The effects of lipoic acid and α-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial

Antioxidants probably play an important role in the etiology of type 2 diabetes (DM2). This study evaluated the effects of supplementation with lipoic acid (LA) and α-tocopherol on the lipid profile and insulin sensitivity of DM2 patients.A randomized, double-blind, placebo-controlled trial involving 102 DM2 patients divided into four groups to receive daily supplementation for 4 months with: 600 mg LA (n = 26); 800 mg α-tocopherol (n = 25); 800 mg α-tocopherol + 600 mg LA (n = 25); placebo (n = 26). Plasma α-tocopherol, lipid profile, glucose, insulin, and the HOMA index were determined before and after supplementation. Differences within and between groups were compared by ANOVA using Bonferroni correction. Student's t-test was used to compare means of two independent variables.The vitamin E/total cholesterol ratio improved significantly in patients supplemented with vitamin E + LA and vitamin E alone (p ≤ 0.001). There were improvements of the lipid fractions in the groups receiving LA and vitamin E alone or in combination, and on the HOMA index in the LA group, but not significant.The results suggest that LA and vitamin E supplementation alone or in combination did not affect the lipid profile or insulin sensitivity of DM2 patients.     

Effects of 12 weeks’ treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study

Aims/hypothesis

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA_1c and cardiovascular risk factors in type 2 diabetes.

Methods

Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n?=?20) or placebo (n?=?21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA_1c and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements.

Results

Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049?±?17,659 vs 27,270?±?32,004 pmol/l × min (p?=?0.838). In the placebo group AUC for insulin decreased from 27,392?±?14,348 pmol/l × min to 22,938?±?11,936 pmol/l × min (p?=?0.002). Esomeprazole treatment (n?=?20) caused a ninefold increase in the AUC for gastrin. HbA_1c increased from 7.0?±?0.6% (53?±?5 mmol/mol) to 7.3?±?0.8% (56?±?6 mmol/mol) in the esomeprazole-treated group and from 7.0?±?0.6% (53?±?5 mmol/mol) to 7.4?±?0.8% (57?±?6 mmol/mol) in the placebo group (n?=?21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p?>?0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p?<?0.05). No change in BP was seen in the patients treated with esomeprazole.

Conclusions/interpretation

Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT00699426

Funding

The study was funded by Novo Nordisk A/S and Christian Hansen A/S.     

Effects of calcium–vitamin D co-supplementation on glycaemic control,inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial

Aims/hypothesis

This study was designed to assess the effects of calcium and vitamin D supplementation on the metabolic status of pregnant women with gestational diabetes mellitus (GDM).

Methods

This randomised placebo-controlled trial was performed at maternity clinics affiliated to Kashan University of Medical Sciences, Kashan, Iran. Participants were 56 women with GDM at 24–28 weeks’ gestation (18 to 40 years of age). Subjects were randomly assigned to receive calcium plus vitamin D supplements or placebo. All study participants were blinded to group assignment. Individuals in the calcium–vitamin D group (n?=?28) received 1,000 mg calcium per day and a 50,000 U vitamin D₃ pearl twice during the study (at study baseline and on day 21 of the intervention), and those in the placebo group (n?=?28) received two placebos at the mentioned times. Fasting blood samples were taken at study baseline and after 6 weeks of intervention.

