METABOLIC AND ENDOCRINE RESPONSES TO A MILK FEED IN SIX-DAY-OLD TERM INFANTS: DIFFERENCES BETWEEN BREAST AND COW'S MILK FORMULA FEEDING

ABSTRACT. Lucas, A., Boyes, S., Aynsley-Green, A. (Department of Paediatrics, John Radcliffe Hospital, Oxford) and Bloom, S. R. (Hammersmith Hospital, London, England). Metabolic and endocrine responses to a milk feed in six-day-old term infants: JMfferences between breast and cow's milk formula feeding. Acta Paediatr Scand, 70:195, 1981. – There is little information on the metabolic and endocrine responses to milk feeding in the neonatal period particularly in relation to the mode of nutrition and composition of the milk. Plasma concentrations of insulin, glucagon and gastric inhibitory polypeptide (GIP) together with blood levels of glucose, ketone bodies, pyruvate, lactate and glycerol were measured pre- and post-prandially in 79 healthy six-day-old term infants who had been either breast fed or fed on a modified cow's milk formula (Cow and Gate Premium) from birth. Formula fed infants had a greater insulin and GIP response to feeding and their basal and postprandial blood ketones were considerably lower than in breast fed infants. In addition a significantly greater post feed rise in both lactate and pyruvate concentrations was observed with formula feeding. These results may have significant implications regarding infant feeding and postnatal metabolism.     

Impaired insulin-mediated glucose uptake in monocytes of short children with intrauterine growth retardation

Abstract: Aims: To determine whether there was an impairment in insulin‐mediated glucose uptake in monocytes from short children with intrauterine growth retardation (IUGR) when compared with control subjects. Methods: Circulating monocytes were isolated by histopaque gradient separation followed by adherence. Monocytes were incubated with insulin at the following concentrations; 0, 0.1, 0.2, 0.6, 1, 2 and 6 nm . 2‐deoxyglucose (2‐DG) uptake was measured after incubation with [³H]2‐DG and expressed as pmol/min/10⁶ cells. Insulin‐stimulated glucose uptake was determined in two ways: 6 nm insulin concentration minus baseline (6–0 nm ) and the regression slope of glucose uptake over the range of log insulin concentrations (slope value). Insulin sensitivity was determined from a 90‐min frequently sampled intravenous glucose tolerance test with the minimal model. Results: Short children with IUGR (n = 16) had lower slope (4.6 ± 1.1 vs. 9.5 ± 2.0, p = 0.002) and 6–0 nm (8 ± 2 vs. 15 ± 3 pmol/min/10⁶ cells, p = 0.048) glucose uptake values than normal children (n = 11). There was no difference in baseline glucose uptake between IUGR and normal children (36 ± 5 vs. 48 ± 7 pmol/min/10⁶ cells). In the five subjects with IUGR that were evaluated, the in vivo insulin sensitivity index and glucose effectiveness were found to be positively correlated with insulin‐mediated glucose uptake in monocytes (r = 0.54) and baseline glucose uptake in monocytes, respectively (r = 0.69). Conclusions: Short children with IUGR have impairment in insulin‐mediated glucose uptake in monocytes when compared with normal children. Our hitherto limited data indicate that insulin‐mediated glucose uptake in monocytes is correlated with in vivo assessment of insulin sensitivity in children with IUGR.     

PLASMA SECRETIN IN NEONATES

Abstract. Lucas, A., Adrian, T. E., Bloom, S. R. and Aynsley-Green, A. (University Department of Paediatrics, John Radcliffe Hospital, Oxford and Hammersmith Hospital, London). Plasma secretin in neonates. Acta Paediatr Scand, 69: 205, 1980.—Plasma secretin has been measured in 96 normal 6-day-old term infants and in 158 healthy preterm infants whose mean post-partum ages were 2½, 6, 13 or 24-days. At birth, plasma secretin levels in both term and preterm infants were high compared with those seen in healthy fasting adults ( p > 0.001), but subsequently declined towards adult values. In contrast, preterm infants who had not been fed for the first 6 days of life, had presistently high basal plasma secretin values. In term infants at 6 days of age and in preterm infants up to 13 days, there was no se-cretin response to a feed. However, by 24 days, preterm infants showed a marked post-prandial secretin elevation ( p > 0.02). No correlations were found between plasma secretin concentrations and either blood glucose or plasma insulin concentrations following a feed. Significant adjustments in plasma secretin levels occur in the early weeks of life which may be influenced by enteral feeding.     

