bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for a Role for Insulin and Growth Hormone in Overnight Regulation of 3-Hydroxybutyrate in Normal and Diabetic Adolescents
Authors: Edge Julie A , Harris Dorothy A , Phillips Paula E , Pal B Rani , Matthews David R , Dunger David B 
Published: March 2007

Objective— To determine the relative effects of growth hormone and insulin on ketogenesis during puberty.
Research Design and Methods— We studied overnight changes in plasma ketones—3-hydroxybutyrate and acetoacetate—in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release.
Results— Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 ± 5 μM), reaching a peak at 0200 (103 ± 16 μM, P &lt; 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = −0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate.
Conclusions— We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis.
Seven Years of Remission in a Type I Diabetic Patient: Influence of cyclosporin and regular exercise
Authors: Koivisto Veikko A , Leirisalo-Repo Marjatta , Ebeling Pertti , Tuominen Juha A , Knip Mikael , Turunen Ulla , Mandrup-Poulsen Thomas , Pelkonen Risto 
Published: March 2007

Objective— To analyze factors contributing to a long-term remission in a patient with type I diabetes.
Research Design and Methods— The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and β-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects.
Results— Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr.
Conclusions— In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.
Glycemic Actions of Alanine and Terbutaline in IDDM
Authors: Wiethop Brian V , Cryer Philip E 
Published: March 2007

OBJECTIVE
To test the hypothesis that the amino acid Ala and the beta 2-adrenergic agonist terbutaline raise plasma glucose concentrations substantially, and do so through different mechanisms, in IDDM patients.

RESEARCH DESIGN AND METHODS
We administered these (Ala: 20 and 40 g, orally; terbutaline: 2.5 and 5.0 mg orally and 0.25 mg subcutaneously) and placebos in random sequence to 6 nondiabetic subjects and 6 insulin-infused, initially euglycemic IDDM patients, each studied on six different occasions. Inhaled terbutaline, 0.4 mg, was also tested on a seventh occasion in IDDM patients.

RESULTS
Ala administration raised plasma glucagon (P = 0.0219), C-peptide (P = 0.0014), and insulin (P = 0.0094), with no significant change in plasma glucose, in nondiabetic subjects. In patients with IDDM it raised glucagon (P = 0.0001), but not C-peptide or insulin, and plasma glucose rose to 8.3 ± 0.3 (Ala 20 g, P = 0.0006) and 10.0 ± 1.0 mM (Ala 40 g, P = 0.0094). Catecholamine levels were unchanged. Terbutaline ingestion raised plasma glucose minimally (e.g., to 6.3 ± 0.3 mM, P = 0.0133) in nondiabetic subjects but substantially, to 10.2 ± 1.0 (terbutaline 2.5 mg, P = 0.0078) and 14.0 ± 0.6 mM (terbutaline 5.0 mg, P = 0.0001), in IDDM patients; subcutaneous terbutaline raised plasma glucose (to a peak of 10.3 ± 0.7 mM, P = 0.0017) with an initial effect within 10 min, but inhaled terbutaline did so more slowly. In addition to its direct glycemic actions, terbutaline stimulated sympathetic neural norepinephrine release (P = 0.0151) and increased nonesterified fatty acid levels (P = 0.0104), potential indirect glycemic actions. Glucagon levels were unchanged; insulin levels increased in the nondiabetic subjects.

CONCLUSIONS
These data demonstrate substantial glycemic responses to Ala and terbutaline, through different mechanisms, in IDDM patients. Thus, Ala and terbutaline represent potential new approaches to the treatment, and perhaps the prevention, of iatrogenic hypoglycemia in IDDM.
Prevalence of Depression in Adults With Diabetes: An epidemiological evaluation
Authors: Gavard Jeffrey A , Lustman Patrick J , Clouse Ray E 
Published: March 2007

OBJECTIVE
To determine the prevalence of depression in adult diabetic populations through a comprehensive literature review and to critically evaluate the methods and findings of such studies from an epidemiological perspective.

RESEARCH DESIGN AND METHODS
A systematic review of the scientific literature revealed a total of 20 studies, 14 of which had been conducted since 1988. Nine of the studies were controlled investigations, whereas the remaining 11 studies did not contain comparison groups. The studies included both treatment and community samples.

