Clinical characteristics and survival of pulmonary arterial hypertension with or without interstitial lung disease in systemic sclerosis.

OBJECTIVES: To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD). METHODS: Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan-Meier estimates and Cox-regression modelling. RESULTS: Of 1561 participants, 7% fulfilled criteria for PAH-only, 24% ILD-only, 7% PAH-ILD and 62% SSc-only. People with PAH-ILD were more frequently male, with diffuse skin involvement, higher inflammatory markers, older age of SSc onset and higher frequency of extensive ILD than the cohort overall (p < 0.001). People of Asian race more frequently developed PAH-ILD (p < 0.001). People with PAH-ILD or PAH-only had worse WHO functional class and 6-min-walk-distance than ILD-only (p < 0.001). HRQoL scores were worst in those with PAH-ILD (p < 0.001). Survival was reduced in the PAH-only and PAH-ILD groups (p < 0.01). Multivariable hazard modelling demonstrated the worst prognosis in extensive ILD and PAH (HR = 5.65 95% CI 3.50-9.12 p < 0.01), followed by PAH-only (HR = 4.21 95% CI 2.89-6.13 p < 0.01) and PAH with limited ILD (HR = 2.46 95% CI 1.52-3.99 p < 0.01). CONCLUSIONS: The prevalence of concurrent PAH-ILD in the ASCS is 7%, with poorer survival in those patients with PAH-ILD compared to ILD or SSc alone. The presence of PAH confers a poorer overall prognosis than even extensive ILD; however, further data are required to better understand the clinical outcomes of this high-risk patient group.

A systematic review of trends in all-cause mortality among people with diabetes.

AIMS/HYPOTHESIS: We examined all-cause mortality trends in people with diabetes and compared them with trends among people without diabetes. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for observational studies published from 1980 to 2019 reporting all-cause mortality rates across ≥2 time periods in people with diabetes. Mortality trends were examined by ethnicity, age and sex within comparable calendar periods. RESULTS: Of 30,295 abstracts screened, 35 studies were included, providing data on 69 separate ethnic-specific or sex-specific populations with diabetes since 1970. Overall, 43% (3/7), 53% (10/19) and 74% (32/43) of the populations studied had decreasing trends in all-cause mortality rates in people with diabetes in 1970-1989, 1990-1999 and 2000-2016, respectively. In 1990-1999 and 2000-2016, mortality rates declined in 75% (9/12) and 78% (28/36) of predominantly Europid populations, and in 14% (1/7) and 57% (4/7) of non-Europid populations, respectively. In 2000-2016, mortality rates declined in 33% (4/12), 65% (11/17), 88% (7/8) and 76% (16/21) of populations aged <40, 40-54, 55-69 and ≥70 years, respectively. Among the 33 populations with separate mortality data for those with and without diabetes, 60% (6/10) of the populations with diabetes in 1990-1999 and 58% (11/19) in 2000-2016 had an annual reduction in mortality rates that was similar to or greater than in those without diabetes. CONCLUSIONS/INTERPRETATION: All-cause mortality has declined in the majority of predominantly Europid populations with diabetes since 2000, and the magnitude of annual mortality reduction matched or exceeded that observed in people without diabetes in nearly 60% of populations. Patterns of diabetes mortality remain uncertain in younger age groups and non-Europid populations. REGISTRATION: PROSPERO registration ID CRD42019095974. Graphical abstract.

The Most Important Predictors of Metabolic Syndrome Persistence after 10-year Follow-Up: YHHP Study.

BACKGROUND: Metabolic syndrome (MetS) is one of the world's largest health epidemics, and its management is a major challenge worldwide. The aim of this 10-year follow-up study was to assess the most important predictors of MetS persistence among an Iranian adult population. METHODS: In this cohort study, 887 out of 2000 participants with MetS aged 20-74 years in the central part of Iran were followed-up for about 10 years from 2005-2006 to 2015-2016. MetS was defined based on the criteria of NCEP-ATP III adopted for the Iranian population. Cox proportional hazards regression was conducted to evaluate the predictors of MetS persistence in crude- and multivariate-adjusted models. RESULTS: Our analyses showed that 648 out of 887 participants (73%) completed the follow-up and 565 (87.2%) of them had persistence of MetS after 10-year follow-up. There was a significant association between age, weight, body mass index, triglyceride, and waist circumference in participants who had MetS compared to those without MetS after 10-year follow-up (P < 0.05). There was a direct association between increases in the mean changes of systolic/diastolic blood pressure, waist circumference, and low HDL-C and risk of MetS persistence after adjusting the model for sex and age in the total population (P trend < 0.05). The trends were the same for women except in diastolic blood pressure. After adjustment for potential confounders, the risk of MetS persistence in men was significantly higher than women (HR = 1.98, 95% CI: 1.38-2.85, Ptrend = 0.001). CONCLUSIONS: Most of the risk factors of MetS were positively associated with persistence of MetS. Therefore, modification of lifestyle is recommended to reduce MetS.

