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Background and Purpose: A promising, yet lengthy measure to identify mastery of patient-identified stress is Younger’s (1991, 1993) Mastery of Stress Instrument (MSI). With a goal for a parsimonious and valid measure, this study determined the psychometric properties of a reduced item instrument with adults diagnosed with type 2 diabetes. Methods: First, an expert content analysis was completed. Second, item and confirmatory factor analysis were completed with a sample of 200 adults with a diagnosis of type 2 diabetes. Results: Eight items were removed through content validity and seven items were removed with Item analysis. Factor analysis supported Younger’s four sub-concepts. Conclusions: Future research with this revised MSI scale is advocated to identify those who may need strategies to increase their mastery of stress.

Low blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes.2423 participants were randomized to 4000 IU/day of vitamin DMean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (-0.45 %, 95%CI -0.75 to -0.15).In people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score.D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.

Objective: Our goal is to measure real-world effects of at-risk driver physiology on safety-critical tasks like driving by monitoring driver behavior and physiology in real-time. Drivers with type ...

OBJECTIVE To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA1c 7.0–10.0% (53–86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA1c from baseline to week 26. RESULTS In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA1c was observed with semaglutide from −1.1% (0.05 mg) to −1.9% (0.3 mg) and with liraglutide from −0.5% (0.3 mg) to −1.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was −0.02% (P < 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8–54.0% and 21.9–41.5% of patients, respectively. CONCLUSIONS Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs.

Aim: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects. Materials and methods: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol-specified composite endpoint was the proportion of participants achieving HbA1c

We previously reported that fish oil in combination with cyclooxygenase (COX) inhibitors exerts enhanced hypolipidemic and anti-inflammatory effects in mice. Here, we sought to determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in adipose tissue (AT) in humans. Obese dyslipidemic patients were randomly assigned to one of these interventions for 12 wk: 1) Standard nutrition counseling (control), 2) ω-3 PUFAs (2 g twice daily), 3) NX (220 mg twice daily), and 4) ω-3 PUFAs (2 g twice daily) + NX (220 mg twice daily). The serum triglycerides showed a trend towards a reduction and a significant reduction (P0.05) in ω-3 and ω3 + NX-treated subjects, respectively, compared to control. The mRNA expression of vascular cell adhesion molecule-1 (Vcam1), an inflammatory marker, increased significantly in AT of ω-3 PUFA-treated subjects but not in ω-3 PUFAs+NX-treated group. The plasma level of glycine-conjugated hyodeoxycholic acid, a secondary bile acid with hypolipidemic property, increased significantly in ω-3 PUFAs + NX-treated group. Our data suggest that combining NX with ω-3 PUFAs increases their effectiveness in reducing serum TG and favorably altering AT gene expression and plasma bile acid profile.

Context Variations in the prevalence and etiology of type 2 diabetes (T2D) across race and ethnicity may affect treatment responses. Semaglutide is a glucagon-like peptide-1 analog approved for once-weekly, subcutaneous treatment of T2D. Objective To compare semaglutide efficacy and safety in race and ethnicity subgroups across the SUSTAIN trials. Design Post hoc analysis of data from phase 3 randomized SUSTAIN 1–5 and 7 (pooled), and SUSTAIN 6 trials. Participants 3074 subjects (SUSTAIN 1–5 and 7) and 1648 subjects (SUSTAIN 6). Interventions Semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100IU/ml and dulaglutide 0.75 or 1.5 mg). Main Outcome Measures Change in hemoglobin A1C (HbA1c) and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints. Results HbA1c was reduced from baseline by 1.0 to 1.5 percentage points and 1.3 to 2.0 percentage points, and body weight was reduced by 2.3 to 4.7 kg and 3.6 to 6.1 kg with semaglutide 0.5 and 1.0 mg, respectively, across race and ethnicity subgroups. Minor changes in blood pressure and lipid profiles were observed. Adverse events (AEs) were reported in similar proportions of subjects across trials. More Asian versus other race subgroups discontinued treatment prematurely due to AEs. The most commonly reported AEs were gastrointestinal disorders. Conclusions In this SUSTAIN trials post hoc analysis, semaglutide was associated with consistent and clinically relevant reductions in HbA1c and body weight in subjects with T2D, with minor variations in efficacy and safety outcomes associated with race or ethnicity.

