bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of Insulin Lispro Across the Human Placenta
Authors: Boskovic Rada , Feig Denice S. , Derewlany Lidia , Knie Brenda , Portnoi Galina , Koren Gideon 
Published: March 2007

OBJECTIVE—Insulin lispro (Humalog), a human insulin analog, has a more rapid onset, earlier peak, and shorter duration of glucose lowering activity than regular human insulin. However, it is not known whether insulin lispro crosses the human placenta and reaches the fetus. Therefore, the objective of the present study was to examine whether insulin lispro crosses the placenta using the technique of perfusing a human placental lobule in vitro.
RESEARCH DESIGN AND METHODS—Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. Insulin lispro, at concentrations ranging from 100 to 1000 μU/ml, was introduced into the maternal reservoir. The maternal side of the placenta was perfused with constant concentration of lispro insulin; the fetal circulation was closed. Samples were drawn from both the maternal and fetal circulations at regular intervals. The appearance of insulin lispro in the fetal circulation was analyzed by a specific radioimmunoassay.
RESULTS—No placental transfer of lispro could be detected during perfusion with 100 and 200 μU/ml. In contrast, there was a small concentration-dependent transfer to the fetus at concentrations of 580 μU/ml and higher, detectable after at least an hour of constant concentration of insulin lispro during perfusion. The rate of placental transfer was 0.019 μU · min−1 · g tissue−1 at maternal levels of 580 μU/ml and 0.045 μU · min−1 · g−1 tissue at maternal levels of 1000 μU/ml. Measuring lispro levels in 11 pregnant women revealed that a dose of 50 units may achieve serum concentrations &gt;200 μU/ml with apparent linear correlation between dose and levels.
CONCLUSIONS—Insulin lispro is not likely to cross the placenta at a single standard dose. This study suggests that insulin lispro is unlikely to reach or harm the unborn baby.
Contribution of Plantar Fascia to the Increased Forefoot Pressures in Diabetic Patients
Authors: D’Ambrogi Emanuela , Giurato Laura , D’Agostino Maria Antonietta , Giacomozzi Claudia , Macellari Velio , Caselli Antonella , Uccioli Luigi 
Published: March 2007

OBJECTIVES—Secondary to peripheral neuropathy, plantar hyperpressure is a proven risk factor for foot ulceration. But limited joint mobility (LJM) and soft tissue abnormalities may also contribute. The aim of this study was to evaluate the relationships among thickness of plantar fascia, mobility of the metatarso-phalangeal joint, and forces expressed under the metatarsal heads.
RESEARCH DESIGN AND METHODS—We evaluated 61 diabetic patients: 27 without neuropathy (D group), 19 with neuropathy (DN group), and 15 with previous neuropathic foot ulceration (DNPU group). We also examined 21 control subjects (C). Ultrasound evaluation was performed with a high resolution 8- to 10-MHz linear array (Toshiba Tosbee SSA 240). The foot loading pattern was evaluated with a piezo-dynamometric platform. First metatarso-phalangeal joint mobility was assessed with a mechanic goniometer.
RESULTS—Diabetic patients presented increased thickness of plantar fascia (D 2.9 ± 1.2 mm, DN 3.0 ± 0.8 mm, DNPU 3.1 ± 1.0 mm, and C 2.0 ± 0.5.mm; P &lt; 0.05), and significantly reduced motion range at the metatarso-phalangeal joint (D 54.0 ± 29.4°, DN 54.9 ± 17.2°, DNPU 46.8 ± 20.7°, and C 100.0 ± 10.0°; P &lt; 0.05). The evaluation of foot-floor interaction under the metatarsal heads showed increased vertical forces in DN and DNPU and increased medio-lateral forces in DNPU. An inverse correlation was found between the thickness of plantar fascia and metatarso-phalangeal joint mobility (r = −0.53). The thickness of plantar fascia was directly correlated with vertical forces under the metatarsal heads (r = 0.52).
CONCLUSIONS—In diabetic patients, soft tissue involvement may contribute to the increase of vertical forces under the metatarsal heads. Changes in the structure of plantar fascia may also influence the mobility of the first metatarso-phalangeal joint.
Factors Affecting Progression of Renal Failure in Patients With Type 2 Diabetes
Authors: Ueda Hideki , Ishimura Eiji , Shoji Tetsuo , Emoto Masanori , Morioka Tomoaki , Matsumoto Naoki , Fukumoto Shinya , Miki Takami , Inaba Masaaki , Nishizawa Yoshiki 
Published: March 2007

