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The case was 71-year-old male patient with type 2 diabetes mellitus (T2DM). He was diagnosed T2DM at the age of 61 associated with thirsty, polydipsia and fatigue. HbA1c value was 12.5% and blood glucose profile was 150-300 mg/dL. Just after starting low carbohydrate diet (LCD), his blood glucose kept under 150 mg/dL all day long. He continued good diabetic control as HbA1c 5.8-6.8% for 10 years. Some beneficial points are found: i) keeping LCD with the feeling not stressful but pleasant for observing the normal glucose level, ii) walking daily for 2 hours, iii) continuing educational activity in the walking association for DM and health care. iv) writing the diary for years every day, including exercise, meal, medicine, activities and so on, v) checking post-prandial hyperglycemia by meal tolerance test (MTT). For details of v), HbA1c was 6.5% in May 2021 and fasting glucose was 107mg/dL. Glucose values 45-min and 60-min after 3 meals showed 210-201-177mg/dL and 195-213-172mg/dL, respectively. His various continuing behaviors contributed satisfactory glycemic control. This article becomes reference in the diabetic practice and research.

Two patients with Type 2 Diabetes Mellitus (T2DM) were treated with Xultophy. Xultophy consists of degludec and liraglutide (IDegLira). It is the combination of long-acting insulin and Glucagon like Peptide-1 Receptor Agonist (GLP-1RA) and is characteristic for effective agent for improving glucose variability for patients with T2DM. However, clinical responses are not always satisfactory due to different complication and background of each patient. We have experienced two impressive T2DM cases. Case 1 was 59-year-old male with hypertension for 20 years and T2DM for 3 years. He was treated on Novolin 30R 30/21 units twice a day, and after that Xultophy 32 doses brought him successful glucose profile. Case 2 was 78-year-old male with hypertension, bronchial asthma, hyperuricemia, and others with heavy alcohol drinking for 50 years. He was formerly treated by Insulin detemir, Liraglutide, exenatide and Degludec/NovoRapid, but has been recently unstable in glucose control. Xultophy up to 40 doses could not successfully improve glucose variability. One of the less responsiveness to Xultophy would be due to impaired liver function. Clinical progress of both cases associated with several perspectives from various points of view are discussed in this article.

Type 2 diabetes mellitus (T2DM) need adequate diet, exercise and pharmacotherapy. Authors have continued diabetic practice and research on low carbohydrate diet (LCD), calorie restriction (CR), continuous glucose monitoring (CGM), and so on. The case is 50-year-old female patient with T2DM for 10 years. She has received insulin treatment with recent HbA1c 7.4 – 8.7%, then her glucose profile was studied on CGM by FreeStyle Libre. Treatment was changed from Glargine 15 units (until day 5) to Zultophy10-12 doses (after day 6), then her glucose variability showed remarkably improved. The average blood glucose on day 3, 5, 6, 8,10,13 was 174, 164, 125, 111, 101, 98 mg/dL, respectively. FreeStyle Libre showed estimated HbA1c as 6.2% and 44 mmol/mol.

The case was 57-year-old male with the past history of post-operation of Tetralogy of Fallot (TOF) at 11 years old. For dental problems, he visited a dentist and was diagnosed as periodontal diseases (PD) and Type 2 diabetes mellitus (T2DM) with 7.8% of HbA1c. His teeth showed moderate to severe PD and chronic periapical periodontitis due to carious teeth. He was treated for PD and T2DM in dental and internal medicine departments of the hospital. As our formula meal, super low carbohydrate diet (LCD) with 12% of carbohydrate ratio was started. Then, his weight decreased from 100kg to 90 kg in 3 months and HbA1c decreased from 7.8% to 5.4% in 4 months with normalized C-reactive protein (CRP) value. His clinical progress was satisfactory with effective results of dental treatment and LCD. Recent consensus guidelines by International Diabetes Federation (IDF) and European Federation of Periodontology (EFP) recommend the both treatments of PD and diabetes by dentist and internist together. Authors have continued clinical practice and research for years concerning LCD through Japan LCD promotion association (JLCDPA). This case would become some reference from PD and diabetic points of view.