Results

The study was completed by 51 participants (calcium–vitamin D n?=?25, placebo n?=?26). However, as the analysis was based on an intention-to-treat approach, all 56 women with GDM (28 in each group) were included in the final analysis. After the administration of calcium plus vitamin D supplements, we observed a significant reduction in fasting plasma glucose (?0.89?±?0.69 vs +0.26?±?0.92 mmol/l, p?p?=?0.02) and HOMA-IR (?0.91?±?1.18 vs +0.63?±?2.01, p?=?0.001) and a significant increase in QUICKI (+0.02?±?0.03 vs ?0.002?±?0.02, p?=?0.003) compared with placebo. In addition, a significant reduction in serum LDL-cholesterol (?0.23?±?0.79 vs +0.26?±?0.74 mmol/l, p?=?0.02) and total cholesterol: HDL-cholesterol ratio (?0.49?±?1.09 vs +0.18?±?0.37, p?=?0.003) and a significant elevation in HDL-cholesterol levels (+0.15?±?0.25 vs ?0.02?±?0.24 mmol/l, p?=?0.01) was seen after intervention in the calcium–vitamin D group compared with placebo. In addition, calcium plus vitamin D supplementation resulted in a significant increase in GSH (+51.14?±?131.64 vs ?47.27?±?203.63 μmol/l, p?=?0.03) and prevented a rise in MDA levels (+0.06?±?0.66 vs +0.93?±?2.00 μmol/l, p?=?0.03) compared with placebo.

Conclusions/interpretation

Calcium plus vitamin D supplementation in women with GDM had beneficial effects on their metabolic profile.

Trial registration

www.irct.ir IRCT201311205623N11

Funding

The study was supported by a grant (no. 92110) from Kashan University of Medical Sciences.     

Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria – A double blind randomized placebo-controlled crossover trial

AimsSodium glucose transport inhibitors (SGLT2i) can reduce risk of heart failure (HF) and cardiovascular death in people with type 2 diabetes (T2D) and existing cardiovascular disease. Our aim was to examine the effect of the SGLT2i dapagliflozin on cardiac function in people with T2D and albuminuria.MethodsA secondary analysis of a double-blind, randomized, cross-over study of 12 weeks treatment with dapagliflozin 10 mg versus placebo. Myocardial function was assessed by echocardiography and biomarkers of cardiac risk were measured. An exploratory diastolic composite of echocardiographic variables was computed.ResultsOf the 36 participants completing the study 89% were male, mean age 64 ± 8 years, diabetes duration 16.4 ± 4.7 years and HbA_1c 73 ± 15 mmol/mol (8.9 ± 1.4%), 30.6% had former cardiovascular events and 32% had macroalbuminuria. Mean left ventricular ejection fraction (LVEF) was 55.4% after placebo and 54.3% after dapagliflozin (p = 0.15), global longitudinal strain −16.1 vs. −15.9, (p = 0.64), E/e′ 7.6 vs. 7.6 (p = 0.082), and tissue Doppler velocity e′ 10.0 vs. 10.6 (p = 0.05). The composite score showed diastolic function improvement of 19.8% (p = 0.021). No other significant changes were observed.ConclusionsDapagliflozin may have minor effects on diastolic function in people with T2D, albuminuria and preserved LVEF.     

Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized,placebo-controlled clinical trial of recombinant human chorionic gonadotropin

OBJECTIVE: In order to assess the hormonal determinants of insulin sensitivity and related components of the metabolic syndrome, we evaluated the effect of subcutaneous recombinant human chorionic gonadotropin (r-hCG; Ovidrel) on insulin sensitivity, vascular reactivity, leptin, insulin-like growth factor-I (IGF-I) and lipids in ambulant, community dwelling men >60 Years of age with serum testosterone 相似文献   

Vitamin D and nifedipine in the treatment of Chinese patients with grades I–II essential hypertension: A randomized placebo-controlled trial

Objectives

Low vitamin D status has been shown to be associated with hypertension. We planned to research the effect of vitamin D and nifedipine in the treatment of patients with essential hypertension.

Methods

Patients with grades I–II essential hypertension were enrolled in this single-center, double-blind, placebo-controlled trial in Beijing. All patients received a conventional antihypertensive drug (nifedipine, 30 mg/d). One hundred and twenty-six patients were randomly assigned to receive vitamin D (n = 63, 2000 IU/d) or a placebo (n = 63) as an add-on to nifedipine, by the method of permutated block randomization. Ambulatory blood pressure monitoring was performed at baseline (month 0), at month 3 and at month 6.

