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.

Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Therapeutic Applications of Plant and Nutraceutical-Based Compounds for the Management of Type 2 Diabetes Mellitus: A Narrative Review.

Diabetes mellitus is a condition caused by a deficiency in insulin production or sensitivity that is defined by persistent hyperglycemia as well as disturbances in glucose, lipid, and protein metabolism. Uncurbed diabetes or incessant hyperglycemic condition can lead to severe complications, including renal damage, visual impairment, cardiovascular disease, neuropathy, etc., which promotes diabetes-associated morbidity and mortality rates. The therapeutic management of diabetes includes conventional medications and nutraceuticals as complementary therapies. Nutraceuticals are bioactive compounds derived from food sources that have health-promoting properties and are instrumental in the management and treatment of various maladies. Nutraceuticals are clinically exploited to tackle DM pathogenesis, and the clinical evidence suggests that nutraceuticals can modulate biochemical parameters related to diabetes pathogenesis and comorbidities. Hypoglycemic medicines are designed to mitigate DM in traditional medicinal practice. This review intends to emphasize and comment on the various therapeutic strategies available to manage this chronic condition, conventional drugs, and the potential role of nutraceuticals in managing the complexity of the disease and reducing the risk of complications. In contrast to conventional antihyperglycemic drugs, nutraceutical supplements offer a higher efficacy and lesser adverse effects. To substantiate the efficacy and safety of various functional foods in conjunction with conventional hypoglycemic medicines, additional data from clinical studies are required.

Grape seed proanthocyanidin extract suppresses oxidative stress in the rat pancreas of type-1 diabetes.

AIM: This study aimed to elucidate the effects of grape seed proanthocyanidin extract (GSPE) on oxidative stress (OS), antioxidant enzymes, free radicals and cytokines in the pancreas of T1DM rats. METHODS: Two-month-old Wistar rats were assigned to the control (CON), CON + GSPE (CON + PA), diabetics (STZ, 60 mg/kg b.w.), diabetes + GSPE (STZ + PA), diabetes + insulin (STZ + INS, 3 U/day) and diabetics + GSPE and INS (STZ + INS + PA) groups. GSPE (75 mg/kg b.w.) was administered daily either alone or with INS for 8 weeks. RESULTS: Glutathione was lowest in diabetics while it increased in the STZ + INS + PA (p < .001) group, similar to catalase activity (p < .05). Hydrogen peroxide, superoxide and lipid peroxidation increased with iNOS, TNF-α and IL-1ß in the diabetic pancreases, while GSPE decreased (p < .001). Further, reduced ß-cells/islet number was improved in diabetics (p < .001) with treatment. CONCLUSION: This study suggests that GSPE with INS is effective in minimising OS and pancreatic degeneration in T1DM rats.

Rumex nervosus could alleviate streptozotocin-induced diabetic nephropathy in rats by activating Nrf2 signaling.

This study tested the protective effect of Rumex nervous (R. nervosus) methanol extract against streptozotocin (STZ)-mediated type 1 diabetes mellitus (T1DM)-induced nephropathy in rats and examined if this protection involves activating the nuclear factor erythroid 2 related factor-2 (Nrf2). Rats were divided into control, R. nervous (300 mg), STZ (T1DM), STZ + R. nervosus (100, 200, or 300 mg/kg), and STZ + R. nervosus (300 mg/kg) + brusatol (an Nrf2 inhibitor). With no effect on fasting glucose and insulin levels, R. nervosus methanol extract preserved kidney histological structure and alterations kidney function markers (e.g. albumin, creatinine, and urine volume) in the STZ-diabetic rats. R. nervosus also reduced levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukine-6 (IL-6), nuclear levels of the nuclear factor kappa beta (NF-κB), and mRNA of caspase-3 and Bax in the kidneys of these diabetic rats. Concomitantly, it stimulated renal mRNA levels of Bcl2 and Nrf2, cytoplasmic and nuclear levels of Nrf2, and levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). All these effects were dose-dependent, with the maximum effect seen with the 300 mg/kg dose, all prevented by brusatol. Also, these effects occurred without any alteration in the transcription of the Kelch-like ECH-associated protein 1 (keap-1). Similar effects on levels of GSH, SOD, CAT, and NF-κB, as well as expression of Nrf2, were also observed in the kidney of control + R. nervous-treated rats. In conclusion, R. nervosus prevents diabetic nephropathy in rats by upregulating and activating Nrf2.

