Clinically isolated syndrome (CIS) refers to the initial clinical episode with symptoms suggestive of multiple sclerosis (MS). Due to limited number of long-term follow-up studies, progression pattern from CIS to more advanced stages remains unclear. In the current study, we constructed a Markov model to simulate the natural course of CIS. The model estimated the probabilities of transition from CIS to more advanced disease stages and the duration needed for the progression. The analysis showed: (1) CIS is a solid disease identity: more than 85% of the subjects with a diagnosis of CIS progress to RRMS or more advanced stages within 20 years; (2) the reduction of life expectancy in subjects with CIS is marginal.

BACKGROUND Multiple studies demonstrate that fluctuating blood glucose level produces greater damage compared with sustained hyperglycemia. Flash glucose monitoring system is an effective method in documenting blood glucose variability, contributing to better glucose management and reduced hypoglycemic event occurrence. AIM To investigate the improvement in glycemic variability (GV), blood glucose level, and metabolic indexes of patients with type 2 diabetes mellitus after combined treatment of exenatide once weekly (EXQW) and metformin. METHODS Twenty-five patients with type 2 diabetes mellitus suffering from poor blood glucose control under metformin treatment were recruited. The recruited patients were prescribed with oral metformin only (maintaining a dosage of metformin at ≥ 1500 mg/day) for 2 wk (screening period), and then given EXQW (2 mg, subcutaneous injection) for 12 wk (experimental period). The flash glucose monitoring system was used to document blood glucose values during the screening period and the last 2 wk of the experimental period. RESULTS Four patients were excluded for various reasons, yielding a total of 21 patients, including 17 males and 4 females, with an average age of 48.8 years, who completed this study. The estimated glycated hemoglobin, mean blood glucose, fasting and postprandial blood glucose levels, and percentage of blood glucose above 7.8 mmol/L decreased compared to those at baseline ( P = 0.003, 0.003, 0.008, 0.010, 0.014, 0.017, and 0.005, respectively), while the percentage of blood glucose between 3.9 and 7.8 mmol/L significantly increased ( P = 0.005). Parameters of GV including standard deviation of blood glucose, mean amplitude of glycemic excursions, mean of daily difference, area under the curve difference between percentiles 25 and 75, and area under the curve difference between percentiles 10 and 90 were significantly lower compared to that of baseline ( P = 0.017, 0.006, 0.000, 0.024, 0.036, respectively). The durations of blood glucose below 3.9 mmol/L during the day and nocturnal periods significantly increased after treatment ( P = 0.041 and 0.028, respectively), but there was no significant increase in severe hypoglycemia (< 3.0 mmol/L) compared with that at baseline ( P = 0.207). In addition, some metabolic indicators improved after EXQW treatment. CONCLUSION EXQW combined with metformin can effectively improve blood glucose levels, reduce GV, and improve metabolic indicators. However, there is still a risk of nocturnal hypoglycemia, and careful attention should be paid to patients with EXQW treatment.