Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Real world use of tirzepatide in the treatment of type 2 diabetes in an Arab population.

AIM: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) dual receptor agonist (RA) that reduces glycated haemoglobin (HbA1c) and weight in patients with type 2 diabetes. We assessed the effectiveness of tirzepatide in real-world use in an Arab population. METHODS: Review of clinical data from a specialist outpatient diabetes centre; study time points and outcome measures were pre-specified. RESULTS: Tirzepatide was initiated in 8945 patients between 24 October 2022 and 31 December 2023. Of these, 3686 individuals reached 40 weeks of follow-up. At initiation, the mean ± SD age was 54.1 ± 11.5 years, body mass index 34.6 ± 6.0 kg/m2 and HbA1c 7.3 ± 1.5% (56 ± 17 mmol/mol); 2296 (62%) were switched to tirzepatide from another GLP-RA and 317 (8.6%) reported previous bariatric surgery. The maximum dose dispensed was ≥12.5 mg/week in 1087, 7.5-10.0 mg/week in 1688 and 2.5-5.0 mg/week in 911. The mean 40-week reduction in HbA1c was 0.6 ± 1.2% (8 ± 13 mmol/mol) and the reduction in weight was 4.5 ± 6.9 kg (4.8 ± 7.3%). GLP-RA-naïve patients experienced a significantly greater reduction in HbA1c [1.0 ± 1.3% (11 ± 14 mmol/mol) versus 0.5 ± 1.2% (6 ± 13 mmol/mol), p < .0001] and weight (7.2 ± 8.6 vs. 4.2 ± 6.6 kg, p < .0001) compared with previously exposed individuals. Post-metabolic bariatric surgery patients lost significantly more weight (7.8 ± 9.4 vs. 4.5 ± 7.0 kg, p < .0001). Improvements in blood pressure, lipid profile, and liver transaminases were noted at 40 weeks. Tirzepatide was well tolerated, with 288 (7.8%) of patients discontinuing treatment because of adverse effects, predominantly gastrointestinal. CONCLUSION: In real-world use, tirzepatide significantly reduced HbA1c levels and weight and was well tolerated. Previous GLP-RA use was associated with significantly lesser HbA1c and weight reduction, and previous metabolic bariatric surgery was associated with greater weight loss.

First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-world Clinical Settings in a Middle East Population.

PURPOSE: Inclisiran is the first small interfering RNA-based treatment approved for reducing pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report the first evaluation of the effects of inclisiran in a Middle East population. METHODS: We conducted a retrospective review of patients initiating inclisiran treatment at an outpatient diabetology, endocrinology, and cardiology center between May 2021 and December 2022. All patients followed up for 90 days or more, or with at least 1 lipid determination post initiation were included. Participants were categorized into primary prevention (n = 57) and secondary prevention (n = 89) groups according to previous atherosclerotic cardiovascular disease. FINDINGS: Inclisiran was initiated in 146 patients; mean (SD) age was 54.8 (12.12) years, 82 patients (56.2%) were male, 28 patients (19.2%) had received a diagnosis of familial hypercholesterolemia, 89 patients (61%) had received a diagnosis of diabetes mellitus, and 35 patients (23.9%) had a statin intolerance. Median (interquartile range) follow-up was 137 (90 to 193) days. At 90 days, median (interquartile range) reductions in serum LDL-C and triglycerides were -37.9% (-9.5% to -51.2%) and -12.0% (-9.8% to -40.5%), respectively, in primary prevention and -54.1% (-17.1% to -71.4%) and -15.3% (-14% to -38.8%), respectively, in secondary prevention (all, P < 0.001). LDL-C goals were attained in 110 patients (75.3%). Nonattainment of LDL-C goal was attributed to system effect in 26 patients (72.2%), biological effect in 5 patients (13.9%), and discontinuation of treatment in 5 patients (13.9%). Therapy was well tolerated. IMPLICATIONS: This study is the first from the Middle East and North Africa region that reported the real-world efficacy and safety profile of inclisiran in a mixed-risk population of patients with heterozygous familial hypercholesterolemia and other non-familial hypercholesterolemia indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation. Fewer AEs were reported in this predominantly Arabic population, consistent with previous safety reports for inclisiran. It is important to note that no patient stopped inclisiran treatment due to AEs. Strengths of our study included an optimal cohort, patient heterogeneity, and high retention. In addition, we were able to report mean robust effects of inclisiran and good medication tolerability, quite like randomized studies and open-label extension periods. Despite this, our study had some limitations, including selection bias due to the retrospective design and the absence of a comparative group.

