Diabetology International最新文献

Aims: We aimed to investigate potential predictors of effectiveness of SGLT2 inhibitors (SGLT2i) in individuals with type 1 diabetes (T1D) on sensor-augmented pump (SAP) therapy.

Methods: We included individuals with T1D receiving SAP therapy at our hospital who were newly initiated on SGLT2i between 2019 and 2020 and were followed for at least 1 year. Data on BMI, blood tests, and continuous glucose monitoring (CGM) were compared before and 12 months after initiation of SGLT2i. Predictors of incremental increases in time in range (ΔTIR) were explored using a multiple regression analysis. Cutoff values for the predictors were determined using an ROC curve analysis.

Results: A total of 17 individuals (females, 70.6%; median age, 44.0 years) were included, excluding three individuals who discontinued SGLT2i due to side effects. During follow-up, their median BMI decreased significantly (P = 0.013), while no significant change was seen in their total daily dose of insulin, basal-to-total insulin ratio. Again, their HbA1c, TIR, and time above range (TAR) improved significantly (P = 0.004, P = 0.003, and P = 0.003, respectively), while their time below range (TBR) showed no significant change. The predictor of increased ΔTIR was high urinary albumin-to-creatinine ratio (UACR) at baseline (P = 0.026) only, with the cutoff value determined to be 28.0 mg/g Cr or higher (AUC = 0.82, P = 0.003).

Conclusions: It may be suggested that individuals with T1D on SAP therapy and having near-microalbuminuria or higher could be expected to show significant improvement in TIR.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00743-4.

[This corrects the article DOI: 10.1007/s13340-023-00688-0.].

Background: Obesity is increasingly being recognized as a chronic disease that exacerbates type 2 diabetes and its related complications. Oral semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in weight loss and diabetes control in Western populations. However, in real-world clinical practice, its effectiveness in Japanese patients, who typically exhibit a leaner phenotype and unique genetic susceptibilities affecting insulin secretion, remains unclear.

Methods: We retrospectively evaluated the electronic medical records of 313 patients treated with oral semaglutide and 11,239 untreated controls at the Keio University School of Medicine. We performed propensity score matching to adjust for covariates, including age, sex, height, weight, blood pressure, blood test data, medications, and compared the cardiometabolic risk factors, including HbA1c, blood pressure, lipids, and liver function 180 days post-treatment, of both patient groups. We conducted a subgroup analysis for patients who achieved ≥ 3% weight loss.

Results: After propensity score matching, the semaglutide group demonstrated significantly better outcomes for HbA1c reduction and weight loss and improvements in systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and liver function than the control group. Subgroup analysis of patients with ≥ 3% weight loss revealed superior HbA1c improvements in the semaglutide group; however, no significant differences in other metabolic parameters, such as SBP, LDL-C, and liver function, were observed.

Conclusion: Oral semaglutide effectively improved metabolic markers in Japanese patients with type 2 diabetes, similar to that in Western populations. Weight loss itself was suggested to significantly contribute to blood pressure, lipid levels, and liver function changes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00744-3.

We report the case of a 33-year-old woman who was referred to the department of endocrinology and diagnosed with gestational diabetes mellitus (GDM). She had been hypertensive from 20 weeks of pregnancy. A 75 g oral glucose tolerance test for screening of GDM at 26 weeks of pregnancy revealed positive results at two points: 183 mg/dL at 60 min, and 193 mg/dL at 90 min. At the first visit to the Department of Endocrinology, Cushing's features were clinically unclear. She started self-monitoring blood glucose levels, and hypokalemia was detected. At 28 weeks of pregnancy, she was admitted to our hospital because of uncontrolled blood pressure. The patient started multiple injections of rapid insulin for postprandial hyperglycemia. Laboratory testing revealed suppressed plasma ACTH (< 1.5 pg/mL) and elevated serum cortisol levels (34.1 μg/dL) in the early morning. Because of uncontrollable pregnancy related complications, the patient delivered a baby by Caesarean section at 29 weeks of pregnancy. After delivery, she was diagnosed with ACTH-independent Cushing's syndrome by endocrinological tests. Computed tomography scan demonstrated a right adrenal tumor measuring 24 mm at greatest dimension. Twenty-three days after delivery, laparoscopic right adrenalectomy was performed. The diagnosis of cortisol-producing adrenocortical adenoma was pathologically confirmed. After surgery, the patient was given glucocorticoids as a replacement, and her blood pressure, blood glucose, and serum potassium levels were normalized. Although rare, GDM may be caused by Cushing's syndrome. Pregnant women with combinations of GDM, hypertension, and hypokalemia should be clinically suspected as harboring Cushing's syndrome even in the absence of specific clinical features.

A diabetic foot ulcer (DFU) is an open sore or wound that typically develops on the bottom of the foot. Almost 15% of people with diabetes are suffering from delayed wound healing worldwide. The main vehicle for the development of ulcers in the diabetic population is poor circulation and peripheral neuropathy. Chronic injuries from diabetes frequently lead to traumatic lower leg amputations. Hydrogels are three-dimensional gels that can be fabricated from natural polymers and synthetic polymers. Biopolymers are flexible, elastic, or fibrous materials that come from a natural source, such as plants, animals, bacteria, or other living things. Some of the naturally occurring polymers that are frequently employed in wound dressing applications include polysaccharides and proteins. These polymers can be employed for many therapeutic applications because of their inherent biocompatibility, low immunogenicity, non-toxicity, and biodegradability. They represent a tuneable platform for enhancing skin healing. Therefore, this review paper interprets how natural biopolymers and their various hydrogel forms can be potentially used for diabetic wound healing.

