The pattern of fall in B-cell function measured as plasma and 24 h urinary C-peptide excretion, as well as levels of islet cell antibodies, insulin antibodies and metabolic parameters, were followed for two years in 39 children aged 1-17 years prospectively from clinical onset of Type 1 (insulin-dependent) diabetes. At onset 32/36 patients had measurable plasma C-peptide (median 0.13 nmol/l). Maximum values of fasting and postprandial plasma C-peptide were reached at a median duration of three months. Thereafter both plasma and urinary C-peptide declined linearly. The median value of the rate of fall in postprandial plasma C-peptide was 0.019 nmol.1-1.month-1. Age at onset was positively correlated to the maximum value of postprandial plasma C-peptide in each patient (rs = 0.57, p = 0.0001) and throughout the observation time positively correlated to fasting and postprandial C-peptide and to the 24 h urinary C-peptide excretion (rs range 0.35-0.70, p = 0.03-0.0001). The rate of fall of postprandial C-peptide was unrelated to age at onset and was strikingly parallel in different age groups. Islet cell antibodies were present in 87% of the patients at onset and decreased to 38% at 24 months. Islet cell antibody titres were not correlated to age at onset or to plasma or urinary C-peptide at any single observation. However, islet cell antibody negative patients had significantly higher (p less than 0.05) postprandial plasma C-peptide values at 1, 9, and 12 months of duration, compared to islet cell antibody positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective Gestational diabetes is associated with increased risk of developing noninsulin-dependent diabetes (NIDDM) later in life. By the time that a diagnosis of NIDDM is established, functional disturbances in the vascular system may be observed. This study was planned to assess macro-and microvascular function in nonpregnant women without signs of diabetes two to four years after a pregnancy complicated with gestational diabetes.Design Cross-sectional study.Setting Vascular research laboratory in the obstetric unit of a university hospital. Participants Seventeen nonpregnant, healthy women with a history of gestational diabetes and 20 nonpregnant control women of similar age without previous diabetes.Methods For quantification of the mechanical properties in large arterial vessels the wall movements of the abdominal aorta and left common carotid artery were recorded with an ultrasonic tracking system. Microvascular perfusion in the skin of the hand and foot was recorded by a laser Doppler technique to assess the vasodilatory response induced by transcutaneous acetylcholine. Results Women in the gestational diabetes group showed evidence of increased wall stiffness in the common carotid artery and a lower maximum incremental velocity of the pulsatile vessel diameter change in both aorta and carotid artery compared with controls. Acetylcholine induced vasodilatation in both hand and foot was lower in women with previous gestational diabetes compared with controls.Conclusion Abnormal vascular function was found in asymptomatic women with a history of gestational diabetes. It is speculated that these abnormalities might be early evidence of vascular complications associated with subsequent NIDDM.

OBJECTIVE -We examined the effect of diazoxide, an ATP-sensitive K ϩ channel opener and inhibitor of insulin secretion, on ␤-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS-A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years.RESULTS -Diazoxide decreased circulating C-peptide concentrations by ϳ50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 Ϯ 0.22 vs. 0.31 Ϯ 0.26 nmol/l, P ϭ 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide-vs. placebo-treated patients (Ϫ0.05 Ϯ 0.24 vs. Ϫ0.18 Ϯ 0.26 nmol/l, P ϭ 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 Ϯ 0.20 and 0.20 Ϯ 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent.CONCLUSIONS -This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of ␤-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest. Diabetes Care 27:2191-2197, 2004A t diagnosis, children with type 1 diabetes display some endogenous insulin production, which in most cases transiently increases after the initiation of insulin therapy (1,2) and subsequently subsides. Two to 3 years after onset of disease, a majority of children have no detectable circulating C-peptide (1,3,4), whereas 11% of adult patients display residual ␤-cell function Ͼ5 years after start of insulin treatment (5). A partially preserved insulin production is associated with a better glycemic control in both children and adolescents (6 -8) and may decrease the risk of microvascular complications and severe hypoglycemia in adults with type 1 diabetes (9 -12). Therefore, partial preservation of ␤-cell function represents an attractive goal of therapy for intervention trials (13).Type 1 diabetes is thought to be due to an autoimmune destruction of insulinproducing ␤-cells, reflected by the appearance of islet cell autoantibodies. Other researchers and we (14,15) have shown that islet cell autoantigen expression is regulated by the ambient glucose concentration and increases upon stimulation of insulin secretion (16). Moderately elevated glucose concentrations have been shown to sensitize ␤-cells to destruction by streptozotocin (17) and interleukin-1 (18), and we recently observed that inhibitors of insulin secretion, e.g., diazoxide and a newer potassium channel opener (NNC-118), protected islet ␤-cells in vitro against the toxic effect of streptozotocin (19). In experimental models of type 1 d...

In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.