Fructosamine as a predictor of incident diabetic microvascular disease in a population with high prevalence of red cell disorders: A cohort study.

AIMS: Fructosamine can be used to estimate glycaemia in individuals in whom HbA1c may be unreliable. We aimed to establish clinically useful fructosamine treatment targets in a population with a high prevalence of conditions affecting erythrocyte survival, including variant haemoglobin and G6PD deficiency. METHODS: Fructosamine was measured on a clinical basis in individuals in whom HbA1c was suspected to be unreliable by their primary physician. Study endpoints were incident retinopathy and albuminuria in individuals with Prediabetes (n = 60), Type 1 (n = 161) or Type 2 diabetes (n = 1350) during follow up of 4.4 ± 2.3 years. RESULTS: Fructosamine ≥ 250 umol/L was significantly associated with incident retinopathy, and fructosamine ≥ 300 umol/L with incident microalbuminuria, in univariate analysis and adjusted for established risk factors. Fructosamine ≥ 250 umol/L was also significantly associated with incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol) at inclusion. CONCLUSIONS: In this patient population, a single measurement of fructosamine significantly and independently predicts incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol). Routine measurement of fructosamine on at least one occasion is recommended as part of assessment of prediabetes or diabetes mellitus in populations with a high prevalence of conditions affecting erythrocyte lifespan.

Validation of the new IDF-DAR risk assessment tool for Ramadan fasting in patients with diabetes.

BACKGROUND: A new IDF-DAR (International Diabetes Federation - Diabetes and Ramadan Alliance) risk stratification tool was published in 2021 to better stratify the risk of Ramadan fasting in people with diabetes. METHODS: We performed a prospective, survey-based study before and after Ramadan 1442/2021 to explore the ability of the new IDF-DAR risk stratification tool to predict the probability of fasting and the risk of complications from fasting in people with diabetes. RESULTS: A pre-Ramadan assessment was completed for 659 patients who intended to fast in Ramadan; 647(98.2%) answered the post-Ramadan follow-up questionnaire. Mean age was 53.5 years and 47.9% were females. 603(91.5%) had type 2 diabetes while 56(8.5%) had type 1 diabetes. Using the IDF-DAR risk criteria at the pre-Ramadan assessment, 339(51.4%) were categorized as low-risk (score <3), 173(26.3%) as moderate-risk (score 3.5-6) and 147(22.3%) as high-risk (score >6). 94.3%, 81.1% and 76.9% patients fasted the full 30 days in the low, moderate and high risk groups respectively (p < 0.0001). Any hypoglycaemia was reported in the low, moderate and high risk groups by 6.3%, 21.9% and 35.0% respectively while severe hypoglycaemia was reported by 3(2.1%) patients in the high, 3(1.8%) in the moderate and none(0%) in the low risk groups. Hyperglycaemia (>250 mg/dL) was reported in the low, moderate and high risk groups by 2.7%, 13.0% and 23.8% respectively. CONCLUSION: The new IDF-DAR risk assessment tool appears to reliably predict both the ability to fast during Ramadan as well as the likelihood of getting hypoglycaemia or hyperglycaemia.

Monogenic diabetes variants in Emirati women with gestational diabetes are associated with risk of non-autoimmune diabetes within 5 years after pregnancy.

Aims: To investigate the prevalence of pathogenic variants in monogenic diabetes genes in Emirati women with gestational diabetes (GDM) and examine the risk of developing hyperglycemia during follow-up in carriers and non-carriers. Methods: Female patients with GDM (n = 370) were identified. Selected monogenic diabetes genes, GCK, HNF1A, HNF4A, HNF1B, INS, ABCC8 and KCNJ1I, were examined by sequencing and identified variants were classified. Anthropometrics and subsequent diagnosis of diabetes were extracted from hospital records. Median follow-up time was 6-years. Results: A total of 34 variants were detected. Seven women (2%) were carriers of pathogenic variants in GCK, HNF1A, INS, ABCC8 or KCNJ11. A significantly larger fraction of women carrying pathogenic variants were diagnosed with any form of hyperglycemia or diabetes postpartum (risk ratio = 1.8 (1.1-2.9), p = 0.02) or 2.5 (1.3-4.8; p = 0.009), respectively) and they had a shorter disease-free period after GDM compared to women without such variants. There were no significant associations between carrying pathogenic variants and anthropometric measures or C-peptide. Conclusions: Pathogenic variants were found in known monogenic diabetes genes in two percent of Emirati women with GDM, allowing for precision medicine utilisation in these women both during and outside pregnancy. Carriers were at an increased risk of being diagnosed with hyperglycemia or type 2 diabetes mellitus within 5 years after pregnancy.

