Risk stratification of cardiac arrhythmias and sudden cardiac death in type 2 diabetes mellitus patients receiving insulin therapy: A population‐based cohort study

IntroductionMetabolic abnormalities may exacerbate the risk of adverse outcomes in patients with type 2 diabetes mellitus. The present study aims to assess the predictive value of HbA1c and lipid variability on the risks of sudden cardiac death (SCD) and incident atrial fibrillation (AF).MethodsThe retrospective observational study consists of type 2 diabetic patients prescribed with insulin, who went to publicly funded clinics and hospitals in Hong Kong between January 1, 2009 and December 31, 2009. Variability in total cholesterol, low‐density lipoprotein‐cholesterol (LDL‐C), high‐density lipoprotein‐cholesterol (HDL‐C), triglyceride, and HbA1c were assessed through their SD and coefficient of variation. The primary outcomes were incident (1) ventricular tachycardia/ventricular fibrillation, actual or aborted SCD and (2) AF.ResultsA total of 23 329 patients (mean ± SD age: 64 ± 14 years old; 51% male; mean HbA1c 8.6 ± 1.3%) were included. On multivariable analysis, HbA1c, total cholesterol, LDL‐C and triglyceride variability were found to be predictors of SCD (p < .05).ConclusionHbA1c and lipid variability were predictive of SCD. Therefore, poor glucose control and variability in lipid parameters in diabetic patients are associated with aborted or actual SCD. These observations suggest the need to re‐evaluate the extent of glycemic control required for outcome optimization.     

Impact of flash glucose monitoring on glycemic control varies with the age and residual β‐cell function of patients with type 1 diabetes mellitus

Aims/IntroductionWe aimed to explore the clinical factors associated with glycemic variability (GV) assessed with flash glucose monitoring (FGM), and investigate the impact of FGM on glycemic control among Chinese type 1 diabetes mellitus patients in a real‐life clinical setting.Materials and MethodsA total of 171 patients were included. GV was assessed from FGM data. A total of 110 patients wore FGM continuously for 6 months (longitudinal cohort). Hemoglobin A1c (HbA1c), fasting and 2‐h postprandial C‐peptide, and glucose profiles were collected. Changes in HbA1c and glycemic parameters were assessed during a 6‐month FGM period.ResultsIndividuals with high residual C‐peptide (HRCP; 2‐h postprandial C‐peptide >200 pmol/L) had less GV than patients with low residual C‐peptide ( 2‐h postprandial C‐peptide ≤200 pmol/L; P < 0.001). In the longitudinal cohort (n = 110), HbA1c and mean glucose decreased, time in range (TIR) increased during the follow‐up period (P < 0.05). The 110 patients were further divided into age and residual C‐peptide subgroups: (i) HbA1c and mean glucose were reduced significantly only in the subgroup aged ≤14 years during the follow‐up period, whereas time below range also increased in this subgroup at 3 months (P = 0.047); and (ii) HbA1c improved in the HRCP subgroup at 3 and 6 months (P < 0.05). The mean glucose decreased and TIR improved significantly in the low residual C‐peptide subgroup; however, TIR was still lower and time below range was higher than those of the HRCP subgroup at all time points (P < 0.05).ConclusionsHRCP was associated with less GV. FGM wearing significantly reduced HbA1c, especially in pediatric patients and those with HRCP. Additionally, the mean glucose and TIR were also found to improve.     

Insulin–glucagon‐like peptide‐1 receptor agonist relay and glucagon‐like peptide‐1 receptor agonist first regimens in individuals with type 2 diabetes: A randomized,open‐label trial study

Aims/IntroductionGlucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP‐1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose‐lowering effects of GLP‐1 receptor agonist liraglutide with and without prior glycemic control.Materials and MethodsIn an open‐label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once‐daily insulin therapy, degludec (Insulin–GLP‐1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP‐1 RA, liraglutide (GLP‐1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end‐points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c).ResultsThe median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin–GLP‐1 RA relay group (P < 0.001) and GLP‐1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin–GLP‐1 RA relay group tended to be larger than that in the GLP‐1 RA first group in the lowest CPR (C‐peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia.ConclusionsThe GLP‐1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity‐induced GLP‐1 resistance.     

