For decades, type 2 diabetes (T2D) has been rapidly increased in the world. The number of T2D patients seemed to be 445 million in 2020, and will rise to 730 million in 2050 when the T2D prevalence remains unchanged [1]. It will be ranged from 657 million to 1095 million, if the prevalence will change from -10% to +50% in 2050. For T2D, cardiovascular disease (CVD) has been the main problem for mortality and morbidity. CVD includes coronary artery disease (CAD) and peripheral artery disease (PAD), in addition to diabetic macroangiopathy [2].

American Diabetes Association (ADA) has announced the standard care guideline in January, 2025 [3]. It indicated clinical importance of the occurrence of arteriosclerotic cardiovascular disease (ASCVD) [4]. Such gradual development of ASCVD has been noted from pre-diabetes situation as actionable entity [5]. For the protection of diabetic complication, low carbohydrate diet (LCD) has been formerly developed by Atkins and Bernstein and informed widely [7,8]. Successively, authors and colleagues have set up the Japan LCD promotion association (JLCDPA) and endeavoured to broaden the information of LCD movement so far [9]. The author have announced the useful LCD pattens that shows clinically simple and accepted for many people. They are petite-LCD, standard-LCD, and super-LCD which include carbohydrate ratio for 40%, 26% and 12%, respectively [10]. Recent reports have shown that LCD has brought more beneficial effect to the control of T2D compared with calorie restriction (CR) [11].

Furthermore, diabetes always increases hyperglycemia for long, and it will bring higher prevalence of neuropathy and GI tract complications. T2D patients with various diseases have been treated and studied from multi-axes points of view. Our clinically diabetic team has treated lots of T2D cases with various complications. We happened to treat a T2D patient with colon diverticula associated with anemia. General medical conditions and related perspective will be described in current article.

Medical History

The patients is a 77-year-old female case with type 2 diabetes (T2D), dyslipidemia, peripheral artery disease (PAD), Gastro Esophageal Reflux Disease (GERD). She has been treated for T2D, PAD, GERD and dyslipidemia more than 6 years, in which her clinical status has been stable. Her glucose variability has been in satisfactory situation by low carbohydrate diet (LCD) as diet therapy, and metformin and oral semaglutide in recent years. She has received blood test regularly twice a year for long (Table 1). During 2021-2023, she did not show any particular symptoms or signs, but complete blood count (CBC) showed lower level of Hb, indicating the existence of anemia.

Table 1: Changes in Laboratory Data for Recent 7 Years.

Physicals and Exams

Physical examination in April 2023 showed as follows: Vitals were pulse 68/min, BP 130/78mmHg, SpO2 98%. Conversation and consciousness revealed normal, and no remarkable findings were observed in the lung, heart, abdomen and neurological tests. Her physique were 152cm in height, 50.0kg in weight and BMI was 21.6 kg/m².

Chest X-P showed unremarkable changes. Electrocardiogram (ECG) revealed regular pulse 60/min, normal axis, ordinary sinus rhythm (OSR) without ST-T specific changes. Detailed analysis included Pulse 60 /min, PR 174 ,s. QRS 0.087 ms, QT 0.441ms, QTc B/F=0.441/0.441, Axis -2 degrees, SV₁ 0.74mV, RV₅ 0.93 mV, and R+S 1.67 mV. The results of CBC and iron metabolism were in the followings: WBC 42 x 102 /μL, RBC 316 x 10⁴ /μL, Hb 9.9 g/dL, Ht 32.2%, MCV 102 fL (85-102), MCH 31.3 pg (28-34), MCHC 30.7 % (30.2-35.1), Plt 31.3 x 104 /μL, serum iron 15 μg/dL (29-154), UIBC 447 μg/dL (180-270), TIBC 432 μg/dL (220-433), ferritin 4.8 ng/mL (4.0-64.2), in March 2023.

Diagnosis and Treatment

Further evaluation of abdominal CT scan in March 2023 revealed the following findings (Figure 1). The liver showed a decrease in density, suggesting fatty liver, but no space occupying lesions (SOL) were observed. Small stones and calcifications were observed in both kidneys. The body of the pancreas was replaced by fat, with small low absorption areas. In the ascending colon, there were many diverticula and fecal stones. Surrounding adipose tissue was observed, but no particular inflammatory changes were observed.

Figure 1: The result of abdominal scan.

From these obtained data, she was diagnosed as anemia of decreased Hb by CBC, normal range of MCV by analysis of CBC and colon diverticula by abdominal CT scan. We have the discussion among internal medicine, surgery and radiology departments, and decided management direction for the future. It included i) the problem would be probably the bleeding from colon diverticula, ii) MCV, MCH, and MCHC values could show normal range regardless of possible iron-deficiency anemia, iii) starting the administration of sodium ferrous citrate 50mg would be adequate for treatment for several months, and iv) future operation of colectomy will be discussed in several months according to the clinical progress of anemia and/or bleeding from colon diverticula.

Clinical Progress

As oral medical treatment before February 2023, she was provided Metformin 1500mg, Empagliflozin 25mg, Esomeprazole Magnesium Hydrate 20mg, Sarpogrelate Hydrochloride 200mg, Voglibose 0.4mg and Semaglutide (Genetical Recombination) 7mg. From February 2023, she was added sodium ferrous citrate 50mg per day and followed up the clinical course. Her anemic status was recovered until July 2024 with increase of Hb from 9.9 g/dL to 14.1 g/dL. She underwent the operation of a single-incision laparoscope in Sept, 2024. It was right colectomy and left hemicolectomy, which was successful and uneventful clinical progress. From pathophysiological point of view, no malignant findings were observed, and the specimen included multiple colonic diverticula.

