In recent year, diabetes, life style-related disease and non-communicable diseases (NCDs) have been in discussion for clinical management [1]. These diseases bring various complications or comorbidities that will occur the exacerbation of metabolic and arteriosclerotic diseases in the body [2]. In such life-style diseases and metabolic-syndrome (Met-S), fundamental applicable nutritional education and its continuation for long will be required for patients [3]. It will also become the adequate basic daily habit for anti-aging medicine, and bring human wellness associated with protective management [4]. 

Concerning the fundamental clinical treatments, three factors are required that are nutrition, exercise and pharmacological agents. Among them, applicable diet therapy has been known as calorie restriction (CR) in former period, and low carbohydrate diet (LCD) in recent years [5]. LCD was introduced to health care world and medical treatment by two doctors of Bernstein and Atkins [6]. Bernstein has continued to educate many people and medical staffs until 2025 for long years [7]. Authors have continued various LCD activities through Japan LCD promoting association (JLCDPA) for years, and presented 3 types of simple and practical method through seminars, lectures, books and medical associations [8].

For diabetic pharmacotherapy, several oral hypoglycemic agents (OHAs) have been developed and introduced to medical practice [9]. Among them, imeglimin (Twymeeg) has become a novel medicine that has specific both function of insulin-secreting and insulin resistance reduction [10]. It has beneficial aspect for the combination of other OHAs [11]. Actual application of imeglimin has shown for its clinical efficacy, usefulness and safety [12,13].  During our actual practice, we have encountered a meaningful diabetic man who showed clinical effect of imeglmin and significant relationship of HbA1c and blood glucose. His general progress and perspectives will be described in this article.

Medical History

The case is 73-year-old man with Type 2 diabetes (T2D) and hypertension. When he was early 50s, he was pointed out to have T2D. He has provided oral hypoglycemic agents (OHAs) after that. HbA1c value has been unstable for long, because he has some episode of overeating for some months so far.

Figure 1: Clinical Progress of the Case.

For recent years, he has given OHAs and anti-hypertensive agent (AHA) with stable situation. Concerning his habit, he doesn’t drink or smoke, but like to eat carbohydrate food. Then, he occasionally eats much and diabetic control aggravates. From January 2024, he had received psychological stressor in his working office, and then could not lessen carbohydrate food.  HbA1c has increased from 6.5% to 8.3% for 10 months (Figure 1). The physician has talked with him about treatment protocol, and he started imeglimin (Twymeeg) associated with standard-low carbohydrate diet (LCD).

After that, HbA1c has remarkably decreased to 5.6% in Oct 2025. During Sept 2024 to Aug 2025, 6 points of fasting blood glucose in the morning were measured associated with HbA1c value. The relationship among HbA1c, actual measured fasting plasma glucose (FPG) and calculated estimated average glucose (eAG) was investigated (Figure 2). As a result, FPG and eAG showed almost consistency or coincidence according to HbA1c level.

Figure 2: Relationship among HbA1c, FPG and eAG.

Physicals and Several Exams

Physical examination in September 2024 showed as follows: conversation and consciousness are normal, and his vital signs are unremarkable as BP 132/78 mmHg, pulse 72, SpO2 99%. No remarkable changes were found in the head, face, neck, lung, heart, abdomen or neurological test. His physique was 156 cm in height and 76 kg in weight with BMI 31.2 kg/m².

The results of biochemical tests in September 2024 and August 2025 are summarized in Figure 3. It showed elevated r-GT for liver function test, and other items were unremarkable for renal, lipids and complete blood count (CBC). Electrocardiogram (ECG) showed ordinary sinus rhythm, pulse 76/min, and no specific ST-T changes. Chest X-P revealed negative exam.

Figure 3: Result of Blood Chemistry.

Ethical Standards

Current article complied with Helsinki Declaration [14]. Certain comment presented the protection for personal right. The principle shows the ethic rule for clinical research as human subjects. Required guideline has been from Ministry of Education, Culture, Sports, Science Technology, Japan and also Ministry of Health, Labour and Welfare. The authors et al. established the ethical committee in Sakamoto Hospital, which includes the hospital director, diabetologist, surgeon, nutritionist, pharmacist, registered nurse and legal professional. We have discussed enough concerning this case, agreed general protocol and took informed consent from the patients.

The current case has some characteristic aspects, which are i) his some medical problems include T2D and hypertension, ii) he tends to eat much leading to weight gain due to some psychological stressors, iii) imeglimin (Twymeeg) showed remarkable effect for HbA1c reduction, iv) continuation of LCD for several months probably contributed much for clinical efficacy, v) the relationship among HbA1c, actual measurement of fasting plasma glucose (FPG) and estimated average glucose (eAG) showed significant consistency or coincidence.

The case showed HbA1c reduction as 8.3% to 6.5% for 10 months. It may have 2 reasons, where one is combined therapy of imeglimin, and another is clinical effect of LCD. This case has continued linagliptin as DPP4-i, metformin as biguanides, and voglibose as alfa-GI. From large trials of Trials of IMeglimin for Efficacy and Safety (TIMES), imeglimin showed HbA1c reduction degree for combined treatment [15]. They are monotherapy 0.46%, DPP4-i 0.92%, biguanide 0.67%, alfa-GI 0.85%. Consequently, imeglimin seems to be recommended for simple or combined therapy with OHAs [16,17].

The relationship between HbA1c and average glucose (AG) has been in discussion for long. Formerly, Diabetes Control and Complications Trial (DCCT) presented quarterly important data of capillary-blood glucose for 7-point during 24 hour [18]. Blood specimens were taken during home setting. The analysis of DCCT profile data was summarized from 1439 subjects, and mean HbA1c and AG were calculated. As a result, the equation was as follows:  AG(mg/dL) = 35.6 x HbA1c(%) - 77.3, with r= 0.82 as a Pearson correlation coefficient [19].

Furthermore, Data from the A1c-Derived Average Glucose (ADAG) Study (2006-2008) was announced from ADA, EASD and IDF. Its purpose was to define the mathematical relationship between HbA1c and AG. It used 507 cases with type 1, type 2 and others without diabetes in 10 international diabetic centers. For the equation, estimated AG (eAG) was presented from the combination of weighted data. Then, linear regression analysis was observed, which was eAG(mg/dl)= (28.7*HbA1c)-46.7, r²=0.84 [20]. Detailed information can be obtained concerning eAG, calculator to convert eAG to HbA1c, and also vice-versa [21]. 

From mentioned above, this case probably showed the coincidence of the data in the FPG and eAG to higher degree. During diabetic improvement, he has kept LCD, and then the mean amplitude of glycemic excursions (MAGE) was probably minimum. Consequently, close relationship among HbA1c, FPG and eAG would be observed. We keep observing mutual relationship of three markers with academic interests. 

Some limitation may exist in this report. From some problems, he showed clinical improvement by the combination of imeglimin as a novel OHA and LCD as a diet therapy [22,23]. In the actual diabetic treatment, we can always select some effective resources. Then, clinical progress will be carefully followed up for long.

In summary, general progress of 73-year-old man with T2D and hypertension was shown with some perspectives. It will give some hint or advice for better diabetic practice and research as one of the possible useful reference.

Conflict of interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

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