Longitudinal effects of one‐leg standing time on neuropathy outcomes in association with glycemic control in non‐elderly patients with type 2 diabetes

Aims/IntroductionDiabetic neuropathy leads to postural instability. This study compared longitudinal changes in neuropathy outcomes relative to long‐term glycemic control in patients aged <60 years with uncontrolled type 2 diabetes with and without a short one‐leg standing time (OLST <60 s).Materials and MethodsIn this retrospective study, 58 hospitalized patients with type 2 diabetes (glycated hemoglobin [HbA1c] >7.0%; aged 17–59 years), who underwent re‐evaluation of neuropathic sensory symptoms, ankle reflexes and nerve conduction attributes, and cardiac autonomic function (R‐R interval), >1 year after discharge were divided into OLST <60 and ≥60 s groups. Patients were followed up every 2–3 months for HbA1c levels for up to 8 years. Neuropathy outcomes relative to OLST and HbA1c levels at baseline and over follow up were compared.ResultsAdditional development of sensory symptoms (one patient) and abnormal ankle reflexes (five patients) were identified during follow up, and decreased peripheral and cardiac autonomic function at both baseline and follow up, only in patients with OLST <60 s. Mean HbA1c levels were significantly higher in patients with OLST <60 s versus ≥60 s (7.8 ± 0.9% vs 7.2 ± 1.2%; P = 0.022). Better glycemic control during follow up was associated with better neuropathy outcomes only in patients with OLST ≥60 s.ConclusionNon‐elderly type 2 diabetes patients with OLST <60 s and decreased peripheral nerve function at baseline are at increased risk for intractable diabetic neuropathy. Better glycemic control alone might not improve neuropathy outcomes in these patients.     

Follow‐up frequency and clinical outcomes in patients with type 2 diabetes: A prospective analysis based on multicenter real‐world data

BackgroundTo determine whether the follow‐up frequency for type 2 diabetes mellitus (T2DM) patients in the National Metabolic Management Centers (MMCs) leads to different clinical outcomes.MethodsA total of 19 908 T2DM patients with at least 6 months of facility‐based follow‐up were recruited in MMCs between June 2017 and April 2021 and divided into lower‐frequency and higher‐frequency follow‐up (LFF and HFF) groups according to the median follow‐up frequency of 2.0 (interquartile range 1.2) times per year. Metabolic parameters at baseline and at the last follow‐up visit were analyzed. Multivariable linear regression models were performed to assess the relationship between follow‐up frequency and between‐group percentage changes, adjusting for the major covariables. Additional stratified analyses were conducted to evaluate the metabolic outcomes in the subgroups.ResultsThe characteristics of the participants in the LFF and HFF groups were significantly different at baseline. Participants had significant improvements in multiple metabolic parameters after follow‐up. Patients with HFF showed significantly greater decrease in percentage changes of fasting blood glucose (−4.95% ± 37.96% vs −2.21% ± 43.08%, P < .0001) and glycosylated hemoglobin (HbA1c) (−12.14% ± 19.78% vs −9.67% ± 20.29%, P < .0001) after adjustments compared to those with LFF. Furthermore, stratification analyses showed that significant between‐group percentage changes of HbA1c were observed in those with younger age (<55 years) and higher HbA1c (>9%) at baseline (P for interaction <.001).ConclusionsHFF is associated with better metabolic outcomes. Participants, especially with younger age or worse HbA1c at baseline in the HFF group achieved better glycemic control than those in the LFF group.     

