Background:It is becoming increasingly important to investigate not only micro-/macrovascular complications, but also comorbidities associated with diabetes. In the Asahi Diabetes Complications Study (Asahi Study), in addition to micro-/macrovascular complications, the onset and progression of dementia and sarcopenia were also investigated in patients with diabetes. Methods:The Asahi Study is a prospective 8-year observational cohort study of subjects with diabetes receiving outpatient care at the Institute of Medical Science, Asahi Life Foundation. Participants were enrolled between November 2014 and December 2017. The baseline data include the age, HbA1c level, and median duration of diabetes. In addition, medication use, prevalence of micro-/macrovascular complications, and presence/absence of malignant neoplasms were also assessed. Results:A total of 49 patients with type 1 DM (T1DM group) and 791 patients with type 2 DM (T2DM group) were enrolled in the study. The mean age was 58.4 years in the T1DM group and 64.9 years in the T2DM group. Other baseline characteristics (T1DM/T2DM) were: mean HbA1c 7.5%/7.0%; median duration of diabetes 23 years/18 years. In regard to medication history, in the T2DM group, 57.3% were receiving oral hypoglycemic agents, 5.6% were receiving injectable GLP-1 receptor agonists, and 28.4% were receiving insulin therapy. The prevalences of microvascular complications, macrovascular complications, and malignant neoplasms were approximately 30-50%, 10%, and 7%, respectively, in the study participants. Conclusion:This 8-year observation study may offer valuable insights into the relationship between risk factor management and development of diabetic complications/comorbidities in persons with diabetes.

Aim This study aims to evaluate the associations between the copper/zinc (Cu/Zn) ratio and inflammatory biomarkers and the incidence of chronic kidney disease (CKD) in individuals with type 2 diabetes and to validate our previous cross-sectional study using the baseline data of this study. Methods We conducted a prospective, observational study of 416 individuals with type 2 diabetes without CKD. We used multivariable Cox proportional hazard models to determine the HRs for CKD incidence. The Cu/Zn ratio and soluble tumor necrosis factor-α receptor 1 (sTNFαR1) concentrations (pg/mL) were analyzed as continuous variables and as categories classified according to each cutoff value for detecting CKD. The high-sensitivity C-reactive protein (hsCRP) concentrations between these categories were compared. Results CKD was identified in 165 participants. The Cu/Zn ratio and sTNFαR1 concentrations were identified as significant predictors, independent of each other, after full adjustment (P = 0.048 and P = 0.006, respectively). Compared to the Cu/Zn <1.281 and sTNFαR1 <1081 group, the HRs for the CKD incidence were significantly higher in the Cu/Zn <1.281 and sTNFαR1 ≥1081 group (HR 2.06, 95% CI 1.34-3.26) and even higher in the Cu/Zn ≥1.281 and sTNFαR1 ≥1081 group (3.29, 1.97-5.50) after full adjustment. The hsCRP concentrations were significantly highest in the Cu/Zn ≥1.281 and sTNFαR1 ≥1081 group compared with the other three groups (all P < 0.05) and were significantly higher in the Cu/Zn ≥1.281 and sTNFαR1 <1081 group and in the Cu/Zn <1.281 and sTNFαR1 ≥1081 group compared with those in the Cu/Zn <1.281 and sTNFαR1 <1081 group (both P < 0.05). Conclusions The Cu/Zn ratio and sTNFαR1 concentrations are independent predictors of the incidence of CKD in individuals with type 2 diabetes. Furthermore, under elevated sTNFαR1 concentrations, an increase in the Cu/Zn ratio may further aggravate inflammation and accelerate the incidence of CKD in individuals with type 2 diabetes. These new findings are supported by the results from our previous cross-sectional study.