RESULTS
The range of the prevalence of current depression obtained from structured diagnostic interviews in diabetic samples was 8.5–27.3% ( = 14.0%) in controlled studies and 11.0–19.9% ( = 15.4%) in uncontrolled studies. These rates are at least three times the prevalence of major depressive disorder found in the general adult population of the U.S. Investigations using depression symptom scales corroborated these findings, as the range of clinically significant depression symptomatology in diabetic samples was 21.8–60.0% ( = 32.4%) in controlled studies and 10.0–28.0% ( = 19.6%) in uncontrolled studies.

CONCLUSIONS
An increased prevalence of depression in diabetes relative to the general population is highly suggested by the literature, but biases and methodological problems commonly encountered in prevalence studies may interfere with the strength of this conclusion. An increased prevalence of depression in diabetes relative to other somatic illnesses remains unproven. The pervasive impact of depression on quality of life and its potential negative effect on diabetes management warrant recognition and treatment of the affective disorder in diabetic individuals.
Effectiveness, Safety, and Acceptability of a Copper Intrauterine Device (CU Safe 300) in Type I Diabetic Women
Authors: Kimmerle Renate , Weiss Reinhard , Berger Michael , Kurz Karl-Heinz 
Published: March 2007

Objective— To evaluate the long-term effectiveness and safety of a copper intrauterine device fulfilling modern standards in type I diabetic women compared with nondiabetic women.
Research Design and Methods— Type I diabetic women (n = 59, age 27 ± 5 yr, duration of diabetes 12 ± 8 yr, HbA1c 7.0 ± 1.2%, 78% nulliparous women) were prospectively evaluated at 3, 6, 12, 24, and 36 mo by a gynecological exam and a standardized questionnaire after insertion of the intrauterine device (CU Safe 300, 300 mm2 of copper). A group of nondiabetic women (n = 1150) of comparable age and parity evaluated according to the same study protocol served as a control group.
Results— In the diabetic women (1754 cumulative months of use), events leading to termination of the intrauterine device during the 1st yr (691 women-mo) were one accidental pregnancy, one expulsion, one removal for pain, two removals for bleeding, and one removal for planned pregnancy. Events during the 2nd (593 women-mo) and 3rd yr (470 women-mo) were zero and one accidental pregnancy., one and two removals for bleeding, one and one removal for pain, one and one removal for other medical reasons, and two and two removals for planned pregnancy, respectively. No case of pelvic inflammatory disease was diagnosed in the diabetic group, and one case was diagnosed in the nondiabetic group (28,369 mo of cumulative use). Events leading to termination of the intrauterine device per women observed per year and continuation with the intrauterine device after each year of use were comparable in the diabetic and nondiabetic groups for the 1st, 2nd, and 3rd yr.
Conclusions— These results, although preliminary because &lt; 100 diabetic women were studied, indicate that the intrauterine device CU Safe 300 is as effective, safe, and well-tolerated in diabetic as in nondiabetic women. Specific objections to the use of intrauterine devices in type I diabetic women do not seem to be justified for modern, copper-mediated models.
Administration of Sulfonylureas Can Increase Glucose-Induced Insulin Secretion for Decades in Patients With Maturity-Onset Diabetes of the Young
Authors: Fajans Stefan S , Brown Morton B 
Published: March 2007

Objective— To ascertain whether the effect of sulfonylureas on glucose-mediated insulin release persists for years to decades in patients with maturity-onset diabetes of the young.
Research Design and Methods— The effect of sulfonylurea treatment on glucose-induced insulin secretion was ascertained prospectively for up to 33 yr in 12 diabetic patients of the maturity-onset diabetes of the young RW pedigree, who are genetically homogeneous because they share DNA markers on chromosome 20q. In 7 of these patients, paired glucose tolerance tests, given while the patients were on and off sulfonylureas, were performed after 7–31 yr.
Results— Glucose-induced insulin secretion showed an average increase of 68% in diabetic patients who remained responsive to chlorpropamide after having been on and off the drug for decades. In most patients, however, glucose-induced insulin secretion declines over time (1–4%/yr). Some patients become unresponsive to sulfonylureas after 3–25 yr and then have very small or no increases in glucose-induced insulin secretion and require treatment with insulin to normalize fasting hyperglycemia.
Conclusions— Increase in glucose-induced insulin secretion remains the most important mechanism of the action of sulfonylureas during long-term administration.
Differences in the Prevalence of Diabetes and Impaired Glucose Tolerance According to Maternal or Paternal History of Diabetes
Authors: Mitchell Braxton D , Valdez Rodolfo , Hazuda Helen P , Haffner Steven M , Monterrosa Ana , Stern Michael P 
Published: March 2007