Low fasting glucose‐to‐estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes

Aims/IntroductionThe benefits of once‐daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established.Materials and MethodsThis was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once‐daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated.ResultsThe IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C‐peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P < 0.001). Considering that the lower FPG despite the comparable HbA1c could be related with the efficacy of IDegAsp, subgroup analysis was carried out according to a ratio of FPG‐to‐estimated average glucose, which is calculated from HbA1c. When compared with each control group, the superiority of IDegAsp in the reduction of HbA1c was significant only in the patients with a lower FPG‐to‐estimated average glucose ratio (0.49 ± 0.09), but not in those with a higher FPG‐to‐estimated average glucose ratio (0.79 ± 0.20).ConclusionsWe observed that IDegAsp was more effective than basal insulin in patients with an FPG lower than predicted by HbA1c, which might be related with insulin deficiency and postprandial hyperglycemia in patients on basal insulin therapy.     

Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Aims/IntroductionThis study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy.Materials and MethodsThis was an exploratory substudy of an open‐label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy.ResultsA total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low‐density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05).ConclusionsNerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.     

Management and outcome across the spectrum of high‐risk patients with myocardial infarction according to the thrmobolysis in myocardial infarction (TIMI) risk‐score for secondary prevention

BackgroundPatients with myocardial infarction (MI) are at increased risk for recurrent cardiovascular events, yet some patients, such as the elderly and those with prior comorbidities, are particularly at the highest risk. Whether these patients benefit from contemporary management is not fully elucidated.MethodsIncluded were consecutive patients with MI who underwent percutaneous coronary intervention (PCI) in a large tertiary medical center. Patients were stratified according to the thrombolysis in myocardial infarction (TIMI) risk score for secondary prevention (TRS2°P) to high (TRS2°P = 3), very high (TRS2°P = 4), or extremely high‐risk (TRS2°P = 5–9). Excluded were low and intermediate‐risk patients (TRS2°P < 3). Outcomes included 30‐day/1‐year major adverse cardiac events (MACE) and 1‐year mortality. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time‐periods.ResultsAmong 2053 patients, 50% were high‐risk, 30% very high‐risk and 20% extremely high‐risk. Extremely high‐risk patients were older (age 74 ± 10 year) and had significant comorbidities (chronic kidney disease 68%, prior CABG 40%, heart failure 78%, peripheral artery disease 29%). Drug‐eluting stents and potent antiplatelets were more commonly used over time in all risk‐strata. Over time, 30‐day MACE rates have decreased, mainly attributed to the very high (11.3% to 5.1%, p = .006) and extremely high‐risk groups (15.9% to 8.0%, p = .016), but not the high‐risk group, with similar quantitative results for 1‐year MACE. The rates of 1‐year mortality remained unchanged in either group.ConclusionWithin a particularly high‐risk cohort of MI patients who underwent PCI, the implementation of guideline‐recommended therapies has improved over time, with the highest‐risk groups demonstrating the greatest benefit in outcomes.     

Effects of salt intervention on serum levels of Klotho influenced by salt sensitivity

Klotho was involved in sodium reabsorption and the regulation of blood pressure. Animal studies indicated Klotho deficiency could mediate the development of salt‐sensitive hypertension, indicating its correlation with salt sensitivity. We aimed to explore the responses of Klotho to salt intake through dietary intervention in Chinese adults. Forty‐four participants were enrolled from Lantian county of Shaanxi, China. All participants sequentially underwent a 3‐day normal diet, a 7‐day low‐Na⁺ diet, and a 7‐day high‐Na⁺ diet. The concentrations of serum Klotho were assessed by using ELISA kits. Serum level of Klotho was 360.44 ± 93.89 pg/mL at baseline and increased while changed to low‐salt diet (478.65 ± 183.25 vs 360.44 ± 93.89 pg/mL, P < .001). During high‐salt diet, serum Klotho decreased to 354.37 ± 98.16 pg/mL (P < .001, compared to low‐salt diet). The overall responses of Klotho were more prominent in salt‐resistant participants. Serum Klotho of salt‐resistant group changed from 353.92 ± 97.65 pg/mL to 496.76 ± 196.21 pg/mL while changed from normal diet to low‐salt diet (P < .001) and decreased to 350.37 ± 99.50 pg/mL during high‐salt intake (P < .001). Furthermore, the response of serum Klotho to low‐salt intervention was much greater in salt‐resistant individuals than in salt‐sensitive ones. The responses of serum Klotho to dietary salt intervention were influenced by salt sensitivity, which was more prominent in salt‐resistant participants.     