Effect of human breast milk on biological metabolism in infants

The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to provide the optimal source of nutrition for infants. Our previous studies examined the effect of feeding type on antioxidative properties, glucose and insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG) metabolism in term and preterm infants. A urinary marker of oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine) was significantly lower in breast‐fed term and preterm infants than in formula‐fed infants. Markers of insulin sensitivity were significantly lower and atherosclerotic indices were significantly higher in breast‐fed preterm infants than in mixed‐fed infants at discharge. On urinary metabolomics analysis, choline, choline metabolites, and lactic acid were significantly lower in breast‐fed term infants than in formula‐fed infants. Urinary PGD₂ metabolite level in breast‐fed term infants was also significantly lower than in formula‐fed term infants. This indicates that human breast milk affects biological metabolism in early infancy.     

Evaluation of insulin sensitivity in obese offspring of diabetic rats by hyperinsulinemic-euglycemic clamp technique

Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance in vivo, hyperinsulinemic-euglycemic clamp studies were performed. Ten-wk-old rats were fasted overnight, and porcine insulin was infused (2.4 mU.kg-1.min-1). Glucose was infused concurrently at varying rates to maintain euglycemia for 40-60 min. Insulin levels were raised from a baseline value of 163 +/- 57 pmol/L (23 +/- 8 microU/mL) (SD) to 476 +/- 57 pmol/L (67 +/- 8 microU/mL) at steady state for males and from 178 +/- 43 pmol/L (25 +/- 6 microU/mL) to 454 +/- 43 pmol/L (64 +/- 6 microU/mL) for females. The results showed that the macrosomic male and female animals were significantly less sensitive to the effects of insulin than were their respective controls; this was evident by a lower increment in glucose disposal rate per unit increase in insulin (0.04 +/- 0.01 versus 0.11 +/- 0.03 for males and 0.05 +/- 0.03 versus 0.18 +/- 0.07 mg.kg-1 per microU/mL for females). The endogenous glucose production by the liver in the basal (fasted) state in the macrosomic group compared to controls was higher, suggesting possible hepatic insulin resistance. However, endogenous glucose production was suppressed to the same degree between the experimental and control groups during the hyperinsulinemic period, suggesting that the hepatic insulin resistance can be overcome by high insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrauterine growth restriction and postnatal steroid treatment effects on insulin sensitivity in preterm neonates

OBJECTIVES: To study whether intrauterine growth restriction (IUGR) is associated with decreased sensitivity to the main fetal growth factor, insulin, and the effect of glucocorticoid therapy on insulin sensitivity in preterm infants. STUDY DESIGN: Newborn infants with a birth weight (BW) of< 1500 g were classified as appropriate for gestational age ([AGA], BW within +/- 1 SD, n = 10), or small for gestational age ([SGA], BW <-2 SD, n = 13); 5 AGA infants and 8 SGA infants received systemic steroids. An abbreviated modified minimal model test was performed, consisting of sequential blood samples for glucose and insulin assays, and intravenous infusions of 0.3 g/kg glucose and 0.02 U/kg regular human insulin. The insulin sensitivity index (S(I)) was calculated using a computer program. RESULTS: The basal insulin/glucose ratio (I/G) and S(I) did not differ between the AGA and SGA groups. Steroids did not influence the I/G nor the S(I) of AGA infants (10.2 +/- 6.7 vs 8.2 +/- 2.3), but decreased the S(I) in the SGA group (12.2 +/- 5.1 vs 5.3 +/- 2.7, P <.05). CONCLUSIONS: Insulin sensitivity of neonates can be measured by the modified minimal model. IUGR is not associated with impaired fetal glucose tolerance. Early neonatal steroid treatment decreases insulin sensitivity in SGA infants, which may contribute to their risk of having hyperglycemia.     