Importance Rural populations have a higher prevalence of obesity and poor access to weight loss programs. Effective models for treating obesity in rural clinical practice are needed. Objective To compare the Medicare Intensive Behavioral Therapy for Obesity fee-for-service model with 2 alternatives: in-clinic group visits based on a patient-centered medical home model and telephone-based group visits based on a disease management model. Design, setting, and participants Cluster randomized trial conducted in 36 primary care practices in the rural Midwestern US. Inclusion criteria included age 20 to 75 years and body mass index of 30 to 45. Participants were enrolled from February 2016 to October 2017. Final follow-up occurred in December 2019. Interventions All participants received a lifestyle intervention focused on diet, physical activity, and behavior change strategies. In the fee-for-service intervention (n = 473), practice-employed clinicians provided 15-minute in-clinic individual visits at a frequency similar to that reimbursed by Medicare (weekly for 1 month, biweekly for 5 months, and monthly thereafter). In the in-clinic group intervention (n = 468), practice-employed clinicians delivered group visits that were weekly for 3 months, biweekly for 3 months, and monthly thereafter. In the telephone group intervention (n = 466), patients received the same intervention as the in-clinic group intervention, but sessions were delivered remotely via conference calls by centralized staff. Main outcomes and measures The primary outcome was weight change at 24 months. A minimum clinically important difference was defined as 2.75 kg. Results Among 1407 participants (mean age, 54.7 [SD, 11.8] years; baseline body mass index, 36.7 [SD, 4.0]; 1081 [77%] women), 1220 (87%) completed the trial. Mean weight loss at 24 months was -4.4 kg (95% CI, -5.5 to -3.4 kg) in the in-clinic group intervention, -3.9 kg (95% CI, -5.0 to -2.9 kg) in the telephone group intervention, and -2.6 kg (95% CI, -3.6 to -1.5 kg) in the in-clinic individual intervention. Compared with the in-clinic individual intervention, the mean difference in weight change was -1.9 kg (97.5% CI, -3.5 to -0.2 kg; P = .01) for the in-clinic group intervention and -1.4 kg (97.5% CI, -3.0 to 0.3 kg; P = .06) for the telephone group intervention. Conclusions and relevance Among patients with obesity in rural primary care clinics, in-clinic group visits but not telephone-based group visits, compared with in-clinic individual visits, resulted in statistically significantly greater weight loss at 24 months. However, the differences were small in magnitude and of uncertain clinical importance. Trial registration ClinicalTrials.gov Identifier: NCT02456636.

Type 1 diabetes has been associated with alterations in attentional processing and other cognitive functions, and previous studies have found alterations in both brain structure and function in affected patients. However, these previous neuroimaging studies have generally examined older patients, particularly those with major comorbidities known to affect functioning independent of diabetes. The primary aim of the current study was to examine the neural dynamics of selective attention processing in a young group of patients with type 1 diabetes who were otherwise healthy (i.e., without major comorbidities). Our hypothesis was that these patients would exhibit significant aberrations in attention circuitry relative to closely-matched controls. The final sample included 69 participants age 19–35 years-old, 35 with type 1 diabetes and 34 matched non-diabetic controls, who completed an Eriksen flanker task while undergoing magnetoencephalography (MEG). Significant group differences in flanker interference activity were found across a network of brain regions, including the anterior cingulate, inferior parietal cortices, paracentral lobule, and the left precentral gyrus. In addition, neural activity in the anterior cingulate and the paracentral lobule were correlated with disease duration in patients with type 1 diabetes. These findings suggest that alterations in the neural circuitry underlying selective attention emerge early in the disease process and are specifically-related to type 1 diabetes and not common comorbidities. These findings highlight the need for longitudinal studies in large cohorts to clarify the clinical implications of type 1 diabetes on cognition and the brain.

It is now generally accepted that diabetes increases the risk for cognitive impairment, but the precise mechanisms are poorly understood. A critical problem in linking diabetes to cognitive impairment is that patients often have multiple comorbidities (e.g., obesity, hypertension) that have been independently linked to cognitive deficits. In the study reported here we focused on young adults with and without type 1 diabetes who were virtually free of such comorbidities. The two groups were matched on major health and demographic factors, and all participants completed a verbal working memory task during magnetoencephalographic brain imaging. We hypothesized that patients would have altered neural dynamics in verbal working memory processing and that these differences would directly relate to clinical disease measures. Accordingly, we found that patients had significantly stronger neural responses in the superior parietal cortices during memory encoding and significantly weaker activity in parietal-occipital regions during maintenance compared with control subjects. Moreover, disease duration and glycemic control were both significantly correlated with neural responses in various brain regions. In conclusion, young healthy adults with type 1 diabetes already have aberrant neural processing relative to their peers without diabetes, using compensatory responses to perform the task, and glucose management and duration may play a central role.

Patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) have impaired endothelial function. Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation. We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD.A double blind, randomized, placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD. Paricalcitol 1 mcg or placebo was administered orally once daily for three months. Brachial artery flow mediated dilatation (FMD), nitroglycerine mediated dilation (NMD), and plasma concentrations of inflammatory cytokines, tumor necrosis factor -α and interleukin-6, highly-sensitive C-reactive protein; endothelial surface proteins, intercellular adhesion molecule -1 and monocyte chemo attractant protein-1, and plasma glucose, insulin, free fatty acids, and urinary isoprostane were measured at baseline and end of three months.27 patients in the paricalcitol group and 28 patients in the control group completed the study, though analysis of FMD at both time points was possible in 23 patients in each group. There was no significant difference in the change in FMD, NMD or the biomarkers examined after paricalcitol or placebo treatment.Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress. The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic, lipid and anti-hypertensive therapies.

OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D(3)) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100–125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140–199 mg/dL, and/or a hemoglobin A(1c) (HbA(1c)) 5.7–6.4% (39–46 mmol/mol). RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m(2). Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA(1c) criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA(1c) criteria only. Black participants had the highest mean HbA(1c) and lowest FPG concentration compared with white, Asian, and other races (P < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA(1c) and FPG concentrations. CONCLUSIONS: D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.

Type 1 diabetes (T1D) has been linked to alterations in both brain structure and function. However, the neural basis of the most commonly reported neuropsychological deficit in T1D, psychomotor speed, remains severely understudied. To begin to address this, the current study focuses on the neural dynamics underlying motor control using magnetoencephalographic (MEG) imaging. Briefly, 40 young adults with T1D who were clear of common comorbidities (e.g., vascular disease, retinopathy, etc.) and a demographically-matched group of 40 controls without T1D completed an arrow-based flanker movement task during MEG. The resulting signals were examined in the time-frequency domain and imaged using a beamforming approach, and then voxel time series were extracted from peak responses to evaluate the dynamics. The resulting time series were statistically examined for group and conditional effects using a rigorous permutation testing approach. Our primary hypothesis was that participants with T1D would have altered beta and gamma oscillatory dynamics within the primary motor cortex during movement, and that these alterations would reflect compensatory processing to maintain adequate performance. Our results indicated that the group with T1D had a significantly stronger post-movement beta rebound (PMBR) contralateral to movement compared to controls, and a smaller neural flanker effect (i.e., difference in neural activity between conditions). In addition, a significant group-by-condition interaction was observed in the ipsilateral beta event-related desynchronization (bERD) and the ipsilateral PMBR. We also examined the relationship between oscillatory motor response amplitude and reaction time, finding a differential effect of the driving oscillatory responses on behavioral performance by group. Overall, our findings suggest compensatory activity in the motor cortices is detectable early in the disease in a relatively healthy sample of adults with T1D. Future studies are needed to examine how these subtle effects on neural activity in young, otherwise healthy patients affect outcomes in aging., Highlights • Type 1 diabetes has been repeatedly associated with deficits in psychomotor speed. • These deficits may reflect the impact of diabetes or common comorbidities. • A large group of otherwise healthy patients and matched controls underwent MEG. • Motor-related neural oscillations were imaged and statistically examined. • Two key oscillations were aberrant in type 1 diabetics and impacted performance.

Obesity disproportionately affects rural residents in the United States, and primary care has the potential to fill a major gap in the provision of weight management services for rural communities. The objective of this cluster-randomized pragmatic trial is to evaluate the comparative effectiveness of three obesity treatment models in rural primary care: the Intensive Behavior Therapy fee-for-service (FFS) model reimbursed by Medicare, a team-based model that recognizes the patient-centered medical home (PCMH) as a preferred delivery approach, and the centralized disease management (DM) model, in which phone-based counseling is provided outside of the primary care practice. We hypothesize that the PCMH and DM treatments will be more effective than FFS in reducing weight at 24 months. Thirty-six practices from the rural Midwestern U.S. are randomized to deliver one of the three interventions to 40 patients (N=1440) age 20 to 75 with a BMI 30-45 kg/m(2). In the FFS arm, primary care providers and their personnel counsel patients to follow evidence-based weight loss guidelines using the Medicare-designated treatment schedule. In the PCMH arm, patients receive a comprehensive weight management intervention delivered locally by practice personnel using a combination of in-person and phone-based group sessions. In the DM arm, the same intervention is delivered remotely by obesity treatment specialists via group conference calls. The primary outcome is weight loss at 24 months. Additional measures include fasting glucose, lipids, quality of life indicators, and implementation process measures. Findings will illuminate effective obesity treatment intervention(s) in rural primary care.