Comparison of prognosis and outcomes of catheter ablation versus drug therapy in patients with atrial fibrillation and stable coronary artery disease: A prospective propensity‐score matched cohort study

BackgroundAtrial fibrillation (AF) and stable coronary artery disease (SCAD) frequently coexist.HypothesisTo investigate the prognosis of catheter ablation versus drug therapy in patients with AF and SCAD.MethodsIn total, 25 512 patients with AF in the Chinese AF Registry between 2011 and 2019 were screened for SCAD. 815 patients with AF and SCAD underwent catheter ablation therapy were matched with patients by drug therapy in a 1:1 ratio. Primary end point was composite of thromboembolism, coronary events, major bleeding, and all‐cause death. The secondary endpoints were each component of the primary endpoint and AF recurrence.ResultsOver a median follow‐up of 45 ± 23 months, the patients in the catheter ablation group had a higher AF recurrence‐free rate (53.50% vs. 18.41%, p < .01). In multivariate analysis, there was no significant difference between the strategy of catheter ablation and drug therapy in primary composite end point (adjusted HR 074, 95%CI 0.54–1.002, p = .0519). However, catheter ablation was associated with fewer all‐cause death independently (adjusted HR 0.36, 95%CI 0.22–0.59, p < .01). In subgroup analysis, catheter ablation was an independent risk factor for all‐cause death in the high‐stroke risk group (adjusted HR 0.39, 95%CI 0.23–0.64, p < .01), not in the low‐medium risk group (adjusted HR 0.17, 95%CI 0.01–2.04, p = .17).ConclusionsIn the patients with AF and SCAD, catheter ablation was not independently associated with the primary composite endpoint compared with drug therapy. However, catheter ablation was an independent protective factor of all‐cause death     

Association of glycemic variability assessed by continuous glucose monitoring with subclinical diabetic polyneuropathy in type 2 diabetes patients

Aims/IntroductionDiabetic peripheral neuropathy is a common diabetes‐related microvascular complication. The relationship between peripheral nerve function and glucose variability is unclear. We investigated the association of glucose variability with subclinical diabetic polyneuropathy in a large‐scale sample of patients with type 2 diabetes.Materials and MethodsWe enrolled 509 individuals with type 2 diabetes who were screened for diabetic peripheral neuropathy and monitored using a continuous glucose monitoring system. Multiple glycemic variability parameters, including the mean amplitude of glycemic excursions, glucose standard deviation (SD_gluc) and glucose coefficient of variation were calculated from 3‐day glucose profiles obtained from continuous glucose monitoring. All participants underwent nerve conduction studies, and the composite Z‐scores for nerve conduction parameters were calculated.ResultsMultivariate logistic regression analyses showed that SD_gluc and the conventional risk factor hemoglobin A1c (HbA1c) were independently associated with abnormal nerve function, and the corresponding odds ratios (95% confidence interval) were 1.198 (1.027–1.397, SD_gluc) and 1.182 (1.061–1.316, HbA1c), respectively. The composite Z‐score of nerve conduction velocity and response amplitude obviously decreased with greater SD_gluc, and the composite Z‐score of distal latency significantly increased with increasing tertiles of SD_gluc (all P trend <0.05). After adjusting for age, sex, body mass index, diabetes duration and HbA1c, SD_gluc was independently associated with nerve conduction velocity (β = −0.124, P = 0.021).ConclusionsThe SD_gluc is a significant independent contributor to subclinical diabetic polyneuropathy, in addition to conventional risk factors including diabetes duration and HbA1c.     

