Blood Glucose Fluctuations in Type 2 Diabetes Patients Treated with Multiple Daily Injections

Abstract

To compare blood glucose fluctuations in type 2 diabetes mellitus (T2DM) patients were treated using three procedures: insulin intensive therapy which is continuous subcutaneous insulin infusion (CSII), MDI3 (three injections daily), and MDI4 (four injections daily). T2DM patients were hospitalized and were randomly assigned to CSII, aspart 30-based MDI3, and glargine based MDI4. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. After completing the baseline assessment, 6-day continuous glucose monitoring (CGM) was performed before and after completion of insulin treatment. Treatment with CSII provided a greater improvement of blood glucose fluctuations than MDI (MDI3 or MDI4) therapy either in newly diagnosed or in long-standing T2DM patients. In long-standing diabetes patients, the MDI4 treatment group had significantly greater improvement of mean amplitude glycemic excursion (MAGE) than the MDI3 treatment group. However, in patients with newly diagnosed diabetes, there were no significant differences in the improvement of MAGE between MDI3 and MDI4 groups. Glargine based MDI4 therapy provided better glucose fluctuations than aspart 30-based MDI3 therapy, especially in long-standing T2DM patients, if CSII therapy was not available.

Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes

“…The total daily insulin (Aspart, Novo Nordisk, Bagsværd, Denmark) dose was 0.5 IU/kg which was given in 2 injection modes: 1/3 of total daily dose was equally given as boluses within 3 meals, the remaining insulin was given as basal dose. Investigators titrated insulin doses on an individual-patient basis at the titration algorithm (if the fasting blood glucose level was less than 4.4 mmol/L, the insulin dose was reduced 2 units; if the fasting blood glucose level was within 4.4 to 6.1 mmol/L, the insulin dose was unchanged; if the fasting blood glucose level was within 6.2 to 7.8, 7.9 to 10.0, and >10.0 mmol/L, the insulin dose was increased subsequently by 2, 4, and 6 units, respectively), as we described before [6] . The saxagliptin dose was unchanged during the study period.…”

“…After the baseline parameters were assessed, patient blood concentrations were monitored by CGM (Medtronic Incorporated, Northridge, Minnesota, USA) for 3 days, as we before described. [ 6 25 ] After CGM data were collected, enrolled subjects received saxagliptin (5 mg once daily, Bristol-Myers Squibb, Indiana, USA) add-on CSII or CSII treatment, without any oral antidiabetic drugs except metformin. The total daily insulin (Aspart, Novo Nordisk, Bagsværd, Denmark) dose was 0.5 IU/kg which was given in 2 injection modes: 1/3 of total daily dose was equally given as boluses within 3 meals, the remaining insulin was given as basal dose.…”

“…MAGE was calculated for each patient by measuring the arithmetic mean of the ascending and descending excursions between consecutive peaks and nadirs for the same 24-hour period, and only absolute excursion values >1 SD were considered, as we described before. [ 6 25 ] …”

“…This improvement of β-cell function might be responsible for the remission described in newly diagnosed T2D patients. [ 1–5 ] We recently observed that patients with newly diagnosed or longstanding T2D treated with CSII therapy confers a greater improvement of mean amplitude glycemic excursion (MAGE) as detected by continuous glucose monitoring (CGM) [6] . It is now believed that glucose fluctuations may be important as independent risk factors for cardiovascular disease in patients with onset T2D.…”

Chinese clinical guidelines for continuous glucose monitoring (2018 edition)

“…Overall, CGM is primarily recommended to patients with type 1 diabetes and those with type 2 diabetes on intensive insulin therapy or who experience dramatic glycemic variability. When appropriate, CGM can also be used in clinical research as a valuable tool for assessing and guiding treatment Real‐time CGM is mainly applicable to the following patients or conditions: children and adolescents with type 1 diabetes whose HbA 1c less than 7%.…”