Search

Metabolic pathways that are corrupted at early stages of insulin resistance (IR) remain elusive. This study investigates changes in body metabolism in clinically healthy and otherwise asymptomatic subjects that may become apparent already under compromised insulin sensitivity (IS) and prior to IR. 47 clinically healthy Arab male subjects with a broad range of IS, determined by hyperinsulinemic-euglycemic clamp (HIEC), were investigated. Untargeted metabolomics and complex lipidomics were conducted on serum samples collected under fasting and HIEC conditions. Linear models were used to identify associations between metabolites concentrations and IS levels. Among 1896 identified metabolites, 551 showed significant differences between fasting and HIEC, reflecting the metabolic switch in energy utilization. At fasting, 336 metabolites, predominantly di- and tri-acylglycerols, showed significant differences between subjects with low and high levels of IS. Changes in amino acid, carbohydrate and fatty acid metabolism in response to insulin were impaired in subjects with low IS. Association of altered mannose and amino acids with IS was also replicated in an independent cohort of T2D patients. We identified metabolic phenotypes that characterize clinically healthy Arab subjects with low levels of IS at their fasting state. Our study is providing further insights into the metabolic pathways that precede IR.

Objectives: Diabetes self-management educational (DSME) interventions can vary considerably, and it is unclear what is the operational conceptualization of the ideal delivery to individuals with type 2 diabetes (T2D). Design: From a search conducted concurrently we extracted and evaluated the 50 most recently published DSME intervention studies. Based on an analysis of these studies, we undertook a concept analysis using the Walker and Avant framework. Results: Five attributes describing the concept were recognized and organized into two groups. Group (a): skills related attributes that included (1) decision making, (2) problem solving and (3) taking action. Group (b): information related attributes that included (4) patient-provider interaction and (5) resource utilization. Conclusions: The outcomes of this study make the operational conceptualization of the ideal DSME intervention measurable through its attributes and hence clarifies its delivery. This will improve the implementation of the key attributes in diabetes self-management intervention programs for T2D. The authors thank the Division of Endocrinology, Hamad General Hospital, for support provided during the conduct of this work. Scopus

IMPORTANCE: The Delta variant is now the predominant circulating SARS-CoV-2 strain worldwide. Severity of illness in persons infected with the SARS-CoV-2 Delta variant compared with the Beta variant is not known. OBJECTIVE: To directly compare clinical outcomes in persons infected with the SARS-CoV-2 Delta variant vs those infected with the Beta variant in Qatar. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the national COVID-19 database in Qatar, which includes information on all individuals who were ever tested for SARS-CoV-2 using a reverse transcriptase–polymerase chain reaction test and all individuals who received any SARS-CoV-2 vaccine in Qatar. Among persons with confirmed SARS-CoV-2 infection between March 22 and July 7, 2021, those infected with the Delta variant were identified and were propensity score matched with control individuals infected with the Beta variant. The variants were ascertained by variant genotyping of the positive samples. EXPOSURES: SARS-CoV-2 infection with the Delta or Beta variant. MAIN OUTCOMES AND MEASURES: The main outcomes were admission to the hospital, admission to the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, or death among those infected with the Delta or Beta variant overall and stratified by vaccination status. RESULTS: Among 1427 persons infected with the Delta variant (252 [55.9%] male; median age, 34 years [IQR, 17-43 years]) and 5353 persons infected with the Beta variant (233 [51.7%] male; median age, 34 years [IQR, 17-45 years]), 451 propensity score–matched pairs were identified. Persons infected with the Delta variant were more likely to be hospitalized (27.3% [95% CI, 23.2%-31.6%] vs 20.0% [95% CI, 16.4-24.0]; P = .01) or to have mild-moderate or severe-critical disease outcomes (27.9% [95% CI, 23.8%-32.3%] vs 20.2% [95% CI, 16.6%-24.2%]; P = .01) compared with persons infected with the Beta variant. Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome (adjusted odds ratio [aOR], 2.53; 95% CI, 1.72-3.72). Compared with being unvaccinated, being vaccinated with a second dose more than 3 months before infection was associated with lower odds of any adverse outcome among persons infected with the Delta variant (aOR, 0.11; 95% CI, 0.04-0.26) and among those infected with the Beta variant (aOR, 0.22; 95% CI, 0.05-0.98). Protection was similar among those who received a second vaccine dose less than 3 months before infection, but having received only a single dose was not associated with a lower odds of any severe outcome among those infected with the Delta variant (aOR, 1.12; 95% CI, 0.41-3.06) or those infected with the Beta variant (aOR, 0.74; 95% CI, 0.20-2.72). CONCLUSIONS AND RELEVANCE: In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