Leptin, insulin, and glucose serum levels in large-for-gestational-age infants of diabetic and non-diabetic mothers

BACKGROUND: It has been suggested that hyperleptinemia could be caused by hyperinsulinemia in infants of diabetic mothers (IDMs). AIM: To compare leptin, insulin, and glucose levels in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants. Methods: A cross-sectional study was conducted in IDMs, infants of non-diabetic mothers (INDM) and AGA infants. RESULTS: Seventy-seven newborns were studied (11 IDM, 16 INDM, and 50 AGA infants). Leptin levels were significantly higher in LGA infants than in the AGA group and a trend for higher levels in IDM than NIDM was observed. Insulin levels and insulin resistance were significantly higher in IDMs. Glucose levels were lower in both groups of LGA infants. CONCLUSIONS: We found insulin resistance, hyperinsulinism and hyperleptinemia in IDMs, and the trend of higher leptin levels in IDMs than INDMs shows that leptin could be related to insulin resistance in these infants.     

Changes in 4E-BP1 and p70S6K phosphorylation in skeletal muscle of the ovine fetus after prolonged maternal fasting: effects of insulin and IGF-I

This study was conducted to investigate fasting-induced alterations in insulin signaling to the regulatory components of the translation machinery. Insulin (890 mIU/h) and IGF-I (40 nM/h) were infused into a chronically catheterized ovine fetus (0.85 gestation) for 7 h following a 5-d maternal fast. Amino acid and glucose concentrations were clamped to minimize the effects of alterations in circulating substrate concentrations. The IGF-I induced increase in 4E-BP1 phosphorylation (percentage in the gamma form) increased from 28% in control to 44% (NS). The insulin-induced increase in 4E-BP1 phosphorylation was more pronounced, and the gamma percentage was 56% on average in the insulin group. The insulin-induced increase in 4E-BP1 phosphorylation was lower than in fed animals and did not result in significant changes in eIF4E.4E-BP1 binding or eIF4E.eIF4G binding. Insulin increased PKB/Akt phosphorylation and p70S6K phosphorylation to a similar extent as in fed animals. We conclude that maternal fasting resulted in reduced insulin sensitivity of 4E-BP1 phosphorylation and eIF4F formation. This reduced insulin-induced 4E-BP1 phosphorylation was not due to a global defect in insulin signaling; the defects underlying the reduced basal phosphorylation and insulin-responsiveness of 4E-BP1 in fasted animals may be in signaling components other than, or downstream of, PKB/Akt. Selective inhibition of downstream components of insulin signaling allows fetuses to adapt to nutritional stress by decreasing the anabolic response to insulin and other growth factors, so that more amino acids can be used as oxidative substrate to compensate for shortage of energy due to reduced glucose supply.     

妊娠期合并糖代谢异常对新生儿胰岛素敏感性的影响

目的探讨妊娠期合并糖代谢异常对子代新生儿期胰岛素敏感性的影响。方法选择2009年12月至2010年11月本院产科出生的新生儿,根据母亲妊娠期是否合并糖代谢异常分为糖代谢异常母亲的新生儿和糖代谢正常母亲的新生儿。所有研究对象均进行出生体格测量,并于生后 3 天内测定空腹血糖( FPG) 和空腹血清胰岛素( FINS) ,计算胰岛素敏感指数( ISI) ,采用胰岛素稳态模型( HOMA) 计算胰岛素抵抗指数( IR) ,即 HOMA-IR,其中 FINS、ISI 和 HOMA-IR 值为胰岛素敏感性的评价指标。以性别、胎龄、出生体重为协变量,分别在早产儿和足月儿中进行胰岛素敏感性的协方差分析。结果 89 例早产新生儿和 96 例足月新生儿纳入分析。糖代谢异常母亲新生儿的出生体重、出生身长和重量指数( PI) 与糖代谢正常母亲的新生儿相比,差异无统计学意义( P >0. 05) 。与糖代谢正常母亲的早产儿相比,糖代谢异常母亲的早产儿 FPG 降低、FINS 升高,差异有统计学意义[FPG( mmol/L) : ( 4. 00 ±0. 25) 比( 4. 82 ±0. 18) ,FINS( 经对数 Lg 转换) : ( 0. 69± 0. 06) 比( 0. 54 ± 0. 04) ,P < 0. 05],ISI 值降低、HOMA-IR 值升高,但差异无统计学意义[ISI( 经对数 Ln 转换) : ( -2. 89 ±0. 15) 比( -2. 78 ±0. 11) ,HOMA-IR 值( 经对数 Lg 转换) : ( -0. 10 ±0. 06)比( -0. 15 ±0. 05) ,P >0. 05]; 足月儿中糖代谢异常母亲的新生儿 FPG、FINS 和 HOMA-IR 值低,ISI 值高,但差异均无统计学意义[FPG( mmol / L) : ( 4. 68 ± 0. 23) 比( 5. 17 ± 0. 13) ,FINS( 经对数 Lg转换) : ( 0. 56 ±0. 06) 比( 0. 61 ±0. 03) ,HOMA-IR 值( 经对数 Lg 转换) : ( -0. 14 ±0. 06) 比( -0. 03± 0. 03) ,ISI( 经对数 Ln 转换) : ( - 2. 79 ± 0. 14) 比( - 3. 04 ± 0. 08) ,P > 0. 05]。结论母亲妊娠期合并糖代谢异常虽然对新生儿的出生体重没有影响,但血糖仍然呈现低水平趋势,且对早产儿胰岛素敏感性可能有一定的影响。     

