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Background: Not only within-day glycemic variability but also day-to-day glycemic variability is a risk factor for diabetic patients. However, the ways of controlling day-to-day glycemic variability are unclear. We hypothesized that the durability of basal insulin plays an important role in controlling day-to-day glycemic variability in type 2 diabetes patients, and we therefore aimed to evaluate whether glargine U300, which exhibits prolonged absorption compared with glargine U100 but the same composition as glargine U100, would lead to improved day-to-day glycemic variability. Materials and Methods: This was a single-center, randomized, open-label, crossover study in type 2 diabetes patients using basal insulin therapy. After switching from 4 weeks of treatment with glargine U100 or U300, the patients performed continuous glucose monitoring (CGM) for 72 h in an environment with routine activities and mealtimes. The mean of daily difference (MODD) was assessed as day-to-day glycemic variability....

A low-carbohydrate/high-monounsaturated fatty acid liquid diet (LC/HMD) was investigated for its role in long-term glycemic control in tube-fed type 2 diabetes patients who require insulin therapy.The study included 10 type 2 diabetes patients requiring insulin therapy who were being tube-fed with a high-carbohydrate liquid diet (HCD). With stable glucose control maintained, these patients were monitored for glucose levels for 4 consecutive days by using continuous glucose monitoring (CGM). The patients were continued on HCD during the first 2 days and were switched to an LC/HMD during the final 2 days. The patients were then continued on the LC/HMD, and seven of the 10 patients were monitored for glucose levels for 2 consecutive days by using CGM after 3 months of feeding with the LC/HMD. Insulin regimens used included basal-bolus insulin in five of these seven patients and intermediate-acting insulin in two patients.Based on CGM data, the indices for glucose variability, such as SDs of 288 glucose levels for 24 h, total area for the range of glucose variability, mean amplitude of glycemic excursions, and 24-h mean glucose levels were significantly decreased 3 months after switching from the HCD to the LC/HMD. Additionally, despite the significant decrease in required insulin dose, the hemoglobin A1c (HbA1c) values were significantly decreased 3 months after switching.Study results demonstrated that the LC/HMD not only narrowed the range of glucose variability, but also decreased the required insulin dose and HbA1c values in diabetes patients on tube feeding who required insulin therapy, suggesting the LC/HMD may be useful in long-term glycemic control in these patients.

This study compared glycemic variability in patients with type 2 diabetes given sitagliptin or voglibose.Seventeen type 2 diabetes patients were given sitagliptin 50 mg/day or voglibose 0.9 mg/day for 2 months and were hospitalized for a 4-day evaluation by continuous glucose monitoring (CGM). On discharge, they were crossed over to the other regimen for 2 months of treatment/4 days of evaluation. The CGM data were used to compare each parameter for glycemic variability.The average glucose levels with sitagliptin and voglibose were significantly different at 138.6 and 152.6 mg/dL for 24 h (P=0.014) and 147.2 and 160.9 mg/dL for during daytime (P=0.050), respectively. The patients' glucose levels with sitagliptin and voglibose were significantly different at 125.3 and 139.7 mg/dL before breakfast (P=0.015) and 112.7 and 131.4 mg/dL before lunch (P=0.049), respectively. The time from before meal to postprandial peak glucose levels was significantly longer after dinner with voglibose than with sitagliptin (91.5 and 122.3 min, respectively; P=0.012). All of the slopes of glucose elevation were significantly lower with voglibose after each meal, with that after breakfast, lunch, and dinner being 1.16 and 0.86 mg/dL/min (P=0.031), 0.70 and 0.45 mg/dL/min (P=0.048), and 1.06 and 0.73 mg/dL/min (P=0.028), respectively.This CGM-based pilot study revealed that sitagliptin significantly lowered 24-h and daytime mean glucose levels and glucose levels before breakfast and lunch compared with voglibose, whereas the time from before dinner to peak postprandial glucose levels was significantly longer, and the slope of postprandial elevation of glucose level was significantly lower after each meal, with voglibose compared with sitagliptin.

In an earlier continuous glucose monitoring (CGM)-based study, we reported that sitagliptin not only reduced 24-h mean glucose levels but also suppressed postprandial glucose increases, thus reducing the range of glycemic fluctuations in type 2 diabetes patients. In this study, we investigated whether sitagliptin might provide similar benefits in type 2 diabetes patients receiving insulin therapy by using CGM.The study included a total of 13 type 2 diabetes patients in whom stable glycemic control had been achieved after admission for glycemic control. Insulin regimens used included long-acting insulin preparations once daily in four patients and biphasic insulin preparations twice daily in nine, with the daily insulin dose being 19.0±12.7 U. During the CGM-based study, the patients were given insulin therapy alone on Days 1 and 2 and were given sitagliptin 50 mg/day as add-on treatment on Days 3-6, with their daily insulin doses maintained.The add-on treatment with sitagliptin led to significant decreases in 24-h mean glucose levels and SDs of 288 glucose levels measured by CGM for 24 h, as well as in the indices for magnitude of glucose variability and proportion of time in hyperglycemia, compared with insulin therapy alone (P0.01), whereas there was no significant change seen in regard to the proportion of time in hypoglycemia with or without add-on treatment with sitagliptin.This CGM-based study clearly demonstrated that insulin therapy alone, whether with long-acting or biphasic insulin preparations, does not provide adequate glycemic control in type 2 diabetes patients. In contrast, add-on sitagliptin was shown to narrow the range of 24-h glucose fluctuations in these patients, suggesting that add-on treatment with sitagliptin is effective for postprandial glucose control in type 2 diabetes patients receiving insulin therapy.

