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1.
Artigo em Inglês | MEDLINE | ID: mdl-32366202

RESUMO

Background: We aimed to assess the burden of metabolic syndrome (MetS), and evaluate the phenotypic variation of MetS in a population at high risk for diabetes in urban Karachi, Pakistan. Methods: This study was embedded in a lifestyle intervention trial for the prevention of type 2 diabetes mellitus. The study population comprised participants who belonged to urban households in Karachi, Pakistan. Results: Among 15,590 individuals who were screened through diabetes risk score (DRS), 3945 individuals met the criteria for a high DRS (≥60). After excluding 1780 participants due to refusals and ineligibility, 2165 were enrolled, a total of 1188 subjects (54.9%) met the International Diabetes Federation criteria for MetS, and a total of 1199 subjects (55.4%) participants met the US National Cholesterol Education Program. Raised serum triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol were significantly associated with MetS. On multivariate logistic regression, higher body mass index levels (obese category: odds ratio [OR] = 2.14, 95% confidence interval [CI] 1.56-2.95), age >44 years (OR = 2.64, 95% CI 1.93-3.60), and family history of diabetes in both parents (OR = 1.71, 95% CI 1.15-2.54) were found to be independently associated with MetS, whereas higher education (OR = 0.78, 95% CI 0.57-1.06) and physical activity levels (OR = 0.74, 95% CI 0.57-0.96) had lower odds of MetS. Conclusion: One in two individuals with a high DRS in an urban low/middle-income country setting met the criteria for MetS. Patients with atherogenic dyslipidemia defined as low HDL and high TGs represent unique subphenotypes of MetS in this population.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32366501

RESUMO

Fasting the Holy month of Ramadan constitutes one of the five pillars of the Muslim faith. Although there is some evidence that intermittent fasting during Ramadan may be of benefit in losing weight and cardiometabolic risk factors, there is no strong evidence these benefits apply to people with diabetes. The American Diabetes Association/European Association for the Study of Diabetes consensus recommendations emphasize the importance of patient factors and comorbidities when choosing diabetes medications including the presence of comorbidities, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, hypoglycemia risk, weight issues and costs. Structured education and pre-Ramadan counseing are key components to successful management of patients with diabetes. These should cover important aspects like glycemic targets, self-monitoring of blood glucose, diet, physical activity including Taraweeh prayers, medication and dose adjustment, side effects and when to break the fast. The decision cycle adapted for the specific situation of Ramadan provides an aid for such an assessment. Children with type 1 diabetes should strongly be advised not to fast due to the high risk of acute complications such as hypoglycemia and probably diabetic ketoacidosis (DKA), although there is very little evidence that DKA is increased in Ramadan. Pregnant women with diabetes or gestational diabetes should be advised to avoid fasting because of possible negative maternal and fetal outcomes. Hypoglycemia is a common concern during Ramadan fasting. To prevent hypoglycemic and hyperglycemic events, we recommend the adoption of diabetes self-management education and support principles. The use of the emerging technology and continuous glucose monitoring during Ramadan could help to recognize hypoglycemic and hyperglycemic complications related to omission and/or medication adjustment during fasting; however, the cost represents a significant barrier.

3.
PLoS One ; 15(4): e0231196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32282852

RESUMO

OBJECTIVES: To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. METHODS: Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. PARTICIPANTS: Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. INTERVENTION: Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. RESULTS: One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. CONCLUSIONS: ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes. REGISTRATION: - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.

4.
Diabetes Metab Res Rev ; : e3332, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343474

RESUMO

Hypoglycaemia is common in patients with type 1 diabetes and type 2 diabetes and constitutes a major limiting factor in achieving glycaemic control among people with diabetes. While hypoglycaemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycaemic control. Severe hypoglycaemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycaemia is the most important safety outcome in clinical studies of glucose lowering agents. The American Diabetes Association Standards of Medical Care recommends that a management protocol for hypoglycaemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycaemic events with the use of newer anti-diabetic drugs. Increased hypoglycaemia risk is observed with the use of insulin and/or sulphonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycaemia and cardiovascular outcomes show features of "frailty." Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia and with history of severe hypoglycaemia. Patients with impaired awareness of hypoglycaemia benefit from real-time CGM. The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycaemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycaemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycaemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycaemia. Several therapeutic considerations are important to reduce hypoglycaemia risk during pregnancy including administration of rapid-acting insulin analogues rather than human insulin, pre-conception initiation of insulin analogues, and immediate postpartum insulin dose reduction.

