bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Continuous Subcutaneous Insulin Infusion With Lispro on Hepatic Responsiveness to Glucagon in Type 1 Diabetes
Authors: Launay Brigitte , Zinman Bernard , Tildesley Hugh D , Strack Thomas , Chiasson Jean-Louis 
Published: March 2007

OBJECTIVE
People with type 1 diabetes frequently develop a blunted counterregulatory hormone response to hypoglycemia coupled with a decreased hepatic response to glucagon, and consequently, they have an increased risk of severe hypoglycemia. We have evaluated the effect of insulin lispro (Humalog) versus regular human insulin (Humulin R) on the hepatic glucose production (HGP) response to glucagon in type 1 diabetic patients on intensive insulin therapy with continuous subcutaneous insulin infusion (CSII).

RESEARCH DESIGN AND METHODS
Ten subjects on CSII were treated for 3 months with lispro and 3 months with regular insulin in a double-blind randomized crossover study. After 3 months of treatment with each insulin, hepatic sensitivity to glucagon was measured in each subject. The test consisted of a 4-h simultaneous infusion of somatostatin (450 μg/h) to suppress endogenous glucagon, regular insulin (0.15 mU · kg−1 · min−1), glucose at a variable rate to maintain plasma glucose near 5 mmol/l, and D-[6,6−2H2]glucose to measure HGP. During the last 2 h, glucagon was infused at 1.5 ng · kg−1 · min−1. Eight nondiabetic people served as control subjects.

RESULTS
During the glucagon infusion period, free plasma insulin levels in the diabetic subjects were 71.7 ± 1.6 vs. 74.8 ± 0.5 pmol/1 after lispro and regular insulin treatment, with plasma glucagon levels of 88.3 ± 1.8 and 83.7 ± 1.5 ng/1 for insulin:glucagon ratios of 2.8 and 3.0, respectively (NS). However, plasma glucose increased to 9.2 ± 1.1 mmol/l after lispro insulin compared with 7.1 ± 0.9 mmol/l after regular insulin (P &lt; 0.01), and the rise in HGP was 5.7 ± 2.8 μmol · kg−1 · min−1 after lispro insulin versus 3.1 ± 2.9 μmol · kg−1 · min−1 after regular insulin treatment (P = 0.02). In the control subjects, HGP increased by 10.7 ± 4.2 μmol · kg−1 · min−1 under glucagon infusion.

CONCLUSIONS
Insulin lispro treatment by CSII was associated with a heightened response in HGP to glucagon compared with regular human insulin. This suggests that insulin lispro increases the sensitivity of the liver to glucagon and could potentially decrease the risk of severe hypoglycemia.
The Action Profile of Lispro Is Not Blunted by Mixing in the Syringe With NPH Insulin
Authors: Joseph Stonny E , Korzon-Burakowska Anna , Woodworth James R , Evans Mark , Hopkins David , Janes Jonathan M , Amiel Stephanie A 
Published: March 2007

OBJECTIVE
To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile.

RESEARCH DESIGN AND METHODS
A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separateoccasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures

RESULTS
Peak plasma insulin levels (2.6 ± 0.8 vs. 2.2 ± 0.6 vs. 1.9 ± 0.6 ng/ml, P = 0.075),total glucose infused (121.5 ± 32.8 vs. 135.0 ± 49.0 vs. 117.3 ± 39.9 mg · kg−1 · min−1 P = 0.53), and maximum glucose infusion rate (GlRmax) (8.3 ± 0.9 vs. 8.0 ± 1.7 vs. 7.1 ± 2.4 mg · kg−1 · min−1 P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 ± 0.3 and 1.2 ± 0.2 vs. 2.0 ± 0.4 h, respectively, P = 0.042). The times until GIRmax were also not different (113.9 ± 41 and 122.0 ± 45 vs. 209.0 ± 51.3 min, , respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 ± 40.5 vs. 292.4 ± 133.3 vs. 399.5 ± 78.3, respectively, P = 0.005).

CONCLUSIONS
The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine typesof insulin before injection to achieve optimal diabetes control.
Mechanism of Impaired Left Ventricular Wall Motion in the Diabetic Heart Without Coronary Artery Disease
Authors: Sakamoto Ken'ya , Yamasaki Yoshimitsu , Shinsuke Nanto , Shimonagata Tsuyoshi , Morozumi Takakazu , Ohara Tomoki , Takano Yuzuru , Nakayama Hiroyuki , Kamado Keiji , Nagata Seiki , Kusuoka Hideo , Nishimura Tsunehiko , Hori Masatsugu 
Published: March 2007

OBJECTIVE
To elucidate whether impairment of the myocardial free fatty acid (FFA)metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease

RESEARCH DESIGN AND METHODS
We performed myocardial imaging with 123I-labeled β-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201 thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum

RESULTS
Nine patients with reduced wall motion documented by left ventriculography (LVG) (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 ± 0.2, mean ± SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 ± 0.2, P &lt;0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P &lt;0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients.

