Use of the Japanese gestational diabetes mellitus diagnostic strategy during the COVID-19 pandemic in Japan: A questionnaire survey.

AIM: Some concerns exist that diagnosis of gestational diabetes mellitus (GDM) may be missed when the simplified diagnostic criteria of the Japanese Society of Diabetes and Pregnancy (JSDP) for GDM (published during the COVID-19 pandemic) are used. Moreover, limited data is available regarding how widespread these diagnostic criteria are used when managing GDM during the COVID-19 pandemic. Therefore, this study aimed to determine how GDM diagnosis has changed during the COVID-19 pandemic in Japan. METHODS: The changes in GDM diagnosis during the COVID-19 pandemic were investigated using an online questionnaire to 2159 obstetric facilities in Japan. The questionnaire collected data on facility type, awareness of Japanese GDM diagnostic strategies, modifications to diagnostic methods for early and late GDM, and opinions on GDM management, with the pandemic divided into seven periods. RESULTS: We received responses from 593 facilities (27%). Approximately 90% of the facilities did not change their diagnostic process for early GDM or late GDM (occurring after 24 weeks gestation). However, during the COVID-19 pandemic, 19 facilities discontinued the use of 75-g oral glucose tolerance tests before 24 weeks of gestation, and 17 facilities discontinued it after 24 weeks of gestation, instead using the aforementioned Japanese GDM diagnostic strategy. CONCLUSIONS: Although a limited number of facilities modified their diagnostic method in response to the COVID-19 pandemic, this study demonstrated that those that adjusted their diagnostic method primarily used the Japanese COVID-19 GDM strategy by the JSDP.

Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes.

Few studies in Asian populations have analyzed how glucagon secretion is affected by ingested glucose, proteins or lipids, individually. To investigate the fluctuations of glucagon secretion after the intake of each of these nutrients, 10 healthy volunteers underwent oral loading tests using each of glucose, proteins and lipids, and blood levels of glucose, insulin and glucagon were measured every 30 min for 120 min. Whereas glucagon secretion was suppressed and minimally affected by oral glucose intake and lipid intake, respectively, oral protein intake robustly increased glucagon secretion, as well as insulin secretion. Further studies are needed to elucidate the mechanism by which protein loading increases glucagon secretion.

Effects of luseogliflozin on the secretion of islet hormones and incretins in patients with type 2 diabetes.

The insufficient activity of insulin and the hyperactivity of glucagon are responsible for glucose intolerance in patients with type 2 diabetes. Whereas sodium-glucose cotransporter-2 (SGLT2) inhibitors improve blood glucose levels in patients with type 2 diabetes, their effects on the secretion profiles of glucagon and incretins remain unclear. Therefore, to investigate the effects of the SGLT2 inhibitor luseogliflozin on metabolic and endocrine profiles, 19 outpatients with type 2 diabetes were administered luseogliflozin for 12 weeks. It is of note that all subjects were treated only with diet and exercise therapy, and we were able to investigate the effects of luseogliflozin separately from the effects of other antidiabetic agents. Body weight, body fat mass, fat-free mass, and muscle mass were significantly reduced after 12 weeks of luseogliflozin administration. Glycosylated hemoglobin significantly decreased from the baseline of 8.2% ± 0.8% to 7.3% ± 0.7% (p < 0.0001). The meal tolerance test demonstrated that luseogliflozin significantly recovered glucose tolerance, accompanied by improved insulin resistance and ß-cell function, whereas glucagon secretion was unaffected. Furthermore, GLP-1 secretion was significantly increased after luseogliflozin administration. Thus, luseogliflozin improved metabolic and endocrine profiles accompanied by increased GLP-1 secretion in type 2 diabetic patients without any antidiabetic medication, but did not affect glucagon secretion.

Basal glucagon hypersecretion and response to oral glucose load in prediabetes and mild type 2 diabetes.

Dysregulation of glucagon secretion plays an important role in the pathogenesis of type 2 diabetes (T2DM). However it hasn't been elucidated involvement of glucagon dysregulation in pathophysiology of T2DM. Recently a new glucagon sandwich enzyme-linked immunosorbent assay (ELISA) became available that can measure plasma glucagon level with higher accuracy and simpler procedure than the conventional RIA method. We performed OGTT for adult subjects aged 20-69 years to define normal glucose tolerance (NGT, n = 25), borderline glucose intolerance (defined as pre-diabetes mellitus: preDM, n = 15), or diabetes mellitus (DM, n = 13), and we measured glucagon levels with this new ELISA method at fasting and during OGTT. Plasma glucose, insulin, glucagon and active GLP-1 were also measured. This study took place in diabetes outpatient clinic in Kitasato University Hospital and an affiliated outpatient clinic. PreDM and DM exhibited higher fasting plasma glucagon levels than NGT (34.4 ± 4.6 and 44.1 ± 5.0 vs. 20.6 ± 3.6 pg/mL), and statistical significance was observed between NGT and DM (p < 0.05). There was significant correlation between fasting glucagon level and indexes of insulin sensitivity. During OGTT, glucagon levels were less suppressed in DM and preDM than in NGT, whereas no apparent relationship was observed between glucagon and GLP-1 secretion. Significant positive correlation was observed between glucagon levels during OGTT and fasting TG. In conclusion, subjects with mild T2DM exhibited fasting hyperglucagonemia and insufficient suppression to oral glucose load compared to NGT subjects.