Associations between neck circumference and markers of dysglycemia, non-alcoholic fatty liver disease, and dysmetabolism independent of Body Mass Index in an Emirati population.

Aim: Neck circumference (NC) is quick and easy to measure and may be a useful surrogate marker for body composition. We investigated NC as a potential marker of dysglycemia, MetS, and NAFLD. Methods: 674 individuals were recruited at the Imperial College London Diabetes Centre in a study of sleep apnea prevalence. Of these, 547 (Age 46 ± 11.4 years, Body Mass Index (BMI) 31 ± 6 kg/m2, 279 (51%) female, 113 normal glucose tolerance (NGT), 108 Prediabetes, 326 Type 2 diabetes (T2DM)) met all inclusion criteria for analysis. NC was measured at the thyroid cartilage, and collar size was recorded. Analysis was performed using univariate and multivariate linear regression. Results: Adjusted for BMI, sex, and age, NC was 0.65 ± 0.3 cm greater in prediabetes (p = 0.0331), and 1.07 ± 0.28 cm greater in T2DM, compared with NGT (p = 0.0002). Adjusting for BMI, sex, and glycemic status, 1-cm increase in NC was associated with a 1.04 ± 1.01 U/L (p <0.0001) increase in ALT and, additionally, correcting for statin use, a 0.03 ± 0.01 mmol/L reduction in HDL (p <0.0001) and a 0.1 ± 0.02 increase in TC : HDL. A 1 cm increase in NC was associated with a 1.15 ± 1.02% (p <0.0001) increase in 10-year AHA cardiovascular risk in individuals over 40 years old and a 0.16 ± 0.02 (p <0.0001) increase in NAFLD fibrosis score. The neck circumference was associated with the hazard of new onset of deranged ALT adjusted for age, sex, glycemic status, and BMI (hazard ratio 1.076 (95% CI 1.015-1.14, p = 0.0131) and with the incidence of Fatty Liver Index associated with high probability of NAFLD (hazard ratio 1.153 (95% CI 1.019-1.304), p = 0.0239). Conclusion: NC is associated with dysglycemia, components of the MetS, and factors predictive of NAFLD, but does not appear to independently predict subsequent progression to high risk of liver fibrosis in this predominantly diabetic population.

The First Report of a Real-world Experience With a PCSK9 Inhibitor in a Large Familial Hyperlipidemia and Very-high-risk Middle Eastern Population.

PURPOSE: Evolocumab, a monoclonal inhibitor of proprotein convertase subtilisin/kexin 9, has been shown to reduce proatherogenic lipoproteins in patients with or without familial hypercholesterolemia (FH), diabetes mellitus, or atherosclerotic cardiovascular disease (ASCVD). We explored the safety profile and clinical effectiveness of evolocumab in an outpatient population of Emirati individuals with FH diagnosed per Dutch Lipid Clinic Network criteria, previous ASCVD, or statin intolerance. METHODS: This study was a retrospective review of patients initiating evolocumab treatment for any indication at Imperial College London Diabetes Centre between 2017 and 2020. All individuals followed up for at least 90 days or with at least one lipid panel postinitiation were included. Participants were subclassified into primary prevention (no previous ASCVD event, n = 81) and secondary prevention (any prior clinical ASCVD event, n = 102) groups. FINDINGS: Evolocumab was initiated in 183 individuals (mean [SD] age, 51.5 [12.4] years; 51% male); 108 (59%) had a clinical or genetic FH diagnosis, and 70.5% had diabetes mellitus. Statin intolerance was a treatment indication in 60 (32.8%) individuals. At 90 days, substantial reductions in serum LDL-C, triglycerides (TG), and total cholesterol:HDL-C (TC:HDL-C) were observed in both the primary and secondary prevention groups, and both FH and non-FH individuals. In the primary prevention group, median (interquartile range) reduction in LDL-C was 43.7% (10.8%; 63.0%); TG, 15.0% (7.2%; 35.3%); and TC:HDL-C, 31.5% (11.1%; 46.0%). In the secondary prevention group, median (interquartile range) reduction in LDL-C was 48.3% (22%; 70%); TG, 19.6% (1.2%; 32.5%); and TC:HDL-C, 32.6% (14.6%; 46.3%) (all, P < 0.0001). American College of Cardiology/American Heart Association LDL-C targets were consistently achieved in 114 (62.3%) patients during a follow-up of 359 (79-639) days. Nonattainment of the LDL-C target was attributed to nonadherence in 36 (52.2%) patients and discontinuation of treatment in 14 (20.3%) patients. Evolocumab was discontinued in 4 patients because of adverse events. IMPLICATIONS: This study is the first from the Middle East and North Africa region that reports the real-world efficacy of evolocumab in a mixed risk population of individuals with FH and other non-FH indications. Clinically meaningful and sustained reductions in LDL-C, TG, and cholesterol ratios were observed after evolocumab initiation. Few adverse events were reported in this predominantly Arabic population, consistent with previous safety reports for evolocumab. Notable strengths of this study include a relatively large cohort, patient heterogeneity and high retention, and a minimum follow-up of 1 year. Despite these strengths, the study has some limitations, including the selection bias due to the retrospective design and absence of comparative group.

Bariatric surgery in the treatment of patients with obesity and type 1 diabetes: A retrospective study of clinical data.

AIM: To evaluate the effectiveness and safety of bariatric surgery in patients with coexisting type 1 diabetes and obesity who choose to undergo bariatric surgery for weight management. MATERIALS AND METHODS: We conducted a retrospective, longitudinal review of the clinical data of patients with type 1 diabetes, followed up at our centre after bariatric surgery had been performed elsewhere. RESULTS: Sixty-one patients were included, of whom 51% were women, and 57 (93%) were Emirati Arab, three (5%) were other Arab, and one (2%) was White in ethnic origin. The mean age at surgery was 31 years. A total of 42 patients (69%) underwent sleeve gastrectomy, 17 (28%) gastric bypass, and two (3%) gastric banding. In 48 patients with complete follow-up data, improvements were observed at 12 months in the median (interquartile range [IQR]) values for body mass index (BMI; 38.5 [34.9-40.9] to 26.1 [24.2-29.6] kg/m2 , P <0.001), glycated haemoglobin concentration (8.6 [7.8-9.2]% to 7.8 [7.2-8.5]%; P <0.001), daily insulin dose (1.0 [0.7-1.2] to 0.8 [0.6-0.9] units/kg/d; P <0.001), systolic blood pressure (127 [116-136] to 116 [110-120] mmHg; P <0.001), total cholesterol: high-density lipoprotein cholesterol ratio (3.4 [2.9-4.3] to 3.0 [2.6-3.5]; P <0.001), and albuminuria. In 32 patients followed up at 3 years, the median (IQR) reduction in BMI was 10.4 (5.9-11.7) kg/m2 , 50% reduced or stopped antihypertensive medication and 58% reduced or stopped lipid-modifying medication. Three patients each reported a single episode of diabetic ketoacidosis; in one case this was due to cessation of insulin treatment. CONCLUSIONS: In our cohort of patients with obesity and type 1 diabetes, bariatric surgery led to significant improvements in weight and cardiometabolic variables, with modest improvements in glycaemia. Few adverse events were reported.

Low Detection Rates of Genetic FH in Cohort of Patients With Severe Hypercholesterolemia in the United Arabic Emirates.

Background: Programs to screen for Familial hypercholesterolemia (FH) are conducted worldwide. In Western societies, these programs have been shown to be cost-effective with hit/detection rates of 1 in 217-250. Thus far, there is no published data on genetic FH in the Gulf region. Using United Arab Emirates as a proxy for the Gulf region, we assessed the prevalence of genetically confirmed FH in the Emirati population sample. Materials and Methods: We recruited 229 patients with LDL-C >95th percentile and employed a customized next generation sequencing pipeline to screen canonical FH genes (LDLR, APOB, PCSK9, LDLRAP1). Results: Participants were characterized by mean total cholesterol and low-density lipoprotein cholesterol (LDL-c) of 6.3 ± 1.1 and 4.7 ± 1.1 mmol/L respectively. Ninety-six percent of the participants were using lipid-lowering medication with mean corrected LDL-c values of 10.0 ± 3.0 mmol/L 15 out of 229 participants were found to suffer from genetically confirmed FH. Carriers of causal genetic variants for FH had higher on-treatment LDL-c compared to those without causal variants (5.7 ± 1.5 vs 4.7 ± 1.0; p = 3.7E-04). The groups did not differ regarding high-density lipoprotein cholesterol, triglycerides, body mass index, blood pressure, glucose, and glycated haemoglobin. Conclusion: This study reveals a low 7% prevalence of genetic FH in Emiratis with marked hypercholesterolemia as determined by correcting LDL-c for the use of lipid-lowering treatment. The portfolio of mutations identified is, to a large extent, unique and includes gene duplications. Our findings warrant further studies into origins of hypercholesterolemia in these patients. This is further supported by the fact that these patients are also characterized by high prevalence of type 2 diabetes (42% in the current study cohort) which already puts them at an increased risk of atherosclerotic cardiovascular disease. These results may also be useful in public health initiatives for FH cascade screening programs in the UAE and maybe the Gulf region.

Parameters of Bone and Cardiovascular Health Related to 25-Hydroxyvitamin D Status in Emirati Nationals attending Primary Care and Diabetes services: a retrospective cohort study.

Vitamin D deficiency is endemic in people living in the Gulf states. We performed a retrospective analysis of data gathered at the first attendance of 82,396 Emirati nationals to outpatient diabetes, endocrinology and general primary care services at two centres in the United Arab Emirates during 2012-2016. Our aim was to explore associations between vitamin D status and markers of cardiovascular and bone health. In the study population, 67.1% of men and 73.5% of women had serum 25(OH)D of less than 50 nmol/L, with the lowest levels being found in young adults. Among Emirati adults with type 2 diabetes, serum 25(OH)D < 50 nmol/L was associated with an increased risk of a coexisting adverse total cholesterol:HDL (TC:HDL) ratio (odds ratio 2.13 (1.60-2.84), p < 0.001). Correcting for age, sex, body mass index, HbA1c and statin therapy, an increase in 25(OH)D of 1 nmol/L was associated with a 0.01 unit reduction in TC:HDL in this population. In a subset of 1064 adult individuals, 25(OH)D < 25 nmol/L was associated with a reduction in DEXA-measured z-score of -0.29 (-0.44 to -0.15, p < 0.001) at the femoral neck and of -0.25(-0.45 to -0.05, p = 0.015) at L1-4, corrected for body mass index, compared with individuals with 25(OH)D ≥ 75 nmol/L. Our findings raise concerns regarding lifetime burden of cardiovascular disease and bone health for young Emiratis with vitamin D deficiency.

Routine clinical use of liraglutide 3 mg for the treatment of obesity: Outcomes in non-surgical and bariatric surgery patients.

In this study we prospectively collected data on the use of liraglutide 3 mg in obese Arab patients. As part of routine care, 2092 patients were dispensed liraglutide 3 mg. Median age was 38 years and 77% were women. Median baseline weight was 95 kg and body mass index was 36.6 kg/m2 . Of the patients, 188 (9%) had previous bariatric surgery. Seven hundred and eighty-seven patients were treated for ≥16 weeks and their median (interquartile range) weight loss was 6.0 (2.4-9.4) kg, equivalent to 6.4% (2.6%-9.7%) of baseline weight (P < 0.0001, n = 787). Of those treated for ≥16 weeks, 474 (60%) achieved a weight loss of >5% of baseline weight while 182 (23%) achieved >10% weight loss. There was no difference in percentage weight loss between postbariatric surgery (n = 76) and non-surgical patients (n = 711). As a result of adverse events, mainly gastrointestinal symptoms, 140 (6.7%) of the patients stopped treatment. One patient developed acute pancreatitis in the context of gallstone disease but made an uneventful recovery. Liraglutide 3 mg was well tolerated and resulted in weight loss in routine clinical care similar to that seen in randomized controlled trials.

Non-alcoholic fatty liver disease: Relationship with cardiovascular risk markers and clinical endpoints.

Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.

