Trial · Interventional

CompletedPhase 1Results postedRegistry data

Contribution of Hyperinsulinemia vs. Hyperglycemia to Insulin Resistance in Type 1 Diabetes and Maturity Onset Diabetes of the Young, Type 2 (MODY2)

NCTNCT02971202Other id161504

Open at ClinicalTrials.govAsk about this trial

This trial does not test a peptide that PepBank tracks.

Names Glucagon, does not test it. It appears in the description.

Overview

Status: Completed
Phase: Phase 1
Enrollment: 33 participants (actual)
Sponsor: Vanderbilt University · Other
Design: Not randomized · Open label (no masking)
Countries: 1 country
United States
Start: Dec 2016
Primary completion: Feb 2019
Completion: Feb 2019
First posted: 22 Nov 2016 (estimated)
Last update posted: 1 Aug 2019
Conditions: Type 1 Diabetes Mellitus · Maturity-Onset Diabetes of the Young, Type 2 · MODY2 · Insulin Resistance

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20162017201820192020

Ph 1
Contribution of Hyperinsulinemia vs. Hyperglycemia to Insulin Resistance in Type 1 Diabetes and Maturity Onset Diabetes of the Young, Type 2 (MODY2)
NCT02971202
Dec 2016 to Feb 2019

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study is to determine the key factors influencing insulin sensitivity in type 1 diabetes (T1DM) and maturity onset diabetes of the young, type 2 (MODY2). Our study tests the hypothesis that decreased insulin sensitivity is primarily driven by chronically elevated insulin levels in the blood rather than chronic elevations in blood sugar.

Interventions

Hyperinsulinemic, euglycemic clampDrug
20% dextroseDrug

Arms3

Other
Hyperinsulinemic, euglycemic clamp: T1DM
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study: * insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes) * glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes) * somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts. A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
Other
Hyperinsulinemic, euglycemic clamp:MODY2
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study: * insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes) * glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes) * somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts. A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
Other
Hyperinsulinemic euglycemic clamp:Control
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study: * insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes) * glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes) * somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts. A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.

Primary outcomes1

Outcomes the sponsor listed as primary.

Whole-body Glucose Utilization (Rd)
Time frame · End of clamp study (the study will last 8 hours)
Registry description
The primary outcome is the degree to which Rd (determined using isotopic glucose tracer techniques) during maximal insulin stimulation differs between cohorts.

Secondary outcomes(2)

Hepatic Insulin Sensitivity
Time frame · 4 1/2 hours into clamp study
Registry description
Glucose production (Ra) will be determined using stable isotopic tracer techniques. The extent to which Ra is suppressed at the end of 4 1/2 hours (when glucose Ra by liver has been submaximally suppressed) compared to basal (ΔRa) is directly proportional to hepatic insulin sensitivity.
Adipose Tissue Insulin Sensitivity
Time frame · 4 1/2 hours into clamp study
Registry description
Insulin sensitivity at fat is directly proportional to insulin's ability to suppress lipolysis. Thus, we will determine the extent to which submaximal insulin stimulation (4 1/2 hours into the study) suppresses glycerol and non-esterified free fatty acids (NEFAs) compared to baseline. The extent to which these two metabolites are suppressed is directly proportional to insulin sensitivity in adipose tissue. Here the suppression of NEFA is taken as the secondary outcome parameter.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· End of clamp study (the study will last 8 hours)

Whole-body Glucose Utilization (Rd)

Group	Value (mg/kg FFM/min)
Hyperinsulinemic, Euglycemic Clamp: T1DM	8.5
Hyperinsulinemic, Euglycemic Clamp:MODY2	11.0
Hyperinsulinemic Euglycemic Clamp:Control	12.1

Secondary and other outcome results(2)

Secondary outcomeMean· 4 1/2 hours into clamp study

Hepatic Insulin Sensitivity

Group	Value (mg/kg FFM/min)
Hyperinsulinemic, Euglycemic Clamp: T1DM	1.9
Hyperinsulinemic, Euglycemic Clamp:MODY2	2.1
Hyperinsulinemic Euglycemic Clamp:Control	1.7

Secondary outcomeMean· 4 1/2 hours into clamp study

Adipose Tissue Insulin Sensitivity

Group	Value (μmol/L)
Hyperinsulinemic, Euglycemic Clamp: T1DM	122.4
Hyperinsulinemic, Euglycemic Clamp:MODY2	382.3
Hyperinsulinemic Euglycemic Clamp:Control	392.7

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Hyperinsulinemic, Euglycemic Clamp: T1DMParticipants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study: * insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes) * glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes) * somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts. A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.	0 / 12	0 / 12	4 / 12
Hyperinsulinemic, Euglycemic Clamp:MODY2Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study: * insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes) * glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes) * somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts. A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.	0 / 10	0 / 10	3 / 10
Hyperinsulinemic Euglycemic Clamp:ControlParticipants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study: * insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes) * glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes) * somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts. A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.	0 / 11	0 / 11	3 / 11

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedGregory JM, Smith TJ, Slaughter JC, Mason HR, Hughey CC, Smith MS, Kandasamy B, Greeley SAW, Philipson LH, Naylor RN, Letourneau LR, Abumrad NN, Cherrington AD, Moore DJ. Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison With GCK-MODY (MODY2). Diabetes. 2019 Aug;68(8):1565-1576. doi: 10.2337/db19-0324. Epub 2019 May 15. PMID 31092478

Eligibility

Who could join, as posted.

Sex: All
Age: from 13 Years up to 51 Years
Healthy volunteers: Accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: Inclusion criteria for all subjects: \- BMI 19-28 kg/m\^2 Additional inclusion criteria for T1DM subjects: * Age 13-51 * T1DM duration 1-20 years * HbA1c 5.9-8.0% Additional inclusion criteria for MODY2 subjects: * age 13-51 * positive GCK genetic sequencing * HbA1c 5.9-8.0% Additional inclusion criteria for control subjects: * age 18-5.1 * HbA1c \< 5.5% Exclusion Criteria: Exclusion criteria for all subjects: * severe hypoglycemia (\>= 1 episode in the past 3 months or diagnosis of hypoglycemia unawareness) * diabetes comorbidities (\>= 1 trip to emergency department for poor glucose control in the past 6 months, New York Heart Association Class II-IV cardiac functional status, systolic blood pressure \> 140 and diastolic blood pressure \> 100 mmHg, fasting triglycerides \> 400 mg/dL, liver transaminases \> 2 times the upper limit of normal, renal transplantation or serum creatinine \> 1.5 mg/dL) * confounding medications (any systemic glucocorticoid, any antipsychotic, atenolol, metoprolol, propranolol, niacin, any thiazide diuretic, any oral contraceptive pill with \> 35 mcg ethinyl estradiol, growth hormone, any immunosuppressant, any anti-hypertensive, any-antilipidemic) * pregnancy * Tanner stage \< 5 Additional exclusion criteria for T1DM subjects * any diabetes medication except insulin * fasting c-peptide \> 0.7 ng/mL

PepBank is a research reference. Talk to a doctor before you use any peptide.