bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Trends in Hospitalization for Diabetic Ketoacidosis in Ontario Children
Authors: Curtis Jacqueline R. , To Teresa , Muirhead Sarah , Cummings Elizabeth , Daneman Denis 
Published: March 2007

OBJECTIVE—To investigate trends and geographic variation in diabetic ketoacidosis (DKA) hospitalization rates among children in Ontario from 1991 to 1999.
RESEARCH DESIGN AND METHODS—Canadian Institute for Health Information (CIHI) data were used to identify 15,872 diabetes-related hospital admissions in children younger than 19 years in Ontario from 1991 to 1999. Of these, 5,008 admissions were because of DKA and 10,864 admissions were because of conditions other than DKA (non-DKA). Small area variation analysis was used to compare areas with high versus low DKA admission rates.
RESULTS—There was a 19% relative decrease in the overall diabetes admission rate over the study period. Non-DKA admissions decreased by 29%, whereas DKA admissions remained stable. Total days of care decreased by 393 days per year for non-DKA admissions and by 99 days per year for DKA admissions. The average length of hospital stay decreased from 4.9 to 3.5 days for non-DKA admissions and from 4.5 to 3.2 days for DKA admissions. The fatality rate was 0.19% for non-DKA admissions and 0.18% for DKA admissions. Variation across geographic areas remained stable for DKA over the study period (Kendall’s correlation coefficient 0.64, P = 0.017) with an average 3.7-fold difference between the lowest and highest regions.
CONCLUSIONS—Increased ambulatory care efforts for children with type 1 diabetes in Ontario have successfully reduced non-DKA admission rates. However, DKA admission rates have remained stable. Geographic variation for DKA admissions is low, but the observed 3.7-fold difference is clinically important for a preventable complication with a significant potential for long-term morbidity and mortality. Prevention strategies are needed, particularly in areas identified with the highest rates.
Intravenous Glargine and Regular Insulin Have Similar Effects on Endogenous Glucose Output and Peripheral Activation/Deactivation Kinetic Profiles
Authors: Mudaliar Sunder , Mohideen Pharis , Deutsch Reena , Ciaraldi Theodore P. , Armstrong Debra , Kim Bo , Sha Xue , Henry Robert R. 
Published: March 2007

OBJECTIVE—To compare the effects of intravenously administered long-acting insulin analog glargine and regular human insulin on activation and deactivation of endogenous glucose output (EGO) and peripheral glucose uptake.
RESEARCH DESIGN AND METHODS—In this single-center, randomized, double-blind, crossover euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 ± 4 years, BMI 24.2 ± 0.7 kg/m2 [mean ± SE]) received a primed continuous intravenous infusion of 40 mU/m2 of insulin glargine or regular human insulin on 2 different study days in a randomized order. Euglycemia was maintained at 90 mg/dl using a simultaneous variable intravenous infusion of 20% dextrose containing d-[3-3H]glucose. EGO and peripheral glucose disposal kinetics were determined during a 4-h insulin infusion activation period and a 3-h deactivation period.
RESULTS—The results demonstrated no significant difference in activation or deactivation kinetics with respect to EGO and peripheral glucose disposal between insulin glargine and regular human insulin when given intravenously. The mean ± SE time required for 50% suppression of EGO after insulin infusion was 73 ± 23 min for regular insulin and 57 ± 20 min for insulin glargine (NS). The mean maximum rate of glucose disposal was 10.10 ± 0.77 and 9.90 ± 0.85 mg · kg−1 · min−1 for regular insulin and insulin glargine, respectively (NS). The mean time required for 50% suppression of incremental glucose disposal rate (GDR), defined as the time required for activation from the basal glucose disappearance rate (Rd) to half-maximum insulin-stimulated Rd, was 32 ± 5 and 42 ± 10 min for regular insulin and insulin glargine, respectively (NS). The time required for deactivation from maximum insulin-stimulated GDR to half-maximum GDR after cessation of insulin infusion was 63 ± 5 and 57 ± 4 min for regular insulin and insulin glargine, respectively (NS).
CONCLUSIONS—Activation and deactivation kinetics of EGO and peripheral glucose uptake as well as absolute disposal rate are similar between regular human insulin and insulin glargine when administered intravenously. Thus, the various biological actions of these insulin preparations when given subcutaneously are completely due to their different absorption kinetics.
Unique Effect of Visceral Fat on Insulin Sensitivity in Obese Hispanic Children With a Family History of Type 2 Diabetes
Authors: Cruz Martha L. , Bergman Richard N. , Goran Michael I. 
Published: March 2007