Association Between Serum Magnesium and Glycemic Control, Lipid Profile and Diabetic Retinopathy in Type 1 Diabetes.

INTRODUCTION: Many studies have shown an association between decreased serum magnesium (Mg) levels and poor glycemic control and dyslipidemia in individuals with type 1 diabetes (T1D). Few studies evaluated the association between magnesium (Mg) levels and diabetic retinopathy (DR) in individuals with type 1 diabetes (T1D). METHODS: Retrospective study of adults with T1D, with an ophthalmological evaluation and a serum Mg level determination. According to Mg levels, the individuals were stratified into two groups: normal Mg levels (1.81-2.60 mg/dL) and low Mg levels (≤1.80 mg/dL). Exclusion criteria were individuals on diuretics or proton-pump inhibitors, malabsorption or diarrhea, oral magnesium supplementation in the recent past, pregnancy, or sepsis. RESULTS: 105 individuals, with median Mg levels of 1.96 (interquartile range 0.23) mg/dL. Hypomagnesemia (≤1.80 mg/dL) was detected in 20.0% individuals and 26.7% had DR. Individuals with hypomagnesemia had higher HbA1c (p = 0.014) and triglycerides (p = 0.024). Mg levels were negatively correlated with systolic blood pressure (r = -0.200, p = 0.041), HbA1c (r = -0.281, p = 0.004) and body mass index (BMI) (r = -0.197, p = 0.041). There was no significant difference between Mg levels or prevalence of hypomagnesemia in individuals with or without DR. Also, there was no significant difference between Mg levels and the severity of DR. CONCLUSION: Hypomagnesemia is a common problem in adults with T1D, and it was correlated with poor glycemic control, although we did not find a significant association between Mg levels and prevalence or severity of DR.

Anti-diabetic and gut microbiota modulation effects of sacha inchi (Plukenetia volubilis L.) leaf extract in streptozotocin-induced type 1 diabetic mice.

BACKGROUND: Sacha inchi (Plukenetia volubilis L.) tea has been used as an adjuvant treatment for diabetes in Pu'er, in the Yunnan province of China. The effects of sacha inchi tea on diabetes and the underlying mechanisms remain unknown. This study was conducted to investigate the influence of a water extract of sacha inchi (P. volubilis L.) leaves (PWE) on hypoglycemic activity and gut microbiota composition in mice with streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM). During the 6 weeks of the study, T1DM mice were administered PWE intragastrically at 400 mg kg-1 body weight (BW) per day. RESULTS: Treatment with PWE reduced excessive loss of BW and excessive intake of food. It significantly decreased blood glucose levels and improved oral glucose tolerance. The treatment caused protective histopathological transformations in sections of the pancreas, leading to decreased insulin resistance and improved insulin sensitivity. Treatment with PWE also significantly ameliorated disorders of the gut microbiota structure and increased the richness and diversity of intestinal microbial species in T1DM mice. At the genus level, the populations of several crucial bacteria, such as Akkermansia, Parabacteroides, and Muribaculum increased in the PWE treatment group but the abundance of Ruminiclostridium and Oscillibacter decreased. CONCLUSIONS: Treatment with PWE can ameliorate hyperglycemic symptoms in STZ-induced T1DM mice, and the anti-diabetic effect of PWE was related to the amelioration of gut microbial structural disorder and the enrichment of functional bacteria. © 2022 Society of Chemical Industry.

Habits, Traditions, and Beliefs Associated With the Use of Complementary and Alternative Medicine Among Diabetic Patients in Al-Qassim Region, Saudi Arabia.

