bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambulatory blood pressure, microalbuminuria, and autonomic neuropathy in adolescents with type 1 diabetes.
Authors: Lafferty A R , Werther G A , Clarke C F
Published: March 2007

OBJECTIVE: To examine the relationship between 24-h blood pressure (BP) measurements, urinary albumin excretion rates, and autonomic neuropathy (AN) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 31 patients with microalbuminuria (MA), 20 patients with intermittent MA (I-MA) and 11 patients with persistent MA (P-MA) were identified from the diabetes clinics at two major Australian tertiary care pediatric hospitals. Two control groups were used; one consisted of 19 age-, sex-, and diabetes duration-matched adolescents with normoalbuminuria (NA), and the other consisted of 46 age- and sex-matched nondiabetic control subjects. A medical history and physical examination were followed by a series of noninvasive tests of cardiovascular and pupillary autonomic function and then by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: ABPM showed an incremental increase in all BP parameters from nondiabetic control subjects through subjects with NA. A parallel incremental increase in diurnal and nocturnal ambulatory heart rates was also evident. Subjects with MA had significantly reduced pupillary adaptation to darkness compared with nondiabetic subjects and subjects with NA. The above results paralleled an incremental increase in HbAlc levels in adolescents with type 1 diabetes from subjects with NA to subjects with P-MA. CONCLUSIONS: Higher 24-h BP values and evidence of subclinical signs of AN are present before P-MA develops and may have important implications for timing the introduction of treatments designed to prevent or retard the microvascular complications of type 1 diabetes in adolescents.
Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial.
Authors: Pham H , Armstrong D G , Harvey C , Harkless L B , Giurini J M , Veves A
Published: March 2007

OBJECTIVE: Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. RESEARCH DESIGN AND METHODS: A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs), joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study. Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. RESULTS: Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT, and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. CONCLUSIONS: Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear.
Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study.
Authors: Meigs J B , Ordovas J M , Cupples L A , Singer D E , Nathan D M , Schaefer E J , Wilson P W
Published: March 2007

OBJECTIVE: Insulin resistance and the apolipoprotein (apo) allele e4 have both been associated with coronary heart disease (CHD). We examined the relationship between insulin resistance and apo(e) polymorphisms among participants in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS: During 1991-1995, subjects underwent a clinical examination and an oral glucose tolerance test with measurement of fasting and 2-h glucose, insulin levels, and fasting lipid levels. We measured insulin resistance using the homeostasis model, in which insulin resistance (HOMA-IR) = fasting insulin x glucose/22.5. Apo(e) isoforms and phenotypes were determined in 1983-1987 using isoelectric focusing of plasma VLDL. Of the 2,120 subjects with complete HOMA-IR and apo(e) data, 204 with type 2 diabetes were excluded. The remainder were classified with features of the insulin resistance syndrome including impaired glucose tolerance (1997 American Diabetes Association criteria), hypertension (criteria from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [6th report]), obesity (BMI >85th percentile), high waist-to-hip ratio (>85th percentile), and high triglyceride and low HDL levels (NCEP-2 criteria). We analyzed data with contingency tables and age- and sex-adjusted logistic regression models. RESULTS: Among the 1,916 subjects, the mean age was 55 (range 28-83 years) and 51% were women. Median HOMA-IR was 6.4 (interquartile range 5.2-8.2), and allele frequencies were 7.8, 79.9, and 12.4% for apo(e) alleles e2, e3, and e4, respectively There were no differences in proportions of apo(e) isoforms or alleles across increasing quintiles of HOMA-IR. A less dramatic increase in proportions occurred with elevated triglycerides associated with increasing HOMA-IR among those with apo(e) isoforms 2/2 and 2/3 compared with the others (P < or = 0.01 for interaction). Otherwise, apo(e) did not substantially modify associations between insulin resistance and features of the insulin resistance syndrome. CONCLUSIONS: There is no association between apo(e) polymorphisms and insulin resistance. These appear to represent 2 completely independent risk factors for CHD.
Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency.
Authors: Juhl C B , Pørksen N , Hollingdal M , Sturis J , Pincus S , Veldhuis J D , Dejgaard A , Schmitz O
Published: March 2007

