bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Pharmacokinetics and Glucodynamics of Two Human Insulin Mixtures 70/30 and 50/50 insulin mixtures
Authors: Woodworth James R , Howey Daniel C , Bowsher Ronald R , Brunelle Rocco L , Rowe Howard M , Compton Joyce , Cerimele Benito 
Published: March 2007

OBJECTIVE
To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg.

RESEARCH DESIGN AND METHODS
We administered single doses of 50/50 and 70/30 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by at least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and Cpeptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (Cmax), time to maximum insulin concentration (tmax), terminal rate constant (β), area under the curve from 0 to ∞, (AUC x0), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [Cmin], time to minimum C-peptide concentration [tmin], area between the C-peptide baseline and the C-peptide suppression curve [AOCc], absolute maximal difference from baseline [Sdiff] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (Rmax) and time to Rmax (TRmax) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h (40Gtot) and total glucose infused (Gtot) during the study.

RESULTS
For the pharmacokinetic assessment, statistically greater values of insulin Cmax and β were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of Rmax and (40Gtot) found with the 50/50 mixture. Notably, differences were not detected for insulin AUCx0 and Gtot values.

CONCLUSIONS
Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.
The Role of Growth Hormone in the Development of Diabetic Retinopathy
Authors: Alzaid Aus A , Dinneen Sean F , Joseph Melton L , Rizza Robert A 
Published: March 2007

OBJECTIVE
To determine the role of growth hormone (GH) in the development of diabetic retinopathy.

RESEARCH DESIGN AND METHODS
Medical records of 1,423 patients who had undergone insulin tolerance tests (1976–1991) at the Mayo Clinic were examined, and diabetic subjects were identified as either GH-deficient (GH increment after hypoglycemia &lt;5 μg/L and peak &lt;10 μg/L) or GH-suificient. Prevalence of retinopathy was determined in these cases and in a cohort group of diabetic subjects selected to match the GH-deficient cases. These control patients (32 cases) were selected from medical records of individuals who had received medical care at Mayo during the same interval but who had not undergone insulin tolerance testing.

RESULTS
Twenty-four patients with diabetes were identified, of whom 16 were GH-deficient and 8 GH-sufficient. Despite comparable age, duration of diabetes, and metabolic control, the prevalence of diabetic retinopathy in the GH-deficient group (2 of 16; 12.5%) was less (P &lt; 0.05) than that observed in the GH-sufficient group (5 of 8; 62.5%). Prevalence in the GH-deficient group also was lower than that observed in the cohort control group (15 of 32, 47%).

CONCLUSIONS
These data strongly suggest that GH contributes to the development of diabetic retinopathy in humans.
Hypoqlycemia Increases Muscle Sympathetic Nerve Activity in IDDM and Control Subjects
Authors: Hoffman Robert P , Sinkey Christine A , Anderson Erling A 
Published: March 2007

OBJECTIVE
The relationship between the increase in adrenomedullary catecholamine secretion and the sympathetic response to hypoglycemia is not well understood in humans. To explore this relationship more closely, we directly recorded muscle sympathetic nerve activity (MSNA) in control subjects and in insulin-dependent diabetes mellitus (IDDM) subjects without clinically evident diabetic complications.

RESEARCH DESIGN AND METHODS
Twelve IDDM subjects (22.5 ± 3.9 years of age, diabetes duration of 9.8 ± 8.3 years) and 12 age-matched control subjects were studied. MSNA was measured during insulin infusion (720 pM·m–2 ·min–1) with 30-min periods of 1) euglycemia, 2) hypoglycemia (target plasma glucose, 2.8 mM), and 3) recovery. The effect of increased insulin dose (1,440 pM· m–2 · min–1) was studied in six subjects in each group, and the effect of prolonged hypoglycemia (1 h) was studied in five IDDM subjects and four control subjects.

