Mechanisms of Hypoglycemia in Patients Without Diabetes
概览
- 阶段
- 不适用
- 干预措施
- Entry of demographic and medical history data into a deidentified database
- 疾病 / 适应症
- Hypoglycemia
- 发起方
- Joslin Diabetes Center
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Entry of demographic data into a deidentified database.
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
The goal of this study is to identify physiologic and molecular mechanisms that underlie hypoglycemia in the absence of diabetes (or medications that can cause hypoglycemia) and to investigate potential genetic and microbiome differences which contribute to hypoglycemia. We will test the hypothesis that hypoglycemia in the absence of diabetes is linked to genetic variation or the microbiome, and identify whether additional medical history or diagnoses are enriched in the population of patients with hypoglycemia.
详细描述
Although there are several conditions which have been identified that cause, or contribute to hypoglycemia, diagnosis can be challenging, as the physiologic, and molecular mechanisms are incompletely understood. Additionally, treatment options are relatively limited, and often incompletely effective and/or not well tolerated. Investigating the causative factors and mechanisms of hypoglycemia is important therefore in improving our understanding in order to develop new and more effective approaches to treatment. The current study aims to: 1. more fully characterize clinical history and demographics in patients with diverse forms of hypoglycemia by creating and analyzing a patient database; 2. for a subset of patients, characterize metabolic and hormonal responses to a standard meal; 3. analyze DNA variants in individuals with hypoglycemia; 4. analyze differences in the intestinal microbiome in individuals with hypoglycemia.
研究者
入排标准
入选标准
- •For hypoglycemia group without a history of bariatric surgery: Males or females diagnosed with hypoglycemia with prior episodes of neuroglycopenia.
- •For hypoglycemia group with history of upper gastrointestinal surgery: Males or females diagnosed with ongoing hypoglycemia with prior episodes of neuroglycopenia.
- •For non-surgical controls only: Males or females with no history of upper gastrointestinal surgery and no history of hypoglycemia or diabetes.
- •Age 18-70 years of age, inclusive, at screening.
- •Willingness to provide informed consent and attend one study visit, with option to attend a second visit with mixed meal test, and follow all study procedures
排除标准
- •Active treatment with any diabetes medications except for acarbose;
- •Known insulinoma, gastrinoma, or other neuroendocrine tumor;
- •Additional exclusion criteria for those participating in optional Visit 2 (meal testing):
- •Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
- •Hepatic disease, including serum alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin \< 3.0 g/dL; or serum bilirubin \> 2.0;
- •Congestive heart failure, New York Hear Association (NYHA) class II, III or IV;
- •History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use;
- •History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia;
- •Concurrent administration of β-blocker therapy;
- •History of a cerebrovascular accident;
研究组 & 干预措施
Hypoglycemia, with history of upper GI surgery
Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery
干预措施: Entry of demographic and medical history data into a deidentified database
Hypoglycemia, with history of upper GI surgery
Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery
干预措施: Blood sample for DNA analysis
Hypoglycemia, with history of upper GI surgery
Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery
干预措施: Stool sample for microbiome analysis
Hypoglycemia, with history of upper GI surgery
Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery
干预措施: Mixed meal tolerance test
Hypoglycemia, with history of upper GI surgery
Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery
干预措施: Continuous glucose monitoring
Hypoglycemia, with history of upper GI surgery
Males or females with hypoglycemia with neuroglycopenia, with history of upper GI surgery
干预措施: activity monitor
Hypoglycemia, no upper gastrointestinal (GI) surgery
Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes
干预措施: Entry of demographic and medical history data into a deidentified database
Hypoglycemia, no upper gastrointestinal (GI) surgery
Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes
干预措施: Blood sample for DNA analysis
Hypoglycemia, no upper gastrointestinal (GI) surgery
Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes
干预措施: Stool sample for microbiome analysis
Hypoglycemia, no upper gastrointestinal (GI) surgery
Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes
干预措施: Mixed meal tolerance test
Hypoglycemia, no upper gastrointestinal (GI) surgery
Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes
干预措施: Continuous glucose monitoring
Hypoglycemia, no upper gastrointestinal (GI) surgery
Males or females with hypoglycemia with neuroglycopenia, but no history of upper GI surgery, diabetes or prediabetes
干预措施: activity monitor
Controls, without hypoglycemia or upper GI surgery
Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.