OBJECTIVE: Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series. RESEARCH DESIGN AND METHODS: We examined 8 healthy lean male subjects in a single-dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn). RESULTS: Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 +/- 3.6 vs. 33.5 +/- 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 +/- 2.2 vs. 19.6 +/- 2.8 pmol x l(-1) x pulse(-1), P = 0.02) and amplitude (6.1 +/- 0.9 vs. 7.7 +/- 1.2 pmol x l(-1) x min(-1), P = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 +/- 0.3 vs. 3.2 +/- 0.4 pmol x l(-1) x min(-1), p = 0.06), while the interpulse interval was unaltered (6.8 +/- 1.0 vs. 5.4 +/- 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 +/- 0.045 vs. 0.670 +/- 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release. CONCLUSIONS: In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.
Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes.
Authors: Upritchard J E , Sutherland W H , Mann J I
Published: March 2007

OBJECTIVE: To compare the effects of short-term dietary supplementation with tomato juice, vitamin E, and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein (C-RP) and cell adhesion molecules in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 57 patients with well-controlled type 2 diabetes aged <75 years treated with placebo for 4 weeks and then randomized to receive tomato juice (500 ml/day), vitamin E (800 U/day), vitamin C (500 mg/day), or continued placebo treatment for 4 weeks. Susceptibility of LDL to oxidation (lag time) and plasma concentrations of lycopene, vitamin E, vitamin C, C-RP, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 were measured at the beginning of the study, after the placebo phase, and at the end of the study. RESULTS: Plasma lycopene levels increased nearly 3-fold (P = 0.001), and the lag time in isolated LDL oxidation by copper ions increased by 42% (P = 0.001) in patients during supplementation with tomato juice. The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E (54%). Plasma C-RP levels decreased significantly (-49%, P = 0.004) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study. CONCLUSIONS: This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E, which also decreases plasma levels of C-RP, a risk factor for myocardial infarction, in patients with diabetes. These findings may be relevant to strategies aimed at reducing risk of myocardial infarction in patients with diabetes.
Diabetic neuropathy examination: a hierarchical scoring system to diagnose distal polyneuropathy in diabetes.
Authors: Meijer J W , van Sonderen E , Blaauwwiekel E E , Smit A J , Groothoff J W , Eisma W H , Links T P
Published: March 2007

OBJECTIVE: Existing physical examination scoring systems for distal diabetic polyneuropathy (PNP) do not fulfill all of the following criteria: validity, manageability, predictive value, and hierarchy The aim of this study was to adapt the Neuropathy Disability Score (NDS) to diagnose PNP in diabetes so that it fulfills these criteria. RESEARCH DESIGN AND METHODS: A total of 73 patients with diabetes were examined with the NDS. Monofilaments and biothesiometry were used as clinical standards for PNP to modify the NDS. RESULTS: A total of 43 men and 30 women were studied; mean duration of diabetes was 15 years (1-43), and mean age was 57 years (19-90). A total of 24 patients had type 1 diabetes, and 49 patients had type 2 diabetes. Clinically relevant items were selected from the original 35 NDS items (specific item scored positive in >3 patients). The resulting 8-item Diabetic Neuropathy Examination (DNE) score could accurately predict the results of the clinical standards and is strongly hierarchical (H value 0.53). The sensitivity and specificity of the DNE at a cut-off level of 3 to 4 were 0.96 and 0.51 for abnormal monofilament scores, respectively. For abnormal vibration perception threshold scores, these values were 0.97 and 0.59, respectively. Reproducibility as assessed by inter- and intrarater agreement was good. CONCLUSIONS: The DNE is a sensitive and well-validated hierarchical scoring system that is fast and easy to perform in clinical practice.
Diabetes Fear of Injecting and Self-Testing Questionnaire: a psychometric evaluation.
Authors: Mollema E D , Snoek F J , Pouwer F , Heine R J , van der Ploeg H M
Published: March 2007

