Neonatal diabetes mellitus.
ABSTRACT An explosion of work over the last decade has produced insight into the multiple hereditary causes of a nonimmunological form of diabetes diagnosed most frequently within the first 6 months of life. These studies are providing increased understanding of genes involved in the entire chain of steps that control glucose homeostasis. Neonatal diabetes is now understood to arise from mutations in genes that play critical roles in the development of the pancreas, of beta-cell apoptosis and insulin processing, as well as the regulation of insulin release. For the basic researcher, this work is providing novel tools to explore fundamental molecular and cellular processes. For the clinician, these studies underscore the need to identify the genetic cause underlying each case. It is increasingly clear that the prognosis, therapeutic approach, and genetic counseling a physician provides must be tailored to a specific gene in order to provide the best medical care.
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ABSTRACT: Insulin synthesis and cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in either aspect leads to development of diabetes. PERK (EIF2AK3) loss of function mutations in humans and mice exhibit permanent neonatal diabetes that is characterized by insufficient β-cell mass and reduced proinsulin trafficking and insulin secretion. Unexpectedly, we found that Perk heterozygous mice displayed lower blood glucose levels.PLoS ONE 01/2014; 9(6):e99684. · 3.53 Impact Factor
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ABSTRACT: Insulin gene mutation (INS) is the second most common cause of permanent neonatal diabetes (PNDM). We present the 1st cases of Saudi monozygotic twins with permanent neonatal diabetes mellitus who had simultaneous onset of disease due to p.C109Y (p.Cys109Tyr, c.326G>A) heterozygous missense mutation in exon 3 of the insulin (INS) gene. The twin patients had the same mutation while their parents are unaffected with normal genetic testing suggesting that this mutation had raised de novo. This p.C109Y mutation affects a highly conserved cysteine residue which is crucial for protein folding. Subjects with this form of diabetes will need lifelong insulin therapy.Journal of Diabetes & Metabolism 01/2014; 5(2).
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ABSTRACT: Diabetes mellitus (DM) is a syndrome characterized by disturbed metabolism of carbohydrate, protein, and fat. It is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin. It presents with very different medical and psychosocial issues in children. Epidemiological studies indicate that there is gradual but steady increase in the incidence of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in both developed and developing countries. The manifestations, therapy goals, clinical course, susceptibility to complications of diabetes differ among childhood cases. T1DM accounts for the majority of cases of diabetes in children. Diabetic ketoacidosis may be the initial presentation of T1DM in many children particularly in Africa probably due to low level of awareness. The focus of this review on T1DM is to provide an overview of the major advances in the aetiology, pathogenesis, and clinical management of newly diagnosed children and their subsequent management with the aim of ensuring optimal growth and development as well as preventing acute and chronic complications. The advances in insulin therapy and regimens and the presentation and management of diabetic ketoacidosis are discussed. The prospects for the cure of the disease are also highlighted in this review.Annals of Ibadan postgraduate medicine. 12/2008; 6(2):9-20.