Trends in incidence of total or type 2 diabetes: systematic review.

OBJECTIVE: To assess what proportions of studies reported increasing, stable, or declining trends in the incidence of diagnosed diabetes. DESIGN: Systematic review of studies reporting trends of diabetes incidence in adults from 1980 to 2017 according to PRISMA guidelines. DATA SOURCES: Medline, Embase, CINAHL, and reference lists of relevant publications. ELIGIBILITY CRITERIA: Studies of open population based cohorts, diabetes registries, and administrative and health insurance databases on secular trends in the incidence of total diabetes or type 2 diabetes in adults were included. Poisson regression was used to model data by age group and year. RESULTS: Among the 22 833 screened abstracts, 47 studies were included, providing data on 121 separate sex specific or ethnicity specific populations; 42 (89%) of the included studies reported on diagnosed diabetes. In 1960-89, 36% (8/22) of the populations studied had increasing trends in incidence of diabetes, 55% (12/22) had stable trends, and 9% (2/22) had decreasing trends. In 1990-2005, diabetes incidence increased in 66% (33/50) of populations, was stable in 32% (16/50), and decreased in 2% (1/50). In 2006-14, increasing trends were reported in only 33% (11/33) of populations, whereas 30% (10/33) and 36% (12/33) had stable or declining incidence, respectively. CONCLUSIONS: The incidence of clinically diagnosed diabetes has continued to rise in only a minority of populations studied since 2006, with over a third of populations having a fall in incidence in this time period. Preventive strategies could have contributed to the fall in diabetes incidence in recent years. Data are limited in low and middle income countries, where trends in diabetes incidence could be different. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42018092287.

Diabetes management and treatment approaches outside of North America and West Europe in 2006 and 2015.

AIMS: The impact of introducing new classes of glucose-lowering medication (GLM) on diabetes management remains unclear, especially outside North America and Western Europe. Therefore, we aimed to analyse trends in glycaemic control and the usage of new and old GLMs in people with type 2 diabetes from 2006 to 2015. METHODS: Summary data from clinical services from nine countries outside North America and Western Europe were collected and pooled for statistical analysis. Each site summarized individual-level data from out-patient medical records for 2006 and 2015. Data included: demographics; HbA1c and fasting plasma glucose levels; and the proportions of patients taking GLM as monotherapy, combination therapy and/or insulin. RESULTS: Between 2006 and 2015, glycaemic control remained stable, although body mass index and duration of diabetes increased in most sites. The proportion of people on GLM increased, and the therapeutic regimens became more complex. There were increases in the use of insulin and triple therapy in most sites, while monotherapy, particularly in relation to sulphonylureas, decreased. Despite the introduction of new GLMs, such as DPP-4 inhibitors, insulin use increased over time. CONCLUSIONS: There was no clear evidence that the use of new classes of GLMs was associated with improvements in glycaemic control or reduced the reliance on insulin. These findings were consistent across a range of economic and geographic settings.

Association between type 2 diabetes mellitus and disability: What is the contribution of diabetes risk factors and diabetes complications?

