We conclude that, in conditions of hyperglycemia, C-peptide reduces monocytes activation via inhibition of the NF-κB pathway.
C-peptide, historically considered a biologically inactive peptide, has been shown to exert insulin-independent biological effects on a number of cells proving itself as a bioactive peptide with anti-inflammatory properties. Type 1 diabetic patients typically lack C-peptide, and are at increased risk of developing both micro- and macrovascular complications, which account for significant morbidity and mortality in this population. Inflammatory mechanisms play a pivotal role in vascular disease. Inflammation and hyperglycemia are major components in the development of vascular dysfunction in type 1 diabetes. The anti-inflammatory properties of C-peptide discovered to date are at the level of the vascular endothelium, and vascular smooth muscle cells exposed to a variety of insults. Additionally, C-peptide has shown anti-inflammatory properties in models of endotoxic shock and type 1 diabetes-associated encephalopathy. Given the anti-inflammatory properties of C-peptide, one may speculate dual hormone replacement therapy with both insulin and C-peptide in patients with type 1 diabetes may be warranted in the future to decrease morbidity and mortality in this population.
Context The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. Objective To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. Design A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment and course of this complication was collated centrally. Results There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range 0.2 to 12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the two oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only two of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while four more stopped the diet during follow-up after resolution of hypercalcemia. Conclusions Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown, but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.
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