RESULTS
MSNA levels increased in IDDM and control subjects, 31 ± 8 and 29 ± 6%, respectively, above euglycemia during hypoglycemia and returned to euglycemic levels during recovery. MSNA levels during hypoglycemia were lower in IDDM subjects than in control subjects (26 ± 3 vs. 35 ± 2 bursts/min, P &lt; 0.01). Importantly, no relationships were found between the MSNA and epinephrine responses to hypoglycemia in either group. Increasing the insulin infusion rate did not alter the MSNA response to hypoglycemia. During prolonged hypoglycemia, MSNA remained elevated above euglycemic levels throughout hypoglycemia.

CONCLUSIONS
These results demonstrate that insulin-induced hypoglycemia increases muscle sympathetic neural outflow in IDDM and control subjects. The lack of correlation between the MSNA and epinephrine responses to hypoglycemia indicates that the adrenomedullary and peripheral sympathetic responses to hypoglycemia are independently mediated.
Frequency of Severe Hypoglycemia in Patients With Type I Diabetes With Impaired Awareness of Hypoglycemia
Authors: Gold Ann E , Macleod Kenneth M , Frier Brian M 
Published: March 2007

OBJECTIVE
To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospective assessment.

RESEARCH DESIGN AND METHODS
A prospective study was undertaken for 12 months in 60 patients with type I diabetes: 29 had impaired awareness of hypoglycemia and 31 retained normal awareness of hypoglycemia. The two groups of patients were matched for age, age at onset of diabetes, duration of diabetes, and glycemic control. Episodes of severe hypoglycemia were recorded within 24 h of the event and verified where possible by witnesses.

RESULTS
During the 12 months, 19 (66%) of the patients with impaired awareness had one or more episodes of severe hypoglycemia with an overall incidence of 2.8 episodes · patient–1 ·year–1. By comparison, 8 (26%) of the patients with normal awareness experienced severe hypoglycemia (P &lt; 0.01) with an annual incidence of 0.5 episode · patient–1 · year–1 (P &lt; 0.001). Severe hypoglycemia occurred at different times of the day in the two groups: patients with impaired awareness experienced a greater proportion of episodes during the evening (P = 0.03), and patients with normal awareness experienced a greater proportion in the early morning (P = 0.05). An assessment of fear of hypoglycemia revealed that patients with impaired awareness of hypoglycemia worried more about hypoglycemia than did patients with normal awareness (P = 0.008), but did not modify their behavior accordingly.

CONCLUSIONS
This prospective evaluation demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hypoglycemia, much of which occurred at home during waking hours.
Day-Night Blood Pressure Variation in Normotensive, Normoalbuminuric Type I Diabetic Subjects: Dippers and non-dippers
Authors: Gilbert Richard , Phillips Paddy , Clarke Caroline , Jerums George 
Published: March 2007

OBJECTIVE
To examine day-night blood pressure (BP) variation in normotensive, normoalbuminuric subjects with type I diabetes and to assess the prevalence of an impaired nocturnal BP fall.

RESEARCH DESIGN AND METHODS
Fourteen healthy volunteers and 13 normotensive, normoalbuminuric subjects with type I diabetes were studied with an ambulatory sphygmomanometric device for 24 h.

RESULTS
No significant difference was found between diabetic and control groups with regard to daytime systolic blood pressure (sBP) or diastolic blood pressure (dBP). However, the mean nighttime sBPs (P &lt; 0.01) and dBPs (P = 0.01) were significantly higher in the diabetic group compared with the control group. Furthermore, the night/day ratio for both sBP (P &lt; 0.01) and dBP (P &lt; 0.01) was significantly higher in the diabetic group. Approximately half of the diabetic subjects studied were non-dippers when defined either by a nocturnal fall in sBP/dBP of &lt; 10/5 mmHg (5/13 vs. 0/14, P &lt; 0.05: diabetic group vs. control group) or a day to night fall in either sBP (7/13 vs. 2/14, P &lt; 0.05) or dBP (6/13 vs. 0/14, P &lt; 0.01) of &lt;10%.

