Prevalence and factors associated with thyroid autoimmunity among children newly diagnosed with type 1 diabetes before and during the COVID-19 pandemic: Evidence from Kuwait.

AIMS: This study reports the prevalence and characteristics related to the development of thyroid autoimmunity among children newly diagnosed with type I diabetes (T1D) during the COVID-19 pandemic in Kuwait. MATERIALS AND METHODS: This is a prospective observational study of all children under age 14 years newly diagnosed with T1D in Kuwait. We define the duration of the COVID-19 pandemic from the official declaration of the first identified positive COVID-19 case on 24 February 2020 until 31 December 2022. For comparison, we use the time period directly before the COVID-19 pandemic, 1 January 2017 to 23 February 2020. RESULTS: One thousand twenty-four (1024) children newly diagnosed with T1D in Kuwait during the study period were included. Among newly diagnosed children, 20.3% tested positive for thyroid antibodies during the COVID-19 pandemic, compared with 14.5% during the pre-pandemic period (p = 0.015). Children with positive COVID-19 status were more likely to present with thyroid antibodies (p = 0.035). After adjusting for other characteristics, patients diagnosed with T1D during the COVID-19 pandemic had double the odds of testing positive for thyroid antibodies (Adjusted odds ratio = 2.173, 95%CI: 1.108, 4.261, p = 0.024). CONCLUSIONS: Incident cases of T1D during the COVID-19 pandemic may be different in aetiology or contextual factors leading to a higher risk of thyroid autoimmunity. Longitudinal studies are needed to understand the role of COVID-19 in the onset and progression of T1D and on thyroid autoimmunity and disease.

Post-operative pain in non-surgical root canal treatment after sealer-based obturation versus warm vertical compaction: A randomized clinical trial.

AIM: Post-operative pain may occur after non-surgical root canal treatment (NSRCT). The root filling technique and choice of sealer may be contributing factors. This randomized controlled clinical trial compared post-operative pain and analgesics intake after NSRCT using a sealer-based obturation technique (SBO) with single-cone gutta-percha and calcium silicate sealer (CSS) versus a warm-vertical compaction (WVC) technique with gutta-percha and a resin-based sealer (RBS). METHODOLOGY: This study was designed as a parallel-two arm, double-blind, randomized superiority clinical trial registered at www. CLINICALTRIALS: gov (NCT04753138). Patients referred for NSRCT fulfilling the inclusion criteria participated in this study. Pre-operative periapical radiographs and CBCT scans were taken and numerical rating scale (NRS) pain scores were recorded. Upon completion of canal instrumentation, participants were randomly allocated to either Group SBO: SBO with CSS or Group WVC: Warm-vertical compaction with RBS. Post-operative pain and analgesics intake were recorded at 1, 3 and 7 days after endodontic treatment completion. Non-parametric Mann-Whitney U and Friedman tests and a generalized estimating equation were used to assess differences in pain scores between the groups, within each treatment group at different time points and for correlations, respectively. RESULTS: The study included 195 participants (212 teeth). One participant declined to submit the NRS form. Therefore, 194 participants (211 teeth) were included in the final analysis (99.5% response rate). No statistically significant differences in post-operative pain or analgesic intake existed between the two groups at any time point (p > .05). Age, pre-operative pain, apical diagnosis and post-operative analgesic intake were significantly related to post-operative pain (p < .05). CONCLUSIONS: Sealer-based obturation technique with CSS was associated with similar post-operative pain levels and analgesics intake as WVC with RBS. Regarding post-operative pain, SBO with CSSs may be a suitable clinical alternative.