Aim: The present study aimed to determine whether decreased masticatory performance and tongue-lip motor function are associated with an increased incidence of adverse health events in patients with metabolic disease. Methods: One thousand patients with metabolic diseases including diabetes, dyslipidemia, hypertension, and hyperuricemia were recruited. Masticatory performance was assessed using a gummy jelly test, wherein glucose elution from chewed gummy jelly was measured. The tongue-lip motor function was measured using repeatedly pronounced syllables per second. Their association with the incidence of adverse health events (a composite of all-cause death, cardiovascular disease, bone fracture, malignant neoplasm, pneumonia, and dementia) was investigated using the generalized propensity score (GPS) method. Results: During a median follow-up period of 36.6 (interquartile range, 35.0-37.7) months, adverse health events were observed in 191 patients. The GPS adjusted dose-response function demonstrated that masticatory performance was inversely associated with the incidence of adverse health events. The 3-year incidence rate was 22.8% (95% confidence interval, 19.0-26.4%) for the lower quartile versus 13.6% (10.5-16.7%) for the upper quartile ( P < 0.001). Similarly, the tongue-lip motor function was inversely associated with the incidence of adverse health events, with a 3-year incidence rate of 23.6% (20.0-27.0%) for the lower quartile versus 13.2% (10.4-15.9%) for the upper quartile ( P < 0.001). Conclusions: De creased masticatory performance and tongue-lip motor function were associated with an increased incidence of adverse health events in patients with metabolic disease.

Objective This prospective observational study explored the changes in the daily glycemic profile after switching from injectable to oral semaglutide in patients with type 2 diabetes mellitus. Methods Patients with type 2 diabetes mellitus who were treated with once-weekly 0.5 mg injectable semaglutide and wished to switch to once-daily oral semaglutide participated in this study. Oral semaglutide was initiated at 3 mg and increased to 7 mg a month later, according to the package insert. Before and two months after the switch, participants wore a sensor for continuous glucose monitoring for up to 14 days. We also evaluated the questionnaire-based treatment satisfaction and the preference between the two formulations. Patients Twenty-three patients participated. Results Mean glucose levels significantly increased by 9 mg/dL on average, from 132±20 to 141±27 mg/dL (p=0.047), which was equivalent to a change of 0.2% in the estimated hemoglobin A1c (6.5±0.5% to 6.7±0.7%). The inter-individual variability assessed with standard deviation also significantly increased (p=0.004). The change in treatment satisfaction varied considerably among patients, with no specific trend in the overall population. After trying oral semaglutide, 48% of patients responded that they preferred the oral formulation, while 35% preferred the injectable formulation, and 17% had no preference. Conclusion The mean glucose levels increased by 9 mg/dL on average after switching from once-weekly 0.5 mg injectable semaglutide to once-daily 7 mg oral semaglutide, with an increased inter-individual variability. The change in treatment satisfaction considerably varied among patients.

PURPOSE:Although the rate of diabetic retinopathy (DR)-related blindness has decreased in developed countries in recent years, the reasons for this decrease have remained unclear. The prevalence/severity trends of DR at the first visit in patients with untreated type 2 diabetes mellitus (T2DM) patients seen between the1986s and 2018s were assessed. METHODS:A total of 1979 Japanese T2DM patients diagnosed between 1986 and 2018 were divided into four groups by the decade of their first visit: the 1986 years (1986-1987), the 1996 years (1996-1997), the 2006 years (2006-2008), the 2016 years (2016-2018). The DR prevalence/severity trends were assessed. RESULTS:A significant decrease in the rate of prevalence of DR from the 1986s to 2016s was observed among previously untreated T2DM patients visiting our hospital for the first time (1986s: 25.5%; 1996s: 26.2%; 2006s: 22.2%; and 2016s: 15.6%). The prevalence was significantly higher in females (30.2%) than in males (21.3%). Although the severity trend of DR did not differ significantly among the four measurement years, the rate of simple DR was the highest in the 2016s. CONCLUSION:We found, for the first time, a significant decrease in the rate of prevalence of DR from the 1986s to 2016s in patients with untreated T2DM visiting our hospital for the first time. A decrease in the rate of DR prevalence could explain, at least in part, the observed reduction in the rate of blindness in patients with T2DM.