5.
Pediatr Endocrinol Rev ; 17(Suppl 1): 198-209, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32208564

RESUMO

Epidemiological data on pediatric type 1 diabetes (T1D), mainly incidence, have become increasingly available since the second half of the 20th century. Comparative incidence data across populations were only obtained since the 1980s. The 2019 IDF Atlas provides T1D incidence, prevalence and mortality estimates for children < 15 years for all 211 countries, but actual data were available for only 94 countries (only 3 low-income). The estimated prevalent cases were 600,900 and incident cases 98,200. Incidence remains highest in Finland (60/100,000/ year), Sardinia and Sweden, followed by Kuwait, some other northern European countries, Saudi Arabia, Algeria, Australia, New Zealand, USA and Canada. The lowest incidence is seen across East and South-East Asia. Globally, the average increase in incidence has been 3-4%/year over past decades, being steeper in low-incidence countries. Although T1D mortality has drastically decreased, there is still a higher risk compared with the non-diabetic population, especially in people with diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Incidência , Itália , Prevalência
6.
Sci Rep ; 10(1): 152, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932636

RESUMO

Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 (RPS6KA1) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; ß-discovery = 8.315; ß-replication = 3.442; ß-combined = 6.551). Further, three suggestive associations (p-values < 8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.

7.
Prim Care Diabetes ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911041

RESUMO

BACKGROUND: Diabetes is prevalent in Kuwait. We aimed to assess the level of glycemic control in Kuwaiti adults with diabetes. METHODS: The World Health Organization's STEPS non-communicable disease risk factor survey was conducted in Kuwait in 2014. Participants' demographics, medical history, physical measurements and blood biochemistry were assessed. A total of 2561 Kuwaiti men and women aged 18-69 years completed all three survey steps. Glycemic control in 278 individuals with diabetes who were on glucose-lowering medication was determined using the US National Institutes of Health guidelines of fasting plasma glucose (FPG) ≤7.2mmol/l and the American Diabetes Association guidelines of glycated hemoglobin (HbA1c) <7% (53mmol/mol). RESULTS: Adequate glycemic control in people with drug-treated diabetes was 34.5% when determined by HbA1c, 37.8% when determined by FPG level, and 24.5% when both criteria were met. Mean body-mass index and fasting serum triglycerides were significantly higher and serum high-density lipoprotein-cholesterol significantly lower in individuals with an inadequate glycemic control than in those with adequate control. Women with diabetes were almost twice as likely to have inadequate HbA1c levels as men with diabetes (OR, 1.9, [95% CI, 1.03, 3.5]). CONCLUSIONS: Glycemic control in Kuwaiti adults with treated diabetes is low. A systemic, multi-disciplinary public health approach is needed to improve diabetes education and adherence to treatment.

8.
J Diabetes Investig ; 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31957345

RESUMO

AIMS/INTRODUCTION: To develop a non-invasive risk score to identify Saudis having prediabetes or undiagnosed type 2 diabetes. METHODS: Adult Saudis without diabetes were recruited randomly using a stratified two-stage cluster sampling method. Demographic, dietary, lifestyle variables, personal and family medical history were collected using a questionnaire. Blood pressure and anthropometric measurements were taken. Body mass index was calculated. The 1-h oral glucose tolerance test was carried out. Glycated hemoglobin, fasting and 1-h plasma glucose were measured, and obtained values were used to define prediabetes and type 2 diabetes (dysglycemia). Logistic regression models were used for assessing the association between various factors and dysglycemia, and Hosmer-Lemeshow summary statistics were used to assess the goodness-of-fit. RESULTS: A total of 791 men and 612 women were included, of whom 69 were found to have diabetes, and 259 had prediabetes. The prevalence of dysglycemia was 23%, increasing with age, reaching 71% in adults aged ≥65 years. In univariate analysis age, body mass index, waist circumference, use of antihypertensive medication, history of hyperglycemia, low physical activity, short sleep and family history of diabetes were statistically significant. The final model for the Saudi Diabetes Risk Score constituted sex, age, waist circumference, history of hyperglycemia and family history of diabetes, with the score ranging from 0 to 15. Its fit based on assessment using the receiver operating characteristic curve was good, with an area under the curve of 0.76 (95% confidence interval 0.73-0.79). The proposed cut-point for dysglycemia is 5 or 6, with sensitivity and specificity being approximately 0.7. CONCLUSION: The Saudi Diabetes Risk Score is a simple tool that can effectively distinguish Saudis at high risk of dysglycemia.

