bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients
Authors: Muscelli Elza , Mari Andrea , Casolaro Arturo , Camastra Stefania , Seghieri Giuseppe , Gastaldelli Amalia , Holst Jens J. , Ferrannini Ele 
Published: December 2007

OBJECTIVE—To quantitate the separate impact of obesity and hyperlycemia on the incretin effect (i.e., the gain in β-cell function after oral glucose versus intravenous glucose).
RESEARCH DESIGN AND METHODS—Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20–61 kg/m2). C-peptide deconvolution was used to reconstruct insulin secretion rates, and β-cell glucose sensitivity (slope of the insulin secretion/glucose concentration dose-response curve) was determined by mathematical modeling. The incretin effect was defined as the oral-to-intravenous ratio of responses. In 8 subjects with NGT and 10 with diabetes, oral glucose appearance was measured by the double-tracer technique.
RESULTS—The incretin effect on total insulin secretion and β-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT (P ≤ 0.05). The results were similar when subjects were stratified by BMI tertile (P ≤ 0.05). In the whole dataset, each manifestation of the incretin effect was inversely related to both glucose tolerance (2-h plasma glucose levels) and BMI (partial r = 0.27–0.59, P ≤ 0.05) in an independent, additive manner. Oral glucose appearance did not differ between diabetes and NGT and was positively related to the GLP-1 response (r = 0.53, P &lt; 0.01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients.
CONCLUSIONS—Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity impair the incretin effect independently of one another.
Insulin Resistance and Progression to Type 1 Diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)
Authors: Bingley Polly J. , Mahon Jeffrey L , Gale Edwin A.M. ,   for the European Nicotinamide Diabetes Intervention Trial (ENDIT) Group
Published: December 2007

OBJECTIVE—Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers.
RESEARCH DESIGN AND METHODS—The retrospective cohort analysis included 213 family members participating in the European Nicotinamide Diabetes Intervention Trial. All were aged &lt;25 years, with at least one islet antibody in addition to ICA ≥20 Juvenile Diabetes Foundation units. Median length of follow-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox regression analysis
RESULTS—The overall cumulative risk of diabetes within 5 years was 54.1% (95% CI 46.0–62.3). Multivariate analysis confirmed that baseline first-phase insulin response (FPIR) quartile (P &lt; 0.0001), number of additional antibody markers (P &lt; 0.0001), and 120-min glucose in the oral glucose tolerance test (P &lt; 0.0001) were independent determinants of risk of progression, whereas addition of homeostasis model assessment of insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0.025) but not in those with preserved FPIR (P = 0.3).
CONCLUSIONS—These data suggest that insulin resistance accelerates progression to type 1 diabetes in antibody-positive relatives in whom insulin secretion is markedly reduced but does not affect progression when insulin secretion is relatively well preserved.
Relationship of Polyunsaturated Fatty Acid Intake to Peripheral Neuropathy Among Adults With Diabetes in the National Health and Nutrition Examination Survey (NHANES) 1999–2004
Authors: Tao Min , McDowell Margaret A. , Saydah Sharon H. , Eberhardt Mark S. 
Published: December 2007

OBJECTIVE—This study investigated the association between dietary intake of polyunsaturated fatty acids (PUFAs) and peripheral neuropathy in the U.S. population.
RESEARCH DESIGN AND METHODS—We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 for adults ≥40 years of age with diagnosed diabetes, an assessment of peripheral neuropathy, and reliable 24-h dietary recall. The dietary intake of PUFAs was analyzed by peripheral neuropathy status. Multivariate logistic regression models were used to estimate the odds of having peripheral neuropathy in higher quintiles of PUFA intake compared with the lowest quintile.
RESULTS—The mean dietary intake of linolenic acid was 1.25 ± 0.07 g among adults with peripheral neuropathy, significantly lower than the 1.45 ± 0.05 g intake among those without peripheral neuropathy. After controlling for potential confounding variables, adults whose linolenic acid intake was in the highest quintile had lower odds of peripheral neuropathy than adults in the lowest quintile (adjusted odds ratio 0.40 [95% CI 0.21–0.77]).
CONCLUSIONS—Among adults with diagnosed diabetes, dietary intake of linolenic acid is positively associated with lower odds of peripheral neuropathy.
Bloodletting Ameliorates Insulin Sensitivity and Secretion in Parallel to Reducing Liver Iron in Carriers of HFE Gene Mutations
Authors: Equitani Francesco , Fernandez-Real Josè Manuel , Menichella Giacomo , Koch Maurizio , Calvani Menotti , Nobili Valerio , Mingrone Geltrude , Manco Melania 
Published: December 2007