CONCLUSIONS
Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes
An Autopsy Case of Troglitazone-Induced Fulminant Hepatitis
Authors: Shibuya Akitaka , Watanabe Masaaki , Fujita Yoshikuni , Saigenji Katsunori , Kuwao Sadahito , Takahashi Hisao , Takeuchi Haruo 
Published: March 2007

OBJECTIVE
To study an autopsy case of troglitazone-induced fulminant hepatitis.

CASE REPORT
A 58-year-old man contracted severe hepatitis 2 months after administration of troglitazone for the treatment of type 2 diabetes. Liver damage progressed gradually, even after withdrawal of the agent. Despite intensive therapy, the hepatitis became fulminant and the patient died 8 weeks after the onset of liver damage. Autopsy revealed massive hepatic necrosis and cholestasis with inflammatory cell infiltration. The pathological findings and the positive result of the drug-induced lymphocyte stimulation test for troglitazone indicated that the liver damage was mediated by hypersensitivity to troglitazone.

CONCLUSIONS
One report has attributed troglitazone-induced liver damage in less severe cases to idiosyncratic reactions. However, the present case indicates that troglitazone can induce hypersensitivity resulting in fulminant hepatitis. Careful monitoring of serum liver enzymes during troglitazone therapy is therefore essential.
The Association Between Diabetic Complications and Exercise Capacity in NIDDM Patients
Authors: Estacio Raymond O , Regensteiner Judith G , Wolfel Eugene E , Jeffers Barrett , Dickenson Matthew , Schrier Robert W 
Published: March 2007

OBJECTIVE
Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It has been demonstrated previously in NIDDM patients that several risk factors (i.e., obesity, smoking, hypertension, and African-American race) are associated with an impaired exercise capacity. We studied 265 male and 154 female NIDDM patients who underwent graded exercise testing with expired gas analyses to determine the possible influences of diabetic neuropathy, nephropathy, and retinopathy on exercise capacity.

RESEARCH DESIGN AND METHODS
Univariate and multiple linear regression analyses were performed to determine the relationship between diabetic neuropathy, urinary albumin excretion (UAE), and retinopathy with respect to peak oxygen consumption (Vo2). Neuropathy was assessed by neurological symptom and disability scores, autonomic function testing, and quantitative sensory exams involving thermal and vibratory sensation. Three categories of UAE were used: normal albuminuria (&lt;20 μg=min), microalbuminuria (20–200 μg/min), and overt albuminuria (&gt;200 μg/min). Retinopathy was assessed by stereoscopic fundus photographs. Multiple linear regression analyses were then performed controlling for age, sex, length of diagnosed diabetes, duration of hypertension, race and ethnicity, GHb, BMI, and smoking to determine whether there was an independent effect of these diabetic complications on exercise capacity.

RESULTS
Univariate analyses revealed that the presence of diabetic retinopathy (P = 0.03), neuropathy (P = 0.002), microalbuminuria (P = 0.04), and overt albuminuria (P = 0.06) were associated with a lower peak Vo2. Multiple linear regression analyses were performed to determine independent relationships with peak Vo2. The results revealed that increasing retinopathy stage (Parameter estimate [PE] = −0.59 ± 0.3 ml · kg−1 · min−1; P = 0.026) and increasing UAE stage (PE = −0.62 ± 0.3 ml · kg−1 · min−1; P = 0.044) were associated with a decrease in peak Vo2.

CONCLUSIONS
In the present study of NIDDM subjects, a significant independent association was demonstrated between diabetic nephropathy and retinopathy with exercise capacity. These results were obtained controlling for age, sex, length of diagnosed diabetes, hypertension, race, and BMI. Thus the findings in this large NIDDM population without a history of coronary artery disease indicate a potential pathogenic relationship between microvascular disease and exercise capacity.
Long-Term Titrated-Dose α-Glucosidase Inhibition in Non-Insulin-Requiring Hispanic NIDDM Patients
Authors: Johnston Peter S , Feig Peter U , Coniff Robert F , Krol Alice , Davidson Jaime A , Haffner Steven M 
Published: March 2007

OBJECTIVE
To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients.

RESEARCH DESIGN AND METHODS
A 1-year double-blind randomized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150, 200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability. Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of tabulation of adverse events and intercurrent illnesses, and of periodic laboratory determinations.

