Dieser Fall veranschaulicht den Verlauf einer ayurvedischen Behandlung bei einer Person mit T1D, begleitet von einer peripheren arteriellen Verschlusskrankheit (pAVK).Der Patient hatte seit seinem 6. Lebensjahr einen insulinabhängigen 'T1D'. Im Alter von 39 Jahren entwickelte er eine fortschreitende bilaterale periphere arterielle Verschlusskrankheit (pAVK) der Oberschenkelarterien. Bei einer Gehstrecke von 150 m zeigte er Claudicatio-Symptome. Es wurden 10 chirurgische Eingriffe zur Rekanalisation durchgeführt. Die pAVK stellte für den Patienten eine starke psychische Belastung dar. Er entwickelte eine mittelschwere Depression mit Angstzuständen und klagte über Tinnitus und Schlafstörungen. Durch eine erste ambulante ayurvedische Behandlung, die sich hauptsächlich auf Ernährungs-, Lebensstiländerungen und Phytotherapeutika konzentrierte, und eine anschließende 6-wöchige stationäre ayurvedische Behandlung in Indien wurde eine Gewichtsreduktion um 12 kg, eine Reduzierung des Insulinbedarfs auf 65% des Ausgangswerts sowie eine bedeutende Verbesserung der Gehstrecke erreicht. Die Depression und die innere Anspannung verschwanden, und der einseitige Tinnitus und bestehende Schlafstörungen lösten sich vollständig auf. Der nachhaltige Effekt war noch 5 Monate nach dem stationären Aufenthalt spürbar.Für diese Person mit T1D mit pAVK konnte eine ambulante und stationäre ayurvedische Therapie eine deutliche Verbesserung der Situation bewirken. Der Fall zeigt, dass Menschen mit T1D von einer individualisierten ayurvedischen Therapie profitieren können. Dieser Fall motiviert dazu, in die ayurvedische Forschung für Menschen mit T1D und Komplikationen zu investieren.

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.

Effects of Whey Protein Combined with Amylopectin/Chromium on the Muscle Protein Synthesis and mTOR Phosphorylation in Exercised Rats.

This study aimed to examine the impact of varying doses of whey protein (WP) and amylopectin/chromium complex (ACr) supplementation on muscle protein synthesis (MPS), amino acid and insulin levels, and the rapamycin (mTOR) signaling pathways in exercised rats. A total of 72 rats were randomly divided into nine groups: (1) Exercise (Ex), (2) Ex + WPI to (5) Ex + WPIV with various oral doses of whey protein (0.465, 1.55, 2.33, and 3.1 g/kg) and (6) Ex + WPI + ACr to (9) Ex + WPIV + ACr with various doses of whey protein combined with 0.155 g/kg ACr. On the day of single-dose administration, the products were given by oral gavage after exercise. To measure the protein fractional synthesis rate (FSR), a bolus dose of deuterium-labeled phenylalanine was given, and its effects were evaluated 1 h after supplementation. Rats that received 3.1 g/kg of whey protein (WP) combined with ACr exhibited the most significant increase in muscle protein synthesis (MPS) compared to the Ex group (115.7%, p < 0.0001). In comparison to rats that received the same dose of WP alone, those given the combination of WP and ACr at the same dosage showed a 14.3% increase in MPS (p < 0.0001). Furthermore, the WP (3.1 g/kg) + ACr group exhibited the highest elevation in serum insulin levels when compared to the Ex group (111.9%, p < 0.0001). Among the different groups, the WP (2.33 g/kg) + ACr group demonstrated the greatest increase in mTOR levels (224.2%, p < 0.0001). Additionally, the combination of WP (2.33 g/kg) and ACr resulted in a 169.8% increase in 4E-BP1 levels (p < 0.0001), while S6K1 levels rose by 141.2% in the WP (2.33 g/kg) + ACr group (p < 0.0001). Overall, supplementation with various doses of WP combined with ACr increased MPS and enhanced the mTOR signaling pathway compared to WP alone and the Ex group.

The Effects of Ginger (Zingiber Officinale Roscoe) on Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blinded Placebo-Controlled Clinical Trial.