OBJECTIVE—Hyperglycemia and hypertension are known to be risk factors for the development of proteinuria in patients with diabetes. Little is known, however, about predictors of progression of renal failure in diabetic patients.
RESEARCH DESIGN AND METHODS—We investigated factors affecting progression of renal failure by measuring the doubling of serum creatinine (s-Cr) as an end point in a cohort of 85 type 2 diabetic patients with chronic renal insufficiency/failure (s-Cr &gt;1.5 and &lt;3.7 mg/dl, 61 ± 11 years old, 51 men and 34 women, mean s-Cr 2.3 ± 0.6 mg/dl).
RESULTS—The survey period (mean ± SD) was 14.2 ± 10.8 months. The cumulative incidence of the end point in patients with insulin therapy (n = 41) was significantly lower than that in patients without it (n = 44) (P = 0.0022, P values by log-rank test). Multivariate Cox analysis revealed insulin therapy (hazard ratio [HR] 0.435, 95% CI 0.252–0.750, P = 0.0027), serum albumin (0.484, 284–0.823, P = 0.0074), mean blood pressure (1.023, 1.004–1.043, P = 0.017), and hemoglobin (0.841, 0.728–0.972, P = 0.0194) to be independent and significant predictors of progression to renal failure, whereas HbA1c or serum cholesterol were not.
CONCLUSION—In type 2 diabetic patients with renal failure, hypoalbuminemia, anemia, higher mean blood pressure, and lack of use of insulin predict rapid progression of renal failure, but HbA1c does not, and insulin therapy may be possibly an indicator of the delay in progression of renal failure.
Changes in Aerobic Capacity and Visceral Fat but not Myocyte Lipid Levels Predict Increased Insulin Action After Exercise in Overweight and Obese Men
Authors: Gan Seng Khee , Kriketos Adamandia D. , Ellis Bronwyn A. , Thompson Campbell H. , Kraegen Edward W. , Chisholm Donald J. 
Published: March 2007

OBJECTIVE—To examine the effect of moderate intensity physical activity on the interactions between central abdominal adiposity, myocyte lipid content, and insulin action in overweight and obese, sedentary men.
RESEARCH DESIGN AND METHODS—Myocyte lipid (biochemical triglyceride and long-chain acyl CoA [LCAC] from vastus lateralis biopsy and soleus and tibialis anterior intramyocellular lipid by 1H-magnetic resonance spectroscopy), regional body and abdominal fat (dual-energy X-ray absorptiometry and magnetic resonance imaging), serum lipids, insulin action (hyperinsulinemic-euglycemic clamp), and substrate oxidation were measured in 18 nondiabetic, sedentary, and overweight to obese men (aged 37.4 ± 1.3 years and BMI 30.9 ± 0.7 kg/m2, range 26.4–37.6) at baseline, after the first two to four bouts of aerobic exercise (55–70% of Vo2max for 40 min/session), and at completion of 4.1 ± 0.2 exercise sessions/week for 9.7 ± 0.5 weeks (postexercise measurements performed 24–36 h after the last exercise bout).
RESULTS—Mean whole body insulin-stimulated glucose uptake and basal fat oxidation rate increased 16 and 41%, respectively, after two to four bouts of exercise, without further increase at program end. Mean aerobic capacity increased 11%, and central abdominal fat decreased 5% at program end, but myocyte lipid levels were not significantly changed. Posttraining increases in insulin-stimulated glucose uptake were predicted by increase in aerobic capacity (r = 0.726, P = 0.001) and magnitude of reduction in visceral fat (r = −0.544, P = 0.02) and not by changes in myocyte lipid or LCAC levels.
CONCLUSIONS—These results suggest that in overweight and obese sedentary men, increase in insulin sensitivity with moderate intensity exercise is predicted by improvement in aerobic capacity and reduction in visceral fat but is independent of myocyte triglyceride or LCAC levels.
A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes
Authors: Hamann Andreas , Matthaei Stephan , Rosak Christoph , Silvestre Louise ,   for the HOE901/4007 Study Group
Published: March 2007