RESULTS
Reductions from baseline in HbA1c levels at the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in the miglitol group than in the placebo group. HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63, 0.73, and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120-min postprandial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits. There was little difference between treatments for changes in fasting insulin or lipid levels. Miglitol-associated reductions versus placebo in fasting plasma glucose (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly statistically significant. These efficacy results were not notably different between the 6-month endpoint, at which time the mean miglitol dose was 100 mg t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d. Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea (or soft stools). The incidence of these gastrointestinal adverse events appeared to be dose dependent.

CONCLUSIONS
Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d. produced statistically and clinically significant reductions of HbA1c, primarily associated with reduction of glucose and insulin levels in the postprandial period, which were sustained over a year of treatment. Adverse events related to the drug's mechanism of action were common, but generally well tolerated. Doses above 100 mg t.i.d. were not associated with notably enhanced efficacy in most patients.
Leptinemia Is Not a Risk Factor for Ischemic Heart Disease in Men: Prospective results from the Quebec Cardiovascular Study
Authors: Couillard Charles , Lamarche Benoît , Mauriège Pascale , Cantin Bernard , Dagenais Gilles R , Moorjani Sital , Lupien Paul-J , Després Jean-Pierre 
Published: March 2007

OBJECTIVE
To investigate the possibility that leptin levels may be predictive of the risk of ischemic heart disease (IHD) through the relationship of leptin to body fat.

RESEARCH DESIGN AND METHODS
The Quebec Cardiovascular Study cohort consisted of 2,103 French-Canadian men without IHD in 1985 who were followed until 1990, by which time 114 had experienced an IHD event. These 114 men were then individually matched for age, BM1, cigarette smoking, and alcohol intake with 114 subjects who were free of IHD at follow-up. After exclusion of diabetic patients and those in whom leptin levels could not be measured, we were able to compare the initial metabolic profiles of 86 men in the IHD group and of 95 control subjects.

RESULTS
Plasma leptin concentrations were positively correlated with BMI (r = 0.67, P &lt; 0.0001) and with fasting insulin concentrations (r = 0.46, P &lt; 0.0001) in the overall sample. These significant associations were also observed when men with IHD and the control subjects were examined separately (control subjects: r = 0.68 for BMI and r = 0.45 for insulin; IHD subjects: r = 0.65 for BMI and r = 0.50 for insulin). With the exception of plasma triglyceride (r = 0.25, P &lt; 0.001), no significant association was found between leptin and plasma lipoprotein and lipid concentrations. Furthermore, plasma insulin remained significantly associated with leptin levels even after adjustment for BMI (r = 0.22, P &lt; 0.005). There was no difference in baseline leptin levels among men who developed IHD versus men who remained IHD-free during the 5-year follow-up (5.56 ± 3.12 vs. 5.36 ± 2.90 ng/ml, respectively). Thus, although significantly correlated with the BMI and fasting insulin levels, plasma leptin concentration was not a significant predictor of the 5-year incidence of IHD. This lack of a relationship to IHD was noted when leptin levels were analyzed as tertiles and when leptin concentration was analyzed as a continuous variable.

CONCLUSIONS
These prospective results suggest that leptinemia, despite being a strong correlate of obesity, does not appear to be an independent risk factor for the development of IHD in men.
Personal and Family Factors Associated With Quality of Life in Adolescents With Diabetes
Authors: Grey Margaret , Boland Elizabeth A , Yu Chang , Sullivan-Bolyai Susan , Tamborlane William V 
Published: March 2007

OBJECTIVE
Quality of life is an important criterion for assessing outcomes of treatment in chronic illness related to psychosocial well-being. The purpose of this study was to evaluate the factors that influence quality of life in adolescents with IDDM.

RESEARCH DESIGN AND METHODS
Self-reports were obtained from 52 adolescents (age 13-20 years, mean 16.1 ± 1.9 [mean ± SD], diabetes duration 8.2 ± 3.4 years, 49% female) using the following scales: Diabetes Quality of Life for Youths, Children's Depression Inventory, Issues in Coping with Diabetes, Diabetes Family Behavior Scale, Family Adaptability and Cohesion, Self-Efficacy for Diabetes, and the Adolescent Coping Orientation. Metabolic control was measured by HbA1c.

