This was a multi-center, prospective, observational study performed at Department of Neurology, Yancheng No. 1 People’s Hospital, the Fourth Affiliated Hospital of Nantong University, China; Department of Neurology, Taizhou People's Hospital; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, China; Department of Neurology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China; and Department of Neurology, people’s Hospital of Dezhou, China between March 2018 and September 2018. The inclusion criteria were 1) Inpatient with acute ischemic stroke (AIS) less than 6 hrs after AIS onset; 2) Patients aged between 18 and 80 years; 3) Patients with or without established T2D history. Patients were excluded if they had 1) hemorrhagic stroke or other etiologic type of stroke; and 2) type 1 diabetes. The study was approved by the ethics committee of Yancheng City No. 1 People’s Hospital, the Fourth Affiliated Hospital of Nantong University, China and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments, including any relevant details. Written informed consent was obtained from each research center.
On day 0 of admission, the patient’s demographic data were collected by specially trained nurses. Modified Rankin scale (mRS) was assessed by a physician9. In addition, diabetic status, such as admission venous plasma glucose levels, the duration of diabetes, and patients receiving glucose-lowering agents, et al. were also recorded. On day 1 of admission, fasting serum samples were collected for HbA1c, glucose, and C-peptide concentrations determination. HbA1c was measured by a DiaSTAT HbA1c analyzer (Bio-Rad, Hercules, CA). C-peptide and glucose levels were analyzed at each research center. All recruited patients were subjected a retrospective CGM (Sof-sensor, CGMS-Gold, Medtronic Incorporated, Northridge, USA) from day 0 of admission to day 4 of admission for consecutive 4-day, as described previously10,11. The CGM sensor was subcutaneously embedded and continually wear the sensor until the sensor functional expired. Four additional capillary finger-pricks for glucose measurements per day were made, with one measurement taken in the interval of no more than 8 hrs, for calibration purposes during CGM period. After 4 days of CGM, subjects had the sensors removed, the CGM data were collected and analyzed by the investigators, as described previously10 − 12. During the CGM period, all subjects were instructed to maintain moderate physical activity and three meals per day consisting of a total daily caloric intake of 25 kcal/kg/day were served at 0700, 1100 and 1700 by research nurses, respectively, if patients were not in coma. Patients in a coma received Fatemulsion, Aminoacids (17) glucose (11) Injection infusions (Kabiveil PI, Sino-Swed Pharmaceutical Corp. Ltd, Wuxi, China) containing macronutrient, dextrose, and short-acting insulin, which was administered at a rate of 110 mL/h as previously prescribed13. Hypoglycemia, glucose level less than 3.9 mmol/L, was treated using IV glucose.
The 24-hr mean glucose (MG), the SDMG, the MAGE, the CV%, the mean highest glucose (MHG), the mean lowest glucose (MLG), the incremental AUC of hyperglycemia (> 10.0 mmol/L) and the incremental AOC of hypoglycemia (< 3.9 mmol/L), the percentage of time spent in hyperglycemia and hypoglycemia, the TIR, and glucose readings were analyzed, as previously described14. In addition, the times of hypoglycemia in each patient were also recorded.
To observe the differences in GV between diabetic AIS patients with or without parental nutrition (PN) therapy, a stratified analysis was performed comparing the MG, the SDMG, the MAGE, the CV%, the MHG, the MLG, the incremental AUC of hyperglycemia and the incremental AOC of hypoglycemia, the percentage of time spent in hyperglycemia and hypoglycemia and the TIR between the two groups.
The primary outcome was the differences in MAGE between AIS patients with and without T2D. Secondary endpoints were the differences in SD, CV%, MG, MHG, MLG, the incremental AUC of hyperglycemia and the incremental AOC of hypoglycemia, the percentage of time spent in hyperglycemia and hypoglycemia and the TIR in the two groups. In addition, the differences in GV in AIS patients with T2D receiving or not receiving PN were also compared.
Statistical analysis
Statistical analysis was performed using SPSS software (version 17.0; SPSS, Inc., Chicago, IL). All data were presented as the mean ± SD. Shapiro-Wilk test was used to verify the distribution of data. A Chi-squared test was performed compare the ratio differences between two groups. The mixed ANOVA model (2 × 2) test was used to compare differences between groups. All repeated data were analyzed by a two-way ANOVA between groups, followed by Bonferroni-Dunn post hoc test. P values were two-tailed with a significance level of 5%.