Higher rates of diabetic ketoacidosis and admission to the paediatric intensive care unit among newly diagnosed children with type 1 diabetes in Kuwait during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic might have a multifaceted effect on children with type 1 diabetes (T1D), either directly through infection itself or indirectly due to measures implemented by health authorities to control the pandemic. OBJECTIVE: To compare data on children newly diagnosed with T1D in Kuwait during the COVID-19 pandemic to the pre-pandemic period. RESEARCH DESIGN AND METHODS: We analysed data on children aged 12 years or less registered in the Childhood-Onset Diabetes electronic Registry (CODeR) in Kuwait. Data were incidence rate (IR), diabetic ketoacidosis (DKA), and its severity and admission to the paediatric intensive care unit (PICU). RESULTS: The IR of T1D was 40.2 per 100,000 (95% CI; 36.0-44.8) during the COVID-19 pandemic period and was not statistically different from pre-pandemic. A higher proportion of incident T1D cases presented with DKA and were admitted to the PICU during the pandemic (52.2% vs. 37.8%: p Ë‚ 0.001, 19.8% vs. 10.9%; p = 0.002, respectively). The COVID-19 pandemic was positively associated with presentation of DKA and admission to PICU (AOR = 1.73; 95% CI, 1.13-2.65; p = 0.012, AOR = 2.04; 95% CI, 1.13-3.67; p = 0.018, respectively). Children of families with a positive history for diabetes were less likely to present with DKA and get admitted to the PICU during the COVID-19 pandemic (AOR = 0.38; 95% CI, 0.20-0.74; p = 0.004, AOR = 0.22; 95% CI, 0.08-0.61; p = 0.004, respectively). CONCLUSION: High rates of DKA at presentation and admission to PICU in incident T1D cases during the COVID-19 pandemic warrant further studies and effective mitigation efforts through increasing awareness, early detection, and timely intervention.

Anthropometric cut-points for discriminating diabetes and the metabolic syndrome among Arabs and Asians: the Kuwait Diabetes Epidemiology Program.

This study aimed to determine anthropometric cut-points for screening diabetes and the metabolic syndrome (MetS) in Arab and South Asian ethnic groups in Kuwait and to compare the prevalence of the MetS based on the ethnic-specific waist circumference (WC) cut-point and the International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute WC criteria. The national population-based survey data set of diabetes and obesity in Kuwait adults aged 18-60 years was analysed. Age-adjusted logistic regression and receiver operating characteristic (ROC) analyses were conducted to evaluate for 3589 individuals the utility of WC, waist:height ratio (WHtR) and BMI to discriminate both diabetes and ≥3 CVD risk factors. Areas under the ROC curve were similar for WC, WHtR and BMI. In Arab men, WC, WHtR and BMI cut-offs for diabetes were 106 cm, 0·55 and 28 kg/m2 and for ≥3 CVD risk factors, 97 cm, 0·55 and 28 kg/m2, respectively. In Arab women, cut-offs for diabetes were 107 cm, 0·65 and 33 kg/m2 and for ≥3 CVD risk factors, 93 cm, 0·60 and 30 kg/m2, respectively. WC cut-offs were higher for South Asian women than men. IDF-based WC cut-offs corresponded to a higher prevalence of the MetS across sex and ethnic groups, compared with Kuwait-specific cut-offs. Any of the assessed anthropometric indices can be used in screening of diabetes and ≥3 CVD risk factors in Kuwaiti Arab and Asian populations. ROC values were similar. The WC threshold for screening the MetS in Kuwaiti Arabs and South Asians is higher for women.

Trends in glycemic, blood pressure, and lipid control in adults with diabetes in Switzerland: the CoLaus|PsyCoLaus Study.

AIM: To assess the 15-year trends in the level of glycemic, blood pressure, and cholesterol control in adults with diabetes in a Swiss population-based cohort. RESEARCH DESIGN AND METHODS: CoLaus|PsyCoLaus is a prospective cohort study of 6733 adults aged 35-75 years in Lausanne, Switzerland. Baseline recruitment was conducted in 2003-6 and was followed by three subsequent follow-ups in 2009-12, 2014-17 and 2018-21. In adults with diabetes, glycemic control was defined as fasting plasma glucose <7 mmol/L, blood pressure control as systolic and diastolic pressures of <140/90 mm Hg, and lipid control as non-high-density lipoprotein (non-HDL) cholesterol control <3.4 mmol/L. RESULTS: Rates of glycemic control improved from 23.2% (95% CI 19.5 to 27.3) in 2003-6 to 32.8% (95% CI 28.1 to 37.8) in 2018-21. Blood pressure control also improved, from 51.5% at baseline (95% CI 46.8 to 56.2) to 63.3% (95% CI 58.2 to 68.1) 15 years later. The largest improvement was in cholesterol control, from 29.1% (95% CI 25.1 to 33.6) in 2003-6 to 56.3% (95% CI 51.1 to 61.4) in 2018-21. Overall, simultaneous control of all three improved from 5.5% (95% CI 3.7 to 8.1) at baseline to 17.2% (95% CI 13.7 to 21.5) 15 years later. Improvements in risk factor control tallied with an increase in the use of glucose-lowering agents, blood pressure-lowering medication, and statins. Men were less likely to achieve blood pressure control but presented with a better control of non-HDL cholesterol. Caucasians were less likely to achieve simultaneous control than non-Caucasians. CONCLUSION: Cardiovascular risk factor control in adults with diabetes in Switzerland has increased in the last 15 years, but there remains a margin for improvement.