Introduction:We investigated the association between history of vaccination for coronavirus disease 2019 (COVID-19) and symptoms at its diagnosis. Methods:We retrospectively analyzed 2566 consecutive individuals suspected of having COVID-19 and visited a designated clinic between January and September 2022 (1733 were diagnosed with COVID-19, and 816 tested negative for COVID-19) in Japan. The individuals were divided by vaccination history for COVID-19. Results:In the COVID-19-free individuals, the vaccination was not significantly associated with any symptoms. Contrarily, those with COVID-19 demonstrated an inverse relationship between the vaccination and body temperature; the adjusted mean value was higher by 0.01°C, 0.04°C, 0.09°C, 0.27°C, and 0.34°C and 0.48°C in individuals vaccinated 2-4, 4-6, 6-8, 8-10, and >10 months before and those unvaccinated, respectively, than in those vaccinated within 2 months (P = 0.96, 0.41, 0.081, 0.006, 0.004, and <0.001). Furthermore, among the affected population, individuals vaccinated long before or never vaccinated more frequently complained of fatigue and headache; the adjusted odds ratios of those vaccinated >10 months before and those unvaccinated compared with those vaccinated within 2 months were 2.53 and 2.45 for fatigue and 2.53 and 2.17 for headache (all P < 0.05). Contrarily, the prevalence of rhinorrhea, sore throat, and cough was higher in recently vaccinated individuals (adjusted odds ratios of those vaccinated within 2 months versus those unvaccinated, 2.40, 2.46, and 2.46; all P < 0.05). Conclusions:Symptoms at the COVID-19 diagnosis differed with the vaccination history. Information on vaccination history would be worth using when suspecting COVID-19 based on symptoms.

AbstractAims/IntroductionPrevious studies have reported that the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) delays gastric emptying, and gastric emptying was assessed by the 13C breath test or paracetamol absorption technique. However, neither of them is clinically familiar in real‐world clinical practice. The purpose of the present study was to investigate the association between GLP‐1RA treatment and gastric residue in an esophagogastroduodenoscopy.Materials and MethodsThis study was a matched pair case–control study. The study population consisted of 1,128 individuals with diabetes who had esophagogastroduodenoscopy at our clinic between July 2020 and June 2022. To account for differences in characteristics, such as age, sex, insulin treatment and glycated hemoglobin, we carried out a one‐to‐one nearest neighbor propensity score matching analysis between diabetes patients with and without GLP‐1RA treatment. After matching, we compared the presence of gastric residue in an esophagogastroduodenoscopy by the McNemar test between patients with and without GLP‐1RA treatment.ResultsAfter the propensity score matching, we selected 205 pairs. In the propensity score‐matched comparison, the proportion of gastric residue was statistically significantly higher in the GLP‐1RA treatment group (0.49% vs 5.4%, P = 0.004). The details of GLP‐1RA prescribed for the 11 patients with gastric residue were liraglutide once daily 1.8 mg (n = 2), dulaglutide once weekly 0.75 mg (n = 5), semaglutide once weekly 0.5 mg (n = 2) and semaglutide once weekly 1.0 mg (n = 2).ConclusionGLP‐1RA treatment is associated with gastric residue in an esophagogastroduodenoscopy in patients with diabetes.

Abstract Aims/Introduction There has been an increase in research on diabetes‐related stigma and its association with glycated hemoglobin (HbA1c) over the past years. However, little is known about the association of self‐stigma with HbA1c in persons with type 1 diabetes. This study aims to examine the association between self‐stigma and HbA1c in Japanese people with type 1 diabetes. Materials and Methods This cross‐sectional study was conducted at a clinic in Tokyo. Questionnaires using nine items from the Japanese version of the Self‐Stigma Scale was distributed to outpatients with type 1 diabetes, aged ≥18 years. We excluded outpatients with serious mental disorder, those who required urgent medical treatment or received hemodialysis. Adjusted linear regression analyses tested the association between the score of the 9‐item Self‐Stigma Scale and HbA1c. Results Questionnaires were distributed to 166 eligible participants. A total of 109 participants were included in the final analysis after excluding participants with incomplete answers and laboratory data. After adjusting for age, sex, employment status, body mass index, duration of diabetes and insulin secretion, there was a significant positive association between self‐stigma and HbA1c (β = 0.05, 95% confidence interval 0.01 to 0.08). Conclusions This cross‐sectional study showed a significant association between self‐stigma and HbA1c in persons with type 1 diabetes. Addressing self‐stigma might be as equally essential as measuring HbA1c in evaluating glycemic outcome among individuals with type 1 diabetes.

Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated disease that manifests as the triad of thrombotic microangiopathy. We identified two aHUS patients with neither anti-complement factor H (CFH) antibodies nor causative variants of seven aHUS-related genes (CFH, CFI, CFB, C3, MCP, THBD, and DGKE); however, their plasma showed increased levels of hemolysis by hemolytic assay, which strongly suggests CFH-related abnormalities. Using a copy number variation (CNV) analysis of the CFH/CFHR gene cluster, we identified CFH-CFHR1 hybrid genes in these patients. We verified the absence of aHUS-related abnormal CNVs of the CFH gene in control genomes of 2036 individuals in the general population, which suggests that pathogenicity is related to these hybrid genes. Our study emphasizes that, for patients suspected of having aHUS, it is important to perform an integrated analysis based on a clinical examination, functional analysis, and detailed genetic investigation.

Introduction: Malignant hypertension (mHTN) damages multiple target organs, including the kidneys. mHTN has been regarded as one of the causes of secondary thrombotic microangiopathy (TMA); however, a high prevalence of complement gene abnormalities was recently reported in cohorts of mHTN. Case report: We herein describe a 47-year-old male who presented with severe hypertension, renal failure (serum creatinine (sCr): 11.6 mg/dL), heart failure, retinal hemorrhage, hemolytic anemia, and thrombocytopenia. Renal biopsy findings were consistent with acute hypertensive nephrosclerosis. The patient was diagnosed with secondary TMA associated with mHTN. However, his previous medical history of TMA of unknown origin and family history of atypical hemolytic uremic syndrome (aHUS) suggested as aHUS presenting mHTN, and genetic testing revealed a pathogenic C3 mutation (p.I1157T). The patient required plasma exchange and hemodialysis for 2 weeks and was able to withdraw from dialysis by antihypertensive therapy without eculizumab. Renal function gradually improved to a sCr level of 2.7 mg/dL under antihypertensive therapy for 2 years after the event. There was no recurrence, and renal function was preserved throughout a 3-year follow-up. Discussion: mHTN is a common presentation of aHUS. In cases of mHTN, abnormalities in complement-related genes may be involved in the development of the disease.

ABSTRACT Aims/Introduction The purpose of this retrospective observational cohort study was to compare outpatient diabetes care and glycated hemoglobin (HbA1c) level during the coronavirus disease 2019 pandemic in 2020 with 2019, and to compare the glucose‐lowering effect of telemedicine and clinic visits during the state of emergency in Japan declared from 7 April to 25 May (inter‐period) 2020. Materials and Methods A total of 13 weeks before and after the inter‐period were designated as the pre‐period and post‐period, respectively. The number of study participants who had clinic visits during the pre‐period and the post‐period were 3,333 in 2020 and 3,608 in 2019. Propensity score matching was carried out to compare the effect of telemedicine and clinic visits on diabetes control in 2020 among diabetes patients with insufficient glucose control (HbA1c ≥7%). The primary outcome was post‐period HbA1c. Results The major difference between 2020 and 2019 was the use of telemedicine in 2020. After adjustment for age, sex, diabetes type, pre‐period HbA1c and pre‐period body mass index, glycemic control evaluated by HbA1c was significantly worse in the post‐period of 2020 than 2019. In the propensity score‐matched 618 pairs, the clinic visit group had significantly better post‐period HbA1c than the telemedicine group (7.5% vs 7.4%, P = 0.023). Conclusions Glycemic control was slightly, but significantly, worse in 2020 than 2019. Although telemedicine significantly improved glycemic control during the coronavirus disease 2019 pandemic in 2020, clinic visits improved HbA1c significantly more. The substitution of telemedicine for clinic visits appears to be a viable option under emergency conditions, but clinic visits might be a better option when possible.

RECK encodes a membrane-anchored protease-regulator which is often downregulated in a wide variety of cancers, and reduced RECK expression often correlates with poorer prognoses. In mouse models, forced expression of RECK in tumor xenografts results in suppression of tumor angiogenesis, invasion, and metastasis. RECK mutations, however, are rare in cancer genomes, suggesting that agents that re-activate dormant RECK may be of clinical value. We found a potent RECK -inducer, DSK638, that inhibits spontaneous lung metastasis in our mouse xenograft model. Induction of RECK expression involves SP1 sites in its promoter and may be mediated by KLF2. DSK638 also upregulates MXI1, an endogenous MYC-antagonist, and inhibition of metastasis by DSK638 is dependent on both RECK and MXI1. This study demonstrates the utility of our approach (using a simple reporter assay followed by multiple phenotypic assays) and DSK638 itself (as a reference compound) in finding potential metastasis-suppressing drugs.

