Co-administration of viscous fiber, Salba-chia and ginseng on glycemic management in type 2 diabetes: a double-blind randomized controlled trial.

PURPOSE: Viscous dietary fiber, functional seeds and ginseng roots have individually been proposed for the management of diabetes. We explored whether their co-administration would improve glycemic control in type 2 diabetes beyond conventional therapy. METHODS: In a randomized, double-blind, controlled trial conducted at two academic centers (Toronto, Canada and Zagreb, Croatia), individuals with type 2 diabetes were assigned to either an active intervention (10 g viscous fiber, 60 g white chia seeds, 1.5 g American and 0.75 g Korean red ginseng extracts), or energy and fiber-matched control (53 g oat bran, 25 g inulin, 25 g maltodextrose and 2.25 g wheat bran) intervention for 24 weeks, while on conventional standard of care. The prespecified primary endpoint was end difference at week 24 in HbA1c, following an intent-to-treat analysis adjusted for center and baseline. RESULTS: Between January 2016 and April 2018, 104 participants (60M:44F; mean ± SEM age 59 ± 0.8 years; BMI 29.0 ± 0.4 kg/m2; HbA1c 7.0 ± 0.6%) managed with antihyperglycemic agent(s) (n = 98) or lifestyle (n = 6), were randomized (n = 52 test; n = 52 control). At week 24, HbA1c levels were 0.27 ± 0.1% lower on test compared to control (p = 0.03). There was a tendency towards an interaction by baseline HbA1c (p = 0.07), in which a greater reduction was seen in participants with baseline HbA1c > 7% vs ≤ 7% (- 0.56 ± 0.2% vs 0.03 ± 0.2%). Diet and body weight remained unchanged. The interventions were well tolerated with no related adverse events and with high retention rate of 84%. CONCLUSIONS: Co-administration of selected dietary and herbal therapies was well-tolerated and may provide greater glycemic control as add-on therapy in type 2 diabetes. Registration: Clinicaltrials.gov NCT02553382 (registered on September 17, 2015).

Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

Correction to: Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

In contrast to statements made in the above paper, measurements of waist and hip circumference were in fact available.

Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

AIMS/HYPOTHESIS: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors' request ( https://doi.org/10.2337/dc16-rt02 ) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. METHODS: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5-8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) 'full-dose nut diet' (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) 'full-dose muffin diet' (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) 'half-dose nut diet' (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. RESULTS: A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by -2.0 mmol/mol (95% CI -3.8, -0.3 mmol/mol) (-0.19% [95% CI -0.35%, -0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 ångström [LDL-c<255Å]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (-2.0 mmol/mol [-0.18%]; p = 0.044), cholesterol (-0.25 mmol/l; p = 0.022), LDL-cholesterol (-0.23 mmol/l; p = 0.019), non-HDL-cholesterol (-0.26 mmol/l; p = 0.020), apolipoprotein B (-0.06 g/l, p = 0.013) and LDL-c<255Å (-0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. CONCLUSIONS/INTERPRETATION: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410722 FUNDING: The study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Loblaw Companies and the Canada Research Chairs Program of the Government of Canada.

Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

BACKGROUND: Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. METHODS: Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. RESULTS: Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). CONCLUSIONS: In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS.

AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m2 ) vs those without CKD. Within the CKD cohort, the same analyses were performed, comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analysed in those who received at least 1 dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. RESULTS: CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants. CONCLUSIONS: Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated, with no meaningful differences in safety outcomes observed between those with CKD assigned to sitagliptin or placebo.

Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS trial.

AIM: To examine fracture incidence among participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). RESEARCH DESIGN AND METHODS: We used data from 14 671 participants in the TECOS study who were randomized double-blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment was examined using multivariable Cox proportional hazards regression. RESULTS: The baseline mean (standard deviation) participant age was 65.5 (8.0) years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was 7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1% were non-white. During 43 222 person-years' follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip, n = 34; upper extremity, n = 81; and clinical spine, n = 31). Adjusted analyses showed fracture risk increased independently with older age (P < .001), female sex (P < .001), white race (P < .001), lower diastolic blood pressure (P < .001) and diabetic neuropathy (P = .003). Sitagliptin, compared with placebo, was not associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P = .944; adjusted HR 1.03, P = .745], major osteoporotic fractures (P = .673) or hip fractures (P = .761). Insulin therapy was associated with a higher fracture risk (HR 1.40, 95% CI 1.02-1.91; P = .035), and metformin with a lower risk (HR 0.76, 95% CI 0.59-0.98; P = .035). CONCLUSION: Fractures were common among people with diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin and metformin treatment were associated with higher and lower fracture risks, respectively.

Latent variable mixture models to test for differential item functioning: a population-based analysis.

