Prandial insulin has been essential for the improved management of the type 1 diabetic patient. Interestingly, many studies have evaluated the addition of prandial insulin to the type 2 diabetic patients with improved control. The greatest drop in A1c with the use of various type of prandial insulins have resulted in the decrease of 1.3% in the A1c measurement. Interestingly, none of the published trials with goal of fasting blood glucose (FBG) have ever obtained the goal A1c. Since a drop in FBG of 28.7mg/dl is equal to a 1% drop in A1c, a simple approach to obtain a target A1c would be to focus on the FBG (per ADA: Average Blood Glucose = A1c (%) x 28.7 - 46.7mg/d). However, average blood glucose requires multiple measurements and may be less accurate then using just a FBG. Since prandial insulin clinical trials have only demonstrated a drop in A1c by 0.3-1.3% the use of only a FBG to help patients get to goal may be easier to teach and to obtain. It might save time and money. Our hypothesis is that if patient obtain a FBG <100 mg/dl for 2-3 months then 70% will be at an A1c goal <7.0%. After a few months of good fasting glucose control the provider can use this equation (FBG+80)/30 to estimate A1c. For example, a FBG of 130mg/dl would be (130 + 80)/30 = 7.0%; or a FBG of 190 would be (190+80)/30 =eA1c 9% (estimate of A1c). While type 1 diabetes has a very complex daily glucose pattern, the approach to type 2 diabetics on insulin could become simplified.

Background

Cardiovascular morbidity and mortality are a major burden in patients with type 2 diabetic mellitus. In a landmark study, semaglutide (an injectable glucagon like peptide-1 receptor agonist) has been shown to significantly reduce cardiovascular events, however, the mechanism of benefit is still unknown. The primary hypothesis of our current study is to assess the effect of semaglutide to reduce progression of noncalcified coronary atherosclerotic plaque volume as measured by serial coronary CTA as compared to placebo in persons with diabetes over 1 year.

Methods

One hundred forty patients will be enrolled after signing informed consent and followed up for 12 months and with a phone call 30 days after medical discontinuation. All the participants will undergo coronary artery calcium scoring and coronary computed tomography angiography at our center at baseline and 12 months. Eligible participants will be randomly assigned to semaglutide 2 mg/1.5 ml (1.34 mg/ml) prefilled pen for subcutaneous (SC) injection or placebo 1.5 ml, pen-injector for SC injection in a 1:1 fashion as add-on to their standard of care.

Results

As of July 2019, the study was approximately 30% enrolled with an estimated enrollment completion by first quarter of 2020 and end of study by first quarter 2021. Thirty patients were enrolled as of 23 July 2019. Preliminary data of demographics and clinical characteristics were summarized.

Conclusion

Our current study will provide important imaging-derived data that may add relevance to the clinically derived outcomes from liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results and semaglutide and cardiovascular outcomes in patients with type 2 diabetic mellitus 6 trials.

BACKGROUND:Cardiovascular morbidity and mortality are a major burden in patients with type 2 diabetic mellitus. In a landmark study, semaglutide (an injectable glucagon like peptide-1 receptor agonist) has been shown to significantly reduce cardiovascular events, however, the mechanism of benefit is still unknown. The primary hypothesis of our current study is to assess the effect of semaglutide to reduce progression of noncalcified coronary atherosclerotic plaque volume as measured by serial coronary CTA as compared to placebo in persons with diabetes over 1 year. METHODS:One hundred forty patients will be enrolled after signing informed consent and followed up for 12 months and with a phone call 30 days after medical discontinuation. All the participants will undergo coronary artery calcium scoring and coronary computed tomography angiography at our center at baseline and 12 months. Eligible participants will be randomly assigned to semaglutide 2 mg/1.5 ml (1.34 mg/ml) prefilled pen for subcutaneous (SC) injection or placebo 1.5 ml, pen-injector for SC injection in a 1:1 fashion as add-on to their standard of care. RESULTS:As of July 2019, the study was approximately 30% enrolled with an estimated enrollment completion by first quarter of 2020 and end of study by first quarter 2021. Thirty patients were enrolled as of 23 July 2019. Preliminary data of demographics and clinical characteristics were summarized. CONCLUSION:Our current study will provide important imaging-derived data that may add relevance to the clinically derived outcomes from liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results and semaglutide and cardiovascular outcomes in patients with type 2 diabetic mellitus 6 trials.

Evidence suggests that asymptomatic and mild SARS-CoV-2 infections comprise > 95% of all cases. Developing a test that indicates past infection and possible immunity against the virus is important. We administered 244 antibody tests to three groups of high-risk population. The test consisted of an IgG component and an IgM component. The overall IgM/IgG positivity for patients with none, mild, moderate, and severe symptoms were 21.1%, 21.8%, 14.2%, and 26.9%, respectively. Those with moderate or severe symptoms were no more or less likely to have positive antibody tests than those with no or mild symptoms.

Impaired endothelial function portends an increased risk of cardiovascular disease. Vascular oxidative stress and systemic inflammation play a critical role in the pathogenesis and progression of vascular disease. Aged garlic extract (AGE) may improve impaired vascular endothelial function, while decreasing the progression of atherosclerotic plaque. We hypothesized that AGE may improve endothelial function, and in this study, we examined this hypothesis to determine whether this can be achieved over a period of 3 months, measured by the cardio-ankle vascular index (CAVI), by reducing intracellular oxidant stress and stimulating nitric oxide generation in endothelial cells. We conducted a double-blinded placebo controlled, randomized clinical trial to investigate the effects of AGE on CAVI in subjects with type 2 diabetes mellitus. A total of 65 individuals (38 men and 27 women) with a mean age of 58.8±11.1 years were enrolled and randomized to the AGE or placebo group in a double-blind placebo controlled trial. An ANOVA model with treatment as the main effect was used to compare changes in CAVI from baseline to follow-up between groups. The primary objective of this study was reduction in CAVI over a 3-month period. In the AGE group, CAVI was reduced on average by 0.71±1.27 vs. a mean reduction of 0.13±0.94 in the placebo group (P=0.04). On the whole, this study demonstrates that AGE has a positive impact on endothelial function in patients with T2DM and may play a role in the primary prevention of cardiovascular disease.

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM.

Background

Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear.

Objective

This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS).

Methods

Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change.

Results

The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (β: -1.61; 95% CI: -2.79, -0.43; P = 0.008).

Conclusions

This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.

Introduction

Thyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients.

Methods

In a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression.

Findings

In unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively.

Discussion

In HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.