OBJECTIVE—To clarify the pathogenesis of diabetes associated with mutations of the hemochromatosis (HFE) gene, 17 carriers, 9 normal glucose tolerant (NGT) and 8 diabetic, were evaluated in an interventional trial.
RESEARCH DESIGN AND METHODS—At enrollment and after a 2-year bloodletting period, euglycemic-hyperinsulinemic clamp, oral glucose tolerance test (OGTT), liver histology (nonalcoholic fatty liver disease activity score [NAS]), and liver iron content (LIC) were assessed.
RESULTS—NGT subjects had significantly higher baseline insulin sensitivity (P ≤ 0.001), secretion, and insulinogenic index (calculated from the OGTT) (P ≤ 0.0001 for both) and lower LIC (P = 0.004) and NAS (P = 0.02) than diabetic patients. Baseline LIC correlated negatively with insulin secretion (NGT r0 = −0.676, P ≤ 0.0001; diabetes r0 = −0.589, P = 0.02) and insulin sensitivity (M value) (NGT r0 = −0.597, P = 0.009; diabetes r0 = −0.535, P = 0.03) and positively with NAS (diabetes r0 = 0.649, P = 0.007) and triglycerides (NGT r0 = 0.563, P = 0.015). At month 24, circulating iron was reduced by 179 ± 26% in NGT and 284 ± 54% in diabetic subjects. Insulin secretion (NGT 20 ± 4%; diabetes 33 ± 7%) and insulin sensitivity (NGT 25 ± 5%; diabetes 18 ± 3%) increased. LIC decreased in both groups (NGT 126 ± 42%; diabetes 61 ± 13%), and NAS ameliorated (NGT 65.1 ± 6.5 vs. 38.1 ± 6.83; P ≤ 0.0001; diabetes 2.1 ± 10.7 vs. 69.9 ± 10; P ≤ 0.0001).
CONCLUSIONS—Iron depletion ameliorates insulin secretion and sensitivity in NGT and diabetic carriers of HFE gene mutations. This amelioration occurs in parallel with decreased LIC and improved NAS. These results justify glucose tolerance testing and prophylactic iron depletion in asymptomatic carriers as well.
A Variant of the Transcription Factor 7-Like 2 (TCF7L2) Gene and the Risk of Posttransplantation Diabetes Mellitus in Renal Allograft Recipients
Authors: Kang Eun Seok , Kim Myoung Soo , Kim Yu Seun , Hur Kyu Yeon , Han Seung Jin , Nam Chung Mo , Ahn Chul Woo , Cha Bong Soo , Kim Soon Il , Lee Hyun Chul 
Published: December 2007

OBJECTIVE—Posttransplantation diabetes mellitus (PTDM) is a major complication associated with kidney transplantation. Defects in insulin secretion play a pivotal role in the pathogenesis of PTDM. A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene was reported to be associated with type 2 diabetes and possibly associated with an insulin secretion defect. The aim of this study was to investigate the association between genetic variations in TCF7L2 and PTDM in renal allograft recipients.RESEARCH DESIGN AND METHODS—A total of 511 unrelated renal allograft recipients without previously known diabetes were enrolled. Six single nucleotide polymorphisms (rs11196205, rs4506565, rs12243326, rs7903146, rs12255372, and rs7901695) were genotyped in the cohort, which consisted of 119 PTDM patients and 392 non-PTDM subjects. The genotyping of TCF7L2 polymorphisms was performed using real-time PCR.RESULTS—rs4506565, rs7901695, and rs7903146 were found to be in complete linkage disequilibrium. The rs7903146 genotype distribution was CC 94.3% and CT 5.7%. The incidence of PTDM was significantly higher in patients with the CT genotype than in patients with the CC genotype (41.4 vs. 22.2%) (odds ratio 2.474 [95% CI 1.146–5.341]; P = 0.024). The effect of this genotype remains significant after adjustment for age, sex, amount of body weight gain, and type of immunosuppressant (2.655 [1.168–6.038]; P = 0.020).CONCLUSIONS—These data suggest that the TCF7L2 rs7903146 genetic variation is associated with an increased risk of PTDM in renal allograft recipients.
Hypoglycemia in Pregnant Women With Type 1 Diabetes
Authors: Nielsen Lene Ringholm , Pedersen-Bjergaard Ulrik , Thorsteinsson Birger , Johansen Marianne , Damm Peter , Mathiesen Elisabeth R. 
Published: December 2007

