Association between infant birth weight and gestational weight gain in Japanese women with diabetes mellitus.

AIMS/INTRODUCTION: In 2021, the guidelines on gestational weight gain (GWG) were revised and increased by 2-3 kg in Japan. This study aimed to investigate whether the revised guidelines would increase the incidence of babies with excessive birth weight in mothers with diabetes. MATERIALS AND METHODS: This retrospective study included 369 deliveries of women with diabetes whose pre-pregnancy body mass index was below 30 kg/m2 between 1982 and 2021. The primary outcome measure was large for gestational age (LGA). We compared the incidence of LGA between women who gained weight within the previous guidelines and women who gained weight within the revised guidelines. We also compared the incidence of macrosomia, preeclampsia, small for gestational age (SGA), and low birth weight. RESULTS: The incidence of LGA was not significantly different between women who gained weight within the revised guidelines and those within the previous guidelines (34.6% [95% confidence interval 25.6-44.6%] for the revised guidelines vs 28.9% [21.6-37.1%] for the previous guidelines; P = 0.246). Neither was the incidence of macrosomia or preeclampsia significantly different (8.7% [4.0-15.8%] vs 5.6% [2.5-10.8%] and 5.8% [2.1-12.1%] vs 6.3% [2.9-11.7%]; P = 0.264 and 0.824, respectively), while women who gained weight within the revised guidelines had a lower incidence of SGA (1.9% [0.2-6.8%] vs 10.6% [6.0-16.8%]; P = 0.001) and low birth weight (1.0% [0.02-5.2%] vs 7.0% [3.4-12.6%]; P = 0.023). CONCLUSIONS: The revised GWG guidelines could be beneficial in women with diabetes in terms of delivering babies with appropriate birth weight.

Effect of sodium-glucose cotransporter 2 inhibitors on serum low-density lipoprotein cholesterol in Japanese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: We aimed to evaluate factors that influence changes in blood low-density lipoprotein cholesterol (LDL-C) levels after treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: We retrospectively analyzed clinical data of outpatients newly initiated on SGLT2 inhibitors (n = 176) and other oral antidiabetic drugs (n = 227). The patients were classified into four subgroups according to statin administration and baseline LDL-C levels (<120 or ≥120 mg/dL). Clinical characteristics were compared among the subgroups. Multivariate analysis was carried out to identify factors contributing to changes in LDL-C. RESULTS: The median follow-up period was 13.0 weeks (range 11.9-14.1 weeks, min 8 weeks, maximum 16 weeks) in the SGLT2i group, and 12.0 weeks (range 10.0-14.0 weeks, min 8 weeks, maximum 16 weeks) in the control group. Both groups showed a significant decrease in LDL-C (SGLT2i group -3.8 ± 24.7 mg/dL, control group -3.4 ± 15.0 mg/dL). Multivariate regression analyses showed that in both groups, the change in LDL-C depended on statin use and baseline LDL-C levels. Stratified analyses showed that LDL-C level was significantly decreased in statin users with baseline LDL-C ≥120 mg/dL (from 148.9 ± 33.5 to 109.3 ± 17.9 mg/dL, P = 0.002), and significantly increased in statin non-users with baseline LDL-C <120 mg/dL (from 96.3 ± 27.3 to 104.7 ± 24.8 mg/dL, P = 0.002). These changes were more characteristic for SGLT2 inhibitors than for other oral antidiabetic drugs (P for interaction = 0.010 and <0.001, respectively). CONCLUSIONS: LDL-C levels and statin medication at baseline influence changes in LDL-C after SGLT2 inhibitors treatment in Japanese patients with type 2 diabetes.

Daily Glucose Profiles after Switching from Injectable to Oral Semaglutide in Patients with Type 2 Diabetes Mellitus.

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.

Evaluation of changes in glycemic control and diabetic complications over time and factors associated with the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications. METHODS: We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis. RESULTS: Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors. CONCLUSIONS: In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis.

Continuous glucose monitoring-derived time in range and CV are associated with altered tissue characteristics of the carotid artery wall in people with type 2 diabetes.

