Biomedical subjects

Jay S Skyler

Publications and source records attributed to Jay S Skyler.

12 recordsLinked to original sources

PubMed2026

The management of type 1 diabetes in adults. The updated 2026 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

This 2026 consensus report from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) builds on the 2021 consensus report to provide guidance for managing type 1 diabetes in adults. Reflecting the rapid advances in the field, this update places particular emphasis on the integration of new technologies, while all sections have been revised to incorporate new evidence, advances in clinical practice and novel therapies, including interventions to delay the onset of stage 3 type 1 diabetes. It also broadens its scope to screening for long-term diabetes complications, and the management of obesity and cardiovascular risk factors. Psychosocial care and diabetes self-management education and support (DSMES) remain key elements. The report was developed using the Accurate Consensus Reporting Document (ACCORD) framework. The guidance aligns with the current ADA 'Standards of Care in Diabetes' (Standards of Care) and relevant EASD and ADA documents and aims to support clinicians globally in delivering high-quality, personalised care for adults with type 1 diabetes, with recommendations that can be adapted across diverse healthcare systems and resource settings.

Adjunctive therapy↗

PubMed2026

The Management of Type 1 Diabetes in Adults. The Updated 2026 Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Journal Article↗

PubMed2025

Evolution of the Artificial Pancreas: Components and Integration-CGMs, Insulin, and AP Systems.

The landmark Diabetes Control and Complications Trial (DCCT) showed that glucose control is critical to reducing the risk of diabetes-related complications. This chapter outlines a series of innovations and investigations that followed the DCCT, aimed at minimizing the risk of hypoglycemia while further improving glucose control. The chapter presents an example of innovations in wired enzyme technology that facilitated the movement from capillary glucose monitoring to continuous glucose monitoring (CGM) and ultimately, the first-factory calibrated CGM system. The next glycemic management innovation was to connect CGM data to an insulin pump containing an algorithm able to adjust insulin delivery based on the changing glucose levels and trends. The key features of automated insulin delivery (AID) systems, currently approved in the United States, are presented. The AID summary table includes type of pump, type and function of the insulin delivery algorithm, the data management system, and the indications for use. The next section explores the innovation of alternative routes of insulin delivery to move toward the goal of a fully automated insulin delivery system. The main trials in developing and implementing an implantable intraperitoneal programmable system are summarized. The last section explores if sensor input in addition to glucose levels such as continuous sensing of ketone, lactate, or insulin levels may provide valuable feedback to move us closer to a fully autonomous AID system. Much of this diabetes innovation and investigation work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases over that last 75 years.

Humans↗

PubMed2007

Increasing the accuracy of oral glucose tolerance testing and extending its application to individuals with normal glucose tolerance for the prediction of type 1 diabetes: the Diabetes Prevention Trial-Type 1.

OBJECTIVE: We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic patients). The maximum follow-up was 7.4 years. Analyses utilized receiver-operator curves (ROCs), proportional hazards models, and survival curves. RESULTS: ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 +/- 0.02) and an OGTT prediction index (0.78 +/- 0.02) were higher (P < 0.001) than those for the fasting (0.53 +/- 0.02) and 2-h glucose (0.66 +/- 0.02). ROCAUCs for the 60- and 90-min glucose (0.71 +/- 0.02 and 0.72 +/- 0.02, respectively) were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT prediction index ranging from 3.77 to 5.30 (P < 0.001 for all). CONCLUSIONS: Certain alternative OGTT indexes appear to better predict type 1 diabetes than standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients. Moreover, even among those with normal glucose tolerance, OGTTs are strongly predictive. This suggests that subtle metabolic abnormalities are present several years before the diagnosis of type 1 diabetes.

Area Under Curve↗

PubMed2006

Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1.

OBJECTIVE: There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis. RESEARCH DESIGN AND METHODS: Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points. RESULTS: Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up. CONCLUSIONS: These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.

Area Under Curve↗

PubMed2005

Pulmonary insulin update.

Explore the source record for details and available documents.

Administration, Inhalation↗

PubMed2005

Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1.

OBJECTIVE: This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes. RESEARCH DESIGN AND METHODS: We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483 were antibody positive; 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes; 388 had a 5-year risk projection of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed every 6 months. The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. RESULTS: Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015). CONCLUSIONS: It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes. Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels.

Administration, Oral↗

PubMed2005

Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: a 6-month, randomized, comparative trial.

OBJECTIVE: Despite the demonstrated benefits of glycemic control, patient acceptance of basal/bolus insulin therapy for type 1 diabetes has been slow. We investigated whether a basal/bolus insulin regimen involving rapid-acting, dry powder, inhaled insulin could provide glycemic control comparable with a basal/bolus subcutaneous regimen. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (ages 12-65 years) received twice-daily subcutaneous NPH insulin and were randomized to premeal inhaled insulin (n = 163) or subcutaneous regular insulin (n = 165) for 6 months. RESULTS: Mean glycosylated hemoglobin (A1C) decreased comparably from baseline in the inhaled and subcutaneous insulin groups (-0.3 and -0.1%, respectively; adjusted difference -0.16% [CI -0.34 to 0.01]), with a similar percentage of subjects achieving A1C <7%. Although 2-h postprandial glucose reductions were comparable between the groups, fasting plasma glucose levels declined more in the inhaled than in the subcutaneous insulin group (adjusted difference -39.5 mg/dl [CI -57.5 to -21.6]). Inhaled insulin was associated with a lower overall hypoglycemia rate but higher severe hypoglycemia rate. The overall hypoglycemia rate (episodes/patient-month) was 9.3 (inhaled) vs. 9.9 (subcutaneous) (risk ratio [RR] 0.94 [CI 0.91-0.97]), and the severe hypoglycemia rate (episodes/100 patient-months) was 6.5 vs. 3.3 (RR 2.00 [CI 1.28-3.12]). Increased insulin antibody serum binding without associated clinical manifestations occurred in the inhaled insulin group. Pulmonary function between the groups was comparable, except for a decline in carbon monoxide-diffusing capacity in the inhaled insulin group without any clinical correlates. CONCLUSIONS: Inhaled insulin may provide an alternative for the management of type 1 diabetes as part of a basal/bolus strategy in patients who are unwilling or unable to use preprandial insulin injections.