OBJECTIVE—This study aimed to establish whether total fat or central fat was related to measures of insulin in obese Hispanic children with a family history of type 2 diabetes.
RESEARCH DESIGN AND METHODS—Subjects were 32 children aged 8–13 years. Visceral fat and subcutaneous abdominal fat were determined by magnetic resonance imaging at the umbilicus and total body fat was determined by dual-energy X-ray absorptiometry. Insulin sensitivity (Si) and acute insulin response (AIR) were determined by frequently sampled intravenous tolerance test with minimal modeling.
RESULTS—Mean fasting glucose and insulin, Si, and AIR (± SD) were 5.3 ± 0.3 mmol/l, 206 ± 105 pmol/l, 11.8 ± 5.7 [× 10−4 min−1/(pmol/l)], and 17,175 ± 9,695 (pmol/l × 10 min), respectively. In multivariate regression analysis, total fat mass was independently and positively related to fasting insulin (P &lt; 0.01) and negatively related to Si (P &lt; 0.05) but was not related to AIR. Visceral fat was independently and positively related to fasting insulin (P &lt; 0.05) and AIR (P &lt; 0.01) and negatively related to Si (P &lt; 0.001).
CONCLUSIONS—These findings support the hypothesis that specific accumulation of visceral fat in addition to overall adiposity in Hispanic children increases the risk of type 2 diabetes.
Metformin as an Adjunct Therapy in Adolescents With Type 1 Diabetes and Insulin Resistance
Authors: Hamilton Jill , Cummings Elizabeth , Zdravkovic Vera , Finegood Diane , Daneman Denis 
Published: March 2007

OBJECTIVE—To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.
RESEARCH DESIGN AND METHODS—This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (&gt;1 unit · kg−1 · day−1), and HbA1c &gt;8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment.
RESULTS—At t = 0, HbA1c was 9.2 ± 0.9%, insulin dosage was 1.2 ± 0.2 units · kg−1 · day−1, fasting glucose was 10.6 ± 2.4 mmol/l, and BMI was 24.2 ± 3.9 kg/m2 (means ± SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P &lt; 0.05). This was achieved at lower daily insulin dosages (metformin group –0.14 ± 0.1 vs. placebo group 0.02 ± 0.2 units · kg−1 · day−1; P &lt; 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P &lt; 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 ± 0.8 vs. 0.9 ± 0.4 events · patient−1 · week−1; P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups.
CONCLUSIONS—Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.
The Relationship Between Dysglycemia and Atherosclerosis in South Asian, Chinese, and European Individuals in Canada
Authors: Gerstein Hertzel C. , Anand Sonia , Yi Qi Long , Vuksan Vladimir , Lonn Eva , Teo Koon , Malmberg Klas , McQueen Matthew , Yusuf Salim ,   For the SHARE Investigators*
Published: March 2007

