Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients

Clerc, Alice; Coupaye, Muriel; Mosbah, H.; Pinto, Graziella; Laurier, Virginie; Mourre, Fabien; Merrien, Christine; Diene, Gwénaëlle; Poitou, Christine; Tauber, Maïthé

doi:10.3390/jcm10225310

Cited by 8 publications

(3 citation statements)

References 47 publications

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“…High leptin resistance may result in excessive eating. Further studies on a larger number of cases are needed to establish whether the treatment of diabetes is difficult in TS 14 patients complicated by T2DM, similar to patients with Prader-Willi syndrome complicated by T2DM (29).…”

Section: Discussionmentioning

confidence: 99%

A Male Japanese Patient with Temple Syndrome Complicated by Type 2 Diabetes Mellitus

Iwanishi,

Yorifuji,

Yamamoto

et al. 2024

Intern. Med.

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We herein present the case of a 21-year-old male Japanese diabetic patient with Temple syndrome, caused by maternal uniparental disomy of chromosome 14. The patient was overweight and had type 2 diabetes, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, and microalbuminuria. He had an increased fat mass in the truncal region and a decreased lean mass throughout the body. This may lead to insulin resistance due to the absence of delta-like homolog 1 (DLK1) and retrotransposon gag-like 1 (RTL1). The patient had experienced social withdrawal at home (hikikomori in Japanese), had poorly controlled type 2 diabetes, and was overweight despite receiving diet therapy and oral hypoglycemic agents.

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Section: Discussionmentioning

confidence: 99%

A Male Japanese Patient with Temple Syndrome Complicated by Type 2 Diabetes Mellitus

Iwanishi,

Yorifuji,

Yamamoto

et al. 2024

Intern. Med.

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“…This prohormone convertase is less well studied, and mutations in PCSK2 are commonly associated with impaired glucose homeostasis in the context of type 2 diabetes [ 63 , 64 , 65 ]. The PWScr m+/p− mice have a mostly normal glucose metabolism, while human PWS patients are thought to suffer from type 2 diabetes, especially in the late stage of disease progression, typically due to severe obesity [ 6 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Reference Genes across Nine Brain Areas of Wild Type and Prader-Willi Syndrome Mice: Assessing Differences in Igfbp7, Pcsk1, Nhlh2 and Nlgn3 Expression

Kummerfeld

Skryabin

Brosius

et al. 2022

IJMS

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Prader–Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by the deletion or inactivation of paternally expressed imprinted genes at the chromosomal region 15q11–q13. The PWS-critical region (PWScr) harbors tandemly repeated non-protein coding IPW-A exons hosting the intronic SNORD116 snoRNA gene array that is predominantly expressed in brain. Paternal deletion of PWScr is associated with key PWS symptoms in humans and growth retardation in mice (PWScr model). Dysregulation of the hypothalamic–pituitary axis (HPA) is thought to be causally involved in the PWS phenotype. Here we performed a comprehensive reverse transcription quantitative PCR (RT-qPCR) analysis across nine different brain regions of wild-type (WT) and PWScr mice to identify stably expressed reference genes. Four methods (Delta Ct, BestKeeper, Normfinder and Genorm) were applied to rank 11 selected reference gene candidates according to their expression stability. The resulting panel consists of the top three most stably expressed genes suitable for gene-expression profiling and comparative transcriptome analysis of WT and/or PWScr mouse brain regions. Using these reference genes, we revealed significant differences in the expression patterns of Igfbp7, Nlgn3 and three HPA associated genes: Pcsk1, Pcsk2 and Nhlh2 across investigated brain regions of wild-type and PWScr mice. Our results raise a reasonable doubt on the involvement of the Snord116 in posttranscriptional regulation of Nlgn3 and Nhlh2 genes. We provide a valuable tool for expression analysis of specific genes across different areas of the mouse brain and for comparative investigation of PWScr mouse models to discover and verify different regulatory pathways affecting this complex disorder.

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“…The frequency of type 2 diabetes is reported to be 0 to 25% depending on the study population ( 34 , 47 , 58-60 ). A recent study showed that diabetes in young, obese adults was diagnosed at a mean age of 16 years with a peak during the transition period, suggesting reinforced glucose monitoring in adolescents and young adults ( 61 ). Insulin resistance and obesity are well known risk factors for type 2 diabetes and higher insulin levels and a high homeostatic model assessment index has been demonstrated in obese compared with nonobese adults with PWS ( 34 , 59 , 60 ).…”

Section: Insulin and Diabetesmentioning

confidence: 99%

Approach to the Patient With Prader–Willi Syndrome

Höybye

Tauber

2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Prader-Willi syndrome (PWS) is a rare, multi-systemic, genetic disorder involving the hypothalamus. It is caused by loss of expression of paternally inherited genes in chromosome 15 q11-13 region. The estimated incidence is around 1 in 20.000 births. PWS is characterized by a complex lifelong trajectory involving neurodevelopmental, nutritional, endocrine, metabolic and behavioral changes. The major symptoms are hypotonia, short stature, hypogonadism, and eating disorders ranging from anorexia in infancy to hyperphagia, a deficit of satiety, and a high risk of severe obesity. The patients display intellectual disability comprising cognitive deficit, delayed motor, and language development, learning deficits, impaired social skills, and emotional regulation. Behavioral features including temper outbursts, anxiety, obsessive–compulsive symptoms and rigidity are common and become more apparent with increasing age. Almost all have hypogonadism and growth hormone deficiency. Central adrenal insufficiency is rare whereas central hypothyroidism occurs in up to 30% of children with PWS. The prevalence of obesity increases with age from almost none in early childhood to more than 90% in adulthood. Up to 25% of adults with obesity have type 2 diabetes. Obesity and its complications are the major causes of comorbidity and mortality in PWS. As there is no specific treatment care consists of comprehensive management of feeding disorders, a restricted, controlled diet, regular exercise, hormone substitution and screening and treatment of comorbidities. Here we present the course of PWS from birth to adulthood in two patients and discuss their symptoms in relation to the literature.

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Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients

Cited by 8 publications

References 47 publications

A Male Japanese Patient with Temple Syndrome Complicated by Type 2 Diabetes Mellitus

A Male Japanese Patient with Temple Syndrome Complicated by Type 2 Diabetes Mellitus

Reference Genes across Nine Brain Areas of Wild Type and Prader-Willi Syndrome Mice: Assessing Differences in Igfbp7, Pcsk1, Nhlh2 and Nlgn3 Expression

Approach to the Patient With Prader–Willi Syndrome

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