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Biomedical subjects

W V Tamborlane

Publications and source records attributed to W V Tamborlane.

At least 19 recordsLinked to original sources
PubMed2006

Ethnic differences in beta cell adaptation to insulin resistance in obese children and adolescents.

AIMS/HYPOTHESIS: The prevalence of altered glucose metabolism in obese children and adolescents is growing at a significant rate, especially in ethnic minorities. It is not clear whether young people of different ethnic backgrounds differ in their adaptive mechanisms to obesity-related insulin resistance. The aim of this study was to evaluate the early insulin response and insulin clearance in response to an oral glucose load in obese children and adolescents. METHODS: Seven hundred and nine obese children and adolescents underwent an OGTT. Indices of the early insulin response and insulin clearance were compared in participants of White European, African American and Hispanic origin. RESULTS: Participants of the three ethnic groups demonstrated similar mechanisms of adaptation to increasing insulin resistance, but with different magnitudes. African American subjects had a greater early insulin response and decreased insulin clearance than their White European and Hispanic counterparts. This happened regardless of whether the cohort was divided by glucose tolerance level or by level of insulin sensitivity. IGT across ethnic groups was characterised by a marked decline in the acute insulin response in the context of severe insulin resistance and very low insulin clearance. CONCLUSIONS/INTERPRETATION: In obese children and adolescents, mechanisms of adaptation to obesity related to insulin resistance are similar across ethnic groups. The greater early insulin response needed to maintain glucose tolerance in young people of ethnic minorities may partially explain their greater tendency to develop type 2 diabetes.

Adaptation, Physiological↗
PubMed2004

Rediscovery of insulin pump treatment of childhood type 1 diabetes.

Currently, goals for the treatment of children and adolescents with type 1 diabetes mellitus are to achieve near normal glycemia; minimize the risks of severe hypoglycemia and excessive weight gain; optimize psychosocial functioning and quality of life (for children and their families); and prevent or delay long-term microvascular complications. Continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of all of these goals in all ages of children. Insulin pump therapy provides the opportunity for greater flexibility in meal timing and content due to the convenience of its bolus delivery of insulin. Insulin pump therapy can potentially reduce the risk of exercise-related and nocturnal hypoglycemia, through the use of programmable variable basal infusion rates. In pediatric patients, usage of CSII has been demonstrated to reduce both glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children and the use of continuous glucose monitoring to optimize insulin pump therapy are reviewed.

Blood Glucose Self-Monitoring↗
PubMed2002

Importance of plasma leptin in predicting future weight gain in obese children: a two-and-a-half-year longitudinal study.

OBJECTIVE: To determine whether relatively low leptin levels predict changes in adiposity in prepubertal and pubertal obese children. RESEARCH METHODS AND PROCEDURES: In a biracial cohort of 68 obese children (33 male and 35 female; 46 Caucasians and 22 African-Americans, age range 7-18 y), we measured at baseline fasting insulin and leptin levels, height and weight and calculated body mass index (kg/m(2)) and expressed body mass index as (BMI) Z-score. After a 2.5-y follow-up, anthropometric measurements were repeated and changes in weight gain were calculated as changes in BMI Z-score. RESULTS: At baseline obese preadolescent boys and girls had similar age and BMI Z-score, fasting insulin and leptin levels. After an average follow-up of 2.5 y, mean weight change calculated by changes in BMI Z-score from baseline was similar in both groups. In obese adolescent boys and girls at baseline, no significant gender differences were observed for BMI Z-score and insulin levels. In contrast, plasma leptin levels were significantly higher in obese girls compared with obese adolescent boys. At follow-up, there was no significant difference in change in BMI Z-score between obese boys and girls. Multiple linear regression analysis revealed that high basal leptin levels were positively associated with greater changes in BMI Z-score only in girls (r(2)=0.18, P<0.02), after adjusting for basal BMI Z-score, Tanner stage, years of follow-up and basal insulin. High basal leptin levels in girls explained 18% of the weight gain. CONCLUSION: High leptin levels are associated with excessive future weight gain only in girls.

Adolescent↗
PubMed2001

Clinical and psychosocial factors associated with achievement of treatment goals in adolescents with diabetes mellitus.

