***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Aims /hypothesis . To test the hypothesis that small size for gestation and poor postnatal growth in preterm infants is associated with higher fasting and post-load plasma glucose and insulin concentrations at 9–12 years of age.¶ Methods . Prospect i ve follow-up at 9–12 years of 385 preterm children with birth weight less than 1850 g , who had anthropometry recorded at birth , 18 months and 7 years .  Fasting plasma glucose , insulin , proinsulin and 32,33 split proinsulin concentrations and glucose and insulin concentrations 30 min after a st and ard glucose load were measured.¶ Results . Post-load glucose concentrations were negatively related to birth weight , independently of gestation or subsequent growth . Fasting split proinsulin and 30-min insulin concentrations were highest in children who showed the greatest increase in weight centile between birth and current follow-up , regardless of gestation . When weight during childhood was included , birthweight centile was , however , no longer statistically significant : concentrations of fasting , split , proinsulin and 30-min insulin were highest in those children who had shown the greatest increase in weight centile between 18 months of age and current follow-up , with no evidence of a greater effect in those who were smallest at 18 months.¶ Conclusion /interpretation . Our findings suggest that fetal growth influences plasma glucose 30 min after a glucose load in preterm children at 9–12 years . In contrast , childhood weight gain is the most important factor influencing insulin concentrations and this effect is the same regardless of early size . [ Diabetologia ( 2000 ) 43 : 714–717 This prospect i ve , 16-week , r and omised , double-blind , parallel-group study assessed the differential impact of the pr and ial glucose regulating oral hypoglycaemic drug , repaglinide , and placebo upon perceptions of quality of life ( QoL ) and treatment satisfaction in pharmacotherapy-naive patients with Type 2 diabetes . In addition , the study assessed whether these outcomes were influenced by the patients ' level of glycaemic control . A total of 253 patients were r and omised in a 2:1 ratio of repaglinide : placebo , with doses taken flexibly with main meals ( 2–4 per day ) , whenever they were eaten . Repaglinide was initiated at 0.5 mg per meal , increased to 1 mg after 4 weeks if fasting plasma glucose exceeded 7.8 mmol/l . QoL and treatment satisfaction outcomes were compared using generic and disease-specific self- assessment measures , previously applied in diabetes : the WHO Well being Question naire ( WHO-WBQ ) , WHO Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) and EuroQoL EQ-5D . Over the trial period , repaglinide-treated patients reported a significant 9 % improvement in ( WHO-DTSQ ) treatment satisfaction score ( p < 0.05 ) . No significant increase was associated with placebo . The correlation between decrease in glycated haemoglobin ( HbAlc ) and increase in treatment satisfaction ( WHO-DTSQ ) was −0.22 ( p < 0.01 ) . Scores obtained with the other measures did not change significantly during the trial in either group , but the cohort exhibited only a slight reduction in wellbeing ( WHO-WBQ ) and health status ( EQ-5D ) at baseline compared with the background population . In conclusion , flexible mealtime dosing with oral medication appears to be well accepted by pharmacotherapy-naïve patients with Type 2 diabetes . The results suggest that repaglinide provides a higher level of treatment satisfaction  than placebo , and this may in part relate to improved glycaemic control AIMS The new non-sulphonylurea oral hypoglycaemic agent nateglinide has been shown to enhance insulin secretion in animals and in healthy human volunteers and thus offers a potential advance in the treatment of Type 2 diabetes mellitus . This study examined whether nateglinide can enhance insulin secretion , and particularly the first phase insulin response , in patients with Type 2 diabetes . METHODS A double-blind , placebo-controlled trial , examining the effects of a single oral dose of 60 mg nateglinide , given 20 min prior to an intravenous glucose tolerance test ( IGTT ) , on insulin secretion in 10 otherwise healthy Caucasian men with recently diagnosed Type 2 diabetes ( duration since diagnosis 0 - 44 months ) . RESULTS Insulin secretion ( both overall and first phase ) was significantly increased by nateglinide ( P < 0.001 ) , as were C-peptide ( P < 0.001 ) and proinsulin ( P < 0.001 ) secretion . Overall glucose concentrations following glucose challenge were lower after nateglinide than after placebo ( P = 0.05 ) . CONCLUSIONS Nateglinide significantly increases insulin secretion in Type 2 diabetic patients , in particular restoring the first phase insulin response . Further study is necessary to determine the effects of chronic administration on insulin secretion and blood glucose concentration OBJECTIVE This study compared the effects of nateglinide , glyburide , and placebo on postmeal glucose excursions and insulin secretion in previously diet-treated patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This r and omized , double-blind , placebo-controlled  multicenter study was conducted in 152 patients who received either nateglinide ( 120 mg before three meals daily , n = 51 ) , glyburide ( 5 mg q.d . titrated to 10 mg q.d . after 2 weeks , n = 50 ) , or placebo ( n = 51 ) for 8 weeks .  