OBJECTIVE—Raised glucose levels extending from normal into the diabetic range (dysglycemia) are an emerging risk factor for clinical cardiovascular events. The relationship between dysglycemia and atherosclerosis (AS) in the general population and in different ethnic groups remains controversial.
RESEARCH DESIGN AND METHODS—Glucose tolerance, HbA1c, other metabolic risk factors for AS, and carotid mean maximal intimal media thickness were assessed in a random sample of 979 Canadians of South Asian, Chinese, and European descent.
RESULTS—The age and sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase in HbA1c in all participants (P &lt; 0.0001) and in those of South Asian (P = 0.018), Chinese (P = 0.002), and European (P &lt; 0.0001) descent. This progressive curvilinear relationship was most apparent at HbA1c levels &gt;5.7%. The HbA1c-AS relationship persisted after adjustment for ethnicity, age, sex, diabetes status, abdominal obesity, insulin resistance, insulin secretion, fasting free fatty acids, blood pressure, and/or dyslipidemia (P &lt; 0.004). Both diabetes (P = 0.002) and HbA1c (P &lt; 0.0001) were determinants of the intimal medial thickness when included in separate statistical models. When included together in a single model, HbA1c (P &lt; 0.0001) but not diabetes (P = 0.6) was a significant determinant.
CONCLUSIONS—The degree of AS is related to the level of HbA1c irrespective of diabetes status and independent of abdominal obesity and other markers of the metabolic syndrome. This progressive relationship between HbA1c and AS was observed within different ethnic groups.
Optimal Dose of Candesartan for Renoprotection in Type 2 Diabetic Patients With Nephropathy
Authors: Rossing Kasper , Christensen Per K. , Hansen Birgitte V. , Carstensen Bendix , Parving Hans-Henrik 
Published: March 2007

OBJECTIVE—We evaluated the optimal dose of the angiotensin II receptor antagonist candesartan cilexetil for renoprotection as reflected by short-term changes in albuminuria in hypertensive type 2 diabetic patients with nephropathy.
RESEARCH DESIGN AND METHODS—A total of 23 hypertensive patients with type 2 diabetes and nephropathy were enrolled in this double-blind randomized cross-over trial with four treatment periods, each lasting 2 months. Each patient received placebo and candesartan: 8, 16, and 32 mg daily in random order. Antihypertensive medication was discontinued before enrollment, except for long-acting furosemide, which all patients received throughout the study in median (range) doses of 40 (30–160) mg daily. End points were albuminuria (turbidimetry), 24-h blood pressure (BP) (Takeda-TM2420), and glomerular filtration rate (GFR) (51Cr-labeled EDTA plasma clearance technique).
RESULTS—Values obtained during placebo treatment: albuminuria [geometric mean (95% CI)] 700 (486–1,007) mg/24-h, 24-h BP (mean ± SE) 147 ± 4/78 ± 2 mmHg, and GFR 84 ± 6 ml/min/1.73 m2. All three doses of candesartan significantly reduced albuminuria and 24-h BP compared with placebo. Mean (95% CI) reductions in albuminuria were 33% (21–43), 59% (52–65), and 52% (44–59) with increasing doses of candesartan. Albuminuria was reduced significantly more by the two highest doses than by the lowest dose (P &lt; 0.01); 24-h systolic BP was reduced by 9 (2–16), 9 (2–16), and 13 (6–20) mmHg and 24-h diastolic BP was reduced by 5 (2–8), 4 (1–7), and 6 (3–9) mmHg with increasing doses of candesartan. There were no significant differences in the reductions in BP between the three doses. GFR was decreased by ∼6 ml/min/1.73 m2 by all three doses of candesartan (P &lt; 0.05 versus placebo).
CONCLUSIONS—The optimal dose of candesartan is 16 mg daily for renoprotection, as reflected by short-term reduction in albuminuria, in hypertensive type 2 diabetic patients with nephropathy.
Progression of Lower-Extremity Disability in Older Women With Diabetes
Authors: Volpato Stefano , Ferrucci Luigi , Blaum Caroline , Ostir Glenn , Cappola Anne , Fried Linda P. , Fellin Renato , Guralnik Jack M. 
Published: March 2007

