Félix Camiña

Progression of Nephropathy in Type 2 Diabetes: The Glycation Gap Is a Significant Predictor After Adjustment for Glycohemoglobin (Hb A1c)

BACKGROUND The glycation gap has been proposed as an index of nonglycemic determinants of glycated hemoglobin (Hb A(1c)). We investigated whether it predicts progression of nephropathy in type 2 diabetic patients. METHODS We recorded albumin excretion rate, Hb A(1c), and serum fructosamine in 2314 patients over an average of 6.5 years. Hb A(1c) was regressed on fructosamine by using a repeated-measures longitudinal regression model and data for all visits of all patients; the raw glycation gap gg was calculated at each visit, as measured by Hb A(1c) minus the value predicted by the regression; and the mean glycation gap (GG) was defined for each patient as the mean of the values for the raw glycation gap (gg) calculated at each visit. The study group was divided into high-, medium- and low-GG groups of equal sizes, which were compared for progression of nephropathy by Cox regression analyses controlling for age, sex, duration of diabetes, initial nephropathy status, therapy, baseline Hb A(1c), mean Hb A(1c), and mean fructosamine. The design of the study was a retrospective cohort study with follow-up for 6.5 (SD 4.2) years. RESULTS The gg exhibited considerable stability over time. In the high- and medium-GG groups, the risk of progression of nephropathy was respectively 2.5 and 1.6 times that of the low-GG group (P < 0.0001 and P = 0.001, respectively) after adjustment as described above. CONCLUSIONS GG predicts the progression of nephropathy in type 2 diabetic patients independently of fructosamine and even after adjustment for Hb A(1c). The joint use of the glycation gap and fructosamine as measures of nonglycemic and glycemic determinants of glycation, respectively, may improve evaluation of the risk of nephropathy and of the glycemic control desirable for the individual patient.

SERUM CARNITINE LEVELS IN EPILEPTIC CHILDREN BEFORE AND DURING TREATMENT WITH VALPROIC ACID, CARBAMAZEPINE, AND PHENOBARBITAL

Serum levels of free, acyl, and total carnitine were determined in 32 patients with seizures, before and after 3, 6, and 12 months of treatment with valproic acid (17 patients), carbamazepine (10 patients), or phenobarbital (5 patients). In all three treated groups, both free and total carnitine levels showed a significant decline with respect to pretreatment levels. This decline was most marked and most consistent in patients treated with valproic acid. In 35% of the patients in this group, carnitine deficiency (ie, total camitine < 30 μmol/L) was observed by month 12. In none of the three groups were serum carnitine levels significantly correlated with the serum concentration of the drug. These findings suggest a need to monitor serum carnitine levels in children treated with any of these drugs. (J Child Neurol 1998;13:546-549).

Intrapersonal HbA1c variability and the risk of progression of nephropathy in patients with Type 2 diabetes

Diabet. Med. 29, 1562–1566 (2012)

Neuron-specific enolase, nucleotides, nucleosides, purine bases, oxypurines and uric acid concentrations in cerebrospinal fluid of children with meningitis

To determine the effects of meningitis on cerebral energy metabolism, cerebrospinal fluid concentrations of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high-performance liquid chromatography, and neuron-specific enolase by an enzyme immunoassay method, in 100 children with meningitis (45 bacterial, 46 viral and nine tuberculous), aged between 1 month and 13 years, and in 160 age-matched controls. Compared with controls, patients with bacterial meningitis showed high concentrations of hypoxanthine, xanthine and urate; patients with viral meningitis showed high concentrations of inosine, guanosine, xanthine, urate and neuron-specific enolase; and patients with tuberculous meningitis showed very high concentrations of inosine, xanthine and urate. Xanthine and urate concentrations were significantly higher in patients with tuberculous meningitis than in patients with viral or bacterial meningitis. These results suggest that in the acute stage of bacterial, viral and tuberculous meningitis, neuronal energy metabolism may be altered. The measurement of cerebrospinal xanthine and uric acid concentrations may be useful for the early diagnosis of a tuberculous origin.

Estimation of the Glycation Gap in Diabetic Patients With Stable Glycemic Control

OBJECTIVE The glycation gap (the difference between measured A1C and the value predicted by regression on fructosamine) is stable and is associated with microvascular complications of diabetes but has not hitherto been estimated within a clinically useful time frame. We investigated whether two determinations 30 days apart suffice for a reasonably reliable estimate if both A1C and fructosamine exhibit stability. RESEARCH DESIGN AND METHODS We studied 311 patients with type 1 or type 2 diabetes for whom simultaneous measurements of A1C and serum fructosamine had been made on at least two occasions separated by 1 month (t0 and t1). Glycemia was deemed stable if A1C(t1) – A1C(t0) and fructosamine(t1) − fructosamine(t0) were both less than their reference change values (RCVs). Instantaneous glycation gaps [gg(t0) and gg(t1)] and their mean (GG), were calculated using the data from all stable patients for the required regression. RESULTS Stable glycemia was shown by 144 patients. In 90% of unstable case subjects, a change in medication was identified as the cause of instability. Among 129 stable patients with an average of eight gg determinations prior to t0, GG correlated closely with the mean of these prior determinations (r2 = 0.902, slope 1.025, intercept −0.038). CONCLUSIONS The glycation gap can be calculated reliably from pairs of A1C and fructosamine measurements taken 1 month apart if these measurements satisfy the RCV criteria for glycemic control.

Cerebrospinal fluid purine metabolite and neuron-specific enolase concentrations after febrile seizures

If febrile seizures cause significant compromise of neuronal metabolism (whether permanent or reversible), this should be reflected in an increase in the cerebrospinal fluid concentrations of neuron-specific enolase (NSE) and/or adenosine triphosphate (ATP) breakdown products. In the present study, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and NSE concentrations were determined in the cerebrospinal fluid of 90 children 1 h after febrile seizure (73 simple febrile seizures (SFS); 17 complex febrile seizures (CFS)), and in a control group of 160 children. There was no statistically significant difference between the SFS group and the control group for any of the substances determined, suggesting that SFS neither significantly depletes neuronal ATP concentration, nor significantly increases NSE concentration; thus, SFS do not appear to constitute a threat to neuronal integrity. However, patients with CFS showed significantly lower IMP concentrations and significantly higher adenine concentrations than controls, and significantly higher AMP concentrations than SFS patients; these results suggest that CFS may affect energy metabolism in the brain. However, NSE concentrations were normal in the cerebrospinal fluid of both SFS and CFS patients, suggesting that neither type of seizure causes significant neuronal damage, at least early after the seizure.

Neuron-specific enolase levels in the cerebrospinal fluid of neurologically healthy children.

Levels of neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF) of children without neurological disease were assessed. CSF samples were obtained from 37 subjects aged between 1 month and 13 years. All subjects had undergone lumbar puncture for diagnostic purposes, and were subsequently shown not to be suffering any form of neurological disease. NSE levels in CSF were determined by an enzyme immunoassay method. NSE level ranged from below the detection limit to 4.8 ng/ml (1.52+/-1.01 ng/ml). The present results may be useful as a basis for defining reference levels of NSE in CSF in post-neonatal children.

Translating the A1C Assay Into Estimated Average Glucose Values: Response to Nathan et al.

Nathan et al. (1) present a regression equation that they propose be used to convert measured values of A1C into estimated average glucose (eAG) values, in accordance with recommendations (2) and subject to the condition that their study fulfill its a priori–specified criterion. The criterion declared is that for ≥90% of patients, average glucose values, calculated from continuous glucose monitoring and 7-point glucose measurements over a 3-month span, fall within 15% of the average glucose using the study-wide average glucose as opposed to the A1C regression equation. This criterion was indeed fulfilled (with surprising narrowness: 89.95% of subjects fell within the ±15% limits) (1). Using the proposed equation thus involves an error limit in eAG …

PURINE METABOLITES AND PYRIMIDINE BASES IN CEREBROSPINAL FLUID OF CHILDREN WITH SIMPLE FEBRILE SEIZURES

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and pyrimidine bases were determined in the CSF of 18 children after simple febrile seizures and in a control group. There was no statistically significant difference between the two groups for any of these metabolites. This suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuron adenosine triphosphate ATP levels.

Concentrations of Purine Nucleotides and Purine and Pyrimidine Bases in Cerebrospinal Fluid of Neurologically Healthy Children

The concentrations of the nucleotides AMP and IMP, the nucleosides adenosine, guanosine and inosine, the purine bases adenine, guanine, hypoxanthine and xanthine, urate, and the pyrimidine bases cytosine, thymine and uracil were determined by high performance liquid chromatography in the cerebrospinal fluid of 63 children aged between 1 month and 13 years who showed no sign of neurological disease. The results are compared with those of other authors, and used to establish reference ranges for the above metabolites in the cerebrospinal fluid of children.