AIMS/HYPOTHESIS: Previous studies have suggested that glucose variability may accelerate atherosclerosis progression in people with type 2 diabetes. Current guidelines recommend assessing glycaemic control using continuous glucose monitoring (CGM), which provides a comprehensive glycaemic profile to supplement HbA1c measurement. However, the association between CGM-derived metrics and atherosclerosis progression is not entirely clear. METHODS: This exploratory study used baseline data and data obtained after 104 weeks from an ongoing prospective, multicentre, observational study. Six hundred study participants with type 2 diabetes and no apparent history of symptomatic cardiovascular disease underwent CGM and ultrasonographic atherosclerosis measurements of the carotid arteries, including the intima-media thickness (IMT) and grey-scale median (GSM), at baseline and 104 weeks. Non-invasive ultrasonic tissue characterisation of the carotid artery wall or plaque using the GSM reflects vascular composition. Multivariate regression models were used to analyse the association between CGM-derived indices, mainly time in range (TIR) and CV, and changes in carotid atherosclerosis index values. RESULTS: Over the 104-week study period, there were modest increases in mean IMT (from 0.759±0.153 to 0.773±0.152 mm, p<0.001) and thickened-lesion GSM (from 43.5±19.5 to 53.9±23.5 units, p<0.001), but no significant changes in common carotid artery maximum-IMT (from 1.109±0.442 to 1.116±0.469 mm, p=0.453) or mean GSM (from 48.7±19.3 to 49.8±20.8 units, p=0.092). In a linear regression model with adjustment for possible atherosclerotic risk factors, including HbA1c, TIR and CV at baseline were significantly associated with the annual change in mean GSM (regression coefficient per 10% increase in TIR 0.52; 95% CI 0.06, 0.98; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV -0.12; 95% CI -0.22, -0.02; Hochberg-adjusted p value 0.038). TIR and CV at baseline were also significantly associated with the annual change in thickened-lesion GSM (regression coefficient per 10% increase in TIR 0.95; 95% CI 0.12, 1.79; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV -0.19; 95% CI -0.36, -0.01; Hochberg-adjusted p value 0.038). Participants who achieved target CGM-derived metrics at baseline, as proposed by an international consensus, showed significant annual changes in mean GSM compared with those who did not (0.94±6.88 vs -0.21±6.19 units/year, p=0.007). CONCLUSIONS/INTERPRETATION: TIR and CV were significantly associated with changes in the tissue characteristics of the carotid artery wall. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, number UMIN000032325.

Long-term efficacy and safety of early alogliptin initiation in subjects with type 2 diabetes: an extension of the SPEAD-A study.

We previously reported in the study of preventive effects of alogliptin on diabetic atherosclerosis (SPEAD-A) that alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the progression of carotid atherosclerosis in subjects with type 2 diabetes and no history of cardiovascular disease. This extension study of the SPEAD-A trial investigated whether early alogliptin initiation improved long-term cardiovascular outcomes. The SPEAD-A trial randomized 341 subjects with type 2 diabetes to either alogliptin or conventional treatment to investigate the effects of alogliptin on atherosclerosis. All subjects who completed that trial were eligible for this prospective, observational cohort study. The primary endpoint was the first occurrence of a major cardiovascular event, defined as death due to any cause, acute myocardial infarction, or stroke. During the 520-week follow-up period, composite primary outcome events occurred in only a few subjects in each group [8 (5.4%) in the alogliptin group and 9 in the conventional treatment group (5.9%)]. There were no significant differences in the incidence rate of the primary outcome between the two groups. Post hoc Poisson regression analysis showed no significant difference between the two groups in the incidence rate of composite recurrence events for the same outcomes as the primary endpoint. On the other hand, this incidence rate was significantly lower in subjects who received DPP-4 inhibitors before an initial cardiovascular event than in those who did not (5.8 vs. 13.3 per 1000 person-years, respectively, p = 0.04). Early initiation of alogliptin was not associated with a reduced risk of composite cardiovascular disease, which could be attributed to fewer events and/or the addition of DPP-4 inhibitors during the follow-up period.

Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial.

BACKGROUND: This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. METHODS: This was a prospective observational 2-year extension study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. RESULTS: The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (- 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (- 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) - 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (- 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (- 100.2 cm/s, 95% CI - 182.8 to - 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. CONCLUSIONS: Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.