Prognostic impact of peak oxygen uptake and heart rate reserve in patients after off‐pump coronary artery bypass grafting

BackgroundPeak oxygen uptake (peak VO₂) and heart rate reserve (HRR) are independent prognostic markers of cardiovascular disease. However, the impact of peak VO₂ and HRR on long‐term prognosis after off‐pump coronary artery bypass grafting (OP‐CABG) remains unclear.HypothesisTo determine the prognostic impact of peak VO₂ and HRR in patients after OP‐CABG.ResultsWe enrolled 327 patients (mean age, 65.1 ± 9.3 years; male, 80%) who underwent OP‐CABG and participated in early phase II cardiac rehabilitation. All participants underwent cardiopulmonary exercise testing (CPET) at the beginning of such rehabilitation. Overall, 48 (14.6%) patients died during the median follow‐up period of 103 months. The non‐survivor had significantly lower levels of peak VO₂ (10.6 ± 0.5 vs. 13.7 ± 0.2 ml/kg/min, p < .01) and HRR (24.2 ± 1.8 vs. 32.7 ± 0.8 beats/min, p < .01) than the survivor. In both groups, peak VO₂ significantly correlated with HRR (p < .01). Moreover, patients were divided into four groups according to the peak VO₂ and HRR levels for predicting total mortality. The low‐peak VO₂/low‐HRR group had a significantly higher mortality risk than the other groups (hazards ratio, 5.61; 95% confidence interval, 2.59–12.16; p < .01). After adjusted the confounding factors, peak VO₂ and HRR were independently associated with total mortality (both p < .05).ConclusionsHRR is a simple parameter of CPET and an important prognostic marker for the risk stratification of total mortality even in patients with low‐peak VO₂ after OP‐CABG.     

Effects of basal and premixed insulin on glycemic control in type 2 diabetes patients based on multicenter prospective real‐world data

BackgroundTo investigate the different efficacies of glycemic control between basal and premixed insulin in participants with type 2 diabetes (T2DM) when non‐insulin medications fail to reach treatment targets.MethodsThis was a prospective, large‐scale, real‐world study at 10 diabetes centers in China. Between June 2017 and June 2021, we enrolled 1104 T2DM participants initiated with either once‐daily basal insulin or twice‐daily premixed insulin when the glycosylated hemoglobin (HbA1c) control target was not met after at least two non‐insulin agents were administered. A Cox proportional hazards regression model adjusting for multiple influencing factors was performed to compare the different effects of basal and premixed insulin on reaching the HbA1c control target.ResultsAt baseline, basal insulin (57.3%) was prescribed more frequently than premixed insulin (42.7%). Patients with a higher body mass index (BMI) or higher HbA1c levels were more likely to receive premixed insulin than basal insulin (both p < 0.001). After a median follow‐up of 12.0 months, compared to those with premixed insulin, the hazard ratio for reaching the HbA1c target to those with basal insulin was 1.10 (95% CI, 0.92‐1.31; p = 0.29) after adjustment, and less weight gain was observed in those with basal insulin than with premixed insulin (percentage change of BMI from baseline −0.37[5.50]% vs 3.40[6.73]%, p < 0.0001).ConclusionsIn this real‐world study, once‐daily basal insulin was more frequently prescribed and had similar glycemic control effects but less weight gain compared with twice‐daily premixed insulin when used as initiation therapy for those in whom glycemic control with non‐insulin medications failed.     

Living and working environments are important determinants of glycemic control in patients with diabetes during the COVID‐19 pandemic: A retrospective observational study

AimTo investigate (1) the association of lifestyle changes and living and working conditions with glycemic control and (2) whether treatment was intensified appropriately in patients with diabetes under the first COVID‐19 state of emergency in Japan.Materials and MethodsA total of 321 participants were included. Participants completed a questionnaire regarding lifestyle changes, including diet, physical activity, and living and working conditions during the COVID‐19 pandemic. The change in hemoglobin A1c (HbA1c) levels was estimated before (June 1, 2019 to August 31, 2019) and during (June 1, 2020 to August 31, 2020) the pandemic. Factors associated with changes in HbA1c levels were examined by multiple linear regression analysis. The proportion of patients who received treatment intensification for diabetes was compared between before and during the pandemic.ResultsThere was no significant change in HbA1c levels before the pandemic and during the pandemic (7.13 ± 0.98% vs 7.18 ± 1.01%, P = 0.186). Teleworking (estimate 0.206, P = 0.004) and living with a dog (estimate −0.149, P = 0.038) were significantly associated with changes in HbA1c levels after adjusting for covariates. There was no significant difference in the proportion of patients who received treatment intensification for diabetes during the pandemic and before the pandemic in either the elderly or non‐elderly patients.ConclusionsOverall glycemic control did not worsen during the pandemic. Nonetheless, environmental factors, including telework, were found to influence glycemic control in patients with diabetes. Further studies are needed to clarify whether the COVID‐19 pandemic could affect treatment intensification for diabetes.     

