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Biomedical subjects

H Peter Chase

Publications and source records attributed to H Peter Chase.

At least 19 recordsLinked to original sources
PubMed2007

Pre-type 1 diabetes dysmetabolism: maximal sensitivity achieved with both oral and intravenous glucose tolerance testing.

OBJECTIVE: To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and to identify an optimal testing strategy for detecting preclinical diabetes. STUDY DESIGN: Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) randomized subjects to oral (n = 372) and parenteral (n = 339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. RESULTS: Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of first phase insulin response (FPIR) at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline body mass index (BMI), FPIR, and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal FPIR and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs 73%). CONCLUSIONS: Most (97%) subjects had abnormal IVGTTs and/or OGTTs before the development of diabetes. The highest sensitivity is achieved using both tests.

Administration, Oral↗
PubMed2007

Increasing the accuracy of oral glucose tolerance testing and extending its application to individuals with normal glucose tolerance for the prediction of type 1 diabetes: the Diabetes Prevention Trial-Type 1.

OBJECTIVE: We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic patients). The maximum follow-up was 7.4 years. Analyses utilized receiver-operator curves (ROCs), proportional hazards models, and survival curves. RESULTS: ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 +/- 0.02) and an OGTT prediction index (0.78 +/- 0.02) were higher (P < 0.001) than those for the fasting (0.53 +/- 0.02) and 2-h glucose (0.66 +/- 0.02). ROCAUCs for the 60- and 90-min glucose (0.71 +/- 0.02 and 0.72 +/- 0.02, respectively) were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT prediction index ranging from 3.77 to 5.30 (P < 0.001 for all). CONCLUSIONS: Certain alternative OGTT indexes appear to better predict type 1 diabetes than standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients. Moreover, even among those with normal glucose tolerance, OGTTs are strongly predictive. This suggests that subtle metabolic abnormalities are present several years before the diagnosis of type 1 diabetes.

Area Under Curve↗
PubMed2006

Prevention strategies for type 1 diabetes.

Type 1 diabetes (T1D) is a common chronic disease of childhood. Patients with T1D are at significant risk for developing serious health complications. Understanding of the genetics, environmental factors, and natural history of diabetes has lead to greater understanding of the etiology and epidemiology of T1D. Furthermore, technology has greatly improved glycemic control and reduction of complications. However, prevention of the development of diabetes remains elusive. This review article describes the past, current and upcoming strategies for diabetes prevention for patients at risk for developing autoimmunity, after antibody production, and patients with new onset diabetes.

Autoimmunity↗
PubMed2006

Mixing rapid-acting insulin analogues with insulin glargine in children with type 1 diabetes mellitus.

OBJECTIVE: To determine whether mixing insulin glargine (IG) with a rapid-acting insulin (RAI) analogue in the same syringe had any deleterious effects on glycemic control in children with type 1 diabetes mellitus. STUDY DESIGN: Data from 55 children mixing the IG with a RAI analogue was collected for 6 months before and 6 months after the insulin mixing began. Data from a control group of 55 children not mixing the insulins was collected at similar intervals. Parameters evaluated included hemoglobin A1c (HbA1c) values, number of non-severe and severe hypoglycemic events, number of diabetic ketoacidosis (DKA) events, and blood glucose distribution patterns. RESULTS: After 6 months of study, HbA1c values were equivalent for the control and test groups (8.54+/-1.14 vs 8.61+/-1.14, respectively; P=1.0000). Percentages of blood glucose values in, above, and below the target range did not vary significantly in the groups. There were no significant differences in the groups in the occurrence of non-severe or severe hypoglycemic events or of DKA events. CONCLUSION: There were no significant differences in glycemic control between children who mixed IG in the same syringe with a RAI analogue compared with children who took separate injections.

Adolescent↗
PubMed2006

Bedside monitoring of blood beta-hydroxybutyrate levels in the management of diabetic ketoacidosis in children.