Objective— To determine whether diabetes risk is influenced by which parent (a parental history of diabetes is a well-documented risk factor for NIDDM) is reported to have diabetes.
Research Design and Methods— We compared the prevalence of NIDDM and IGT for 4914 subjects according to their parental history of diabetes (mother only, father only, both parents, neither parent). Subjects were drawn from the San Antonio Heart Study, a population-based survey of diabetes and cardiovascular risk factors conducted in Mexican American and non-Hispanic white individuals between 1979–1988.
Results— Men with a parental history of diabetes had a higher prevalence of both NIDDM and impaired glucose tolerance than men reporting no parental history of diabetes. Prevalence was equally high regardless of which parent, or whether both parents, had diabetes. In contrast, in women, only a maternal history of diabetes was associated with a higher prevalence of NIDDM and impaired glucose tolerance. Virtually no difference in NIDDM prevalence was found between women with a paternal-only history of diabetes and women with no parental history of diabetes.
Conclusions— Results differed markedly between men and women. The reason for this sex difference is unclear. It may represent a measurement bias, a sex-specific environmental effect, or a genetic effect that is expressed or transmitted differently between the sexes.
Cow's Milk Exposure and Type I Diabetes Mellitus: A critical overview of the clinical literature
Authors: Gerstein Hertzel C 
Published: March 2007

OBJECTIVE
To critically review and summarize the clinical evidence relating a short duration of breast-feeding or early cow's milk exposure to insulin-dependent (type I) diabetes.

RESEARCH DESIGN AND METHODS
All relevant citations retrieved through comprehensive searching of the medical literature were critically reviewed and analyzed. Those case-control studies that minimized the possibility of bias were meta-analyzed to determine overall odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS
Ecological and time-series studies consistently showed a relationship between type I diabetes and either cow's milk exposure or diminished breast-feeding. In the case-control studies, patients with type I diabetes were more likely to have been breast-fed for &lt;3 months (overall OR 1.43; 95% CI 1.15–1.77) and to have been exposed to cow's milk before 4 months (overall OR 1.63; 95% CI 1.22–2.17). Slightly lower ORs were obtained when all of the case-control studies were metaanalyzed in a sensitivity analysis.

CONCLUSIONS
Early cow's milk exposure may be an important determinant of subsequent type I diabetes and may increase the risk ∼1.5 times.
Effects of the Carbohydrase Inhibitor Miglitol in Sulfonylurea-Treated NIDDM Patients
Authors: Johnston Peter S , Coniff Robert F , Hoogwerf Byron J , Santiago Julio V , Pi-Sunyer F Xavier , Krol Alice 
Published: March 2007

OBJECTIVE
To examine the effects of the carbohydrase inhibitor miglitol (BAY m 1099) on the metabolic profiles of non-insulin-dependent diabetes mellitus (NIDDM) patients suboptimally controlled on maximal daily doses of sulfonylurea (SFU) agents.

RESEARCH DESIGN AND METHODS
Multicenter, double-blind, randomized, placebo-controlled 14-week clinical trial with six-week, single-blind placebo lead-in and run-out periods. NIDDM volunteers (192) with fasting plasma glucose (FPG) 140–250 mg/dl and hemoglobin A1c (HbA1c) 6.5–12.0% after at least 4 weeks of treatment with SFU at maximal dose were stratified by baseline HbA1c (above and below 9.0%) and then randomly assigned within strata to placebo (n = 63), 50 mg miglitol 3 times a day (n = 61), or 100 mg miglitol 3 times a day (n = 68). Efficacy was assessed by HbA1c, FPG, insulin, and lipid concentrations, and by plasma glucose and serum insulin responses to a standard meal.