OBJECTIVE—Older patients with diabetes are more likely to have a higher prevalence of multiple risk factors for physical disability, as a result of diabetic complications. We evaluated the pace of decline in lower-extremity function and the risk for progression of disability in older women with diabetes.
RESEARCH DESIGN AND METHODS—We conducted a 3-year longitudinal cohort study of a random sample of 729 physically impaired older women (age ≥65 years) living in the community (Baltimore, MD). Diabetes was ascertained by standard criteria. Self-reported functional status and objective performance measures were assessed at baseline and over six semiannual follow-up visits.
RESULTS—The baseline prevalence of diabetes was 14.4%. After adjustment for age and compared with women without diabetes, those with diabetes had an RR of 1.8 (95% CI 1.3–2.5) for incident mobility disability and 1.6 (1.2–2.1) for incident activity of daily living disability. The increased incidence of new disability associated with diabetes was paralleled by a greater decline in objective measures of lower-extremity function. Adjustment for multiple risk factors for disability did not significantly attenuate the risk for disability associated with diabetes.
CONCLUSIONS—In older patients, impaired lower-extremity function is a long-term diabetic complication. Comprehensive assessment of older diabetic patients should include a standardized evaluation of lower-extremity performance.
Low Insulin Sensitivity (Si = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study
Authors: Haffner Steven M. , D’Agostino Ralph , Festa Andreas , Bergman Richard N. , Mykkänen Leena , Karter Andrew , Saad Mohammed F. , Wagenknecht Lynne E. 
Published: March 2007

OBJECTIVE—To determine the meaning of Si = 0 derived from the frequently sampled intravenous glucose tolerance test.
RESEARCH DESIGN AND METHODS—The issue of assessing insulin resistance in large studies is important because the most definitive method (“gold standard”), the hyperinsulinemic-euglycemic clamp, is expensive and invasive. The frequently sampled intravenous glucose tolerance test (FSIGTT) has been widely used, but in insulin-resistant subjects (especially diabetic subjects), it yields considerable numbers of subjects whose Si is zero. The interpretation of an Si equaling zero is unknown.
RESULTS—To address this issue, we examined 1,482 subjects from the Insulin Resistance Atherosclerosis Study (IRAS) using an insulin-modified FSIGTT and minimal model calculation of Si. The proportion of insulin-resistant subjects (Si &lt; 1.61 × 10−4 [min−1 · μU−1 · ml−1] based on the median of the nondiabetic population) was 38.6% in subjects with normal glucose tolerance (NGT), 74% in subjects with impaired glucose tolerance (IGT), and 92% in subjects with type 2 diabetes. The proportion of subjects with Si = 0 was 2.2% in subjects with NGT, 13.2% in subjects with IGT, and 35.7% in subjects with type 2 diabetes. In subjects with IGT, those with Si = 0 had significantly lower HDL cholesterol levels and higher BMI, waist circumference, fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), C-reactive protein (CRP), and 2-h insulin levels than insulin-resistant subjects with Si &gt; 0. In type 2 diabetes, subjects with Si = 0 had significantly greater BMI and waist circumference and higher triglyceride, PAI-1, CRP, fibrinogen, and fasting and 2-h insulin levels than insulin-resistant subjects with Si &gt; 0. In addition, diabetic subjects with Si = 0 had more metabolic disorders related to the insulin resistance syndrome than diabetic insulin-resistant subjects with Si &gt; 0.
CONCLUSIONS—We found very few subjects with Si = 0 among subjects with NGT and few subjects with Si = 0 among subjects with IGT. In contrast, Si = 0 was common in subjects with diabetes. Subjects with Si = 0 tended to have more features of the insulin resistance syndrome than other insulin-resistant subjects with Si &gt; 0, as would be expected of subjects with almost no insulin-mediated glucose disposal, thus suggesting that subjects with Si = 0 are correctly classified as being very insulin resistant rather than having failed the minimal model program.
Estrogen Therapy and Risk of Cardiovascular Events Among Women With Type 2 Diabetes
Authors: Newton Katherine M. , LaCroix Andrea Z. , Heckbert Susan R. , Abraham Linn , McCulloch David , Barlow William 
Published: March 2007