Results

In vitamin D supplementation group, there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (19.4 ± 11.6 ng/ml) to 6 months (34.1 ± 12.2 ng/ml; p < 0.001). At 6 months, the primary end points, a difference in the fall of 24-h mean blood pressure, between the groups was −6.2 mm Hg (95% CI −11.2; −1.1) for systolic blood pressure (p < 0.001) and −4.2 mm Hg (95% CI −8.8; −0.3) for diastolic blood pressure (p < 0.001) under intention to treat analysis. In patients with vitamin D <30 ng/ml at baseline (n = 113), 24-h mean blood pressure decreased by 7.1/5.7 mm Hg (p < 0.001). Safety and tolerability were similar among the two groups.

Conclusions

Vitamin D supplementation can reduce blood pressure in patients with hypertension, it can be an adjuvant therapy for patients with grades I–II essential hypertension.Clinical Trial Registration: This study was registered in the Chinese Clinical Trial Registry, it is available in Website: http://www.chictr.org/cn/; Registration number: ChiCTR-ONC-13003840.     

Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial

Aim: To assess the safety and efficacy of the potent and selective dipeptidyl peptidase‐4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment‐naive or who had received one oral antidiabetes drug (OAD). Methods: This multicentre, randomized, parallel group, phase III study compared linagliptin treatment (5 mg once daily, n = 336) with placebo (n = 167) for 24 weeks in type 2 diabetes patients. Before randomization, patients pretreated with one OAD underwent a washout period of 6 weeks, which included a placebo run‐in period during the last 2 weeks. Patients previously untreated with an OAD underwent a 2‐week placebo run‐in period. The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment. Results: Linagliptin treatment resulted in a placebo‐corrected change in HbA1c from baseline of ?0.69% (p < 0.0001) at 24 weeks. In patients with baseline HbA1c ≥ 9.0%, the adjusted reduction in HbA1c was 1.01% (p < 0.0001). Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5% at 24 weeks than those in the placebo arm (47.1 and 19.0%, respectively; odds ratio, OR = 4.2, p < 0.0001). Fasting plasma glucose improved by ?1.3 mmol/l (p < 0.0001) with linagliptin vs. placebo, and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2‐h postprandial glucose of ?3.2 mmol/l (p < 0.0001). Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio (p = 0.025), Homeostasis Model Assessment‐%B (p = 0.049) and disposition index (p = 0.0005). There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third‐party intervention. Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin. Conclusions: Monotherapy with linagliptin produced a significant, clinically meaningful and sustained improvement in glycaemic control, accompanied by enhanced parameters of β‐cell function. The safety profile of linagliptin was comparable with that of placebo.     

A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients

Aim: The purpose of this study was to evaluate if superior glycaemic control could be achieved with Avandamet® (rosiglitazone/metformin/AVM) compared with metformin (MET) monotherapy, and if glycaemic effects attained with AVM are durable over 18 months of treatment. Bone mineral density (BMD) and bone biomarkers were evaluated in a subgroup of patients. Methods: This was a phase IV, randomized, double‐blind, multi‐centre study in 688, drug naÏve, male and female patients who had an established clinical diagnosis of type 2 diabetes mellitus (T2DM). Patients were randomized in a 1 : 1 ratio either to AVM or MET. Results: As initial therapy in patients with T2DM, AVM was superior to MET in achieving statistically significant reductions in glycated haemoglobin (HbA1c) (p < 0.0001) and fasting plasma glucose (FPG) (p < 0.001), with more patients reaching recommended HbA1c and FPG targets for intensive glycaemic control. The glycaemic effects attained with AVM compared to MET monotherapy were durable over 18 months of treatment. In the bone substudy, AVM was associated with a significantly lower BMD in comparison with MET at week 80 in the lumbar spine and total hip (p < 0.0012 and p = 0.0005, respectively). Between‐treatment differences were not statistically significant for distal one‐third of radius BMD, femoral neck BMD or total BMD. Conclusion: Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip.