Maternal hypothyroidism and subsequent metabolic outcomes in children: a systematic review and meta-analysis.

INTRODUCTION: As the fetus relies on maternal thyroid hormones in early pregnancy, maternal hypothyroidism plays an important role in fetal development. However, the association between maternal hypothyroidism and metabolic disease in offspring is unclear. OBJECTIVE: To examine the association between maternal hypothyroidism in pregnancy and metabolic outcomes (obesity, hypertension, type 2 diabetes mellitus, and dyslipidemia) in children < 18 years. METHODS: We systematically searched 5 databases from inception to May 2023. Eligible studies included cohort, case-control, and randomized controlled trials involving children born to mothers with or without hypothyroidism in pregnancy. Data were pooled across studies using random-effects models for outcomes reported in at least three studies. Quality assessment was performed using the ROBINS-E tool for observational studies and the Cochrane Risk of Bias tool for trials. RESULTS: The search identified 3221 articles, of which 7 studies were included (1 trial, 6 observational). All studies were conducted outside of North America and ranged in size from 250 to > 1 million children. The follow-up time ranged from 6 to 20 years. Included studies support an increased risk of hypertension and glucose dysregulation in offspring exposed to maternal hypothyroidism (hypertension: OR 1.08, 95% CI 0.75, 1.57 and HR 1.81, 95% CI 1.21, 2.69; diabetes: RR 2.7, 95% CI 0.7, 10). In the pooled analysis, maternal hypothyroidism was not associated with obesity in offspring (OR 1.04, 95% CI 0.64, 1.70). CONCLUSION: This study found inconsistent evidence on the association between maternal hypothyroidism in pregnancy and metabolic outcomes in offspring, though associations with hypertension and glucose dysregulation are possible.

A review on cell-free RNA profiling: Insights into metabolic diseases and predictive value for bariatric surgery outcomes.

BACKGROUND: The advent of liquid biopsies presents a novel, minimally invasive methodology for the detection of disease biomarkers, offering a significant advantage over traditional biopsy techniques. Particularly, the analysis of cell-free RNA (cfRNA) has garnered interest due to its dynamic expression profiles and the capability to study various RNA species, including messenger RNA (mRNA) and long non-coding RNA (lncRNA). These attributes position cfRNA as a versatile biomarker with broad potential applications in clinical research and diagnostics. SCOPE OF REVIEW: This review delves into the utility of cfRNA biomarkers as prognostic tools for obesity-related comorbidities, such as diabetes, dyslipidemia, and non-alcoholic fatty liver disease. MAJOR CONCLUSIONS: We evaluate the efficacy of cfRNA in forecasting metabolic outcomes associated with obesity and in identifying patients likely to experience favorable clinical outcomes following bariatric surgery. Additionally, this review synthesizes evidence from studies examining circulating cfRNA across different physiological and pathological states, with a focus on its role in diabetes, including disease progression monitoring and treatment efficacy assessment. Through this exploration, we underscore the emerging relevance of cfRNA signatures in the context of obesity and its comorbidities, setting the stage for future investigative efforts in this rapidly advancing domain.

The effect of cognitive behavioral therapy for insomnia on sleep and glycemic outcomes in people with type 2 diabetes: A randomized controlled trial.

STUDY OBJECTIVES: Investigate whether aiding sleep by online cognitive behavioral therapy for insomnia (CBT-I) can improve glycemic and metabolic control, mood, quality of life (QoL) and insomnia symptoms in people with type 2 diabetes and assess the mediating role of lifestyle factors. METHODS: Adults with type 2 diabetes and insomnia symptoms were randomly assigned to CBT-I or care as usual. At baseline, three and six months we assessed HbA1c as primary outcome and glycemic control, metabolic outcomes, sleep, mood and QoL as secondary outcomes. Mixed models were used to determine within-person and between-persons differences in outcomes and mediation analysis for lifestyle factors. RESULTS: We randomized 29 participants to CBT-I and 28 to care as usual. Intention-to-treat analysis showed no significant differences in glycemic control, metabolic outcomes, anger, distress or QoL, but showed a significantly larger decrease in insomnia (-1.37(2.65: 0.09)) and depressive symptoms (-0.92(-1.77: 0.06)) and increase in BMI (0.29 kg/m2(0.00:0.57)) in the intervention compared to the control group. Only half of the intervention participants completed the CBT-I. Per protocol analysis showed a not statistically significant decrease in HbA1c (-2.10 mmol/l(-4.83:0.63)) and glucose (-0.39 mmol/l(-1.19:0.42)), metabolic outcomes and increase in QoL. Furthermore, the intervention group showed a significant decrease in insomnia (-2.22(-3.65: 0.78)) and depressive symptoms (-1.18(-2.17: 0.19)) compared to the control group. Lifestyle factors partially mediated the effect of the intervention. CONCLUSIONS: CBT-I might improve insomnia symptoms and mood, and perhaps improves glycemic control, albeit not significant, in people with type 2 diabetes and insomnia symptoms, compared to care as usual.

Effect of intermittent fasting 16:8 and 14:10 compared with control-group on weight reduction and metabolic outcomes in obesity with type 2 diabetes patients: A randomized controlled trial.

AIMS/INTRODUCTION: To compare the percent weight change and metabolic outcomes among diabetic participants with obesity on intermittent fasting (IF) 16:8, IF 14:10, or normal controlled diets. MATERIALS AND METHODS: A randomized controlled trial was conducted to randomize participants into three groups. Each group followed IF 16:8, IF 14:10, according to the protocol 3 days/week for 3 months or a control group. RESULTS: A total of 99 participants completed the study. The percentage weight change from baseline was -4.02% (95% CI, -4.40 to -3.64) in IF 16:8, -3.15% (95% CI, -3.41 to -2.89) in IF 14:10, and -0.55% (95% CI, -1.05 to -0.05) in the control group. The percentage weight loss from baseline was significantly more in both IF groups (P < 0.001, both) when compared with the control group. Weight loss was significantly more in the IF 16:8 group than in that of the IF 14:10 group (P < 0.001). Metabolic outcomes (decrease in FBS and HbA1C, and improvement in lipid profiles) were significantly improved from baseline in both IF groups in comparison with the control group. CONCLUSIONS: Either IF 16:8 or 14:10 had a benefit in the percentage weight change, glucose and lipid profiles in obese diabetic patients compared with the control group when consumed for 3 days a week for 3 months.

Donor and recipient genetics: Implications for the development of posttransplant diabetes mellitus.

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity.

A safety estimand for late phase clinical trials where the analysis period varies over the subjects.

BACKGROUND/AIMS: Evaluating safety is as important as evaluating efficacy in a clinical trial, yet the tradition for safety analysis is rudimentary. This article explores more complex methodologies for safety evaluation, with the aim of improving the interpretability, as well as generalizability, of the results. METHODS: For studies where the analysis periods vary over the subjects, using the International Council for Harmonisation estimand framework, we construct a formal estimand that could be used in the setting of safety surveillance that answers the clinical question of 'What is the magnitude of the increase in risk of experiencing an adverse event if the treatment is taken, as prescribed, for a specific period of time?'. Estimation methodologies for this estimand are also discussed. RESULTS: The proposed estimand is similar to that found in the efficacy analyses of time to event data (e.g. in outcome studies), with the key difference of utilization of hypothetical intercurrent event strategy for the intercurrent event of treatment discontinuation. This is motivated by what we perceive to be a key difference for the safety objective compared to efficacy objectives, namely a desire for sensitivity (i.e. greater possibility of detecting a negative impact of the drug, if such exists) as opposed to the need to prove a positive effect of the drug in a conservative manner. CONCLUSION: It is valuable, and possible, to use the International Council for Harmonisation estimand framework not only for efficacy but also for safety evaluation, with the estimand driven by an interpretable, and relevant, clinical question.

Effects of Bariatric Surgery on Sarcopenic Obesity Outcomes: A One-Year Prospective Study in Middle-Aged Women.

INTRODUCTION: Sarcopenic obesity (SO) is characterised by the confluence of muscle deterioration and high adiposity. When non-surgical interventions prove insufficient, bariatric surgery (BS) becomes the primary approach. This study aimed to address BS effects on SO outcomes 1 year post-surgery among middle-aged women, also considering physical exercise's impact. METHODS: Prospective single-centre study of 140 patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between November 2019 and December 2022. Participants were categorised into tertiles according to SO's diagnosis and severity (group 1-patients with the most severe SO; group 2-intermediate; group 3-the least severe or without SO), calculated considering the consensus issued by ESPEN and EASO in 2022. Evaluations of clinical and biochemical parameters were conducted before and 12 months after BS, and the variation was used for comparative purposes. Body composition was assessed using bone density scans. Linear regression analysis accounted for both surgery type and baseline body mass index (BMI). RESULTS: Before BS, SO prevalence in the overall sample was 89.3%, decreasing to 2.9% after BS. Group 1 had more body fat mass (56.9 vs 54.8 vs 50.7 kg, p < 0.001), total, trunk and leg fat at baseline and a significantly lower total skeletal muscle mass (47.2 vs 49.4 vs 51.8 kg, p < 0.001). One year post-BS, group 1 presented more weight loss (- 39.8 ± 11.4 kg, p = 0.031), BMI reduction (- 15.9 ± 4.6 kg/m2, p = 0.005) and lost more fat mass (- 32.6 vs - 30.5 vs - 27.9 kg, p = 0.005), but not total skeletal muscle mass (- 5.8 vs - 5.9 vs - 6.8 kg, p = 0.130). Remission rates for comorbidities were substantial among all groups, but more marked among patients within group 1 (type 2 diabetes mellitus 75%, hypertension 47.1% and dyslipidemia 52.8%). Engagement in physical exercise of any kind has increased post-BS (33.1% vs 79.1%). CONCLUSION: Despite concerns about malabsorptive mechanisms potentially worsening muscle loss, patients with the most severe SO undergoing BS lost more fat mass while experiencing the smallest reduction in total skeletal muscle mass. Remission rates for comorbidities following BS were notable among all groups.

Resistant starch and the gut microbiome: Exploring beneficial interactions and dietary impacts.

The intricate relationship between resistant starch (RS) and the gut microbiome presents a dynamic frontier in nutrition science. This review synthesizes current understandings of how RS, an indigestible form of starch found naturally in certain foods and also enhanced through various modification methods, interacts with the gut microbiome. We particularly focus on how RS fermentation in the colon contributes to the production of beneficial volatile fatty acids (VFAs) such as butyrate, acetate, and propionate. These VFAs have been recognized for their vital roles in maintaining gut barrier integrity, modulating inflammation, and potentially influencing systemic health. Additionally, we discuss the dietary implications of consuming foods rich in RS, both in terms of gut health and broader metabolic outcomes. By consolidating these insights, we emphasize the significance of RS in the context of dietary strategies aimed at harnessing the gut microbiome's potential to impact human health.

Longitudinal changes in body fat and metabolic complications in young people with perinatally acquired HIV.

BACKGROUND: The role of body fat on metabolic complications remains poorly understood in young people living with perinatally acquired HIV (YPHIV). OBJECTIVE: Our objective was to assess the association of changes in adiposity over 2 years with metabolic outcomes in YPHIV. METHODS: The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from 2007 to 2009 across 15 US sites, including Puerto Rico. We included YPHIV aged 7-19 years with body composition data assessed by whole-body dual-energy X-ray absorptiometry (DXA) at baseline and 2 years later. Metabolic outcomes included homeostatic model assessment of insulin resistance (HOMA-IR) and non-high-density lipoprotein cholesterol (non-HDL-C). We fitted linear regression models to assess the association of increase in body fat over 2 years with metabolic outcomes at years 2 and 3. RESULTS: In all, 232 participants had a second DXA and either HOMA-IR or non-HDL-C measured at year 2. Participant characteristics at the first DXA were: age 12 years (9-14) [median (Q1-Q3)], 69% Black, and median CD4 count 714 cells/µL; 70% with HIV RNA <400 copies/mL. In adjusted analyses for every 1% increase in body fat from baseline to year 2, HOMA-IR was higher by 1.03-fold at year 3 (95% CI: 1.00, 1.05). We observed that for every 1% increase in body fat from baseline to year 2, non-HDL-C was 0.72 mg/dL higher at year 2 (95% CI: -0.04-1.49) and 0.81 mg/dL higher at year 3 (95% CI: -0.05-1.66). CONCLUSIONS: Increases in adiposity over time may lead to downstream decreased insulin sensitivity and dyslipidaemia in YPHIV.

Exclusive human milk feeding and prevalence of early adiposity rebound in ELBW infants: a retrospective cohort study.

The purpose of the present study was to evaluate the prevalence of early adiposity rebound (EAR) and factors associated with its occurrence in a cohort of extremely low birth weight infants (ELBW). We conducted a retrospective longitudinal study including ELBW infants followed-up for up to 10 years after discharge. EAR was defined as occurring before 5 years of age. A multivariate binary logistic regression analysis was performed to evaluate maternal and perinatal variables independently associated with EAR. Out of 212 ELBW infants included in the analysis, 40.6% developed EAR and 21.5% showed it before 4 years of age. Only formula milk feeding at discharge was independently associated with a higher risk of EAR. The mean BMI of children with EAR was higher than that of children without EAR. Furthermore, the prevalence of overweight and obesity was higher in the EAR group than in the timely AR group.  Conclusions: ELBW infants in our cohort developed EAR in a relatively high percentage of cases. In this already at-risk population, EAR may represent a further risk factor for an adverse metabolic outcome. Monitoring preterm infants' growth within a long-term follow-up program and promoting and supporting human milk feeding is advisable. What is Known: • Preterm-born infants are at high risk for long-term adverse health outcomes, especially cardiovascular and metabolic. • The occurrence of early adiposity rebound (EAR) is associated with the risk of later obesity and metabolic syndrome. What is New: • The occurrence of EAR in ELBW infants may represent an additional risk factor for later adverse metabolic outcomes in an already vulnerable population. • Future preventive strategies should include a long-term follow-up and the promotion of exclusive breastfeeding.

Mechanisms of Action of Bariatric Surgery on Body Weight Regulation.

Bariatric surgery is an effective treatment modality for obesity and obesity-associated complications. Weight loss after bariatric surgery was initially attributed to anatomic restriction or reduced energy absorption, but now it is understood that surgery treats obesity by influencing the subcortical areas of the brain to lower adipose tissue mass. There are three major phases of this process: initially the weight loss phase, followed by a phase where weight loss is maintained, and in a subset of patients a phase where weight is regained. These phases are characterized by altered appetitive behavior together with changes in energy expenditure. The mechanisms associated with the rearrangement of the gastrointestinal tract include central appetite control, release of gut peptides, change in microbiota and bile acids. However, the exact combination and timing of signals remain largely unknown.

C-reactive protein during pregnancy and in the early postpartum predicts adverse metabolic health outcomes at 1 year postpartum in women with gestational diabetes.

BACKGROUND: Women with gestational diabetes mellitus (GDM) have higher insulin resistance and/or reduced secretion, an increased risk of future diabetes and cardiovascular disease, which may be due to a pathological activation of the innate immune system. C-reactive protein (CRP) is induced by inflammatory cytokines and reflects innate immune activity. We investigated the prospective associations between CRP during the perinatal period with adverse metabolic outcomes at 1 year postpartum in women with previous GDM. METHODS: We analyzed data from the MySweetheart trial that included 211 women with GDM at 28-32 weeks gestational age (GA). CRP was measured during  pregnancy at 28-32 weeks GA, at 6-8 weeks and at 1 year postpartum. Metabolic outcomes at 1 year postpartum included weight, total and central body fat, measures of insulin resistance and secretion and presence of the metabolic syndrome (MetS). A 75 g oral glucose tolerance test was performed to measure glucose and insulin values every 30 min over 2 h to calculate indices of insulin resistance (MATSUDA, HOMA-IR) and of absolute (AUCins/glu, HOMA-B) and insulin resistance-adjusted insulin secretion (ISSI-2). RESULTS: CRP during pregnancy and at 6-8 weeks postpartum predicted increased weight, body fat and visceral adipose tissue (VAT), insulin resistance (higher HOMA-IR, lower MATSUDA), absolute insulin secretion (HOMA-B, AUCins/glu), a reduced adjusted insulin secretion (ISSI-2) and a higher prevalence of the MetS at 1 year postpartum (all p ≤ 0.036). These relationships particularly those concerning CRP during pregnancy, were independent of weight ( for VAT, insulin resistance and secretion indices, MetS; all p ≤ 0.032) and of body fat ( for VAT, MATSUDA, MetS; all p ≤ 0.038).  CONCLUSION: CRP during pregnancy and in the early postpartum predicted an adverse cardio-metabolic profile in women with prior GDM at 1 year postpartum independent of weight. The prospective association of CRP with increased insulin resistance and reduced adjusted insulin secretion hint to the role of inflammation in the development of impaired metabolism after GDM and could be used as an early marker for risk stratification.

Rat models of diet-induced obesity and metabolic dysregulation: Current trends, shortcomings and considerations for future research.

Rat diet-induced obesity and metabolic dysregulation (DIO/DIMD) is widely used as a pre-clinical model for human obesity and for testing weight-loss interventions. The aim of this review was to utilise a systematic literature survey of rat DIO/DIMD studies as a tool to document trends around study design and metabolic outcomes of these studies, and to consider ways in which the design of these studies may be improved to enhance the relevance thereof for human obesity research. In total, 110 comparisons between control and obesogenic dietary groups were included in the survey. Young male rats were found to be the model of choice, but fewer than 50% of studies provided comprehensive information about diet composition and energy intake. In addition, it was found that the majority of expected DIO/DIMD responses (hyperglycemia, hyperinsulinemia, dyslipidemia, hypoadiponectinemia) occurred at < 80% frequency, drawing into question the concept of a "typical" or "appropriate" response. We discuss the impact of differences in diet composition and energy intake on metabolic outcomes against the context of large heterogeneity of obesogenic diets employed in rat DIO/DIMD studies, and provide recommendations for the improvement of reporting standards around diet composition and dietary intake. In addition, we highlight the lack of data from female and older rats and describe considerations around the inclusion of sex and age as a variable in rat DIO/DIMD studies, aiming towards improving the applicability of these studies as a model of human obesity, which is most prevalent in women and older individuals.

Assessment of Patient-reported Satisfaction and Metabolic Outcomes Following Initiation of the Second Generation of Flash Glucose Monitoring in Patients with Type 1 Diabetes

BACKGROUND AND AIMS: This study aims to assess patient-reported satisfaction and metabolic outcomes following the initiation of the second generation of the Freestyle Libre 2 (FSL2) system in patients with type 1 diabetes (T1D). METHODS: This non-randomized single-arm observation study was conducted on 86 patients with T1D living in Saudi Arabia, who were asked to wear the FSL2 for 12 weeks. The demographic data were collected at baseline, while the continuous glucose monitoring (CGM) metrics were gathered, i.e., Glucose Variability (GV) (%), mean Time in Range (TIR), Time Above Range (TAR), Time Below Range (TBR), and average duration of hypoglycemic events were collected at baseline, 6th week and 12 weeks. Further, the Continuous Glucose Monitoring Satisfaction (CGM-SAT) was collected at the end of the follow-up RESULTS: Compared to the 6th week, significant differences were observed in the low glucose events (p = 0.037), % TIR (p = 0.045), and % below 70 mg/dL (p = 0.047) at 12 weeks. Improvement was seen in the other glucometric variables, but no significant changes were evident (p > 0.05). On completion of the study period, the ambulatory glucose profile (AGP) metrics showed a 74.3 ± 5.01 (mg/dL) FSL2 hypoglycemia alarm threshold and a 213 ± 38.1 (mg/dL) hyperglycemia alarm threshold. A majority of the patients stated that CGM-SAT had benefits (mean score > 3.58), although they felt FSL2 had 'additional benefits. With regard to the problems with the use of FSL2 majority of the patients stated that FSL2 has minimal discomfort. CONCLUSION: Using second-generation FSL2 in patients with T1D is positively associated with patient-reported satisfaction and metabolic outcomes.

Developmental origins of health and disease: Impact of paternal nutrition and lifestyle.

Most epidemiological and experimental studies have focused on maternal influences on offspring's health. The impact of maternal undernutrition, overnutrition, hypoxia, and stress is linked to adverse offspring outcomes across a range of systems including cardiometabolic, respiratory, endocrine, and reproduction among others. During the past decade, it has become evident that paternal environmental factors are also linked to the development of diseases in offspring. In this article, we aim to outline the current understanding of the impact of male health and environmental exposure on offspring development, health, and disease and explore the mechanisms underlying the paternal programming of offspring health. The available evidence suggests that poor paternal pre-conceptional nutrition and lifestyle, and advanced age can increase the risk of negative outcomes in offspring, via both direct (genetic/epigenetic) and indirect (maternal uterine environment) effects. Beginning at preconception, and during utero and the early life after birth, cells acquire an epigenetic memory of the early exposure which can be influential across the entire lifespan and program a child's health. Potentially not only mothers but also fathers should be advised that maintaining a healthy diet and lifestyle is important to improve offspring health as well as the parental health status. However, the evidence is mostly based on animal studies, and well-designed human studies are urgently needed to verify findings from animal data.

Metabolic Outcomes After Pancreas Transplant Alone From Donation After Circulatory Death Donors-The UK Transplant Registry Analysis.

Extrapolating data from early DCD (donation after circulatory death) kidney transplantation, pancreas transplants from DCD grafts were feared to have worse metabolic outcomes. Hence, we aimed to address the question of pancreas transplant alone (PTA) from DCD donors-are our concerns justified? A UK transplant registry analysis of 185 PTA performed between 2005 and 2018 was done. All early graft losses (<3 months) were excluded to allow focus on the metabolic outcomes (HbA1c, weight gain and incidence of secondary diabetic macrovascular complications). The aim was to compare the metabolic outcomes, rejection rates (including the need for steroids), patient and graft survival between DBD (Donation after brainstem death) and DCD groups. After excluding early graft losses, data from 162 PTA (DBD = 114 and DCD = 48) were analyzed. Body mass index of the donor was less in DCD group (DBD = 23.40 vs. DCD = 22.25, p = 0.006) and the rest of the baseline transplant characteristics were comparable. There were no significant differences in the HbA1c, weight gain, rejection rate, and incidence of secondary diabetic macrovascular complications post-transplant between DBD and DCD recipients. The 1-, 5-, and 10-year patient and graft survival were similar in both the groups. PTA from DCD donors have equivalent metabolic outcomes and survival (patient/graft) as that of DBD donors.

Adverse metabolic consequences of androgen deprivation therapy (ADT) on Asian patients with prostate cancer: Primary results from the real-life experience of ADT in Asia (READT) study.

BACKGROUND: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population. METHODS: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed. RESULTS: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p < 0.001) and 2.7% (p < 0.001), respectively. Triglycerides level was also elevated by 16.1% at 6th month and by 20.6% at 12th month compared to baseline (p < 0.001). Mean body weight was 1.09 kg above baseline at 18th month (p < 0.001). CONCLUSION: ADT was associated with adverse metabolic parameters in terms of glycemic profiles, lipid profiles, and body weight in the Asian population. These changes developed early in the treatment and can persist beyond the first year. Regular monitoring of the biochemical profiles during treatment is paramount in safeguarding the patients' metabolic health.

Factors influencing bariatric surgery outcomes.

The outcomes of bariatric surgery, while often impressive, are not universally satisfactory; they vary from patient to patient and from operation to operation. Between 20-30% of patients experience suboptimal weight loss or substantial weight regain early in their postoperative course. Confronted with this chronic disease, and given that failures are difficult to manage, it is essential to better characterize obesity preoperatively, considering other metrics beyond just the body mass index (BMI), to select the best candidates for surgery and optimize the benefit/risk ratio. Based on the data of the most recent studies on bariatric surgery, our objective is to identify the predictive factors of weight loss as well as the risk factors of failure. Our analysis indicates that the choice of the surgical technique, age, initial BMI, ethnic origin, the presence of eating disorders and metabolic factors all have an impact on weight-loss outcomes after bariatric surgery. Thus, it is of major importance to carefully select patients during a preoperative multidisciplinary discussion in order to optimize weight loss and metabolic outcomes.

A machine-learning algorithm integrating baseline serum proteomic signatures predicts exercise responsiveness in overweight males with prediabetes.

The molecular transducers conferring the benefits of chronic exercise in diabetes prevention remain to be comprehensively investigated. Herein, serum proteomic profiling of 688 inflammatory and metabolic biomarkers in 36 medication-naive overweight and obese men with prediabetes reveals hundreds of exercise-responsive proteins modulated by 12-week high-intensity interval exercise training, including regulators of metabolism, cardiovascular system, inflammation, and apoptosis. Strong associations are found between proteins involved in gastro-intestinal mucosal immunity and metabolic outcomes. Exercise-induced changes in trefoil factor 2 (TFF2) are associated with changes in insulin resistance and fasting insulin, whereas baseline levels of the pancreatic secretory granule membrane major glycoprotein GP2 are related to changes in fasting glucose and glucose tolerance. A hybrid set of 23 proteins including TFF2 are differentially altered in exercise responders and non-responders. Furthermore, a machine-learning algorithm integrating baseline proteomic signatures accurately predicts individualized metabolic responsiveness to exercise training.

The prevalence of self-reported insomnia symptoms and association with metabolic outcomes in people with type 2 diabetes: the Hoorn Diabetes Care System cohort.

STUDY OBJECTIVES: We investigated the prevalence of self-reported insomnia symptoms in people with type 2 diabetes and assessed the association with metabolic outcomes and the mediating role of lifestyle factors. METHODS: In a prospective cohort of 1,272 participants with type 2 diabetes (63.4% male, age 68.7 ± 9 years) we measured insomnia symptoms using the Insomnia Severity Index and metabolic outcomes as hemoglobin A1c, glucose, lipids, and body mass index at baseline and at 1 year follow-up. Linear regression analyses assessed the association between insomnia symptoms and metabolic outcomes, corrected for demographic factors, comorbidities, and body mass index. Mediation analyses were conducted for lifestyle factors. RESULTS: The prevalence of mild and severe insomnia symptoms was 23.0% and 10.7%, respectively. When adjusted for demographic factors and comorbidities, cross-sectionally severe insomnia symptoms were associated with higher body mass index (ß = 0.97 kg/m2; 95% confidence interval 0.04: 1.89) compared to no insomnia symptoms. Cross-sectionally, no associations were observed for the other metabolic outcomes. Additionally, no prospective associations were observed with any of the outcomes. Finally, physical activity mediated the association between severe insomnia symptoms and body mass index by 29.3%. CONCLUSIONS: About a third of people with type 2 diabetes experience self-reported insomnia symptoms, but insomnia symptoms were not associated with metabolic outcomes in people with type 2 diabetes. CITATION: Groeneveld L, den Braver NR, Beulens JWJ, et al. The prevalence of self-reported insomnia symptoms and association with metabolic outcomes in people with type 2 diabetes: the Hoorn Diabetes Care System cohort. J Clin Sleep Med. 2023;19(3):539-548.