This study aimed to compare glycemic variations seen among Japanese patients with type 1 diabetes treated with insulin glargine versus insulin detemir using continuous glucose monitoring (CGM) in a crossover design.Twenty-three patients with type 1 diabetes were enrolled in this study. The subjects were on either insulin glargine followed by insulin detemir twice daily, or vice versa, with no change in the timing of injections. The glycemic variations during 4-day hospitalizations were monitored by CGM while the patients were on either regimen, with a second hospitalization scheduled more than 1 month after the change of the long-acting insulin analogs. CGM data obtained on Day 3 of both hospitalizations were compared.The subjects had a median age of 44.0 years, a median body mass index of 22.2 kg/m(2), and a median glycosylated hemoglobin of 7.3%. There was no significant difference between the two treatments with a mean glucose level of 156 mg/dL with the insulin glargine treatment versus 150 mg/dL with the insulin detemir treatment; their SD values were 60 versus 51 mg/dL, their mean amplitude of glycemic excursions values were 121 versus 105 mg/dL, and their mean of daily differences values were 45.7 versus 41.4 mg/dL, respectively. In addition, the insulin detemir treatment was associated with a narrower range of postprandial glucose increases after lunch (80 vs. 59 mg/dL; P=0.007).A comparison of the long-acting insulin analogs administered twice daily in type 1 diabetes demonstrated that insulin detemir may potentially offer better glycemic control after lunch than insulin glargine.

This study compare the effect of various liquid diets on 24-h glycemic variability in diabetes patients on tube feeding.The study included type 2 diabetes patients in whom percutaneous endoscopic gastrostomy had been performed for dysphagia as a sequela of cerebrovascular disease and who had been put on tube feeding with a standard high-carbohydrate liquid diet (HCD). Once stable glycemic control was achieved, these patients were continuously monitored for glucose levels for 5 days on continuous glucose monitoring. Of the 14 patients included, seven were given HCD on day 1, a low-carbohydrate/high-monounsaturated fatty acid liquid diet (LCD) on Days 2 and 3, and a isoleucine-containing liquid diet (ICD), which is known to promote glycemic uptake by skeletal muscle, thus suppressing increases in glucose levels, on Days 4 and 5, with the remaining seven given the same diets but ICD given on Days 2 and 3 and LCD given on Days 4 and 5. All comparisons were made under the same caloric conditions (caloric intake, 800-1200 kcal/day).The 24-h mean glucose level was significantly lower with LCD and ICD than with HCD but was also significantly lower with LCD than with ICD. On the other hand, the SD of 288 glucose levels over a 24-h period, 24-h total area for glycemic fluctuations, and mean amplitude of glycemic excursion were significantly lower with LCD than with HCD or ICD, whereas they did not differ significantly between HCD and ICD.LCD and ICD led to significant decreases in mean glucose levels, compared with HCD. However, of the diets compared, LCD had the greatest effect on glycemic variability in these patients on tube feeding.

We compared the effects of miglitol as an add-on to bolus insulin and dose-intensified bolus insulin on postprandial glycemic excursions by continuous glucose monitoring (CGM).The glucose levels of 21 type 2 diabetes patients admitted for glycemic control were monitored for three consecutive days by CGM after stable glycemic control was achieved with bolus or basal-bolus insulin therapy. During the 3-day period, bolus insulin administration was continued in 11 patients on Day 1; the dose of bolus insulin in these patients was increased by 2 U before each meal on day 2, and on day 3, 50 mg of miglitol was administered before each meal in addition to the initial dose of bolus insulin given on Day 1. In the remaining 10 patients, the order of administration on Day 2 and Day 3 was reversed.Of the glycemic fluctuations observed during the 24-h period, postprandial glycemic excursions showed a greater reduction during treatment with dose-intensified bolus insulin and during treatment with miglitol plus bolus insulin than during treatment with bolus insulin alone; however, miglitol plus bolus insulin treatment had a more potent effect than treatment with dose-intensified bolus insulin on reducing postprandial glycemic excursions immediately after meals. Changes in area under the curve (ΔAUC) occurring within 1 h and 2 h after each meal were significantly smaller during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin, whereas ΔAUC within2 h after each meal, except dinner, was significantly greater during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin.Our findings suggest that miglitol as an add-on to bolus insulin in patients with type 2 diabetes may be one of the beneficial therapeutic options that provides a more rigorous postprandial glycemic control without increasing the risk for hypoglycemia before the next meal.

The intensive treatment aimed at achieving optimal A1C may increase a risk of hypoglycemia. Therefore, we examined the rate and duration of hypoglycemia (70 mg/dL) and the duration of hyperglycemia (≥200 mg/dL) according to their A1C status, using continuous glucose monitoring (CGM) in Japanese patients with type 2 diabetes who were treated with hypoglycemic agents.Forty subjects were equally divided into three groups according to their A1C levels (low, intermediate, and high A1C groups). The 24-h CGM data were collected immediately upon admission to hospital with the patients continuing to take the same medications they had prior to hospitalization.There was a significant difference in the total duration of hyperglycemia among the groups, with the low A1C group having a median duration of hyperglycemia of 50 min (25-75(th) percentile, 0-550 min) compared with 302.5 min (220-500 min) in the intermediate A1C group and 660 min (185-830 min) in the high A1C group. However, the incidence rate and total duration of hypoglycemia were similar for all A1C groups.The A1C level did not predict the presence or the duration of hypoglycemia.