PATIENTS AND METHODS: A total of 120 men, aged 40-70 years, with TD (serum total testosterone [TT] ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo. In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study. Participants were seen six times in the 48-week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone-binding globulin, liver function test, prostate- specific antigen (PSA) and adverse events.
RESULTS: The mean (sd) age of the participants was 53.4 (7.6) years. A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48-week period. Two men in the placebo arm and one man in the treatment arm developed myocardial infarction. Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne. Overall, TU injections were well tolerated.
CONCLUSIONS: TU significantly increases serum testosterone in men with TD. PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits. There was no significant adverse reaction that led to the cessation of treatment.
METHODS: Two parameters were measured (i) rate of glucose uptake by 3T3-L1 adipocyte cells in-vitro (ii) degree of pancreatic destruction in streptozotocin-nicotinamide induced male diabetic rats receiving M. pumilum aqueous extract (M.P) (250 and 500mg/kg/day) as reflected by levels of pancreatic oxidative stress, inflammation and apoptosis. In the meantime, phyto-chemical compounds in M.P were also identified by using LC-MS.
RESULTS: M.P was found able to enhance glucose uptake by 3T3-L1 adipocyte cells in-vitro while its administration to the male diabetic rats causes decreased in the fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) levels but causes increased in insulin and high-density lipoprotein (HDL) levels, to near normal. Levels of oxidative stress in the pancreas as reflected by levels of lipid peroxidation product (LPO) decreased while levels of anti-oxidantive enzymes (SOD, CAT and GPx) in pancreas increased. Additionally, levels of inflammation as reflected by NF-κB p65, Ikkβ and TNF-α levels decreased while apoptosis levels as reflected by caspase-9 and Bax levels decreased. Anti-apoptosis marker, Bcl-2 levels in pancreas increased.
CONCLUSIONS: The ability of M.P to enhance glucose uptake and reduces pancreatic complications could account for its beneficial effects in treating DM.
METHODS: We recruited 54 abdominally obese subjects to participate in a prospective cross-over design, single-blind trial comparing isocaloric 2000 kcal MUFA or carbohydrate-enriched diet with SFA-enriched diet (control). The control diet consisted of 15E% protein, 53E% carbohydrate and 32E% fat (12E% SFA, 13E% MUFA). A total of ∼7E% of MUFA or refined carbohydrate was exchanged with SFA in the MUFA-rich and carbohydrate-rich diets respectively for 6-weeks. Blood samples were collected at fasting upon trial commencement and at week-5 and 6 of each dietary-intervention phase to measure levels of cytokines (IL-6, IL-1β), C-reactive protein (CRP), thrombogenic markers (E-selectin, PAI-1, D-dimer) and lipid subfractions. Radial pulse wave analysis and a 6-h postprandial mixed meal challenge were carried out at week-6 of each dietary intervention. Blood samples were collected at fasting, 15 and 30 min and hourly intervals thereafter till 6 h after a mixed meal challenge (muffin and milkshake) with SFA or MUFA (872.5 kcal, 50 g fat, 88 g carbohydrates) or CARB (881.3 kcal, 20 g fat, 158 g carbohydrates)- enrichment corresponding to the background diets.
RESULTS: No significant differences in fasting inflammatory and thrombogenic factors were noted between diets (P > 0.05). CARB meal was found to increase plasma IL-6 whereas MUFA meal elevated plasma D-dimer postprandially compared with SAFA meal (P
METHODS: Patients who were 10 to less than 17 years of age were randomly assigned, in a 1:1 ratio, to receive subcutaneous liraglutide (up to 1.8 mg per day) or placebo for a 26-week double-blind period, followed by a 26-week open-label extension period. Inclusion criteria were a body-mass index greater than the 85th percentile and a glycated hemoglobin level between 7.0 and 11.0% if the patients were being treated with diet and exercise alone or between 6.5 and 11.0% if they were being treated with metformin (with or without insulin). All the patients received metformin during the trial. The primary end point was the change from baseline in the glycated hemoglobin level after 26 weeks. Secondary end points included the change in fasting plasma glucose level. Safety was assessed throughout the course of the trial.
RESULTS: Of 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients). Demographic characteristics were similar in the two groups (mean age, 14.6 years). At the 26-week analysis of the primary efficacy end point, the mean glycated hemoglobin level had decreased by 0.64 percentage points with liraglutide and increased by 0.42 percentage points with placebo, for an estimated treatment difference of -1.06 percentage points (P<0.001); the difference increased to -1.30 percentage points by 52 weeks. The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group. The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo), but the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.
