Remarkable Improvement of Glucose Variability by Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors using Continuous Glucose Monitoring (CGM)

Authors have continued clinical research of Calorie Restriction (CR) and Low Carbohydrate Diet (LCD) and present a case with precise observation of continuous glucose monitoring (CGM). The patient is 38 years-old females with type 2 diabetes mellitus (T2DM), who showed BMI 19.6, postprandial blood glucose 277 mg/dL. HbA1c 12.6%, glycoalbumin 31.8% (11.6-16.4), HOMA-R 2.8, HOMA-β 8.5, urinary excretion of C-peptide 67 μg/day, and normal range of liver, renal, lipid exams. She was given three stage intervention. The protocol was • Day 1-2; CR meal with 60% carbohydrate, • Day 3-5; LCD meal with 12% carbohydrate, • Day 6-13; LCD+Sodium–glucose cotransporter 2(SGLT2) inhibitors (Suglat 50 mg, Ipragliflozin L-Proline). The glucose variability was monitored using FreeStyle Libre Pro (Abbott) for 14 days. Blood glucose was decreased as • More than 350 mg/dL, • 180-200 mg/dL, • 100-150 mg/dL in day 7-9, and 90-120 mg/dL in day 10-13. Acute decrease of blood glucose was found 3 hours after giving Suglat, which was remarkable finding. These results suggest the improving glucose variability of LCD in short term, the acute and strong efficacy of SGLT2 inhibitors for glucose metabolism, and clinical usefulness of simultaneous observation of glucose fluctuation

Investigation of Low Carbohydrate Diet for Type 2 Diabetes Mellitus with Elevated Immunoreactive Insulin

Background: There are discussion of Calorie Restriction (CR) and Low Carbohydrate Diet (LCD). Authors and colleagues have continued research concerning LCD, CR and Morbus (M) value. Furthermore, this study also included homeostasis model assessment (HOMA). Subjects and Methods: Subjects enrolled were 40 type 2 diabetes mellitus (T2DM) cases with more than 10 μU/mL of fasting immunoreacitve insulin (IRI). Methods included fundamental tests such as glucose, IRI, HOMA-R, HOMA-β, average blood glucose on day 2 and 14 during CR and LCD meal. Results: Current data were in the following: average age 56.8 ± 12.3 years old, median values are HbA1c 7.2%, fasting glucose 141 mg/dL, IRI 13.1 μU/mL, HOMA-R 4.6, HOMA-β 57.1. Median values on day 2 vs 14 were average blood glucose 160 vs 120 mg/dL, M value 37.1 vs 7.4, Triglyceride 137 vs 97 mg/dL, respectively. M value showed significant correlation with HOMA-R (p<0.05) and HOMA-β (p<0.01). Discussion and Conclusion: The results suggested that LCD showed clinical effect for decreasing of glucose and M value in glucose variability and those patients would have insulin resistance and decreased β cell function. Furthermore, these findings would become basal and useful data for future research in this field

Rapid Efficacy of Low Carbohydrate Diet for Diabetic Patient by Use of FreeStyle Libre

In recent years, continuous glucose monitoring (CGM) has been introduced and used in clinical diabetic research. Authors have investigated research about Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) and developed medical and social LCD movement through Japan LCD Promotion Association (JLCDPA). In this study, a case with remarkable improving effect for change from CR to LCD is presented using CGM. The case is 41 years-old female with type 2 diabetes mellitus (T2DM). She was newly diagnosed as T2DM with HbA1c 11.0%, glucose >400 mg/dL, BMI 26.0, AST 30 IU/mL, Hb 16.3 g/dL. She was given CR meal with 60% carbohydrate on day 1 to 4, and LCD meal with 12% carbohydrate on day 5 to 7. Daily profile of blood glucose showed 200-400 mg/dL in day 1-4, 160-240 mg/dL on day 5 and 110-150 mg/dL on day 7. FreeStyle Libre (Abbott, USA) has been valid and useful medical apparatus for monitoring the the detailed fluctuation of blood glucose. Blood glucose value was immediately decreased just after starting LCD, and the short-term effect of the LCD was found. These results would become basal and reference data and contribute to the development of future research