The effects of Ramadan fasting on activity and energy expenditure.

Background: Fasting during the month of Ramadan entails abstinence from eating and drinking between dawn and sunset and a major shift in meal times and patterns with associated changes in several hormones and circadian rhythms; whether there are accompanying changes in energy metabolism is unclear. Objective: We have investigated the impact of Ramadan fasting on resting metabolic rate (RMR), activity, and total energy expenditure (TEE). Design: Healthy nonobese volunteers (n = 29; 16 women) fasting during Ramadan were recruited. RMR was measured with the use of indirect calorimetry. In subgroups of participants, activity (n = 11; 5 women) and TEE (n = 10; 5 women) in free-living conditions were measured with the use of accelerometers and the doubly labeled water technique, respectively. Body composition was measured with the use of bioelectrical impedance. Measurements were repeated after a wash-out period of between 1 and 2 mo after Ramadan. Nonparametric tests were used for comparative statistics. Results: Ramadan fasting did not result in any change in RMR (mean ± SD: 1365.7 ± 230.2 compared with 1362.9 ± 273.6 kcal/d for Ramadan and post-Ramadan respectively, P = 0.713, n = 29). However, controlling for the effects of age, sex, and body weight, RMR was higher in the first week of Ramadan than in subsequent weeks. During Ramadan, the total number of steps walked were significantly lower (n = 11, P = 0.001), while overall sleeping time was reduced and different sleeping patterns were seen. TEE did not differ significantly between Ramadan and post-Ramadan (mean ± SD: 2224.1 ± 433.7 compared with 2121.0 ± 718.5 kcal/d for Ramadan and post-Ramadan, P = 0.7695, n = 10). Conclusions: Ramadan fasting is associated with reduced activity and sleeping time, but no significant change in RMR or TEE. Reported weight changes with Ramadan in other studies are more likely to be due to differences in food intake. This trial is registered at clinicaltrials.gov as NCT02696421.

Environmental determinants of previtamin D synthesis in the United Arab Emirates.

Despite abundant sunshine throughout the year, vitamin D deficiency is endemic in the UAE. Solar radiation within the UVB range of the spectrum is required for the photosynthesis of previtamin D3 in the skin. Atmospheric transmission of UVB is strongly influenced by atmospheric conditions and solar zenith angle. We investigated the effects of diurnal and seasonal variation on the availability of sufficient UVB radiation for adequate previtamin D3 synthesis using an established in vitro model. Borosilicate ampoules of 7-dehydrocholesterol, the precursor of previtamin D3, in ethanol (50 µg/mL) were exposed to direct sunlight in an urban area of Abu Dhabi, at one hourly intervals between 0800 and 1700, on one day of each month over a period of one year. Conversion to previtamin D3, vitamin D3 and metabolically inactive photoisomers was analyzed using high performance liquid chromatography. The efficiency of 7-dehydrocholesterol conversion to previtamin D3 varied estimated UVB intensity. At the latitude of Abu Dhabi (24.2 N) previtamin D3 synthesis can occur throughout the year. However very little if any previtamin D3 was produced before 0900 hrs.and after 1600 hrs. Local conditions in Abu Dhabi are likely sufficient to maintain vitamin D levels throughout the year given adequate sun exposure.

Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy.

CONTEXT: In vitro fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication, ovarian hyperstimulation syndrome (OHSS). OBJECTIVE: This study aimed to investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS. SETTING AND DESIGN: This was a phase 2, multi-dose, open-label, randomized clinical trial of 60 women at high risk of developing OHSS carried out during 2013-2014 at Hammersmith Hospital IVF unit, London, United Kingdom. INTERVENTION: Following a standard recombinant FSH/GnRH antagonist protocol, patients were randomly assigned to receive a single injection of kisspeptin-54 to trigger oocyte maturation using an adaptive design for dose allocation (3.2 nmol/kg, n = 5; 6.4 nmol/kg, n = 20; 9.6 nmol/kg, n = 15; 12.8 nmol/kg, n = 20). Oocytes were retrieved 36 h after kisspeptin-54 administration, assessed for maturation, and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos. Women were routinely screened for the development of OHSS. MAIN OUTCOME MEASURE: Oocyte maturation was measured by oocyte yield (percentage of mature oocytes retrieved from follicles ≥ 14 mm on ultrasound). Secondary outcomes include rates of OHSS and pregnancy. RESULTS: Oocyte maturation occurred in 95% of women. Highest oocyte yield (121%) was observed following 12.8 nmol/kg kisspeptin-54, which was +69% (confidence interval, -16-153%) greater than following 3.2 nmol/kg. At all doses of kisspeptin-54, biochemical pregnancy, clinical pregnancy, and live birth rates per transfer (n = 51) were 63, 53, and 45%, respectively. Highest pregnancy rates were observed following 9.6 nmol/kg kisspeptin-54 (85, 77, and 62%, respectively). No woman developed moderate, severe, or critical OHSS. CONCLUSION: Kisspeptin-54 is a promising approach to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.