Distinct clinical characteristics and therapeutic modalities for diabetic ketoacidosis in type 1 and type 2 diabetes mellitus.

AIMS: Patients with type 1 diabetes often develop diabetic ketoacidosis (DKA). Reportedly, DKA in type 2 diabetes has higher mortality despite its limited occurrence. The exact clinical characteristics and therapeutic modalities yielding successful outcomes in DKA type 2 diabetes remain unknown. METHODS: This retrospective study compared the clinical features and detailed treatment of consecutive type 1 and type 2 diabetes patients hospitalized with DKA between January 2001 and December 2014. RESULTS: We report on 127 patients with type 1 and 74 patients with type 2 diabetes whose DKA was successfully treated. The most frequent precipitating cause for DKA was infectious disease for patients with type 1 diabetes and consumption of sugar-containing beverages for those with type 2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels than those with type 1 diabetes (48.4±21.6, vs. 37.1±16.4mmol/l, P<0.01) and higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which normalized after DKA resolution. Compared with type 1 diabetes patients, those with type 2 diabetes required distinctly higher daily total insulin dosage (35.9±37.0U, vs. 20.2±23.3U, P<0.01), larger replacement fluid volumes (4.17±2.69L, vs. 2.29±1.57L, P<0.01) and greater potassium supplementation (23.9±36.5mEq, vs. 11.2±17.9mEq, P<0.01) to resolve DKA and reduce plasma glucose level to ≤16.7mmol/l. CONCLUSIONS: DKA patients with type 2 diabetes required management with a modified treatment protocol to resolve their profound hyperglycemia and dehydration compared with those with type 1 diabetes.

Levels of albuminuria and risk of developing macroalbuminuria in type 2 diabetes: historical cohort study.

Although increased urinary albumin excretion may increase the risk of adverse renal outcomes in patients with diabetes, it remains unclear whether microalbuminuria is associated with a higher incidence of macroalbuminuria in the absence of non-diabetic kidney events that frequently develop during the long-term course of type 2 diabetes. This historical cohort study included patients with type 2 diabetes, spot urine albumin:creatinine ratio (ACR) <300 mg/gCr and normal serum creatinine concentrations treated between August 1988 and April 2015. Patients with any evidence suggesting non-diabetic kidney diseases at baseline were excluded. Over a median follow-up of 50 months, 70 of the 1760 included patients developed macroalbuminuria. Twenty-one of these patients were diagnosed with non-diabetic renal events. The five-year cumulative incidence of macroalbuminuria in patients with ACRs of 0-7.5 mg/gCr, 7.5-30 mg/gCr, 30-150 mg/gCr, and 150-300 mg/gCr were 0%, 0.53%, 3.5%, and 36.0%, respectively, with significant differences between each pair of ACR categories. In type 2 diabetes, higher urinary ACR, even within a level of normoalbuminuria, was associated with a greater incidence of macroalbuminuria when non-diabetic renal events were excluded. These results conflict with findings suggesting that microalbuminuria is a poor indicator for the progression of diabetic nephropathy.

Circulating levels of human salusin-ß, a potent hemodynamic and atherogenesis regulator.

Using bioinformatics analysis, we previously identified salusin-ß, an endogenous bioactive peptide with diverse physiological activities. Salusin-ß is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-ß acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-ß concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA). Salusin-ß was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-ß peak coincided with synthetic authentic salusin-ß. Plasma salusin-ß concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-ß concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-ß levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-ß levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-ß levels and for confirming the presence of authentic salusin-ß in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin-ß concentrations and a role for plasma total salusin-ß concentrations as an indicator of systemic vascular diseases.

A woman with salt-wasting congenital adrenal hyperplasia presenting with a mucinous ovarian cystadenoma during pregnancy.

Women with congenital adrenal hyperplasia (CAH) caused by steroid 21-hydroxylase deficiency show reduced fertility, especially with the salt-wasting form. A 27-year-old pregnant woman with this disease underwent laparotomy and oophorectomy to remove a multilocular ovarian tumor at 14 weeks of pregnancy. This proved to be a mucinous cystadenoma. Toward the third trimester, she presented with marked elevations of 17α-hydroxyprogesterone and plasma renin activity. Careful management of endocrine and body fluid homeostasis allowed her to give birth to a healthy female infant with normal external genitalia. This case illustrates endocrinological parameters during pregnancy in a woman with classical salt-wasting CAH.