Background Since diabetes mellitus (DM) affects every aspect of a person's being, more and more people are using complementary and alternative therapies such as ingesting ginger and cinnamon in addition to conventional medical care and lifestyle changes to manage their condition and enhance their well-being. Although this population uses complementary and alternative medicine (CAM) at a high rate, it is unclear what causes this use. Objective We aim to know the habits, traditions, and beliefs associated with the use of complementary and alternative medicine among type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients in the Al-Qassim region of Saudi Arabia. Methods This is an observational cross-sectional study conducted among diabetes patients in Al-Qassim, Saudi Arabia, in 2022. Participants were selected via a non-probability sampling technique. Patients were interviewed in the diabetic clinics using validated questionnaires. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software (IBM SPSS Statistics, Armonk, NY, USA). Results A total of 444 validated responses were received in this study. The average age was 50 ± 16.9 years, and females represented the highest proportion (58.6%). Moreover, we found that most of the participants had type 2 diabetes (79.1%) and 93 (20.9%) had type 1 diabetes. Hypertension was the most reported chronic disease. Our results revealed that the prevalence of CAM usage was 29.1%. Regarding the sources of information on herbal medicines, we found that more than half of the respondents (57.4%) obtained information from friends, relatives, and neighbors. Ginger, vitamins and minerals, and cinnamon were the most frequently used herbals among our participants. Our results found that 38% of CAM users used herbal products on a regular basis. As regards the frequency of using herbal products, 29.5% of the respondents used herbal medicine weekly and 21.7% used it daily. In addition, we found that gender, marital status, and monthly income were significantly associated with the use of CAM (P value = 0.008, 0.011, and 0.011, respectively). The significantly higher CAM use was associated with females, married participants, and participants with a monthly income of 10,000-15,000 Saudi riyal (SAR). Conclusion According to our research, CAM use among diabetes patients in the Al-Qassim region was found to be relatively common. The prevalence of type 2 diabetes mellitus was higher (79.1%) in comparison to type 1 diabetes mellitus (20.9%). Also, the most commonly used herb was ginger (47.66%), followed by vitamins and minerals (44.53%), and cinnamon (42.19%). Patients with diabetes need to be informed of the significance of telling their doctors about their use of CAM.

Ellagic acid protects against non-alcoholic fatty liver disease in streptozotocin-diabetic rats by activating AMPK.

CONTEXT: Ellagic acid (EA) is used in traditional medicine to treated hyperlipidaemia. OBJECTIVE: This study examined if AMPK mediates the anti-steatotic effect of ellagic acid (EA) in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats. MATERIALS AND METHODS: Adult male Wistar rats (130 ± 10 g) were divided into 6 groups (n = 8 rats/group) as control, control + EA, control + EA + CC an AMPK inhibitor), T1DM, T1DM + EA, and T1DM + EA + CC. The treatments with EA (50 mg/kg/orally) and CC (200 ng/rat/i.p.) were given the desired groups for 12 weeks, daily. RESULTS: In T1DM-rats, EA reduced fasting glucose levels (44.8%), increased fasting insulin levels (92.8%), prevented hepatic lipid accumulation, and decreased hepatic and serum levels of total triglycerides (54% & 61%), cholesterol (57% & 48%), and free fatty acids (40% & 37%). It also reduced hepatic levels of ROS (62%), MDA (52%), TNF-α (62%), and IL-6 (57.2%) and the nuclear activity of NF-κB p65 (54%) but increased the nuclear activity of Nrf-2 (4-fold) and levels of GSH (107%) and SOD (87%). Besides, EA reduced downregulated SREBP1 (35%), SREBP2 (34%), ACC-1 (36%), FAS (38%), and HMG-CoAR (49%) but stimulated mRNA levels of PPARα (1.7-fold) and CPT1a (1.8-fold), CPT1b (2.9-fold), and p-AMPK (4-fold). All these events were prevented by the co-administration of CC. DISCUSSION AND CONCLUSIONS: These findings encourage the use of EA to treat hepatic disorders, and non-alcoholic fatty liver disease (NAFLD). Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

1H NMR-based urinary metabonomic study of the antidiabetic effects of Rubus Suavissimus S. Lee in STZ-induced T1DM rats.

Long-term hyperglycemia associated with diabetes mellitus (DM) causes damage to various organs and tissues, including the eyes, kidneys, heart, blood vessels and nerves. Rubus Suavissimus S. Lee (RS), a shrub whose leaves are used in traditional Chinese medicine (TCM), has been shown to exert hypoglycemic effects in DM patients. However, the underlying mechanism is unclear. This was investigated in the present study in a rat model of streptozotocin-induced type 1 diabetes mellitus (T1DM) by 1H NMR analysis. We identify 9 metabolites whose levels were altered in T1DM rats compared to control rats, namely, lactate, acetate, pyruvate, succinate, 2-oxoglutarate, citrate, creatinine, allantoin, and hippurate, which are mostly related to glycolysis/gluconeogenesis, pyruvate metabolism, TCA cycle, and other metabolism. The observed pathologic changes in the levels of these metabolites in T1DM rats were reversed by treatment with RS. Thus, RS exerts effects in T1DM rats by regulating the three abnormal metabolic pathways synergistically. These findings provide supporting evidence for the therapeutic efficacy of this TCM formulation in the treatment of DM.