CONCLUSIONS: In children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events. (Funded by Novo Nordisk; Ellipse ClinicalTrials.gov number, NCT01541215.).
OBJECTIVES: To compare techniques of blood glucose monitoring and their impact on maternal and infant outcomes among pregnant women with pre-existing diabetes.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016), searched reference lists of retrieved studies and contacted trial authors.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing techniques of blood glucose monitoring including SMBG, continuous glucose monitoring (CGM) or clinic monitoring among pregnant women with pre-existing diabetes mellitus (type 1 or type 2). Trials investigating timing and frequency of monitoring were also included. RCTs using a cluster-randomised design were eligible for inclusion but none were identified.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS: This review update includes at total of 10 trials (538) women (468 women with type 1 diabetes and 70 women with type 2 diabetes). The trials took place in Europe and the USA. Five of the 10 included studies were at moderate risk of bias, four studies were at low to moderate risk of bias, and one study was at high risk of bias. The trials are too small to show differences in important outcomes such as macrosomia, preterm birth, miscarriage or death of baby. Almost all the reported GRADE outcomes were assessed as being very low-quality evidence. This was due to design limitations in the studies, wide confidence intervals, small sample sizes, and few events. In addition, there was high heterogeneity for some outcomes.Various methods of glucose monitoring were compared in the trials. Neither pooled analyses nor individual trial analyses showed any clear advantages of one monitoring technique over another for primary and secondary outcomes. Many important outcomes were not reported.1. Self-monitoring versus standard care (two studies, 43 women): there was no clear difference for caesarean section (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.40 to 1.49; one study, 28 women) or glycaemic control (both very low-quality), and not enough evidence to assess perinatal mortality and neonatal mortality and morbidity composite. Hypertensive disorders of pregnancy, large-for-gestational age, neurosensory disability, and preterm birth were not reported in either study.2. Self-monitoring versus hospitalisation (one study, 100 women): there was no clear difference for hypertensive disorders of pregnancy (pre-eclampsia and hypertension) (RR 4.26, 95% CI 0.52 to 35.16; very low-quality: RR 0.43, 95% CI 0.08 to 2.22; very low-quality). There was no clear difference in caesarean section or preterm birth less than 37 weeks' gestation (both very low quality), and the sample size was too small to assess perinatal mortality (very low-quality). Large-for-gestational age, mortality or morbidity composite, neurosensory disability and preterm birth less than 34 weeks were not reported.3. Pre-prandial versus post-prandial glucose monitoring (one study, 61 women): there was no clear difference between groups for caesarean section (RR 1.45, 95% CI 0.92 to 2.28; very low-quality), large-for-gestational age (RR 1.16, 95% CI 0.73 to 1.85; very low-quality) or glycaemic control (very low-quality). The results for hypertensive disorders of pregnancy: pre-eclampsia and perinatal mortality are not meaningful because these outcomes were too rare to show differences in a small sample (all very low-quality). The study did not report the outcomes mortality or morbidity composite, neurosensory disability or preterm birth.4. Automated telemedicine monitoring versus conventional system (three studies, 84 women): there was no clear difference for caesarean section (RR 0.96, 95% CI 0.62 to 1.48; one study, 32 women; very low-quality), and mortality or morbidity composite in the one study that reported these outcomes. There were no clear differences for glycaemic control (very low-quality). No studies reported hypertensive disorders of pregnancy, large-for-gestational age, perinatal mortality (stillbirth and neonatal mortality), neurosensory disability or preterm birth.5.CGM versus intermittent monitoring (two studies, 225 women): there was no clear difference for pre-eclampsia (RR 1.37, 95% CI 0.52 to 3.59; low-quality), caesarean section (average RR 1.00, 95% CI 0.65 to 1.54; I² = 62%; very low-quality) and large-for-gestational age (average RR 0.89, 95% CI 0.41 to 1.92; I² = 82%; very low-quality). Glycaemic control indicated by mean maternal HbA1c was lower for women in the continuous monitoring group (mean difference (MD) -0.60 %, 95% CI -0.91 to -0.29; one study, 71 women; moderate-quality). There was not enough evidence to assess perinatal mortality and there were no clear differences for preterm birth less than 37 weeks' gestation (low-quality). Mortality or morbidity composite, neurosensory disability and preterm birth less than 34 weeks were not reported.6. Constant CGM versus intermittent CGM (one study, 25 women): there was no clear difference between groups for caesarean section (RR 0.77, 95% CI 0.33 to 1.79; very low-quality), glycaemic control (mean blood glucose in the 3rd trimester) (MD -0.14 mmol/L, 95% CI -2.00 to 1.72; very low-quality) or preterm birth less than 37 weeks' gestation (RR 1.08, 95% CI 0.08 to 15.46; very low-quality). Other primary (hypertensive disorders of pregnancy, large-for-gestational age, perinatal mortality (stillbirth and neonatal mortality), mortality or morbidity composite, and neurosensory disability) or GRADE outcomes (preterm birth less than 34 weeks' gestation) were not reported.