9.
BMJ Open Diabetes Res Care ; 7(1): e000769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803483

RESUMO

Objective: The Finnish Diabetes Risk Score (FINDRISC) is a recommended tool for type 2 diabetes prediction. There is a lack of studies examining the performance of the current 0-26 point FINDRISC scale. We examined the validity of FINDRISC in a contemporary Norwegian risk environment. Research design and methods: We followed 47 804 participants without known diabetes and aged ≥20 years in the HUNT3 survey (2006-2008) by linkage to information on glucose-lowering drug dispensing in the Norwegian Prescription Database (2004-2016). We estimated the C-statistic, sensitivity and specificity of FINDRISC as predictor of incident diabetes, as indicated by incident use of glucose-lowering drugs. We estimated the 10-year cumulative diabetes incidence by categories of FINDRISC. Results: The C-statistic (95% CI) of FINDRISC in predicting future diabetes was 0.77 (0.76 to 0.78). FINDRISC ≥15 (the conventional cut-off value) had a sensitivity of 38% and a specificity of 90%. The 10-year cumulative diabetes incidence (95% CI) was 4.0% (3.8% to 4.2%) in the entire study population, 13.5% (12.5% to 14.5%) for people with FINDRISC ≥15 and 2.8% (2.6% to 3.0%) for people with FINDRISC <15. Thus, FINDRISC ≥15 had a positive predictive value of 13.5% and a negative predictive value of 97.2% for diabetes within the next 10 years. To approach a similar sensitivity as in the study in which FINDRISC was developed, we would have to lower the cut-off value for elevated FINDRISC to ≥11. This would yield a sensitivity of 73%, specificity of 67%, positive predictive value of 7.7% and negative predictive value of 98.5%. Conclusions: The validity of FINDRISC and the risk of diabetes among people with FINDRISC ≥15 is substantially lower in the contemporary Norwegian population than assumed in official guidelines. To identify ~3/4 of those developing diabetes within the next 10 years, we would have to lower the threshold for elevated FINDRISC to ≥11, which would label ~1/3 of the entire adult population as having an elevated FINDRISC necessitating a glycemia assessment.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31781037

RESUMO

Urocortin3 (UCN3) regulates metabolic functions and is involved in cellular stress response. Although UCN3 is expressed in human adipose tissue, the association of UCN3 with obesity and diabetes remains unclear. This study investigated the effects of Type 2 diabetes (T2D) and increased body weight on the circulatory and subcutaneous adipose tissue (SAT) levels of UCN3 and assessed UCN3 modulation by a regular physical exercise. Normal-weight (n = 37) and overweight adults with and without T2D (n = 98 and n = 107, respectively) were enrolled in the study. A subset of the overweight subjects (n = 39 for each group) underwent a supervised 3-month exercise program combining both moderate intensity aerobic exercise and resistance training with treadmill. UCN3 levels in SAT were measured by immunofluorescence and RT-PCR. Circulatory UCN3 in plasma was assessed by ELISA and was correlated with various clinical and metabolic markers. Our data revealed that plasma UCN3 levels decreased in overweight subjects without T2D compared with normal-weight controls [median; 11.99 (0.78-86.07) and 6.27 (0.64-77.04), respectively; p < 0.001], whereas plasma UCN3 levels increased with concomitant T2D [median; 9.03 (0.77-104.92) p < 0.001]. UCN3 plasma levels were independently associated with glycemic index; fasting plasma glucose and hemoglobin A1c (r = 0.16 and r = 0.20, p < 0.05, respectively) and were significantly different between both overweight, with and without T2D, and normal-weight individuals (OR = 2.11 [1.84-4.11, 95% CI] and OR = 2.12 [1.59-3.10, 95% CI], p < 0.01, respectively). Conversely, the UCN3 patterns observed in SAT were opposite to those in circulation; UCN3 levels were significantly increased with body weight and decreased with T2D. After a 3-month supervised exercise protocol, UCN3 expression showed a significant reduction in SAT of both overweight groups (2.3 and 1.6-fold change; p < 0.01, respectively). In conclusion, UCN levels are differentially dysregulated in obesity in a tissue-dependent manner and can be mitigated by regular moderate physical exercise.

