The case is 85-year-old female with Type 2 diabetes (T2D). She felt general malaise and thirsty in February 2024, and visited our clinic. Biochemistry showed HbA1c 9.2% for severe T2D. She was advised to start mild degree of petite low carbohydrate diet (LCD) and taking for a walk. For oral hypoglycemic agents (OHAs), she began vildagliptin (Equa) at first, followed by Metformin (Metgluco) with gradual increase of the doses, to EquMet LD. HbA1c decreased to 6.7% for 3 months, which was satisfactory without gastro-intestinal adverse effects (GI-AE). EquMet LD is expected for lower mean amplitude of glycemic excursions (MAGE).

Type 2 diabetes (T2D) has been observed for crucial medical problem across the world [1]. From international point of view, diabetic management has been in focus for many countries [2]. Considering the age group of people affected by diabetes, recent problem would be the adequate management for the elderly T2D cases. American Diabetes Association (ADA) has announced the standard measure for T2D in Jan 2024 [3]. It would be applied to the elderly T2D with applicable treatment using several types of oral hypoglycemic agents (OHAs). Among them, metformin has been the first-line agent for years and dipeptidyl peptidase-4 inhibitors (DPP-4i) has been used widely for its effectiveness. From these, the combined oral hypoglycemic agents (OHAs) have been used in the clinical practice. The combination of vildagliptin/metformin (EquMet) has been used with clinical effectiveness [4].

As to T2D, basic therapeutic principle would be nutrition therapy, exercise and OHAs or insulin. As diet therapy, calorie restriction (CR) method was previously standard, but low carbohydrate diet (LCD) has been evaluated for applicable measure [5]. LCD was initiated at first by the doctors of Atkins and Bernstein [6,7]. Successively, LCD was begun in Japan by our research group through the activities of Japan LCD promotion Association (JLCDPA) [8,9]. In addition, our team has developed LCD socially in Japan by seminars, books and medical societies [10]. We have announced useful three kinds of LCD diets for a variety of chances. They are petite-LCD, standard-LCD and super-LCD. It presents the ratio of including carbohydrate as 40%, 26% and 12%, respectively [11].

We have continued diabetic practice and research for years, and published lots of reports for various types of T2D and treatments [12,13]. Recently, we have an experience of meaningful T2D case. She was elderly female and showed significant effect by petite LCD and EquMet administration. Her clinical course and related perspectives will be described in this article.

Presentation of Cases

History and physicals

This case is 85-year-old female with T2D. As her past history, she was pointed out to have mild T2D about 4 years ago, and treated at another family physician. She had medical problems of T2D, mild hypertension, Gastro esophageal reflux disease (GERD) and has been stable for a few years. Recently, she cannot take medicine regularly for several months, and she visited our clinic in February 2024 associated with general malaise and thirsty.

The physical examination revealed in the following: conversation, consciousness and general movement were unremarkable. Vitals were pulse 80/min, BP 172/82, BT 36.8, respiration normal and SpO2 97%. Her head, lung, heart, abdomen and neurological findings were negative. Her physique showed height 150.4cm, weight 41.2 kg and BMI 18.2 kg/m². The chest X-ray showed negative, and electrocardiogram (ECG) showed within normal limits.

By rapid testing of HbA1c in the out-clinic, she was diagnosed as severe degree of T2D with HbA1c 9.2%. In addition, blood chemistry was conducted, and the results of liver, renal, lipids and complete blood count showed unremarkable (Table 1). 

Clinical course and treatment

After she was currently judged as severe level of T2D, she was provided diabetic treatment for diet therapy, exercise, and pharmacotherapy. She was advised to start mild degree of petite low carbohydrate diet (LCD), and taking for a walk around her home for 30 minutes. For oral hypoglycemic agents (OHAs), she was advised to take vildagliptin (Equa) at first, followed by Metformin (Metgluco) with gradual increase of the doses. From May 2024, she was provided the combined agent of EquMet LD, which includes vildagliptin 50mg and metformin 250mg per tablet. Other medicines included amlodipine besilate 2.5mg, empagliflozin 10mg, miglitol 150 mg, and vonoprazan fumarate 10mg.

