Efficacy of Exenatide Administered Twice Daily in Body Mass Index Reduction in Patients with Type 2 Diabetes Mellitus.

Background: Exenatide is a glucagon-like peptide-1 receptor agonist that can reduce body weight. This study aimed to determine the efficacy of exenatide on body mass index (BMI) reduction in patients with type 2 diabetes mellitus (T2DM) with differing baseline body weight, blood glucose, and atherosclerotic status and to determine if there is a correlation between BMI reduction and cardiometabolic indices in these patients. Methods: This retrospective cohort study used data from our randomized controlled trial. A total of 27 T2DM patients treated with combination therapy of exenatide twice daily and metformin for 52 weeks were included. The primary endpoint was a change in the BMI from the baseline to week 52. The secondary endpoint was a correlation between BMI reduction and cardiometabolic indices. Findings. The BMIs of overweight and obesity patients and those with glycated hemoglobin (HbA1c) ≥ 9% significantly decreased -1.42 ± 1.48 kg/m2(P=0.015) and -0.87 ± 0.93 kg/m2(P=0.003), respectively, at the baseline after 52 weeks of treatment. There was no reduction in BMI in patients with normal weight, HbA1c <9%, the nonatherosclerosis group, and the atherosclerosis group. The decrease in BMI was positively correlated with changes in blood glucose, high-sensitivity C-reactive protein (hsCRP), and systolic blood pressure (SBP). Conclusion: BMI scores improved after exenatide treatment for 52 weeks in T2DM patients. Weight loss was affected by baseline body weight and blood glucose level. In addition, BMI reduction from the baseline to 52 weeks was positively correlated with baseline HbA1c, hsCRP, and SBP. Trial Registration. Chinese Clinical Trial Registry (ChiCTR-1800015658).

Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: a 52-week randomized, open-label, controlled trial.

BACKGROUND: Exenatide, a glucagon like peptide 1 analog, has been suggested to reduce the cardiovascular disease risk factors, such as body weight, blood pressure and subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). This was the first randomized, open-label, controlled trial to compare the effects of exenatide versus insulin on subclinical atherosclerosis, as assessed by carotid-intima media thickness (CIMT), in patients with T2DM. METHODS: A total of 66 patients with T2DM admitted from March 10, 2015 to June 20, 2017 in the Department of Endocrinology, Beijing Hospital were randomized to receive twice-daily exenatide or aspartate 70/30 insulin for 52 weeks. The primary endpoint was change from baseline in CIMT, and secondary endpoints included changes at week 52 from baseline in body weight, glycemic markers, lipid metabolism markers, blood pressure, C-reactive protein, fibrinogen, 8-hydroxydeoxyguanosine, irisin, and brain natriuretic peptide. RESULTS: Exenatide more significantly reduced the CIMT from baseline compared with insulin after 52 weeks, with a mean difference of - 0.14 mm (95% interval confidence: - 0.25, - 0.02; P = 0.016). Weight and body mass index were both significantly reduced in the exenatide group over 52 weeks. Exenatide reduced total lipoprotein and low-density lipoprotein cholesterol levels more significantly than insulin at weeks 16 and 40. Correlation analyses showed that CIMT was positively correlated with low-density lipoprotein cholesterol. CONCLUSIONS: Twice-daily exenatide could prevent atherosclerosis progression in patients with T2DM over a 52-week treatment period compared with insulin therapy. Trial registration Chinese Clinical Trial Registry ChiCTR-1800015658.

Associations between urinary iodine concentration, lipid profile and other cardiometabolic risk factors in adolescents: a cross-sectional, population-based analysis.