OBJECTIVE: To study the psychometric properties of the Diabetes Fear of Injecting and Self-Testing Questionnaire (D-FISQ). RESEARCH DESIGN AND METHODS: Two groups of patients were studied. Sample A consisted of 252 insulin-treated diabetes patients. Sample B incorporated 24 insulin-treated patients with high scores (> or = 95th percentile) on the D-FISQ. Test-retest correlations were assessed in both samples. Discriminant and convergent validity of the D-FISQ were assessed with questionnaires concerning fear of hypoglycemia, trait anxiety, and fear of bodily injury, illness, or death. To evaluate criterion-related validity, sample B participated in a behavioral avoidance test (BAT), in which the current level of avoidance of either self-injecting or self-testing was determined. Exploratory factor analysis (EFA) was performed to study whether 2 factors (fear of self-injecting [FSI] and fear of self-testing [FST]) could be detected. RESULTS: Test-retest correlations ranged from 0.50 to 0.68 (P < 0.001). Correlations between D-FISQ and fear of hypoglycemia, trait anxiety, and fear of bodily injury, illness, or death ranged from 0.28 to 0.45 (P < 0.001). Patients who refused to do a BAT for self-injecting or self-testing had higher scores on FSI (P = 0.095) and FST (P = 0.01). EFA yielded 2 separate factors, FSI and FST. CONCLUSIONS: Results from this study support reliability and validity of the D-FISQ, a self-report instrument that can be used for both clinical and research purposes.
Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites.
Authors: Owens D R , Coates P A , Luzio S D , Tinbergen J P , Kurzhals R
Published: March 2007

OBJECTIVE: To determine the subcutaneous absorption rates and the appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine (HOE 901) differing only in zinc content (15, 30, and 80 microg/ml). RESEARCH DESIGN AND METHODS: We conducted 2 studies. Study 1 compared the subcutaneous abdominal injection of 0.15 U/kg of 125I-labeled insulin glargine[15], insulin glargine[80], NPH insulin, and placebo. In study 2, 0.2 U/kg of insulin glargine[30] was injected into the arm, leg, and abdominal regions. Both studies had a randomized crossover design; each enrolled 12 healthy men, aged 18-50 years. RESULTS: In study 1, the time in hours for 25% of the administered radioactivity to disappear after bolus subcutaneous injection (T75%) for NPH insulin indicated a significantly faster absorption rate compared with the 2 insulin glargine formulations (3.2 vs. 8.8 and 11.0 h, respectively P < 0.0001). Mean residual radioactivity with NPH insulin was also significantly lower at 24 h (21.9 vs. 43.8 and 52.2%, P < 0.0001). The calculated plasma exogenous insulin concentrations after NPH insulin were substantially higher than those with insulin glargine, reaching a peak within the first 6 h after administration before declining. Insulin glargine, however, did not exhibit a distinct peak. Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine (P < 0.001). In study 2, there were no significant differences in the absorption characteristics of insulin glargine between the 3 injection sites (T75% = 11.9, 15.3, and 13.2 h for arm, leg, and abdomen, respectively) or in residual radioactivity at 24 h. CONCLUSIONS: Subcutaneous absorption of insulin glargine is delayed compared with NPH insulin. There is little or no difference in the absorption rate of insulin glargine between the main subcutaneous injection sites.
Lipoprotein concentrations and carotid atherosclerosis by diabetes status: results from the Insulin Resistance Atherosclerosis Study.
Authors: Goff D C , D'Agostino R B , Haffner S M , Saad M F , Wagenknecht L E
Published: March 2007

OBJECTIVE: Lipoprotein concentrations are associated with the development of atherosclerosis in people with and without diabetes. The relative strength of these associations could differ by diabetes status as a result of diabetes-related lipoprotein modifications. RESEARCH DESIGN AND METHODS: The associations between lipoprotein concentrations and internal and common carotid artery intimal-medial thickness (IMT) assessed by B-mode ultrasonography were examined by diabetes status in a cross-sectional analysis among 1,391 participants in the Insulin Resistance Atherosclerosis Study. Participants included 442 individuals with type 2 diabetes, 308 with impaired glucose tolerance, and 641 with normal glucose tolerance. RESULTS: The differences in internal and common carotid IMT between the highest and lowest tertiles of LDL were 58.1 microm (P = 0.054) and 51.0 microm (P < 0.001), respectively. The differences in internal and common carotid IMT between the lowest and highest tertiles of HDL were 56.2 microm (P = 0.07) and 37.8 microm (P = 0.003), respectively Triglycerides and VLDL were not associated with IMT. These associations did not differ significantly because of diabetes status. CONCLUSIONS: These results support the importance of dyslipidemia as a major risk factor for atherosclerosis in people with diabetes. Future research in humans should measure lipoprotein oxidizability, glycation, size, and composition directly in people of differing glucose tolerance status to address the importance of diabetes-related lipoprotein modifications more conclusively.
Long-term follow-up of infants of mothers with type 1 diabetes: evidence for hereditary and nonhereditary transmission of diabetes and precursors.
Authors: Weiss P A , Scholz H S , Haas J , Tamussino K F , Seissler J , Borkenstein M H
Published: March 2007

