Summary Background Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve β-cell function and ...decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. Methods In this 2-year trial, patients aged 8–35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protégé study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0·5 U/kg per day and glycated haemoglobin A1c (HbA1C ) of less than 6·5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , number NCT00385697. Findings 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19·8% (41/207) in the 14-day full-dose group; 13·7% (14/102) in the 14-day low-dose group; 20·8% (22/106) in the 6-day full-dose group; and 20·4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0·03). Across the four study groups, similar proportions of patients had adverse events (414/417 99% in the teplizumab groups vs 98/99 99% in the placebo group) and serious adverse events (42/417 10% vs 9/99 9%). The most common clinical adverse event in the teplizumab groups was rash (220/417 53% vs 20/99 20% in the placebo group). Interpretation Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children. Funding MacroGenics, the Juvenile Diabetes Research Foundation, and Eli Lilly.
Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. ...Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.
The variation of O/N2 (reference to N2 column density 1017 cm−2) and nitric oxide radiative emission flux exiting the thermosphere have been studied over the Northern Hemisphere during the superstorm ...event of 7–12 November 2004. The data have been obtained from Global Ultraviolet Imager (GUVI) and Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) on board the National Aeronautics and Space Administration (NASA)'s Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics (TIMED) satellite. The NO radiative flux is observed to show an anti‐correlation with O/N2 on a global scale. Both NO radiative flux and O/N2 ratio show equatorward motion with maximum penetration in western longitude sectors. A local variation of O, O2, and N2 densities have been calculated using NRLMSISE‐00 model over a midlatitude location (55°N,180°E). On a local scale, model calculated O/O2 and O/N2 ratios are found to follow the observations made by GUVI. The collisional excitation of NO with atomic oxygen is the most dominant process for the total cooling rate. The SABER‐retrieved NO cooling rate (CR) at a local site suggests an enhancement during the storm period with the peak emission rate closely correlated to the progression of the storm. The peak emission altitude of NO CR moves upward during the main phase of the storm. The NO abundance has been calculated by using cooling rate and Nitric Oxide Empirical Model (NOEM) model. Both these suggest a vary large (3–15 times) increase in NO density during the storm, which is required to account the changes in NO radiative flux. A similar kind of enhancement in NO abundance is also noticed in Student Nitric Oxide Explorer observations during intense geomagnetic storms.
Key Points
The variation of nitric oxide radiative flux exiting the thermosphere has been studied during the superstorm event of November 2004
The cooling rate profiles are used to model the fluctuations in NO during the storm, suggesting a huge increase in NO during the storm
The collisional excitation of NO with atomic oxygen is the most dominant process for the total cooling rate
Aim
To compare the effect of liraglutide or placebo added on to sodium‐glucose co‐transporter‐2 inhibitor (SGLT2i) ± metformin on glycaemic control in patients with type 2 diabetes.
Materials and ...Methods
Patients with type 2 diabetes on a stable SGLT2i dose ± metformin (with HbA1c 7.0%–9.5% and body mass index BMI ≥ 20 kg/m2) were randomized 2:1 to add‐on liraglutide 1.8 mg/day or placebo in this parallel, double‐blind, multinational trial. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 26, respectively. The proportions of patients achieving HbA1c (<7.0%) targets and safety events after week 26 were also assessed.
Results
Of 303 patients randomized (one in error), 280 completed treatment. Mean changes in HbA1c from baseline to week 26 with liraglutide (n = 202) and placebo (n = 100) were − 0.98% and − 0.30%, respectively (estimated treatment difference ETD: −0.68% 95% CI: −0.89, −0.48; P < 0.001). Mean body weight changes from baseline were − 2.81 versus −1.99 kg, respectively (ETD: −0.82 kg 95% CI: −1.73, 0.09; P = 0.077); 51.8% of liraglutide‐treated patients achieved HbA1c < 7.0% versus 23.2% receiving placebo (odds ratio: 5.1 95% CI: 2.67, 9.87; P < 0.001). More patients treated with liraglutide reported ≥1 treatment‐emergent adverse events (66.3%) versus placebo (47.0%).
Conclusions
Liraglutide significantly improved glycaemic control compared with placebo in patients with type 2 diabetes, insufficiently controlled with SGLT2is with/without metformin, with no unexpected safety findings.
India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals ...aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).
We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.
Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among ...adults with self-reported diabetes.
The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbA
of less than 7·0% (A), blood pressure control was defined as less than 140/90 mm Hg (B), and the LDL cholesterol target was defined as less than 100 mg/dL (C). ABC control was defined as the proportion of individuals meeting glycaemic, blood pressure, and LDL cholesterol targets together. We also performed multiple logistic regression to assess the factors influencing achievement of diabetes treatment targets.
Between Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (<10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose.
Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India.
Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.
Diabetes insipidus: The other diabetes Kalra, Sanjay; Zargar, Abdul; Jain, Sunil ...
Indian journal of endocrinology and metabolism,
01/2016, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Diabetes insipidus (DI) is a hereditary or acquired condition which disrupts normal life of persons with the condition; disruption is due to increased thirst and passing of large volumes of urine, ...even at night. A systematic search of literature for DI was carried out using the PubMed database for the purpose of this review. Central DI due to impaired secretion of arginine vasopressin (AVP) could result from traumatic brain injury, surgery, or tumors whereas nephrogenic DI due to failure of the kidney to respond to AVP is usually inherited. The earliest treatment was posterior pituitary extracts containing vasopressin and oxytocin. The synthetic analog of vasopressin, desmopressin has several benefi ts over vasopressin. Desmopressin was initially available as intranasal preparation, but now the oral tablet and melt formulations have gained significance, with benefits such as ease of administration and stability at room temperature. Other molecules used for treatment include chlorpropamide, carbamazepine, thiazide diuretics, indapamide, clofibrate, indomethacin, and amiloride. However, desmopressin remains the most widely used drug for the treatment of DI. This review covers the physiology of water balance, causes of DI and various treatment modalities available, with a special focus on desmopressin.
Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are ...impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country.
We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration.
We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050.
Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa.
Novo Nordisk.
The lack of awareness among health care providers (HCPs) is one of the biggest challenges for the management of patients with type 1 diabetes mellitus (T1DM) in India. Major challenges faced by HCPs ...include lack of awareness about the disease among general physicians and inadequately trained staff to deal with children with T1DM. The changing diabetes in children (CDiC) program is helping in overcoming these barriers faced by HCPs. CDiC provides treatment, monitoring tools, and education to children affected with T1DM and has been instrumental is developing various education and awareness tools.
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