Diabetes has been crucial disease across the world, and type 2 diabetes (T2D) has been managed by the standard guideline of American Diabetes Association (ADA) [1]. It shows the adequate diagnosis and therapy associated with various evidences. For diabetic complications, both of microangiopathy and macroangiopathy have been always managed with attention [2]. Then, arteriosclerosis has been found as atherosclerotic cardiovascular disease (ASCVD), including cerebral vascular accident (CVA), ischemic heart disease (IHD), and peripheral artery disease (PAD). [3].  

For basic therapeutic principle of T2D, nutritional treatment has been in discussion for long. Formerly calorie restriction (CR) was known for standard method for treating T2D. After that, however, the novel method of low carbohydrate diet (LCD) has been introduced by Drs. of Atkins and Bernstein who was two supreme physicians [4,5]. In addition, the efficacy of LCD was presented by the research of Dietary Intervention Randomized Controlled Trial (DIRECT) [6,7]. It was the historical milestone from diet therapy point of view. Authors and co-researchers continued medical practice and research of LCD, and developed social and medical activities of Japan LCD promoting association (JLCDPA) [8,9]. We have informed practically simple method of 3 basic types. They are super-LCD, standard-LCD and petite-LCD, in which they include carbohydrate ratio of 12%, 26% and 40%, respectively [10]. 

Our diabetic and clinical team has continued medical research for patients with various diseases. Among them, recent useful oral hypoglycemic agents (OHAs) have been reported associated with adequate perspectives such as imeglimin (Twymeeg) and other agents. We happened to experience a 62-year-old man who showed T2D and multiple arteriosclerosis. His general clinical course and problems will be described in the report.

Medical History and Physical Examination

The patient was a 62-year-old man with some health problems, including T2D, hypertension, and hyperuricemia. He was diagnosed with T2D in 2016 at age 53. Since then, his medication compliance has been somewhat unstable, but his HbA1c has generally remained at approximately 6.5%. A cervical ultrasound was performed in February 2023, revealing no significant plaque. He had been receiving treatment in Osaka, but due to a job change, he moved to Kagawa Prefecture in March 2024 and continued his treatment at our hospital.

Physical exam was conducted. He showed unremarkable results of consciousness, vital signs, heart, lung, abdomen or neurological findings. His physique revealed 172.2cm in height, 69.3kg in weight, and 23.4 kg/m² in BMI.

Several Examinations

Some basic examinations were underwent. Chest X-ray showed negative results, and electrocardiogram (ECG) revealed that regular, ordinary sinus rhythm (OSR), pulse 68/min, and ST-T depression in V₂-V₅ (Figure 1). Urinalysis findings revealed negative for protein (-), glucose (++), urobilinogen (+/-), pH 6, occult blood (+/-), bilirubin (-) and ketone bodies (-). Medical course of blood biochemistry was shown in Table 1. It revealed higher HbA1c values for years, and other biomarkers showed almost normal ranges.

Figure 1: Electrocardiogram (ECG) ST-T Depression In V2-5 Is Found. 

Table 1: Progress of Biochemistry Data.

He received the examination of pulse wave velocity (PWV) (Figure 2). The value of Cardio-Ankle Vascular Index (CAVI) showed 9.4/9.3 (right/left), in which their standard range was approximately 8.6 +/- 0.8. Consequently, the rather elevated degree of arteriosclerosis was found. The ankle-brachial index (ABI) showed 1.07/0.99 (right/left), where it suggested the borderline value. The detailed results of PWV were that that L (132) = L1(67) + L2(35) + L3(30), PEP 81, ET 313, R-AI 1.25 and PEP/ET 0.26. These data were within normal range.

Figure 2: Pulse Wave Velocity (PWV) Some Irregular Waves Are Found.

CT scan Results

For head CT scan, ventricular enlargement and severe atrophy of the bilateral frontal lobes were observed, with slightly increased fluid space (Figure 3). No other significant signs of vasculopathy or major vascular disease were noted. Age-related changes were more pronounced than expected for a patient of this age.

Figure 3: The Result of Head CT scan

a. No Remarkable Abnormal Images

b. Atrophy of the Bilateral Frontal Lobes.

An abdominal CT scan was performed in December, 2025 (Figure Hypodensity tendency was found in the liver parenchyma, which suggests the presence of fatty infiltration. Pancreatic parenchyma showed some fatty replacement. A calcified aneurysm of the splenic artery is suspected. An accessory spleen is present. Small stones are observed in both renal pelvises, where some fuzziness is found at the margins. The prostate is enlarged and calcified. No obvious masses or enlarged lymph nodes are observed.