OBJECTIVE: To estimate the impact of type 1 diabetes during pregnancy on transgenerational genetically caused and/or fuel-mediated amplification of types 1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin levels. RESEARCH DESIGN AND METHODS: A total of 75 white offspring of type 1 diabetic mothers and 49 control subjects of similar age and pubertal stage were examined at 5-15 years of age. All offspring had an oral glucose tolerance test. Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after loading. Lipids and autoimmune antibodies were measured in fasting plasma. RESULTS: Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%) had autoimmune antibodies. Offspring of diabetic mothers had significantly higher BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and insulin resistance than control subjects. With the exception of cholesterol, these values were significantly elevated in offspring who had elevated amniotic fluid insulin levels (>8 microU/ml, >48 pmol/l) during pregnancy compared with normoinsulinemic offspring and control subjects. CONCLUSIONS: Offspring of type 1 diabetic mothers have an increased risk for diabetes later in life. The relative risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2 diabetes-associated risk factors, such as high BMI; elevated glucose, insulin, and C-peptide levels; and insulin resistance, are related to the fetal metabolic experience in utero, as reflected by amniotic fluid insulin concentration.
Performance status of health care facilities changes with risk adjustment of HbA1c.
Authors: Zhang Q , Safford M , Ottenweller J , Hawley G , Repke D , Burgess J F , Dhar S , Cheng H , Naito H , Pogach L M
Published: March 2007

OBJECTIVE: To develop a risk adjustment method for HbA1c, based solely on administrative data and to determine the extent to which risk-adjusted HbA1c changes the identification of high- or low-performing medical facilities. RESEARCH DESIGN AND METHODS: Through use of pharmacy records, 204,472 diabetic patients were identified for federal fiscal year 1996 (FY96). Complete information (HbA1c levels, demographic data, inpatient records, outpatient pharmacy utilization records) was available on 38,173 predominantly male patients from 48 Veterans Health Administration (VHA) medical facilities. Hierarchical mixed-effects models were used to estimate risk-adjusted unique facility-level HbA1c. RESULTS: Predicted HbA1c demonstrated expected patterns for major factors known to influence glycemic control. Poorer glycemic control was seen in minorities and patients with greater disease severity, longer duration of disease (using treatment type or presence of amputation as surrogates), and more extensive comorbidity (measured by an adapted Charlson index). Better glycemic control was seen in Caucasians, older diabetic patients, and patients with higher outpatient utilization. The number of performance outliers was reduced as a result of risk adjustment. For mean HbA1c levels, 7 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. For high-risk HbA1c (>9.5%) rates, 12 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. CONCLUSIONS: Risk adjustment using only administrative data resulted in substantial changes in identification of high or low performers compared with non-risk-adjusted HbA1c. Although our findings are exploratory, risk adjustment using administrative data may be a necessary and achievable step in quality assessment of diabetes care measured by rates of high-risk HbA1c (>9.5%).
Autonomic dysfunction and urinary albumin excretion rate are associated with an abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic patients.
Authors: Pecis M , Azevedo M J , Moraes R S , Ferlin E L , Gross J L
Published: March 2007

OBJECTIVE: To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND METHODS: A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9) and nondipper patients (>0.9). RESULTS: Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. CONCLUSIONS: The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.
Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study.
Authors: Pyörälä M , Miettinen H , Laakso M , Pyörälä K
Published: March 2007