The complement system is part of the innate immune system. The crucial step in activating the complement system is the generation and regulation of C3 convertase complexes, which are needed to generate opsonins that promote phagocytosis, to generate C3a that regulates inflammation, and to initiate the lytic terminal pathway through the generation and activity of C5 convertases. A growing body of evidence has highlighted the interplay between the complement system, coagulation system, platelets, neutrophils, and endothelial cells. The kidneys are highly susceptible to complement-mediated injury in several genetic, infectious, and autoimmune diseases. Atypical hemolytic uremic syndrome (aHUS) and lupus nephritis (LN) are both characterized by thrombosis in the glomerular capillaries of the kidneys. In aHUS, congenital or acquired defects in complement regulators may trigger platelet aggregation and activation, resulting in the formation of platelet-rich thrombi in the kidneys. Because glomerular vasculopathy is usually noted with immunoglobulin and complement accumulation in LN, complement-mediated activation of tissue factors could partly explain the autoimmune mechanism of thrombosis. Thus, kidney glomerular capillary thrombosis is mediated by complement dysregulation and may also be associated with complement overactivation. Further investigation is required to clarify the interaction between these vascular components and develop specific therapeutic approaches.

Abstract Aims/Introduction We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. Materials and Methods A cross‐sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m2. Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor‐α receptor 1 (sTNFαR1), and high‐sensitivity C‐reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined. Results DKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006). Conclusions Under an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.

ABSTRACT Aims/Introduction Aging of society is accelerating in many countries. The purpose of this study was to describe the clinical features and sulfonylurea usage among diabetes outpatients aged ≥90 years (nonagenarians). Materials and Methods This study was a retrospective observational study. The study population consisted of 69 nonagenarian diabetes outpatients and 857 diabetes outpatients aged <90 years. Patients were classified into four groups: group 1, <65 years; group 2, 65–74 years; group 3, 75–89 years; and group 4, ≥90 years. The presence of hypoglycemic episodes was defined as having self‐reported symptoms, or self‐monitored or clinically measured blood glucose level <70 mg/dL. Results The median glycated hemoglobin (HbA1c) in group 1 and group 4 was 7.0% and 7.2%, respectively (P = 0.506). The proportion of sulfonylurea treatment in group 4 was 45.5%, which is significantly higher compared with the other three groups (20.0–27.8%, P < 0.001). In group 4, there was no difference between patients with or without sulfonylurea in age, sex, body mass index, HbA1c and number of antihyperglycemic agents. Five out of 25 nonagenarian sulfonylurea‐treated patients had hypoglycemic episodes within the last 2 years, their HbA1c were all 7.0 ≤ HbA1c < 8.0, and sulfonylurea or insulin was tapered in all cases after confirming hypoglycemia. Tapering dosage was attempted in all 25 sulfonylurea‐treated nonagenarian patients, but 15 needed to continue sulfonylurea for glycemic control, and 10 continued sulfonylurea with unknown reasons from their medical records. Conclusions Although tapering the dosage of sulfonylurea was attempted in nonagenarian patients, sulfonylurea was widely continued for glycemic control. Reverse clinical inertia may exist in some sulfonylurea‐treated nonagenarian patients.