An inadequate glycaemic response to glucagon is linked to insulin resistance in preterm infants?

AIMS: To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. METHODS: Two phase study of 78 preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating discharge home at 36 weeks mean corrected gestation. In phase 1 infants were fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic profiles were obtained at completion. Phase 2 was performed the following day. A feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro g/kg). Main outcome measures were measurements of blood glucose and lactate concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was defined as an adequate response to glucagon. An inadequate glycaemic response was <1 mmol/l (23 infants). RESULTS: Several differences in fasting blood glucose and hormone concentrations were identified in infants with an inadequate glycaemic response to glucagon compared to those with an adequate response: relative fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict response to glucagon. CONCLUSION: Some preterm infants show an inadequate glycaemic response to glucagon and have features suggestive of insulin resistance. The potential long term implications of such insulin resistance may have appreciable public health consequences.     

Clinical and metabolic consequences of two regimens of total parenteral nutrition in the newborn

The clinical and metabolic effects of two regimens of total parenteral nutrition delivering the same amino-acid (2·8 g/kig per 24 h), fat (4·8 g/kg per 24 h), and glucose (12 g/kg per 24 h) load over 24 hours were studied. The regimens differed in the distribution of the infusate during the 24-hour period. With the continuous regimen (7 infants) all nutrients were infused together at a constant rate, whereas with the sequential regimen (9 infants) the daily doses of Vamin/glucose and Intralipid were infused together, followed by the glucose dose. The infants studied had a mean birthweight of 2·8 kg and mean gestational age of 37·9 weeks. Blood levels of glucose, lactate, pyruvate, 3-hydroxybutyrate, acetoacetate, alanine, glycerol, and insulin were measured longitudinally from day 1 to day 21 of total parenteral nutrition. The 7 infants who received the continuous regimen had blood metabolite levels comparable with those of infants fed enterally, with minor fluctuations. Insulin levels were higher than in enterally-fed infants. The 9 infants who received the sequential regimen had wide fluctuations in alanine, glycerol, insulin, 3-hydroxybutyrate, and acetoacetate levels with high peak levels of ketones at the end of the Vamin/glucose and Intralipid infusion, falling to low levels at the end of the 24-hour cycle. There was a gradual reduction in the peak ketone levels from day 6-8 to day 18-21. Clinically unsuspected hypoglycaemia occurred on 6 occasions in each group of infants. There was no significant difference in the incidence of jaundice or infection between the two groups, and the weight velocity during total parenteral nutrition was similar. Wide fluctuations in the infusion rates of individual substrates should be avoided during total parenteral nutrition in the newborn.     

Effects on Plasma Glucose Concentration of Light-for-date Infants and Infants of Diabetic Mothers of Feeds Supplemented with a Glucose Polymer

ABSTRACT. Serial plasma glucose estimations were performed in 44 light-for-date infants and 17 infants of diabetic mothers fed 2, 3 or 4-hourly with feeds containing 10 % additional carbohydrate in the form of a glucose polymer (Caloreen). In the infants fed 2 and 3-hourly, plasma glucose was higher following the high carbohydrate feeds, particularly immediately before the next feed was due. Given 4-hourly, the high carbohydrate feed had little effect in most light-for-date infants, and in one light-for-date infant and two infants of diabetic mothers the plasma glucose was lower at the end of 4 hours than following normal formula. It is concluded that the addition of glucose polymer to feeds given 2 and 3 hourly has a potentially useful effect in neonates at risk of developing hypoglycaemia, but it cannot be used to increase the feed interval to 4 hours.     

