Type 1 Diabetes, Monogenic Diabetes
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year Medalist Study (Medalists), who are characterized by ≥50 years of insulin-dependent diabetes. Our primary objective is to evaluate whether the presence of human leukocyte antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of OHA in these subjects.
Interventions
Initial oral hypoglycemic agent added to existing insulin treatment
DRUGSitagliptin
Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)
Sponsors
Joslin Diabetes Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 85 Years
Healthy volunteers
No
Inclusion criteria
* Existing participants in the Joslin 50-Year Medalist Study * Residing in the United States * Capable of giving informed consent * Known detectable C-peptide \>0.05 ng/mL
Exclusion criteria
* Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis, lupus, and inflammatory bowel disease * Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure, angina, stroke, or uncontrolled hypertension\>160/100 during the past 3 months * Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease * Pre-existing liver disease or liver function tests (AST or ALT)\>3x the upper limit of normal * Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated glomerular filtration rate\<45 mL/min/1.73 m2) * Active use of immunosuppressants * Recipients of prior islet cell or pancreas transplantation * Inability to travel due to frailty or health reasons * Donated blood within the previous two (2) months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycated hemoglobin (HbA1c) | 3 months and 6 months | Change in HbA1c (%) between the two study groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Triglycerides | 3 months and 6 months | Change in triglycerides (mg/dL) between the two study groups |
| Total cholesterol | 3 months and 6 months | Change in total cholesterol (mg/dL) between the two study groups |
| Low density lipoprotein (LDL)-cholesterol | 3 months and 6 months | Change in LDL-cholesterol (mg/dL) between the two study groups |
| High density lipoprotein (HDL)-cholesterol | 3 months and 6 months | Change in HDL-cholesterol (mg/dL) between the two study groups |
| Body mass index (BMI) | 3 months and 6 months | Change in BMI between the two study groups. Weight and height will be combined to report BMI in kg/m\^2. |
| C-peptide | 3 months and 6 months | Change in C-peptide (ng/mL) between the two study groups |
| Area under the plasma concentration versus time curve (AUC) of C-peptide | 6 months | Change in AUC of C-peptide between the two study groups, as measured by the hyperglycemic/arginine clamp, at the end of the study |
| Daily insulin dose | 3 months and 6 months | Change in daily insulin dose (units/kg body weight) between the two study groups |
Countries
United States
Outcome results
None listed