Neurokinin B administration induces hot flushes in women.

Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes. However, the effects of NKB administration on hot flushes have not been investigated in humans. To address this, we performed a randomised, double-blinded, placebo-controlled, 2-way cross-over study. Ten healthy women were admitted to a temperature and humidity-controlled research unit. Participants received 30 minute intravenous infusions of NKB and vehicle in random order. Symptoms, heart rate, blood pressure, sweating and skin temperature were compared between NKB and vehicle in a double-blinded manner. Eight of ten participants experienced flushing during NKB infusion with none experiencing flushing during vehicle infusion (P = 0.0007). Significant elevations in heart rate (P = 0.0106 vs. pre-symptoms), and skin temperature measured using skin probe (P = 0.0258 vs. pre-symptoms) and thermal imaging (P = 0.0491 vs. pre-symptoms) characteristic of menopausal flushing were observed during hot flush episodes. Our findings provide evidence that NKB administration can cause hot flushes in women. Further studies are required to determine if pharmacological blockade of NKB signalling could inhibit hot flushes during the menopause and during treatment for sex-steroid dependent cancers.

Circulating pancreatic polypeptide concentrations predict visceral and liver fat content.

CONTEXT AND OBJECTIVE: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat. PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy. RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01). CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.

Melioidosis in a returning traveller.

A 66-year-old man returned to the UK from Thailand with a 2-week history of new confusion, hallucinations, fever with rigours and productive cough. He had not responded to (unspecified) antibiotic treatment in Thailand. On examination he was afebrile, with an abbreviated mental test score of 8/10 and no other findings on systemic examination. He was treated with ceftriaxone in response to discovery of a Gram-negative organism in blood. This was converted to meropenem on the clinical suspicion of our microbiologist, on the basis of a history of contact with surface water in the Far East. A blood culture subsequently confirmed Burkholderia pseudomallei. His condition remained stable for approximately 4 days, but then deteriorated over the course of the next 2 weeks with pneumonia and subsequent formation of disseminated abscesses. Treatment was withdrawn as his condition deteriorated to the point at which survival was deemed impossible and he subsequently died.

Comparison of Nintendo Wii and PlayStation2 for enhancing laparoscopic skills.

BACKGROUND AND OBJECTIVE: The increase in laparoscopic surgery has led to a growing need to train residents in this skill. Virtual reality simulators and box trainers have been used as educational tools outside of the operating room, but both approaches have advantages and disadvantages. Video games have been an area of interest in the search for other modalities to train residents. Experience with the traditional single controller unit video games have been correlated with better surgical skill acquisition. In 2006, Nintendo introduced the Wii, a novel gaming modality that mimics movements in laparoscopy better than traditional games do. Our objective was to compare the Nintendo Wii and PlayStation2 for enhancing laparoscopy skills. METHODS: The study included stratified randomization of 23 less experienced ( 12 laparoscopy cases per year) and 19 more experienced ( 12 per year) physicians, residents, and medical students to 30 min of Wii versus PlayStation2 in a university-affiliated hospital Department of Obstetrics and Gynecology. Pre- and posttest bead transfer and suturing scores were obtained. RESULTS: Baseline characteristics were similar for both video game groups. Participants assigned to Wii and PlayStation2 both demonstrated significant improvement in bead transfer. Neither Wii nor PlayStation2 participants improved in suturing scores. The Wii group improved more in bead transfer scores when compared to the PlayStation2 group (60 points vs. 40 points, respectively), but this difference was not statistically significant. CONCLUSIONS: Both Wii and PlayStation2 significantly improved laparoscopic skills in bead transfer. These video games may be inexpensive alternatives to laparoscopy training simulators.