The American Diabetes Association (ADA) has undergone a significant evolution in its stance on carbohydrate-restricted diets for diabetes management. Prior to 2008, the ADA largely rejected low-carbohydrate approaches. From 2008 onward, it progressively acknowledged their short-term efficacy for weight loss, extended this recognition to 2 years by 2011, removed time limits in the 2013 consensus report, and by 2019 explicitly positioned low-carbohydrate eating patterns as among the most studied and viable options for adults with type 2 diabetes (T2D). This supportive position has remained consistent through 2025. In parallel, the newly released United States Department of Agriculture (USDA) Dietary Guidelines for Americans 2025–2030 reflect a paradigm shift toward higher protein intake (1.2–1.6 g/kg), emphasis on whole foods, restriction of processed foods and added sugars, and inclusion of healthy fats, aligning closely with core principles of low-carbohydrate diets. In contrast, the Japan Diabetes Society (J
The term “AGEs” is an acronym derived from “Advanced Glycation End Products (AGEs).” The medical community has been focusing on AGEs in recent years. So, what exactly is “glycation”? Glycation refers to the reaction in which monosaccharides such as glucose or fructose directly bind to proteins or other substances. AGEs produced in the body cause diabetic complications. AGEs have garnered attention because they are now considered a primary cause of various diabetic complications. The processes involved are diverse, but the most straightforward example is when AGEs accumulate in the inner walls of blood vessels, leading to atherosclerosis. Depending on which part of the blood vessels is affected by atherosclerosis, the resulting diabetic complications vary, but it is no exaggeration to call them all vascular diseases. AGEs in the vessel walls are like an unpayable debt, often referred to as the “memory of high blood sugar.”
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have their origins in phlorizin, which was discovered in apple bark in 1835. SGLT-2i has been effective in treating type 2 diabetes (T2D), chronic kidney disease (CKD), and cardiovascular disease (CVD). In heart failure, cardiac tissue becomes less able to metabolize glucose and fatty acids, and begins to rely more on ketone bodies. Subjects with heart failure with reduced ejection fraction showed higher cardiac output at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels when treated with ketone esters. As an adverse effect of SGLT-2i, euglycemic ketoacidosis (eKA) has been reported and requires careful attention.
The American Diabetes Association (ADA) announced the Standard of Care (SoC)-2025 in January 2025. It included useful information about the low-carbohydrate diet (LCD), chronic kidney disease (CKD), and Metformin. Historically, the ADA has re-evaluated LCD in 2008, 2011, 2013, and 2019. Authors have developed LCD medically and socially through the Japan LCD Promotion Association (JLCDPA). From the latest report of post hoc analysis, Metformin may have a beneficial effect on CKD cases with an eGFR of less than 30 ml/min/1.73 m². For diabetic nephropathy (DN), impressive findings have been observed for major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE).
Various discussions have continued concerning low carbohydrate diet (LCD) and calorie restriction (CR). The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have gradually recognized LCD as the recommendation for nutritional treatment. Recent reports have shown the predominance of LCD with clinical evidence from the accumulated data of the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS), with analyses of total LCD scores (TLCDS). Using TLCDS to analyze 139 thousand person-years, the hazard ratio (HR) of total mortality was 0.87 for TLCDS and 0.76 for vegetable (VLCDS). Authors continue developing LCD activities through the Japan LCD Promotion Association (JLCDPA).
The American Diabetes Association (ADA) presented the Standards of Care in Diabetes-2025 online in December 2024. The authors immediately reviewed and provided perspectives on the latest developments regarding glucagon-like peptide-1 receptor agonists (GLP-1RA). Some newly added content about GLP-1RA is included, such as its application for heart failure with preserved ejection fraction (HFpEF), obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH). Concurrent use of DPP-4 inhibitors (DPP-4i) with GLP-1RA (GIP/GLP-1RA) is not recommended due to a lack of additional glucose-lowering effects beyond GLP-1RA alone. GLP-1RA is expected to demonstrate various positive clinical effects.
For type 2 diabetes (T2D), the recommended meal has shifted from calorie restriction (CR) to a low carbohydrate diet (LCD). LCD gained worldwide prevalence through the efforts of Atkins and Bernstein, and we further developed LCD both medically and socially through the Japan LCD Promotion Association (JLCDPA). The beneficial and convenient methods of LCD include petite, standard, and super LCD, which have carbohydrate ratios of 40%, 26%, and 12%, respectively. For these three types, the approximate permitted carbohydrate amounts in each meal appear to be 20g, 30g, and 40g. Some foods with lower carbohydrate content include eggs (0.1g), a piece of cheese (0.2g), chicken meat (180g) (0.4g), and Japanese tofu (300g) (4g).
The presented case is a 68-year-old female with Type 1 diabetes (T1D). She was admitted for an emergency case with acute distress in January 2018 and was diagnosed with T1D with a blood glucose (BG) level of 459 mg/dL, HbA1c of 13.7%, glutamic acid decarboxylase autoantibody (GADA) level >2000 U/mL (<5 U/mL), and C-reactive protein (CRP) level of 1.10 ng/mL. She received Multiple Daily Injections (MDI) of insulin for 3 months, and then her HbA1c decreased to 7.3%. After that, she has been on a super-low carbohydrate diet (LCD) and received only Lantus XR and ipragliflozin. Serum CRP showed 0.2 ng/mL, suggesting a prolonged honeymoon period for years through continuous LCD.
Authors and collaborators have continued research and social movement on the Low Carbohydrate Diet (LCD) through Japan LCD Promotion Association (JLCDPA). Recommended 3 types of LCDs are petite-, standard-, super-LCD with 40%, 26%, 12% of carbohydrate ratio, respectively. Concerning the meal tolerance test (MTT), we have reported glucose and insulin responses to CR breakfast and LCD breakfast with 70g and 6g, respectively. This article described the tips for a useful dish with LCD and sufficient protein. It can be made of eggs, cheese, raw ham, and chicken by microwave cooking for 75 seconds. This petite dish can be applied in various situations.
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.
type 1 diabetes mellitus; MAGE, mean amplitude of glycemic excursions; MDI, multiple
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.
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.
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.
DATA); Prospective Urban Rural Epidemiology (PURE); Japanese LCD Promotion Association (JLCDPA).concerning diet therapy [15].It includes 9 kinds of diet way, which are LCD, High-protein diet, Mediterranean diet, vegetarian diet, low-fat diet, DASH-diet, Paleo diet, Low-glycemic index/load diet and control diet.In summary, we described the topics concerning diet therapy, such as LCD, CR and other methods.As this article becomes the initiator, we expect lots of remarkable papers and opinions will come associated with further significant discussion and development.
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.
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.
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-, sexglucose- 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.