PURPOSE: To examine the following questions with regard to the initiation of a new intensive management program for adolescents with Type 1 diabetes mellitus: (a) What clinical and psychosocial factors are associated with achievement of metabolic control treatment goals after 1 year? and (b) What baseline clinical and psychosocial factors are associated with improvement in the quality of life after 12 months? METHODS: Eighty-one subjects (of 83 who began; aged 14.3 +/- 2.0 years at entry; 48 females, 33 males; 95% white; diabetes duration 8.9 +/- 3.9 years) with Type 1 diabetes completed 12 months of follow-up in a study of intensified treatment of diabetes. Assessments at baseline and at 12 months used the Diabetes Quality of Life for Youth scale, the Self-efficacy for Diabetes Scale, the Children's Depression Inventory, the Issues in Coping with Diabetes Scale, and the Diabetes Family Behavior Scale. Data were analyzed using multiple and logistic regression. RESULTS: From a baseline of >9%, HbA1c levels decreased to a mean of 7.8 +/- 0.7%, with 30% of the subjects achieving our treatment goal of <or=7.2%. Logistic regression demonstrated that achievement of goal levels of HbA1c were associated with better metabolic control at study entry (p = .05), participation in coping skills training (p = .003), and more parental participation in guidance and control (p = .05). Multiple regression analysis demonstrated that participation in coping skills training with lower impact of diabetes on quality of life at baseline and less depression at baseline contributed significantly to the variance (0.57) in quality of life at 12 months. CONCLUSIONS: Providers need to pay particular attention to adolescents with poorer metabolic control and impact of diabetes on quality of life when they intensify their treatment because they are less likely to reach treatment goals. Furthermore, behavioral interventions such as coping skills training may help teens achieve their goals.

Adaptation, Psychological↗
PubMed2001

Recent advances in treatment of youth with Type 1 diabetes: better care through technology.

While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas.

Administration, Inhalation↗
PubMed2001

Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT).

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type 1 diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. STUDY DESIGN: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until EDIC year 4 were assessed. RESULTS: In contrast to the 7.4 years of the DCCT, during which mean hemoglobin A(1c) levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P <.0001), the subsequent first 4 years of EDIC had mean hemoglobin A(1c) levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P <.001) and 78% (P <.007), respectively, in the former intensive therapy group compared with the former conventional group. CONCLUSIONS: These findings provide further support for the DCCT recommendation that most adolescents with type 1 diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications.

Adolescent↗
PubMed2001

Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients.

Insulin-induced hypoglycemia occurs commonly in intensively treated patients with type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these patients are not known. We studied left ventricular systolic [left ventricular ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by equilibrium radionuclide angiography during insulin infusion (12 pmol. kg(-1). min(-1)) under either hypoglycemic (approximately 2.8 mmol/l) or euglycemic (approximately 5 mmol/l) conditions in intensively treated patients with type 1 diabetes and healthy nondiabetic subjects (n = 9 for each). During hypoglycemic hyperinsulinemia, there were significant increases in LVEF (DeltaLVEF = 11 +/- 2%) and PFR [DeltaPFR = 0.88 +/- 0.18 end diastolic volume (EDV)/s] in diabetic subjects as well as in the nondiabetic group (DeltaLVEF = 13 +/- 2%; DeltaPFR = 0.79 +/- 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but occurred earlier in the nondiabetic group. A blunted increase in plasma catecholamine, cortisol, and glucagon concentrations occurred in response to hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF also increased in both the diabetic (DeltaLVEF = 7 +/- 1%) and nondiabetic (DeltaLVEF = 4 +/- 2%) groups, but PFR increased only in the diabetic group. In the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia, only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac output in the hypoglycemic study (P < 0.05 for each). Thus intensively treated type 1 diabetic patients demonstrate delayed augmentation of ventricular function during moderate insulin-induced hypoglycemia. Although diabetic subjects have a more pronounced cardiac response to hyperinsulinemia per se than nondiabetic subjects, their response to hypoglycemia is blunted.