BACKGROUND: The aim of this study was to evaluate the association between type 2 diabetes and disability in Mauritius and to assess the extent to which the effect of diabetes is explained by diabetes risk factors and concomitant complications. METHODS: Data from a national survey in the multiethnic nation of Mauritius, which comprises South Asians and African Creoles, were analyzed. Disability was measured using the Katz activities of daily living questionnaire in participants aged >50 years. RESULTS: Among 3692 participants, 487 (13.2%) had some level of disability. Diabetes was associated with significantly higher risk of disability (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.34-2.08). After adjusting for demographic, behavioral, and metabolic factors, as well as comorbidities, disability was significantly associated with diabetes among African Creoles (OR 2.03; 95% CI 1.16-3.56), but not South Asians (OR 1.27; 95% CI 0.98-1.66). Obesity explained much of the association between diabetes and disability (excess percentage of risk: 26.3% in South Asians and 12.1% in African Creoles). Obesity, history of cardiovascular disease (CVD), asthma-like symptoms, and depression together explained 46.5% and 29.0% of the excess risk in South Asians and African Creoles, respectively. CONCLUSIONS: Diabetes is associated with a 67% increased risk of disability. Diabetes risk factors and comorbidities explain more of the association between diabetes and disability among South Asians than Africans. Obesity and history of CVD explained the largest percentage of the relationship between diabetes and disability, indicating that weight and CVD management may be helpful in controlling disability related to diabetes.

The effect of nurse prescribers on glycaemic control in type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: The creation of advanced nursing roles in diabetes management, with specific skills such as nurse prescribing, has resulted in nurses taking on roles that have traditionally been associated with doctors. OBJECTIVES: We aimed to examine the effectiveness of nurse-led clinics, in which nurses were involved in prescribing, on haemoglobin A1c (HbA1c) among people with type 2 diabetes. METHODS: We systematically searched the literature, Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Allied Health Literature database guide (CINAHL) databases, to identify randomised controlled trials (RCTs) assessing the effect of nurse prescribers on HbA1c. We focused on randomised controlled trials which compared nurse prescriber interventions with usual care in adults aged 18 years or over with a diagnosis of type 2 diabetes. The main outcome measure was change in HbA1c levels. We performed a random effects model meta-analysis to assess the pooled effect size of the intervention. Studies were divided into two groups according to the role of nurses in the intervention. In one group, the nurses supplemented a team, as an add-on to usual care; in the other group, they worked independently, and were compared directly to a doctor. RESULTS: Nine RCTs were identified and included in this study. All studies were from developed countries, with a medium risk of bias and a moderate heterogeneity between studies. In the five RCTs in which nurse prescribers supplemented a team, there was no significant difference in change of HbA1c compared to usual care (-0.34 percentage points; 95% CI: -0.71, 0.02). In the four RCTs in which nurses replaced doctors, the outcomes of nurse prescribers were comparable to those of doctors. No data on adverse events were available. CONCLUSION: There was no clear evidence of benefit on glycaemic control, when nurses who undertake prescribing work alongside a doctor and other practitioners. However, in those studies in which nurses replaced physicians, the glycaemic control was comparable between nurses and doctors. Therefore, there may be value in providing nurse-led prescribing services where there is limited access to doctor-led services.

Effects of Calcium Plus Vitamin D Supplementation on Anthropometric Measurements and Blood Pressure in Vitamin D Insufficient People with Type 2 Diabetes: A Randomized Controlled Clinical Trial.

BACKGROUND: Up to 75% of the risk of type 2 diabetes is attributable to obesity. Therefore, finding a way to control obesity can be useful for management of diabetes. OBJECTIVE: This study was performed to assess the effects of vitamin D3 and calcium supplementation on anthropometric measurements and blood pressure in vitamin D insufficient people with type 2 diabetes. METHODS: One hundred eighteen patients with diabetes were enrolled in this randomized placebo-controlled clinical trial. All subjects were randomly assigned into 4 groups receiving (1) 50,000 IU/wk vitamin D3 plus (equal to 7143 IU/d) calcium placebo; (2) 1000 mg/d calcium plus vitamin D3 placebo; (3) 50,000 IU/wk vitamin D3 (equal to 7143 IU/d) plus 1000 mg/d calcium; or (4) vitamin D3 placebo plus calcium placebo for 8 weeks. Anthropometric measurements and blood pressure were assessed at study baseline and after 8 weeks of intervention. RESULTS: A greater reduction in body mass index was observed in calcium plus vitamin D group than other groups (p = 0.03). Comparison of changes in waist circumference among 4 groups revealed no significant difference in crude model (p = 0.21) and when the effect of confounders was taken into account (p = 0.08). Calcium supplementation resulted in a significant reduction in hip circumference compared to other groups (p <0.001). Systolic blood pressure significantly decreased in the calcium plus vitamin D group compared to placebo (-7.3 ± 8.7 mmHg vs 0.5 ± 8.2 mmHg; p = 0.001). However, calcium and vitamin D supplementation had no significant effects on diastolic blood pressure. CONCLUSION: Calcium-vitamin D3 cosupplementation can have beneficial effect on body mass index (BMI), hip circumference, and systolic blood pressure in vitamin D-insufficient type 2 diabetics.