Effects on plasma glucose concentration of light-for-date infants and infants of diabetic mothers of feeds supplemented with a glucose polymer

Serial plasma glucose estimations were performed in 44 light-for-date infants and 17 infants of diabetic mothers fed 2, 3 or 4-hourly with feeds containing 10% additional carbohydrate in the form of a glucose polymer (Caloreen). In the infants fed 2 and 3-hourly, plasma glucose was higher following the high carbohydrate feeds, particularly immediately before the next feed was due. Given 4-hourly, the high carbohydrate feed had little effect in most light-for-date infants, and in one light-for-date infant and two infants of diabetic mothers the plasma glucose was lower at the end of 4 hours than following normal formula. It is concluded that the addition of glucose polymer to feeds given 2 and 3 hourly has a potentially useful effect in neonates at risk of developing hypoglycaemia, but it cannot be used to increase the feed interval to 4 hours.     

Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

Diabetes mellitus in patients with thalassaemia major is caused by secondary haemochromatosis due to transfusional iron overload. The pathogenetic mechanisms leading from siderosis to diabetes are still poorly understood. This study aimed at assessing the influence of insulin resistance and insulin deficiency on that process. Glucose, insulin and C-peptide levels during oral glucose tolerance tests (OGTT) from 36 thalassaemic patients with normal ( n=23), impaired ( n=6), or diabetic glucose tolerance ( n=7) and 32 control subjects were examined. Insulin secretion and insulin sensitivity were assessed by established calculated indices. Fasting, 2h and integrated glucose concentration were significantly increased in thalassaemic patients with normal glucose tolerance compared to controls (5.01/4.59 mmol/l, 6.33/5.17 mmol/l, and 844.2/739.3 mmol/l per min, respectively; all P<0.03). Patients with impaired glucose tolerance presented hyperinsulinaemia and delayed peak insulin during OGTT. The C-peptide/insulin ratio was decreased in patients with abnormal glucose tolerance compared to controls (5.85/7.33 x 10(3)pmol/l per min, P<0.03). It was negatively correlated with age in patients ( r=-0.45, P<0.01), but positively in controls ( r=0.43, P<0.03). Insulin sensitivity was significantly reduced in patients with impaired glucose tolerance or diabetes compared to controls. In addition, a significant decrease in patients with normal glucose tolerance was shown by two insulin sensitivity indices (all P<0.05). In thalassaemia patients, insulin sensitivity was negatively correlated with age. Insulin secretion capacity according to the homeostasis assessment model was significantly reduced in patient groups compared to controls (Kruskal-Wallis-test, P<0.004). CONCLUSION: Insulin resistance is of central importance for the development of diabetes mellitus in patients with secondary haemochromatosis. An additional early defect in beta-cell secretion cannot be excluded.     

Glucose homeostasis in the newborn

Hepatic glucose production by glycogenolysis and gluconeogenesis is essential to maintain blood glucose levels, and the glucose-6-phosphatase system catalyses the terminal step of both pathways. Developmental delays in the postnatal up-regulation of hepatic glucose-6-phosphatase enzyme activity are common in preterm infants. Two groups of infants have been identified with failure of developmental regulation of glucose homeostasis. Firstly, up to 20% of preterm infants about to be discharged home are at risk of hypoglycaemia if a feed is delayed. Cortisol, corticotrophin and epinephrine levels are higher in the infants with severe and persistent hypoglycaemia, but insulin, glucagon and human growth hormone do not differ from normoglycaemic infants. Secondly, preterm infants with an inadequate glycaemic response to glucagon (30% at the time of discharge home) have relative fasting hyperglycaemia, hyperinsulinaemia, increased insulin:glucagon ratios and a lower insulin sensitivity index. Hormonal dysfunctions in preterm infants may contribute to failures in postnatal expression of hepatic enzymes.     

DEVELOPMENTAL ASPECTS OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) AND ITS POSSIBLE ROLE IN THE ENTEROINSULAR AXIS IN NEONATES

Abstract. Lucas, A., Sarson, D. L., Bloom, S. R. and Aynsley-Green, A. (University Department of Paediatrics, John Radcliffe Hospital, Oxford and Hammersmith Hospital, London, England). Developmental aspects of gastric inhibitory polypeptide (GIP) and its possible role in the enteroinsular axis in neonates. Acta Paediatr Scand, 69: 321, 1980.—Little is known on the development of the release of gastric inhibitory polypeptide (GIP) in neonates or on its potential role in the enteroinsular axis. Using cross-section data collection we studied: ( a ) 100 preterm neonates either at birth (cord blood), or before or after a feed on the sixth or 24th day and ( b ) 63 term neonates at birth or on the sixth day. Blood samples were assayed for GIP, insulin and glucose. At birth plasma GIP concentrations were low compared with fasting adults ( p > 0.01). Basal plasma levels were significantly higher at six days in fed infants, but not in a group of sick preterm infants who had never been fed orally. On sixth day there was no GIP response to a feed, but by 24th day there was a marked postprandial elevation ( p > 0.01). In preterm infants the insulin response was 68 % greater at 24 days than at six days in spite of a similar glycaemic response. We hypothesize that this increasing postnatal insulin response to enteral feeding may be due to the commencement of the postprandial release of GIP, thought to be an important effector in the enteroinsular axis.     

Insulin resistance of puberty in African-American children: lack of a compensatory increase in insulin secretion

Type 2 diabetes has been increasing in children, mostly affecting minority populations at around the age of puberty. Despite a multitude of studies demonstrating pubertal insulin resistance/hyperinsulinemia in white children, data are almost non-existent in African-American children. The aim of the present study was to investigate the impact of puberty on glucose metabolism, insulin sensitivity and secretion in African-American children. Twenty prepubertal and 16 pubertal African-American subjects participated. All underwent a 3-h hyperinsulinemic (40 mU/m(2)/min) euglycemic clamp to determine insulin-stimulated glucose disposal, and a 2-h hyperglycemic (12.5 mmol/L) clamp to assess first- and second-phase insulin secretion. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and visceral and subcutaneous abdominal adiposity with computed tomography (CT) scan at L4-L5. Total glucose disposal, glucose oxidation and non-oxidative glucose disposal were significantly lower in the pubertal group compared with the prepubertal one (53.8 +/- 3.9 vs. 72.2 +/- 5.0 micromol/kg/min, p = 0.009; 23.3 +/- 1.1 vs. 31.6 +/- 1.7 micromol/kg/min, p = 0.001; and 30.0 +/- 3.3 vs. 40.5 +/- 3.9 micromol/kg/min, p = 0.049, respectively). Insulin sensitivity was approximately 30% lower in the adolescents compared with the prepubertal children. However, first- and second-phase insulin secretions were not different between the two groups (971.4 +/- 180.6 vs. 1044.0 +/- 191.4 pmol/L and 999.6 +/- 159.6 vs. 955.8 +/- 142.2 pmol/L, respectively). In conclusion, despite approximately 30% lower insulin sensitivity in African-American adolescents compared with prepubertal children, insulin secretion is not higher. This is in contrast to published findings in white children in whom insulin secretion is higher during puberty. These racial differences in physiologic adaptation to puberty could play a role in the higher prevalence of type 2 diabetes in African-American children at the time of puberty.     

Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers

OBJECTIVE: To investigate associations between maternal diabetes and blood pressure (BP), obesity, impaired glucose tolerance, and serum lipids in offspring and whether these parameters correlate with metabolism during pregnancy. STUDY DESIGN: Body mass index, BP, serum glucose, and insulin during an oral glucose tolerance test, and lipid concentrations were measured in 99 offspring of diabetic mothers (ODM) and 80 members of a control group. RESULTS: ODM were more obese (body mass index 22.5 +/- 5.6 vs 20.3 +/- 4.0 kg/m(2)) and had higher systolic (8 mm Hg) and mean arterial BP (4 mm Hg) but similar diastolic BP compared with the control group. ODM had higher 2-hour glucose (6.6 +/- 1.3 vs 5.7 +/- 0.9 mmol/L) and insulin (580 +/- 544 vs 377 +/- 239 pmol/L) concentrations but lower fasting concentrations of low-density lipoprotein (2.54 +/- 0.67 vs 2.82 +/- 0.70 mmol/L) and total cholesterol (4.01 +/- 0.80 vs 4.40 +/- 0.78 mmol/L). In both groups body mass index, triglycerides, and fasting and 2-hour glucose concentrations showed correlations with BP measurements. Fasting insulin was correlated with BP readings only in the ODM. Correlations were found between second- and third-trimester maternal free fatty acid concentrations and diastolic and mean arterial BP. Third-trimester beta-hydroxybutyrate was correlated with mean arterial BP. CONCLUSIONS: In ODM, abnormalities in weight and glucose tolerance are associated with abnormal maternal metabolism. Higher BP is an additional abnormality associated with fetal overnutrition.     

Type 2 diabetes mellitus in African-American adolescents: impaired beta-cell function in the face of severe insulin resistance

We have previously demonstrated abnormalities in insulin secretion in adolescents with type 2 diabetes mellitus (DM2) in response to the mixed meal test and to glucagon. In order to further assess beta-cell function in DM2, we measured insulin and C-peptide responses to oral glucose in adolescents with DM2 in comparison to non-diabetic obese and lean adolescents. We studied 20 patients with DM2, 25 obese adolescents with matching body mass index (BMI) (33.8 +/- 1.4 vs 34.3 +/- 1.0 kg/m2), and 12 non-obese control adolescents (BMI 22.6 +/- 0.6 kg/m2). Mean age, sex and sexual maturation did not differ between the three groups. All adolescents with DM2 had negative islet cell antibodies (ICA); five patients were on diet and 15 on insulin treatment. Fasting lipid profiles were determined in all participants. Plasma glucose and serum C-peptide and insulin levels were measured at 0, 30, 60, 90, and 120 min after an oral glucose load. The C-peptide increment (deltaCP) was calculated as peak minus fasting C-peptide. Area under the curve (AUC) was estimated using the trapezoid method. Insulin resistance was estimated using the HOMA model (HOMA-IR). The first phase of insulin secretion (PH1) was computed using a previously published formula. Serum triglyceride levels were significantly higher in the patients with DM2 compared to the non-obese controls (1.4 +/- 0.1 vs 0.9 +/- 0.1 mmol/l; p = 0.02). Plasma glucose AUC was greater in the patients with DM2 compared to the obese and non-obese control groups (1,660 +/- 130 vs 717 +/- 17 vs 647 +/- 14 mmol/l x min; p < 0.0001). ACP was lower in adolescents with DM2 than in obese and non-obese adolescents (761 +/- 132 vs 1,721 +/- 165 vs 1,225 +/- 165 pmol/l; p < 0.001). Insulin AUC was lower in the patients with DM2 compared to obese controls (888 +/- 206 vs 1,606 +/- 166 pmol/l x h; p = 0.009), but comparable to that of the non-obese controls (888 +/- 206 vs 852 +/- 222 pmol/l x h; p = 0.9). Insulin AUC was also higher in the obese than in the non-obese group (p = 0.05). PH1 was significantly higher in the obese group compared to the patients with DM2 as well as to the non-obese controls (2,614 +/- 2,47.9 vs 929.6 +/- 403.5 vs 1,946 +/- 300.6 pmol/l, respectively; p = 0.001). PH1 was also higher in the non-obese controls than in the patients with DM2 (p = 0.05). HOMA-IR was three-fold higher in the patients with DM2 than in the BMI-matched obese group, and five-fold higher than in the lean controls (14.3 +/- 1.2 vs 5.4 +/- 0.8 vs 2.9 +/- 0.4; p = 0.0002). Adolescents with DM2 have dyslipidemia, a significant cardiovascular risk factor. Decreased beta-cell function is characteristic of adolescents with DM2 in the presence of severe insulin resistance.     

Serum concentrations of growth hormone, insulin, free thyroxine, thyrotropin, and cortisol in very-low-birth-weight infants receiving total parenteral nutrition

Serum concentrations of growth hormone, insulin, free thyroxine, thyrotropin, cortisol, and glucose were measured during four time periods (0 to 4, 5 to 11, 12 to 18, and greater than or equal to 19 days of life) in 16 mechanically ventilated very-low-birth-weight infants (mean [+/- SD] birth weight, 1017 +/- 196 g) receiving total parenteral nutrition and in 21 very-low-birth-weight infants not requiring mechanical ventilator support (mean [+/- SD] gestational age, 30 +/- 1.7 weeks; mean [+/- SD] birth weight, 1149 +/- 210 g) fed enterally. There were no significant differences in the serum concentrations of the hormones or in the glucose levels between the two groups at any time interval. Present data demonstrate no significant difference in the serum concentration of glucose, insulin, growth hormone, cortisol, free thyroxine, and thyrotropin between very-low-birth-weight infants fed enterally and those maintained on a regimen of total parenteral nutrition.