 Figure 4: Abdominal CT scan

a. Fatty Liver Is Found

b. Bilateral Renal Stones.

Clinical Problems and Progress

From mentioned information above, clinical problems and related treatments are summarized. They are #1 hypertension: Azilsartan 40mg as Angiotensin II Receptor Blocker (ARB), Nifedipine 20mg as Calcium Channel Blocker (CCB), #2 hyperuricemia: Febuxostat 10mg as medicine for hyperuricemia, #3 type 2 diabetes (T2D): Linagliptin (Trazenta) as DPP4-i, Empagliflozin 10mg (Jardiance) as SGLT2-i, Metformin 1000mg/day, #4 possible cerebral vascular accident (CVA), #5 ischemic heart disease (IHD), and #6 peripheral artery disease (PAD): aspirin 100mg as anti-coagulant against #4-#6.

As the clinical progress related with oral hypoglycemic agents (OHAs), HbA1c has shown gradual increase for 7.2%-7.4% with glimepiride 1mg until 2024 November. Then, OHAs were changed by discontinuing glimepiride and initiating imeglimin (Twymeeg) 2000 mg/day. Subsequently, the patient's HbA1c level improved to 6.8-6.9%, and stable situation has been observed until today.

Ethical Standards

Current report has complied with the Helsinki Declaration [11]. Some comment revealed the protection for personal information. The principle has ethical rule for practice and research in human subjects. Necessary guideline is from Ministry of Health, Labour and Welfare, and Ministry of Education, Culture, Sports, Science Technology. The authors et al. established ethical committee in Sakamoto Hospital. It includes the director, physicians, registered nurse, pharmacist and also legal professional. All members discussed enough concerning this case, agreed this protocol and obtained informed consent of the case.

In this report, the characteristic points of this case would be multiple medical problems associated with possible presence of multiple arteriosclerosis in several organs. They include hypertension, hyperuricemia, T2D, CVA, IHD and PAD. The onset of T2D was 9 years ago, and his HbA1c has kept almost stable degree for years. However, he seemed to develop various gradual arteriosclerosis during the period.

Furthermore, clinical focus includes the administration of imeglimin (Twymeeg) as a novel OHA which was recently introduced to clinical diabetic practice [12]. Imeglimin has been developed, which is to possess both efficacy of stimulating insulin secretion from beta cell of the pancreas and decreasing the degree of insulin resistance [13,14]. It has been recognized to present effect and safely for T2D patients [15]. Imeglimin is also used for add-on treatment with other OHAs. Some larger studies were performed for international trials for various application of imeglimin. They include Trials of IMeglimin for Efficacy and Safety (TIMES) 1,2 and also 3. Clinical effect have been studied in the case of monotherapy and also combination treatment in TIMES 2 [16]. The HbA1c-decreasing degree was compared, in which -0.46% for monotherapy, -0.92% for DPP4-i, -0.67% as biguanides, -0.85% as alfa-GI, and -0.57% for SGLT2i. In addition, some attractive results were shown in TIMES 3 [17], where GLP-1RA of subcutaneous injection brought the combined effect for only 0.12%. Probably, certain route may be involved in this pharmaco-physiology, where some mechanism exist related to this function. It seems to be other than usual mitochondrial pathway and it may be involved in pharmaco-physiological aspect.

For the exam of PWV, this case showed higher CAVI and borderline value of ABI. These results may suggest the existence of multiple arteriosclerosis in the brain, heart and peripheral artery. For his clinical progress in the PWV exam, his results of CAVI and ABI have been rather stable for years [18]. For clinical arterial stiffness (AS), the degree of brachial-ankle pulse wave velocity (baPWV) has showed the evaluation of arteriosclerosis [19]. Some influencing factors may be involved in his fundamental lifestyle, daily habits, proper control of HbA1c and blood glucose and psychological stressors in his daily life.

Certain limitation may exist for this report. Current case is likely to keep stable life with light degree of T2D, and probable arteriosclerosis of CVA, IHD, and PAD, which are diabetic macroangiopathies. The administration of imeglimin (Twymeeg) seemed to show clinical efficacy for reduction of HbA1c [20]. The case would be followed up carefully for diabetes and arteriosclerosis [21].

In conclusion, 62-year-old man who showed T2D and probable arteriosclerosis due to macroangiopathies was presented associated with some perspectives. This patient can have certain useful clinical perspectives. It is expected that this article become some reference for diabetic practice and research.

Conflict Of Interest

The authors declare no conflict of interest.

Funding

There was no funding received for this paper.