Low urinary iodine concentration (UIC) is associated with dyslipidaemia in adults but is not well characterised in adolescents. Because dyslipidaemia is a cardiovascular risk factor, identifying such an association in adolescents would allow for the prescription of appropriate measures to maintain cardiovascular health. The present study addresses this question using data in the 2001-2012 National Health and Nutrition Examination Survey for 1692 adolescents aged 12-19 years. Primary outcomes were UIC, cardiometabolic risk factors and dyslipidaemia. Data for subjects categorised by low and normal UIC and by sex were analysed by univariate and multivariate logistic regression. Treating UIC as the independent variable, physical activity level, apoB and lipid profiles differed significantly between subjects with low and normal UIC. Subjects with low UIC had a significantly greater risk of elevated total cholesterol (TC) (95 % CI 1·37, 2·81), elevated non-HDL (95 % CI 1·33, 2·76) and elevated LDL (95 % CI 1·83, 4·19) compared with those with normal UIC. Treating UIC as a dependent variable, the risk of low UIC was significantly greater in those with higher apoB (95 % CI 1·52, 19·08), elevated TC (≥4·4mmol/l) (95 % CI 1·37, 2·81) and elevated non-HDL (≥3·11mmol/l) (95 % CI 1·33, 2·76) than in those with normal UIC. These results show that male and female adolescents with low UIC tend to be at greater risk of dyslipidaemia and abnormal cardiometabolic biomarkers, though the specific abnormal parameters differed between sexes. These results may help to identify youth who would benefit from interventions to improve their cardiometabolic risk.

Comparing the effects of twice-daily exenatide and insulin on renal function in patients with type 2 diabetes mellitus: secondary analysis of a randomized controlled trial.

This is a secondary analysis of a randomized controlled trial (RCT) on the effects of the glucagon-like peptide-1 receptor agonists exenatide and insulin aspartate 30 injection on carotid intima-media thickness. Here, we report the renal outcomes of the intervention in patients with type 2 diabetes mellitus (T2DM). Data from the RCT study was used to evaluate the effect of exenatide or insulin given for 52 weeks on estimated glomerular filtration rate (eGFR) in patients with T2DM. The primary end point was the change in the eGFR from baseline between the exenatide and insulin groups in normal versus overweight patients and patients with obesity. The secondary end point was the correlation between change in eGFR and oxidative stress, glycemic control, and dyslipidemia. There was a significant difference in eGFR between the insulin and exenatide groups at 52 weeks (p=0.0135). Within the insulin group, the eGFR remained below baseline at 52 weeks in all patients, and there was an increase in body weight in the normal group compared with the overweight patients and patients with obesity. The opposite was observed in the exenatide group. A decrease in body weight was prominent in the exenatide group at 52 weeks (p<0.05), the eGFR was below baseline in overweight patients and patients with obesity and significantly above baseline in the normal group (p<0.05). The eGFR was positively correlated to 8-oxo-7,8-dihydroguanosine in the insulin group (p<0.05) but not the exenatide group. It can be concluded that compared with insulin, exenatide may improve renal function in overweight patients and patients with obesity more than in normal-weight patients with T2DM, but a further RCT is needed to confirm this effect.

Novel role of SF1 in alleviating thyroid-associated ophthalmopathy through the AMPK/mTOR signaling pathway.

BACKGROUND/AIM: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue. This study aims to explore whether steroidogenic factor 1 (SF1) is implicated in development of TAO through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Initially, we extracted orbital preadipocytes from 10 TAO patients for culture and identification. After differentiation, cells were inoculated with plasmids with overexpressed SF1, and plasmids with siRNA against SF1, respectively. Then fat content and PGE2 secretion were measured by using ELISA. The levels of SF1, Bax, Bcl-2, Caspase3, Pref-1, PPARγ, Leptin, Adiponectin, p-AMPKαThr172, p-mTORSer2448, and p-S6KThr389 were detected by RT-qPCR and western blot analysis. Cell proliferation and apoptosis were measured by EdU and flow cytometry. RESULTS: TAO patients showed reduced SF1 expression in orbital preadipocytes. Overexpression of SF1 led to inhibited expression of Bcl-2, PPARγ, Leptin, Adiponectin and p-AMPKαThr172, fat content, cell proliferation and differentiation, but increased levels of Bax, Caspase3, Pref-1, p-mTORSer2448 and p-S6KThr389, PGE2 secretion and apoptosis rate. CONCLUSION: Our result showed up-regulated SF1 may relieve TAO through suppressing cell proliferation and differentiation, but accelerating cell apoptosis by inhibiting the activation of the AMPK/mTOR signaling pathway.

