Hyperinsulinemia

Background: The adrenal gland makes the hormone aldosterone. This helps regulate blood pressure. An adrenal gland tumor that makes too much aldosterone can cause high blood pressure and low potassium. The cause of these tumors is unknown, but sometimes they are inherited. Objective: To study the genes that may cause primary aldosteronism in Black individuals. Eligibility: People ages 18-70 who: Are Black, African American, or of Caribbean descent And have difficult to control blood pressure or primary aldosteronism Relatives of people with primary aldosteronism Design: Participants who are relatives of people with primary aldosteronism will have only 1 visit, with medical history and blood tests. Participants with primary aldosteronism or difficult to control blood pressure (suspected to possibly have primary aldosteronism) will be screened with a 1-2 hour visit. If they qualify, they will return for a hospital stay for 7-10 days. Tests may include: Medical history Physical exam Blood tests: Participants will have a small tube (IV catheter) inserted in a vein in the arm. They may drink a glucose-containing liquid or get a salt solution. If medically indicated, they may have invasive blood tests with a separate consent. Urine tests: Some require a high-salt diet for 3 days. Heart tests Scans: Participants lie in a machine that takes pictures of the body. A dye may be injected through a vein. Small hair sample taken from near the scalp. Kidney ultrasound Bone density scan: Participants lie on a table while a camera passes over the body. If the doctors feel it is medically necessary, they will offer participants treatment depending on their results. These treatments may cure the patient of their disease and may include: 1. Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients will have follow-up visits 2-4 weeks after surgery. 2. Taking drugs to block the effects of aldosterone Participants may return about 1 year later to repeat testing.

This cross-sectional study aims to further subdivide diabetes mellitus into more homogeneous subgroups by focusing on extreme glucose metabolism phenotypes, including monogenic diabetes with β cell dysfunction, hyperinsulinemia caused by excessive β cell secretion, and postprandial hypoglycemia phenotypes. By utilizing continuous glucose monitoring (CGM) technology and the FreeStyle Libre 2 glucose monitoring device, this study will evaluate glycemic variability patterns in patients with extreme glucose metabolism phenotypes and perform comparative analyses using existing CGM data from healthy populations and patients with type 2 diabetes in our center's database. The study aims to address current gaps in understanding glycemic variability characteristics under extreme β cell functional states, provide novel dynamic monitoring evidence to support early identification, precise classification, and personalized management of these special metabolic states, and simultaneously screen for biomarkers to enable more accurate disease identification, thereby offering potential avenues for improving personalized treatment of diabetes mellitus.

The goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Participants will be asked to come in for a one-day study visit in which they will undergo a "graded insulin suppression test" ("GIST"). The GIST involves intravenous (into the vein) infusions of octreotide, a medication that turns off the body's own production of insulin, as well as replacement of insulin at two different levels (low and high), with or without replacement of glucagon, and glucose (sugar). The study investigators will check blood sugar levels every few minutes during the procedure to determine the effect of the two different insulin levels. This study will evaluate the GIST in both healthy volunteers and those at higher risk for type 2 diabetes.

The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology. Participants will: * Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose \[mpk\]) or another 14 doses of placebo, over 7 days * Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice * Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study * Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period * Consume their total calculated daily caloric needs as divided into three meals per day Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.

This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the impact of lowering insulin levels on hepatic glucose production (HGP) vs de novo lipogenesis (DNL) in people with insulin resistance. The investigators will recruit participants with a history of overweight/obesity and evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and/or impaired fasting glucose and/or Homeostasis Model Assessment of Insulin Resistance \[HOMA-IR\] score \>=2.73), and with evidence of metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo two pancreatic clamp procedures -- one in which serum insulin levels are maintained near hyperinsulinemic baseline (Maintenance Hyperinsulinemia or "MH" Protocol) and the other in which serum insulin levels are lowered by 50% (Reduction toward Euinsulinemia or "RE" Protocol). In both clamps the investigators will use stable-isotope tracers to monitor hepatic glucose and triglyceride metabolism. The primary outcome will be the impact of steady-state clamp insulinemia on HGP vs DNL.

The goal of this study is to learn about how the hormone insulin controls blood sugar. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. People with obesity and high insulin levels will receive eight doses of diazoxide, a drug that suppresses the pancreas's production of insulin, and will have their fasting blood sugar and insulin levels checked daily while taking the drug.