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.

Rat Models of Human Type 1 Diabetes.

Rat models of human type 1 diabetes have been shown to be of great importance for the elucidation of the mechanisms underlying the development of autoimmune diabetes. The three major well-established spontaneous rat models are the BioBreeding (BB) diabetes-prone rat, the Komeda diabetes-prone (KDP) rat, and the IDDM (LEW.1AR1-iddm) rat. Their distinctive features are described with special reference to their pathology, immunology, and genetics and compared with the situation in patients with type 1 diabetes mellitus. For all three established rat models, a distinctive genetic mutation has been identified that is responsible for the manifestation of the diabetic syndrome in these rat strains.

Dietary vitamin and mineral intakes in a sample of pregnant women with either gestational diabetes or type 1 diabetes mellitus, assessed in comparison with Polish nutritional guidelines.

OBJECTIVES: Maintaining proper nutrition during pregnancy is crucial for pregnant women and especially for who have been diagnosed with type 1 diabetes mellitus (T1DM) or who develop gestational diabetes mellitus (GDM). MATERIAL AND METHODS: To measure differences in vitamin and mineral intakes among women with normal pregnancies, pregnant women with GDM, and pregnant women with pre-gestational T1DM; and to assess the women's dietary intakes in comparison with Polish nutritional guidelines. The analysis was conducted among 83 pregnant women (29 GDM patients, 26 T1DM patients and 28 normal pregnancy participants) from whom we collected seven-day 24-hour dietary records during the second part of their pregnancies. RESULTS: There were no statistically significant differences observed for most of the vitamin and mineral intakes across the three groups. However, we did observe a significant difference in the vitamin C and calcium intakes between groups. The mean vitamin C and calcium intakes were significantly higher in the control group than among the diabetic patients. Insufficient dietary calcium intakes were found among 52.3% of the GDM patients and 61.6% of the T1DM participants, while only 28.6% of the normal pregnancy patients experienced a calcium deficiency. The highest incidence of inadequate intake in each of the GDM, T1DM and control groups was observed for vitamin D (100%, 100%, 100%), folate (97.7%, 100%, 100%), iron (97.7%, 100%, 100%), and iodine (97.7%, 92.4%, 85.7%), respectively. CONCLUSIONS: Diet alone may not be enough to provide adequate levels of vitamins and minerals for most micronutrients. Supplement use reduces the risk of inadequate intake for many micronutrients, but diet-related issues during pregnancy and pregnancy diagnosed with diabetes remain, and they deserve to be addressed during public health interventions.

Baicalin prevents tumor necrosis factor-α-induced apoptosis and dysfunction of pancreatic ß-cell line Min6 via upregulation of miR-205.

Baicalin (BAI), one major flavonoid from Scutellaria baicalensis, possesses anticancer and anti-inflammatory properties. However, the effect of BAI on diabetes mellitus has not been investigated. This study explored the antidiabetic effect of BAI on pancreatic ß-cell line Min6. Min6 cells were treated with tumor necrosis factor-α (TNF-α) to mimic ß-cell destruction in type 1 diabetes mellitus. The effects of BAI on viability and apoptosis of Min6 cells were analyzed by the cell counting kit-8 assay and Annexin V-fluoresceine isothiocyanate/propidium iodide staining method. The insulin secretion of Min6 cells was determined using radioimmunoassay. Expression of apoptosis-associated proteins and inducible nitric oxide synthase (iNOS), and activation of phosphatidylinositol 3'-kinase/protein kinase B (PI3K/AKT) and nuclear factor ΚB (NF-κB) pathways were analyzed by Western blot analysis. Relative microRNA-205 (miR-205) expression was determined by quantitative real time polymerase chain reaction. TNF-α treatment inhibited cell growth and insulin secretion, but promoted iNOS expression. All of these effects were reversed by BAI treatment. BAI promoted viability; suppressed apoptosis; regulated caspase-3, B-cell lymphoma 2 and Bcl-2-associated X protein; decreased iNOS level; and increased insulin production. BAI protected Min6 cells by upregulating miR-205. Besides, the Min6 cell-protective effect of BAI was PI3K/AKT pathway and NF-κB pathway dependent. BAI activated the PI3K/AKT pathway and inhibited the NF-κB pathway by regulating miR-205. In conclusion, BAI protected Min6 cells from TNF-α-induced injury by upregulating miR-205, which acts, at least in part, via activation of the PI3K/AKT pathway and inactivation of the NF-κB pathway.