RESULTS
In the 50 and 100 mg miglitol treatment groups, the mean changes from baseline in HbA1c (with placebo values subtracted) were 0.82 and 0.74%, respectively, and were highly significant (P = 0.0001 in each case). Mean peak plasma glucose levels after a standard test meal were comparably lowered by 57 mg/dl with the 50 mg miglitol dose, and by 64 mg/dl with the 100 mg miglitol dose compared with placebo (P = 0.0001 for each), with associated reductions in integrated serum insulin response (P &lt; 0.05). No significant drug-associated changes in FPG, insulin, or cholesterol levels were noted, but fasting triglyceride levels were lowered significantly with the 50 mg miglitol dose. Miglitol's side effects were limited to flatulence, loose stools, and abdominal discomfort, which were dose-related, rapidly resolved on drug discontinuation, and led to withdrawal from the study of 5 and 15% of patients taking 50 and 100 mg miglitol, respectively.

CONCLUSIONS
Miglitol may be indicated as effective adjuvant therapy in NIDDM patients with suboptimal metabolic control despite conventional treatment with diet and maximal daily doses of SFU. The dose of 50 mg miglitol 3 times a day may be preferable to 100 mg miglitol 3 times a day because of comparable efficacy and substantially reduced side effects.
Dietary Fat Predicts Conversion From Impaired Glucose Tolerance to NIDDM: The San Luis Valley Diabetes Study
Authors: Marshall Julie A , Hoag Sharon , Shetterly Susan , Hamman Richard F 
Published: March 2007

OBJECTIVE
To determine if dietary fat intake measured at a baseline exam in subjects with impaired glucose tolerance (IGT) predicted the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS
Based on an oral glucose tolerance test (OGTT) (World Health Organization criteria), we identified 134 eligible subjects with IGT from a geographically based sample of subjects with no prior history of diabetes. One to three years after the baseline exam, 123 subjects (92%) had a repeat OGTT. Diet was assessed by a 24-h diet recall reported before the baseline OGTT.

RESULTS
The mean percentage of energy eaten as fat was 43.4% in 20 people subsequently developing NIDDM compared with 40.6% in 43 people remaining IGT and 38.9% in 60 subjects who subsequently reverted to normal glucose tolerance. In comparing the 20 subjects who developed NIDDM with the 103 who remained IGT or normal, an increase in fat intake of 40 g/day was associated with an increase in risk of NIDDM of 3.4-fold (95% confidence interval [CI] 0.8–13.6) adjusted for energy intake, age, sex, ethnicity, and obesity. The odds ratio increased to sixfold (95% CI 1.2–29.8) after adjustment for fasting glucose, insulin, and 1-h insulin.

CONCLUSIONS
Fat consumption significantly predicts NIDDM risk in subjects with IGT after controlling for obesity and markers of glucose metabolism.
Effect of Metformin on Postprandial Lipemia in Patients With Fairly to Poorly Controlled NIDDM
Authors: Jeppesen Jorgen , Zhou Ming-Yue , Chen Y-D Ida , Reaven Gerald M 
Published: March 2007

OBJECTIVE
To quantify the effect of metformin on the metabolism of triglyceride (TG)-rich lipoprotein of intestinal origin in patients with non-insulin-dependent diabetes mellitus (NIDDM) who had responded to sulfonylurea but still had fasting hyperglycemia.

RESEARCH DESIGN AND METHODS
Sixteen patients with NIDDM who had demonstrated a fall in fasting plasma glucose concentration &gt; 2.2 mmol/l in response to glipizide treatment but continued to have fasting plasma glucose concentrations &gt; 8.3 mmol/l were studied. Fasting glucose, GHb, lipid and lipoprotein concentrations were determined, and resistance to insulin-mediated glucose disposal was estimated by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, glucose, andinsulin. In addition, plasma glucose, insulin, and TG concentrations were measured at frequent intervals from 0800 to 2400, with patients eating breakfast at 0800 and lunch at 1200. Vitamin A was also given at lunch, and the retinyl ester content in plasma and in chylomicron (Svedberg flotation constant [Sr] &gt; 400) and the chylomicron remnant (Sr 20–400) fractions were used to quantify the concentration of postprandial intestinal TG-rich lipoprotein from 1200 to 2400.