Evaluate the performance of glycated albumin (GA) monitoring by comparing it to other measures of glycemic control during intensification of antidiabetic therapy.This 12-week, prospective, multicenter study compared the diagnostic clinical performance of GA to glycated hemoglobin A1C (A1C), fructosamine corrected for albumin (FRA), fasting plasma glucose (FPG), and mean blood glucose (MBG) estimated from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in 30 patients with suboptimally controlled type 1 or 2 diabetes.Mean A1C decreased from 9.5% to 8.1%. Mean SMBG correlated closely with CGM (Pearson r = 0.783 for daily estimates and r = 0.746 for weekly estimates, P.0001). Both GA and FRA levels significantly correlated with changes from baseline in A1C and mean weekly SMBG (P.001). The lowest observed median GA occurred at 4 weeks, followed by a small increase and then a slight reduction, mirroring changes in overall mean SMBG values. The median A1C fell throughout the treatment period, failing to reflect short-term changes in SMBG. A ≥1% reduction in GA at 4 weeks was significantly associated with a ≥0.5% change in A1C at 12 weeks (odds ratio [OR] = 19.0, 95% confidence interval [CI]: 1.4, 944, P = .018).In patients receiving glucose-lowering therapy, changes in GA at 4 weeks were concordant with changes in A1C at 12 weeks, and both GA and FRA more accurately reflected short-term blood glucose fluctuations than A1C.

OBJECTIVE—Flow-mediated dilatation (FMD), induced by occlusion of the brachial artery, is an index of nitric oxide-dependent endothelial function that is impaired in patients with type 2 diabetes. Sildenafil (Viagra) is an inhibitor of phosphodiesterase 5 (PDE-5), which is used for management of erectile dysfunction in a broad range of patients, including those with type 2 diabetes. Its effects on endothelial function in these patients have not been previously assessed.RESEARCH DESIGN AND METHODS—We assessed the acute and prolonged effects of a low dose of sildenafil (25 mg) on FMD in patients with type 2 diabetes. We performed a double-blind, placebo-controlled cross-over trial in 16 patients (14 of whom completed the study) with type 2 diabetes who had erectile dysfunction without overt clinical heart disease.RESULTS—In these patients, the mean ± SD brachial artery diameter (BAD) measured by ultrasound was 4.33 ± 0.6 mm. After inducing FMD, the BAD increased 8% to 4.66 ± 0.6 mm (P = 0.2). One hour after oral administration of sildenafil 25 mg, FMD increased the BAD significantly by 15% to 4.99 ± 0.5 mm (P ≤ 0.01), whereas it did not change with placebo (4.6 ± 0.6 mm, P = 0.1). After treatment with sildenafil 25 mg daily for 2 weeks and testing 24 h after the last dose, the mean FMD was 14% (P = 0.01). In contrast, the mean FMD with placebo was 9% (P = 0.45).CONCLUSIONS—We conclude that acute and prolonged sildenafil treatment has a favorable effect on brachial artery flow-mediated dilatation that persists for at least 24 h after the last dose. Further investigation is needed to determine whether this prolonged effect has clinical implications in patients with type 2 diabetes.

Weight gain is a frequent side-effect of thiazolidinediones, possibly related to fluid retention and stimulation of pre-adipocyte differentiation.We report our experience with a low-calorie diet (800 cal, sodium content 1500 mmol/day) combined with behavior modification on eight patients treated with thiazolidinediones (six pioglitazone and two rosiglitazone).All patients had reported previous weight gain following treatment with thiazolidinediones. All patients lost weight over 12 weeks in the program with their mean +/- SD body weight falling from 270 +/- 54 lbs (123 +/- 25 kg) to 244 +/- 61 lbs (111 +/- 28 kg) (p0.01). The weight loss observed was no different from that observed in 16 age- and gender-matched patients with type 2 diabetes not treated with thiazolidinediones (from 263 +/- 54 lbs (120 +/- 25 kg) to 239 +/- 52 lbs (109 +/- 24 kg); p0.01). Glycemic control improved while reducing insulin treatment. Blood pressure control also improved and antihypertensive medications were decreased. The degree and time course of weight loss is no different from that in patients treated with other diabetic therapies and is associated with improved glycemic and blood pressure control.We conclude that a program of caloric restriction and behavior modification is effective in leading to weight loss in patients treated with thiazolidinediones. This effect is reassuring, since thiazolidinediones stimulate adipogenesis.