Objectively measured patterns of physical activity in primary school children in Coventry: the influence of ethnicity.

AIMS: The aetiology of increased metabolic risk in South Asians is incompletely understood, but may include modifiable factors such as physical activity. This study assessed patterns of physical activity in UK primary school children and examined the influence of ethnicity. METHODS: We studied a community sample of children aged 8-9 years attending primary schools in Coventry, UK. One hundred and sixty-one children wore combined physical activity and heart rate monitors for 7 days. Levels of activity and energy expenditure were compared between White European (n = 96) and South Asian children (n = 65). Patterns of physical activity during the school week were also described. RESULTS: Seventy-three per cent of White Europeans compared with only 35% of South Asians achieved international recommendations of 60 minutes of moderate to vigorous physical activity daily (P < 0.0000). South Asians were less active during the week (106 ± 28 vs. 120 ± 32 counts/min, respectively, P = 0.0054) and at weekends (92 ± 34 vs. 108 ± 54 counts/min, P = 0.0118) compared with White Europeans. There were differences in energy expenditure with lower physical activity levels in South Asians (daily average 1.68 ± 0.13 vs. 1.76 ± 0.17, P < 0.0001). Differences were attributable to less activity after school in South Asians (97 ± 29 vs. 120 ± 43 counts/min, P < 0.0000) as daytime activity was comparable between groups (120 ± 41 vs. 124 ± 39 counts/min, P > 0.05). CONCLUSION: South Asian children in Coventry do significantly less physical activity than White Europeans, mainly attributable to differences in after-school activity. Ethnically tailored interventions should explore whether physical activity can be increased in South Asian children and, if so, whether this increased physical activity improves metabolic health.

Metformin in obese children and adolescents: the MOCA trial.

CONTEXT: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the evidence in obese children and young people is inconclusive. OBJECTIVE: The objective of the study was to assess the effect of metformin on body mass index sd score (BMI-SDS), metabolic risk factors, and adipokines. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at six pediatric endocrine centers in the United Kingdom. PARTICIPANTS: One hundred fifty-one obese children and young people with hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6% postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants. The age range was 8-18 yr, the mean age was 13.7 (SD 2.3) yr, and the mean BMI-SDS was +3.4 (SD 0.5). INTERVENTIONS: The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months. MAIN OUTCOME MEASURE: The main outcome measure was a reduction in BMI-SDS at 6 months. Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio (ALR) at 3 and 6 months. RESULTS: Metformin was associated with a significant reduction in BMI-SDS compared with placebo at 6 months [mean difference -0.1 SD (95% confidence interval -0.18 to -0.02), P = 0.02]. Significant improvements at 3 months were found in the metformin group: fasting glucose, -0.16 mmol/liter (-0.31 to -0.00), P = 0.047; ALT, 19% (5-36%), P = 0.008; and ALR, 32% (4-67%), P = 0.02. CONCLUSIONS: Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.

Setting research priorities for Type 1 diabetes.

AIMS: Research priorities are often set by academic researchers or the pharmaceutical industry. The interests of patients, carers and clinicians may therefore be overlooked and research questions that matter may be neglected. The aims of this study were to collect uncertainties about the treatment of Type 1 diabetes from patients, carers and health professionals, and to collate and prioritize these uncertainties to develop a top 10 list of research priorities, using a structured priority-setting partnership of patients, carers, health professionals and diabetes organizations, as described by the James Lind Alliance. METHODS: A partnership of interested organizations was set up, and from this a steering committee of 10 individuals was formed. An online and paper survey was used to identify uncertainties. These were collated, and the steering group carried out an interim priority-setting exercise with partner organizations. This group of uncertainties was then voted on to give a smaller list that went forward to the final priority-setting workshop. At this meeting, a final list of the top 10 research priorities was agreed. RESULTS: An initial 1141 uncertainties were described. These were reduced to 88 indicative questions, 47 of which went out for voting. Twenty-four were then taken forward to a final priority-setting workshop. This workshop resulted in a list of top 10 research priorities in Type 1 diabetes. CONCLUSION: We have shown that it is possible using the James Lind Alliance process to develop an agreed top 10 list of research priorities for Type 1 diabetes from health professionals, patients and carers.