Genetic risk scores: are they important for diabetes management? results from multiple cross-sectional studies.

BACKGROUND: Several genetic risk scores (GRS) for type 2 diabetes (T2DM) have been published, but not replicated. We aimed to 1) replicate previous findings on the association between GRS on prevalence of T2DM and 2) assess the association between GRS and T2DM management in a sample of community-dwelling people from Switzerland. METHODS: Four waves from a prospective study conducted in Lausanne. Seven GRS related to T2DM were selected, and compared between participants with and without T2DM, and between controlled and uncontrolled participants treated for T2DM. RESULTS: Data from 5426, 4017, 2873 and 2170 participants from the baseline, first, second and third follow-ups, respectively, was used. In all study periods, participants with T2DM scored higher than participants without T2DM in six out of seven GRS. Data from 367, 437, 285 and 207 participants with T2DM was used. In all study periods, approximately half of participants treated for T2DM did not achieve adequate fasting blood glucose or HbA1c levels, and no difference between controlled and uncontrolled participants was found for all seven GRS. Power analyses showed that most GRS needed a sample size above 1000 to consider the difference between controlled and uncontrolled participants as statistically significant at p = 0.05. CONCLUSION: In this study, we confirmed the association between most published GRS and diabetes. Conversely, no consistent association between GRS and diabetes control was found. Use of GRS to manage patients with T2DM in clinical practice is not justified.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 µSiemens) and estimated glomerular filtration rate (eGFR). RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Incidence of SARS-CoV-2 reinfection in a paediatric cohort in Kuwait.

OBJECTIVE: Subsequent protection from SARS-CoV-2 infection in paediatrics is not well reported in the literature. We aimed to describe the clinical characteristics and dynamics of SARS-CoV-2 PCR repositivity in children. DESIGN: This is a population-level retrospective cohort study. SETTING: Patients were identified through multiple national-level electronic COVID-19 databases that cover all primary, secondary and tertiary centres in Kuwait. PARTICIPANTS: The study included children 12 years and younger between 28 February 2020 and 6 March 2021. SARS-CoV-2 reinfection was defined as having two or more positive SARS-CoV-2 PCR tests done on a respiratory sample, at least 45 days apart. Clinical data were obtained from the Pediatric COVID-19 Registry in Kuwait. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary measure is to estimate SARS-CoV-2 PCR repositivity rate. The secondary objective was to establish average duration between first and subsequent SARS-CoV-2 infection. Descriptive statistics were used to present clinical data for each infection episode. Also, incidence-sensitivity analysis was performed to evaluate 60-day and 90-day PCR repositivity intervals. RESULTS: Thirty paediatric patients with COVID-19 had SARS-CoV-2 reinfection at an incidence of 1.02 (95% CI 0.71 to 1.45) infection per 100 000 person-days and a median time to reinfection of 83 (IQR 62-128.75) days. The incidence of reinfection decreased to 0.78 (95% CI 0.52 to 1.17) and 0.47 (95% CI 0.28 to 0.79) per person-day when the minimum interval between PCR repositivity was increased to 60 and 90 days, respectively. The mean age of reinfected subjects was 8.5 (IQR 3.7-10.3) years and the majority (70%) were girls. Most children (55.2%) had asymptomatic reinfection. Fever was the most common presentation in symptomatic patients. One immunocompromised experienced two reinfection episodes. CONCLUSION: SARS-CoV-2 reinfection is uncommon in children. Previous confirmed COVID-19 in children seems to result in a milder reinfection.