OBJECTIVE—In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, vomiting, and other potential predictors of occurrence of severe hypoglycemia.
RESEARCH DESIGN AND METHODS—A prospective observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild (managed by the patient) and severe (requiring assistance from others) hypoglycemia.
RESULTS—Forty-nine (45%) women experienced 178 severe hypoglycemic events, corresponding to 5.3, 2.4, and 0.5 events/patient-year in the first, second, and third trimesters, respectively. The incidence of mild hypoglycemia was 5.5 events/patient-week in early pregnancy and decreased throughout pregnancy (P &lt; 0.0001), regardless of presence of severe hypoglycemia. Prevalence of nausea and vomiting, mild hypoglycemia, and fraction of SMPG readings ≤3.9 mmol/l did not differ between women with and without severe hypoglycemia. A1C, median SMPG, and fluctuations in SMPG decreased during pregnancy, with no differences between women with and without severe hypoglycemia. Logistic regression analysis identified history of severe hypoglycemia the year preceding pregnancy (odds ratio 3.3 [95% CI 1.2–9.2]) and impaired awareness or unawareness (3.2 [1.2–8.2]) as independent predictors for severe hypoglycemia.
CONCLUSIONS—In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors for severe hypoglycemia were history of severe hypoglycemia and impaired awareness.
Increased Risks of Hip Fracture in Diabetic Patients of Taiwan
Authors: Chen Hua-Fen , Ho Ching-An , Li Chung-Yi 
Published: December 2007

OBJECTIVE—Using Taiwan's National Health Insurance claim data, we evaluated the age-, sex-, and urbanization-specific incidence density and relative risks of hip fracture in the diabetic population.
RESEARCH DESIGN AND METHODS—Diabetic patients (n = 500,868) and an age- and sex-matched control group (n = 500,248) were linked to inpatient claims (1997–2002) to identify hospitalizations for nontransport accident hip fracture. The person-year approach with Poisson assumption and Kaplan-Meier analysis were used to estimate the incidence and the cumulative event rates. We also assessed the age-, sex-, and urbanization-specific relative risks of hip fracture in relation to diabetes with the Cox proportional hazard regression model.
RESULTS—The overall incidences of hip fracture for diabetic men and women, respectively, were 3.01 and 6.75/1,000 person-years, which were higher than those for control men and women. There were significant interactions of diabetes and age and diabetes and urbanization statuses. Hazard ratios (HRs) of diabetic patients aged 35–44 years (men 2.45 [95% CI 1.65–3.64]; women 3.19 [1.39–7.33]) were higher than those of diabetic patients aged 55–64 years (men 1.90; women 2.81), but in diabetic men aged &gt;74 years and diabetic women aged &gt;84 years, the HRs were compared with null statistically (HRs 0.98 and 0.91, respectively). Diabetic patients living in rural areas tended to have higher HRs of hip fracture.
CONCLUSIONS—In Taiwan, diabetes increased the risk of hip fracture in both sexes in all age-groups except in diabetic men aged &gt;74 years and diabetic women aged &gt;84 years. Higher HRs of hip fracture were disproportionately observed in younger diabetic patients and in those living in rural areas.
Advancing Insulin Therapy in Type 2 Diabetes Previously Treated With Glargine Plus Oral Agents
Authors: Rosenstock Julio , Ahmann Andrew J. , Colon Gildred , Scism-Bacon Jamie , Jiang Honghua , Martin Sherry 
Published: December 2007

