Insulin

The goal of this clinical trial is to investigate whether metformin improves vascular function in individuals with prediabetes. The main questions it aims to answer are:

1. Does metformin improve large conduit artery endothelial function in individuals with prediabetes?
2. Does metformin improve microvascular endothelial function in individuals with prediabetes?

Researchers will compare metformin to a placebo to see if metformin improves vascular function in prediabetes.

The trial duration is 12 weeks. Participants will take metformin or a placebo once a day for 2 weeks. After 2 weeks, participants will take metformin or a placebo twice a day for the remaining 10 weeks. There will be a screening visit, two baseline visits, a 4-week safety visit, and two 12-week end-of-study visits. Adherence will be calculated from pill count and adverse events will be quantified via a questionnaire.

Women with a history of gestational diabetes mellitus (GDM) are at a 2-fold greater risk for the development of overt cardiovascular disease (CVD) following the effected pregnancy. While subsequent development of type II diabetes elevates this risk, prior GDM is an independent risk factor for CVD morbidity, particularly, within the first decade postpartum. GDM is associated with impaired endothelial function during pregnancy and decrements in macro- and microvascular function persist postpartum, despite the remission of insulin resistance following delivery. Collectively, while the association between GDM and elevated lifetime CVD risk is clear, and available evidence demonstrates a link between GDM and vascular dysfunction in the decade following pregnancy, the mechanisms mediating this persistent dysfunction remain unexamined.

The purpose of this investigation is to examine the role of endothelin-1, a potent vasoconstrictor, in aberrant microvascular function in otherwise healthy women with a history of GDM and to identify whether this mechanism is influenced by physical activity and sedentary behavior.

The objective of DIAGNODE-3 is to evaluate the efficacy and safety of three intranodal injections of 4 μg of Diamyd compared to placebo, along with oral Vitamin D supplementation, to preserve endogenous beta cell function and influence glycemic parameters in adolescent and adults recently diagnosed with T1D carrying the HLA DR3-DQ2 haplotype.

Researchers are looking for a better way to treat people with chronic kidney disease (CKD), a progressive decrease in the kidneys' ability to work properly, and type 1 diabetes.

In people with type 1 diabetes, the body does not make enough of a hormone called insulin, resulting in high blood sugar levels that can cause damage to the kidneys. CKD often occurs together with or as a consequence of type 1 diabetes.

The study treatment finerenone works by blocking certain proteins, called mineralocorticoid receptors. An increased stimulation of these proteins is thought to damage the kidneys and the heart. By lowering their stimulation, finerenone reduces the risk of kidney disease progressively getting worse. Finerenone is approved for doctors to prescribe to people with CKD and type 2 diabetes.

In this study, researchers want to learn if finerenone works better than placebo in reducing the participants' kidney disease from getting worse when given in addition to standard of care (SOC) treatment. A placebo looks like a treatment but does not have any medicine in it. SOC is a procedure or treatment that medical experts consider most appropriate for a condition or disease. To find out how well finerenone works, the level of a protein (albumin) in the urine will be measured.

Researchers also want to know how safe finerenone is. To do this, the researchers will collect the number of participants with:

* medical problems (also called treatment-emergent adverse events (TEAEs))
* serious TEAEs. An TEAE is considered 'serious' when it leads to death, puts the participant's life at risk, requires hospitalization, causes disability, causes a baby being born with medical problems, or is medically important
* higher than normal blood levels of potassium (hyperkalaemia). Depending on the treatment group, the participants will either take finerenone or placebo, Importantly, the participants will also continue to take their regular SOC medicines.

The participants will be in the study for up to 7.5 months and will take the study treatments for 6 months. During the study, they will visit the study site at least 6 times.

The study team will:

* collect blood and urine samples
* check the participants' vital signs such as blood pressure and heart rate
* do a physical examination including height and weight
* check the participants' heart health by using an electrocardiogram (ECG)
* do pregnancy tests in women of childbearing potential

The main purpose of this study is to determine safety and efficacy of orforglipron compared with insulin glargine in participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study will last approximately 2 years may include up to 27 visits.

The purpose of this investigation is to examine the mechanisms mediating vascular dysfunction in women who have had gestational diabetes and how metformin may be a valuable treatment tool to improve microvascular function in these women before the onset of disease.

The purpose of this investigation is to examine NADPH oxidase as a source of reactive oxygen species contributing to aberrant microvascular function in otherwise healthy women with a history of GDM.

The overarching hypothesis is that CF carriers are at increased risk for developing most of the extrapulmonary conditions associated with CF compared to the general population. Specifically, it is hypothesized that this pilot data will detect subclinical evidence of pancreatic and kidney disorders among CF carriers. This will be determined by bringing CF carriers and controls to the CRU for one visit where they will answer survey questions and undergo laboratory testing. Additionally, they will collect urine and stool samples at home that will be sent to outside laboratories for testing.

Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity which can progress to deadly complications like end-stage liver disease and hepatocellular carcinoma. In the wake of the obesity epidemic, NAFLD is becoming the main etiology of liver transplantation in the US. Currently, there are no FDA approved pharmacological treatments for NAFLD. Weight loss through lifestyle modifications, pharmacotherapy and bariatric surgery can be effective strategies for the management of NAFLD. Even though substantial weight loss and improvement in NAFLD can be achieved with bariatric surgery, only a small proportion of patients with obesity undergo surgery. Very-low calorie diets (VLCD) are replacement meals manufactured to substitute natural foods and limited total intake of 800-960 kcal in divided meals. Very low-calorie diets can produce substantial weight loss of 10% over 2 to 3 months. We hypothesize that VLCD reduce liver steatosis and, fibrosis measured non-invasively with transient elastography. Our main aim is #1 to assess the effect of VLCD on liver fatty infiltration and fibrosis. We also have three exploratory aims exploring novel pathogenic factors that mediate the improvement of NAFLD by VLCD: #2 assess the effect of VLCD on micro RNAs (miRs) associated with pathophysiology of NAFLD: #3 assess the effect of VLCD on changes of salivary and fecal microbiome in the setting of NAFLD: #4 to determine the effect of VLCD on platelet function. This pilot project will produce preliminary data for the development of a larger grant application to study the efficacy of VLCD in the management of NAFLD. Furthermore, it will potentially identify factors that mediate improvement of NAFLD after VLCD. We will treat 10 subjects with obesity and NAFLD for 8 weeks with VLCD or lower calorie diet (control group) and obtain transient elastography before and after the interventions along with other measurements of interest. Our project may have significant impact by establishing VLCD as a clinically effective option for the improvement of liver steatosis and fibrosis in patients with obesity and NAFLD ineligible or without access to bariatric surgery.

The purpose of this investigation is to examine the role of oxidative stress in aberrant microvascular function in otherwise healthy women with a history of GDM.