Laughter yoga as an enjoyable therapeutic approach for glycemic control in individuals with type 2 diabetes: A randomized controlled trial.

Background: Laughter has been reported to have various health benefits. However, data on the long-term effects of laughter interventions on diabetes are limited. This study aimed to investigate whether laughter yoga can improve glycemic control among individuals with type 2 diabetes. Methods: In a single-center, randomized controlled trial, 42 participants with type 2 diabetes were randomly assigned to either the intervention or the control group. The intervention consisted of a 12-week laughter yoga program. Hemoglobin A1c (HbA1c), body weight, waist circumference, psychological factors, and sleep duration were evaluated at baseline and week 12. Results: Intention-to-treat analysis showed that participants in the laughter yoga group experienced significant improvements in HbA1c levels (between-group difference: -0.31%; 95% CI -0.54, -0.09) and positive affect scores (between-group difference: 0.62 points; 95% CI 0.003, 1.23). Sleep duration tended to increase in the laughter yoga group with a between-group difference of 0.4 hours (95% CI -0.05, 0.86; P = 0.080). The mean attendance rate for laughter yoga program was high (92.9%). Conclusions: A 12-week laughter yoga program is feasible for individuals with type 2 diabetes and improves glycemic control. These findings suggest that having fun could be a self-care intervention. Further studies with larger numbers of participants are warranted to better evaluate the effects of laughter yoga. Clinical trial registration: http://www.chinadrugtrials.org.cn, identifier UMIN000047164.

Characteristic changes in plasma glutamate levels and free amino acid profiles in Japanese patients with type 1 diabetes mellitus.

AIMS/INTRODUCTION: In addition to absolute insulin deficiency, dysregulated glucagon in type 1 diabetes is considered pathophysiologically important. Previously, we confirmed the presence of dysregulated glucagon in Japanese patients with type 1 diabetes, and found a significant correlation between plasma glucagon and blood urea nitrogen levels, suggesting an association between glucagon and amino acid metabolism. In this study, we evaluated plasma amino acid levels in Japanese patients with type 1 diabetes in the context of their functional relationship with glucagon. MATERIALS AND METHODS: We assessed plasma free amino acid levels using liquid chromatography-mass spectrometry in 77 Japanese patients with type 1 diabetes, and statistically analyzed their characteristics and relationships with clinical parameters, including glucagon. RESULTS: Participants with type 1 diabetes showed a large decrease in glutamate levels together with a characteristic change in plasma free amino acid profiles. The network structural prediction analyses showed correlations between each amino acid and glucagon in type 1 diabetes. CONCLUSIONS: Participants with type 1 diabetes showed characteristic changes in plasma glutamate levels and free amino acid profiles compared with controls and type 2 diabetes patients. Glucagon showed a closer correlation with amino acids than with parameters of glucose metabolism, suggesting that type 1 diabetes includes dysregulation in amino acids through dysregulated glucagon from remaining pancreatic α-cells, together with that in glucose by insulin deficiency.

Changes of HbA1c variability after the switch to a longer-acting insulin analog in people with type 1 diabetes.

This study investigated whether longer-acting basal analogs (insulin degludec and insulin glargine U300) could reduce visit-to-visit hemoglobin A1c (HbA1c) variability in patients with type 1 diabetes. Ninety adults with type 1 diabetes for whom the basal insulin was switched to a longer-acting insulin analog were analyzed retrospectively. The coefficient of variation of HbA1c levels (CV-HbA1c) during the year before and after the switch was compared. The CV-HbA1c after the switch was not significantly different from that before the switch (4.39 ± 2.24% vs 4.25 ± 2.07%; P = 0.506). The linear regression model revealed that CV-HbA1c before the switch was independently associated with the change of CV-HbA1c (regression coefficient per standard deviation = -0.568, P < 0.001), whereas the other variables were not (all P > 0.05). In conclusion, CV-HbA1c remained unchanged after the switch on average, but CV-HbA1c before the switch was associated with the decrease of CV-HbA1c in individuals with type 1 diabetes.