Concerning her clinical course, remarkable reduction of HbA1c was observed every month. HbA1c was decreased to 6.7% linearly until May 2024 with significant reduction for 3 months (Figure 1).

Table 1: Changes in laboratory data.

Figure 1: Clinical course of the case with HbA1c and medication.

During her improving period, she did not complain of any symptoms for gastro-intestinal adverse effects (GI-AE). She can tolerate the treatment well, and no other clinical problems were found.

Ethical standards

This report was complied with the ethical guideline of Declaration of Helsinki [14]. Moreover, certain comment is with the protection regulation. The principle has been accompanied with ethic regulation for clinical practice and research. This guideline is observed in Japanese Ministry, including Ministry of Education, Culture, Sports, Science Technology and Ministry of Health, Labor and Welfare in Japan.

The authors and collaborators have set the ethical committee in the hospital. It has hospital director, doctors, nurse, pharmacist, and legal professional. These members discussed fully the protocol and agreed. The informed consent was given from the case with the document.

Discussion

This case is 85-year-old case with T2D, who showed remarkable improvement of glucose variability for a few months. She is elderly patient with T2D, hypertension and GERD, without apparent high degree of arteriosclerosis, because she did not have distinct macroangiopathy, such as cerebrovascular accident (CVA), ischemic heart disease (IHD), or peripheral artery disease (PAD). During her clinical course, her body weight has been stable. It would be because the muscle volume did not change so much, irrespective of the improvement of glucose variability.

Concerning the remarkable effectiveness, another reason may be considered. This elderly case has applied petite LCD, in which she did not change the meal pattern so much. She continued to eat less carbohydrate amount than before, and then she always ate some rice or carbohydrate in the supper. Among some types of DPP4-i, Equa or EquMet shows the characteristic point, which is administering twice a day. From this benefit, vildagliptin can suppress the fluctuation of blood glucose for all day. In other words, she possibly obtained smaller mean amplitude of glycemic excursions (MAGE) than before [15]. When vildagliptin is given at night, glucose elevation can be reduced during midnight. This mechanism may bring the significant improvement of glucose variability in this case.

As regards to macroangiopathy in T2D, protection of the exacerbation of arteriosclerosis would be considered. Earlier administration of combined vildagliptin/metformin (EquMet) showed the satisfactory reduction of risk for macrovascular events [4,16]. It was the sub-analysis of investigations of VERIFY, which stands for vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY) [4,16]. Among VERIFY exams, two categories were compared for young and late-onset T2D. As the protocol, end point was set for the treatment failure (TF) that means the elevation of HbA1c as 7.0%. As a result, the risk was calculated as 46% vs 48% for late-onset cases vs young-onset cases with significant difference [17]. Consequently, treatment-naïve young cases showed the improvement of early durability and later exacerbation for glycemic variability.

Petite LCD was applied for this case, which seemed to be beneficial and satisfactory. From historical point of view in medical region, the comparison of CR, LCD and Mediterranean Diet (MD) was conducted by Shai et al [18]. LCD was proved to be effective for almost cases in short period, but the rebound phenomenon has been often observed [19]. Then, the compromised method has been found for the combined therapy of LCD and MD, where LCD would be started at first, followed by MD several months later [5].  In addition, MD and Paleolithic diet have been compared for beneficial measure [20]. Future interests may attract attention for MD, LCD and prevention of CVD [21,22].

Authors and co-researchers have presented diabetic reports [23]. Among them, seasonal changes of HbA1c with EquMet for 6 years was included [24]. We will continue diabetic research with various points of view [25].

Some limitation may be found in this report. This is only one case, and she showed significant improvement by petite LCD and EquMet. She did not have currently apparent diabetic macroangiopathy, but we should pay attention to the exacerbation of complication. Diabetic strategy is to minimize the aggravation of Atherosclerotic Cardiovascular Disease (ASCVD) for the clinical progress.

In summary, 85-year-old female was presented with some perspectives. Clinical course will be followed up with careful attention for preventing development of arteriosclerosis. We expect that this article will become useful reference for diabetic practice.

Conflict of Interest

The authors declare no conflict of interest.

Funding

There was no funding received for this paper.

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