干预措施: Entry of demographic and medical history data into a deidentified database
Controls, without hypoglycemia or upper GI surgery
Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.
干预措施: Blood sample for DNA analysis
Controls, without hypoglycemia or upper GI surgery
Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.
干预措施: Stool sample for microbiome analysis
Controls, without hypoglycemia or upper GI surgery
Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.
干预措施: Mixed meal tolerance test
Controls, without hypoglycemia or upper GI surgery
Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.
干预措施: Continuous glucose monitoring
Controls, without hypoglycemia or upper GI surgery
Males or females with no history of upper gastrointestinal surgery, hypoglycemia, or diabetes.
干预措施: activity monitor
结局指标
主要结局
Entry of demographic data into a deidentified database.
时间窗: March 2020 through March 2025
Demographic data will be entered into RedCap for analysis.
Entry of medical history data into a deidentified database.
时间窗: March 2020 through March 2025
Medical history data will be entered into RedCap for analysis.
Analysis of participant demographics and medical history, comparing the 3 study groups.
时间窗: March 2025
Demographic and medical history data will be summarized in RedCap and compared between groups using ANOVA or chi-square testing, depending on the variable analyzed.
Entry of physical exam data into a deidentified database.
时间窗: March 2020 through March 2025
Pertinent physical exam data will be entered into RedCap for analysis.
Entry of laboratory data into a deidentified database.
时间窗: March 2020 through March 2025
Laboratory data will be entered into RedCap for analysis.
Analysis of metabolic responses during mixed meal testing.
时间窗: March 2025
For a subset of participants who consent to participate in optional Visit 2, magnitude of hypoglycemia will be correlated with metabolite levels during meal testing. Metabolites will be measured at set time points after the start of the mixed meal. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in metabolic responses. Data will be checked to ensure variables conform to assumptions of the analysis. Sensitivity analysis will determine whether missing data are randomly associated with clinical or experimental phenotypes, and assess the impact of missing data on conclusions. The relationship between clinical and metabolic variables will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Targeted resequencing of DNA to identify variants associated with hypoglycemia, comparing patients with hypoglycemia (both surgical and non-surgical) and healthy controls.
时间窗: March 2025
Sequence variants identified during targeted resequencing will be summarized and prevalence will be compared between groups and with population databases. Depending on results of targeted resequencing, additional expanded genotyping may be performed.
Analysis of microbiome, comparing study groups.
时间窗: March 2025
Microbiome will be characterized by sequencing to obtain metagenomic data and pathway analysis; all data will be adjusted for multiple comparisons.
Analysis of hormonal responses during mixed meal testing.
时间窗: March 2025
For a subset of participants who consent to participate in optional Visit 2, magnitude of hypoglycemia will be correlated with hormone levels during meal testing. Counterregulatory hormones will be measured at set time points after the start of the mixed meal. Linear mixed effects modeling will be utilized to identify group- and time-dependent differences in counterregulatory hormone responses. Data will be checked to ensure variables conform to assumptions of the analysis. Sensitivity analysis will determine whether missing data are randomly associated with clinical or experimental phenotypes, and assess the impact of missing data on conclusions. The relationship between clinical and hormonal variables will be analyzed using Pearson correlation, and adjusted for multiple comparisons using Benjamini-Hochberg testing.
Analysis of glucose patterns during masked continuous glucose monitoring (CGM), including time in range, time in hypoglycemia, time in hyperglycemia, comparing the study groups.
时间窗: March 2025
For a subset of participants who consent to participate in optional Visit 2, CGM data will be analyzed to assess mean, median, peak, and nadir sensor glucose values, glycemic variability (GV), severity and length of hypoglycemia (% time glucose \<70, \<60, \<54 mg/dL), and number and duration of severe hypoglycemia (sensor glucose \<54, duration \>15 minutes) will be quantified. Metrics will be assessed over 24 hours and during daytime (6 AM to midnight) and nighttime (midnight to 6 AM) independently.
次要结局
- Relationship between hormonal responses and microbiome.(March 2025)
- Relationship between metabolic responses and magnitude of hypoglycemia as determined by CGM.(March 2025)
- Relationship between hormonal responses and magnitude of hypoglycemia as determined by CGM.(March 2025)
- Relationship between metabolic responses and microbiome.(March 2025)