Nonalcoholic fatty liver disease (NAFLD) is a prominent etiological factor for liver cirrhosis worldwide. It is frequently associated with obesity, diabetes, dyslipidemia, and hypertension. The objective of this study is to assess the efficacy and safety of ginger (Zingiber officinale Roscoe) supplementation in patients with type 2 diabetes mellitus (T2DM) who have NAFLD. In a two-arm, double-blind, placebo-controlled clinical trial, seventy-six patients diagnosed with both T2DM and NAFLD were randomly assigned to receive either ginger powder capsules (1000 mg, twice daily) or placebo capsules (administered in the same manner) for a period of three months. Anthropometric measurements, blood pressure readings, biochemical profiles, and imaging parameters were assessed before and after the intervention. Safety measures were also evaluated. In both the ginger and placebo groups, there was a significant reduction in mean body mass index (BMI), waist and hip circumferences, as well as liver transaminase levels. Moreover, significant improvements in mean systolic and diastolic blood pressures were observed in the ginger group (p = 0.02 and < 0.0001, respectively). Within the ginger group, there was a decrease in serum insulin levels and insulin resistance (HOMA-IR) (p = 0.002 and 0.004, respectively). Furthermore, the ginger group exhibited an improvement in serum HDL-cholesterol level (p = 0.01). However, there were no significant changes in the assessed inflammatory markers or the indices obtained from fibroscan imaging, including steatosis percent and controlled attenuation parameter. This study demonstrates that ginger supplementation can significantly improve mean systolic and diastolic blood pressures. However, it does not have a significant impact on inflammatory markers or fibroscan imaging indices. Nonetheless, the three-month use of ginger improves serum insulin level, insulin resistance (HOMA-IR), and HDL-cholesterol level compared to baseline values. Further investigations with longer durations and larger sample sizes are recommended.

Formononetin, a bioactive isoflavonoid constituent from Astragalus membranaceus (Fisch.) Bunge, ameliorates type 1 diabetes mellitus via activation of Keap1/Nrf2 signaling pathway: An integrated study supported by network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Type 1 diabetes mellitus (T1DM) results from insulin deficiency due to the destruction of pancreatic ß-cells. Previously, our studies showed that inhibition of Keap1/Nrf2 signaling pathway promoted the onset of T1DM, which suggests that finding drugs that can activate the Keap1/Nrf2 signaling may be a promising therapeutic strategy for the T1DM treatment. Astragalus membranaceus (Fisch.) Bunge is a common traditional Chinese medicine that has been frequently applied in Chinese clinics for the treatment of diabetes and other diseases. Formononetin (FMNT), one of the major isoflavonoid constituents isolated from this herbal medicine, possesses diverse pharmacological benefits and T1DM therapeutic potential. However, the exact molecular mechanisms underlying the action of FMNT in ameliorating T1DM have yet to be fully elucidated. AIMS OF THE STUDY: This study is to investigate the regulation of FMNT on the Keap1/Nrf2 signaling pathway to ameliorate T1DM based on network pharmacology approach combined with experimental validation. MATERIALS AND METHODS: A mouse-derived pancreatic islet ß-cell line (MIN6) was used for the in vitro studies. An alloxan (ALX)-induced T1DM model in wild-type and Nrf2 knockout (Nrf2-/-) C57BL/6J mice were established for the in vivo experiments. The protective effects of FMNT against ALX-stimulated MIN6 cell injury were evaluated using MTT, EdU, apoptosis and comet assays. The levels of blood glucose in mice were measured by using a blood monitor and test strips. The protein expression was detected by Western blot analysis. Furthermore, the binding affinity of FMNT to Keap1 was evaluated using cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and solvent-induced protein precipitation (SIP) assay. The interaction pattern between FMNT and Keap1 was assessed by molecular docking and molecular dynamics simulation techniques. RESULTS: Network pharmacology analysis revealed that FMNT exerted its therapeutic effect against T1DM by mainly regulating oxidative stress response-associated signaling molecules and pathways, such as Nrf2 regulating anti-oxidant/detoxification enzymes and Keap1-Nrf2 signaling pathway. The in vivo results showed that FMNT significantly deceased the ALX-induced high blood glucose levels and conversely increased the ALX-induced low insulin contents. In vitro, FMNT markedly protected MIN6 cells from ALX-induced cytotoxicity, proliferation inhibition and DNA damage and reduced the ALX-stimulated cell apoptosis. FMNT also inhibited ALX-induced overproduction of intracellular ROS to alleviate oxidative stress. In addition, FMNT could bind to Keap1 to notably activate the Keap1/Nrf2 signaling to upregulate Nrf2 expression and promote the Nrf2 translocation from the cytoplasm to the nucleus, resulting in enhancing the expression of antioxidant proteins HO-1 and NQO1. Inhibition of Keap1/Nrf2 signaling by ALX was also markedly abolished in the cells and mice exposed to FMNT. Moreover, these effects of FMNT in ameliorating T1DM were not observed in Nrf2-/- mice. CONCLUSIONS: This study demonstrates that FMNT could bind to Keap1 to activate the Keap1/Nrf2 signaling to prevent intracellular ROS overproduction, thereby attenuating ALX-induced MIN6 cell injury and ameliorating ALX-stimulated T1DM. Results from this study might provide evidence and new insight into the therapeutic effect of FMNT and indicate that FMNT is a promising candidate agent for the treatment of T1DM in clinics.