Aims: To clarify the impact of Breslow's scores consisting of only lifestyle habits or American Heart Association's (AHA) Life's Simple 7 scores consisting of lifestyle habits and control targets on starting dialysis in people with or without diabetes mellitus (DM).

Methods: To pursue the study aims, we examined a nationwide database on 294,647 individuals with and without DM aged 19-72 y in Japan to pursue the study aims. Using multivariate Cox modeling, we evaluated and compared 5 risk factors based on the unfavorable lifestyle factors in Breslow's scores and the unfavorable lifestyle factors and clinical values in AHA Life's Simple 7 scores.

Results: DM increased the risk of the initiation of dialysis 5- to sixfold but that risk did not increase with worsening of Breslow risk factors. Compared with no risk factor, 5 risk factors derived from AHA's Life's Simple 7 presented 9.8-fold and 4.2-fold risks for the initiation of dialysis in non-DM and DM, respectively. In comparison with non-DM and no risk factor, risk of the initiation of dialysis dramatically increased up to 32.3 times according to the number of AHA risk factors in those with DM.

Conclusions: DM and risk factors derived from AHA's Life's Simple 7 synergistically increased the risk of the initiation of dialysis. Factors similar to those used to predict cardiovascular disease would also be useful to predict the initiation of dialysis. These approaches might be helpful in clinical practice and patient education.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00739-0.

Diabetic kidney disease (DKD) represents the most lethal complication in both type 1 and type 2 diabetes. The disease progresses without obvious symptoms and is often refractory when apparent symptoms have emerged. Although the molecular mechanisms underlying the onset/progression of DKD have been extensively studied, only a few effective therapies are currently available. Pathogenesis of DKD involves multifaced events caused by diabetes, which include alterations of metabolisms, signals, and hemodynamics. While the considerable efficacy of sodium/glucose cotransporter-2 (SGLT2) inhibitors or angiotensin II receptor blockers (ARBs) for DKD has been recognized, the ever-increasing number of patients with diabetes and DKD warrants additional practical therapeutic approaches that prevent DKD from diabetes. One plausible but promising target is the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, which senses cellular nutrients to control various anabolic and catabolic processes. This review introduces the current understanding of the mTOR signaling pathway and its roles in the development of DKD and other chronic kidney diseases (CKDs), and discusses potential therapeutic approaches targeting this pathway for the future treatment of DKD.

There is growing evidence suggesting an association between severe acute respiratory coronavirus syndrome coronavirus 2 (SARS-CoV-2) infection and various extrapulmonary diseases since the advent of coronavirus disease 2019 (COVID-19) pandemic. However, case reports of fulminant type 1 diabetes mellitus (FT1D) following SARS-CoV-2 infection are limited. We encountered a 44-year-old Japanese woman who developed FT1D accompanied by subclinical thyrotoxicosis caused by autoimmune thyroid disease (AITD) approximately one week after SARS-CoV-2 infection. The patient developed fever and flu-like symptom 4 days before transportation and tested positive then for the SARS-CoV-2 antigen self-test. She subsequently developed sudden thirst, polyuria, and fatigue of 1 day duration and was urgently brought to our emergency room. Laboratory findings indicated diabetic ketoacidosis (DKA) without marked elevation of serum glycated hemoglobin (HbA1c) levels (glucose, 930 mg/dL; HbA1c, 7.4%). Her insulin secretory capacity was almost completely depleted, and islet-specific autoantibodies were negative. Endocrine examinations revealed subclinical thyrotoxicosis, which was positive for thyroid stimulation hormone receptor antibodies. Based on these results, the patient was diagnosed with FT1D accompanied by AITD and immediately started on intensive insulin therapy with a basal-bolus subcutaneous insulin regimen. Human leukocyte antigen analysis revealed haplotypes, indicating susceptibility to both FT1D and AITD. Further studies are required to elucidate the causal relationship between SARS-CoV-2 infection, FT1D, and AITD. However, clinicians must be vigilant about possible development of FT1D and AITD to enable accurate diagnosis and treatment of patients with DKA during the COVID-19 pandemic.

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4is) are the most widely used oral hypoglycemic drugs in Japan. However, once-daily oral semaglutide has been reported to reduce glycated hemoglobin (HbA1c) and body weight (BW) without causing significant hypoglycemia. Here, we aimed to evaluate the efficacy and safety of switching from a DPP-4i to oral semaglutide in Japanese patients with type 2 diabetes (T2D).

Methods: We performed a single-center retrospective study of the changes in HbA1c and BW in 68 patients with T2D who were switched from a DPP-4i and took oral semaglutide for  ≥ 6 months, without changes in any other oral hypoglycemic agent.

Results: Mean HbA1c decreased from 7.8 to 7.0% (p < 0.001) and BW decreased from 74.2 to 71.2 kg (p < 0.001) over 6 months. The decrease in HbA1c was more pronounced in participants with high baseline HbA1c (r =  - 0.542, p < 0.001). There was also a trend (r = 0.236, p = 0.052) toward a decrease in BW in individuals with shorter disease duration. There were reductions in either HbA1c or BW in 65 participants (95.6%). In addition, the larger the decrease in HbA1c was, the greater was the decrease in BW (r = 0.480, p < 0.001). Eighteen participants (20.1%) discontinued the drug within 6 months, of whom 10 (11.6% of the total) did so because of suspected adverse effects and the discontinuation rate was the highest in older, non-obese patients.

Conclusions: Switching from a DPP-4i to oral semaglutide may be useful for Japanese patients with T2D who have inadequate glycemic or BW control. However, its utility may be limited by gastrointestinal adverse effects in certain patients.