Type 2 Diabetes
Conditions
Keywords
beta-cell function, type 2 diabetes, intermittent insulin
Brief summary
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). The investigators propose a pilot randomized controlled trial to determine whether intermittent intensive insulin therapy is an effective therapeutic strategy that can preserve pancreatic beta-cell function and maintain glycemic control early in the course of type 2 diabetes.
Detailed description
In this study, eligible patients with type 2 diabetes will be randomized to either intermittent insulin therapy or continuous metformin therapy, after both arms have first undergone a short course of intensive insulin therapy. The hypothesis under study is whether intermittent insulin therapy can better preserve beta-cell function.
Interventions
DRUGIntermittent insulin therapy
DRUGContinuous metformin
Sponsors
Canadian Institutes of Health Research (CIHR)
Mount Sinai Hospital, Canada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women between the ages of 30 and 80 years inclusive 2. T2DM diagnosed by a physician \</= 5 years prior to enrolment 3. Negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies 4. On either no anti-diabetic medication or on metformin monotherapy, with no change in dose/regimen within 4 weeks prior to enrolment 5. A1c at screening between 5.5% and 9.0% inclusive if on metformin, or between 6.0% and 9.5% inclusive if on no oral anti-diabetic medication 6. BMI \>/= 23 kg/m2 7. Negative pregnancy test at recruitment for all women with childbearing potential
Exclusion criteria
1. Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, GLP-1 agonist or dipeptidyl peptidase-4 inhibitor 2. Type 1 diabetes or secondary forms of diabetes 3. History of hypoglycemia unawareness or severe hypoglycemia requiring assistance 4. Any major illness with a life expectancy of \<5 years 5. Hypersensitivity to insulin, metformin or the formulations of these products 6. Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) \<50 ml/min 7. Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, previous liver transplant) or transaminases \>2.5 X upper limit of normal 8. History of congestive heart failure 9. Excessive alcohol consumption, defined as \>14 alcoholic drinks per week for males and \>9 alcoholic drinks per week for females 10. Unwillingness to administer insulin therapy or perform capillary blood glucose monitoring at least 4 times per day while receiving IIT 11. Pregnancy or unwillingness to use reliable contraception. Women should not be planning pregnancy for the duration of the study or the first 3 months after the study. Reliable contraception includes birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide. 12. Non-adherence to the induction phase or any factor likely to limit adherence to the study protocol, in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2). | 2 years | ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted glycemic control at 2-years. | 2 years | The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Achievement of target glycemic control | 2 years | Achievement of target glycemic control will be assessed by the proportion of participants with A1c \<7.0% |
| achievement of glucose tolerance in the non-diabetic range | 2 years | The proportion of participants with glucose tolerance in the non-diabetic range will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT. |
| achievement of normal glucose tolerance | 2 years | The proportion of participants with normal glucose tolerance will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT. |
| insulin sensitivity | 2 years | Insulin sensitivity will be measured by Matsuda index, a clamp-validated measure of whole-body insulin sensitivity that can be obtained from the oral glucose tolerance test |
Countries
Canada
Outcome results
None listed