The efficacy of magnesium supplementation for gestational diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of magnesium supplementation is unclear for the treatment of gestational diabetes. This meta-analysis aimed to study the efficacy of magnesium supplementation for glycemic control and pregnant outcomes in women with gestational diabetes. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been systematically searched up to July 2023, and we included randomized controlled trials (RCTs) assessing the efficacy of magnesium supplementation for gestational diabetes. The meta-analysis was performed using the random-effect model or fixed-effect model based on the heterogeneity. RESULTS: Five RCTs and 266 patients were included in the meta-analysis. Overall, compared with control intervention for gestational diabetes, magnesium supplementation was able to significantly decrease FPG (MD = -7.33 mg/dL; 95 % CI = -7.64 to -7.02 mg/dL; P < 0.00001) and HOMA-IR (MD = -0.99; 95 % CI = -1.76 to -0.22; P = 0.01), but resulted in no obvious impact on serum insulin (MD = -4.17 µIU/mL; 95 % CI = -8.49 to 0.14 µIU/mL; P = 0.06), preterm delivery (OR = 0.42; 95 % CI = 0.06 to 2.95; P = 0.38), macrosomia (OR = 0.34; 95 % CI = 0.08 to 1.35; P = 0.13) or BMI change (MD = -0.01 kg/m2; 95 % CI = -0.06 to 0.04 kg/m2; P = 0.63). CONCLUSIONS: Magnesium supplementation may be effective for the treatment of gestational diabetes without taking insulin treatment.

Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on High Fructose Induced Insulin Resistance in Experimental Animals.

BACKGROUND: Insulin resistance (IR) is a condition characterized by reduced sensitivity of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised disposal of glucose from the body. In the search for effective treatments, Plant-derived formulations have gained popularity because to their ability for treating a variety of ailments. One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used in the treatment of diabetes and its consequences. This study investigates the insulin-resistant activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective role of Punica granatum against insulin resistance through various analyses, including serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP, SGOT, SGPT), and histopathological examination of liver sections. METHODS: The study involves several key methods to evaluate the insulin-resistant activity of Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract was administered orally to the experimental animals. These methods include the measurement of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of liver tissue sections. These analyses collectively provide insights into the impact of Punica granatum extract on insulin resistance and related metabolic parameters. RESULTS: Findings of this study provide insight on the possible benefits of Punica granatum extract on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on key metabolic indicators. Additionally, the histopathological examination of liver sections provides visual insights into the structural changes that may occur as a result of the treatment. CONCLUSION: In conclusion, this study highlights the ability of Punica granatum extract as a candidate for addressing insulin resistance. The findings suggest that the extract may have a protective role against insulin resistance, as evidenced by improvements in serum glucose and insulin levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research and investigations are warranted to fully understand the mechanisms underlying these observed effects and to validate the potential of Punica granatum extract as a therapeutic option for managing insulin resistance and its associated complications.