Possible Relationship between the Deteriorated Accuracy of Intermittent-Scanning Continuous Glucose Monitoring Device and the Contact Dermatitis: Post-hoc analysis of the ISCHIA Study.

OBJECTIVE: We previously reported the mean average relative difference (MARD) of the sensor glucose (SG) of the first-generation FreeStyle Libre with the original algorithm, an intermittent scanning continuous glucose monitoring (isCGM) device, was 15.6% in the Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study). In the present study, we aimed to further analyze its accuracy in detail by conducting a post-hoc analysis of the study. METHODS: The ISCHIA Study was a multicenter, randomized, cross-over trial to assess the efficacy of isCGM. The SG levels of isCGM and the measured capillary blood glucose (BG) levels of 91 participants were used for the analysis. RESULTS: Bland-Altman analysis showed bias of -13.0 mg/dl when the SG levels were compared to the BG levels, however no proportional bias was observed (r = 0.085). MARD of the participants without and with contact dermatitis were 15.0 ± 6.0% and 27.4 ± 21.4% (P = 0.001), respectively. CONCLUSION: There was negative bias in the SG levels of isCGM compared to the BG levels. There is a possibility that the complication of the contact dermatitis during isCGM use may be related with deteriorated accuracy of the SG levels.

Association of Impaired Awareness of Hypoglycemia with Driving Safety and Hypoglycemia Problem-solving Abilities among Patients with Type 1 Diabetes in Japan: The PR-IAH Study.

Objective Patients with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) are at an elevated risk of experiencing automobile accidents. We therefore investigated the association of IAH with driving safety and hypoglycemia problem-solving abilities in adults with T1D. Methods This cross-sectional survey used Gold's method in adult patients with T1D at the National Hospital Organization (NHO) Hospital from February 14, 2020, to October 31, 2021. The participants were divided into control and IAH groups. The data included information on demographics, worries and distress regarding hypoglycemia, hypoglycemia problem-solving abilities, and adverse driving events. Patients We enrolled 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%) from NHO collaborating centers in Japan. Results Among a total of 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%), the prevalence rate of IAH was 11.6% [95% confidence interval (CI): 7.8-16.4%]. IAH was significantly associated with near-miss car accidents (odds ratio: 5.41; 95% CI:1.64-17.80). Diabetic peripheral neuropathy was associated with an increased risk of IAH, while treatment with continuous subcutaneous insulin infusion was not associated with a decreased risk of IAH. The average hypoglycemia problem-solving perception, detection control, and seeking preventive strategies scores in the IAH group were significantly reduced compared with those in the control group. Conclusion IAH was associated with an increased risk of near-miss car accidents among adults with T1D. Furthermore, good hypoglycemia problem-solving abilities were associated with a decreased risk of IAH.

Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study.

BACKGROUND: Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D. METHODS: This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected. RESULTS: The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13-5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22-0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37-0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups. CONCLUSION: We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020.

Higher Serum Soluble TREM2 as a Potential Indicative Biomarker for Cognitive Impairment in Inadequately Controlled Type 2 Diabetes Without Obesity: The DOR-KyotoJ-1.

Objective: Type 2 diabetes is a risk factor for dementia. We investigated whether serum levels of soluble triggering receptor expressed on myeloid cell 2 (sTREM2), a soluble form of the cell surface receptor TREM2, were predictive of cognitive impairment in type 2 diabetes without obesity. Methods: A total of 166 Japanese patients with type 2 diabetes without obesity were followed-up for 2 years. We measured clinical parameters, assessed cognitive function using the mini-mental state examination (MMSE), quantified and divided serum sTREM2 levels into quartiles, and examined the longitudinal associations. Results: During the follow-up, HbA1c levels were elevated in 98 patients and decreased in 68 patients. In the HbA1c-elevated group, higher sTREM2 levels at baseline showed a significant association with a greater tendency for reduction in MMSE scores (P for trend = 0.015), whereas they were not significantly associated with other examined parameters. In the HbA1c-decreased group, there was no significant association between sTREM2 levels at baseline and changes in MMSE scores, but higher sTREM2 levels at baseline were significantly associated with a greater tendency for reduction in waist circumference (P for trend = 0.027), homeostasis model assessment of insulin resistance (P for trend = 0.039), and sTREM2 levels (P for trend = 0.023). Conclusions: Glycemic control is suggested to be important in preventing cognitive impairment in patients with type 2 diabetes without obesity. Higher serum sTREM2 levels would be a predictive marker for cognitive impairment in inadequately controlled type 2 diabetes without obesity.

A pilot study to examine the management of asymptomatic hyperparathyroidism in Japanese patients in accordance with the guidelines for asymptomatic PHPT proposed at the Third International Workshop in 2008.