Adult↗
PubMed2001

Temporal patterns of circulating leptin levels in lean and obese adolescents: relationships to insulin, growth hormone, and free fatty acids rhythmicity.

Alterations in nutritional status, such as obesity, markedly influence insulin, leptin, GH secretion, and free fatty acid (FFA) levels. We measured every hour for 24 h circulating leptin, insulin, GH, and FFA levels in lean and obese adolescents to determine: 1) the impact of adolescent obesity on the diurnal changes in leptin concentrations; and 2) the temporal relationships between the diurnal patterns of circulating leptin levels and insulin, GH, and FFA levels. During puberty, we found that the 24-h profile of circulating plasma leptin levels follows a bimodal pattern with minimal concentrations occurring early in the afternoon and a nocturnal elevation starting after midnight and culminating early morning. The time course of the diurnal variation in leptin levels in the obese adolescents was not different from that in lean controls. Of note, however, in obese girls leptin 24-h excursion and leptin night to day ratio were lower than those found in lean girls. In obese adolescents, mean GH levels varied significantly less during the day and night than lean controls. During the day, there were distinct preprandial increases and postprandial decreases in FFA levels, whereas after midnight FFA levels rose in both lean and obese adolescents. A significant positive correlation was found between mean plasma insulin levels between 0800 h and 2000 h and peak in leptin in lean and obese girls and boys (r = 0.63, P: < 0.001). Peak leptin was inversely correlated with the area under the nocturnal GH levels in all groups (r = -0.31, P: < 0.0003), whereas it was positively correlated with the nocturnal peak in FFA levels (r = 0.45, P: < 0.004). In summary, we report in obese adolescent girls a blunted relative diurnal excursion in leptin levels. This abnormal rhythmicity may, in part, explain their leptin resistance state. The nocturnal rise in leptin was paralleled by a nocturnal rise in GH and FFA levels. Additional studies are needed to test the potential link between the adipose-derived peptide and GH axis in humans.

Adolescent↗
PubMed2001

Oral glucose augments the counterregulatory hormone response during insulin-induced hypoglycemia in humans.

It has been suggested that the counterregulatory hormone (CRH) response to acute hypoglycemia is triggered via glucose sensors situated in either the hypothalamus or the portohepatic area. If the latter were critical during hypoglycemia, one would anticipate that ingestion of glucose, by raising glucose levels in the portal circulation, should attenuate CRH responses previously described in animal studies. To evaluate the effect of raising portal, but not peripheral, glucose levels during insulin-induced hypoglycemia, we performed hypoglycemic clamp studies in five healthy adult males on two occasions. On one occasion, subjects received oral glucose (OG) (25 g) during hypoglycemia; and on one occasion, noncarbohydrate-containing drink of equal volume, while maintaining plasma glucose at 55 +/- 2 mg/dL (3.08 mmol/L). As a result, there were no significant differences in systemic plasma glucose levels between the two hypoglycemic clamp studies, and basal CRH concentrations were also similar. As expected, there was a brisk rise in all CRH during the control (hypoglycemia+noncarbohydrate drink) study. In the experimental study, administration of OG (hypoglycemia+OG), to raise intraportal glucose levels during systemic hypoglycemia, did not attenuate CRH responses. Indeed, OG enhanced the rise in epinephrine, glucagon, and GH. Increases in cortisol and norepinephrine did not differ between the two studies. Therefore, our data suggest that increasing the level of glucose in the portal vein above that in the systemic circulation, during hypoglycemia, enhances (rather than suppresses) CRH responses. Thus, ingestion of glucose may reverse hypoglycemia directly by provision of substrate, as well as indirectly by stimulating counteregulatory mechanisms.

Administration, Oral↗
PubMed2001

Limitations of conventional methods of self-monitoring of blood glucose: lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes.

OBJECTIVE: Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA(1c) measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring. RESEARCH DESIGN AND METHODS: A total of 56 children with type 1 diabetes (age 2-18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified. RESULTS: Despite satisfactory HbA(1c) levels (7.7 +/- 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were >180 mg/dl (above target), and almost 50% were >300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose <60 mg/dl) in almost 70% of the children. CONCLUSIONS: Despite excellent HbA(1c) levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes.

