Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to evaluate the degree of beta-cell dysfunction among participants with type 2 diabetes and the association between beta-cell dysfunction and demographic, clinical, and treatment variables.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
41 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Physician diagnosis of type 2 diabetes mellitus by American Diabetes Association (ADA) criteria * Oral hypoglycemic drug therapy for ≥1 year * Continuous care at the clinic (at least 2 visits) for at least one year * Medical records completed with a minimum core data set * Completed consent form
Exclusion criteria
* Participation in a clinical trial in the previous 1 year * Currently using insulin * Type 1 diabetes * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) at 4 Years | Baseline and 4 years | HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5. |
| Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at 4 Years | Baseline and Year 4 | Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. A raised proinsulin-to-insulin ratio due to impaired processing of proinsulin is an early marker of beta cell dysfunction. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion. |
| Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio | Baseline | HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion. |
Participant flow
Recruitment details
This observational study was conducted at 9 outpatient diabetes clinics in Italy.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants receiving routine care under a diabetologist. | 507 |
| Total | 507 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 9 |
| Overall Study | Laboratory parameters unavailable | 25 |
| Overall Study | Lost to Follow-up | 52 |
| Overall Study | Started insulin therapy | 55 |
| Overall Study | Started therapy with a DPP-IV/GLP-1 | 92 |
| Overall Study | Withdrawal by Subject | 39 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 209 Participants |
| Sex: Female, Male Male | 298 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 507 |
| serious Total, serious adverse events | 1 / 507 |
Outcome results
Primary
Change From Baseline in Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) at 4 Years
HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5.
Time frame: Baseline and 4 years
Population: Participants who had laboratory parameters at Baseline and at Year 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) at 4 Years | HOMA-B at Baseline | 50.2 Percentage of Beta Cell Function | Standard Deviation 49.1 |
| All Participants | Change From Baseline in Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) at 4 Years | HOMA-B at Year 4 | 48.3 Percentage of Beta Cell Function | Standard Deviation 36.3 |
p-value: 0.24Multivariate regression analysis
Primary
Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at 4 Years
Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. A raised proinsulin-to-insulin ratio due to impaired processing of proinsulin is an early marker of beta cell dysfunction. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion.
Time frame: Baseline and Year 4
Population: Participants who had laboratory parameters at Baseline and at Year 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at 4 Years | PI/I at Baseline | 1.19 PI/I | Standard Deviation 1.86 |
| All Participants | Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at 4 Years | PI/I at Year 4 | 1.61 PI/I | Standard Deviation 1.72 |
p-value: 0.001Multivariate regression analysis
Primary
Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio
HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion.
Time frame: Baseline
Population: Participants with fasting plasma insulin and glucose concentration assessments at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio | I. PI/PII <=0.485 | 73.4 Percentage Beta Cell Function | Standard Deviation 63.8 |
| All Participants | Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio | II. PI/PII 0.485 to 0.80 | 51.6 Percentage Beta Cell Function | Standard Deviation 33.2 |
| All Participants | Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio | III. PI/PII 0.81 to 1.355 | 37.7 Percentage Beta Cell Function | Standard Deviation 30.4 |
| All Participants | Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio | IV PI/PII >1.355 | 29.9 Percentage Beta Cell Function | Standard Deviation 33.4 |
p-value: <0.0001Multivariate regression analysis