Glucose , insulin , and C-peptide profiles during liquid meal challenges were measured at weeks 0 and 8 . At weeks -1 and 7 , 19-point daytime glucose and insulin profiles , comprising three solid meals , were measured . RESULTS During the liquid-meal challenge , nateglinide reduced the incremental glucose area under the curve ( AUC ) more effectively than glyburide ( = -4.94 vs. -2.71 mmol . h/l , P < 0.05 ) , whereas glyburide reduced fasting plasma glucose more effectively than nateglinide ( = -2.9 vs. -1.0 mmol/l , respectively , P < 0.001 ) . In contrast , C-peptide induced by glyburide was greater than that induced by nateglinide ( = + 1.83 vs. + 0.95 nmol . h/l , P < 0.01 ) , and only glyburide increased fasting insulin levels . During the solid meal challenges , nateglinide and glyburide elicited similar overall glucose control ( 12-h incremental AUC = -13.2 vs. -15.3 mmol . h/l ) , but the insulin AUC induced by nateglinide was significantly less than that induced by glyburide ( 12-h AUC = + 866 vs. + 1,702 pmol . h/l , P = 0.01 ) . CONCLUSIONS This study demonstrated that nateglinide selectively enhanced early insulin release and provided better mealtime glucose control with less total insulin exposure than glyburide Nateglinide is a fast-acting insulin secretion agent that specifically targets postpr and ial hyperglycemia in patients with type 2 diabetes . The recent reduction in the diagnostic criteria for diabetes and improved underst and ing of the importance of early insulin secretion served as the rationale for this multicenter , double-blind , r and omized , parallel-group , 24-wk study performed in 675 patients with type 2 diabetes but only moderately elevated fasting plasma glucose ( FPG ) ( FPG = 7.0 - 8.3 mmol/liter ) to assess the efficacy and safety of three fixed doses of nateglinide ( 30 , 60 , or 120 mg , with meals ) . A sub study of the effects on early insulin release and pr and ial glucose excursions following a st and ardized breakfast was performed in 127 subjects . Nateglinide was well tolerated and elicited a dose-dependent reduction of placebo-adjusted hemoglobin A(1c ) ( Delta = -0.26 to -0.39 % ) and FPG ( Delta = -0.51 to -0.73 mmol/liter ) accompanied by a dose-related increase in suspected hypoglycemic episodes . However , confirmed hypoglycemia occurred in only 5.3 % of patients treated with the highest dose , compared with 1.2 % in placebo-treated patients ( P < 0.05 ) . Nateglinide increased early insulin release and reduced pr and ial glucose excursions ( P < 0.05 vs. placebo ) . In sum , nateglinide is a safe and effective therapeutic option for treatment of patients with mild to moderate fasting hyperglycemia Insulin secretion is impaired in type 2 diabetes with the early response being essentially absent . The loss of this early insulin secretion is hypothesized to be important in the deterioration of glucose tolerance . To determine whether enhancement of the early-phase insulin response can enhance glucose tolerance , we administered 1 ) 120 mg nateglinide , an insulinotropic agent that enhances early insulin secretion ; 2 ) 10 mg glyburide , which enhances the later phases of insulin secretion ; or 3 ) placebo in r and om order to 21 subjects with type 2 diabetes ( 14 males and 7 females ; aged 59.2 + /- 2.1 yr , x + /- SEM ; body mass index 29.7 + /- 1.0 kg/m(2 ) ; fasting plasma glucose 8.1 + /- 0.1 mM ) . beta-Cell function was quantified as the incremental area under the curve for different time periods for the 5 h following iv glucose administration and glucose tolerance as the glucose disappearance constant ( Kg ) from 10 to 60 min . Insulin release commenced immediately after nateglinide administration , even before glucose injection , but this was not observed with glyburide . Both nateglinide and glyburide enhanced glucose-induced insulin release , compared with placebo ( area under the curve -15 - 300 min : nateglinide 23,595 + /- 11,212 pM/min , glyburide 54,556 + /- 15,253 pM/min , placebo 10,242 + /- 2,414 pM/min ) . The profiles of insulin release demonstrated significant enhancement of release between -15 and 30 min for nateglinide , compared with glyburide and between 60 and 300 min for glyburide over nateglinide . Kg increased by 15 % with nateglinide ( 0.87 + /- 0.04%/min ) , but it did not increase significantly with glyburide ( 0.79 + /- 0.04%/min ) , compared with placebo ( 0.76 + /- 0.04%/min ) . The enhancement of insulin release by glyburide result ed in a lower minimal glucose concentration with glyburide ( 3.8 + /- 0.2 mM ) , compared with nateglinide ( 5.0 + /- 0.2 mM ) and placebo ( 5.9 + /- 0.2 mM ) . Thus , enhancement of the early phase of insulin secretion improves iv glucose tolerance , whereas delaying it by 30 min results in a slower rate of glucose disappearance for the first 2 h after iv glucose administration . Further , the differences in the kinetics of nateglinide and glyburide action results in continued insulin release with glyburide despite the fact that glucose levels have returned to basal , thus result ing in a further reduction in glucose levels and a lower nadir OBJECTIVE To examine the dose-related pharmacodynamics and pharmacokinetics of a single prepr and ial oral dose of repaglinide in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 16 Caucasian men with type 2 diabetes participated in two placebo-controlled double-blind r and omized cross-over studies . Patients were r and omized to receive a single oral dose of repaglinide ( 0.5 , 1.0 , and 2.0 mg in study 1 and 4.0 mg in study 2 ) or placebo ( both studies ) administered 15 min before the first of two sequential identical st and ard meals ( breakfast and lunch ) that were 4 h apart . During each of the study days , which were 1 week apart , blood sample s were taken at frequent intervals over a period of approximately 8 h for measurement of plasma glucose , insulin , C-peptide , and repaglinide concentrations . RESULTS During the first meal period ( 0 - 240 min ) , administration of repaglinide reduced significantly the area under the curve ( AUC ) for glucose concentration and significantly increased the AUC for insulin levels , C-peptide levels , and the insulin secretion rate . These results , compared with those of administering placebo , were dose dependent and log linear 
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Diarrhoea occurred less frequently and hypoglycaemia occurred more frequently but rarely severely enough as to require assistance .
Meglitinides may offer an alternative oral hypoglycaemic agent of similar potency to metformin , and may be indicated where side effects of metformin are intolerable or where metformin is contraindicated .
However , there is no evidence available to indicate what effect meglitinides will have on important long-term outcomes , particularly mortality