Adolescent↗
PubMed2001

Epipen as an alternative to glucagon in the treatment of hypoglycemia in children with diabetes.

OBJECTIVE: Fear of a severe hypoglycemic reaction is a major obstacle to achieving near-normal plasma glucose levels. Although parenteral glucagon is effective in treating these reactions, it is cumbersome to use, causes severe nausea, and is impractical in the school setting. Epinephrine is available as a premixed injection (Epipen) that may be used by all care providers. Using Epipen to treat hypoglycemia may be an effective, safe, and easy-to-use alternative to glucagon. RESEARCH DESIGN AND METHODS: Ten children (age 11.7 +/- 2.4 years) with type 1 diabetes were studied on two occasions. After an overnight equilibration period, hypoglycemia was induced via an insulin pump (1 mU x kg(-1) x min(-1)). At a blood glucose level of 2.8 mmol/l, either glucagon (1 mg) or epinephrine (0.3 mg), in random order, was administered intramuscularly and responses were monitored. RESULTS: Plasma free insulin concentrations were similar in both studies. Plasma glucose levels increased by 1.7 +/- 0.2 mmol/l (mean +/- SEM) in 10 min and by 2.6 +/- 0.2 mmol/l in 15 min with administration of glucagon and were not consistently increased with administration of epinephrine (P < 0.01). Peak glucagon concentrations after administration of glucagon were >60-fold higher than basal concentrations. After administration of epinephrine, peak epinephrine levels were 20-fold higher than basal concentrations. CONCLUSIONS: Epinephrine does not seem to be an adequate substitute for glucagon in the treatment of severe hypoglycemia. The effectiveness of glucagon in reversing hypoglycemia and its side effects of nausea and vomiting are likely related to the markedly supraphysiologic plasma levels achieved with the standard intramuscular dose.

Adrenergic beta-Agonists↗
PubMed2000

Changes in body composition after a 12-wk aerobic exercise program in obese boys.

UNLABELLED: Previous studies have shown that vigorous aerobic training programs for obese children result in minimal weight changes, and concluded that they may not be beneficial. Weight change alone may not detect important beneficial changes in body composition associated with vigorous training in these children. Fifteen obese boys (aged 9-12 yr, body mass index (BMI) 31.8+/-6.5, average percent body fat (%BF) 41+/-4.2) underwent a supervised aerobic and resistance training program (12 wk, 2 days/wk for 30 min/session), to investigate the effects on weight and body composition. After the 3-month training period, weight loss averaged only 1.5+/-1.0 kg (not significant), but total body fat decreased by 4.1+/-1.8 kg (p<0.05) and fat-free mass (FFM) increased by 2.6+/-1.1 kg (p<0.05) based on hydrostatic weighing. As a result, %BF fell by 10% (p<0.01). There was a 5.8+/-2.8 mL/kg/min (p<0.05) increase in peak volume of oxygen uptake (VO(2)), along with a 248+/-120 kcal/d (p<0.05) increase in resting energy expenditure (REE). Activity questionnaires showed a significant increase in high intensity recreational activities (6.5+/-1.5 vs 3.5+/-0.5 h physical activity/wk; p<0.01) in the home and a significant decrease in low intensity activities (7+/-2.0 vs 12+/-3.5 h TV viewing/wk; p<0.01). CONCLUSIONS: Vigorous supervised aerobic training in obese boys has beneficial effects on body composition, fitness and leisure time activities that are not apparent by measurement of changes in body weight alone.

Journal Article↗
PubMed2000

Coping skills training for youth with diabetes mellitus has long-lasting effects on metabolic control and quality of life.

