Pathogenesis of the Cardiometabolic Risk in Youth With Type 1 Diabetes

Not Applicable

Terminated

• Conditions: De Novo Lipogenesis; Type 1 Diabetes
• Interventions: Diagnostic Test: Oral Glucose Tolerance Test

• Registration Number: NCT04101045
• Lead Sponsor: Yale University

Brief Summary

The purpose of this study is to quantitate hepatic de novo lipogenesis (DNL) in youth with poorly-controlled type 1 diabetes (T1D) (HbA1c \>8.5%), youth with T1D who achieve targeted glycemic control (HbA1c \<7.5%) and lean controls. Hypothesis: Youth with poor glycemic control experience higher fractional hepatic DNL during the fasting and the postprandial states than youth who achieve targeted glycemic control and lean controls.

Detailed Description

What is not known, is whether hepatic de novo lipogenesis (DNL) contributes to dyslipidemia in this in patients with type 1 diabetes (T1D). The aim of the study is to test the hypothesis that an enhanced rate of DNL largely contributes to dyslipidemia occurring in youth with poorly-controlled T1D. According to this hypothesis, youth with poorly-regulated T1D experience a state of persistent insulin independent, highly variable fluctuations of glucose, and other sugars, through the glycolytic pathway that result in an enhancement of hepatic DNL and an increased production of triglycerides (TG). Newly-formed TG are packaged into large-VLDL that are secreted into the circulation contributing to an increase in plasma TG. When the TG concentration in the hepatocytes exceeds the ability of the liver to secrete TG, the latter start accumulating leading to hepatic steatosis.

Study Timeline

• Study First Submitted: 2019-09-17
• Study First Submitted QC: 2019-09-19
• Study First Posted: 2019-09-24
• Study Start: 2019-11-21
• Primary Completion: 2022-03-30
• Study Completion: 2022-03-30
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-08
• Last Update Posted: 2023-02-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• HbA1c >8.5% for the group with poorly controlled diabetes
• HbA1c <7.5% for the well-controlled patients
• T1D for at least 12 months (T1D groups only)
• Negative pregnancy test (all groups)

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Exclusion Criteria

• Baseline creatinine >1
• Being on medications affecting glucose concentrations other than insulin
• Positive pregnancy test
• Endocrinopathies

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Controlled T1D	Oral Glucose Tolerance Test	Patients in this group will have T1D and achieve targeted glycemic control (HbA1c \<7.5%).
Lean controls	Oral Glucose Tolerance Test	Patients in this group will not have T1D.
Poorly-controlled T1D	Oral Glucose Tolerance Test	Patients in this group will have poorly-controlled T1D (HbA1c \>8.5%).

Primary Outcome Measures

Name	Time	Method
Fractional hepatic DNL	Baseline to Six hours	% Fractional hepatic DNL

Trial Locations

Locations (1)

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States