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Authors and colleagues have continued clinical diabetic research in the light of Continuous Glucose Monitoring (CGM) and M value. M value is calculated from the daily profile of blood glucose, and it indicates the total numerical value of two factors, which are average blood glucose and mean amplitude of glycemic excursions (MAGE). The case is 53 years old female with Type 1 diabetes mellitus (T1DM), who was on multiple daily insulin injection (MDI). Using FreeStyle Libre, blood glucose was studied for 14 days. Average blood glucose in a day was 169 mg/dL, 163 mg/dL, 164 mg/dL and 166 mg/dL in day 3,5,9,11, respectively with almost same level. In contrast, the levels of the M value distributed widely from 12.5 to 98.3. A discrepancy of HbA1c was found between estimated value and laboratory data on out clinic, which was 7.4% and 8.0%, respectively. These results suggest that there would be rather large difference in MAGE even though the average blood glucose was almost the same in the 4 days. Furthermore, this investigation would be beneficial for check the detail blood glucose variability associated with various activities, and for better and stable control of blood glucose in T1DM.

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.

Background: Authors have continued research for meal tolerance test (MTT) by calorie restriction diet (CRD) and low carbohydrate diet (LCD), besides M value and glucose variability. Methods: Subjects were 38 patients of two groups. Group-1 has 19 patients (57.6±12.9 years) with type 2 diabetes mellitus (T2DM) and positive glutamic acid decarboxylase antibody (GADA), which is possible to latent autoimmune diabetes in adults (LADA). Group-2 has recruited 19 cases with T2DM and negative GADA, who showed age, sex, glucose variability-matched subjects. They were given CRD on day 1-2, and LCD day 3-14, and biomarkers were compared between Group-1 and Group-2. Results: Average values of the daily profile of blood glucose on day2(CRD)/day4(LCD) in Group-1 vs 2 were studied. Obtained data were 202/148 mg/dL vs 205/143 mg/dL, respectively with similarity. However, M value showed 174/58 vs 179/22, respectively with difference. There were significant correlations of M value between day2 and day4 in Group-1 vs Group-2. Further, both showed contrast tendency, associated with wide distribution vs narrow distribution, respectively. Conclusions: These results suggested that Group-1 with positive GADA may have insufficient pancreas secretion compared with that of Group-2, and these data may become a basal reference for future study of LADA.

Background: Authors and collaborators have continued clinical research for Low Carbohydrate Diet (LCD) and Calorie Restriction Diet (CRD), glucose variability and M value. We investigated patients with Type 2 Diabetes Mellitus (T2DM) with positive Glutamic Acid Decarboxylase Antibody (GADA). Subjects and methods: Subjects were 12 patients with T2DM showing positive GADA (group 1). They were given CRD on day 1,2, and LCD on day 3-14. Daily profile of blood glucose was measured each day, and data were calculated to M value expressing average glucose and Mean Amplitude of Glycemic Excursions (MAGE). Further, 12 T2DM cases with negative GADA were recruited, who were age-, sex-glucose-related data-matched (group 2). Results: Data of group 1 were as follows: age 54.9 ± 14.3 yo, HbA1c 7.1 ± 0.9%, average blood glucose and M value on day 2 vs 4 were 187 (157-255) vs 145 (114-172), 76.9 (45.9-278) vs 27.2 (19.3-83.5), respectively. In group 2, M value on day 2 vs 4 were 69.9 (37.8-149) vs 5.8 (3.5-13.3), respectively. Group 1 showed insufficient decreased glucose in M value. Discussion and conclusion: These results suggested that cases with positive GADA would have insufficient insulin secretion in response to LCD, and may lead to Slowly Progressive Insulin-Dependent Diabetes Mellitus (SPIDDM) status in the future.