11.
Eur J Prev Cardiol ; 26(2_suppl): 33-46, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31766917

RESUMO

A cluster of metabolic factors have been merged into an entity named the metabolic syndrome. Although the characteristics of this syndrome have varied over time the presently used definition was established in 2009. The presence of three abnormal findings out of five components qualifies a person for the metabolic syndrome: elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting plasma glucose. Cut points have been defined for all components apart from waist circumference, for which national or regional values are used. The metabolic syndrome predicts cardiovascular disease and type 2 diabetes. This associated risk does not exceed its components whereof elevated blood pressure is the most frequent. A successful management should, however, address all factors involved. The management is always based on healthy lifestyle choices but has not infrequently to be supported by pharmacological treatment, especially blood pressure lowering drugs. The metabolic syndrome is a useful example of the importance of multiple targets for preventive interventions. To be successful management has to be individualized not the least when it comes to pharmacological therapy. Frail elderly people should not be over-treated. Knowledge transfer of how risk factors act should be accompanied by continuous trust building and motivation. In complex situations with a mix of biological risk factors, adverse social conditions and unhealthy lifestyle, everything cannot be changed at once. It is better to aim for small steps that are lasting than large, unsustainable steps with relapses to unhealthy behaviours. A person with the metabolic syndrome will always be afflicted by its components, which is the reason that management has to be sustained over a very long time. This review summarizes the knowledge on the metabolic syndrome and its management according to present state of the art.

12.
Cardiovasc Diabetol ; 18(1): 135, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623625

RESUMO

BACKGROUND: Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. METHODS: We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. RESULTS: Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67-0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89-1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. CONCLUSIONS: Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.

13.
PLoS One ; 14(10): e0221467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603914

RESUMO

BACKGROUND AND AIMS: The DE-PLAN was a European multicenter study, with the primary objective of testing whether a community-based lifestyle modification programme could serve as a means of primary prevention for type 2 diabetes (T2D) in high-risk individuals (based on the FINDRISC questionnaire). The aim of this study was to examine the impact of a 1-year community-based lifestyle intervention on health-related quality of life (HRQOL) in individuals from four participating European centers (Athens, Barcelona, Krakow, Kaunas), through a post-hoc analysis. MATERIALS AND METHODS: Each center was allowed to implement different intervention strategies specifically tailored to the needs of their corresponding population sample. Before and after the intervention, participants underwent clinical evaluation, anthropometric measurements, an oral glucose tolerance test and lipid profile measurements. Health-related quality of life was assessed using the validated HRQOL-15D questionnaire. A difference of ±0.015 in the 15D questionnaire score was set as the threshold of clinically meaningful change. RESULTS: Data from 786 participants (67% females, mean age 59.7±9.4 years, BMI 31.5±4.5 kg/m2) with complete data regarding the HRQOL were analyzed (Athens: 104, Barcelona: 434, Krakow: 175, Kaunas: 70). After 1 year, a significant overall improvement in HRQOL was shown, as depicted by a change of 15D score from baseline value (0.88±0.9) to post-intervention (0.90±0.87, P<0.001), achieving the threshold of clinically meaningful change. A significant weight reduction was also observed (-0.8±4.0 kg, P<0.001). In multivariate analysis, improvement in HRQOL was independently associated with lower 15D score at baseline (P<0.001) and self-reported increase in overall exercise time (P<0.001) as assessed through specifically designed trial questionnaires. CONCLUSION: A community-based lifestyle intervention programme aiming at T2D prevention, applied on a heterogeneous population and with varied methods, was shown to improve overall health-related quality of life to a clinically meaningful degree.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31616376

RESUMO

Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring. Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP. Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P < 0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65-5.34) and GDM alone (2.06, 95% CIs 1.20-3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group. Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.