Change in fatty acid composition of plasma triglyceride caused by a 2 week comprehensive risk management for diabetes: A prospective observational study of type 2 diabetes patients with supercritical fluid chromatography/mass spectrometry-based semi-target lipidomic analysis.

AIMS/INTRODUCTION: Hypertriglyceridemia is common in patients with diabetes. Although the fatty acid (FA) composition of triglycerides (TGs) is suggested to be related to the pathology of diabetes and its complications, changes in the fatty acid composition caused by diabetes treatment remain unclear. This study aimed to identify short-term changes in the fatty acid composition of plasma triglycerides after diabetes treatment. MATERIALS AND METHODS: This study was a sub-analysis of a prospective observational study of patients with type 2 diabetes aged between 20 and 75 years who were hospitalized to improve glycemic control (n = 31). A lipidomic analysis of plasma samples on the 2nd and 16th hospital days was conducted by supercritical fluid chromatography coupled with mass spectrometry. RESULTS: In total, 104 types of triglycerides with different compositions were identified. Most of them tended to decrease after treatment. In particular, triglycerides with a lower carbon number and fewer double bonds showed a relatively larger reduction. The inclusion of FA 14:0 (myristic acid), as a constituent of triglyceride, was significantly associated with a more than 50%, and statistically significant, reduction (odds ratio 39.0; P < 0.001). The total amount of FA 14:0 as a constituent of triglycerides also decreased significantly, and its rate of decrease was the greatest of all the fatty acid constituents. CONCLUSIONS: A 2 week comprehensive risk management for diabetes resulted in decreased levels of plasma triglycerides and a change in the fatty acid composition of triglycerides, characterized by a relatively large reduction in FA 14:0 as a constituent of triglycerides.

The Importance of Continuous Glucose Monitoring-derived Metrics Beyond HbA1c for Optimal Individualized Glycemic Control.

CONTEXT: Current guidelines recommend assessing glycemic control using continuous glucose monitoring (CGM) and hemoglobin A1c (HbA1c) measurement. OBJECTIVE: This study aimed to clarify the characteristics of patients who might benefit from CGM metrics in addition to HbA1c monitoring. METHODS: CGM metrics, specifically time in range (TIR), time below range (TBR), and time above range (TAR), were determined in 999 outpatients with type 2 diabetes and compared between HbA1c categories (HbA1c < 53 mmol/mol [7.0%, HbA1c <  53], HbA1c 53-63 mmol/mol [7.0-7.9%, HbA1c 53-63], HbA1c 64-74 mmol/mol [8.0-8.9%, HbA1c 64-74], and HbA1c ≥ 75 mmol/mol [9.0%, HbA1c ≥  75]) and between patients with identical HbA1c categories who were stratified by age, types of antidiabetic agents, and renal function. RESULTS: For HbA1c <  53 category, patients aged ≥ 65 years had a significantly higher nocturnal TBR than those aged < 65 years. For HbA1c <  53 and HbA1c 53-63 categories, patients receiving insulin and/or sulfonylureas had a significantly higher TAR and TBR, and a lower TIR than those not receiving these drugs, and for HbA1c 64-74 category, they had a significantly higher TBR. For HbA1c <  53, HbA1c 53-63, and HbA1c 64-74 categories, patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 had a significantly higher TBR during some periods than those with an eGFR ≥ 60. CONCLUSION: Higher HbA1c levels do not always protect against hypoglycemic episodes. Our data demonstrate that using CGM metrics to complement HbA1c monitoring is beneficial, especially in older people, users of insulin and/or sulfonylureas, and patients with chronic kidney disease.

Changes in Treatment Satisfaction Over 3 Years in Patients With Type 2 Diabetes After Initiating Second-line Treatment.