Discrepancies in glycemic metrics derived from different continuous glucose monitoring systems in adult patients with type 1 diabetes mellitus

BackgroundContinuous glucose monitoring systems have been widely used but discrepancies among various brands of devices are rarely discussed. This study aimed to explore differences in glycemic metrics between FreeStyle Libre (FSL) and iPro2 among adults with type 1 diabetes mellitus (T1DM).MethodsParticipants with T1DM and glycosylated hemoglobin of 7%–10% were included and wore FSL and iPro2 for 2 weeks simultaneously. Datasets collected on the insertion and detachment day, and those with insufficient quantity (<90%) were excluded. Agreements of measurement accuracy and glycemic metrics were evaluated.ResultsA total of 40 498 paired data were included. Compared with the values from FSL, significantly higher median value was observed in iPro2 (147.6 [106.2, 192.6] vs. 144.0 [100.8, 192.6] mg/dl, p < 0.001) and the largest discordance was observed in hypoglycemic range (median absolute relative difference with iPro2 as reference value: 25.8% [10.8%, 42.1%]). Furthermore, significant differences in glycemic metrics between iPro2 and FSL were also observed in time in range (TIR) 70–180 mg/dl (TIR, 62.8 ± 12.4% vs. 58.8 ± 12.3%, p = 0.004), time spent below 70 mg/dl (4.4 [1.8, 10.9]% vs. 7.2 [5.4, 13.3]%, p < 0.001), time spent below 54 mg/dl (0.9 [0.3, 4.0]% vs. 2.6 [1.3, 5.6]%, p = 0.011), and coefficient of variation (CV, 38.7 ± 8.5% vs. 40.9 ± 9.3%, p = 0.017).ConclusionsDuring 14 days of use, FSL and iPro2 provided different estimations on TIR, CV, and hypoglycemia‐related parameters, which needs to be considered when making clinical decisions and clinical trial designs.     

Glycemic Metrics Derived From Intermittently Scanned Continuous Glucose Monitoring

Background:Glucose data from intermittently scanned continuous glucose monitoring (isCGM) is a combination of scanned and imported glucose values. The present knowledge of glycemic metrics originate mostly from glucose data from real-time CGM sampled every five minutes with a lack of information derived from isCGM.Methods:Glucose data obtained with isCGM and hemoglobin A1c (HbA1c) were obtained from 169 patients with type 1 diabetes. Sixty-one patients had two observations with an interval of more than three months.Results:The best regression line of HbA1c against mean glucose was observed from 60 days prior to HbA_1c measurement as compared to 14, 30, and 90 days. The difference between HbA1c and estimated HbA1c (=glucose management indicator [GMI]) first observed correlated with the second observation (R2 0.61, P < .001). Time in range (TIR, glucose between 3.9 and 10 mmol/L) was significantly related to GMI (R2 0.87, P < .001). A TIR of 70% corresponded to a GMI of 6.8% (95% confidence interval, 6.3-7.4). The fraction of patients with the optimal combination of TIR >70% and time below range (TBR) <4% was 3.6%. The fraction of patients with TBR>4% was four times higher for those with high glycemic variability (coefficient of variation [CV] >36%) than for those with lower CV.Conclusion:The individual difference between HbA1c and GMI was reproducible. High glycemic variability was related to increased TBR. A combination of TIR and TBR is suggested as a new composite quality indicator.     