15.
Cells ; 8(10)2019 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-31635130

RESUMO

Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.

16.
Ther Adv Chronic Dis ; 10: 2040622319878997, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632623

RESUMO

Background: Obesity is a risk factor for many chronic diseases, and its prevalence and trends vary among populations. Saudi Arabia shows a greater rise in prevalence than many other countries. We aimed to study the association between several chronic disorders, demographic, and lifestyle factors with increased body mass index (BMI) in the adult population of Jeddah. Methods: Data were obtained from a door-to-door cross sectional study. A three-stage stratified cluster sampling technique was adopted. Individuals in selected households agreeing to participate were interviewed to complete a predesigned questionnaire covering demographic and lifestyle variables, medical history, and family history of chronic diseases. This was followed by anthropometric and blood pressure measurements. A random capillary plasma glucose (RPG) was measured, followed by further testing using fasting plasma glucose and glycated hemoglobin (HbA1c) to verify whether participants were normal, diabetic, or prediabetic. Multiple logistic regression analyses were used to adjust for confounding factors. Results: A total of 1419 individuals were included in the study: 667 men and 752 women. The prevalence of overweight and obesity was 35.1 and 34.8%, respectively, in men, and 30.1% and 35.6%, respectively, in women. Both overweight and obesity increased in prevalence to 60 years of age, and decreased in the oldest age group in both sexes. After adjusting for age, risk of obesity in men was increased with having a postgraduate degree [odds ratio (OR), 95%CI = 2.48, 1.1-5.61] and decreased with increased physical activity (OR, 95%CI = 0.49, 0.26-0.91). Risk of prediabetes and diabetes was increased in obese women (OR, 95%CI = 2.94, 1.34-6.44, and 3.61, 1.58-8.26 respectively), that of hypertension in obese men (OR, 95%CI =2.62, 1.41-4.87), and that of dyslipidemia in both sexes (OR, 95%CI = 2.60, 1.40-4.83 in men, and 2.0, 1.01-3.85 in women). A family history of dyslipidemia was associated with reduced risk of obesity among women (OR, 95%CI = 0.33, 0.12-0.92), whereas, in people with above normal weight (BMI ⩾25), there was increased risks of prediabetes, diabetes, and dyslipidemia among women (OR, 95%CI = 2.50, 1.21-5.17; 3.20, 1.45-7.03, and 1.88, 1.02-3.49, respectively ), and of hypertension among men (OR, 95%CI = 1.80, 1.00-3.23). Conclusions: The prevalence of overweight and obesity in the Saudi population remain high, indicating ineffectiveness or lack of preventive measures. Risk of prediabetes, diabetes, dyslipidemia, and hypertension increased with increasing BMI, with some sex differences in these associations.

17.
Diabetes Res Clin Pract ; 156: 107828, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31472162

RESUMO

OBJECTIVE: To evaluate the independent or combined effects of gestational diabetes (GDM) and pre-pregnancy and postpartum BMI on the odds of postpartum diabetes and hyperglycemia. METHODS: The study samples included 1263 women with prior GDM and 705 women without GDM. Postpartum 1-7 years diabetes was diagnosed by the standard oral glucose tolerance test. RESULTS: The multivariable-adjusted odds ratios among women with prior GDM, compared with those without it, were 7.52 for diabetes and 2.27 for hyperglycemia. The multivariable-adjusted odds ratios at different postpartum BMI levels (<24, 24-27.9, and ≥ 28 kg/m2) were 1.00, 2.80, and 8.08 for diabetes (Ptrend < 0.001), and 1.00, 2.10, and 4.42 for hyperglycemia (Ptrend < 0.001), respectively. Women with high body fat (≥31.9%) or abdominal obesity (≥85 cm) had a 2.7-6.9-fold higher odds ratio for diabetes or hyperglycemia. Women with both obesity and prior GDM had the highest risk of diabetes or hyperglycemia compared with non-obese women without GDM. Non-obese women with prior GDM had the same risk of diabetes and hyperglycemia as non-GDM women with obesity. When using Cox regression models, the results were very close to those using logistic regression models. CONCLUSIONS: Maternal prior GDM and pre-pregnancy or postpartum obesity contribute equally to postpartum diabetes and hyperglycemia risk.