CONTEXT: J-DISCOVER is a prospective observational cohort study aiming to understand the current management of patients with early-stage type 2 diabetes mellitus (T2DM) in Japan, enrolling patients initiating second-line treatment. OBJECTIVE: The current analysis examined the change in treatment satisfaction during the study period and factors affecting this change among patients in J-DISCOVER. METHODS: We used data from the J-DISCOVER study, in which 1798 patients with T2DM aged ≥ 20 years were enrolled from 142 sites across Japan. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). RESULTS: The mean DTSQ treatment satisfaction score increased from 25.9 points at baseline to 27.3 points at 6 months, which was maintained through 36 months. Among the baseline characteristics examined, higher baseline DTSQ treatment satisfaction scores (P < 0.0001), older age (≥ 75 vs < 65 years, P = 0.0096), living alone (P = 0.0356), and type of facility (clinics vs hospitals, P = 0.0044) had a significantly negative impact on the changes in DTSQ treatment satisfaction scores. Improvement in mean glycated hemoglobin (HbA1c) from baseline (7.7%) to 36 months (7.1%) was associated with positive changes in the DTSQ treatment satisfaction score (P = 0.0003). CONCLUSION: Changes in DTSQ treatment satisfaction scores were related to HbA1c improvement, suggesting that the management strategy was appropriately planned for each patient. The results also suggest that the availability of social support for patients with T2DM who are elderly or living alone may be an important factor affecting treatment satisfaction, adherence, and clinical outcomes.

Improvement of beta-cell function in conjunction with glycemic control after medical nutrition therapy in newly-diagnosed type 2 diabetes mellitus.

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.

Trends in maternal characteristics and perinatal outcomes among Japanese pregnant women with type 1 and type 2 diabetes from 1982 to 2020.

AIMS/INTRODUCTION: This study investigated the time trends of the maternal characteristics and perinatal outcomes of Japanese pregnant women with diabetes. MATERIALS AND METHODS: This retrospective study included 621 deliveries in 429 Japanese women with diabetes between 1982 and 2020. The association of the delivery date with clinical features was analyzed using the generalized estimating equations to adjust for the within-person correlation. RESULTS: The mean age of delivery and the mean diabetes duration increased over time (both P < 0.001), while the prevalence of diabetic retinopathy decreased (P = 0.006). The mean HbA1c values during pregnancy decreased significantly over time (all P < 0.001). The decreasing trends were associated with preterm delivery (P = 0.021) but not with other perinatal outcomes. The time trends were significantly different between patients with type 1 diabetes mellitus and with type 2 diabetes mellitus in large for gestational age (LGA) and stillbirth (both P for interaction <0.05). The rate of LGA decreased among patients with type 2 diabetes (P = 0.003) but not those with type 1 diabetes (P = 0.413). In contrast, the prevalence of stillbirth was decreased among those with type 1 diabetes (P < 0.001) but not those with type 2 diabetes (P = 0.768). The proportion of major congenital anomalies did not change in the overall population (P = 0.259) and among patients with type 2 diabetes (P = 0.229), but it increased among those with type 1 diabetes (P = 0.044), although the difference between those with type 1 diabetes and type 2 diabetes was not statistically significant (P for interaction = 0.166). CONCLUSIONS: Maternal glycemic control has improved over the decades, whereas the improvement of perinatal outcomes has been limited. Perinatal outcomes still need to be improved in Japanese women with diabetes.

Comparison of continuous subcutaneous insulin infusion treatment and multiple daily injection treatment on the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

To evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima-media thickness and brachial-ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile-onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments.

Associations between continuous glucose monitoring-derived metrics and HbA1c in patients with type 2 diabetes mellitus.

AIMS: The aim of this study was to define the relationship between time in range (TIR) and hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: The glycemic profile of 999 Japanese patients was analyzed with FreeStyle Libre Pro Continuous Glucose Monitoring (FLP-CGM) while they continued their prescribed glucose-lowering medications. FLP-CGM data recorded over 8 consecutive days were analyzed. RESULTS: The regression model for HbA1c on TIR was HbA1c = 9.4966-0.0309 × TIR. The predicted HbA1c level for TIR of 70% was 7.33% and is higher than reports subjecting mostly T1DM. The TIR corresponding to HbA1c 7.0% was 80.64%. The patients with low TIR tended to have long duration of diabetes, used high dose of daily insulin, high body mass index, high HbA1c, liver dysfunction and high triglyceride. Relatively higher percentages of patients of this group used sulfonylureas, glucagon like peptide-1 receptor agonists and insulin. CONCLUSIONS: Our data showed predicted HbA1c corresponding to TIR is largely depends on study population, thus is not uniform. Our results provide new insights on the management of T2DM. However, caution should be exercised in extending the HbA1C-TIR relationship using FLP-CGM to any other sensors since there could be a risk of hypoglycemia in doing so.