HbA1c, blood pressure, and cholesterol control in adults with diabetes: A report card for Kuwait.

AIM: To assess the level of glycemic, blood pressure, and cholesterol control (the 'ABCs') nationally amongst adults with diabetes living in Kuwait. MATERIALS AND METHODS: Using data from two national cross-sectional surveys, the levels of risk factor control were assessed in 1,801 adults with diabetes, aged 18-82 years. Glycemic control was defined as HbA1c < 7%, blood pressure control as systolic and diastolic blood pressures of <140/90 mmHg, and non-HDL cholesterol control as <3.4 mmol/L. RESULTS: The percentage of adults with diabetes achieving control was 39.2% (95% CI, 37.0-41.5) for glycemia, 58.4% (95% CI, 56.0-60.7) for blood pressure, and 28.3% (95% CI, 26.3-30.4) for non-HDL cholesterol. The percentage of adults who were non-smokers was 77.6% (95%, CI 75.6-79.4). The percentage of adults with diabetes achieving control on all three risk factors was 7.4% (95% CI, 6.3-8.8), and only 5.8% (95% CI, 4.8-7.0) achieved ABC control and were nonsmokers. ABC control was 30% higher in women compared with men. Non-Kuwaitis were almost twice as likely to have uncontrolled ABC factors compared with Kuwaitis. CONCLUSIONS: Only 1 in 13 people with diabetes in Kuwait achieved good control of glycemia, blood pressure, and cholesterol. Only 2 in 5 achieved glycemic control, 6 in 10 blood pressure control, and 2 in 7 cholesterol control. A national diabetes quality improvement program is urgently needed to improve the quality of care and to prevent long-term complications.

Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination.

The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people (81 diabetic and 181 non-diabetic persons) that took two doses of BNT162b2 (Pfizer-BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. The mean ( ± 1 standard deviation) levels were 154 ± 49.1 vs. 138 ± 59.4 BAU/ml for IgG and 87.1 ± 11.6 vs. 79.7 ± 19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection, and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95% CI: 27.08 to 0.64 BAU/ml, p=0.041) less IgG antibodies and 4.42% (95% CI: 8.53 to 0.32%, p=0.036) fewer neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity. Nonetheless, it is important that people get their COVID-19 vaccination especially people with diabetes.

Previous COVID-19 Infection and Antibody Levels After Vaccination.

Background: The emergence of new COVID-19 variants of concern coupled with a global inequity in vaccine access and distribution has prompted many public health authorities to circumvent the vaccine shortages by altering vaccination protocols and prioritizing persons at high risk. Individuals with previous COVID-19 infection may not have been prioritized due to existing humoral immunity. Objective: We aimed to study the association between previous COVID-19 infection and antibody levels after COVID-19 vaccination. Methods: A serological analysis to measure SARS-CoV-2 immunoglobulin (Ig)G, IgA, and neutralizing antibodies was performed on individuals who received one or two doses of either BNT162b2 or ChAdOx1 vaccines in Kuwait. A Student t-test was performed and followed by generalized linear regression models adjusted for individual characteristics and comorbidities were fitted to compare the average levels of IgG and neutralizing antibodies between vaccinated individuals with and without previous COVID-19 infection. Results: A total of 1,025 individuals were recruited. The mean levels of IgG, IgA, and neutralizing antibodies were higher in vaccinated subjects with previous COVID-19 infections than in those without previous infection. Regression analysis showed a steeper slope of decline for IgG and neutralizing antibodies in vaccinated individuals without previous COVID-19 infection compared to those with previous COVID-19 infection. Conclusion: Previous COVID-19 infection appeared to elicit robust and sustained levels of SARS-CoV-2 antibodies in vaccinated individuals. Given the inconsistent supply of COVID-19 vaccines in many countries due to inequities in global distribution, our results suggest that even greater efforts should be made to vaccinate more people, especially individuals without previous COVID-19 infection.

Adult Diabetes and Prediabetes Prevalence in Kuwait: Data from the Cross-Sectional Kuwait Diabetes Epidemiology Program.