IntroductionGestational Diabetes Mellitus (GDM) development is related to underlying metabolic syndrome that is associated with elevated complement C3 and C4. Elevated C3 levels have been associated with preeclampsia and the development of macrosomia.MethodsThis case-control study included 34 pregnant women with GDM and 16 non-diabetic (ND) women in their second trimester. Complement-related proteins were measured and correlated with demographic, biochemical, and pregnancy outcome data.ResultsGDM women were older with a higher BMI (pnd term diastolic blood pressure (pConclusionThe increased C3, C4 and Factor-H during the second trimester of pregnancy in GDM are not independently associated with GDM; inflammation and high BMI may be responsible for their elevation. The elevation of second trimester C3 in GDM is associated with earlier delivery and further work is needed to determine if this is predictive.

Introduction: Aerobic exercise activates the complement system in the peripheral blood. However, the effect of age and high intensity endurance training on the levels of circulating complements and sassociated inflammatory cytokines, oxidative stress markers and cellular aging remains unknown.Methods: In this study, serum samples from 79 elite athletes who belong to high (n = 48) and low/moderate (n = 31) endurance sports and two age groups (below 30 years old, n = 53, and above 30 years old, n = 26) were profiled for 14 complements. Linear models were used to assess differences in complements levels between sport and age groups. Spearmann’s correlation was used to assess the relationship among detected complements and proinflammatory cytokines, oxidative stress markers and telomere lengths.Results: High endurance elite athletes exhibited significantly lower levels of circulating C2, C3b/iC3b and adipsin complements than their age-matched low/moderate endurance counterparts. Levels of C2, adipsin and C3b/iC3b were positively correlated with most detected complements, the pro-inflammatory cytokines TNF-alpha and IL-22 and the anti-oxidant enzyme catalase. However, they were negatively correlated with telomere length only in younger elite athletes regardless of their sport groups. Furthermore, high endurance elite athletes showed significantly lower concentrations of C3b/iC3b, C4b, C5, C5a, C1q, C3, C4, factor H and properdin in younger athletes compared to their older counterparts.Conclusion: Our novel data suggest that high endurance elite athletes exhibit age-independent lower levels of circulating C2, C3b/iC3b and adipsin, associated with lower inflammatory, oxidative stress and cellular aging, as well as lower levels of 10 other complements in younger athletes compared to older counterparts. Assessing the effect of various levels of endurance sports on complements-based immune response provides a better understanding of exercise physiology and pathophysiology of elite athletes.

Aims: Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations. Methods: A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM). Results: In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P = 0.432), 2.86 fold (P < 0.001) and 3.35 fold (P < 0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P = 0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years. Conclusions: The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM.