Calcium-vitamin D cosupplementation influences circulating inflammatory biomarkers and adipocytokines in vitamin D-insufficient diabetics: a randomized controlled clinical trial.

CONTEXT: To the best of our knowledge, no study has examined the effects of vitamin D-calcium cosupplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient type 2 diabetics. OBJECTIVE: This study was performed to assess the effects of vitamin D and calcium supplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient people with type 2 diabetes. METHODS: Totally, 118 diabetic patients were enrolled in this randomized, placebo-controlled clinical trial. After matching for age, sex, body mass index, type and dose of hypoglycemic agents, and duration of diabetes, subjects were randomly assigned into 4 groups receiving the following: 1) 50000 IU/wk vitamin D + calcium placebo; 2) 1000 mg/d calcium + vitamin D placebo; 3) 50 000 IU/wk vitamin D + 1000 mg/d calcium; or 4) vitamin D placebo + calcium placebo for 8 weeks. Blood sampling was done for the quantification of inflammatory biomarkers and adipocytokines at the study baseline and after 8 weeks of intervention. RESULTS: Calcium (changes from baseline: -75 ± 19 ng/ml, P = .01) and vitamin D alone (-56 ± 19 ng/mL, P = .01) and joint calcium-vitamin D supplementation (-92 ± 19 ng/mL, P = .01) resulted in a significant reduction in serum leptin levels compared with placebo (-9 ± 18 ng/mL). This was also the case for serum IL-6, such that calcium (-2 ± 1 pg/mL, P < .001) and vitamin D alone (-4 ± 1 pg/mL, P < .001) and their combination (-4 ± 1 pg/mL, P < .001) led to significant reductions compared with placebo (3 ± 1 pg/mL). After adjustment for potential confounders, individuals in the calcium (-3.1 ± 1.3, P < .05), vitamin D (-3.1 ± 1.3, P < .05), and joint calcium-vitamin D groups (-3.4 ± 1.3, P < .05) had greater reductions in serum TNF-α concentrations compared with placebo (0.1 ± 1.2). Individuals who received joint calcium-vitamin D supplements tended to have a decrease in serum high-sensitivity C-reactive protein levels compared with placebo after controlling for baseline levels (-1.14 ± 0.25 vs 0.02 ± 0.24 ng/mL, P = .09). CONCLUSION: Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-α concentrations in vitamin D-insufficient people with type 2 diabetes.

Effects of calcium-vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial.

AIMS/HYPOTHESIS: This study was performed to assess the effects of vitamin D and calcium supplementation on the metabolic profiles of vitamin D insufficient persons with type 2 diabetes. METHODS: In a parallel designed randomised placebo-controlled clinical trial, a total of 118 non-smoker individuals with type 2 diabetes and insufficient 25-hydroxyvitamin D, aged >30 years, were recruited from the Isfahan Endocrine and Metabolism Research Centre. Participants were randomly assigned to four groups receiving: (1) 50,000 U/week vitamin D + calcium placebo; (2) 1,000 mg/day calcium + vitamin D placebo; (3) 50,000 U/week vitamin D + 1,000 mg/day calcium; or (4) vitamin D placebo + calcium placebo for 8 weeks. A study technician carried out the random allocations using a random numbers table. All investigators, participants and laboratory technicians were blinded to the random assignments. All participants provided 3 days of dietary records and 3 days of physical activity records throughout the intervention. Blood samples were taken to quantify glycaemic and lipid profiles at study baseline and after 8 weeks of intervention. RESULTS: 30 participants were randomised in each group. During the intervention, one participant from the calcium group and one from the vitamin D group were excluded because of personal problems. Calcium-vitamin D co-supplementation resulted in reduced serum insulin (changes from baseline: -14.8 ± 3.9 pmol/l, p = 0.01), HbA1c [-0.70 ± 0.19% (-8.0 ± 0.4 mmol/mol), p = 0.02], HOMA-IR (-0.46 ± 0.20, p = 0.001), LDL-cholesterol (-10.36 ± 0.10 mmol/l, p = 0.04) and total/HDL-cholesterol levels (-0.91 ± 0.16, p = 0.03) compared with other groups. We found a significant increase in QUICKI (0.025 ± 0.01, p = 0.004), HOMA of beta cell function (HOMA-B; 11.8 ± 12.17, p = 0.001) and HDL-cholesterol (0.46 ± 0.05 mmol/l, p = 0.03) in the calcium-vitamin D group compared with others. CONCLUSIONS/INTERPRETATION: Joint calcium and vitamin D supplementation might improve the glycaemic status and lipid profiles of vitamin D insufficient people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01662193 FUNDING: Clinical Research Council, Isfahan University of Medical Sciences, Isfahan, Iran.