OBJECTIVE—Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime.
RESEARCH DESIGN AND METHODS—Patients with type 1 diabetes on basal-bolus therapy (n = 378, 18–68 years, HbA1c 5.5–9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks.
RESULTS—Baseline characteristics were similar in the three groups (overall age 40.9 ± 11.9 years, diabetes duration 17.3 ± 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine–to–total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA1c from baseline to end point occurred in all patients (7.6–7.4, 7.6–7.5, and 7.6–7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA1c &lt;7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P = 0.005).
CONCLUSIONS—These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.
Prevalence and Major Risk Factors of Reduced Flow Volume in Lower Extremities With Normal Ankle-Brachial Index in Japanese Patients With Type 2 Diabetes
Authors: Suzuki Eiji , Egawa Katsuya , Nishio Yoshihiko , Maegawa Hiroshi , Tsuchiya Masanobu , Haneda Masakazu , Yasuda Hitoshi , Morikawa Shigehiro , Inubushi Toshiro , Kashiwagi Atsunori 
Published: March 2007

OBJECTIVE—To clarify the prevalence and major risk factors of reduced flow volume in lower extremities with normal ankle-brachial index (ABI) in Japanese patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—We recruited 208 consecutive type 2 diabetic patients and 33 age-matched nondiabetic subjects (control group) admitted to our hospital. Thirty-two of the patients had low ABI (&lt;0.90) and intermittent claudication (peripheral arterial disease [PAD] group), and 176 patients had normal ABI (&gt;0.9) (non-PAD group). We evaluated flow volume and resistive index, as an index of arterial resistance to blood flow, at the popliteal artery using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging.
RESULTS—Simple linear regression analysis showed a negative correlation between resistive index and total flow volume in the non-PAD group (r = −0.714, P &lt; 0.001). We defined the means ± 2 SD of these parameters in the control group as the normal range; abnormal resistive index was &gt;1.017, and abnormal flow volume was &lt;50.8 ml/min. The non-PAD group was divided according to the levels of these parameters: 80 patients had both normal resistive index and normal flow volume (normal group); of 96 patients with higher resistive index, 63 had normal flow volume (borderline group) and 33 had reduced flow volume (reduced group). Multiple regression analysis demonstrated that the major risk factors for reduced flow volume were age, hypertension, and diabetic nephropathy (r2 = 0.303, P &lt; 0.001).
CONCLUSIONS—The prevalence of patients without PAD with reduced flow volume in the lower extremities was 16% (n = 33) and comparable with that of patients with PAD with intermittent claudication (n = 32), suggesting that increase in arterial resistance to blood flow may be one of the major causes of lower extremity arterial disease in Japan.
Correlation Between Midthigh Low- Density Muscle and Insulin Resistance in Obese Nondiabetic Patients in Korea
Authors: Kim Dolmi , Nam Suyoun , Ahn Chulwoo , Kim Kyungwook , Yoon Soojee , Kim Junuh , Cha Bongsoo , Lim Sungkil , Kim Kyungrae , Lee Hyunchul , Huh Kapbum 
Published: March 2007