OBJECTIVE: To determine whether initial effects on metabolic control and quality of life associated with a behavioral intervention combined with intensive diabetes management (IDM) can be sustained over 1 year in youth implementing intensive therapy regimens. STUDY DESIGN: Seventy-seven patients (43 females, 95% white) 12 to 20 years (mean = 14.2 +/- 1.9; duration, 8.7 +/- 3.9) electing to initiate IDM were randomly assigned to one of two groups: with or without coping skills training (CST), which consists of 6 small group sessions and monthly follow-up to help youth cope with their lives in the context of diabetes management; skills included social problem solving, cognitive behavior modification, and conflict resolution. Data were collected before the intervention and at 3, 6, and 12 months after the intervention by using the Self-Efficacy for Diabetes Scale, Children's Depression Inventory, Issues in Coping with IDDM, and the Diabetes Quality of Life: Youth scales. Clinical data (glycosylated hemoglobin level, height, weight, adverse effects) were collected monthly. RESULTS: The CST and IDM groups were comparable at baseline. CST subjects had lower glycosylated hemoglobin (P =.001) and better diabetes (P =.002) and medical (P =. 04) self-efficacy, and less impact of diabetes on their quality of life (P =.005) than youth receiving IDM alone after 1 year. In males, CST did not affect adverse outcomes of IDM hypoglycemia, diabetic ketoacidosis, and weight gain, but CST decreased the incidence of weight gain (P =.05) and hypoglycemia in females (P =.03). CONCLUSIONS: The addition of behavioral intervention to IDM in adolescence results in improved metabolic control and quality of life over 1 year.

Adaptation, Psychological↗
PubMed2000

Vacuum-assisted lancing of the forearm: an effective and less painful approach to blood glucose monitoring.

A vacuum-lancet device was applied to the forearm for the purpose of obtaining capillary blood samples for glucose monitoring with minimal pain. In four clinical trials, a total of 215 individuals aged 12-77 years were tested four times using standard conditions and four times with either a different depth of lancing, different brand of lancet or a larger-sized device. The volume of blood collected using one-half atmosphere of vacuum in 40 sec was measured. The sensation and visual appearance of each lancet puncture on the forearm was recorded. Glucose was measured in forearm and in conventional fingerstick blood samples. The distribution of volumes was skewed to higher values with median values for each trial in the range of 3-10 microL. Ninety-five percent of the lancet sticks were judged as less painful than a fingerstick. Redness and bruising around the lanced sites were noted in some patients but disappeared within a few days. Overall correlation of the forearm versus fingerstick glucose values was 0.96. The vacuum-lancet device was very successful in obtaining capillary blood samples for glucose testing in a relatively painless manner. Incorporation of a glucose measuring system into the device might improve testing compliance among those who fear pain or the sight of blood.

Adolescent↗
PubMed2000

Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity.

Insulin secretion rates are greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented beta-cell secretory response to an oral glucose load results from the release of mainly two gut hormones: gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1, which potentiate glucose-induced insulin secretion. Because of their insulinotropic action, their abnormal secretion may be involved in the pathogenesis of the hyperinsulinemia of childhood obesity. In this study, we used the hyperglycemic clamp with a small oral glucose load to assess the effect of childhood obesity on GIP response in seven prepubertal lean and 11 prepubertal obese children and in 14 lean adolescents and 10 obese adolescents. Plasma glucose was acutely raised to 11 mM by infusing i.v. glucose and kept at this concentration for 180 min. Each subject ingested oral glucose (30 g) at 120 min, and the glucose infusion was adjusted to maintain the plasma glucose plateau. Basal insulin and C-peptide concentrations and insulin secretion rates (calculated by the deconvolution method) were significantly greater in obese children compared with lean children (p < 0.001). Similarly, during the first 120 min of the clamp, insulin secretion rates were higher in obese than lean children. After oral glucose, plasma insulin, C-peptide, and insulin secretion rates further increased in all four groups. This incretin effect was 2-fold greater in obese versus lean adolescents (p < 0.001). Circulating plasma GIP concentrations were similar at baseline in all four groups and remained unchanged during the first 120 min of the clamp. After oral glucose, plasma GIP concentrations rose sharply in all groups (p < 0.002). Of note, the rise in GIP was similar in both lean and obese children. In conclusion, under conditions of stable hyperglycemia, the ingestion of a small amount of glucose elicited equivalent GIP responses in both lean and obese children. However, despite similar GIP responses, insulin secretion was markedly augmented in obese adolescents. Thus, in juvenile obesity, excessive alimentary beta-cell stimulation may be independent of the increased release of GIP.

Administration, Oral↗