Short Term Effect of Low Carbohydrate Diet in Diabetic Male Patients

Background: Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) have been discussed for long. Authors have continued clinical research on LCD, CR and M value. Subjects and Methods: Subjects were 67 male patients with type 2 diabetes mellitus (T2DM). Methods were i) daily profile of blood glucose, average glucose, M value for CR meal, ii) same exam of i) after 2 days of LCD, iii) Delta and AUC ratio for 70g of carbohydrate (0 - 30 minutes) in meal tolerance test (MTT), iv) Triglyceride check for 12 days of LCD, v) analyses of correlation of biomarkers. Results: Obtained data were as follows: average age 61.2 years old, median values are HbA1c 7.8%, fasting glucose 151 mg/dL, IRI 4.4 μU/mL, HOMA-R 2.1, HOMA-β 15.9, respectively. Median values on day 2 vs 14: average glucose 198 vs 151 mg/dL, M value 134 vs 14.4, respectively. AUC ratio for Carbo70 showed more separate distribution as insulin secretion ability than Delta ratio. There were significant correlations among HbA1c, average glucose and M value. Discussion and Conclusion: These results suggested that LCD would have beneficial effects for glucose variability. Furthermore, it would become basal and reference data for the future research development in this field

Response of Insulin Secretion to Small Amount of Meal on Low Carbohydrate Diet (LCD)

Diabetic nutritional therapy has been changing from Calorie Restriction (CR) to a Low Carbohydrate diet (LCD). Authors et al. have developed LCD medically and socially through the Japan LCD promotion association (JLCDPA), and proposed meal tolerance test (MTT) using LCD breakfast. For our research protocol, healthy subjects (n=8, M/F=4/4, BMI 20.5kg/m2) received 75g oral glucose tolerance test (OGTT) and MTT, and changes in blood glucose and immunoreactive insulin (IRI) were measured. LCD meal included energy 307kcal, protein 13.8g, fat 23.9g, and carbohydrate 5.7g. The results from 0-30 min in average showed: i) 75gOGTT; 87.3-124.6mg/dL, 4.9-41.4μU/mL, ii) LCD; 90.3-84.3mg/dL, 5.4-12.2μU/mL, respectively. Decreased glucose may be from enough ability to secrete insulin to a glucose stimulus. These results would become reference data for future diabetic research

Difference of Glucose variability between Low Carbohydrate Diet (LCD) and Calorie Restriction (CR)

Background: There have been lots of discussion and controversy concerning the difference between Low Carbohydrate Diet (LCD) and Calorie Restriction (CR). The important points include glucose variability, glucose-lowering effect, weight reduction degree and influence on lipid metabolism. Subjects and Methods: Enrolled subjects were 47 patients with T2DM. Methods included the study for providing subjects CR meal with 60% carbohydrate on day 1-2 and LCD meal with 12% on day 3-14. Daily profile of blood glucose was studied seven times a day on day 2 and day 4. Further, biomarkers including HbA1c, average blood glucose, and M value were investigated and analyzed for mutual correlations. Results: Subjects were categorized into 4 groups according to the average glucose value, which were 124mg/dL, 160mg/dL, 206mg/dL, and 281mg/dL, respectively. Data in 4 groups were as follows: Number; 12,12,12,11, Male/Female; 6/6, 3/9, 6/6, 5/6, mean age; 51.3, 60.9, 65.3, 60.6 years old, HbA1c; 6.1%, 7.1%, 8.0%, 8.9%, fasting glucose on day 2; 109 mg/dL, 136 mg/dL, 178 mg/dL, 224mg/dL, respectively. Daily profiles of blood glucose in 4 groups on day 4 were remarkably decreased than those of day 2. The levels of M value indicating average blood glucose and mean amplitude of glycemic excursions (MAGE) on day 2 vs 4 were compared in 4 groups, which are 7.1 vs 10.5, 39.7 vs 5.0, 139 vs 15.7, 367 vs88, respectively. Correlations among HbA1c, M value and average blood glucose showed significant correlations (p<0.01). Discussion and Conclusion: Obtained results showed that the distribution of daily profile of blood glucose in 4 groups is separated. Further similar tendency was observed in HbA1c and M value. There was remarkable decrease of blood glucose from CR to LCD. These findings suggested that LCD would have remarkable efficacy for improving glucose variability. Furthermore, obtained findings could become basal and reference data for the developing research for CR and LCD

Improved Glucose Variability by Low Carbohydrate Diet in Female Diabetic Patients

Background: Discussion of Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) has been observed. Authors have continued clinical research on LCD, CR and Morbus (M) value for years. Subjects and Methods: Subjects were 81 female patients with type 2 diabetes mellitus (T2DM). Methods included i) basal tests on diabetes, ii) daily profile of blood glucose, average glucose, M value for CR meal, iii) same exam of ii) for 2 days of LCD, iv) Triglyceride check for 12 days of LCD, v) analyses of these biomarkers. Results: Obtained data were as follows: average age 62.4 years old, median values are HbA1c 7.2%, fasting glucose 147 mg/dL, IRI 6.8 μU/mL, HOMA-R 2.5, HOMA-β 28.7, respectively. Median values on day 2 vs 14: average glucose 173 vs 130 mg/dL, M value 62.4 vs 9.6, respectively. There was significant correlations between M value and HbA1c (p<0.01), and between average glucose and HbA1c (p<0.01). Triglyceride value was decreased for 12 days of LCD from 103 to 79 mg/dL. Discussion and Conclusion: The results suggested that LCD showed positive effects for improving glucose variability and lipid metabolism. Furthermore, these findings would become fundamental and reference data for the future research development in this field