Prescription opioid use (POU) is often a precursor to opioid use disorder (OUD) and subsequent consequences. Persons with chronic hepatitis C virus infection (CHC) may be at a higher risk of POU due to a higher comorbidity burden and social vulnerability factors. We sought to determine the burden of POU and associated risk factors among persons with CHC in the context of social vulnerability. We identified CHC persons and propensity-score matched HCV− controls in the electronically retrieved Cohort of HCV-Infected Veterans and determined the frequency of acute, episodic long-term and chronic long-term POU and the prevalence of social vulnerability factors among persons with POU. We used logistic regression analysis to determine factors associated with POU. Among 160,856 CHC and 160,856 propensity-score matched HCV-controls, acute POU was recorded in 38.4% and 38.0% (P = 0.01) respectively. Episodic long-term POU was recorded in 3.9% in each group (P = 0.5), while chronic long-term POU was recorded in 28.4% and 19.2% (P

Context The comparative efficacy of gestational diabetes (GDM) treatments lack conclusive evidence for choice of first-line treatment. Objectives The aim of this study was to compare the efficacy of metformin and glibenclamide to insulin using a core outcome set (COS) to unify outcomes across trials investigating the treatment of gestational diabetes mellitus. Study design A network meta-analysis (NMA) was conducted. Data-source PubMed, Embase, and Cochrane Controlled Register of Trials were searched from inception to January 2020. Study selection RCTs that enrolled pregnant women who were diagnosed with GDM and that compared the efficacy of different pharmacological interventions for the treatment of GDM were included. Meta-analysis A generalized pairwise modelling framework was employed. Results A total of 38 RCTs with 6046 participants were included in the network meta-analysis. Compared to insulin, the estimated effect of metformin indicated improvements for weight gain (WMD −2·39 kg; 95% CI −3·31 to −1·46), maternal hypoglycemia (OR 0.34; 95% CI 0.12 to 0·97) and LGA (OR 0.61; 95% CI 0.38 to 0·98). There were also improvements in estimated effects for neonatal hypoglycemia (OR 0.48; 95% CI 0.19 to 1·25), pregnancy induced hypertension (OR 0.63; 95% CI 0.37 to 1·06), and preeclampsia (OR 0.74; 95% CI 0.538 to 1·04), though with limited evidence against our model hypothesis of equivalence with insulin for these outcomes. Conclusion Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin.

Background: Mitochondrial dysfunction is implicated in the pathogenesis of Type 2 diabetes (T2D) and the development of diabetes related complications such as cardiovascular disease and stroke. Mitochondria produce several small polypeptides that may influence mitochondrial function and may impact on insulin sensitivity, such as humanin (HN) and the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) that are mitochondrial derived proteins (MDP). The aim of this study was to determine MDP in normal, prediabetes and diabetes subjects.Subjects and Measurements: In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects. The relationship of serum MDP and ADP concentrations with biochemical and anthropometric measurements were performed and assessed by multilinear regression.Results: Serum HN concentrations were lower in T2D (p < 0.0001) and negatively correlated with age (p < 0.0001), HbA1c (p < 0.0001), glucose (p < 0.0001), triglycerides (p < 0.003), ALT (p < 0.004), and TG/HDL ratio (p < 0.001). Circulating HN levels were positively correlated to cholesterol (p < 0.017), LDL (p < 0.001), and HDL (p < 0.001). Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN. Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls (p < 0.007). Circulating MOTS-c positively correlated with BMI (p < 0.035), total cholesterol (p < 0.0001), and LDL (p < 0.001) and negatively correlated with age (p < 0.002), HbA1c (p < 0.001), and glucose (p < 0.002). Serum ADP concentrations were lower in T2D (p < 0.002) and negatively correlated with HbA1c (p < 0.001), weight (p < 0.032) TG (p < 0.0001), and ALT (p < 0.0001); and positively correlated with HDL (p < 0.0001) and HN (p < 0.003). Linear regression analysis showed that HbA1c and weight were two independent predictors of circulating ADP. Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c.Conclusion: The MDPs HN and MOT-c, similar to ADP, are decreased in T2D and correlate with HbA1c. The data provide an additional evidence that mitochondrial dysfunction contributes to glycemic dysregulation and metabolic defects in T2D.

Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation. Results Among 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline. Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population. Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary