[show abstract][hide abstract] ABSTRACT: Rates of obesity and type 2 diabetes are higher in African-American (AA), compared with American white (AW), adults and children. It is not known whether biologic and/or environmental differences are responsible for this racial disparity. We and others have demonstrated that AA children are hyperinsulinemic, compared with their AW peers. This investigation tested the hypothesis that hyperinsulinemia in AA children is associated with lower rates of lipolysis, which could be a risk factor for future obesity. Forty prepubertal children (20 AA and 20 AW) with comparable body composition (assessed by dual-energy x-ray absorptiometry) and visceral adiposity (evaluated with computed tomography scan) were studied. Total body lipolysis was measured with [(2)H(5)]glycerol after overnight fasting. Basal lipolysis was approximately 40% lower in AA vs. AW children, whether the data were expressed for total body (85.7 +/- 8.9 vs. 130.3 +/- 14.1 micromol/min, P = 0.011) or per-kilogram BW (2.4 +/- 0.2 vs. 3.8 +/- 0.4 micromol/min.kg, P = 0.002) or per kilogram fat free mass (FFM) (3.3 +/- 0.3 vs. 5.2 +/- 0.5 micromol/min.kg FFM, P = 0.004), or per kg fat mass (FM) (13.7 +/- 1.6 vs. 21.3 +/- 3.3 micromol/min.kg FM, P = 0.046). Fasting insulin levels were higher in AA children (99.6 +/- 7.8 vs. 77.4 +/- 5.9 pmol/L, P = 0.032). Lipolysis correlated positively with fat mass, percent body fat, and abdominal fat mass. However, in multiple-regression analysis models after controlling for insulin and body composition, race remained a significant contributor to the variance in lipolysis. In summary, the present study demonstrates that rates of lipolysis are significantly lower in AA children, compared with their white peers. This may constitute an early metabolic phenotype that may mediate fat trapping and susceptibility to obesity in a specific environmental context of energy excess conducive to fat accretion.
[show abstract][hide abstract] ABSTRACT: To investigate insulin sensitivity and secretion in young adolescent girls with childhood onset polycystic ovarian syndrome (PCOS) and to identify the early metabolic derangement(s).
Twelve obese girls with PCOS (age 12.0+/-0.7 years) were compared with 10 obese nonhyperandrogenic girls (control group). The groups were matched for age, percent body fat, and abdominal fat. All subjects underwent a 3-hour hyperinsulinemic (80 mu/m(2)/min)-euglycemic clamp to determine in vivo insulin sensitivity and a 2-hour hyperglycemic clamp (225 mg/dL) to determine insulin secretion. Fasting hepatic glucose production was determined with the use of [6,6-(2)H(2)]glucose.
Fasting glucose and hepatic glucose production were comparable between the 2 groups, but fasting insulin was 2-fold higher in the PCOS group. The fasting glucose to insulin ratio was lower in the PCOS group versus the control group (1.9+/- 0.3 vs 3.1+/-0.3, P =.02). During the hyperinsulinemic-euglycemic clamp, insulin sensitivity was lower in the PCOS group (1.4+/-0.2 vs 2.7+/-0.3 mg/kg/min per microu/mL, P =.002). During the hyperglycemic clamp, insulin secretion was significantly higher in the PCOS group. Insulin sensitivity correlated negatively with fasting insulin (r = -0.71, P =.0002) and positively with the fasting glucose to insulin ratio (r = 0.79, P<.0001).
Adolescent girls with PCOS have profound metabolic derangements detected early in the course of the syndrome, including (1) approximately 50% reduction in peripheral tissue insulin sensitivity, (2) evidence of hepatic insulin resistance, and (3) compensatory hyperinsulinemia. These observations may predict an increased risk of type 2 diabetes mellitus in adolescents with PCOS.
Journal of Pediatrics 01/2001; 138(1):38-44. · 4.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To determine if the Trp(64)Arg (W64R) variant of the beta(3)-adrenergic receptor (ADRB3) could be used as a genetic marker to define risk for polycystic ovary syndrom (PCOS) and/or obesity in children and adolescents. DESIGN: Association study. SETTING: Academic research environment. PATIENT(s): Children referred for evaluation of premature pubic hair (n = 63), adolescent girls referred for evaluation of hirsutism and/or oligomenorrhea (n = 33), and healthy adult controls (n = 67). INTERVENTION(s): None. MAIN OUTCOME MEASURE(s): Relationship of body mass index (BMI) to presence or absence of W64R variant and frequency of W64R variant in our patient population. RESULT(s): Body mass index (kg/m(2)) was determined for 63 children (55 girls and 8 boys) and 33 adolescent girls. Presence or absence of the W64R variant was assayed by polymerase chain reaction (PCR) amplification followed by allele-specific restriction fragment digest. Twelve subjects and 11 healthy controls were found to be heterozygous for the W64R variant. One subject was found to be homozygous for the W64R variant. Allele frequency for the W64R variant was comparable between patients and controls. Among the patients, mean BMI values were not different between carriers and noncarriers. CONCLUSION(s): Although other studies suggest that the W64R variant is associated with the development of obesity and insulin resistance, we cannot demonstrate that it has a major effect on BMI in children with premature pubarche or in adolescent girls with hyperandrogenism. Serial observations are necessary to determine if this variant predicts the development of obesity and/or PCOS in adulthood.
Fertility and Sterility 04/2000; 73(3):509-15. · 4.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Polycystic ovary syndrome is a heterogeneous disorder characterized by signs and symptoms of hyperandrogenism and insulin resistance. We present the clinical and hormonal features in an adolescent girl who had distinct intervals of insulin deficiency and insulin resistance/hyperinsulinaemia. This case report confirms that insulin resistance/hyperinsulinaemia exacerbates ovarian hyperandrogenism.
[show abstract][hide abstract] ABSTRACT: Body compositional differences between Black and White adults are well-known. It has become increasingly apparent that these racial variations may begin in childhood. Previously, our group validated tetrapolar bioelectrical impedance (BIA) measurements against H2(18O) dilution method to develop prediction formulas of fat free mass (FFM) in healthy White-American children: FFM = 0.524 Ht2/R + 0.415 Wt 0.32. In the present study we used BIA to establish a FFM prediction equation for forty African-American children (19 males and 21 females). Of the females, six were diagnosed with polycystic ovary syndrome (PCOS) and were obese. FFM was determined by dual energy X-ray absorptiometry (DEXA). Impedence measurements by BIA showed a strong correlation with FFM determined by DEXA. In healthy Black children, FFM = 0.84 Ht2/R + 1.10 with a standard error of estimate (SEE) of 1.47 kg (R2 = 0.97). In Black females with PCOS, FFM = 0.62 Ht2/R + 0.21 Wt - 1.94 with a SEE of 1.43 kg (R2 = 0.99). The observed differences in the prediction equations of FFM between White-American and African-American children underline the importance of using race-specific formulas in evaluating body composition. With the overall increase in rates of childhood obesity and more so in the Black race, BIA is an easy and useful tool for the assessment and follow up of body compositional changes with lifestyle interventions.
[show abstract][hide abstract] ABSTRACT: Leptin, the protein product of the obesity gene, produced by adipose tissue, regulates body weight and energy expenditure through CNS feedback mechanisms. In obesity, leptin levels are elevated suggestive of leptin resistance. Because of increased prevalence of obesity in African-Americans, the aim of this study was to assess leptin and its relationship to adiposity in African-American children. We measured plasma leptin levels in 42 African-American children (23 M, 19 F), age 11.8 +/- 0.3 yr, and compared them with 30 American-White children matched for age, body composition and puberty. Body composition was assessed by bioelectrical impedance and plasma leptin by RIA. Data are presented as means +/- SEM and statistical significance is implied by p < 0.05. There was no racial difference in plasma leptin levels (Blacks: 9.8 +/- 1.6, Whites 9.8 +/- 1.9 ng/ml). Leptin correlated with %BF in Black (r = 0.75, p = 0.005) and White (r = 0.79, p = 0.005) children. There were no gender or puberty related differences in leptin levels in African-American children. We concluded that leptin levels are comparable between African-American and American White children of similar body composition. The major determinant of serum leptin levels in these children is degree of adiposity with no gender or puberty related differences. Longitudinal studies are needed to assess leptin's role during puberty in both genders.
[show abstract][hide abstract] ABSTRACT: Nutritional status and body composition influence the development and maintenance of reproductive competence in mammals. It has been suggested that leptin concentrations communicate nutritional status to the neuroendocrine reproductive axis. To determine the interrelationship between circulating gonadotropin and leptin concentrations, leptin concentrations were measured in 39 children treated for GnRH dependent precocious or untimely puberty. Leptin concentrations were obtained during pubertal suppression with GnRH analogue therapy and during spontaneous pubertal gonadotropin secretion. The status of gonadotropin secretion (suppressed vs not suppressed) was verified by simultaneous GnRH stimulation tests and sex steroid concentrations. Leptin concentrations were similar at both time-points and correlated only with body mass index. Thus, no relationship was apparent between circulating concentrations of gonadotropins, sex steroids, and leptin.
[show abstract][hide abstract] ABSTRACT: Racial differences in insulin secretion and insulin sensitivity in healthy children were studied by administering a 2-hour hyperglycemic clamp (225 mg/dL) to 14 black and 16 white healthy adolescents (Tanner II-V), and 12 black and 11 white prepubertal children, matched for age, body mass index, and Tanner I pubertal development. In prepubertal children, fasting and first-phase insulin concentrations were higher in blacks compared with whites (14.7+/-1.3 vs 10.4+/-1.2, P=0.02, and 76.9+/-6.8 vs 52.1+/-6.4 microu/mL, P=0.016). There were no differences in second-phase insulin levels and insulin sensitivity index. In pubertal adolescents, first-phase and second-phase insulin concentrations were higher in blacks compared with whites (first-phase: 157.3+/-18.3 vs 77.0+/-8.7 microu/mL, P=0.0003; second-phase: 175.0+/-24.3 vs 108.7+/-8.8 microu/mL, P=0.012). Insulin sensitivity index was 35% lower in black adolescents compared with whites (P=0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable early in childhood in healthy African-American vs American whites. However, genetic (race) vs environmental factors (physical activity/fitness, energy balance) should be carefully scrutinized as potential factors responsible for such differences.
[show abstract][hide abstract] ABSTRACT: Leptin has been demonstrated to reflect body fat mass (FM) in humans, but the regulation of leptin levels during childhood growth and development is poorly understood. We studied the relation between plasma leptin, fasting insulin, insulin sensitivity, and resting energy expenditure in 22 healthy prepubertal children and 27 adolescents. Body composition was assessed by the H2(18)O-dilution principle, insulin sensitivity by a hyperinsulinemic (40 mU/m2/min)-euglycemic clamp, and energy expenditure by indirect calorimetry. Plasma leptin in prepubertal children (9.3 +/- 2.0 ng/mL) was not different from that in pubertal adolescents (10.9 +/- 2.2 ng/mL). Plasma leptin correlated with FM (r = .77, P < .001). There were no gender differences in leptin after controlling for FM differences. In prepubertal and pubertal subjects, plasma leptin correlated with fasting insulin independently of FM (r = .60, P < .001), but did not correlate with insulin sensitivity independently of body fat content. Leptin showed no relationship to resting energy expenditure after adjusting for body composition. The present cross-sectional evaluation of normal children shows that (1) plasma leptin reflects body fat content, (2) leptin concentrations are similar between prepubertal children and pubertal adolescents, (3) there are no gender differences in leptin independent of adiposity, and (4) leptin correlates with fasting insulin but not with insulin sensitivity. Contrary to animal data, our cross-sectional results in healthy children do not suggest a role for leptin in puberty or a female-related leptin resistance as reported in adults. It remains to be determined at which stage of human development the sexual dimorphism in leptin becomes evident.
[show abstract][hide abstract] ABSTRACT: Previously, we demonstrated decreased protein breakdown and insulin resistance in pubertal adolescents compared with prepubertal children. Puberty-related increases in sex steroids and/or GH could be potentially responsible. In the present study, the effects of 4 months of testosterone enanthate (50 mg in every 2 weeks) on body composition, protein, fat, and glucose metabolism and insulin sensitivity were evaluated in adolescents with delayed puberty. Body composition was assessed by H218O-dilution principle. Protein breakdown, oxidation, and synthesis were measured during primed constant infusion of [1-13C]leucine. Whole-body lipolysis was measured during primed constant infusion of [2H5]glycerol. Insulin action in suppressing proteolysis and lipolysis and stimulating glucose disposal was assessed during a stepwise hyperinsulinemic (10 and 40 mU-m2.min) euglycemic clamp. Fat and glucose oxidation rates were calculated from indirect calorimetry measurements. After 4 months of testosterone treatment, height, weight, and fat free mass (FFM) increased and fat mass, percent body fat, plasma cholesterol, high- and low-density lipoproteins, and leptin levels decreased significantly. Whole-body proteolysis and protein oxidation were lower after testosterone treatment (proteolysis, 0.49 +/- 0.03 vs 0.54 +/- 0.04 g.h.kg FFM, P = 0.032; oxidation, 0.05 +/- 0.01 vs. 0.09 +/- 0.01 g.h.kg FFM, P = 0.015). Protein synthesis was not different, and resting energy expenditure was not different. Total body lipolysis was not affected by testosterone treatment, however, fat oxidation was higher after testosterone (pre-: 2.4 +/- 0.7 vs. post-: 3.5 +/- 0.7 mumol.kg.min, P = 0.031). During the 40 mU.m2.min hyperinsulinemia, insulin sensitivity of glucose metabolism was not affected with testosterone therapy (59.1 +/- 8.8 vs. 57.1 +/- 8.2 mumol.kg.min per muU/mL). However, metabolic clearance rate of insulin was higher posttestosterone (13.6 +/- 1.1 vs. 16.7 +/- 0.8 mL.kg.min, P = 0.004). In conclusion, after 4 months of low-dose testosterone treatment in adolescents with delayed puberty 1) FFM increases and fat mass and leptin levels decrease; 2) postabsorptive proteolysis and protein oxidation decrease; 3) fat oxidation increases; and 4) insulin sensitivity in glucose metabolism does not change, whereas insulin clearance increases. These longitudinal observations are in agreement with our previous cross-sectional studies of puberty and demonstrate sparing of protein breakdown of approximately 1.2 g.kg.day FFM, wasting of fat mass, but no change in insulin sensitivity after short periods of low-dose testosterone supplementation.
[show abstract][hide abstract] ABSTRACT: We had previously demonstrated greater insulin secretion and lower insulin sensitivity in black pubertal adolescents compared with whites. This study aimed to investigate whether similar black/white differences are present in the prepubertal period or are characteristics of the pubertal period. Twelve black and 11 white healthy prepubertal children, matched for age, body mass index, and Tanner I pubertal development, underwent a 2-h hyperglycemic clamp (225 mg/dL). Physical fitness was assessed by maximal oxygen consumption (VO2max) measurement during graded bicycle ergometry, and resting energy expenditure was measured by indirect calorimetry after overnight fast. Fasting and first phase insulin concentrations were higher in blacks than in whites [14.7 +/- 1.3 vs. 10.4 +/- 1.2 (P = 0.02) and 76.9 +/- 6.8 vs. 52.1 +/- 6.4 microU/mL (P = 0.016)]. There were no differences in second phase insulin levels and insulin sensitivity index. Both maximal oxygen consumption (VO2max) and resting energy expenditure were lower in black children, whereas insulin-like growth factor I was higher. After controlling for these differences, race contributed significantly to basal insulin, but not to first phase insulin. In summary, previously reported black/white differences in insulin secretion and sensitivity during adolescence may have their origin in early childhood manifested as hyperinsulinemia. However, genetic (race) vs. environmental factors (physical activity/fitness and energy balance) should be carefully scrutinized as potential factors responsible for such differences.
[show abstract][hide abstract] ABSTRACT: This investigation examined whether puberty differs from prepuberty in regard to the effects of increased free fatty acid (FFA) on in vivo glucose metabolism. Nine prepubertal and 13 pubertal healthy children were studied. Each subject was studied twice, once with 0.9% sodium chloride solution (control study) and once with 20% Intralipid infusion in the basal state and during a 3-h hyperinsulinemic-euglycemic clamp, with [6,6-2H2]glucose tracer. During control studies, prepubertal children had lower basal fat oxidation and higher insulin-mediated glucose disposal than pubertal adolescents. During Intralipid infusion, basal glucose uptake increased in prepubertal children but did not change in pubertal adolescents. Insulin-stimulated whole body glucose disposal did not change in prepubertal children (control 77.6 +/- 8.9, Intralipid 84.5 +/- 13.3 micromol x kg(-1) x min(-1)) but decreased in pubertal adolescents (control 55.0 +/- 3.6, Intralipid 46.7 +/- 3.4 micromol x kg(-1) x min(-1), P = 0.01) despite comparable decrements in glucose oxidaion. We conclude that in prepubertal children lipids exert effects in the basal state by stimulating hepatic glucose production and glucose disposal, whereas in pubertal adolescents they induce peripheral tissue insulin resistance by decreasing insulin-stimulated glucose uptake. This differential response could be due to developmental-maturational changes in tissue sensitivity and/or specificity to the glucose-FFA interaction.
The American journal of physiology 05/1997; 272(4 Pt 1):E523-9. · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Fourteen black and 16 white healthy adolescents underwent a 2-hour hyperglycemic clamp (12.5 mmol/L) to investigate racial differences in insulin secretion and sensitivity. First-phase and second-phase insulin concentrations were higher in black subjects than in white subjects (first phase: 944 +/- 110 pmol/L vs. 462 +/- 52 pmol/L, p = 0.0003; second phase: 1050 +/- 146 pmol/L vs. 652 +/- 53 pmol/L, p = 0.0012). The insulin sensitivity index was lower in black adolescents (8.21 +/- 1.05) compared with white adolescents (12.55 +/- 1.42 mumol/kg per minute per picomole per liter, p = 0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable in healthy black versus white adolescents.
Journal of Pediatrics 10/1996; 129(3):440-3. · 4.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Syndrome X, or the syndrome of insulin resistance, is a cluster of related metabolic abnormalities of hyperinsulinemia, glucose intolerance, increased very low density lipoprotein (VLDL), decreased high density lipoprotein (HDL), and hypertension in nonobese adults and plays an important role in the genesis of cardiovascular disease. The aim of the present study was to examine the relationships among insulin sensitivity, plasma lipid levels, and body composition in the pediatric age group to determine whether these associations are present in childhood. Twenty healthy Caucasian Tanner stage I (TI) children (age, 10.7 +/- 0.3 yr; body mass index, 18.9 +/- 0.8 kg/m2) and 22 pubertal Tanner stage II-IV (TII-IV) adolescents (age, 14.0 +/- 0.3 yr; body mass index, 20.0 +/- 0.4 kg/m2) were studied. In vivo insulin-mediated glucose disposal (Rd) was evaluated during a 40 mu/m2. min hyperinsulinemic-euglycemic clamp. Body composition was assessed isotopically by the H218O dilution principle. Fasting blood was obtained for cholesterol, triglyceride (TG), VLDL, low density lipoprotein (LDL), and HDL determinations. In both groups, the strongest correlation of Rd was with percent body fat (%BF) (TI: r = -0.82; P < 0.001; TII-IV: r = -0.73; P < 0.001). In addition, in TI, Rd was correlated with TG (r = 0.64; P = 0.001), VLDL (r = 0.64; P = 0.001), and diastolic blood pressure (r = -0.50; P = 0.01). There were no such correlations in TII-IV. In TI, % BF correlated positively with LDL and negatively with TG and VLDL. In TII-IV, % BF correlated positively with cholesterol and LDL. After correcting for %BF, partial correlation analysis revealed no relationship between Rd and lipid levels in either group. This suggests that the relationship of insulin sensitivity to lipid levels was secondary to the effect of body composition on lipid levels. However, regardless of body composition, the basal insulin level was correlated with TG (r = 0.38; P = 0.04) and VLDL (r = 0.40; P = 0.04) in TII-IV subjects. We conclude that 1) the primary correlate of insulin sensitivity is %BF in both prepubertal and pubertal subjects, with no relationship to plasma lipids; 2) in prepubertal children, diastolic blood pressure is negatively correlated with insulin sensitivity and positively with insulin levels, independent of adiposity; and 3) after the onset of puberty, basal insulin levels are positively correlated with VLDL and TG regardless of the degree of adiposity. This observation could be a very early manifestation of the genesis of syndrome X in childhood.
[show abstract][hide abstract] ABSTRACT: To determine whether acute hyperglycemia adversely affects mental efficiency to the same extent as acute mild hypoglycemia.
We administered a battery of cognitive tests to adolescents studied at hyperglycemic (20 mmol/L (360 mg/dl)), hypoglycemic (3.3 mmol/L (60 mg/dl)), or euglycemic (5.5 mmol/L (100 mg/dl)) targets, which were maintained by an insulin-glucose clamp. The study included 36 children, 9 to 19 years of age (mean = 14.7 years), with diabetes duration more than 2 years (mean = 6.9 years).
Cognitive test performance did not deteriorate during hyperglycemia. In contrast, there was a significant decline in performance on all cognitive tests during mild hypoglycemia. Autonomic symptoms did not change significantly during hyperglycemia or during the rapid return from hyperglycemia to euglycemia. Although significant increments in epinephrine and pancreatic polypeptide levels occurred during mild hypoglycemia, no changes in counterregulatory hormones occurred during hyperglycemia. An exploratory regression analysis demonstrated that changes in mental efficiency were best predicted by increases in pancreatic polypeptide, a marker of autonomic activation.
These results confirm our previous finding that mild hypoglycemia causes transient decrements in cognitive function. In contrast, neither hyperglycemia, nor the rapid drop from acute hyperglycemia to euglycemia, affected symptoms, cognitive function, or counterregulatory hormone secretion.
Journal of Pediatrics 03/1995; 126(2):178-84. · 4.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The roles of insulin deficiency and insulin resistance in the pathogenesis of glucose intolerance in cystic fibrosis (CF) were evaluated in eight patients (aged 16.5 +/- 1.9 yr), four with normal glucose tolerance (NGT) and four with impaired glucose tolerance (IGT), and in seven healthy control (CN) subjects. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Hepatic glucose production (HGP) and insulin-stimulated glucose disposal were measured using [6,6-2H2]glucose and a stepwise hyperinsulinemic-euglycemic clamp. First and second phase insulin levels were significantly lower in both groups of CF patients compared with control values. There was an inverse relationship between glycohemoglobin level and first phase insulin (r = -0.81; P = 0.015) and second phase insulin (r = -0.97; P < 0.001). During the hyperglycemic clamp, the insulin sensitivity index was lower in CF-IGT, but not CF-NGT, compared with control values (6.66 +/- 1.79, 12.82 +/- 1.61, and 13.02 +/- 1.78 mumol/kg.min/pmol.L, respectively; P < 0.05). Basal HGP and fasting plasma glucose were higher in CF vs. CN [24.8 +/- 2.9 vs. 16.9 +/- 1.4 mumol/kg.min (P = 0.036) and 5.8 +/- 0.2 vs. 5.4 +/- 0.1 mmol/L (P = 0.035), respectively]. During the hyperinsulinemic euglycemic clamp, insulin-stimulated glucose disposal was significantly lower in CF-IGT (45.68 +/- 4.87 mumol/kg.min) vs. CF-NGT (78.99 +/- 1.34 mumol/kg.min) and CN (71.74 +/- 6.88 mumol/kg.min). Insulin sensitivity was lower in CF-IGT vs. CF-NGT (7.04 +/- 0.86 and 14.38 +/- 0.84 mumol/kg.min/pmol.L; P < 0.05). We conclude that 1) glycohemoglobin is a strong correlate of insulin deficiency in CF; and 2) glucose intolerance in this group of CF patients occurred as a consequence of concomitant insulin deficiency and insulin resistance.
[show abstract][hide abstract] ABSTRACT: Children with long-standing IDDM have impaired counterregulatory responses to hypoglycemia. To determine whether children with new onset IDDM also have altered counterregulation, we studied the counterregulatory responses to hypoglycemia in twenty children with new onset IDDM (5-6 days, age 12.6 +/- 2.9 yr, mean +/- SD), and compared these responses to 47 subjects with long-standing IDDM (duration 7.8 +/- 3.6 yr, age 15.3 +/- 2.5 yr) and 21 controls (age 14.2 +/- 2.8 yr). Six new onset subjects were restudied three months later during their remission. Glucose nadir in new onset (2.7 +/- 0.1 mmol.l-1) was similar to controls (2.4 +/- 0.1 mmol.l-1), but was higher than in long-standing IDDM (2.2 +/- 0.1 mmol.l-1). Both groups of diabetic subjects had lower glucagon responses to hypoglycemia than controls (p < 0.005). Glucagon responses in new and long-standing diabetes did not differ. Epinephrine was diminished in new IDDM compared to controls (p < 0.01). Glucose recovery was faster in new onset than in long-standing IDDM (p < 0.001) and the same as in controls. Responses remained diminished 3 months after diagnosis despite increased C-peptide and lower glycosylated hemoglobin. Thus, children with IDDM have diminished counterregulatory responses to hypoglycemia at diagnosis, that are similar to those in long-standing IDDM. The reasons for this impairment and its clinical application in childhood require further investigation.