OBJECTIVETo determine the prevalence of residual β-cell function (RBF) in children after 3–6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.RESEARCH DESIGN AND METHODSA total of 342 children (173 boys) 4.8–18.9 years of age with type 1 diabetes for 3–6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA1c, and daily insulin requirements was retrieved from the medical records and through patient interviews.RESULTSNinety-two children (27%) had RBF >0.04 nmol/L. Patients with RBF <0.04 nmol/L were significantly more likely to have severe hypoglycemia than patients with RBF >0.04 nmol/L (odds ratio, 2.59; 95% CI, 1.10–7.08; P < 0.03). HbA1c was significantly higher in patients with RBF <0.04 nmol/L compared with patients with RBF >0.04 nmol/L (mean, 8.49 ± 0.08% [69.3 ± 0.9 mmol/mol] vs. 7.92 ± 0.13% [63.1 ± 1.4 mmol/mol]; P < 0.01), and insulin requirements were significantly lower in patients with RBF >0.2 nmol/L (mean ± SE: 1.07 ± 0.02 vs. 0.93 ± 0.07 units/kg/day; P < 0.04).CONCLUSIONSWe demonstrated considerable phenotypic diversity in RBF among children after 3–6 years of type 1 diabetes. Children with RBF are at lower risk for severe hypoglycemia, have better diabetes regulation, and have lower insulin requirements compared with children without RBF. There appears to be a lower limit for stimulated RBF of ∼0.04 nmol/L that confers a beneficial effect on hypoglycemia and metabolic control.

Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3-6 years Sorensen, J. S.; Vaziri Sani, Fariba; Maziarz, M.; Kristensen, K.; Ellerman, A.; Breslow, N.; Lernmark, Åke; Pociot, F.; Brorsson, C.; Birkebaek, N. H.

Independent of pubertal status, T1D was associated with an abnormal IGF system. However, a positive RBF status appeared important but only in prepubertal children, in whom all IGF components but IGFBP-1 were normalized. We speculate that the pubertal GH surge induces insulin resistance, which overrides the stimulatory effect that an RBF may exert on the liver-derived IGF system.

We report on a boy with diabetes mellitus and a phenotype indicating glucokinase (GCK) insufficiency, but a normal GCK gene examination applying direct gene sequencing. The boy was referred for diabetes mellitus at 7.5 years old. His father, grandfather and great grandfather suffered type 2 DM. Several blood glucose profiles showed (BG) of 6.5–10 mmol/L L. After three years on neutral insulin Hagedorn (NPH) in a dose of 0.3 IU/kg/day haemoglobin A1c (HbA1c) was 6.8%. Treatment was changed to sulphonylurea 750 mg a day, and after 4 years HbA1c was 7%. At that time a multiplex ligation-dependent amplification gene dosage assay (MLPA) was done, revealing a whole GCK gene deletion. Medical treatment was ceased, and after one year HbA1c was 6.8%. This case underscores the importance of a MLPA examination if the phenotype of a patient is strongly indicative of GCK insufficiency and no mutation is identified using direct sequencing.

Background In patients with aortic valve stenosis (AS), the pathophysiological abnormalities involved in the transition to symptomatic heart failure are unclear. During progression of chronic heart failure, the coupling between myocardial stroke work and myocardial oxygen consumption, i.e. myocardial external efficiency (MEE), deteriorates. However, in AS patients it is unknown whether changes in MEE over time are involved in disease progression and whether MEE has prognostic information. Purpose In patients with AS, we 1) investigated changes in MEE over time and 2) studied if MEE was associated with long-term prognosis. Methods In a prospective design, we studied 10 healthy controls and 38 patients with moderate-severe, asymptomatic AS (aortic valve area 0.5±0.1 cm2/m2, mean gradient 31±12 mmHg) and left ventricular ejection fraction ≥50%. The patient group was evaluated by serial 11C-acetate positron emission tomography, cardiovascular magnetic resonance imaging and echocardiography with a median follow-up period of 2.8 years. Furthermore, we conducted an extended follow-up of patients for a median of 5.2 years to detect clinical events (defined as symptoms due to AS, aortic valve replacement, hospitalization due to heart failure or cardiovascular death) and related them to MEE changes. Results During follow-up AS patients mean aortic valve pressure gradients increased by 13 mmHg (9 to 17; p&lt;0.001) (mean (95% confidence interval)) and aortic valve opening area declined by −0.15 cm2 (−0.20 to −0.09; p&lt;0.001). Global longitudinal strain worsened by 2.6% (1.8 to 3.5; p&lt;0.001) and N-terminal pro-B-type natriuretic peptide increased by 162 ng/L (28 to 296; p=0.02) whereas left ventricular ejection fraction and cardiac index did not change significantly. MEE increased during follow-up by 4.3% (1.9 to 6.8; p=0.001) from 25.2% (24.0 to 26.5) to 29.5% (27.3 to 31.8) and was higher compared to healthy volunteers 19.9% (18.1 to 21.8; p&lt;0.001). The changes in MEE were positively correlated to changes in end-diastolic volume (r=0.58, p=0.005) and wall stress (r=0.54, p=0.01). There were no changes in MVO2 0.0 mL/min/100g (−0.8 to 0.8; p=0.98) during follow-up. As compared to event-free patients, patients who experienced a clinical event during long-term follow-up (n=24, 63%) had higher baseline MEE 26.5% (24.3 to 28.6) vs 23.8% (22.6 to 25.1) (p=0.04) and did not increase MEE during follow-up 1.9% (−1.8 to 5.6; p=0.28) vs 5.9% (2.6 to 9.2; p=0.002). Conclusion In asymptomatic AS patients, MEE increased over time in tandem with increasing transvalvular gradients and wall stress. Thus, the myocardium displayed an inherent capacity to improve the coupling between oxidative metabolism and contractile function in response to pressure overload. High baseline MEE and blunted MEE increase predicted a poor prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Lundbeck FoundationArvid Nilssons Foundation

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