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Objective: 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., Patients and Methods: 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., Results: 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., Conclusions: 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.

Background: 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., Patients and Methods: 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., Results: 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 (P<0.01), whereas there was no significant change seen in regard to the proportion of time in hypoglycemia with or without add-on treatment with sitagliptin., Conclusions: 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.

Objective: This study compare the effect of various liquid diets on 24-h glycemic variability in diabetes patients on tube feeding., Patients and Methods: 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)., Results: 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., Conclusions: 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.

Background: 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)., Subjects and Methods: 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., Results: 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 within >2 h after each meal, except dinner, was significantly greater during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin., Conclusion: 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.

Background: This study was performed to examine the efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes using continuous glucose monitoring (CGM) of 24-h glycemic changes., Subjects and Methods: The study was a prospective open-label pilot study in patients with type 2 diabetes who were admitted to our hospital and treated with sitagliptin alone or concomitantly with another oral hypoglycemic drug. CGM was performed for 2 days before sitagliptin administration and for another 2 days after administration. The average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, mean amplitude of glycemic excursions (MAGE), and hyperglycemic and hypoglycemic time periods were compared before and after administration., Results: Sitagliptin administration alone and with a concomitant drug decreased the average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, MAGE, and hyperglycemic time, compared with these parameters before administration. There were significant correlations between the average 24-h blood glucose level before administration and the decrease in the average 24-h blood glucose level after administration and between MAGE before administration and the decrease in MAGE after administration., Conclusions: Sitagliptin decreased the average glycemic level and also improved 24-h glycemic fluctuation, including postprandial hyperglycemia.

During the course of treatment with a DPP-4 inhibitor, 24-hour glycemic variations were assessed by continuous glucose monitoring to evaluate the magnitude of postprandial glycemic excursions as well as nighttime/late-night glycemic variations. The DPP-4 inhibitor given alone or in combination with a sulfonylurea (SU) reduced not only the 24-hour mean glucose level as equivalent to the HbAlc value but also the SD of 288 glucose levels for 24 hour and the mean amplitude glucose excursions (MAGE). Particularly, the DPP-4 inhibitor, when given in addition to SU, produces not only additive reductions in mean glucose levels but also reductions in the magnitude of glycemic variations, while at the same time exhibiting the potential to serve as a glucose modulator in low glucose levels. Furthermore, while monotherapy with a DPP-4 inhibitor improves postprandial hyperglycemia, combination therapy with a DPP-4 inhibitor and an alphaglucosidase inhibitor leads to additive improvements in postprandial hyperglycemia, thus exhibiting the potential to flatten the 24-hour glycemic variations. In summary, when assessed for its effects on 24-hour glycemic variations, the DPP-4 inhibitor produces reductions not only in the 24-hour mean glucose level but also in the magnitude of glycemic excursions, thus likely representing a new type of anti-diabetic agent that combines the merits of an SU, which potently lowers HbAlc primarily by reducing fasting glucose levels, and an alpha-glucosidase inhibitor, which reduces the magnitude of glycemic variations primarily by lowering postprandial glucose levels.

Background: The objective of this study was to evaluate the effects of the α-glucosidase inhibitor acarbose on glucose fluctuations in patients with type 2 diabetes using continuous glucose monitoring (CGM)., Methods: CGM was performed for 4 days (72 h), and acarbose at 300 mg/day was administered on two of these days but not on the other two days. The effects on blood glucose fluctuations were evaluated., Results: We recruited a total of 10 patients (five men and five women) with a mean ± SD age of 63.1 ± 12.1 years, body mass index of 22.6 ± 5.4 kg/m(2), and glycohemoglobin of 9.9 ± 1.9%. During treatment with acarbose, significant decreases in median (range) SD of 24-h mean blood glucose (22.48 [6.39-47.22] mg/dL vs. 32.78 [18.83-58.93] mg/dL, P = 0.004), 24-h blood glucose fluctuations (453.27 [128.51-903.94] mg·h/dL vs. 677.05 [358.03-1,234.57] mg·h/dL, P = 0.002), and mean amplitude of glycemic excursions (65.00 [18.17-117.50] vs. 97.09 [53.00-166.67], P = 0.010) occurred compared with no treatment., Conclusions: Acarbose reduced excessive blood glucose fluctuations.