OBJECTIVE—The purpose of this study was to compare two analog insulin therapies (prandial premixed therapy [PPT] versus basal/bolus therapy [BBT]) in type 2 diabetic patients previously treated with insulin glargine (≥30 units/day) plus oral agents, with the aim of demonstrating noninferiority of PPT to BBT.
RESEARCH DESIGN AND METHODS—Patients were randomly assigned to PPT (lispro mix 50/50: 50% insulin lispro protamine suspension and 50% lispro; n = 187) t.i.d. with meals or BBT (glargine at bedtime plus mealtime lispro; n = 187) in a 24-week, multicenter, open-label, noninferiority trial. Investigators could replace lispro mix 50/50 with lispro mix 75/25 at the evening meal if the fasting plasma glucose target was unachievable.
RESULTS—Baseline A1C was similar (PPT 8.8%; BBT 8.9%; P = 0.598). At week 24, A1C was lower with BBT (6.78 vs. 6.95%, P = 0.021). A1C was reduced significantly from baseline for both therapies (P &lt; 0.0001). The difference in A1C change from baseline to the end point (BBT minus PPT) was −0.22% (90% CI −0.38 to −0.07). Noninferiority of PPT to BBT was not demonstrated based on the prespecified noninferiority margin of 0.3%. The percentages of patients achieving target A1C &lt;7.0% (PPT versus BBT, respectively) were 54 vs. 69% (P = 0.009) and for target ≤6.5% were 35 vs. 50% (P = 0.01) but did not differ for target ≤6.0% or &lt;7.5%. Rates of hypoglycemia were similar for both groups.
CONCLUSIONS—Although noninferiority of PPT to BBT was not demonstrated, findings for A1C reduction, percentage of patients achieving A1C targets, hypoglycemia, and number of required injections should be considered in the individual decision-making process of advancing insulin replacement to PPT versus BBT in type 2 diabetes.
Disorders of Glucose Regulation in Adults and Birth Weight
Authors: Al Salmi Isa , Hoy Wendy E. , Kondalsamy-Chennakesavan Srinivas , Wang Zhiqiang , Gobe Glenda C. , Barr Elizabeth L. M. , Shaw Jonathan E. 
Published: December 2007

OBJECTIVE—The purpose of this study was to examine the association of birth weight with indexes of glycemia in a population-based survey.
RESEARCH DESIGN AND METHODS—A total of 10,788 participants in the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study were asked to complete a birth weight questionnaire. Fasting plasma glucose (FPG), postload glucose (PLG), and A1C were modeled against birth weight. World Health Organization criteria were used to define impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes.
RESULTS—Among 7,157 participants who responded to the questionnaire, 4,502 reported their birth weights, with a mean ± SD of 3.4 ± 0.7 kg. FPG, PLG, and A1C were strongly and inversely correlated with birth weight. The odds ratios (95% CI) for high (&gt;90th sex-specific percentile) FPG, PLG, and A1C were 0.83 (0.71–0.96), 0.74 (0.65–0.84), and 0.81 (0.70–0.94), respectively, for a 1-kg increase in birth weight after adjustment for age and sex. In those with low birth weight (LBW), the risks for having IFG, IGT, and diabetes and for all abnormalities combined were increased by 1.75, 2.22, 2.76, and 2.28, respectively, for women and by 1.40, 1.32, 1.98, and 1.49 for men compared with risks for those with normal birth weight. These trends applied across categories of age and BMI.
CONCLUSIONS—In an affluent Western country with a good adult health profile, birth weight has an inverse relationship with indexes of glycemia, and individuals with LBW were predisposed to higher rates of glycemic dysregulation in adult life. These associations were independent of BMI and of other factors significantly correlated with glycemic dysregulation.
Reduction in Diabetic Amputations Over 11 Years in a Defined U.K. Population
Authors: Krishnan Singhan , Nash Fiona , Baker Neil , Fowler Duncan , Rayman Gerry 
Published: December 2007