Diabetes mellitus causes macrovascular, microvascular angiopathy, and increased cancer risk. Authors et al. have continued clinical practice and research on diabetes cases. Current case is impressive 79-year-old female with various diseases. They include asthma and COPD, steroid intake for years, sleep apnea syndrome (SAS), Continuous Positive Airway Pressure (CPAP) therapy, tongue cancer, arteriosclerosis, bone complications, Carpal tunnel syndrome (CTS), and so on. When she developed hyperglycemia with 9.0% of HbA1c, Xultophy® was started. It contains insulin degludec and liraglutide which is Glucagon-like peptide-1 receptor agonist (GLP-1 RA). HbA1c values decreased as 7.9%, 7.3%, 6.9%, 6.5% in 1-4 months, with remarkable effect. The satisfactory efficacy may be from double agents of Xultophy® or probable secondary diabetes due to continuation of steroid of the case. This report will be expected to be some reference in the future diabetic research development.

Among several kinds of nutritional therapy for diabetes, a low-carbohydrate diet (LCD) has been effective for weight reduction and improving glucose variability. Authors and colleagues have continued clinical practice, research and education for developing LCD through various activities of Japan LCD promotion association (JLCDPA). The diet protocol includes super-LCD, standard-LCD and petite-LCD, which has a carbohydrate ratio of 12%, 26% and 40%, respectively. Recommended food for LCD would be an egg, cheese, meat, tofu, beans and so on because of their less carbohydrate content. We hope further understanding and prevalence of LCD in health and medical care.

Continuous Glucose Monitoring (CGM) has been recently applied in the clinical diabetic practice. Authors have continued research of glucose variability. In this study, 51 year-old female patient with Type 1 diabetes mellitus (T1DM) was investigated. She has given multiple daily insulin injection (MDI) for long and her recent daily glucose profile was unstable. After applied with FreeStyle Libre, her blood variability was improved with the average glucose from 222 mg/dL to 135 mg/dL, which was partly from her motivation for better diabetic control. Thus, CGM may become a trigger to give beneficial influence for regular lifestyle of the patients.

Diabetes has been a crucial medical and social problem worldwide. For adequate nutritional therapy, there have been discussions concerning Calorie Restriction (CR) and Low Carbohydrate Diet (LCD). We have investigated glucose variability of diabetic patients applying CR, LCD, continuous glucose monitoring (CGM) and applied FreeStyle Libre which is flash glucose monitoring (FGM). The patient is a 40-year-old female with type 2 diabetes mellitus (T2DM), who showed BMI 20.7, postprandial blood glucose 257 mg/dL. HbA1c 12.1%, Glycoalbumin 31.6% (11.6-16.4), serum C-peptide 2.0 ng/ml and unremarkable data of liver function, renal, lipids. She was provided the intervention of three stages, which are i) CR with 60% carbohydrate in Day 1-2, ii) LCD meal with 12% carbohydrate in Day 3-5; iii) LCD + Sodium-glucose cotransporter 2 (SGLT2) inhibitor (Ipragliflozin L-Proline 50mg) in Day 6-12. The glucose profile was measured by FreeStyle Libre Pro (Abbott) for 14 days. The daily profile of blood glucose was abruptly decreased on Day 6. Time percentage of satisfactory blood glucose 70-180 mg/dL (/24h) was 0%, 0%, 2%, 14%, 0%, 54%, 100% in Day 1-7, respectively. These results suppose the acute clinical efficacy of SGLT2 inhibitor, and this report would become a reference for future diabetic practice and research.

From the biological point of view, humans have undergone various evolutions for long. Humans and monkeys are belonged to the primate species, which have neuroendocrine system (NES) with an important role in controlling several axes for regulating the growth, stress, metabolism and reproduction. There are important metabolic systems of glucose and also ketone bodies (KB) which can produce much energies. Recent topics for nutrition therapy include the comparison of calorie restriction (CR) and low carbohydrate diet (LCD). Continuing LCD meal to some strict degree can bring hyperketonemia, which may have beneficial effects on cardiovascular system and anti-cancer in humans.

