Introduction
Several studies have examined the incidence of childhood T1DM in Japan from the 1970s onwards, but none have been long‐term studies using registration data. We estimate the incidence of childhood type 1 diabetes mellitus (T1DM) from 1986 to 2018 in Yamanashi Prefecture, Japan.
Methods
We began a population‐based, long‐term study of childhood T1DM in 1986 involving every hospital paediatrics department in Yamanashi Prefecture. In the Prefecture, every child newly diagnosed with T1DM is referred to a hospital, and therefore, almost 100% of new patients aged <15 years are registered. We calculated the incidence of T1DM among children aged <15 years from 1986 to 2018. All cases met the Japan Diabetes Society diagnostic criteria and were tested for T1DM‐related autoantibodies whenever possible.
Results
Ninety‐nine patients (44 boys and 55 girls) were newly diagnosed with T1DM. The annual incidence among 5‐ to 9‐year‐olds increased by 5.35% over the study period (95% confidence interval 2.34%‐8.35%, p = .0005), and there was a trend towards increasing 3‐year incidence (15.52% increase, p = .0516). There were also trends towards increasing annual and 3‐year incidence among 0‐ to 14‐year‐olds. However, there were no changes over time in annual or 3‐year incidence in the 0–4 year or 10–14 year age groups.
Conclusions
The incidence of T1DM in Yamanashi Prefecture increased among children aged 0‐14 years over the study period, with the most significant increase occurring among 5‐ to 9‐year‐olds. These data suggest that the number of children aged <15 years with T1DM is gradually increasing in one of the local prefectures in Japan, Yamanashi Prefecture and that the age of onset is decreasing.
Summary
Prader–Willi syndrome (PWS) is a genetic imprinting disorder that is characterized by obesity, short stature, and hypogonadism. Hypogonadism is characterized by normal luteinizing hormone (LH), high follicle-stimulating hormone (FSH), low testosterone, low inhibin B, and relatively low anti-Müllerian hormone (AMH). Only a few cases of central precocious puberty (CPP) have been reported in PWS, and follow-up for CPP with PWS is not established. Hence, we present a boy with PWS accompanied by CPP. Gonadotropin-releasing hormone analog (GnRHa) therapy was started at 7 years of age, CPP was adequately arrested, and GnRHa therapy was discontinued at 11.3 years of age. Growth hormone (GH) therapy was started at 12 years of age due to inadequate growth. He grew close to his final height, and his testes developed with normal LH, increased FSH, normal testosterone, and reduced AMH corresponding to puberty at 13.5 years of age. The features of 16 patients with PWS with CPP, including our patient, were summarized. Out of seven male patients, five were treated with GnRHa, as well as four out of nine female patients. Out of 16 patients, 6 were assessed with pubertal development over 13 years of age. Pubertal development was considered to be restored in four patients who had GnRHa therapy discontinuation. We should carefully follow-up on pubertal development in CPP. GnRHa therapy is useful for adequate puberty blockage, and pubertal development could be restored with GnRHa therapy discontinuation.
Learning points
Pubertal development in Prader–Willi syndrome (PWS) varies from hypogonadism to precocious puberty.
Pubertal development assessment based on clinical features and hormone levels is needed in central precocious puberty (CPP) treatment with PWS.
Gonadotropin-releasing hormone analog (GnRHa) therapy is useful for CPP with PWS, and pubertal development can be restored with GnRHa therapy discontinuation.
To elucidate the mechanism of insulin resistance due to insulin counterregulatory
hormones (ICRHs) and evaluate ICRH secretion kinetics, ICRH concentrations were measured
and correlated with blood glucose levels in 28 type 1 diabetic patients. Blood glucose was
measured before bedtime. Early morning urine samples were collected the next morning
before insulin injection and breakfast. Fasting blood glucose, cortisol, glucagon and
HbA1c levels were measured. Growth hormone (GH), adrenaline, cortisol and C-peptide levels
in morning urine samples were measured; SD scores were calculated for urine GH. The
laboratory values (mean ± SD) were as follows; HbA1c of 8.1% ± 1.4%; pre-bedtime glucose
of 203 ± 105 mg/dl; fasting blood glucose of 145 ± 87 mg/dl; serum cortisol of 21.6 ± 5.5
µg/dl; plasma glucagon of 98 ± 41 pg/ml; urinary GH, 27.2 ± 13.0 ng/gCr; urinary cortisol
of 238 ± 197 ng/gCr; and urinary Adrenaline of 22.9 ± 21.0 ng/gCr. The mean urinary GH SD
score was increased (+1.01 ± 0.70; p=0.000); the mean plasma glucagon lebel (98 ± 41
pg/ml) was not. Fasting blood glucose was positively correlated with plasma glucagon
(R=0.378, p=0.0471) and negatively correlated with urinary cortisol (R=–0.476, p=0.010).
Urinary adrenaline correlated positively with urinary GH (R=0.470, p=0.013) and urinary
cortisol (R=0.522, p=0.004). In type 1 diabetes, GH, glucagon and cortisol hypersecretion
may contribute to insulin resistance, but the mechanism remains unclear.
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