Search

We measured serum C-peptide, glucose, pH, islet antibodies and insulin antibody binding at diagnosis in 84 children with Type 1 (insulin-dependent) diabetes. In a subgroup of 33 children, residual insulin secretion (basal and peak C-peptide response to Sustacal), insulin antibody binding and HbA were measured at 10 days, 1, 3, 6 and 12 months. At presentation C-peptide correlated positively with age at onset and negatively with the blood glucose concentration. Median C-peptide concentration at diagnosis was low, rose significantly ( p<0.05) at 10 days, reached a maximum at 1-3 months and declined gradually to 1 year. C-peptide concentration both at diagnosis and at 10 days correlated with that at 3 and 6 months. Of the factors investigated, only age ( p<0.005) and sex (higher in females, p<0.01) were found to have a significant influence on basal/peak C-peptide levels throughout the first year. In particular there was no relationship between C-peptide, HbA and insulin dose during this period. A peak C-peptide response at 3-6 months>/<0.32 nmol/l was used to divide the group into two: 16 had a peak response <0.32 nmol/l (low secretors) while in 17, the peak C-peptide was >0.32 nmol/l (high secretors). While the low secretors had significantly ( p<0.05) lower C-peptide levels during the first year, there were no differences between low and high secretors in HbA or insulin dose. These data suggest that there are two patterns of residual insulin secretion during the first 12 months after diagnosis of Type 1 diabetes. One pattern shows good amplitude and duration of residual insulin secretion, while both these features are significantly ( p<0.05) reduced in the other. The C-peptide concentration both at diagnosis and at 10 days, as well as age at onset and sex are important predictors of the pattern to be followed. Our data suggest further that the magnitude of residual insulin secretion does not play a decisive role in metabolic control during this period. [ABSTRACT FROM AUTHOR]

Glycosylated haemoglobin (HbA) was measured serially by microcolumn chromatography in 38 children with newly diagnosed insulin-dependent diabetes. Initial HbA levels of 13.6±0.5% fell significantly from day 0 (prior to therapy) both to day 1 (1.6±0.2% decrease) and to day 3-5 (2.6±0.4% decrease) (p < 0.001). This drop correlated closely with changes in blood glucose (p < 0.001), less closely and inversely with plasma bicarbonate levels (p < 0.01), but not with prior duration of symptoms or changes in serum cholesterol and triglyceride concentrations. HbA levels reached a nadir of 8.2±0.3% 3 weeks to 6 months after diagnosis, and correlated with decreasing insulin dosage (p < 0.001). HbA levels rose again to 11.4±0.5% in 21 patients followed for more than 3-6 months. Our results indicate that (1) HbA levels change rapidly during initial stabilization of insulin-dependent diabetes suggesting that glycosylation may not be entirely irreversible, and (2) HbA levels are consistent with clinical assessment of control during remission and postremission phases. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Acute clamped hyperglycaemia activates the renin-angiotensin-aldosterone system (RAAS) and increases the urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Our objective was to determine whether blockade of the RAAS would blunt the effect of acute hyperglycaemia on urinary cytokine/chemokine excretion, thereby giving insights into potentially protective effects of these agents prior to the onset of clinical nephropathy., Methods: Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances) and urinary cytokines/chemokines were measured after 6 h of clamped euglycaemia (4-6 mmol/l) and hyperglycaemia (9-11 mmol/l) on two consecutive days in patients with type 1 diabetes mellitus (n = 27) without overt nephropathy. Measurements were repeated after treatment with aliskiren (300 mg daily) for 30 days., Results: Before aliskiren, clamped hyperglycaemia increased filtration fraction (from 0.188 ± 0.007 to 0.206 ± 0.007, p = 0.003) and urinary fibroblast growth factor-2 (FGF2), IFN-α2 and macrophage-derived chemokine (MDC) (p < 0.005). After aliskiren, the filtration fraction response to hyperglycaemia was abolished, resulting in a lower filtration fraction after aliskiren under clamped hyperglycaemic conditions (p = 0.004), and none of the biomarkers increased in response to hyperglycaemia. Aliskiren therapy also reduced levels of urinary eotaxin, FGF2, IFN-α2, IL-2 and MDC during clamped hyperglycaemia (p < 0.005)., Conclusions/interpretation: The increased urinary excretion of inflammatory cytokines/chemokines in response to acute hyperglycaemia is blunted by RAAS blockade in humans with uncomplicated type 1 diabetes mellitus.