Cardiovascular Exams

Plethysmography was performed in March 2024 [11]. The data of pulse wave velocity (PWV) is shown in Figure 2. It showed decreased values of ankle brachial pressure index (ABI) as 0.57/0.75 in right/left and normal ranges of cardio-ankle vascular index (CAVI) as 7.5/7.9 (r/l). From these results of arteriosclerosis, decreased ABI has suggested the presence of peripheral artery disease (PAD). During 2019-2024, PWV exam had been checked annually, where ABI showed 0.57-0.81/0.78-0.93 in right/left with similar values. Her PAD problem has been followed up in another heart and cardiovascular clinic so far.

Figure 2: The Result of PWV.

Ethical Consideration

This patient complied with Helsinki Declaration for ethical guideline associated with some commentary for the regulation [12]. The principle had certain rule for medical research and human clinical problems. The standard guideline was shown from Ministry of Culture, Sports, Science Technology and Ministry of Health, Labor and Welfare and Ministry of Education. The authors and collaborators established the ethical committee in Sakamoto Hospital, Kagawa, Japan. The committee had several members, including hospital director, physician, nurse, pharmacist, and legal professional. All staffs discussed satisfactory and agreed the protocol. We obtained the informed consent by the document from the case.

As regards to current case, several clinical problems were found. They are i) T2D, ii) arteriosclerosis, iii) GERD, iv) PAD, v) anticoagulant agent, vi) occasional bleeding from colon diverticula, and vii) iron-deficiency anemia. From her medical history and laboratory data, the patient may have a few times of gastro-intestinal (GI) bleeding due to colon diverticula. However, the evidence of the bleeding from diverticula could not apparently detected during clinical progress for years.

This patient has clinical problems of occasional anemia due to obscure bleeding. The cause and/or the bleeding focus were not apparent, where occult bleeding was probably from colon diverticula [13]. Among various cases with lower GI bleeding, diverticular bleeding has been the most common genesis and it accounts for 21-42% in the medical situation in Western countries [14]. Clinical management can involve initial resuscitation accompanied by diagnostic assessment. Similar case was reported who had multiple episodes of GI bleeding by pan-colonic diverticulosis. Intraoperative colonoscopy was conducted for precise identification of the anatomy and pathology [14]. Among the similar reports, some pathologies may include Meckel’s diverticulum that exists in the lower intestine [15]. In recent years, lots of patients have been prescribed direct oral anticoagulants (DOACs), who have received endoscopic examinations for the diagnosis of various diseases in GI tract [16]. In contrast, the current case did not have DOAC with strong effect, but took Sarpogrelate Hydrochloride with weak pharmacological ability.  

This patient had continued LCD for diabetic nutritional treatment for years. As a result, the HbA1c values showed stable situation. As dietary therapies for diabetes, calorie restriction (CR) and LCD have long been debated, and in recent years the superiority of LCD has been reported [17]. From recent study, the valid clinical effect was analyzed from carbohydrate amount per day. For 2821 cases in 33 RCT studies, the applicants with less than 100g carbohydrate intake per day did not lead to decrease of fatty mass [2]. In contrast, when overweight or obesity cases would limit less than daily 50g carbohydrate more than 1 month by LCD and/or ketogenic diet (KD), they could achieve the improvements of biomarkers including fatty mass. Consequently, daily intake of <50g carbohydrate may be necessary for effective LCD therapy. By actual treatment of LCD, RCT study was performed for 1197 obesity cases [18]. The results showed decrease of HbA1c -0.36% and fasting plasma glucose (FPG) -10.7 mg/dL. Furthermore, it showed reduction of TG -19.9 mg/dL, and HDL +2.49 mg/dL. Thus, LCD will bring improvements of glucose and lipid values for obesity cases. Consequently, LCD can show clinically glucose control and lipid profile with patients with overweight and obesity. It emphasizes the standardization of dietary guideline.

This case had arteriosclerosis or diabetic macroangiopathy, such as PAD. The latest report showed the changes for CVD risk in diabetic patients [19]. Certain cohort matching program was included for life-style modification for intervention group and control group. As a result, the former showed better improvement for -0.29 kg/m2 as BMI, -0.84mmol/L as fasting plasma glucose (FPG), -0.13mmol/L as LDL, -0.77% as atherosclerotic CVD risk and -0.94% as 10-year CVD risk. Consequently, program for CVD risk may be effective for reduction of ASCVD. For recent study for Cardiovascular-Kidney-Metabolic Syndrome (CKM), the database of National Health and Nutrition Examination Survey (NHANES) were analyzed for 10 years [20]. CKM individuals (stage 1,2,3,4) and non-CKM individuals (stage 0) were analyzed. The results showed that cases on LCD showed -62% risk for all-cause mortality compared with those on not-LCD. Some limitation may exist for this report. This case showed several clinical problems for T2D, arteriosclerosis, PAD, colonic diverticula and related anemia. Current clinical progress will give meaningful perspectives of adequate management for diabetes and gastroenterology.

In summary, current article described the meaningful case with several problems we hope that it will become useful reference for clinical research and practice in the future.

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

Funding: There was no funding received for this paper.

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