Does Vitamin D Supplementation Improve Glycaemic Control In Children With Type 1 Diabetes Mellitus? - A Randomized Controlled Trial.

INTRODUCTION: Vitamin D endocrine system is a potential immune system modulator and has been implicated in the pathogenesis of several autoimmune diseases including Type 1 Diabetes Mellitus (T1DM). Studies have demonstrated an inverse risk relationship between T1DM and Vitamin D levels and also, shown a reduced risk of the disease with its supplementation. AIM: To evaluate the role of Vitamin D as an adjuvant in improving glycaemic control and residual pancreatic beta-cell function. Primary outcome was the mean change in HbA1c levels over a period of six months. MATERIALS AND METHODS: This double-blinded randomized controlled trial was done in a tertiary care hospital, Southern India and included 52 children aged 1-18 years with T1DM, with 26 participants each in the intervention and standard of care arm. Oral Vitamin D therapy was administered once a month for six months in addition to insulin in intervention arm while only insulin was continued for other arm. Plasma HbA1c, serum 25-Hydroxy vitamin D (25OHD), insulin dose and C-peptide were measured at baseline and repeated after 6 months. RESULTS: Prevalence of Vitamin D deficiency was as high as 63.5% i.e., 33 of total 52 children with T1DM. The mean C-peptide levels were significantly high in intervention arm as compared to standard of care after six months. However, there was no significant difference in HbA1c, and insulin requirement at six months between the two groups. No adverse events due to Vitamin D therapy were noted. CONCLUSION: Oral Vitamin D may serve as an adjuvant to insulin therapy for children with T1DM by augmenting residual beta-cell function and improving insulin secretion. However, a significant decrease in HbA1c level and requirement for exogenous insulin was not achieved in our study.

Antidiabetic effect of total flavonoids from Sanguis draxonis in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated (Tang et al., 1995; Wei et al., 1998), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats. MATERIALS AND METHODS: T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF. RESULTS: SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). CONCLUSIONS: This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF.

A randomized placebo-controlled trial of alphacalcidol on the preservation of beta cell function in children with recent onset type 1 diabetes.

BACKGROUND & AIMS: This participant-blinded parallel-group randomized placebo-controlled study demonstrated that alfacalcidol (vitamin D analogue) preserves beta cell function in newly diagnosed type 1 diabetes (T1DM) in children. METHODS: Subjects from outpatient clinic were randomized to intervention and control groups. Inclusion: (1) age 8-15, (2) T1DM, (3) duration <8 weeks, (4) no chronic diseases, (5) stable diet. Exclusion: (1) vitamin D, calcium supplements or fortified foods, (2) hypercalcemia. Intervention group received alfacalcidol 0.25 µg twice daily, while control group received placebo. Insulin given physician-titrated to blood glucose. Safety monitored by serum calcium and phosphate. Beta cell function assessed at 0, 3, 6 months using fasting C-peptide (FCP) and daily insulin dosage per body weight (DID). Primary outcome measured using multivariate repeated measures GLM-ANOVA, with FCP and DID as primary measures and age, gender, sunlight exposure, 25-hydroxy vitamin D, and HbA1c as covariates. RESULTS: Of 61 subjects, 7 dropped out. GLM-ANOVA showed that groups were different (p=0.019, Eta-squared=0.087), with no significant covariates. FCP was higher and DID lower in the intervention group, with males having stronger responses to alfacalcidol (p=0.001). No adverse effects were observed. CONCLUSIONS: The study confirmed that alfacalcidol can safely preserve beta cell function in newly diagnosed T1DM in children, with a stronger effect in males. CLINICAL TRIAL REG NO: IRCT201205159753N1.