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Nocturnal Glycemic Control with Glargine Titration Based on Bedtime in Addition to Fasting Plasma Glucose in Type 1 Diabetes
For patients with type 1 diabetes, taking into account the relationship of fasting plasma glucose (FPG) and bedtime plasma glucose to “titrate basal insulin in a more dynamic way may result in several advantages in glycemic control,” according to Francesca Porcellati, MD, University of Perugia, Perugia, Italy. Although there are several algorithms that have been studied and proposed for titrating basal insulin in subjects with type 2 diabetes, use of such algorithms in type 1 diabetes is less frequent and less popular. No study so far to her knowledge, Dr. Porcellati said in an oral presentation at the 2016 American Diabetes Association Annual Meeting, has specifically compared basal insulin titration options in type 1 diabetes.
Current practice in type 1 diabetes is to titrate basal insulin based on mean or median FPG over three consecutive days. FPG, however, may easily be impacted by carried over effects of post-dinner hypoglycemia or hyperglycemia (both of which are common in type 1 diabetes), preventing the interpretation of FPG as the specific effect of basal insulin or misleading its titration, Dr. Porcellati said.
She proposed that rather than FPG per se, the relationship of the bedtime plasma glucose to the morning FPG should be considered in order to titrate basal insulin more adequately in type 1 diabetes. An algorithm based on that would use this relationship between bedtime plasma glucose and next morning FPG on days in which post-dinner, clinically relevant hyperglycemia or hypoglycemia have not occurred.
Dr. Porcellati’s study compared efficacy and safety of such an algorithm with one based on FPG only. It compared standard evening glargine titration based on FPG (a mean of 6 consecutive days) as algorithm #1 (as a once-weekly titration) with an algorithm based on increments/decrements of nocturnal plasma glucose (the difference between bedtime plasma glucose and next morning FPG on days with post-dinner plasma glucose at target, with optimized evening prandial insulin titrated every 2 weeks) as algorithm #2. Both algorithms aimed at a target FPG of 100-130 mg/dl.
Seventy-four patients entered a 1 month run-in followed by 3 months of treatment with either algorithm #1 or algorithm #2 (37 in each group, mean age ~43 years). Diabetes durations was 21.2 years (± 12.3) in the algorithm #1 group and 24.5 years (±10.7) in the algorithm #2 group. Mean FPG was 159 mg/dL in the algorithm #1 group and 158 mg/dL in the algorithm.
At study end, FPG was lower in both groups but significantly lower (P<0.001) only in the algorithm #2 group. Results for HbA1c followed the same pattern, with significantly greater reductions in the algorithm #2 group than in the algorithm #1 group (P<0.002). Dr. Porcellati reported an opposite pattern for insulin doses which at study end had significantly smaller increases (P=0.038) in the algorithm #2 group.
Confirmed nocturnal hypoglycemia was significantly lower in the algorithm #2 group with respect to total confirmed events (P<0.001), percentage of subjects affected (P=0.065) and events/patient-3 month (P<0.001).
Dr. Porcellati concluded that as compared to an algorithm based on FPG only, one considering the relationship of bedtime plasma glucose to morning FPG may result in lower HbA1c , lower FPG, reduced intra-subject FPG variability, and risk of nocturnal hypoglycemia.
She said further, “The use of fasting plasma glucose to titrate basal insulin in type 1 diabetes is necessary but not sufficient...Indirectly, the study suggests that optimization of post-dinner plasma glucose to avoid hypoglycemia and hyperglycemia is a pre-requisite for interpreting FPG for basal insulin titration.” She noted also that in regions where dinner is eaten not as close to bedtime as it is in Italy, a bedtime glucose check may be important.
Developed by Elsevier B.V., supported by an unrestricted educational grant from Novo Nordisk