SunText Reviews

Commentary Article

Medical problems of type 2 diabetes (T2D) and obesity has been crucial [1]. General prevalence of obesity, overweight, and T2D have been evaluated until now, and it seems to be more than one-third across the world [2]. Furthermore, world patients of diabetes mellitus (DM) has been acutely increasing from 537 million to 783 million during 2021-2045 [3]. In those cases, clinical development of atherosclerotic cardiovascular disease (ASCVD) would become the inevitable cause of mortality and morbidity. Main goal for the diabetic important therapy could be the preventive direction for ASCVD and related diseases [4].

T2D has been understood for its complications of microangiopathy and macroangiopathy. The latter would lead to cerebral vascular accident (CVA), coronary artery disease (CAD) and peripheral artery disease (PAD). The aggravation of macroangiopathy can be prevented by remarkable weight reduction and continuing therapy of T2D. Basic treatment include indispensable nutritional treatment for DM. Formerly, calorie restriction (CR) was rather standard method for diet therapy, but latest trend can show the predominance of low carbohydrate diet (LCD) [5,6]. LCD has been for itself proposed by doctors of Bernstein and Atkins in European and north American countries [7,8]. For health care and clinical regions, LCD has been accepted broadly. Authors and co-researchers have initiated LCD social movement by Japan LCD promotion association (JLCDPA). We informed LCD medically and socially of people through seminars, books, workshops and other beneficial chances [9,10]. For useful and simple measure, we proposed 3 kinds of practical LCDs, which are super-LCD, standard-LCD and petite-LCD. They include carbohydrate ratio as 12%, 26% and 40%, respectively [11].

On the other hand, previous standard data were observed about the mutual relationship between periodontitis (PD) and DM by a meta-analysis of cohort studies. As a result, 24% elevated PD are found in diabetic cases, and 26% elevated risk of DM in PD cases [12]. From the data of American Academy of Periodontology (AAP) and European Federation of Periodontology (EFP), those who with PD seem to develop T2D more as HR 1.19-1.33, than those without PD [13].

Authors group continued medical practice and research for ASCVD, and treated various kinds of patients. Recently, we happened to experience an impressive case with T2D, PD, obesity, with persisting positive inflammatory markers. After he was diagnosed as T2D, he was treated by LCD and oral hypoglycemic agents (OHAs). In this report, his general clinical progress and its related perspectives will be described.

Case Presentation

History and Physicals

Current patient is a 42-year-old man who did not have any special diseases before. When he was 37 years old, he was introduced to our diabetes department for further evaluation of diabetes in January, 2020. At that time, his HbA1c showed 10.6 % at the first contact.

Concerning his physical examination in 2020, he showed unremarkable findings of consciousness, speech, head, neck, chest, abdomen and neurological situations. His vitals showed hypertension of BP 146/90 mmHg, pulse 72/min and normal respiration and SpO₂ saturation. His stature was 171cm, 110.6 kg, BMI 37.8 kg/m², in which it showed the 2-degree of obesity in the international category of obesity evaluation.

Several exams and diagnoses

Laboratory biochemistry showed some abnormal data, which are shown in Table 1. They include elevated liver function tests, dyslipidemia, increased values of WBC, Hb, RBC, and HbA1c. Chest X-ray and electrocardiogram (ECG) showed unremarkable.

From mentioned above, the case was diagnosed with several life style-related diseases and Metabolic syndrome (Met-S). They include i) T2D, ii) obesity with BMI more than 35, iii) hypertension, iv) dyslipidemia, v) increased value of WBC, RBC and Hb.

During recent 5 years, changes in several blood biomarkers are summarized in Table 1. A pulse wave velocity (PWV) exam has been annually evaluated during 2022-2024 (Figure 1). The value of Cardio-Ankle Vascular Index (CAVI) were almost stable for 5.8-6.8 and 5.6-6.6 for right/left, respectively. PWV was compared between that of 2022 and 2024, in which ankle-brachial index (ABI) was improved from 0.99/0.96 to 1.17/1.10 during 2 years (Figure 2).

Abdominal CT scan was conducted for further evaluation of Met-S (Figure 3). Strong fatty infiltration was observed in the liver, and nodular high absorption was found on the edge of the lower pole of the right lobe of the liver, suggesting residual fatty liver. In addition, a ring-shaped stone with high density was noted near the neck of the gallbladder, which is thought to be of mixed type. Fatty replacement and atrophy were also observed in the parenchyma of the pancreas, but no obvious swelling or inflammatory changes were observed. No significant changes were observed in the common bile duct or both kidneys. A diverticulum was found in the right colon.