Pharmacotherapy for overweight/obesity in ethnic minorities and White Caucasians: a systematic review and meta-analysis.

Ethnic minorities in the West exhibit a higher prevalence of obesity and also under-achieve in weight management compared to White Caucasians. A systematic review of randomized controlled trials (RCTs) in adults (mean age ≥18 years, duration ≥6 months and published in the English language) was undertaken to evaluate the effectiveness of antiobesity drugs in ethnic minorities and White Caucasians. Data sources between 1990 and 2010 were searched including MEDLINE, EMBASE, Cochrane Controlled Trials Register, CINAHL and references cited in the included studies of other reviews. Eighteen RCTs that met the inclusion criteria were included in this review (6 sibutramine and 12 orlistat). A random effects model was used for meta-analysis. An indirect comparison of weight loss in sibutramine-treated patients in ethnic minorities was significantly lower than in White Caucasians: -2.7 kg (95% CI: -3.1 to -2.3) versus -4.4 kg (95% CI: -5.0 to -3.8), respectively. For orlistat, weight loss was similar in the two groups: -2.3 kg (95% CI: -2.6 to -2.0) in ethnic minorities and -2.8 kg (95% CI: -5.1 to -0.5) in White Caucasian participants. Overall, there were few studies of weight loss pharmacotherapy for comparison of this review and it was not possible to analyse data based on ethnic groupings. More ethnically tailored studies are needed to assess the most effective weight loss strategies in these most metabolically vulnerable groups.

Managing childhood obesity: when lifestyle change is not enough.

The management of childhood obesity is a clinical dilemma. Paediatricians will see those children whose weight is at the severe end of the spectrum with obesity-related co-morbidities and for whom more intensive weight loss therapies may be appropriate. A literature review was performed (January 1995-January 2010) of the roles of pharmacotherapy or bariatric surgery in the management of childhood obesity. Three hundred and eighty-three abstracts were reviewed and 76 full-text articles were requested. Of these, 34 were excluded and a total of 21 pharmacotherapy papers and 22 papers on surgery were reviewed in detail. All studies involved adolescents. Pharmacotherapy: Most studies were small and of short duration, the notable exceptions being two large RCTs of sibutramine and orlistat. Sibutramine led to a mean estimated change in BMI from baseline of -3.1 kg/m(2) vs. -0.3 kg/m(2) for placebo over 12 months. Orlistat was also beneficial with a mean reduction in BMI of 0.55 vs. an increase of 0.31 kg/m(2) in the placebo group at 12 months. Bariatric surgery: Most papers presented clinical observations and there were no randomised controlled trials (RCTs). Robust selection criteria were not used and ideal candidate selection remains unclear. Most papers showed a significant benefit of surgery in severely obese adolescents in the short term but long-term data were sparse. There were a surprisingly large number of papers examining the benefits of intensive weight management in obese adolescents. The study design of many was inadequate and the role of pharmacotherapy or surgery in childhood obesity remains unclear.

Self-Reported Psychosocial Health in Obese Patients before and after Weight Loss.

Psychosocial profiles were examined in 255 morbidly obese patients attending a hospital service offering access to standard weight loss therapies. 129 patients were reassessed after at least 6-month follow-up. At baseline, 51.8% and 32.7% of patients, respectively, had evidence of anxiety and depressive disorders, 24% had severe impairments in self esteem, and 29.7% had an increased risk of eating disorders. At follow-up, weight loss from baseline was significant in all 3 therapies: diet only is 0.74 +/- 1.8 kg; pharmacotherapy is 6.7 +/- 4.2 kg; and surgery is 20.1 +/- 13.6 kg. Anxiety scores improved in all three groups (P < .05). Patients having pharmacotherapy or surgery had significant improvements in physical and work function and public distress compared to those having dietary treatment only (P < .05). Our observational data suggest that weight management services can lead to psychosocial benefit in morbidly obese patients. Well-designed studies are necessary to examine the link between weight loss and emotional health.

Dietary and lifestyle interventions for weight management in adults from minority ethnic/non-White groups: a systematic review.