OBJECTIVE—To assess changes in diabetic lower-extremity amputation rates in a defined relatively static population over an 11-year period following the introduction of a multidisciplinary foot team.
RESEARCH DESIGN AND METHODS—All diabetic patients with foot problems admitted to Ipswich Hospital, a large district general hospital, were identified by twice-weekly surveillance of all relevant in-patient areas and outcomes including amputations recorded.
RESULTS—The incidence of major amputations fell 62%, from 7.4 to 2.8 per 100,000 of the general population. Total amputation rates also decreased (40.3%) but to a lesser extent due to a small increase in minor amputations. Expressed as incidence per 10,000 people with diabetes, total amputations fell 70%, from 53.2 to 16.0, and major amputations fell 82%, from 36.4 to 6.7.
CONCLUSIONS—Significant reductions in total and major amputation rates occurred over the 11-year period following improvements in foot care services including multidisciplinary team work.
Insulin Reduces Plasma Arginase Activity in Type 2 Diabetic Patients
Authors: Kashyap Sangeeta R. , Lara Abigail , Zhang Renliang , Park Young Mi , DeFronzo Ralph A. 
Published: December 2007

OBJECTIVE—We sought to determine whether dysregulation of arginine metabolism is related to insulin resistance and underlies impaired nitric oxide (NO) generation in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—We measured plasma arginase activity, arginine metabolites, and skeletal muscle NO synthase (NOS) activity in 12 type 2 diabetic and 10 age-/BMI-matched nondiabetic subjects before and following a 4-h euglycemic-hyperinsulinemic clamp with muscle biopsies. Arginine metabolites were determined by tandem mass spectroscopy. Arginase activity was determined by conversion of [14C] guanidoinoarginine to [14C] urea.
RESULTS—Glucose disposal (Rd) was reduced by 50% in diabetic versus control subjects. NOS activity was fourfold reduced in the diabetic group (107 ± 45 vs. 459 ± 100 pmol · min−1 · mg protein−1; P &lt; 0.05) and failed to increase with insulin. Plasma arginase activity was increased by 50% in the diabetic versus control group (0.48 ± 0.11 vs. 0.32 ± 0.12 μmol · ml−1 · h−1; P &lt; 0.05) and markedly declined in diabetic subjects with 4-h insulin infusion (to 0.13 ± 0.04 μmol · ml−1 · h−1 vs. basal; P &lt; 0.05). In both groups collectively, plasma arginase activity correlated positively with fasting plasma glucose (R = 0.46, P &lt; 0.05) and A1C levels (R = 0.51, P &lt; 0.02) but not with Rd.
CONCLUSIONS—Plasma arginase activity is increased in type 2 diabetic subjects with impaired NOS activity, correlates with the degree of hyperglycemia, and is reduced by physiologic hyperinsulinemia. Elevated arginase activity may contribute to impaired NO generation in type 2 diabetes, and insulin may ameliorate this defect via reducing arginase activity.
Sex Disparities in Control and Treatment of Modifiable Cardiovascular Disease Risk Factors Among Patients With Diabetes
Authors: Ferrara Assiamira , Mangione Carol M. , Kim Catherine , Marrero David G. , Curb David , Stevens Mark , Selby Joseph V. ,   for the Translating Research Into Action for Diabetes (TRIAD) Study Group
Published: December 2007

OBJECTIVE—Cardiovascular disease (CVD) mortality has decreased in men but not in women with diabetes. We investigated whether sex differences in control and treatment of CVD risk factors might underlie this disparity.
RESEARCH DESIGN AND METHODS—We performed cross-sectional analyses from a cohort of patients with diabetes sampled from 10 U.S. managed care health plans. Study end points included not being in control for CVD risk factors (≥140 mmHg for systolic blood pressure [SBP], ≥3.35 mmol/l for LDL cholesterol, and ≥8.0% for A1C) and the intensity of medication management (number of medication classes) for patients not in control. Logistic regression models with random intercepts were used to adjust probabilities of control and management for demographics, clinical characteristics, and clustering within health plans.
RESULTS—There were 1,315 women and 1,575 men with a history of CVD and 3,415 women and 2,516 men without a history of CVD. Among patients with CVD, adjusted estimated probabilities for not being in control and risk differences varied significantly between men and women for SBP (men 41.2%, women 46.6%; risk difference −5.4% [95% CI −9.5 to −1.3]) and LDL cholesterol (men 22.4%, women 28.3%; risk difference −5.9% [−9.9 to −1.8]). There were no significant sex differences in intensity of medication management for patients not in control. In patients without CVD there were no significant differences in control or intensity of medication management.
CONCLUSIONS—In diabetic patients with CVD, poorer control of SBP and LDL cholesterol for women may contribute to the sex disparity in CVD mortality trends.