INTRODUCTION: Diabetic ketoacidosis (DKA) affects many children with type 1 diabetes. Insulin treatment of DKA is traditionally guided by changes in the blood glucose levels and blood gases, whereas beta-hydroxybutyrate (beta-OHB)--the main ketoacid causing acidosis--is rarely measured. The purpose of this study was to evaluate if bedside monitoring of blood beta-OHB levels can simplify management of DKA through elimination of superfluous laboratory monitoring. METHODS: Our emergency department treated 68 children with DKA using a standard protocol with monitoring of venous pH, partial pressure of CO(2) (pCO(2)), bicarbonate, glucose, blood urea nitrogen, and electrolytes (two to 10 time points per patient). Venous beta-OHB levels were measured using the Precision Xtra meter (MediSense/Abbott Diabetes Care, Abbott Park, IL) and, on duplicate batched serum samples, using a reference laboratory method (Cobas Mira Plus; Roche Diagnostics, Indianapolis, IN). Correlations between bedside meter beta-OHB and other parameters were evaluated in a series of general linear models with a time series covariance structure fit using spatial power law. RESULTS: The bedside meter beta-OHB levels were significantly correlated with pH (r = -0.63; P <0.0001), bicarbonate (r = -0.74; P <0.0001), and pCO(2) (r = -0.55; P <0.0001) at all points of measurement during the treatment (unadjusted Pearson correlations). The pH, bicarbonate, and pCO(2) were entered into separate time series analysis models with treatment duration as a measure of time. The results confirmed that bedside levels of beta-OHB correlated very closely with time-dependent levels of venous pH, bicarbonate, and pCO(2). Good agreement between the two methods of beta-OHB measurement (r = 0.92; P <0.0001) was confirmed using the Bland-Altman plot analysis. CONCLUSIONS: The Precision Xtra accurately measures blood beta-OHB levels, particularly at lower levels. While the initial measurement of pH and/or bicarbonates is warranted, real-time beta-OHB levels may replace repeat laboratory measurement of these parameters in the management of DKA. Future studies should evaluate safety and cost-effectiveness of such simplified DKA treatment protocol.

3-Hydroxybutyric Acid↗
PubMed2006

Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1.

OBJECTIVE: There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis. RESEARCH DESIGN AND METHODS: Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points. RESULTS: Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up. CONCLUSIONS: These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.

Area Under Curve↗
PubMed2006

The use of insulin pumps with meal bolus alarms in children with type 1 diabetes to improve glycemic control.

OBJECTIVE: The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH DESIGN AND METHODS: This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA(1c) (A1C) values > or =8.0%. Twenty-four subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus alarms (experimental group), while the other 24 subjects continued use of their current insulin pumps (control group) without meal bolus alarms. RESULTS: After 3 months of study, the number of missed meal boluses per week was significantly lower in the experimental group (from 4.9 +/- 3.7 to 2.5 +/- 2.5; P = 0.0005) but not significantly lower in the control group (from 4.3 +/- 2.7 to 4.2 +/- 3.9; P = 0.7610). Also after 3 months, the mean A1C value of the experimental group declined significantly (from 9.32 +/- 1.12 to 8.86 +/- 1.10; P = 0.0430). No significant decline in A1C was present for the control group (from 8.93 +/- 1.04 to 8.67 +/- 1.17; P = 0.1940). After 6 months of study, the significant decline in A1C from baseline in the experimental group was no longer present. Pooling of all available data from the control and experimental groups showed that at baseline and 3 and 6 months, the number of missed meal boluses per week was significantly correlated with A1C values. CONCLUSIONS: While meal bolus alarms may have the potential to improve suboptimal glycemic control in youth using CSII, our results demonstrated that these alarms had only a transient, modest effect in doing so.

Adolescent↗
PubMed2005

Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus.