Both humans and animals generate energy by tricarboxylic acid (TCA) cycle from carbohydrates, fats and proteins. Among them, carbohydrates axis seemed to be the main route for energy production so far. In the case of diabetes, however, the restraint of glucose metabolism would be beneficial by low carbohydrate diet (LCD) or newly-introduced oral hyperglycemic agent (OHA), Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i). Author and colleagues have developed LCD movement by Japan LCD promotion association (JLCDPA). Our lectures include useful and practical 3 LCD meals, which are petite-LCD, standard-LCD and super-LCD with carbohydrate content ratio as 40%, 26% and 12%, respectively.

In diabetic practice, continuous glucose monitoring (CGM) has been more used for glucose variability. Authors have reported and developed the clinical study of Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) through Japan LCD Promotion Association (JLCDPA). A diabetic case is presented with normalizing glucose variability by LCD meal checked by CGM. Case is 51 years female with type 2 diabetes mellitus (T2DM). At first visit, HbA1c was 10.0%, glucose was 288mg/dL, BMI 39.1, GOT 16IU/mL, HDL-C 33mg/dL, Triglyceride 152mg/dL. CR meal was provided on day-1 to day-5 and LCD meal with 12% carbohydrate on day-6 to day-13. Average glucose value from CGM was 292mg/dL, 235mg/dL, 160mg/dL, 140mg/dL, 124mg/dL in day 3,5,7,9,11 respectively. On day-13, total Ketone bodies (T-KB) 540μmol/L (-131), Acetoacetic acid (AcAc) 86μmol/L (-55) and 3-hydroxybutyric acid (3-OHBA) 454μmol/L (-85). Weight reduction was 5kg on day-14 and 11.2kg on day-70 with BMI 34.6. Thus, LCD showed a remarkable glucose-lowering effect in short term. FreeStyle Libre (Abbott, USA) seems to be a useful apparatus for monitoring the detailed fluctuation of blood glucose. These results would become fundamental and reference data and contribute to the LCD research development in the future.

Authors and collaborators have continued diabetic practice and research on low carbohydrate diet (LCD), continuous glucose monitoring (CGM), and so on. The case is a 64-year-old male with type 2 diabetes mellitus (T2DM) treated with multiple daily insulin injections (MDI). When his HbA1c was 8.2% before, he changed to take tofu instead of rice and bread. HbA1c decreased to 7.1% and 4kg of weight reduction in 2 months. Tofu is a traditional Japanese food made from soybeans, which is a suitable LCD with Protein:Fat:Carbohydrate (PFC) ratio=40:45:15 in this case. His HbA1c is recently unstable, then glucose variability was investigated by CGM using FreeStyle Libre. The glucose pattern was different due to his lifestyle, including working day, off day, playing golf, respectively. The average glucose was 143-167 mg/dL and the estimated HbA1c was 7.1%, whereas HbA1c in outclinic was 8.1%, respectively. This report will hopefully become reference data for future research.

Background: The problem of glucose variability has been in focus for type 1 diabetes mellitus (T1DM) on insulin treatment. Daily profile of blood glucose was studied on Continuous Glucose Monitoring (CGM) using Free Style Libre. Case presentation and results: Patient is 54 year-old T1DM female, with HbA1c 7.8%. The blood glucose variability was measured by Free Style Libre. Insulin therapy included multiple daily insulin injection (MDI) of Insulin Glargin and Aspart. The result revealed unstable blood glucose profile in day 1 and 2. After that, the level and fluctuation of blood glucose gradually decreased from day 3 to 14. Average blood glucose in a day was 174mg/dL, 159mg/dL, 138mg/dL, 125mg/dL and 110mg/dL, in day 2, 4, 7, 9, 11, respectively. There was a discrepancy of HbA1c between 7.8% by laboratory measurement and 6.3% presumed value by Free Style Libre. Discussion and Conclusion: Free Style Libre showed satisfactory results as CGM. There was lower HbA1c value by presumed calculation, which would be possibly due to every 15minutes measurement and difficulty in checking abrupt glucose surges. CGM application would probably bring diabetic subjects behavioral change of life style, leading to better diabetic control. These results would become reference data in CGM study for future research.