RESULTS
Fasting plasma glucose concentrations (6.8 ± 0.4 vs. 10.5 ± 0.4 mmol/l), GHb levels (7.9 ± 0.3 vs. 10.8 ± 0.5%), and day-long plasma glucose concentrations were all significantly lower after metformin treatment (P &lt; 0.001), which was associated with a significant (P &lt; 0.001) fall in SSPG concentration (11.0 ± 0.9 to 9.6 ± 0.6 mmol/l). In addition, postprandial concentrations of glucose, insulin, free fatty acids, and TG were lower (P &lt; 0.001) following metformin treatment. Postprandial retinyl ester concentrations were also lower in plasma by 33 ± 5.7% (P &lt; 0.001) and in both the chylomicron (32 ± 7.2%, P &lt; 0.001) and chylomicron remnant (26 ± 7.0%, P &lt; 0.005) fractions.

CONCLUSIONS
Addition of metformin to sulfonylurea-treated patients with NIDDM with less than optimal glycemic control was associated with improved glycemic control, lower postprandial insulin and TG concentrations, and a decrease inpostprandial concentration of TG-rich lipoproteins of intestinal origin. All of these changes might be expected to decrease risk of coronary heart disease.
The Relationship Between Serum Lipoprotein(a) and Insulinemia in Healthy Nondiabetic Adult Men
Authors: Duell P Barton , Hagemenas Fay , Connor William E 
Published: March 2007

OBJECTIVE
To test the hypothesis that variations in serum insulin concentrations and insulin action may influence serum concentrations of lipoprotein(a) [Lp(a)].

RESEARCH DESIGN AND METHODS
A cross-sectional analysis of fasting serum insulin and Lp(a) concentrations were conducted in a group of 54 healthy adult men 23–61 years of age. Measures of dietary intake, exercise, smoking, alcohol ingestion, body mass index (BMI), fasting plasma lipoprotein lipid concentrations, and serum sex hormone and fasting glucose levels were also determined.

RESULTS
The fasting serum concentrations of insulin and Lp(a) were negatively correlated (r = −0.339, P = 0.014) by univariate regression analysis. Several confounding variables were also significantly correlated with Lp(a) concentrations: testosterone (r = 0.348, P = 0.012), strenuous exercise (r = 0.287, P = 0.041), and BMI (r = −0.276, P = 0.050). As expected, these additional variables and serum insulin concentrations were highly interrelated. In a stepwise regression model, the serum insulin level was identified as the single best predictor of Lp(a) levels. Nearly 25% of the heterogeneity in serum concentrations of Lp(a) could be predicted by serum levels of insulin and testosterone, BMI, and the amount of strenuous exercise.

CONCLUSIONS
The results of these studies have shown that serum concentrations of insulin and testosterone, BMI, and strenuous exercise appear to account for the majority of predicted nongenetic variability in serum levels of Lp(a). These observations suggest the possibility in this group of healthy men that serum concentrations of Lp(a) may be modulated by a complex interplay between insulin action, obesity, androgen levels, and strenuous exercise.
Effects of Postprandial Exercise on Glycemic Response in IDDM Subjects: Studies at constant insulinemia
Authors: Rasmussen Ole W , Lauszus Finn F , Hermansen Kjeld 
Published: March 2007

OBJECTIVE
To determine the influence of postprandial exercise on blood glucose responses in insulin-dependent diabetes mellitus (IDDM) subjects.

RESEARCH DESIGN AND METHODS
Two identical test meals were served with a 7-day interval. On one occasion, a 30-min cycle exercise was performed 15 min after the meal. Patients had achieved normoglycemia by means of an artificial pancreas (Biostator) before the meals, which also ensured constant insulin infusion in the study periods. Seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied.

RESULTS
The 30 min of cycling reduced postprandial blood glucose response areas by 34 ± 12% (P &lt; 0.01) from 638 ± 30 to 492 ± 61 mmol/l × 180 min (P &lt; 0.03), whereas similar peak blood glucose values were found (13.7 ± 0.3 vs. 12.0 ± 1.3 mmol/l).

CONCLUSIONS
Thirty minutes of moderate exercise done postprandially reduces the blood glucose response to 50 g carbohydrate by about one-third.