Objective The treatment for asymptomatic primary hyperparathyroidism (PHPT) remains controversial. In 2008, the Third International Workshop on the Management of Asymptomatic PHPT proposed a set of guidelines for the management of asymptomatic PHPT. We therefore evaluated the application of the Workshop recommendations in Japanese patients with asymptomatic PHPT. Methods We analyzed each parameter of the guidelines in 87 Japanese patients with asymptomatic PHPT who underwent methoxy-isobutyl-isonitrile (MIBI) scintigraphy. Results Fewer than 10% of the patients were less than 50 years of age. The bone mineral density T-score was below -2.5 SD in 20 women (46.5% of all women analyzed) and in none of the men. The eGFR was <60 mL/min/1.73 m(2) in 17 patients. A majority of patients (43) satisfied only one parameter, while 25 patients satisfied none of the parameters. Furthermore, the MIBI-positive and surgically treated patients tended to satisfy a larger number of the parameters. The Workshop criteria and levels of PTH, daily Ca excretion, serum ALP and 1,25(OH)2 Vitamin D were further analyzed in relation to the findings of MIBI scans, and almost all of the parameters were found to be significantly correlated with the results of the MIBI studies. Conclusion Our results suggest the need to reassess the Workshop guidelines for the treatment of hyperparathyroidism in Japanese patients. It is desirable that MIBI scintigraphy be performed whenever possible, as this modality is anticipated to play an important role in determining whether or not surgery is appropriate.

Two rare cases of familial (mother and daughter) adrenocorticotropic hormone-independent Cushing's syndrome due to adrenal adenoma, as well as the asynchronous development of another contralateral adrenal adenoma in the mother.

We herein report two cases involving a mother and daughter who presented with clinical features of Cushing's syndrome (CS) at 50 and 29 years of age, respectively, and were both found to have adrenocorticotropic hormone-independent adrenal adenoma. Furthermore, a new adenoma was detected in the contralateral adrenal gland in the mother 10 years after surgical treatment, when she presented with subclinical CS. The pathogenesis of this disorder, including the presence of unknown genetic abnormalities causing hereditary CS, is currently poorly understood. In this report, we describe our experience with and consider the pathophysiological implications of two rare and very interesting cases of familial CS.

Recombinant human growth hormone replacement in a Japanese man with a novel PROP1 gene mutation (R112X).

Congenital combined pituitary hormone deficiency (CPHD) is associated with deficiencies of anterior pituitary hormones. PROP1 gene mutations are often responsible for CPHD, but few such cases have been reported in Japan. This study describes a 37-year-old Japanese man with CPHD, treated with hydrocortisone, testosterone, and L-thyroxine, who was evaluated for adult growth hormone deficiency (GHD). Gene analysis revealed a previously unknown PROP1 mutation (R112X). After 10 months of recombinant human growth hormone (rhGH) administration, cortisol and urinary free cortisol levels were significantly lower than before therapy. This case underscores the importance of reassessing hypothalamic-pituitary-adrenal axis function in GHD patients, especially those with a PROP1 mutation, during rhGH therapy.

A decrease in the dose of pegvisomant was needed for the treatment of acromegaly after adrenalectomy in a patient with coexisting preclinical Cushing's syndrome.

We herein describe the case of a 47-year-old woman with pre-clinical Cushing's syndrome caused by a left adrenal adenoma, which was diagnosed 6 years after trans-sphenoidal selective removal of a pituitary adenoma for acromegaly at age 35. The patient was started on bromocriptine and then somatostatin analogues after the surgery; however, since her serum insulin-like growth factor-1 (IGF-1) values remained above the age-adjusted normal range, the treatment for acromegaly was switched from somatostatin analogues to pegvisomant (10 mg daily), before a left laparoscopic adrenalectomy. After the subsequent adrenalectomy, the dose of pegvisomant could be reduced gradually to once every 4 days without any increase in the serum IGF-1 values. This is the first report describing the need for a different dose of pegvisomant for the treatment of acromegaly before and after adrenalectomy for pre-clinical Cushing's syndrome.

Impact of metabolic syndrome on the progression of Intima-Media Thickening in Japanese--a follow-up study.

The presence of metabolic syndrome (MetS) and its individual components is related to an increased IMT. MetS and increasing numbers of individual MetS components predicted future progression of IMT. Improvement of MetS was related to smaller increases in IMT, especially in females. These findings may suggest a benefit of intervention for MetS, which needs to be confirmed by prospective studies.

The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets.

CONTEXT: The molecular mechanisms by which triglycerides in lipid droplets (LDs) are synthesized, stored, and degraded need to be elucidated. OBJECTIVE: The objectives were to report siblings with neutral lipid storage disease with myopathy (NLSDM) with a novel mutation of adipose triglyceride lipase (ATGL) and determine whether the C-terminal part of ATGL containing the hydrophobic region plays a role in the interaction with LDs. DESIGN AND PATIENTS: Skin fibroblasts and peripheral blood leukocytes were obtained from NLSDM patients. In vitro experiments were performed with fibroblasts and COS7 cells. MAIN OUTCOME MEASURES: Transfection studies were used to assess the effects of various recombinant ATGL proteins on lipase activities and lipid contents. Fluorescence microscopy were used for determination of intracellular distribution of ATGL proteins. RESULTS: The direct sequence of ATGL cDNA reveals that a patient is a homozygote for the 4-bp deletion, leading to a premature stop codon and causes the lack of the C terminus of the protein including the hydrophobic domain. Overexpressed control ATGL in NLSDM fibroblasts was found around the rims of LDs and caused significantly reduced cellular lipid accumulation. In contrast, NLSDM ATGL was homogeneously located in the cytoplasm despite the presence of LDs and had almost no effect on LD degradation despite its similar lipase activity. A series of C-terminal truncated ATGLs without the intact hydrophobic domain failed to localize around and degrade LDs. CONCLUSIONS: These findings indicate that the domain including the hydrophobic region of ATGL was essential for association with LDs.