Astaxanthin is a carotenoid that is present in high quantities in the meat of fish like salmon and the shells of shrimp and crab. It exhibits free radical scavenging antioxidant activity when consumed di- etarily. Astaxanthin is absorbed by the small intestine before exerting its antioxidant effect; however, a portion of dietary intake remains unabsorbed in the digestive tract and reaches the large intes- tines . We hypothesized that astaxanthin may exert its antioxidant action in the large intestine to influence the gut microbiota. In this review we introduce the results of two studies of astaxanthin. Firstly, a clinical trial targeting post-menopausal women screened for high oxidative stress burden. Astaxanthin was administered orally for eight weeks in order to examine its effects and safety, and subjects were surveyed for any changes in subjective symptoms. Secondly, in a mouse model, real time PCR (polymerase chain reaction) was used to examine the ability of astaxanthin to prevent changes in the enteric flora induced by a high-fat diet. When fat intake increases due to changes in diet, the equilibrium between the various species that constitute the intestinal flora is altered. As a result, degenerative changes in lifestyle-related disease and aging of the host are promoted. Here we find that the intake of astaxanthin was able to inhibit these changes in the gut microbiota of mice induced by a high-fat diet. Even in humans, it is highly probably that the unabsorbed astaxanthin that remains in the intestinal tract exerts a positive effect against disturbance of the intestinal flora caused by a high-fat diet., Astaksantin je karotenoid prisutan u velikom količinama u mesu riba poput lososa i oklopima kozica i rakova. Kada se uzima kao hrana ispoljava svoju sposobnost hvatanja slobodnih radikala i antioksidativnog djelovanja. Prije no što započne svoje antioksidativno djelovanje apsorbira se preko tankog crijeva, međutim , dio ostaje neapsorbiran i dospijeva u debelo crijevo. Razmatrali smo mogućnost da astaksantin pomoću svojih antioksidativnih svojstava može utjecati na crijevnu mikrobiotu. U okviru ovog preglednog rada osvrnut ćemo se na rezultate dvaju istraživanja. Prvo je kliničko ispitivanje usmjereno na postmenopauzalne žene koje su prošle screening na opterećenost oksidativnim stresom. Astaksantin su dobivale oralno kroz 8 tjedana kako bi se procijenili njegovi učinci i sigurnost, a ispitanice su anketirane vezano za promjene u subjektivnim simptomima. Dru- gi, mišji model, koristio je PCR (Lančanu reakciju polimeraze) u pravom vremenu kako bi ispitao potencijal astaksantina u sprječavanju promjena u crijevnoj flori induciranih dijetom bogatom mas- tima. Pri dijeti bogatoj mastima povećava se unos masti što narušava ravnotežu raznih vrsta koje sačinjavaju intestinalnu floru. Posljedična neravnoteža rezultira degenerativnim promjenama i boles- tima vezanima za način života. U ovom istraživanju nalazimo da unos astaksantina može spriječiti promjena u mikrobioti miševa izazvane prehranom bogatom mastima. Čak i u ljudi je za vjerovati da neapsorbirani astaksantin koji ostaje u debelom crijevu ima pozitivan učinak protiv poremećaja uzrokovanih prehranom bogatom mastima.

Background: Continuous Glucose Monitoring (CGM) has been in focus for treatment of diabetes. Recently, a sensor-based flash glucose monitoring system, FreeStyle Libre (Abbott), has been introduced to clinical practice. Case and results: The patient was 53 year-old female with type 1 diabetes mellitus (T1DM), who showed BMI 25.1 kg/m2, HbA1c 9.5% in January, 6.0% in June and 7.7% in November, 2017 as data on outclinic. CGM measured glucose every 15 minutes in 24 hours for 14 days on June and November, and estimated HbA1c was 5.4% and 6.1%, respectively with discrepancy. Discussion and conclusion: The beneficial points of FreeStyle Libre have been accurate, convenient and small size for clinical use for lessen hypoglycemia episodes. Key benefits of CGM monitoring are frequency of testing, trends, alarms, therapy optimization. Former studies for FreeStyle Libre tended to show lower values and larger mean absolute relative difference (MARD) in lower range of glucose levels, suggesting possible cause of the discrepancy for HbA1c levels. FreeStyle Libre for CGM would lead to better balance optimization of glucose control and current results would become basal data for future investigation of CGM.

Background: Arguments have continued about Low Carbohydrate Diet (LCD) and Calorie Restriction (CR). Authors have reported clinical research of LCD and Morbus (M) value. Subjects and Methods: Subjects enrolled are 84 patients with Type 2 diabetes mellitus (T2DM), 60.9 ± 10.9 years. The protocol were as follows: 1) CR diet on day 1, 2 with 60% carbohydrates, and LCD on day 3-14 with 12% carbohydrates, 2) Daily profile of blood glucose 7 times a day on day 2 (CR) and day 4 (LCD), 3) urinary C-Peptide radioimmunoassay (u-CPR) excretion, 4) M value calculation, 5) investigation of these data with correlation. Results: Subjects were classified into 4 groups according to M value, which were .4–21, 23–66, 29–192, 200–728, respectively. HbA1c value was 6.2, 8.0, 7.8, 9.2 %, respectively. Blood glucose in median from day 2 to day 4 were 123 to 107 mg/dL, 164 to 130 mg/dL, 193 to 156 mg/dL, 277 to 201 mg/dL, respectively. M value in median from day 2 to 4 was 6.3 to 9, 41 to 7, 108 to 16, 367 to 88, respectively. u-CPR was 88 to 58, 53 to 35, 65 to 52, 74 to 64, respectively. There were significant correlations among among glucose, M value and u-CPR. Discussion and Conclusion: Average glucose, M value and u-CPR decreased remarkably on day 4. As average glucose and M value were higher, decrease degree were larger. These results suggested that carbohydrate in meal would influence glucose variability in T2DM. Our data would become basic data for pathophysiological analysis of glucose variability research in the future.

Background: Diabetes has been great problem worldwide. Continuous Glucose Monitoring (CGM) has been in focus, and useful CGM, FreeStyle Libre (Abbott) has been introduced to clinical ordinary practice of medicine. Case and results: The patient was 57 year-old female with type 1 diabetes mellitus (T1DM), who showed BMI 20.6 kg/m2, HbA1c 8.6%. She was on CGM measured glucose every 15 minutes in 24 hours for 14 days. Treatment included 3 times of Insulin Aspart and once of Insulin Glargin. She showed characteristic pattern of blood glucose profile according to the working schedule of the day. Discussion and conclusion: The beneficial points of FreeStyle Libre have been convenient and accurate for clinical use for reducing hypoglycemia episodes. Treatment using CGM associated with multiple daily insulin injection (MDI) confers similar or greater benefits for glycemic profile. When evening insulin was not injected one day, blood glucose increased 320 mg/dL, suggesting 64 g of carbohydrate ingested for supposed calculation. These results suggest that CGM could recommend the timing and doses of insulin injection according to the lifestyle of the patients with clinical merit.

Background: Authors have continued research concerning Low Carbohydrate Diet (LCD) and its related biomarkers. We also investigated correlation among several factors such as daily profile, fasting and average of blood glucose, Morbus value, and insulin and C-peptide. Subjects and Methods: Subjects were patients with type 2 diabetes mellitus (T2DM), classified into three groups due to HbA1c value. Methods included 1) basal blood exams, 2) intake of Calorie Restriction (CR) meal with 1400kcal/day with 60% of carbohydrates, 3) check of daily blood glucose 7 times a day, 4) calculation of average glucose and M value, 5) analyses of biomarkers. Results: Average blood glucose was 168 mg/dL, 206 mg/dL, 265mg/dL in low, middle, high group, respectively. Fasting ratio of C-peptide/glucose in 3 groups was 0.37, 0.34, 0.26, respectively period. There was significant correlation among HbA1c, M value and fasting ratio of C-peptide/glucose. Discussion and Conclusion: Among 3 groups, high group revealed lower tendency of fasting C-peptide and fasting ratio of C-peptide/glucose than other groups, suggesting that high group might has lower ability of insulin secretion. Fasting ratio of C-peptide/glucose would be useful for indicating beta cell function and predicting insulin requirement in clinical practice.

Background: Authors and colleagues have reported nutritional research so far concerning Low Carbohydrate Diet (LCD). Formerly, we proposed useful method for insulin response to 70 g of carbohydrate. Similarly, C-peptide index for Carbohydrate-70 (CPI-Carbo70) is studied and proposed in this report. Subjects and Methods: Subjects enrolled were diabetic patients that were divided into three groups due to diabetic severity. Among them, average HbA1c was 6.6%, 7.8%, 10.0% in low, middle, high group, n=15, 15, 16 respectively. As in-patients, they were on Calorie Restriction meal on day 1 and 2, which has 1400kcal/day with carbohydrates 60%, lipids 25%, protein 15%. On day 2, breakfast with carbohydrate 70 g was provided, and glucose and C-peptide levels were measured at 0, 30 minutes. Results: Biomarkers were analyzed in 3 groups. Increment C-peptide (CP) and CPI-Carbo70 in 3 groups were 0.58, 0.57, 0.27 and 2.1, 3.2, 1.2, respectively. As for M value, CP increment, CP on 30 min, CPI-Carbo70 was investigated, which were lower in high group. There is significant correlation between HbA1c and CPI-Carbo70 (p<0.05). Discussion and Conclusion: CPI-Carbo70 may be useful for evaluating pancreas function and glucose variability. These data could be basal and useful in the light of clinical evaluation and further research development.

Background: Discussion concerning Carbohydrate Restriction (CR) and Low Carbohydrate Diet (LCD) has been continued. Authors formerly proposed insulinogenic index-carbohydrate 70 g (IGI-carbo70). Along this, C-peptide index for Carbohydrate-70 g (CPI-Carbo70) is studied. Subjects and Methods: Subjects were 46 patients (62.5 yo. in average) with Type 2 diabetes mellitus (T2DM) and admitted for evaluation. CR diet was given on day 1-2 with 60% carbohydrates, 25% lipids and 15% protein with 1400 kcal/day. On day 2, breakfast with Carbo70 was given, and glucose and C-peptide (CP) were measured at 0 and 30 minutes and analyzed. Results: As basal data, average HbA1c was 8.1%, median HbA1c, average daily glucose, median M value was 7.7%, 187 mg/dL, 71, respectively. In response to Carbo70, median values of glucose-0, glucose-30, delta-glucose, CP-0, CP-30, delta-CP was 142, 186, 22 mg/dL, 0.9, 1.4, 0.4 ng/mL, respectively. CPI-Carbo70 was 1.54 in median. There were significant correlation between glucose and CP on 0, 30min, delta-0-30min (p<0.01). Significant correlation was observed between CPI and HbA1c, CPI and M value (p<0.01). Discussion and Conclusion: CPI-Carbo70 might be useful for evaluating pancreas function and glucose variability in clinical research. Current data would become the fundamental data for the future diabetic practice and research development.