Cardiology clinic visit increases likelihood of evidence‐based cholesterol prescribing in severe hypercholesterolemia

BackgroundPatients with phenotypic severe hypercholesterolemia (SH), low‐density lipoprotein‐cholesterol (LDL‐c) ≥ 190 mg/dl, atherosclerotic cardiovascular disease (ASCVD) or adults 40–75 years with diabetes with risk factors or 10‐year ASCVD risk ≥20% benefit from maximally tolerated statin therapy. Rural patients have decreased access to specialty care, potentially limiting appropriate treatment.HypothesisPrior visit with cardiology will improve treatment of severe hypercholesterolemia.MethodsWe used an electronic medical record‐based SH registry defined as ever having an LDL‐c ≥ 190 mg/dl since January 1, 2000 (n = 18 072). We excluded 3205 (17.7%) patients not alive or age 20–75 years. Patients defined as not seen by cardiology if they had no visit within the past 3 years (2017–2019).ResultsWe included 14 867 patients (82.3%; mean age 59.7 ± 10.3 years; 58.7% female). Most patients were not seen by cardiology (n = 13 072; 72.3%). After adjusting for age, sex, CVD, hypertension, diabetes and obesity, patients seen by cardiology were more likely to have any lipid‐lowering medication (OR = 1.46, 95% CI: 1.29–1.65), high‐intensity statin (OR = 1.81, 95% CI: 1.61–2.03), or proprotein convertase subtilisin‐kexin type 9 (PCSK9) inhibitor (OR = 5.96, 95% CI: 3.34–10.65) compared to those not seen by cardiology. Mean recent LDL‐c was lower in patients seen by cardiology (126.8 ± 51.6 mg/dl vs. 152.4 ± 50.2 mg/dl, respectively; p < .001).ConclusionIn our predominantly rural population, a visit with cardiology improved the likelihood to be prescribed any statin, a high‐intensity statin, or PCSK9 inhibitor. This more appropriately addressed their high life‐time risk of ASCVD. Access to specialty care could improve SH patient''s outcomes.     

Bariatric surgery versus medical treatment in mildly obese patients with type 2 diabetes mellitus in Japan: Propensity score‐matched analysis on real‐world data

Aims/IntroductionTo compare glycemic control 1 year after treatment in patients with mildly obese (body mass index 27.5–34.9 kg/m²) type 2 diabetes mellitus who underwent bariatric surgery (BS) to those who received medical treatment (MT) in Japan.Materials and MethodsA retrospective study using real‐world data was carried out in electronic medical records from a tertiary care hospital and in the Japanese Medical Data Center Inc. claim database from 2008 to 2019. Each patient was propensity score‐matched between the BS and the MT group by age, sex, body mass index, glycated hemoglobin and type 2 diabetes mellitus duration, and compared from the index date to the 1 year post‐index.ResultsThe study included 78 patients in the BS group and 238 patients in the MT group. The mean body mass index in the BS and the MT group was 32.1 and 32.0 kg/m², respectively. In the BS group, the patients underwent either laparoscopic sleeve gastrectomy with or without duodenojejunal bypass. The diabetes remission rate (glycated hemoglobin <6.5% without diabetes medication) at 1 year was 59.0% in the BS group and 0.4% in the MT group (P < 0.0001). Optimal glycemic control of glycated hemoglobin <7.0% was achieved in 75.6% in the BS group and in 29.0% in the MT group (P < 0.0001). The median monthly drug costs for metabolic syndrome decreased from $US126.5 (at baseline) to $US0.0 (at 1 year) in the BS group, whereas it increased from $US52.4 to $US58.3 in the MT group.ConclusionsBS for mildly obese patients with type 2 diabetes mellitus is more clinically‐ and cost‐effective than MT in Japan.     