Screening for a Decreased Masticatory Function by a Color-changeable Chewing Gum Test in Patients with Metabolic Disease.

Objective This study aimed to reveal the screening performance of a color-changeable chewing gum test for a decreased masticatory function in the assessment of oral hypofunction in patients with metabolic diseases. Methods We analyzed 1,000 patients with metabolic diseases, including diabetes, dyslipidemia, hypertension, and hyperuricemia. A decreased masticatory function was diagnosed by a gummy jelly test. Patients were asked to chew a test gum, which changed from green to red by thorough mastication, 60 times for 1 minute. The color change was visually evaluated using the color scale, from 1 (green-dominant) to 10 points (red-dominant), and was colorimetrically quantified as delta E in the L*a*b* color space. The screening performance for a decreased masticatory function was evaluated with the receiver operating characteristic (ROC) curve. Results Seventy-seven patients (7.7%) were diagnosed with a decreased masticatory function. The mean color scale and delta E of the gum test were 6.7±1.8 points and 42.9±6.7 units, respectively. The area under the ROC curve was 0.822 (95% confidence interval, 0.768-0.872) for the color scale and 0.838 (0.781-0.890) for delta E (p=0.41). The optimal cut-off point of the color scale was 5.5 (5.0-6.5) points, whereas that of delta E was 37.7 (35.5-38.8) units. The optimal cut-off points were not significantly different between the subgroups divided by clinical characteristics. Conclusions A color-changeable chewing gum test using the color scale as well as delta E would be a useful tool for screening patients with metabolic diseases for a decreased masticatory function in the assessment of oral hypofunction.

Evaluation of the effect of tofogliflozin on the tissue characteristics of the carotid wall-a sub-analysis of the UTOPIA trial.

BACKGROUND: Since sodium-glucose cotransporter 2 (SGLT2) inhibitors have a pleiotropic antiatherogenic effect, they are expected to attenuate the progression of atherosclerosis. However, whether SGLT2 inhibitors affect the tissue characteristics of the human arterial wall remains unclear. This study aimed to evaluate the effects of tofogliflozin, a selective SGLT2 inhibitor, on the tissue characteristics of the human arterial wall in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD). METHODS: The present study was a post hoc analysis based on data obtained from the Using Tofogliflozin for Possible Better Intervention against Atherosclerosis for Type 2 Diabetes Patients (UTOPIA) trial, which was a multicenter prospective, randomized, open-label, blinded-endpoint study conducted to evaluate the efficacy of tofogliflozin in preventing the progression of atherosclerosis in patients with T2DM. We evaluated the longitudinal change in the ultrasonic tissue characteristics of the carotid wall using gray-scale median (GSM), an established index of ultrasonic tissue characteristics. The right and left intima-medial areas were delineated, and the GSM values were evaluated (right GSM-CCA and left GSM-CCA). The average values of the right and left carotid arteries were defined as "mean GSM-CCA value." RESULTS: In a mixed-effects model for repeated measures, mean GSM-CCA, along with the right and left GSM-CCA values, did not significantly change in either the tofogliflozin (n = 168) or conventional treatment group (n = 169). In addition, the tofogliflozin and conventional treatment groups did not significantly differ regarding the change of the mean GSM-CCA (mean difference [95% CI] - 1.24[- 3.87, 1.38], P = 0.35), along with the right (mean difference [95% CI] - 2.33[- 5.70, 1.05], P = 0.18) and the left GSM-CCA (mean difference [95% CI] - 0.29 [- 3.53, 2.95], P = 0.86) values. Similar findings were obtained even after adjusting for traditional cardiovascular risk factors and/or the administration of drugs at baseline. CONCLUSIONS: The tissue characteristics of the carotid arterial wall did not change in either the tofogliflozin or conventional treatment group during the 104-week treatment period, and there was no significant difference between the treatment groups. Clinical trial registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).

Correction to: Glycemic control of people with diabetes over months after the 2018 North Osaka Earthquake.

[This corrects the article DOI: 10.1007/s13340-020-00438-6.].