In Vivo Corneal Confocal Microscopy Detects Improvement of Corneal Nerve Parameters following Glycemic Control in Patients with Type 2 Diabetes.

AIM: This study aimed to investigate whether in vivo corneal confocal microscopy (CCM) can detect the improvement of corneal nerve parameters following glycemic control in patients with type 2 diabetes in natural history. METHODS: Thirty-two patients with diabetes complicated by DPN and 12 age-matched control subjects underwent detailed clinical examination and were assessed per the Toronto Clinical Scoring Scale for DPN, nerve conduction studies, and IVCCM at baseline and after approximately one year from the first visit. RESULTS: At follow-up, 16 diabetic patients had improved glycemic control (group A, HbA1c < 7.0%, 7.78 ± 1.62% versus 6.52 ± 0.59%, P = 0.005), while the remainder continued to have elevated HbA1c levels (group B, HbA1c ≥ 7.0%, 8.55 ± 1.57% versus 8.79 ± 1.05%, P = 0.527). For patients in group A, corneal nerve fiber density (CNFD) (18.55 ± 5.25 n/mm2 versus 21.78 ± 6.13 n/mm2, P = 0.005) and corneal nerve fiber length (CNFL) (11.62 ± 2.89 mm/mm2 versus 13.04 ± 2.44 mm/mm2, P = 0.029) increased significantly compared to baseline. For patients in group B, sural sensory nerve conduction velocity (47.93 ± 7.20 m/s versus 44.67 ± 6.43 m/s, P = 0.024), CNFD (17.19 ± 5.31 n/mm2 versus 15.67 ± 4.16 n/mm2, P = 0.001), corneal nerve branch density (19.33 ± 12.82 n/mm2 versus 14.23 ± 6.56 n/mm2, P = 0.033), and CNFL (11.16 ± 2.57 mm/mm2 versus 9.90 ± 1.75 mm/mm2, P = 0.011) decreased significantly. CONCLUSIONS: The results of this study suggest that morphological repair of corneal nerve fibers can be detected when glycemic control improves. In vivo CCM could be a sensitive method that can be applied in future longitudinal or interventional studies on DPN.

A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients.

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients.In total 13,400 participants were analyzed based on the results of the glucose tolerance test. Using a cross-sectional study, we showed the relationship between IR and the level of sex hormones among 3 different glucose tolerance states: normal control people, IGT, and T2DM patients. We also analyzed the relationship between IR and abnormal lipid metabolism.Significantly, luteinizing, progesterone, estradiol, prolactin, and follicle-stimulating hormone levels decreased in T2DM and IGT patients compared with those in normal control people. The association between IR and lipid metabolism disorders in T2DM and IGT patients was also observed.Our clinical findings may offer new insights into understanding the mechanism of metabolic disorders and in new therapeutic methods for the treatment of the prevalence of type 2 diabetes.

[Impacts of atorvastatin on blood lipids and arterial media thickness in new-onset type 2 diabetes patients].

OBJECTIVE: To analyze the impact of atorvastatin on blood lipids and arterial media thickness (IMT) in new-onset type 2 diabetes patients. METHODS: 333 patients, 30-70 years old and diagnosed within one year as type 2 diabetes, were selected from the Chinese Diabetes Complication Prevention Study (CDCPS) to take part in this study. Changes of blood lipids and IMT of carotid, femoral and iliac artery pre and post the administration of atorvastatin were tested and followed for 24 months. RESULTS: Total cholesterol, triglycerides and low-density lipoprotein decreased significantly (P = 0.000) and maintained at a low level. The carotid artery IMT decreased significantly (P = 0.022) at the end of this study, but the femoral and iliac artery IMT did not show any obvious change. There were no serious adverse events noticed, during the study period. CONCLUSION: Long-term use of atorvastatin seemed to be safe and effective in reducing blood lipids in patients with type 2 diabetes thus could delay the development of atherosclerosis.