1. American Diabetes Association Professional Practice Committee for Diabetes. Introduction and Methodology: Standards of Care in Diabetes-2026 Diabetes Care 2026; 49: S1-S5.
2. Reurean-Pintilei D, Potcovaru CG, Salmen T, Mititelu-Tartau L, Cinteza D, Lazar S, et al. Assessment of Cardiovascular Risk Categories and Achievement of Therapeutic Targets in European Patients with Type 2 Diabetes. J Clin Med. 2024; 13: 2196.
3. Association for Research into Arterial Structure and Physiology (ARTERY), the European Society of Hypertension Working Group on Large Arteries, European Cooperation in Science and Technology (COST) Action VascAgeNet, North American Artery Society, ARTERY LATAM, Pulse of Asia and Society for Arterial Stiffness-Germany-Austria-Switzerland (DeGAG). 2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices. Hypertension. 2024; 81: 183-192.
4. Atkins and Robert. Dr. Atkins' New Carbohydrate Gram Counter. M. Evans and Company.1996.
5. Bernstein RK. Dr. Bernstein's Diabetes Solution. Little, Brown and company, New York.1997.
6. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, et al. Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean or low-fat diet. N Engl J Med. 2008; 359: 229-241.
7. Yokose C, McCormick N, Rai SK, Lu N, Curhan G, Schwarzfuchs D, et al. Effects of Low-Fat, Mediterranean or Low-Carbohydrate Weight Loss Diets on Serum Urate and Cardiometabolic Risk Factors: A Secondary Analysis of the Dietary Intervention Randomized Controlled Trial (DIRECT). Diabetes Care. 2020; 43: 2812-2820.
8. Ebe K, Wood M, Bando H. American Diabetes Association (ADA) Standards of Care-2025: Sustained Euglycemia on Low-Carbohydrate Diet (LCD). Int J Case Rep Clin Image. 2024; 6: 237.
9. Wood M,  Bando  H, Ebe  Immune  Function  Augmentation  in  Low-Carbohydrate  Diet  (LCD). Int J Endocrinol Diabetes. 2025; 8: 186.
10. Bando H, Ebe K. Beneficial and Convenient Method of Low Carbohydrate Diet (LCD) as Petite, Standard and Super LCD. Asp Biomed Clin Case Rep. 2023; 7: 1-4.
11. General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent. 2014; 81: 14-18.
12. Bando H, Okada M, Iwatsuki N, Ogawa T, Sakamoto K. Diabetic Elderly with Keeping Less Arteriosclerosis Treated by Imeglimin (Twymeeg). Asp Biomed Clin Case Rep. 2024; 7: 126-130.
13. Gogikar SK, Sen S, Pathinti S, Samanthula G, Dikundwar AG. Forced Degradation Study of an Anti-Diabetic Drug Imeglimin: Impurity Profiling and Structure Elucidation Using LC-Q-ToF-MS/MS and NMR. Rapid Commun Mass Spectrom. 2025; 39: e9960.
14. Hou T, Zhang J, Shi W. Mechanisms and clinical perspectives on imeglimin for insulin resistance in obese patients. Eur J Pharmacol. 2025; 1003: 177937.
15. Bando H, Ogawa T, Sakamoto K, Okada M, Iwatsuki N. A Diabetic Male with Arteriosclerosis and Pericardial Cyst Treated by Imeglimin. Asp Cardio Case Rep and Res. 2025; 2: 11-16.
16. Dubourg J, Fouqueray P, Quinslot D, Grouin JM, Kaku K. Long-term safety and efficacy of imeglimin as monotherapy or in combination with existing antidiabetic agents in Japanese patients with type 2 diabetes (TIMES 2): A 52-week, open-label, multicentre phase 3 trial. Diabetes Obes Metab. 2021; 24: 609-619.
17. Reilhac C, Dubourg J, Thang C, Grouin JM, Fouqueray P, Watada H. Efficacy and safety of imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period. Diabetes Obes Metab. 2022; 24: 838-848.
18. Marzoog BA, Govnieva D, Chomakhidze P, Kopylov P. Cardi-Ankle Vascular Index Optimizes Ischemic Heart disease Diagnosis. medRxiv. 2024; 07: 24309877.
19. Li Z, Gu Z, Xiang J, Man X, Zhang X. Association between serum uric acid levels and arterial stiffness in patients with psoriasis. Arch Dermatol Res. 2025; 317: 386.
20. Bando H, Okada M, Ogawa T, Iwatsuki N and Sakamoto K. Aged Female with Dementia, Zinc Deficiency and Type 2 Diabetes (T2D) Treated By Imeglimin (Twymeeg). J Aging Sci Geronto. 2025; 127. 25.
21. American Diabetes Association Professional Practice Committee for Diabetes*. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2026. Diabetes Care. 2026; 49: S61-S88.