OBJECTIVE—We investigated the link between lipid-rich skeletal muscle, namely low-density muscle, and insulin resistance in Korea.
RESEARCH DESIGN AND METHODS—Abdominal adipose tissue areas and midthigh skeletal muscle areas of 75 obese nondiabetic subjects (23 men, 52 women; mean age ± SD, 41.9 ± 14.1 years) were measured by computed tomography (CT). The midthigh skeletal muscle areas were subdivided into low-density muscle (0 to +30 Hounsfield units) and normal-density muscle (+31 to +100 Hounsfield units). The homeostasis model assessment (HOMA) score was calculated to assess whole-body insulin sensitivity.
RESULTS—The abdominal visceral fat area and the midthigh low-density muscle area were found to be well correlated with the HOMA score (r = 0.471, P &lt; 0.01 and r = 0.513, P &lt; 0.01, respectively). The correlation between low-density muscle area and insulin resistance persisted after adjusting for BMI or total body fat mass (r = 0.451, P &lt; 0.01 and r = 0.522, P &lt; 0.01, respectively) and even after adjusting for abdominal visceral fat area (r = 0.399, P &lt; 0.01).
CONCLUSIONS—The midthigh low-density muscle area seems to be a reliable determinant of insulin resistance in Korean obese nondiabetic patients.
Association Between Serum Testosterone Concentration and Carotid Atherosclerosis in Men With Type 2 Diabetes
Authors: Fukui Michiaki , Kitagawa Yoshihiro , Nakamura Naoto , Kadono Mayuko , Mogami Shinichi , Hirata Chizuko , Ichio Naoko , Wada Katsuya , Hasegawa Goji , Yoshikawa Toshikazu 
Published: March 2007

OBJECTIVE—There is evidence to suggest that low concentrations of testosterone are associated with an increased risk of cardiovascular disease in men. The aim of this study was to evaluate the relationship between serum testosterone concentration and carotid atherosclerosis as well as major cardiovascular risk factors in men with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Serum free and total testosterone concentrations were measured in 253 consecutive men with type 2 diabetes. The relationships between serum testosterone concentration and carotid atherosclerosis, determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score (PS) in a subgroup of 154 diabetic patients, as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations, were evaluated.
RESULTS—Inverse correlations were found between free testosterone (F-tes) concentration and IMT (r = −0.206, P = 0.0103) and between F-tes concentration and PS (r = −0.334, P &lt; 0.001). The IMT and PS were significantly greater in patients with lower concentrations of F-tes (&lt;10 pg/ml) than in patients with higher concentrations of F-tes (1.01 ± 0.29 vs. 0.91 ± 0.26 mm, P = 0.038; 4.5 ± 3.8 vs. 2.4 ± 3.2, P = 0.0003; respectively). An inverse correlation was found between serum F-tes concentration and age (r = −0.420, P &lt; 0.0001). A positive correlation was found between serum F-tes and total cholesterol concentrations (r = 0.145, P = 0.0238).
CONCLUSIONS—Serum F-tes concentration is inversely associated with carotid atherosclerosis determined by ultrasonographically evaluated IMT and PS in men with type 2 diabetes.
Comparison of Insulin Aspart and Lispro
Authors: Homko Carol , Deluzio Antonio , Jimenez Carolyn , Kolaczynski Jerzy W. , Boden Guenther 
Published: March 2007

