Regression from stage 3 to stage 2 type 1 diabetes mellitus after discontinuing growth hormone therapy.

Summary: Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH. Learning points: Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement. Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment. The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment.

Cystic fibrosis related diabetes: Nutrition and growth considerations.

Nutritional considerations are crucial to the optimal management of cystic fibrosis related diabetes (CFRD). The development of abnormal glucose tolerance and CFRD can have negative effects on CF nutritional status. Treatment of CFRD with insulin replacement is essential; however, medical nutrition therapy is important to maintain nutritional status while normalizing blood glucose levels. CF Foundation Nutritional Guidelines are recommended for the nutritional management of CFRD; specifically, the diet should be high in calories, protein, fat, and salt. Carbohydrate intake is not limited, but carbohydrate counting can be used to guide insulin dosing and maintain consistent blood glucose levels. CFTR modulator therapy shows early promise for the improvement of growth and nutritional parameters in CF.

Hypophosphatemic rickets: lessons from disrupted FGF23 control of phosphorus homeostasis.

Fibroblast growth factor-23 (FGF23) regulates phosphate reabsorption in the kidney and therefore plays an essential role in phosphate balance in humans. There is a host of defects that ultimately lead to excess FGF23 levels and thereby cause renal phosphate wasting and hypophosphatemic rickets. We describe the genetic, pathophysiologic, and clinical aspects of this group of disorders with a focus on X-linked hypophosphatemia (XLH), the best characterized of these abnormalities. We also discuss autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR) and tumor-induced osteomalacia (TIO) in addition to other rarer FGF23-mediated conditions. We contrast the FGF23-mediated disorders with FGF23-independent hypophosphatemia, specifically hypophosphatemic rickets with hypercalciuria (HHRH). Errant diagnosis of hypophosphatemic disorders is common. This review aims to enhance the recognition and appropriate diagnosis of hypophosphatemia and to guide appropriate treatment.

Prenylation of the floral transcription factor APETALA1 modulates its function.

The Arabidopsis MADS box transcription factor APETALA1 (AP1) was identified as a substrate for farnesyltransferase and shown to be farnesylated efficiently both in vitro and in vivo. AP1 regulates the transition from inflorescence shoot to floral meristems and the development of sepals and petals. AP1 fused to green fluorescent protein (GFP) retained transcription factor activity and directed the expected terminal flower phenotype when ectopically expressed in transgenic Arabidopsis. However, ap1mS, a farnesyl cysteine-acceptor mutant of AP1, as well as the GFP-ap1mS fusion protein failed to direct the development of compound terminal flowers but instead induced novel phenotypes when ectopically expressed in Arabidopsis. Similarly, compound terminal flowers did not develop in era1-2 transformants that ectopically expressed AP1. Together, the results demonstrate that AP1 is a target of farnesyltransferase and suggest that farnesylation alters the function and perhaps specificity of the transcription factor.