Study of Efficacy for Low Carbohydrate Diet (LCD) and Homeostasis Model Assessment (HOMA) in Diabetes

Background: Discussion of Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) has been continued. Authors have reported research about LCD, CR and Morbus (M) value. In current study, homeostasis model assessment (HOMA) was also investigated together, with the purpose of study for insulin resistance and secretory ability. Subjects and Methods: Subjects were 56 type 2 diabetes mellitus (T2DM) patients with fasting immunoreacitve insulin (IRI) in 5-10 μU/mL. Methods included basal tests, glucose, IRI, HOMA-R, HOMA-β, daily profile of glucose on day 2 and 14 during LCD meal. Results: The obtained data were as follows: average age 63.1 ± 10.5 yo., average HbA1c 7.9 ± 1.9%. Median values are fasting glucose 150 mg/dL, HOMA-R 2.6, HOMA-β 25.9. Divided into 4 groups due to M value, HOMA-R and HOMA-β in each group were 2.3, 2.6, 2.2, 3.5, and 46.1, 40.7, 24.3, 15.9, respectively. Median values on day 2 vs. 14 were: average blood glucose 181mg/dL vs. 139mg/dL, M value 60.7 vs. 10.2, triglyceride 129 mg/dL vs. 89.5 mg/dL. The level of M value showed significant correlation to average glucose, M value, and HOMA-β (p<0.01). Discussion and Conclusion: The results suggested that patients have insulin resistance and decreased β cell function, LCD would have effects for improving glucose variability, and data would be useful and beneficial for future research

Evaluating pancreas function by meal tolerance test (MTT) in diabetes

Background: Diabetic nutritional treatment involves the discussion of Low Carbohydrate Diet (LCD) and Calorie Restriction (CR). Authors have initiated and developed LCD in Japan and continued clinical research. In this study, we investigated glucose variability in patients with type 2 diabetes mellitus (T2DM). Subjects and Methods: Subjects were 60 T2DM patients of 62.7 years in average with its fasting immunoreactive insulin (IRI) less than 5μU/mL. Methods include basal blood test, daily profile of blood glucose and insulinogenic index (IGI) for 70g of carbohydrate (0-30min) in CR breakfast. Correlation among these and comparison in 4 groups categorized by Morbus value were analyzed. Results: Basal data revealed HbA1c 7.9%, daily glucose 222 mg/dL in average, and Triglyceride 83 mg/dL, Morbus value 150, HOMA-R 1.1, HOMA-β 11.0 in median. Delta Ratio of IGI and AUC ratio of IGI showed significant correlations with M value and HbA1c (p<0.01). Discussion and Conclusion: Meal Tolerance Test (MTT) has been recently used for convenient methods and meaningful results. AUC ratio suggests a little superior than Delta ratio for its higher correlation coefficient. These results would become the basal data in this field, and further development of related research is expected in the future

A Trial of Analysis Method for Insulin Secretion Response to Carbohydrate Loading

Authors et al. have continued diabetic practice and research for long, and started Low Carbohydrate Diet (LCD) first in Japan. We developed social LCD movement by Japanese LCD Promotion Association (JLCDPA), and proposed petite-, standard-, super LCDs with carbohydrate 40%, 26%, 12%, respectively. Methods included 9 healthy medical staffs and two exams of 75g Oral Glucose Tolerance Test (OGTT) and Meal Tolerance Test (MTT). MTT means super-LCD breakfast with carbohydrate 6g. Results showed that blood glucose / immunoreactive insulin (IRI) at 0-30 min on average changed 88.0-130.6 mg/dL/5.1-46.5 μU/mL for GTT, and 90.1-86.3 mg/dL/4.8-12.5 μU/mL for MTT. IRI responses in GTT and MTT were calculated by 3 methods, which are i) increment (delta), ii) Area Under the Curves (AUC), iii) Multiple (times) of basal value. Both data from GTT and MTT showed significant correlation in i) and ii) (p<0.05), but not significant in iii) (p=0.07, n=9). These results suggested that insulin secretion in MTT would be enough and relatively excessive for 6g of carbohydrate, leading to relatively decreased glucose at 30 min. Current analyses methods will become some reference for future development of diabetic research