OBJECTIVE—To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro.
RESEARCH DESIGN AND METHODS—Seven C-peptide–negative patients with type 1 diabetes (two men and five women) were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart. Their plasma glucose was normalized overnight by intravenous infusion of insulin. The next morning, they received subcutaneous injections of either aspart or lispro (9.4 ± 1.9 U) in random order. For the next 4–5 h, their plasma glucose was clamped at ∼5.5 mmol/l with a variable infusion of 20% glucose. The study was terminated after 8 h.
RESULTS—Both insulin analogs produced similar serum insulin levels (250–300 pmol/l) at ∼30 min and disappeared from serum after ∼4 h. Insulin aspart and lispro had similar effects on glucose and fat metabolism. Effects on carbohydrate metabolism (glucose uptake, glucose oxidation, and endogenous glucose production) peaked after ∼2–3 h and disappeared after ∼5–6 h. Effects on lipid metabolism (plasma free fatty acid, ketone body levels, and free fatty acid oxidation) appeared to peak earlier (at ∼2 h) and disappeared earlier (after ∼4 h) than the effects on carbohydrate metabolism.
CONCLUSIONS—We conclude that both insulin aspart and lispro are indistinguishable from each other with respect to blood levels and that they are equally effective in correcting abnormalities in carbohydrate and fat metabolism in patients with type 1 diabetes.
Predicting Impaired Glucose Tolerance Using Common Clinical Information
Authors: Nelson Karin M. , Boyko Edward J. 
Published: March 2007

OBJECTIVE—To develop a score to predict impaired glucose tolerance (IGT) using common clinical data.
RESEARCH DESIGN AND METHODS—We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III) for 2,746 individuals aged 40–74 years who completed an oral glucose tolerance test. IGT was defined as a 2-h postchallenge glucose ≥140 mg/dl (7.7 mmol/l). We performed bivariate and multivariate analyses to describe the association of IGT with commonly available clinical information. A numerical score to predict IGT was derived from the results of the multivariate logistic regression models.
RESULTS—Fasting glucose levels between 101 and 109 mg/dl (5.6 and 6.0 mmol/l) or between 110 and 125 mg/dl (6.1 and 6.9 mmol/l) were associated with IGT (odds ratio 1.8 and 6.2, respectively; P &lt; 0.05). BMI ≥25 kg/m2, Mexican-American ethnicity, age between 60 and 74 years, hypertension, and triglyceride level ≥150 mg/dl (1.69 mmol/l) were also associated with IGT. The area under the receiver operating characteristic curve for an 8-point scale derived from the multivariate analysis was 0.74 (95% CI 0.72–0.76). Setting a low cut point of 2 on this scale resulted in high sensitivity (86%), whereas a high cut point of 6 yielded high specificity (97%) for the detection of IGT.
CONCLUSIONS—A numerical score based on common clinical data can identify individuals with a low or high likelihood of having IGT.
Efficacy and Safety of Combination Therapy
Authors: Raskin Philip , Klaff Leslie , McGill Janet , South Stephen A. , Hollander Priscilla , Khutoryansky Naum , Hale Paula M. ,   Repaglinide vs. Nateglinide Metformin Combination Study Group
Published: March 2007

OBJECTIVE—An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes.RESEARCH DESIGN AND METHODS—Enrolled patients (n = 192) had HbA1c &gt;7% and ≤12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide ≤2.5 mg, metformin ≤500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16.RESULTS—Final HbA1c values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA1c (−1.28 vs. −0.67%; P &lt; 0.001) and of fasting plasma glucose (FPG) (−39 vs. −21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 a.m. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens.CONCLUSIONS—The addition of repaglinide to metformin therapy resulted in reductions of HbA1c and FPG values that were significantly greater than the reductions observed for addition of nateglinide.
Etiological Investigation of Diabetes in Young Adults Presenting With Apparent Type 2 Diabetes
Authors: Owen Katharine R. , Stride Amanda , Ellard Sian , Hattersley Andrew T. 
Published: March 2007

OBJECTIVE—Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial.
RESEARCH DESIGN AND METHODS—A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18–45 years and not treated with permanent insulin for ≤6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1α (HNF-1α) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1α gene.
RESULTS—A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a β-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1α mutations, the novel missense mutation A501T, and the previously reported R583Q.
CONCLUSIONS—This unselected series shows that there is considerable heterogeneity in apparent YT2D. β-Cell autoantibodies should be performed in all those presenting at ages 18–45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.