BACKGROUND: This study aimed to estimate the prevalence of diabetes and prediabetes in adults in Kuwait. METHODS: The Kuwait Diabetes Epidemiology Program was a nationally representative, cross-sectional study of diabetes and obesity in Kuwait conducted between 2011 and 2014. The survey sampled 4937 adults in Kuwait aged 20 years or more and recorded participants' demographics, behaviours, medical history, physical measurements and blood biochemical measurements. Prediabetes was defined as fasting plasma glucose between 6.1 and 6.9 mmol/L or HbA1c between 6 and 6.4% (42-47 mmol/mol). Diabetes was defined as self-reported history with prescribed glucose-lowering medication or FPG ≥7mmol/L or HbA1c level ≥6.5% (≥48 mmol/mol). RESULTS: The overall adjusted prevalence of diabetes was 19.1%. The overall adjusted prevalence of prediabetes was 13.5%. Diabetes prevalence was 5.4%, 14.2%, 38.7% and 64.8% in adults aged 20-29, 30-44, 45-59 and 60 years or more, respectively. Diabetes prevalence was 22.4% in men and 14.4% in women. Prediabetes prevalence was 14.8% in men and 11.5% in women. In Kuwaitis, diabetes and prediabetes prevalence was 21.8% and 11.1%, respectively, while prevalence in non-Kuwaitis was 18.2% for diabetes and 14.3% for prediabetes. CONCLUSION: These findings illustrate the severe public health challenge posed by diabetes in Kuwait.

Glycemic control in Kuwaiti diabetes patients treated with glucose-lowering medication.

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.

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data.

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.

Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function.

Background: Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involved in the regulation of renal function. Materials and methods: Twenty-four bariatric patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy donated urine pre-operatively and at 2-6 months and 1-2 years post-operatively. Urine samples were also obtained from 10 healthy weight and 7 morbidly obese non-surgical controls. Expression levels of kidney microRNAs were assessed in urine and the function of microRNAs was assessed through the in vitro transfection of HK-2 cells, a kidney proximal tubule cell line. Results: Levels of miR 192, miR 200a, and miR 200b were upregulated in urine following bariatric surgery. This increase was consistent across surgical type and diabetes status and was maintained and enhanced with time. Bariatric surgery alters urinary miR 192 expression from levels seen in morbidly obese patients to levels seen in healthy weight control patients. In mechanistic studies, the transfection of miR 192 in HK-2 cells increased miR 200a expression and decreased ZEB2, a key transcriptional promoter of kidney fibrosis. Conclusions: Bariatric surgery increased miR 192 and miR 200 urinary levels, key anti-fibrotic microRNAs that could contribute to a renal-protective mechanism and may be of value as urinary biomarkers following surgery. These findings suggest that urinary microRNAs may represent potential novel biomarkers for obesity-associated renal function.

The Prevalence of Overweight and Obesity in an Adult Kuwaiti Population in 2014.

Background: According to World Health Organization (WHO) estimates, Kuwait is ranked amongst the top countries in the world in obesity prevalence. This study aims to describe the prevalence of overweight, obesity, and various types of adiposity in Kuwaiti adults. Methods: This cross-sectional study of 3,915 Kuwaiti adults aged 18-69 years used the STEP-wise approach to surveillance of non-communicable diseases, a WHO Instrument for Chronic Disease Risk Factor Surveillance. We assessed demographic information, lifestyle, personal and family history of diseases and physical measurements (height, weight, waist, and hip circumferences). All participants with valid height and weight measurements (n = 3,589) were included in the present analysis. Overweight was defined as BMI 25-29.9 kg/m2 and obesity as BMI ≥30 kg/m2. Results: Obesity prevalence was 40.3% [95% confidence interval, 38.6-42.0%] (men, 36.5%; women, 44.0%); and overweight prevalence was 37% [35.4-38.7%] (men, 42%; women, 32.1%). The median BMI was 28.4 kg/m2 among men and 29.1 kg/m2 among women. Obesity prevalence was directly associated with female sex, age, history of diabetes, and being married in both men and women; and was inversely associated with education level in women. The prevalence of elevated waist-to-hip ratio was 46.9% among men and 37.9% among women. Waist circumference, waist-hip and waist-height ratios were directly associated with diabetes in both men and women, and inversely associated with education level in women. Conclusion: Almost eight in ten Kuwaiti adults were overweight or obese. Urgent public health action is warranted to tackle the obesity epidemic in Kuwait.