CONCLUSIONS
Ambulatory BP may reveal impaired nocturnal BP fall in normotensive, normoalbuminuric subjects with type I diabetes. These subjects may be at greater risk of certain complications as a consequence of an increased BP burden.
Altered Postprandial Insulin Requirement in IDDM Patients With Gastroparesis
Authors: Ishii Masataka , Nakamura Teruo , Kasai Fukio , Onuma Tomio , Baba Tsuneharu , Takebe Kazuo 
Published: March 2007

OBJECTIVE
To evaluate the effect of gastric emptying on postprandial insulinrequirement in insulin-dependent diabetes mellitus (IDDM) patients with and without gastroparesis.

RESEARCH DESIGN AND METHODS
Postprandial insulin requirement and gastric emptying were simultaneously evaluated in five IDDM patients with gastroparesis and in six control IDDM patients without gastroparesis. Postprandial insulin requirement after test-meal intake was assessed by measuring the insulin infusion rate during a 4-h feedback control with an artificial endocrine pancreas device (Biostator, Life Science Instruments, Miles, Elkhart, IN). Gastric solid and liquid emptyings were evaluated during the Biostator study by measuring the disappearance rate of 99mTc in the stomach and in the time course of plasma acetaminophen concentration, respectively.

RESULTS
Total insulin requirement during the first 120 min after the test-meal intake was significantly lower in the gastroparetic patients than in the control patients. The gastroparetic patients showed no apparent postprandial peak for insulin infusion rate during the 4-h study, although the peak rate was observed within 120 min after the test-meal intake in the control patients. The disappearance of 99mTc in the stomach was significantly slower, and plasma acetaminophen concentrations were significantlylower in the gastroparetic patients compared with those in the control patients, respectively.

CONCLUSIONS
The results suggest that IDDM patients with gastroparesis, accompanied by impaired solid and liquid emptying, have an altered postprandial insulin requirement.
Membrane Fluidity, Membrane Lipid Pattern, and Cytosolic Ca2+ Content in Platelets from a Group of Type II Diabetic Patients with Macrovascular Complications
Authors: Caimi Gregorio , Presti Rosalia Lo , Montana Maria , Canino Baldassare , Ventimiglia Giuseppe , Romano Adele , Catania Anna , Sarno Antonio 
Published: March 2007

OBJECTIVE
To evaluate platelet membrane fluidity and some platelet metabolic parameters in type II diabetic patients with macrovascular complications.

RESEARCH DESIGN AND METHODS
In a group of 21 type II diabetic patients with macrovascular complications, we evaluated platelet membrane fluidity [marking intact resting platelets with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH)], platelet membrane lipid pattern (cholesterol :phospholipid [C:PL] ratio and individual phospholipids), and platelet cytosolic Ca2+ content (marking intact resting platelets with the fluorescent probe Fura 2AM).

RESULTS
Platelet membrane fluidity is decreased in type II diabetic patients with macrovascular complications compared with normal subjects (P &lt; 0.001). Platelet membrane C:PL ratio and cytosolic Ca2+ content do not discriminate normal subjects from diabetic patients, and for individual phospholipids, only phosphatidylethanol-amine is decreased in diabetic patients compared with control subjects (P = 0.051). In normal subjects, the polarization degree of TMA-DPH is related to phosphatidylserine (P &lt; 0.05) and phosphatidylcholine (P &lt; 0.05), and in diabetic patients the polarization degree of TMA-DPH is related to C:PL ratio (P &lt; 0.05) and sphyngomyelin (P &lt; 0.05).

CONCLUSIONS
In type II diabetic patients with macrovascular complications, we observed an abnormality of platelet membrane fluidity, which may contribute to platelet functional alteration present in this clinical condition.
Pregnancy Outcomes in Women Without Gestational Diabetes Mellitus Related to the Maternal Glucose Level: Is there a continuum of risk?
Authors: Moses Robert G , Calvert Dennis 
Published: March 2007

OBJECTIVE
To examine selected pregnancy outcomes in women without gestational diabetes mellitus to see whether there was a continuum of risk related to the maternal glucose level.

RESEARCH DESIGN AND METHODS
Consecutive women attending two prenatal clinics and three obstetricians in private practice were tested for GDM at the beginning of the third trimester using a 75-g glucose load in the fasting state. The rate of induction, the number of assisted deliveries, the presence of pregnancy-induced hypertension, fetal birth weights, and morbidity were examined with respect to the maternal 2-h glucose level.

RESULTS
Data were available for 1,441 women with a 2-h glucose level &lt; 8.0 mmol/l (144 mg/dl). For each 1.0 mmol/l (18 mg/dl) increase in the glucose level, the odds in favor of an assisted delivery increased by 15.2%, and the odds in favor of the baby being admitted to a special care nursery (SCN) increased by 22.6%. There was no significant association between maternal glucose levels and the probability of either pregnancy-induced hypertension or a large-for-gestational-age (LGA) baby after adjustment for other variables.

CONCLUSIONS
In normal women there is a continuum of risk related to the maternal glucose level 2 h after a glucose tolerance test for the probability of having an assisted delivery and the likelihood of the baby being admitted to an SCN. The chance of having pregnancy-induced hypertension or a LGA baby also increased as the maternal glucose level increased but could be largely explained by an increasing body mass index.
Long-Term Glycemic Control Relates to Mortality in Type II Diabetes
Authors: Andersson Dan K , Svärdsudd Kurt 
Published: March 2007

OBJECTIVE
To study the influence of long-term glycemic control on mortality in a cohort of newly detected type II diabetic individuals.

RESEARCH DESIGN AND METHODS
A total of 411 newly detected type II diabetic individuals diagnosed between 1972 and 1987 were followed until 31 December 1989. Clinical data concerning fasting blood glucose (FBG) values, body mass index (BMI), type of treatment, and concomitant diseases were collected during 8 randomly selected years. Long-term glycemic control was measured as annual averages of FBG values during these years. Mortality data were obtained from official registers.

RESULTS
There were 161 diabetic subjects who died during a mean follow-up time of 7.4 years. In univariate analyses, higher age at diagnosis; higher baseline or average FBG; and the presence of heart disease, cerebrovascular disease, or kidney disease at the beginning or during the course of diabetes were related to higher mortality. Type of diabetes treatment or having a diagnosis of hypertension was not related to mortality. In multiple logistic regression analyses, age at diagnosis and average FBG were independently related to all-cause (P = 0.0002), cardiovascular (P = 0.0006), and ischemic heart disease mortality (P = 0.03). No correlations between glycemic control and noncardiovascular deaths were found. In a Cox's regression analysis, average FBG was significantly related to length of survival when age at diabetes diagnosis was taken into account (P &lt; 0.05). Diabetic subjects with average FBG ≥ 7.8 mmol/l had 50% higher mortality compared with diabetic subjects with average FBG &lt; 7.8 mmol/l.

CONCLUSIONS
Diabetic patients with good long-term glycemic control had a better survival rate than subjects with high average FBG values. The findings should be interpreted cautiously because possible confounding factors such as dyslipoproteinemia and smoking were not studied.
Incidence and Prevalence of Childhood Diabetes in Slovakia (1985–1992)
Authors: Michalková Dagmar M , Černay Jozef , Danková Anna , Rusnák Martin , Fandáková Katarína ,   Slovak Childhood Diabetes Epidemiology Study Group
Published: March 2007

OBJECTIVE
To provide reliable data on the incidence and prevalence of insulin–dependent diabetes mellitus (IDDM) in children in Slovakia.

RESEARCH DESIGN AND METHODS
A total of 754 Slovak children with IDDM, aged 0–14 years, were identified during an 8-year study period. There were 369 boys and 385 girls from an average population of 1,363,499 children. All patients were prospectively recorded. The primary ascertainment was based on notifications by physicians from outpatient departments. The second independent source of information was from all hospitals where the diabetic patients were hospitalized. The completeness of ascertainment was based on the capture-recapture procedure.

RESULTS
The completeness of the ascertainment was 95%. In 1992, the annual incidence rate of IDDM (per 100,000) in the 0- to 14-year-old age-group was 8.92 for both sexes (7.95 for boys and 9.93 for girls). In the youngest age-group, an increase in the incidence rates from 2.89 in 1985 to 6.54 in 1992 was observed. Seasonality, with a higher incidence in autumn and winter, was observed in children older than 4 years. The prevalence rates of IDDM (per 1,000) were 0.28–0.50% in the 8-year period.

CONCLUSIONS
The incidence of IDDM in Slovak children (0–14 years) is similar to what has been found in other Central European countries. In children younger than 4 years of age, in the last 2 years (1991 and 1992) more patients with diabetes were found than in any period during the preceding 6 years. The recent conspicuous increase in the incidence of IDDM among the younger children in Slovakia urges us to study its mechanisms, so far unknown, and to search for possible means of prevention.
Glucose, Insulin, and Glucagon Levels During Exercise in Pancreas Transplant Recipients
Authors: Redmon J Bruce , Kubo Spencer H , Robertson R Paul 
Published: March 2007

OBJECTIVE
To determine whether pancreas transplant recipients maintain normal blood glucose levels during physical exercise.

RESEARCH DESIGN AND METHODS
We measured serum glucose, insulin, C-peptide, and plasma glucagon levels in six pancreas transplant recipients and six healthy control subjects matched for age, sex, body size, and level of conditioning during 1 h of bicycle exercise at a workload set to achieve 40% of each individual's previously determined peak oxygen consumption (VO2).

RESULTS
Serum glucose values were not different between control subjects and transplant recipients before the start of exercise (5.0 ± 0.1 and 4.9 ±0.1 mmol/l, respectively). Serum glucose levels fell slightly but significantly in both recipients and control subjects during exercise. There were no significant differences in glucose levels between the two groups at any time point during exercise, although mean nadir glucose during exercise was slightly lower in transplant recipients compared with control subjects (4.4 ± 0.1 vs. 4.8 ± 0.1 mmol/l, P = 0.04). In control subjects, insulin and C-peptide levels fell significantly within 15–30 min of exercise and glucagon levels rose significantly after 60 min of exercise. In transplant recipients, there was a trend for insulin and C-peptide levels to fall and glucagon levels to rise during exercise, although these changes were delayed and were not statistically significant.

CONCLUSIONS
No significant abnormalities in blood glucose were detected in pancreas transplant recipients during bicycle exercise at 40% of peak VO2 for 1 h. Compared with levels in control subjects, subtle alterations in insulin and glucagon levels may occur in transplant recipients during exercise. However, these alterations do not appear to result in either hyperglycemia or hypoglycemia during light exercise for up to 1 h.
Screening for Diabetes Mellitus in Adults: The utility of random capillary blood glucose measurements
Authors: Engelgau Michael M , Thompson Theodore J , Smith Philip J , Herman William H , Aubert Ronald E , Gunter Elaine W , Wetterhall Scott F , Sous Edward S , Ali Mohamed A 
Published: March 2007

OBJECTIVE
Because half of the people with non-insulin-dependent diabetes mellitus (NIDDM) are undiagnosed and because near-normal glycemic control can prevent diabetic complications, we evaluated the use of field-based random capillary blood glucose measurement as a screening test for NIDDM.

RESEARCH DESIGN AND METHODS
A cross-sectional sample of 828 Egyptians ≥20 years of age underwent both a random capillary blood glucose measurement performed with a portable reflectance meter in the field and an oral glucose tolerance test in the laboratory. The sensitivity and specificity of random capillary blood glucose measurements in predicting the presence of NIDDM were evaluated.

RESULTS
Multivariate analyses showed that the screening test performed better when subjects had eaten shortly before the test (area under receiver operating characteristic curve, 0.87 for a 1-h postprandial period compared with 0.69 for an 8-h postprandial period) and that the optimal capillary blood glucose cutoff points to define a positive test increased with age. For a postprandial period of 1 h, cutoff points of 115 mg/dl for individuals 30 years of age and 140 mg/dl for those 75 years of age yielded similar performance characteristics (sensitivity 82% and specificity 78% for those 30 years old; sensitivity 81% and specificity 80% for those 75 years old).

CONCLUSIONS
Adjusting random capillary blood glucose measurements for the postprandial period and using age-specific cutoff point values can improve performance of the screening test.