We report a sporadic case of maturity-onset diabetes of the young type 5 (MODY5) with a whole-gene deletion of the hepatocyte nuclear factor-1beta (HNF1B) gene. A 44-year-old Japanese man who had been diagnosed with early-onset non-autoimmune diabetes mellitus at the age of 23 was examined. He showed multi-systemic symptoms, including a solitary congenital kidney, pancreatic hypoplasia, pancreatic exocrine dysfunction, elevation of the serum levels of liver enzymes, hypomagnesemia, and hyperuricemia. These clinical characteristics, in spite of the absence of a family history of diabetes, prompted us to make the diagnosis of maturity-onset diabetes of the young 5 (MODY 5). One allele deletion of the entire HNF1B gene revealed by multiplex ligation-dependent probe amplification (MLPA) led us to the diagnoses of 17q12 microdeletion syndrome even though there were negative chromosomal analyses with array comparative genomic hybridization (CGH). 17q12 microdeletion syndrome, which is not rare especially in sporadic cases since 17q12 is a typical hot spot for chromosomal deletion, could have complicated the clinical heterogeneity of MODY5.

Objectives. A single-arm prospective study was conducted among Japanese patients with type 2 diabetes having preserved ejection fraction. The aim was to investigate (1) whether liraglutide therapy could improve B-type natriuretic peptide (BNP) levels and diastolic cardiac function assessed by the E -wave to E ′ ratio ( E / E ′ ) using transthoracic echocardiography (TTE), and (2) whether E / E ′ contributed to BNP improvement independent of bodyweight reduction (UMIN000005565). Methods. Patients with type 2 diabetes and left   ventricular   ejection   fraction   LVEF ≥ 40 % without heart failure symptoms were enrolled, and daily injection with liraglutide (0.9 mg) was introduced. Cardiac functions were assessed by TTE before and after 26 weeks of liraglutide treatment. Diastolic cardiac function was defined as septal E / E ′ ≥ 13.0 . Results. Thirty-one patients were analyzed. BNP and E / E ′ improved, with BNP levels declining from 36.8 ± 30.5   pg / mL to 26.3 ± 25.9   pg / mL ( p = 0.0014 ) and E / E ′ dropping from 12.7 ± 4.7 to 11.0 ± 3.3 ( p = 0.0376 ). The LVEF showed no significant changes. E / E ′ improved only in patients with E / E ′ ≥ 13.0 . Favorable changes in E / E ′ were canceled when adjusted for body mass index (BMI). Multivariate linear regression analysis revealed that the left ventricular diastolic diameter and ∆ E / E ′ /∆BMI contributed to ∆BNP/baseline BNP ( p = 0.0075 , R 2 = 0.49264 ). Conclusions. Liraglutide had favorable effects on BNP and E / E ′ but not on LVEF. E / E ′ improvement was only seen in patients with diastolic cardiac function. Body weight reduction affected the change of E / E ′ . The BMI-adjusted E / E ′ significantly contributed to the relative change of BNP. GLP-1 analog treatment could be considered a therapeutic option against diabetic diastolic cardiac dysfunction regardless of body weight. This trial is registered with the University Hospital Medical Information Network in Japan, with clinical trial registration number: UMIN000005565.

Aims/Introduction: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients. Materials and Methods: Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets-; 103 participants); diabetes mellitus-MetS+ (133 participants); and diabetes mellitus-MetS-(302 participants). fQRS was assessed using the results of electrocardiography. Results: The prevalence of fQRS was statistically higher in patients with diabetes melli-tus+ MetS+ (37%) and diabetes mellitus+ MetS-(35%), than those with diabetes mellitus-MetS+ (14%) or diabetes mellitus-MetS-(10%; P < 0.0001). Significant differences were observed between the fQRS(+) and fQRS(-) groups for age, sex, waist circumference, heart rate, hypertension, hemoglobin A1c, total cholesterol, MetS and diabetes mellitus. The area under the receiver operating characteristic curve for traditional risk factors and diabetes mellitus was 0.72 (P = 0.0007, 95% confidence interval 0.67-0.76), and for traditional risk factors and MetS it was 0.67 (P = 0.28, 95% confidence interval 0.62-0.72). Patients with diabetes mellitus had more than threefold higher likelihood of showing fQRS (odds ratio 3.41; 95% confidence interval 2.25-5.22; P < 0.0001) compared with the reference group without diabetes mellitus, after adjusting for age, sex, dyslipidemia, hypertension and waist circumference. Conclusions: fQRS was observed more frequently in diabetes mellitus patients than in MetS and control individuals. Diabetes mellitus was the most significant determinant for fQRS among MetS and other traditional metabolic risk factors.

Aims/Introduction Diastolic cardiac dysfunction in type 2 diabetes (DD2D) is a critical risk of heart failure with preserved ejection fraction. However, there is no established biomarker to detect DD2D. We aimed to investigate the predictive impact of fragmented QRS (fQRS) on electrocardiography on the existence of DD2D. Materials and Methods We included in‐hospital patients with type 2 diabetes without heart failure symptoms who were admitted to our institution for glycemic management between November 2017 and April 2021. An fQRS was defined as an additional R′ wave or notching/splitting of the S wave in two contiguous electrocardiography leads. DD2D was diagnosed according to the latest guidelines of the American Society of Echocardiography. Results Of 320 participants, 122 patients (38.1%) had fQRS. DD2D was diagnosed in 82 (25.6%). An fQRS was significantly associated with the existence of DD2D (odds ratio 4.37, 95% confidence interval 2.33–8.20; p < 0.0001) adjusted for seven potential confounders. The correlation between DD2D and diabetic microvascular disease was significant only among those with fQRS. Classification and regression tree analysis showed that fQRS was the most relevant optimum split for DD2D. Conclusions An fQRS might be a simple and promising predictor of the existence of DD2D. The findings should be validated in a larger‐scale cohort.

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