BACKGROUND: Comparisons of population health status using self-report measures such as the SF-36 rest on the assumption that the measured items have a common interpretation across sub-groups. However, self-report measures may be sensitive to differential item functioning (DIF), which occurs when sub-groups with the same underlying health status have a different probability of item response. This study tested for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scales in population-based data using latent variable mixture models (LVMMs). METHODS: Data were from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective national cohort study. LVMMs were applied to the ten PF and five MH SF-36 items. A standard two-parameter graded response model with one latent class was compared to multi-class LVMMs. Multivariable logistic regression models with pseudo-class random draws characterized the latent classes on demographic and health variables. RESULTS: The CaMos cohort consisted of 9423 respondents. A three-class LVMM fit the PF sub-scale, with class proportions of 0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting greater limitations were consistently higher in classes 2 and 3 than class 1. For MH items, respondents in class 2 reported more health problems than in class 1. Differences in item thresholds and factor loadings between one-class and multi-class models were observed for both sub-scales. Demographic and health variables were associated with class membership. CONCLUSIONS: This study revealed DIF in population-based SF-36 data; the results suggest that PF and MH sub-scale scores may not be comparable across sub-groups defined by demographic and health status variables, although effects were frequently small to moderate in size. Evaluation of DIF should be a routine step when analysing population-based self-report data to ensure valid comparisons amongst sub-groups.

Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ.

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.

Bilateral atypical femoral fractures: how much symmetry is there on imaging?

OBJECTIVE: To evaluate bilateral atypical femoral fractures (AFFs) and to compare imaging features of paired fractures. MATERIALS AND METHODS: Bilateral femoral imaging studies of 124 patients on bisphosphonate therapy with at least one AFF were retrospectively reviewed. Time between AFF diagnoses was determined. The following imaging features were evaluated for each AFF: fracture location, femoral angle, length of cortical thickening, medial spike location, fracture orientation, and comminution. Associations between imaging findings on pairs of bilateral AFFs were assessed with Spearman's correlation (rs) and the Kappa statistic (κ). RESULTS: Bilateral AFFs were present in 78/124 (62.9%) cases (3 men, 75 women; mean age 67.3 years). Average time between contralateral AFF diagnoses was 10.3 months. Contralateral AFFs were diagnosed within 12 months of the index fracture in 60/78 (76.9%) cases and within 3 years in 69/78 (88.5%) cases. There was a strong correlation between bilateral AFF locations (rs = 0.65), with 58/76 (76.3%) occurring within a distance of <5 cm and 41/76 (53.9%) within a distance of ≤2.5 cm. Bilateral AFF pairs had moderately correlated femoral angles (rs = 0.42), and weakly correlated lengths of cortical thickening (rs = 0.28). There was substantial agreement for medial spike location (κ = 0.68) and fracture orientation (κ = 0.64), and moderate agreement for lack of comminution (κ = 0.42). All findings were independent of time between AFF diagnoses. CONCLUSIONS: Patients with unilateral atypical femoral fractures are likely to be diagnosed with a contralateral AFF within the first year of presentation. Bilateral AFFs commonly have similar imaging features, including location along the femur.

Intensive blood pressure control, falls, and fractures in patients with type 2 diabetes: the ACCORD trial.

BACKGROUND: There are few rigorous studies to confirm or refute the commonly cited concern that control of blood pressure to lower thresholds may result in an increased risk of falls and fractures. OBJECTIVE: To compare falls and fractures in participants with type 2 diabetes in the intensive (targeting a systolic blood pressure of < 120 mmHg) and standard (targeting a systolic blood pressure of < 140 mmHg) blood pressure control arms of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial (N = 4,733). PARTICIPANTS: A subset of 3,099 participants self-reported annually on the occurrence of falls and non-spine fractures. Fractures were centrally adjudicated. MAIN MEASURES: The incidence of falls in the two treatment groups was compared using a random-effects negative binomial model, and fracture risk was compared using Cox proportional hazards models. KEY RESULTS: At enrollment in both groups, the mean age was 62 years, 44% were women, 25% were Black, and mean blood pressure was 138/75 mmHg. During follow-up, all classes of medications, particularly thiazide diuretics, were more commonly prescribed in the intensive group. After 1 year of follow-up, the mean systolic blood pressure was 133 ± 15 mmHg in the standard group and 119 ± 14 mmHg in the intensive group. The adjusted rate of falls did not differ in the intensive and standard groups (62.2/100 person-years vs. 74.1/100 person-years, RR = 0.84, 95% CI 0.54-1.29, p = 0.43). The risk of non-spine fractures was nonsignificantly lower in the intensive than in the standard blood pressure group (HR 0.79, 95% CI 0.62-1.01, p = 0.06). CONCLUSIONS: We conclude that intensive antihypertensive treatment that lowered mean systolic blood pressure to below 120 mmHg was not associated with an increased risk of falls or non-spine fractures in patients age 40 to 79 years with type 2 diabetes.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. METHODS: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks' duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non-high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. RESULTS: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference -0.17 mmol/L, 95% confidence interval -0.25 to -0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. INTERPRETATION: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01594567.