OBJECTIVE: To examine the effect of exercise on overnight hypoglycemia in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: At 5 clinical sites, 50 subjects with T1DM (age 11 to 17 years) were studied in a clinical research center on 2 separate days. One day included an afternoon exercise session on a treadmill. On both days, frequently sampled blood glucose levels were measured at the DirecNet central laboratory. Insulin doses were similar on both days. RESULTS: During exercise, plasma glucose levels fell in almost all subjects; 11 (22%) developed hypoglycemia. Mean glucose level from 10 pm to 6 am was lower on the exercise day than on the sedentary day (131 vs 154 mg/dL; P=.003). Hypoglycemia developed overnight more often on the exercise nights than on the sedentary nights (P=.009), occurring on the exercise night only in 13 (26%), on the sedentary night only in 3 (6%), on both nights in 11 (22%), and on neither night in 23 (46%). Hypoglycemia was unusual on the sedentary night if the pre-bedtime snack glucose level was>130 mg/dL. CONCLUSIONS: These findings indicate that overnight hypoglycemia after exercise is common in children with T1DM and support the importance of modifying diabetes management after afternoon exercise to reduce the risk of hypoglycemia.

Adolescent↗
PubMed2005

Accuracy of newer-generation home blood glucose meters in a Diabetes Research in Children Network (DirecNet) inpatient exercise study.

BACKGROUND: The objective of this study was to assess how the accuracy of the FreeStyle Flash (Abbott Diabetes Care, Alameda, CA) meter compares with that of the One Touch Ultra (Lifescan, Milpitas, CA) home glucose meter (HGM). RESEARCH DESIGN AND METHODS: Fifty children with type 1 diabetes (T1D), 10-17 years old, were admitted for two separate 24-h periods to assess the effect of exercise on subsequent nocturnal hypoglycemia. Resulting data were used in a preplanned analysis of the accuracy of the Ultra and FreeStyle HGMs. Glucose levels were measured throughout the day and night and every 15-20 min during a standardized exercise protocol. Reference samples were assayed in a central laboratory using a hexokinase enzymatic method. These reference glucose measurements were paired with HGM values from venous blood obtained within +/- 5 min. RESULTS: The median relative absolute difference was 5% for both the Ultra and FreeStyle HGMs, and the percentages of pairs meeting the International Organisation for Standardization criteria were 99% and 98%, respectively. The FreeStyle tended to read slightly higher than the reference method (median difference = +3 mg/dL; P < 0.001), and there was trend in this direction for the Ultra (median difference = +2 mg/dL, P = 0.15). Sensitivities for detection of hypoglycemia (reference < or = 60 and HGM < or = 70 mg/dL) were 96% and 100% for the Ultra and FreeStyle, respectively, and corresponding false-positive rates were both 5%. CONCLUSIONS: In a controlled clinical setting using venous blood samples, both the Ultra and FreeStyle meters demonstrated a high degree of accuracy compared with the laboratory reference over a broad range of glucose concentrations in children with T1D.

Adolescent↗
PubMed2005

Use of insulin glargine in children under age 6 with type 1 diabetes.

AIM: Children under 6 yr have the highest incidence of severe hypoglycemia (SH) and the greatest likelihood of brain damage from SH. The purpose of this study is to evaluate the use of insulin glargine (Lantus in children under age 6 with type 1 diabetes (T1D). METHODS: The electronic medical records were reviewed for patients under age 6 during the first 6 months of insulin glargine therapy and compared with age, sex, and duration of diabetes for matched control patients on neutral protamine Hagedorn (NPH) insulin. Data from 128 subjects (32 male pairs and 32 female pairs) were collected relating to the incidence of severe and non-severe hypoglycemic events, hemoglobin A1c (HbA1c) values, body mass index (BMI), and daily insulin dose. Additionally, parents were asked to complete a diabetes Quality of Life (QoL) survey. RESULTS: In the 6 months before the study period, the glargine group had 16 SH events compared with three in the 6 months post-glargine. The comparison (NPH) group had seven and six SH events in their respective 6-month periods. Nighttime SH events in the glargine group decreased from 12 prestudy events to one during the study period. The average daily insulin dose in the glargine group was higher than that in the NPH group (0.8+/- 0.2 vs. 0.7+/- 0.2 U/kg/day; p=0.03). The HbA1c values, BMI, and QoL responses were not significantly different between the two groups. CONCLUSIONS: SH was decreased, particularly at night (from 12 episodes to one), after the introduction of glargine in young children with T1D.

Body Mass Index↗
PubMed2005

Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1.