Assuntos
Diabetes Mellitus/etiologia , Diabetes Gestacional/etiologia , Hiperglicemia/etiologia , Obesidade/complicações , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Período Pós-Parto , Gravidez , Fatores de Risco
18.
Sci Rep ; 9(1): 11866, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413305

RESUMO

Obesity impacts the endocrine and metabolic functions of the adipose tissue. There is increasing interest in the role of epigenetic factors in obesity and its impact on diabetes and dyslipidemia. One such substance, miR-181, reduces plasma triglyceride levels in mice by targeting isocitrate dehydrogenase 1. In the other hand, the adipocyte differentiation and lipid regulating hormone angiopoietin-like 3 (ANGPTL3) is a known regulator of circulating apolipoproteins through its inhibition of the lipoprotein lipase activity. We aimed to study the miR-181d expression in the blood and adipose tissue in a cohort of obese and non-obese people, assessing its possible role in obesity. We also aimed to confirm whether miR-181d can bind and regulate ANGPTL3. miR-181d expression levels were investigated in 144 participants, 82 who were non-obese (body mass index [BMI] < 30) and 62 who were obese (BMI > 30). miR-181d levels in plasma and adipose tissue were measured by RT-PCR. Hepatocyte cell cultures were assessed by overexpression and 3'-UTR-luciferase assays for miR-181d binding to its target protein and its effect on the protein. The plasma levels of ANGPTL3 were also measured by ELISA. The miR-181d levels were significantly lower in obese than in non-obese individuals. In vitro analysis confirmed miR-181 binding to and repression of the ANGPTL3 transcript. Obesity leads to alterations in miR-181d expression. Its downregulation in obese humans was inversely correlated with ANGPTL3, a protein involved in adipocyte differentiation and lipid metabolism. miR-181d can be used as an inhibitor of ANGPTL3 to reduce the TG plasma level.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31396158

RESUMO

Objective: The family of angiopoietin-like proteins (ANGPTLs) is composed of eight ANGPTLs members that are involved in regulating various metabolic processes and have been implicated in type 2 diabetes (T2D) and obesity. ANGPTL5 is an understudied member of this family that has been suggested to regulate triglyceride metabolism with a potential role in obesity. This study was designed to investigate the expression levels of ANGPTL5 protein in the circulation of subjects with obesity and T2D. Methods: A total of 204 subjects were enrolled in this cross-sectional study, of which 95 had diagnosed T2D and 109 did not (non-T2D). Within the non-T2D group, 39 subjects were obese (BMI ≥ 30 Kg/m2) and 70 were not (BMI < 30 Kg/m2). Among subjects with T2D, 61 were obese and 34 were non-obese. Circulating ANGPTL5 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: In this study, we showed that ANGPTL5 levels were higher in the plasma of subjects with T2D [mean ± standard error of the mean (SEM): 5.78 ± 2.70 ng/mL] compared with individuals without T2D (mean ± SEM: 4.42 ± 2.22 ng/mL; P < 0.001). Obese and non-T2D subjects had significantly higher levels of ANGPTL5 (mean ± SEM: 5.115 ± 0.366 ng/mL) compared with non-obese, non-T2D subjects (mean ± SEM: 4.02 ± 0.271 ng/mL; P = 0.003). Similarly, among subjects with diagnosed T2D, those who were obese had higher ANGPTL5 plasma levels than non-obese subjects, although this difference did not reach statistical significance (P = 0.088). Correlation analyses revealed that ANGPTL5 levels positively associated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), triglycerides (TGL), and insulin resistance as measured by HOMA-IR. Conclusion: our data shows for the first time that circulating ANGPTL5 levels were higher in obese individuals and those with T2D. Further analysis will be required to better understand the interaction between ANGPTL5 and other metabolic related biomarkers to shed more light on its role in diabetes and obesity.

20.
J Clin Lipidol ; 13(5): 735-743, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31377052

RESUMO

BACKGROUND: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. OBJECTIVE: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. METHODS: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104 weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status. RESULTS: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups. CONCLUSIONS: In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.

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