OBJECTIVE—To evaluate the association between estrogen therapy and cardiovascular disease risk among women with type 2 diabetes.
RESEARCH DESIGN AND METHODS—A retrospective, case-cohort study was conducted among 6,017 women aged 45–80 years with type 2 diabetes from 1 January 1986 to 31 December 1992 at the Group Health Cooperative in Washington state. Cardiovascular outcomes, including nonfatal myocardial infarction (n = 215), coronary revascularization (n = 253), and cardiovascular deaths (n = 229), were ascertained through 31 December 1998. Use of estrogen and progestin was derived from automated pharmacy records and modeled as a time-dependent variable. Median follow-up was 6.8 years. Multivariable-adjusted relative risk (RR) and 95% CI were calculated using Cox proportional hazard models for case-cohort analyses.
RESULTS—Current use of estrogen with (RR 0.43, 95% CI 0.22–0.85) or without (0.48, 0.30–0.78) progestin was associated with a decreased risk of cardiovascular events compared with never having used estrogen. Risk of cardiovascular events associated with a first episode of estrogen use (with or without progestin) of &lt;25 months’ duration (1.12, 0.49–2.54), first episode of use ≥25 months’ duration (0.32, 0.06–1.70), and current use that was not the first episode of use (0.42, 0.42–0.67) indicated that recent initiation was not associated with an increase or decrease in risk.
CONCLUSIONS—These results show an association of estrogen therapy, with or without progestin, with decreased risk of cardiovascular events among women with type 2 diabetes. This association should be further investigated in large randomized, controlled trials.
Effects of 3 Months of Continuous Subcutaneous Administration of Glucagon-Like Peptide 1 in Elderly Patients With Type 2 Diabetes
Authors: Meneilly Graydon S. , Greig Nigel , Tildesley Hugh , Habener Joel F. , Egan Josephine M. , Elahi Dariush 
Published: March 2007

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an insulinotropic gut hormone that, when given exogenously, may be a useful agent in the treatment of type 2 diabetes. We conducted a 3-month trial to determine the efficacy and safety of GLP-1 in elderly diabetic patients.
RESEARCH DESIGN AND METHODS—A total of 16 patients with type 2 diabetes who were being treated with oral hypoglycemic agents were enrolled. Eight patients (aged 75 ± 2 years, BMI 27 ± 1 kg/m2) remained on usual glucose-lowering therapy and eight patients (aged 73 ± 1 years, BMI 27 ± 1 kg/m2), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol · kg−1 · h−1. Patients recorded their capillary blood glucose (CBG) levels (four times per day, 3 days per week) and whenever they perceived hypoglycemic symptoms. The primary end points were HbA1c and CBG determinations. Additionally, changes in β-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined.
RESULTS—HbA1c levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of ≤3.6 mmol/l during the study, and only 1 such measurement (3.5 mmol/l) was recorded in the GLP-1 group. Infusion of GLP-1 enhanced glucose-induced insulin secretion (pre: 119 ± 21; post: 202 ± 51 pmol/l; P &lt; 0.05) and insulin-mediated glucose disposal (pre: 29.8 ± 3.3; post: 35.9 ± 2.3 μmol · kg−1 · min−1; P &lt; 0.01). No effect of GLP-1 treatment was seen on the fasting plasma ghrelin levels. Although plasma ghrelin levels decreased during both portions of the clamp, a drug effect was not present.
CONCLUSIONS—A GLP-1 compound is a promising therapeutic option for elderly diabetic patients.
Characterization of GLP-1 Effects on β-Cell Function After Meal Ingestion in Humans
Authors: Ahrén Bo , Holst Jens J. , Mari Andrea 
Published: March 2007

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known.
RESEARCH DESIGN AND METHODS—Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m2) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg–1 · min–1), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data).
RESULTS—GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m2 with GLP-1 versus 21.0 ± 1.6 nmol/m2 with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min−1 · m2 · mmol−1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P &lt; 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI.
CONCLUSIONS—Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.