RESULTS
Teenagers whose diabetes had the greater impact (R2 = 0.48) and were less satisfied (R2 = 0.45) felt that management was more difficult (r = 0.56) and that diabetes was more upsetting (r = 0.63). They also used fewer rebellion strategies for coping (r = −0.44), had lower diabetes self-efficacy (r = −0.36), and had more depressive symptoms (r = 0.61). Higher impact was also associated with higher family warmth and caring (r = −0.54) and lower family adaptability (r = −0.42). Teenagers who were more worried (R2 = 0.37) about their diabetes felt that management was more difficult (r = 0.40) and that diabetes was more upsetting (r = 0.58), and they used less rebellion (r = −0.49) and more ventilation (r = 0.42) to cope, had lower diabetes (r = −0.40) and medical (r = −0.30) self-efficacy, were more depressed (r = 0.55), and their families were less warm and caring (r = −0.33). HbA1c levels were not associated with quality of life or any other psychosocial factors except in teenagers who perceived their families as providing more guidance and control. These teenagers had lower HbA1c values than those whose families were less involved.

CONCLUSIONS
Even teenagers who are successfully achieving HbA1c goals of therapy may perceive diabetes as having a negative impact on their lives, be depressed, and find diabetes difficult to manage. Diabetes treatment teams need to pay equal attention to the psychosocial needs to the quiet, nonrebellious teen with well-controlled diabetes from a supportive family as they do to the rebellious adolescent with poorly controlled diabetes.
Identification and Treatment of Cystic Fibrosis-Related Diabetes: A survey of current medical practice in the U.S
Authors: Allen Holley F , Gay Elizabeth C , Klingensmith Georgeanna J , Hamman Richard F 
Published: March 2007

OBJECTIVE
To describe physicians' attitudes and practices in screening for and treating abnormalities in glucose homeostasis in cystic fibrosis (CF) patients and to test the hypotheses that guidelines for screening for CF-related diabetes (CFRD) are not followed at most centers and that screening and treatment vary by the care provider's background.

RESEARCH DESIGN AND METHODS
This cross-sectional survey included three groups of physicians: 1) 593 members of the Lawson Wilkins Pediatric Endocrine Society (LWPES), 2) 462 members of the pediatric assembly of the American Thoracic Society (ATS), and 3) 194 directors of cystic fibrosis centers (CFD). A mailed questionnaire was used for the survey.

RESULTS
The overall response rate was 67%. Of these, 224 LWPES, 143 ATS, and 135 CFD physicians reported actively seeing CF patients. About two-thirds of CF physicians (ATS and CFD) reported routine screening for impaired glucose tolerance (IGT) in asymptomatic CF patients; a random glucose is most often used (60%), followed by HbA1c (50%), urine glucose (44%), fasting glucose (21%), and oral glucose tolerance test (2%). Only 40% of LWPES physicians reported intervening for stress-induced hyperglycemia, but 61% reported use of insulin for persistent IGT. Management of CFRD was similar for all groups; most physicians used insulin (91%). LWPES recommended more intensive glucose testing and nutritional guidelines than did ATS/CFD (P &lt; 0.0001). LWPES reported less concern about risks of diabetes complications (P &lt; 0.0001) and the importance of minimizing burdensome interventions (P &lt; 0.01). All groups considered weight management a top priority.

CONCLUSIONS
Screening for IGT is not routinely done in CF patients and screening tests vary. Greater agreement exists on methods of treating patients with persistent IGT or CFRD, although goals and aggressiveness of treatment vary with the provider's background. A consensus conference is recommended.
Prevalences of Type 2 Diabetes, the Insulin Resistance Syndrome, and Coronary Heart Disease in an Elderly, Biethnic Population
Authors: Lindeman Robert D , Romero Linda J , Hundley Rosalina , Allen Andrew S , Liang Hwa Chi , Baumgartner Richard N , Koehler Kathleen M , Schade David S , Garry Philip J 
Published: March 2007

OBJECTIVE
To compare the prevalences of type 2 diabetes, the various cardiovascular risk factors encompassing the insulin resistance syndrome (IRS), and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic whites.

RESEARCH DESIGN AND METHODS
Elderly Hispanics (n = 414) and non-Hispanic whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County (Albuquerque, NM; age ≥ 65 years), underwent a home interview followed by an interview/examination by a nurse-practitioner, nurse, and nutritionist that included an evaluation of glucose tolerance. Prevalences of total and central obesity, dyslipidemia, hypertension, and microalbuminuria also were determined. History of myocardial infarction, recent angina, and/or coronary bypass graft, and electrocardiograms (ECGs) were used to document CHD.

RESULTS
Elderly Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic whites, but the prevalence of impaired glucose tolerance was not increased in Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations, fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics were shorter, weighed less, and had more total body and central obesity. The higher prevalences of dyslipidemia in Hispanics could be explained by a higher prevalence of diabetes. The prevalences of hypertension and CHD were not different for the two ethnic groups.

CONCLUSIONS
Elderly Hispanics had twice the prevalence of diabetes and higher prevalences of cardiovascular risk factors associated with IRS. Prevalences of hypertension and CHD were similar in the two ethnic groups.