Minority ethnic/non-White populations are more prone to weight gain and more susceptible to obesity-related complications. The objective of this study was to systematically review dietary and lifestyle interventions for weight management in minority ethnic groups. Electronic databases and reference lists of original studies and reviews were searched for studies on dietary and lifestyle weight management interventions published. Randomized clinical trials with ≥6-month duration were included. Nineteen studies met the inclusion criteria. Fourteen studies involved African-Americans, one in non-White Hispanics, one in Japanese Americans and three in both African-Americans and non-White Hispanics. Most of the interventions proved relatively effective. However, significant drawbacks were noted for several of these studies, such as small sample size, high attrition rates and lack of follow-up data. Better quality and long-term trials are required in order to investigate in detail the effectiveness of lifestyle changes for weight management in these populations and eventually support evidence-based recommendations.

Type 2 diabetes in childhood: epidemiological and clinical aspects.

BACKGROUND: The global obesity epidemic has raised concerns about the risk of a tide of Type 2 diabetes (T2DM) in childhood. This paper aims to review the recent data on the epidemiology of this problem as well as the clinical concerns. SOURCES OF DATA: A literature search was performed on Medline, and articles about childhood T2DM, in English and published from 2000 to 2008, were reviewed. AREAS OF AGREEMENT: A review of 16 paediatric studies suggest that although T2DM is now more widely reported in childhood, the numbers are still reasonably small although the data do suggest that ethnicity is an important risk factor. AREAS OF CONTROVERSY: Although there are emerging data on what appears to be a significant risk of both microvascular and macrovascular complications in youth onset T2DM, the most appropriate management remains unclear. Currently, adult guidelines for management of T2DM are being extrapolated to the adolescent population with T2DM. GROWING POINTS: Studies are currently underway to examine the pharmacological management of childhood T2DM. AREAS TIMELY FOR DEVELOPING RESEARCH: More data are necessary on the exact prevalence of T2DM among a variety of populations to provide a greater understanding of the risk factors for T2DM and provide indications for screening. In the meantime, great emphasis needs to be placed on obesity prevention if we are to protect the health of future generations of children.

An AFM study on mechanical properties of native and dimethyl suberimidate cross-linked pericardium tissue.

Changes in the stiffness of hog pericardium tissue, native and treated with dimethyl suberimidate (DMS), are investigated by atomic force microscopy (AFM). Young's modulus is calculated on the basis of the Hertz-Sneddon model. The cross-linking process increases the stiffness of the tissue. The values of Young's modulus are higher for the DMS stabilized pericardium than for the native one. We also observe that the Young's modulus of native tissue increases when the time between getting the biological material and performing the measurements is longer. This process is probably connected with natural degradation of the biological samples.

Insulin increases angiotensinogen expression in human abdominal subcutaneous adipocytes.

The renin-angiotensin system is an important regulator of blood pressure, and blockade of this system improves blood pressure in obesity and type 2 diabetes. Recently, components of the system have been described in adipose tissue. However, to date no study has investigated the influence of varying insulin concentrations on angiotensinogen (AGT) protein expression in human subcutaneous abdominal fat. Isolated subcutaneous adipocytes were treated with insulin (1-1000 nm) for 48 h. As part of the studies, a novel AGT antibody was developed and validated by Western blotting and immunohistochemistry. Western blotting was performed on the protein extracted from the adipocytes treated with insulin to determine AGT expression. Increasing doses of insulin raised AGT protein expression in a dose-dependent manner (control 1.0 +/- 0.0 (mean +/- s.e.) - protein expression standardized relative to control; 1 nm insulin: 2.64 +/- 0.0.32 upward arrow ***; 100 nm insulin: 4.37 +/- 0.57 upward arrow ***; 1000 nm insulin: 6.50 +/- 0.97 upward arrow ***; ***p < 0.001, n = 3). In conclusion, increasing insulin doses stimulates AGT production. In this study, protein analysis suggests that hyperinsulinaemia may be an important factor in obesity-related hypertension.

Hypoglycaemia and counterregulation during childhood.