AUTHORS' CONCLUSIONS: This review found no evidence that any glucose monitoring technique is superior to any other technique among pregnant women with pre-existing type 1 or type 2 diabetes. The evidence base for the effectiveness of monitoring techniques is weak and additional evidence from large well-designed randomised trials is required to inform choices of glucose monitoring techniques.
METHODS: This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1).
RESULTS: The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk.
CONCLUSION: Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.
METHODS: This was a quasi-experimental study conducted in two sub-urban communities in Seremban, Malaysia. A total of 268 participants with prediabetes aged between 18 to 65 years old were assigned to either the community-based lifestyle intervention (Co-HELP) (n = 122) or the usual care (n = 146) groups. The Co-HELP program was delivered in partnership with the existing community volunteers to incorporate diet, physical activity, and behaviour modification strategies. Participants in the Co-HELP group received twelve group-based sessions and two individual counselling to reinforce behavioural change. Participants in the usual care group received standard health education from primary health providers in the clinic setting. Primary outcomes were fasting blood glucose, 2-hour plasma glucose, and HbA1C. Secondary outcomes included weight, BMI, waist circumference, total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure, physical activity, diet, and health-related quality of life (HRQOL).
RESULTS: An intention-to-treat analysis of between-groups at 12-month (mean difference, 95% CI) revealed that the Co-HELP participants' mean fasting plasma glucose reduced by -0.40 mmol/l (-0.51 to -0.28, p<0.001), 2-hour post glucose by -0.58 mmol/l (-0.91 to -0.24, p<0.001), HbA1C by -0.24% (-0.34 to -0.15, p<0.001), diastolic blood pressure by -2.63 mmHg (-3.79 to -1.48, p<0.01), and waist circumference by -2.44 cm (-4.75 to -0.12, p<0.05) whereas HDL cholesterol increased by 0.12 mmol/l (0.05 to 0.13, p<0.01), compared to the usual care group. Significant improvements were also found in HRQOL for both physical component (PCS) by 6.51 points (5.21 to 7.80, p<0.001) and mental component (MCS) by 7.79 points (6.44 to 9.14, p<0.001). Greater proportion of participants from the Co-HELP group met the clinical recommended target of 5% or more weight loss from the initial weight (24.6% vs 3.4%, p<0.001) and physical activity of >600 METS/min/wk (60.7% vs 32.2%, p<0.001) compared to the usual care group.
CONCLUSIONS: This study provides evidence that a culturally adapted diabetes prevention program can be implemented in the community setting, with reduction of several diabetes risk factors and improvement of HRQOL. Collaboration with existing community partners demonstrated a promising channel for the wide-scale dissemination of diabetes prevention at the community level. Further studies are required to determine whether similar outcomes could be achieved in communities with different socioeconomic backgrounds and geographical areas.
TRIAL REGISTRATION: IRCT201104106163N1.
METHODS: PCOS was induced in rats except for normal control by administering LTZ at 1 mg/kg/day for 21 days. Methanolic extract of F. deltoidea leaf was then orally administered to the PCOS rats at the dose of 250, 500, or 1000 mg/kg/day, respectively for 15 consecutive days. Lipid profile was measured enzymatically in serum. The circulating concentrations of reproductive hormone and antioxidant enzymes were determined by ELISA assays. Ovarian and uterus histomorphometric changes were further observed by hematoxylin and eosin (H&E) staining.
RESULTS: The results showed that treatment with F. deltoidea at the dose of 500 and 1000 mg/kg/day reduced insulin resistance, obesity indices, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), malondialdehyde (MDA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to near-normal levels in PCOS rats. The levels of high-density lipoprotein cholesterol (HDL), estrogen, and superoxide dismutase (SOD) are also similar to those observed in normal control rats. Histomorphometric measurements confirmed that F. deltoidea increased the corpus luteum number and the endometrial thickness.
CONCLUSIONS: F. deltoidea can reverse PCOS symptoms in female rats by improving insulin sensitivity, antioxidant activities, hormonal imbalance, and histological changes. These findings suggest the potential use of F. deltoidea as an adjuvant agent in the treatment program of PCOS.
METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.
RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.
CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.
METHODS: Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels.
RESULTS: Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group.
CONCLUSIONS: The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.