Maternal vitamin D status and risk of pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Although several studies have investigated the association between maternal serum vitamin D levels and risk of pre-eclampsia, findings are inconsistent. This systematic review and meta-analysis of published observational studies was conducted to summarize the evidence on the association between maternal serum vitamin D levels and risk of pre-eclampsia. METHODS: PubMed, ISI (Web of science), SCOPUS, SCIRUS, Google Scholar, and EMBASE databases were searched to identify related articles published through December 2012. For systematic review, we found 15 articles that assessed the association between maternal serum vitamin D levels and risk of pre-eclampsia. The meta-analysis was done on 8 studies that reported odds ratios or relative risks for pre-eclampsia. Between-study heterogeneity was examined using Cochran's Q test and I(2). Subgroup analysis and meta-regression were used to find possible sources of heterogeneity. RESULTS: The meta-analysis on 8 relevant papers revealed an overall significant association between vitamin D deficiency and risk of pre-eclampsia; however, there was significant between-study heterogeneity (I(2) = 52.7%; P = .039). In the subgroup analysis, we found that the overall effect was significant for studies that defined vitamin D deficiency as 25(OH)D ≤ 50 nmol/L (20 ng/mL), but not for those that considered it as <38 nmol/L (15.2 ng/mL). The association was seen for "cohort or nested case-control studies" as well as for "cross-sectional or case-control studies" (2.78; 1.45-5.33; P = .002). When the analysis was done by study location, the associations remained significant only for studies that came from the United States. CONCLUSION: There was a significant relationship between vitamin D deficiency and increased risk of pre-eclampsia. Further studies are required, particularly in developing countries.

The Relationship Between Vegetables and Fruits Intake and Glycosylated Hemoglobin Values, Lipids Profiles and Nitrogen Status in Type II Inactive Diabetic Patients.

BACKGROUND: The prevalence of obesity and associated chronic disease such as diabetes is rapidly increasing in all part of the world. The World Health Organization has predicted that between 1997 and 2025 the number of diabetic patients will increase from 143 million to about 300 million. In diabetic patients, oxidative stress leads to non-enzymatic glycosylation of proteins such as hemoglobin and albumin, these proteins can play a significant role in pathogenesis of diabetes and development of chronic disorders in diabetic patients. Antioxidant nutrients can reduce the chronic disorders and complications of diabetes by inhibiting the oxidative reactions. Some important antioxidant such as vitamin A, vitamin C, vitamin E and selenium occur in vegetables and fruits. Our objective of this study was investigation of the relationship between vegetables and fruits intake ssand glycosylated hemoglobin (HbA1C) values in diabetic patients. METHODS: One hundred and five diabetic patients participated in this cross-sectional study. The patients were referred to health center in Khomeini shahr. Glycosylated hemoglobin (HbA1C) values were measured by chromatography method. Data on dietary intake and vegetables and fruits consumption were obtained from validated food frequency questionnaires. RESULTS: The unadjusted mean glycosylated hemoglobin (HbA1C) is significantly associated with the amount of vegetables and fruits intake (P = 0.014), but the relationship between consumption of fruits and HbA1C is not significant and the relationship between consumption of vegetables and HbA1C was roughly significant (P = 0.049). There were no significant relationship between vegetables and fruits intake and lipids profiles, BUN/creatinine and 24 h urinary protein (P > 0.05). CONCLUSIONS: Intake of vegetables and fruits may reduce the glycosylated hemoglobin, therefore choosing the appropriate diet with high fruits and vegetables may help to develop antioxidant defense and reduce the HbA1C in diabetic patients but it did not have any impact on lipids profiles, BUN/creatinine and urine protein 24 h.