Hypoglycaemia is particularly common in young children with type 1 diabetes mellitus yet the normal protective counterregulatory responses have been little studied in this age group. The studies reported have shown conflicting results, in part related to prior glycaemic control and also to the method of investigation used. Counterregulatory hormone responses during both spontaneous and experimentally induced episodes of nocturnal hypoglycaemia do appear to be blunted, which may be a function of sleep itself. Although studies of cognitive function have consistently shown defects in certain areas of neurocognitive performance, particularly in those children with early-onset diabetes or a prior history of severe hypoglycaemia, the contribution of nocturnal hypoglycaemia to the development of these impairments has not been evaluated. In young adults and adolescents, nocturnal hypoglycaemia has been linked to cardiac arrhythmia and the risk of sudden death. The development of new techniques for continuous subcutaneous glucose monitoring may allow detailed study of counterregulatory responses and symptom recognition in young children. Effective intensification of insulin therapy without an increased risk of hypoglycaemia may be possible using new insulin analogues or continued subcutaneous intravenous infusion (CSII), thus improving patient compliance and overall quality of clinical care.

Daytime liver glycogen accumulation, measured by 13C magnetic resonance spectroscopy, in young children with Type 1 diabetes mellitus.

AIM: To examine daytime liver glycogen accumulation in prepubertal children with Type 1 diabetes mellitus (Type 1 DM) compared with non-diabetic controls. METHODS: Liver glycogen content was ascertained in the fasting (morning) and fed (afternoon) state using 13C magnetic resonance (MR) spectroscopy. Data were analysed from six children with Type 1 DM (median (range) age 8.7 (6.3-12.2) years), who were all on conventional insulin regimens, and six healthy controls (age 8.9 (7-10.2) years). RESULTS: Children with diabetes tended to have lower fasting glycogen values than controls but this did not reach statistical significance (median (range) 154 (70-177) vs. 178 (120-203) mM glycosyl units, Type 1 DM vs. controls respectively; P = 0.06). Glycogen increased in all children with diabetes during the day and concentrations were similar to those in controls by the afternoon (175 (157-299) vs. 172 (136-238) mM glycosyl units; P = 0.7). CONCLUSIONS: The ability of young children with Type 1 DM to replace liver glycogen depleted after an overnight fast was at least as good as that in control subjects, suggesting that impaired glycogen storage is not a contributory factor in nocturnal hypoglycaemia.

Alterations in sleep physiology in young children with insulin-dependent diabetes mellitus: relationship to nocturnal hypoglycemia.

OBJECTIVES: To examine the effect of diabetes per se and nocturnal hypoglycemia on sleep in children with insulin-dependent diabetes mellitus (IDDM). DESIGN: Overnight polysomnography was performed on 3 occasions in 29 children with IDDM - twice during metabolic profiling. Sleep data were analyzed from 14 children (median [range], 8.7 [5.9 to 12.9] years) with a night of hypoglycemia and a nonhypoglycemic night. Seven children in the control group (9 [5.6 to 11.4] years) underwent 2 nights of polysomnography, once during metabolic profiling (to assess the effects of metabolic profiling), and 15 members of the control group had polysomnography only (to assess the effects of diabetes per se and to compare with the index group). RESULTS: Children with IDDM had disrupted sleep compared with the control group (short wakes, percentage of sleep time, 0.8 [0.5 to 1.9] vs 0.0 [0.0 to 0.3], median [interquartile range], IDDM vs control group, respectively, P =.001; long wakes, 1.2 [0.7 to 3. 0] vs 0.0 [0.0 to 0.0], P =.033; total number of wakes, 6 [3.5 to 11. 5] vs 1 [0 to 2], P =.002). Blood sampling disrupted sleep with increased long wakes as percentage of sleep time (0.3 [0.0 to 3.8] vs 4.3 [3.1 to 16.9], nonsampling vs sampling night, respectively, P =.003). Episodes of hypoglycemia were profound, with a glucose nadir of 2.0 [1.4 to 3.3] mmol/L (35.0 [24.5 to 57.8] mg/dL) and prolonged, 308 [30 to 630] minutes, with no effect on sleep. CONCLUSIONS: Children with diabetes had disrupted sleep compared with a control group, but there was no effect of profound nocturnal hypoglycemia on sleep quality. J Pediatr 2000;137:233-8)

Cognitive function and mood after profound nocturnal hypoglycaemia in prepubertal children with conventional insulin treatment for diabetes.

OBJECTIVES: To examine the frequency of nocturnal hypoglycaemia, and the effects on cognitive function and mood, in children with insulin dependent diabetes mellitus (IDDM). DESIGN: Two overnight glucose profiles, in the home environment, and assessments of cognitive function and mood the following day. Twenty nine prepubertal patients with IDDM (median age, 9.4 years; range, 5.3-12.9) and 15 healthy controls (single overnight profile), median age 9.5 (range, 5.6-12.1) years were studied. RESULTS: Asymptomatic hypoglycaemia (glucose < 3.5 mmol/l) was observed in 13 of 29 patients studied on night 1: four of these and seven others were hypoglycaemic on night 2. The median glucose nadir was 1.9 (range, 1.1-3.3) mmol/l and the median duration of hypoglycaemia was 270 (range, 30-630) minutes. Hypoglycaemia was related to insulin dose, but not glycosylated haemoglobin (HbA1c) values, and was partially predicted by a midnight glucose of < 7.2 mmol/l. Cognitive performance was not altered after hypoglycaemia but a lowering of mood was observed. CONCLUSIONS: Young children on conventional insulin regimens are at high risk for profound, asymptomatic nocturnal hypoglycaemia, which is difficult to predict. There was no short term effect on cognitive function but mood change was detected.

Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.

OBJECTIVE: To examine counterregulatory responses during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 29 prepubertal patients with type 1 diabetes underwent two overnight profiles. Data were analyzed from 16 children (median [range] 8.7 [5.9-12.9] years of age) with a night of hypoglycemia and a nonhypoglycemic night. Children hypoglycemic (< 3.5 mmol/l) on night 1 were given 25% extra carbohydrate as uncooked cornstarch with their usual evening snack on night 2 to avoid hypoglycemia. Glucose, growth hormone, and cortisol were measured every 15 min, catecholamines every 30 min, and glucagon, pancreatic polypeptide, insulin, and ketones every 60 min. A group of 15 healthy control subjects, aged 9.5 (5.6-12.1) years, underwent one overnight profile. RESULTS: Median duration of hypoglycemia was 225 (30-630) min, and glucose nadir was 2.0 (1.2-3.3) mmol/l. Insulin levels were not different on the two nights (P = 0.9, analysis of variance), but children with diabetes had higher insulin levels than normal control subjects between 2300 and 0300, maximal at 0200 (mean +/- SEM 57.4 +/- 5.7 vs. 31.6 +/- 5.0 pmol/l, P = 0.002). Peak epinephrine was higher on the night of hypoglycemia (0.98 [0.52-2.09] nmol/l) versus nonhypoglycemia (0.32 [0.21-0.62] nmol/l), P = 0.001, but norepinephrine (1.29 [1.07-2.64] vs. 1.26 [1.04-1.88] nmol/l, P = 0.5), glucagon (93 [64.2-125.6] vs. 100.5 [54.6-158] ng/l, P = 0.6), pancreatic polypeptide (410.2 [191-643.2] vs. 270.8 [158.2-777.8] ng/l, P = 0.5), and cortisol (513 [300-679] vs. 475 [235-739] nmol/l, P = 0.6) were not different. Glucose threshold for epinephrine release was very low, 1.9 +/- 0.2 mmol/l. There was a short-lived rise in growth hormone from 75-105 min after onset of hypoglycemia, maximal at 90 min (7.8 +/- 1.2 vs. 3.5 +/- 0.9 ng/ml, P = 0.02). CONCLUSIONS: The prolonged nature of nocturnal hypoglycemic episodes may be explained in part by defective counterregulation. The risk of nocturnal hypoglycemia needs to be reduced before intensification of insulin therapy can be contemplated in this age-group.

Lispro or regular insulin for multiple injection therapy in adolescence. Differences in free insulin and glucose levels overnight.

OBJECTIVE: Regular insulin given with the evening meal could contribute to the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes using a multiple injection regimen. To test this hypothesis, we compared glucodynamics and free insulin levels on two separate study nights. RESEARCH DESIGN AND METHODS: A total of 14 adolescents were recruited. On both nights, identical doses of regular insulin or insulin lispro were administered 30 min or 10 min, respectively, before the evening meal, using a double-blind randomized crossover study design. Doses of NPH insulin and carbohydrate content of the evening meal and snack were kept identical. Blood samples were taken every 15 min for blood glucose and every 60 min for free insulin and ketones. RESULTS: After insulin lispro administration, glucose levels were significantly lower between the evening meal and the bedtime snack (analysis of variance [ANOVA] P = 0.02), and four hypoglycemic episodes were recorded. This corresponded to a higher (458 +/- 48 vs. 305 +/- 33 pmol/l, P = 0.02), earlier (64 +/- 4.6 vs. 103 +/- 12 min, P = 0.01), and shorter-lasting (245 +/- 21 vs. 365 +/- 39 min, P = 0.01) insulin peak in contrast to regular insulin. After the bedtime snack, glucose levels increased dramatically during the lispro night and stayed higher, up to 0300 in the morning (ANOVA P = 0.01), corresponding to lower mean insulin levels (146 +/- 20 vs. 184 +/- 27 pmol/l, P = 0.04). No differences were seen in glucose and insulin levels between 0300 and 0800. Four episodes of nocturnal hypoglycemia were documented after the bedtime snack during the regular insulin night, in contrast to one episode after insulin lispro. No differences in ketone levels were observed. CONCLUSIONS: The replacement of regular insulin with insulin lispro may reduce the risk of late hypoglycemia, but redistribution of the evening carbohydrate may be needed to ensure good metabolic control and prevent early postprandial hypoglycemia.

Effects of low-dose recombinant human insulin-like growth factor-I on insulin sensitivity, growth hormone and glucagon levels in young adults with insulin-dependent diabetes mellitus.

Despite recent interest in the therapeutic potential of recombinant human insulin-like growth factor-I (rhIGF-I) in the treatment of diabetes mellitus, its mechanism of action is still not defined. We have studied the effects of low-dose bolus subcutaneous rhIGF-I (40 microg/kg and 20 microg/kg) on insulin sensitivity, growth hormone (GH) and glucagon levels in seven young adults with insulin-dependent diabetes mellitus (IDDM) using a randomized double-blind placebo-controlled crossover study design. Each was subjected to a euglycemic clamp (5 mmol/L) protocol consisting of a variable-rate insulin infusion clamp (6:00 PM to 8:00 AM) followed by a two-dose hyperinsulinemic clamp (insulin infusion of 0.75 mU x kg(-1) x min(-1) from 8 to 10 AM and 1.5 mU x kg(-1) x min(-1) from 10 AM to 12 noon) incorporating [6,6 2H2]glucose tracer for determination of glucose production/utilization rates. Following rhIGF-I administration, the serum IGF-I level (mean +/- SEM) increased (40 microg/kg, 655 +/- 90 ng/mL, P < .001; 20 microg/kg, 472 +/- 67 ng/mL, P < .001; placebo, 258 +/- 51 ng/mL). Dose-related reductions in insulin were observed during the period of steady-state euglycemia (1 AM to 8 AM) (40 microg/kg, 48 +/- 5 pmol/L, P = .01; 20 microg/kg, 58 +/- 8 pmol/L, P = .03; placebo, 72 +/- 8 pmol/L). The mean overnight GH level (40 microg/kg, 9.1 +/- 1.4 mU/L, P = .04; 20 microg/kg, 9.6 +/- 2.0 mU/L, P = .12; placebo, 11.3 +/- 1.7 mU/L) and GH pulse amplitude (40 microg/kg, 18.8 +/- 2.9 mU/L, P = .04; 20 microg/kg, 17.0 +/- 3.4 mU/L, P > .05; placebo, 23.0 +/- 3.7 mU/L) were also reduced. No differences in glucagon, IGF binding protein-1 (IGFBP-1), acetoacetate, or beta-hydroxybutyrate levels were found. During the hyperinsulinemic clamp conditions, no differences in glucose utilization were noted, whereas hepatic glucose production was reduced by rhIGF-I 40 microg/kg (P = .05). Our data demonstrate that in subjects with IDDM, low-dose subcutaneous rhIGF-I leads to a dose-dependent reduction in the insulin level for euglycemia overnight that parallels the decrease in overnight GH levels, but glucagon and IGFBP-1 levels remain unchanged. The decreases in hepatic glucose production during the hyperinsulinemic clamp study observed the following day are likely related to GH suppression, although a direct effect by rhIGF-I cannot be entirely discounted.