Angiotensin II receptor blockers as a class are reported to act as insulin sensitizers. Of these, telmisartan has been shown to have additional unique peroxisome proliferator-activated receptor-gamma-mediated, insulin-sensitizing properties. In this study, investigators explored the effects of telmisartan on glycemic control and lipid metabolism in hypertensive patients with type 2 diabetes who had switched to telmisartan from another angiotensin II receptor blocker. The study subjects were 42 hypertensive outpatients with type 2 diabetes who were being treated with candesartan 8 mg/d and who agreed to switch to treatment with telmisartan 40 mg/d. Relevant laboratory variables were measured 6 mo before treatment switching, at the time of switching, and 6 mo after switching. No significant differences were noted in blood pressure, body mass index, or glycosylated hemoglobin among subjects before and after therapy was switched. No adverse reactions such as edema or hepatic toxicity were noted. No significant changes in fasting plasma glucose, fasting insulin, HOMA-R (insulin resistance as measured by the homeostasis model), preheparin lipoprotein lipase mass, high-density lipoprotein cholesterol, and free fatty acids were noted. Triglyceride levels were significantly decreased, however, and adiponectin levels were significantly increased (8.1+/-3.1 microg/mL at switching; 8.6+/-3.0 microg/mL 6 mo after switching; P<.01) after the switch to telmisartan therapy. Study results show that telmisartan did not affect glycemic control, but it improved lipid metabolism and adiponectin production in patients with type 2 diabetes, suggesting that AT(1)-receptor antagonism and selective peroxisome proliferator-activated receptor-gamma activation by telmisartan combine to account for observed effects on lipid metabolism and adiponectin production.

We investigated the relationship between insulin reaction and glycemic control in a 75-g oral glucose tolerance test of lipid in the paraspinal muscles using computed tomography (CT). The subjects were 79 males aged from 30 to 60 years old whose body mass index (BMI) was 25 or more. Those who had already been diagnosed as having type-2 diabetes mellitus in a regular health check and whose fasting plasma glucose was 126 mg/dl or more were excluded. Abdominal CT scan at the umbilicus level was conducted, and the visceral fat area (VFA) and subcutaneous fat area (SFA) were obtained. As an index of the relative lipid content within muscle, the mean skeletal muscle attenuation (MA) was determined. The age-adjusted odds ratio caused by the MA size for each variable was calculated. Compared with those with smaller intramuscular fat volume, those with larger volume demonstrated 8.75 times higher BMI, 3.73 times higher VFA and 2.88 times higher HOMA-IR. A significant difference was observed between the groups with high and low lipid content in the muscle in the values of Age, BMI, VFA, Fasting immunoreactive insulin (IRI) and HOMA-IR. It was suggested that MA of the paraspinal muscles reflected fat content, and this regional body composition parameter was closely related to insulin secretion response and glycemic control.

Objective: The aim of the present study was to determine the effects of dietary diacylglycerol (DG) on the metabolism of lipids and glucose in type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats., Methods: In experiment 1, the rats were orally administered 10 mL/kg of a triacylglycerol (TG) or DG emulsion (15% [w/v] oil), and the subsequent changes in the serum lipid levels were compared. In experiment 2, the rats were fed diets containing 15% DG or TG oil. After 22 weeks, the serum levels of lipids, glucose, and cytokines were determined. In addition, an oral glucose tolerance test (OGTT) was performed on the rats., Results: Administration of an oral fat load caused marked hypertriglyceridemia with a peak at 2 h. Oral DG loading reduced the serum TG increase; the difference between the groups was significant at 4 and 6 h (P < 0.05). Diacylglycerol also markedly reduced the serum free fatty acid concentration increase due to the fat load. After 22 weeks of feeding, dietary DG reduced serum TG levels in the non-fasting state. Moreover, an OGTT revealed enhanced glucose disposal in the DG-fed rats compared with the TG-fed rats. Serum levels of adiponectin, an important insulin-sensitizing adipocytokine, were higher in the DG-fed rats than in the TG-fed rats (P < 0.05). In addition, DG-feeding reduced serum levels of C-reactive protein, a cardiovascular risk factor (P < 0.05)., Conclusion: These results suggested that dietary DG improves lipid metabolism and glucose tolerance, and retards the progress of diabetes mellitus in OLETF rats.