Administration, Inhalation↗

PubMed2004

Diabetes mellitus: pathogenesis and treatment strategies.

This article introduces the disease state of diabetes mellitus and provides a background of the impact of the disease on the population, its biology and pathophysiology, and the current treatment strategies for treating diabetes.

Blood Glucose↗

PubMed2004

HIV, metabolic syndrome X, inflammation, oxidative stress, and coronary heart disease risk : role of protease inhibitor exposure.

Differences on measures of metabolic syndrome X and coronary heart disease (CHD) risk, as well as potential pathophysiological mediators, inflammation, and oxidative stress, were examined as a function of HIV serostatus and highly active antiretroviral therapy (HAART) regimen with and without protease inhibitors (PIs). Data from 164 men and women, aged 18 to 55 yr, were used to compare 82 HIV+ subjects who were free of hepatitis C virus and were on a stable HAART regimen for >/=6 mo, with 82 seronegative subjects matched on age, sex, body mass index, and ethnicity. For the HIV+ subjects, after controlling for diabetes status and HIV disease progression, PI exposure was associated with greater oxidative stress, triglyceridemia, and lipidemia than it was for non-PI-exposed HIV+ subjects, and the risk of a future myocardial infarction was up to 56% greater in PI-exposed than in non-PI-exposed subjects and 129% greater than in controls. Although it is likely that the greatest proportion of CHD risk in the HIV+ subjects may be accounted for by pathological conditions linked to HIV infection in interaction with mediating processes such as inflammation, central obesity, and dyslipidemia, which was greater than in controls, it appears that PI medications may exacerbate oxidative stress and hypertriglyceridemia to enhance this risk.

Adolescent↗

PubMed2004

C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001.

The underlying cause of type 1 diabetes, loss of beta-cell function, has become the therapeutic target for a number of interventions in patients with type 1 diabetes. Even though insulin therapies continue to improve, it remains difficult to achieve normal glycemic control in type 1 diabetes, especially long term. The associated risks of hypoglycemia and end-organ diabetic complications remain. Retention of beta-cell function in patients with type 1 diabetes is known to result in improved glycemic control and reduced hypoglycemia, retinopathy, and nephropathy. To facilitate the development of therapies aimed at altering the type 1 diabetes disease process, an American Diabetes Association workshop was convened to identify appropriate efficacy outcome measures in type 1 diabetes clinical trials. The following consensus emerged: While measurements of immune responses to islet cells are important in elucidating pathogenesis, none of these measures have directly correlated with the decline in endogenous insulin secretion. HbA(1c) is a highly valuable clinical measure of glycemic control, but it is an insensitive measure of beta-cell function, particularly with the currently accepted standard of near-normal glycemic control. Rates of severe hypoglycemia and diabetic complications ultimately will be improved by therapies that are effective at preserving beta-cell function but as primary outcomes require inordinately large and protracted trials. Endogenous insulin secretion is assessed best by measurement of C-peptide, which is cosecreted with insulin in a one-to-one molar ratio but unlike insulin experiences little first pass clearance by the liver. Measurement of C-peptide under standardized conditions provides a sensitive, well accepted, and clinically validated assessment of beta-cell function. C-peptide measurement is the most suitable primary outcome for clinical trials of therapies aimed at preserving or improving endogenous insulin secretion in type 1 diabetes patients. Available data demonstrate that even relatively modest treatment effects on C-peptide will result in clinically meaningful benefits. The development of therapies for addressing this important unmet clinical need will be facilitated by trials that are carefully designed with beta-cell function as determined by C-peptide measurement as the primary efficacy outcome.

C-Peptide↗

PubMedDate not supplied

Diabetes trends in the USA.

In the United States (US), diabetes mellitus is a serious and costly public health problem, affecting more than 16 million people. Its incidence will continue to grow, as indicated by high rates of impaired fasting glucose levels, increased rates of obesity, and the trend toward more sedentary lifestyles. The prevalence of diabetes increases with age and varies by gender, race, and ethnicity. Diabetes also presents an enormous economic burden in the US. In 1996, total health care costs were 1 trillion dollars, 120 million dollars of which was for diabetes. A large proportion of the per-person costs associated with diabetes is for treating diabetic complications. Morbidity and mortality rates are higher in patients with diabetes than in patients without diabetes. There has been some recent improvement in type 2 diabetes treatment with the availability of newer medications, including secretagogues, metformin, acarbose, and the 'glitazones'. More patients are now using oral combination therapy, and fewer patients are using insulin. Unfortunately, many patients with type 2 diabetes are delaying the use of insulin, even when it is indicated for their treatment. Moreover, even with the new classes of oral antidiabetic agents, glycemic control remains suboptimal and patients still are not reaching the recommended target values for HbA(1c) (<7%). Primary medical care for diabetes patients is also less than optimal and must be improved. On an arbitrary gradient scale of 1 to 4 (with 1 being primitive and 4 being comprehensive), the US is only at stage 2 for diabetes care systems, indicating a pressing need for improvement in diabetes care.

Adult↗