OBJECTIVE: This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes. RESEARCH DESIGN AND METHODS: We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483 were antibody positive; 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes; 388 had a 5-year risk projection of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed every 6 months. The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. RESULTS: Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015). CONCLUSIONS: It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes. Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels.

Administration, Oral↗
PubMed2005

A randomized multicenter trial comparing the GlucoWatch Biographer with standard glucose monitoring in children with type 1 diabetes.

OBJECTIVE: This study assesses whether use of the GlucoWatch G2 Biographer (GW2B) in addition to standard glucose monitoring lowers HbA(1c) and reduces hypoglycemia compared with standard glucose monitoring alone. RESEARCH DESIGN AND METHODS: In all, 200 subjects aged 7 to <18 years with type 1 diabetes were randomly assigned at five centers to standard glucose monitoring (usual care) or standard glucose monitoring plus GW2B use for 6 months. Study outcomes included HbA(1c) values obtained at 6 months and occurrence of severe hypoglycemia. RESULTS: The mean HbA(1c) at baseline was 8.0% in both groups; at 6 months, HbA(1c) was 7.9% in the usual care group and 8.1% in the GW2B group (95% CI for mean reduction in the GW2B group compared with the usual care group -0.4 to 0.1%; P = 0.15). A decrease in HbA(1c) of > or =0.5% was achieved in 21% of the usual care group and 28% of the GW2B group (P = 0.29). Severe hypoglycemia events occurred in 7% of the GW2B group and in 2% of the usual care group (P = 0.10). In the GW2B group, sensor use declined throughout the study from a mean value of 2.1 times/week in the 1st month to 1.5 times/week in the 6th month. Reasons given for declining use included skin irritation (76%), frequent skips (56%), excessive alarms (47%), and inaccurate readings (33%). CONCLUSIONS: Use of the GW2B in addition to standard glucose monitoring did not improve glycemic control or reduce the frequency of severe hypoglycemia. Skin reactions and other problems led to decreasing sensor use over time.

Adolescent↗
PubMed2004

Continuous glucose monitoring in type 1 diabetes.

Continuous glucose monitoring is becoming increasingly more widespread for the routine care of people with type 1 diabetes mellitus and may eventually be used in closed-loop artificial beta-cell systems. The current "state of the art" of this technology, including accuracy, performance in clinical trials, limitations, and recommendations for use, is discussed for the two currently approved continuous glucose monitoring devices.

Blood Glucose↗
PubMed2004

Improved glycemic control without an increase in severe hypoglycemic episodes in intensively treated patients with type 1 diabetes receiving morning, evening, or split dose insulin glargine.

OBJECTIVE: To see if insulin glargine improves glycemic control in a clinical setting. RESEARCH DESIGN AND METHODS: A questionnaire and electronic database were used to assess glycemic parameters for 292 type 1 diabetic subjects taking > or =4 injections per day and receiving glargine as their only long-acting basal insulin for at least 6 months. Sixty-three subjects were taking glargine in the morning, 125 were taking glargine in the evening, and 104 were splitting the glargine dose between the morning and evening. RESULTS: The mean (+/-S.D.) age and duration of diabetes were 32 +/- 10 years and 15.9 +/- 10.3 years, respectively. The mean (+/-S.E.M.) durations of treatment with glargine were 13.1 +/- 0.6 months, 12.2 +.- 0.4 months, and 14.3 +/- 0.5 months for the morning, evening, and split treatment groups, respectively (P < 0.01). The A1C values improved significantly from baseline for the evening and the split dosage groups or when all groups were combined. The mean basal insulin dose was significantly reduced at the end of the study in all the three groups from baseline with no change in the short-acting insulin dose. The number of severe hypoglycemic episodes decreased from 379 in the year prior to glargine treatment to 167 in the post-glargine year. The weight gain was significantly higher in the group that took the split glargine dose (P < 0.01). CONCLUSIONS: Similar or improved glycemic control was achieved by administering glargine in the morning, evening, or using a split dose without any further increase in severe hypoglycemic episodes. Splitting the glargine dose did not offer any advantages in glycemic control parameters.

Adult↗