DUAL I China: Improved glycemic control with IDegLira versus its individual components in a randomized trial with Chinese participants with type 2 diabetes uncontrolled on oral antidiabetic drugs

BackgroundDUAL I China, one of the DUAL trials, assessed efficacy/safety of insulin degludec/liraglutide (IDegLira) in Chinese adults with type 2 diabetes (T2D) not controlled by oral antidiabetic drugs (OADs).MethodsThis phase 3a, treat‐to‐target multicenter trial randomized participants (glycated hemoglobin [HbA1c] 53.0‐85.8 mmol/mol; previous metformin ± another OAD) 2:1:1 to IDegLira (n = 361), degludec (n = 179), or liraglutide (n = 180). Primary endpoint was change in HbA1c after 26 weeks. Secondary endpoints included: HbA1c < 53.0 mmol/mol attainment, weight change, treatment‐emergent hypoglycemia, end‐of‐treatment insulin dose, and safety.ResultsAt 26 weeks, HbA1c had decreased by a mean 18.12 mmoL/moL (IDegLira), 12.37 mmoL/moL (degludec) (estimated treatment difference [ETD] −6.50 mmoL/moL; 95% confidence interval [CI] −7.96, −5.04; P < .0001), and 11.33 mmoL/moL (liraglutide) (ETD −6.87 mmoL/moL; 95% CI −8.33, −5.41; P < 0.0001), indicating noninferiority for IDegLira vs degludec and superiority vs liraglutide. HbA1c < 53.0 mmoL/moL attainment was 77.0% (IDegLira), 46.4% (degludec), and 48.3% (liraglutide). Mean weight change with IDegLira (0.1 kg) was superior to degludec (1.2 kg) (ETD −1.08 kg; 96% CI −1.55, −0.62; P < 0.0001). Severe or confirmed hypoglycemic event rates were 0.24 (IDegLira) and 0.17 (degludec) episodes/participant‐year (estimated rate ratio 1.46; 95% CI 0.71, 3.02; P = .3008, not significant). At the end of treatment, the IDegLira insulin dose was lower (24.5 U/d) vs degludec (30.3 U/d) (ETD −5.49 U; 95% CI −7.77, −3.21; P < 0.0001). No unexpected safety issues occurred.ConclusionsIDegLira is efficacious and well tolerated in Chinese adults with T2D not controlled by OADs.     

Combination of disease duration‐to‐age at diagnosis and hemoglobin A1c‐to‐serum C‐peptide reactivity ratios predicts patient response to glucose‐lowering medication in type 2 diabetes: A retrospective cohort study across Japan (JDDM59)

Aims/IntroductionKnowing the collective clinical factors that determine patient response to glucose‐lowering medication would be beneficial in the treatment of type 2 diabetes. We carried out a retrospective cohort study to explore the combination of clinical factors involved in its therapeutic efficacy.Materials and MethodsThe results of cohort studies retrieved using the CoDiC^® database across Japan from January 2005 to July 2018 were analyzed based on criterion that using insulin therapy indicates severe type 2 diabetes.ResultsA logistic regression analysis showed that age at diagnosis, disease duration, hemoglobin A1c (HbA1c) and serum C‐peptide reactivity (CPR) at medication commencement were associated with the probability of insulin treatment. Receiver operating characteristic curve showed that these clinical factors predicted insulin treatment positivity with an area under the curve of >0.600. The area under the curve increased to 0.674 and 0.720 for the disease duration‐to‐age at diagnosis ratio and HbA1c‐to‐CPR ratio, respectively. Furthermore, area under the curve increased to 0.727 and 0.750 in the indices (duration‐to‐age ratio at diagnosis × 43 + HbA1c) and (duration‐to‐age ration at diagnosis × 21 + HbA1c‐to‐CPR ratio), respectively. After stratification to three groups according to the indices, monthly HbA1c levels during 6 months of treatment were higher in the upper one‐third than in the lower one‐third of patients, and many patients did not achieve the target HbA1c level (53 mmol/mol) in the upper one‐third, although greater than fourfold more patients were administered insulin in the upper one‐third.ConclusionsThe combination of disease duration‐to‐age at diagnosis and HbA1c‐to‐CPR ratios is a collective risk factor that predicts response to the medications.