Abstract Background The current study aimed to reveal the correlation of beta-cell function and insulin sensitivity with glycemic control and weight control before and after medical nutrition therapy (MNT) in patients with newly-diagnosed type 2 diabetes mellitus. Methods We retrospectively analyzed consecutive 68 patients with newly-diagnosed type 2 diabetes mellitus who started MNT without antihyperglycemic medications and underwent a 75-g oral glucose tolerance test (OGTT) before and after the therapy. Beta-cell function was evaluated by the OGTT-derived disposition index, whereas insulin sensitivity was evaluated by Matsuda’s insulin sensitivity index. Results After 4.0 ± 1.5 months of MNT, mean HbA1c and body mass index significantly decreased from 9.6 ± 1.8% to 7.2 ± 1.0% and from 26.9 ± 4.1 to 25.4 ± 3.7 kg/m2 (both P < 0.001), while the median disposition index and Matsuda’s index significantly increased from 0.34 (0.20–0.68) to 0.88 (0.53–1.52) (P < 0.001) and from 4.70 (2.95–5.93) to 5.17 (3.48–6.89) (P = 0.003), respectively. The disposition index was significantly correlated with HbA1c levels both before and after MNT (r = -0.61 and -0.68; both P < 0.001). The magnitude of the correlation after MNT was not different from that before MNT (P = 0.42). Matsuda’s index was correlated not with HbA1c levels but with body mass index, both before (r = 0.07 [P = 0.57] and r = -0.58 [P < 0.001]) and after MNT (r = -0.01 [P = 0.95] and r = -0.52 [P < 0.001]). Conclusions Beta-cell function was improved in conjunction with glycemic control after MNT in patients with newly-diagnosed type 2 diabetes mellitus. Insulin sensitivity was linked with weight control rather than glycemic control.

Atypical hemolytic uremic syndrome (aHUS) is a disease associated with dysregulation of the immune complement system, especially of the alternative pathway (AP). Complement factor H (CFH), consisting of 20 domains called complement control protein (CCP1-20), downregulates the AP as a cofactor for mediating C3 inactivation by complement factor I. However, anomalies related to CFH are known to cause excessive complement activation and cytotoxicity. In aHUS, mutations and the presence of anti-CFH autoantibodies (AAbs) have been reported as plausible causes of CFH dysfunction, and it is known that CFH-related aHUS carries a high probability of end-stage renal disease. Elucidating the detailed functions of CFH at the molecular level will help to understand aHUS pathogenesis. Herein, we used biophysical data to reveal that a heavy-chain antibody fragment, termed VHH4, recognized CFH with high affinity. Hemolytic assays also indicated that VHH4 disrupted the protective function of CFH on sheep erythrocytes. Furthermore, Xray crystallography revealed that VHH4 recognized the Leu1181-Leu1189(CCP20) loop, a known anti-CFH AAbs epitope. We next analyzed the dynamics of the C-terminal region of CFH and showed that the epitopes recognized by anti-CFH AAbs and VHH4 were the most flexible regions in CCP18-20. Finally, we conducted mutation analyses to elucidate the mechanism of VHH4 recognition of CFH and revealed that VHH4 inserts the Trp1183(CCP20) residue of CFH into the pocket formed by the complementary determining region 3 loop. These results suggested that anti-CFH AAbs may adopt a similar molecular mechanism to recognize the flexible loop of Leu1181Leu1189(CCP20), leading to aHUS pathogenesis.

Abstract Aims/Introduction This study aimed to reveal lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 (COVID‐19) pandemic in Japan. Materials and Methods We retrospectively analyzed 1,402 outpatients with diabetes at a clinic in Osaka, Japan, who responded to an interview sheet regarding lifestyle changes during the COVID‐19 pandemic between 28 March and 30 May 2020. The association of lifestyle changes with hemoglobin A1c (HbA1c) and weight changes from February to May 2020 was investigated using the linear regression model. We also investigated the association with clinically important change of HbA1c (by ≥0.3%) and bodyweight (by ≥3%), using the cumulative link model. Results Leisure time and other outside physical activities were decreased in one‐quarter of patients during the COVID‐19 pandemic, whereas the amount of meals and snacks was decreased and increased in approximately 10%, respectively. The change in leisure time physical activities was inversely associated with HbA1c and weight changes, whereas the quantitative change of meals with the decline in eating out and that of snacks were positively associated with HbA1c and weight changes (all P < 0.05). The quantitative change of meals without the decline in eating out was also positively associated with weight change (P = 0.012). The cumulative link model for clinically important HbA1c and weight change showed broadly similar associations, except for that between snacks and bodyweight (P = 0.15). Conclusions A considerable number of outpatients with diabetes experienced lifestyle changes during the COVID‐19 pandemic. The lifestyle changes were associated with HbA1c and weight changes.