Treatment and clinical progress

Among his medical problems, the most main therapeutic option was the rapid treatment for decreasing the hyperglycemia from T2D. Our diabetic team has taught him how to regulate his daily meal style, where LCD was basically necessary for the treatment. By LCD, he had 10 kg of weight reduction. For oral medication, he has been provided for long in the following. They are valsartan 80mg, amlodipine besilate 5mg for hypertension, and metformin 500mg, teneligliptin hydrobromide hydrate 20mg, canagliflozin hydrate 100mg, voglibose 0.6mg for T2D, which are provided per day.

By combination of various treatments, he showed stable HbA1c level during 2021-2022 with weight reduction about 10 kg until this period. However, his HbA1c and CRP increased again during 2023-2024 with stable body weight. Furthermore, clinically related clinical problem has persisted for long, which is unstable periodontitis (PD) for long, and he has occasionally visited dentist when he felt the exacerbated symptom of PD.

Ethical standards

The case was complied with the guideline of the Declaration in Helsinki [14]. The principle was along with ethical regulation for medical research. This guideline is from Ministry of Education, Culture, Sports, Science Technology and Ministry of Health, Labor and Welfare, in Japan. Authors established ethical committee in the hospital, which includes director, physician, nurse, pharmacist, dietitian, and legal professional. Our staffs discussed this protocol enough and agreed. Informed consent was taken by the patient.

Discussion

In this report, current case showed several clinical problems. They are i) T2D, ii) obesity, iii) hypertension, iv) dyslipidemia, v) increased values of WBC, RBC and Hb. Furthermore, other problems could be suggested, which are vi) fatty liver with lower ratio of AST/ALT, vii) persisting elevated value of CRP as inflammatory situation, and viii) persisting dental problem as periodontitis (PD) for years. Among these factors, persisting inflammation may be involved in increased WBC (v), positive CRP (vii) and PD (viii) for long and they may exacerbate diabetic control so far. Mutual relationship between diabetes and PD has been known as vicious cycle [15].

This case seems to have underlying obesity and developed T2D at middle age. The relationship between weight change and risk of developing T2D was evaluated [16]. A weight increase with >5% increased the T2D risk by more than 60%. On the other hand, a weight loss with >5% reduced the risk by more than 40%. For details, odd ratios (ORs) showed 1.58, 1.76, and 1.70 for 3-, 6-, 9-year follow-ups, respectively in multivariable analysis. Similarly, weight loss ? 5% showed 0.48, 0.57, and 0.51 for 3 period follow-ups.

The case showed 10kg of weight reduction by continuing LCD, which seemed to be satisfactory result. The latest RCT reviews for dietary interventions has revealed that LCDs consistently showed larger reductions in fasting glucose, HbA1c, triglycerides with superior weight loss with comparison with low-fat diets (LFDs) [17]. LCDs include very low-carbohydrate ketogenic (VLCK) diets, where it typically has less than 10% of total caloric intake from carbohydrates. Such super-LCD usually contribute greater results of reducing weight. From our medical group data, LCD contributed remarkable >10% weight reduction in 666 (24.0%) out of 2773 cases [18].

By evaluating the relationship among his medical history, clinical progress, symptoms, and laboratory data, unstable situation of PD may be related with the HbA1c value with certain inflammation. For the relationship of DM and PD, a systematic review and meta-analysis was reported as the latest data [19]. The inclusion criteria was required at least 3-6 months of follow-up, and 11 investigations met the criteria. As a result of dental treatment, significant reductions of HbA1c showed -0.64% for 3 months, and -0.33% for 6 months. Furthermore, CRP values showed significant decrease, suggesting the improvement in systemic inflammatory situation.

In order to enhance the health condition of patients with T2D and periodontitis (PD), clinicians have to manage the optimization of adjunctive therapies. The latest study showed the meta-analysis of 30 RCTs for short-term and medium-term with the statins/metformin influence to PD. As a result, adjunctive local therapy with statins or metformin showed significant improvement of PD [20]. This treatment showed superiority to root planning (SRP) and scaling with/without additional various interventions.

The latest report was to enroll 1223 cases from 14 studies for investigating positive efficacy of PD treatment on CRP value [21]. As a result, non-surgical treatment for PD has improved short-term inflammatory biomarker of high sensitivity-CRP for 0.39, while the treatment without antibiotics use was 0.34. As a large cohort study, the participants included T2D 251 thousands/ non-DM 539 thousands and they were compared in the light of PD and other markers [22]. PD was found more in T2D for 22% than non-T2D for 17%. Its difference was larger in younger age cases. When adjusted relative ratio (RR) at the age of 30s, it showed 1.92 and exacerbated as glycemic control became aggravation.

Some limitation may exist in this report. Current middle-aged case showed T2D and periodontitis (PD), and these factors are involved in several diabetic complications. His diabetic control was good for some period, and worse for later period. By following up the future clinical progress, we will investigate various biomarkers and factors that may influence the glucose variability and inflammatory situation.

In summary, 42-year-old male with T2D and PD was reported here with several related perspectives. Such case seems to be rather rare, and such clinical progress contribute detail pathophysiological influences of diabetic study in the future.