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men.

PURPOSE: To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data. METHODS: Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

BACKGROUND: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. OBJECTIVE: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. METHODS: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. RESULTS: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased ß-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted ß-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; ß-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; ß-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and ß-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. CONCLUSION: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos).

OBJECTIVES: Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk. METHODS: We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years. RESULTS: In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up. CONCLUSIONS: PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

A Web-Based Health Application to Translate Nutrition Therapy for Cardiovascular Risk Reduction in Primary Care (PortfolioDiet.app): Quality Improvement and Usability Testing Study.

BACKGROUND: The Portfolio Diet, or Dietary Portfolio, is a therapeutic dietary pattern that combines cholesterol-lowering foods to manage dyslipidemia for the prevention of cardiovascular disease. To translate the Portfolio Diet for primary care, we developed the PortfolioDiet.app as a patient and physician educational and engagement tool for PCs and smartphones. The PortfolioDiet.app is currently being used as an add-on therapy to the standard of care (usual care) for the prevention of cardiovascular disease in primary care. To enhance the adoption of this tool, it is important to ensure that the PortfolioDiet.app meets the needs of its target end users. OBJECTIVE: The main objective of this project is to undertake user testing to inform modifications to the PortfolioDiet.app as part of ongoing engagement in quality improvement (QI). METHODS: We undertook a 2-phase QI project from February 2021 to September 2021. We recruited users by convenience sampling. Users included patients, family physicians, and dietitians, as well as nutrition and medical students. For both phases, users were asked to use the PortfolioDiet.app daily for 7 days. In phase 1, a mixed-form questionnaire was administered to evaluate the users' perceived acceptability, knowledge acquisition, and engagement with the PortfolioDiet.app. The questionnaire collected both quantitative and qualitative data, including 2 open-ended questions. The responses were used to inform modifications to the PortfolioDiet.app. In phase 2, the System Usability Scale was used to assess the usability of the updated PortfolioDiet.app, with a score higher than 70 being considered acceptable. RESULTS: A total of 30 and 19 users were recruited for phase 1 and phase 2, respectively. In phase 1, the PortfolioDiet.app increased users' perceived knowledge of the Portfolio Diet and influenced their perceived food choices. Limitations identified by users included challenges navigating to resources and profile settings, limited information on plant sterols, inaccuracies in points, timed-logout frustration, request for step-by-step pop-up windows, and request for a mobile app version; when looking at positive feedback, the recipe section was the most commonly praised feature. Between the project phases, 6 modifications were made to the PortfolioDiet.app to incorporate and address user feedback. At phase 2, the average System Usability Scale score was 85.39 (SD 11.47), with 100 being the best possible. CONCLUSIONS: By undertaking user testing of the PortfolioDiet.app, its limitations and strengths were able to be identified, informing modifications to the application, which resulted in a clinical tool that better meets users' needs. The PortfolioDiet.app educates users on the Portfolio Diet and is considered acceptable by users. Although further refinements to the PortfolioDiet.app will continue to be made before its evaluation in a clinical trial, the result of this QI project is an improved clinical tool.

Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine.

OBJECTIVE: Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. RESEARCH DESIGN AND METHODS: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. RESULTS: Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low BMI; cluster III included women with noncoronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred, respectively, in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (hazard ratio 2.74 [95% CI 2.29-3.29]). Similar phenotypes and outcomes were identified in EXSCEL. CONCLUSIONS: In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.

Low-carbohydrate vegan diets in diabetes for weight loss and sustainability: a randomized controlled trial.

BACKGROUND: Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option. OBJECTIVES: We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes. METHODS: One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants. RESULTS: Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (-5.9 kg; 95% CI: -6.5, -5.28 kg; and -5.23 kg; 95% CI: -5.84, -4.62 kg), glycated hemoglobin (-0.99%; 95% CI: -1.07, -0.9%; and -0.88%; 95% CI: -0.97, -0.8%), systolic blood pressure (-4 mmHg; 95% CI: -7, -2 mmHg; and -6 mmHg; 95% CI: -8, -3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of -0.63 kgCO2/d (95% CI: -0.99, -0.27 kgCO2/d) favoring the low-carbohydrate vegan diet. CONCLUSIONS: Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions. TRIAL REGISTRATION NUMBER: clinicaltrials.gov identifier NCT02245399.

Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.

OBJECTIVE: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.