Reduced miR-181d level in obesity and its role in lipid metabolism via regulation of ANGPTL3.

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.

Improved physiology and metabolic flux after Roux-en-Y gastric bypass is associated with temporal changes in the circulating microRNAome: a longitudinal study in humans.

BACKGROUND: The global pandemic of obesity and the metabolic syndrome are leading causes of mortality and morbidity. Bariatric surgery leads to sustained weight loss and improves obesity-associated morbidity including remission of type 2 diabetes. MicroRNAs are small, endogenous RNAs that regulate gene expression post-transcriptionally, controlling most of the human transcriptome and contributing to the regulation of systemic metabolism. This preliminary, longitudinal, repeat sampling study, in which subjects acted as their own control, aimed to assess the temporal effect of bariatric surgery on circulating microRNA expression profiles. METHODS: We used Exiqon's optimized circulating microRNA panel (comprising 179 validated miRNAs) and miRCURY locked nucleic acid plasma/serum Polymerase Chain Reaction (PCR) to assess circulating microRNA expression. The microRNAome was determined for Roux-en-Y gastric bypass (RYGB) patients examined preoperatively and at 1 month, 3 months, 6 months, 9 months and 12 months postoperatively. Data was analysed using multivariate and univariate statistics. RESULTS: Compared to the preoperative circulating microRNA expression profile, RYGB altered the circulating microRNAome in a time dependent manner and the expression of 48 circulating microRNAs were significantly different. Importantly, these latter microRNAs are associated with pathways involved in regulation and rescue from metabolic dysfunction and correlated with BMI, the percentage of excess weight loss and fasting blood glucose levels. CONCLUSIONS: The results of this pilot study show that RYGB fundamentally alters microRNA expression in circulation with a time-dependent progressive departure in profile from the preoperative baseline and indicate that microRNAs are potentially novel biomarkers for the benefits of bariatric surgery.

The prevalence of pre-diabetes and diabetes in the Kuwaiti adult population in 2014.

BACKGROUND: Kuwait ranks among the top 20 countries worldwide in diabetes prevalence. This study's objectives were to assess the prevalence of pre-diabetes and diabetes in Kuwaiti adults. METHODS: Kuwaiti citizens aged 18-69 years (n = 3915) were studied using the WHO's STEPwise survey methodology, including its Instrument for Chronic Disease Risk Factor Surveillance. Participants' demographics, medical history, physical measurements and blood biochemistry were assessed. A subset of 2561 individuals completed all three survey steps, including fasting plasma glucose (FPG) and HbA1c assays. The study assessed the prevalence of pre-diabetes (FPG 6.1-6.9 mmol/L or HbA1c level 5.7-6.4%) and diabetes (self-reported history of diabetes with prescription of diabetes medications or FPG ≥ 7 mmol/L or HbA1c level ≥6.5%). RESULTS: The prevalence of pre-diabetes was 19.4% [95% CI: 17.9-21.0%] (By sex: Men, 19.3%; Women, 19.5%; p = 0.92; By age (years): 18-29 y, 13.9%; 30-44 y, 22.6%; 45-59 y, 25.8%; 60-69 y, 16.4%; p < 0.001). The prevalence of diabetes was 18.8% [17.3-20.4%] (By sex: Men, 20.4%; Women, 17.4%; p = 0.055; By age: 18-29 y, 6.6%; 30-44 y, 14.0%; 45-59 y, 36.7%; 60-69 y, 62.8%; p < 0.001), of whom 41.5% were previously undiagnosed. Diabetes prevalence was 27.4% among those with body mass index (BMI) ≥ 30 kg/m2, 29% among those with elevated waist-hip ratio and 36% among those with hypertension. Diabetes was positively associated with BMI, waist-hip ratio and blood pressure level. Pre-diabetes was positively associated with BMI and waist-hip ratio, but not blood pressure level. CONCLUSIONS: Almost 40% of Kuwaiti citizens had pre-diabetes or diabetes. Urgent public health action is needed to decrease diabetes prevalence and thus avoid associated morbidity and mortality.