OBJECTIVE: To investigate the association of plasma insulin with all-cause, cardiovascular, and noncardiovascular mortality. RESEARCH DESIGN AND METHODS: We studied 22-year mortality data from the Helsinki Policemen Study The study population comprised 970 men, 34-64 years of age, who were free of coronary heart disease, other cardiovascular disease, and diabetes. Area under the insulin response curve (AUC insulin) during an oral glucose tolerance test was used to reflect plasma insulin levels. RESULTS: During the follow-up period, 276 men died: 130 from cardiovascular and 146 from noncardiovascular causes. The hazard ratio (HR) for hyperinsulinemia (highest AUC insulin quintile vs. combined lower quintiles) with regard to all-cause mortality adjusting for age, was 1.94 (95% CI 1.20-3.13) during the first 10 years of the follow-up period and 1.51 (1.15-1.97) during the entire 22 years; adjusting for other risk factors, the HR was 1.88 (1.08-3.30) and 1.37 (1.00-1.87) during 10 and 22 years, respectively The corresponding HRs for cardiovascular mortality during 10 and 22 years were 2.67 (1.35-5.29) and 1.73 (1.19-2.53), respectively, for age-adjusted and 2.30 (1.03-5.12) and 1.39 (0.90-2.15), respectively, for multiple-adjusted HRs. A U-shaped association was observed between insulin and noncardiovascular mortality, multiple-adjusted HRs for lowest and highest versus middle AUC insulin quintiles were 1.85 (1.20-2.86) and 1.43 (0.91-2.24), respectively CONCLUSIONS: Hyperinsulinemia was associated with increased all-cause and cardiovascular mortality in Helsinki policemen independent of other risk factors, although these associations weakened with the lengthening of the follow-up period. The association of insulin with noncardiovascular mortality was U-shaped.
Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes.
Authors: Gabir M M , Hanson R L , Dabelea D , Imperatore G , Roumain J , Bennett P H , Knowler W C
Published: March 2007

OBJECTIVE: The 1997 American Diabetes Association (ADA) and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia were evaluated and compared with respect to prediction of microvascular and macrovascular disease and mortality RESEARCH DESIGN AND METHODS: The prevalence of retinopathy and nephropathy at baseline and during the subsequent 10 years and mortality rates were examined in relation to baseline fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) among 5,023 Pima Indian adults and in relation to the cut points defined by the ADA and WHO criteria. RESULTS: The frequencies of retinopathy and nephropathy were directly related to baseline FPG and 2-h PG with approximate thresholds near or below the current diagnostic criteria for diabetes (FPG > or =7.0 and 2-h PG > or = 11.1 mmol/l). The rates of retinopathy were 4.7% in impaired fasting glucose (IFG) and 20.9% in diabetes by ADA criteria; 1.6% for impaired glucose tolerance (IGT) and 19.7% for diabetes by 1985 WHO criteria; and 1.2% for IGT and 19.2% for diabetes by the 1999 WHO criteria. Mortality rates from cardiovascular-renal-related diseases were higher in diabetic individuals (FPG > or =7.0 or 2-h PG > 11.1 mmol/l) than in those with normal FPG and 2-h PG but were not elevated in those with IFG or IGT. CONCLUSIONS: Retinopathy and nephropathy were directly related to higher FPG or 2-h PG. FPG, which identifies those at high risk of microvascular disease and mortality, can be used to predict these outcomes and to diagnose diabetes when oral glucose tolerance testing is not practical.
Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy.
Authors: Nakamura T , Ushiyama C , Shimada N , Sekizuka K , Ebihara I , Hara M , Koide H
Published: March 2007

OBJECTIVE: To determine whether the antiplatelet drug dilazep dihydrochloride affects the number of urinary podocytes in diabetic patients with microalbuminuria. RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and microalbuminuria (30 men and 20 women, mean age 48.6 years) and 30 age-matched control subjects (18 men and 12 women, mean age 49.2 years) were included in the study. No patients showed serum creatinine levels in excess of 2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy with monoclonal antibodies against podocalyxin. RESULTS: Urinary podocytes were detected in 18 of the 50 microalbuminuric diabetic patients (mean, 1.3 cells/ml). Urinary podocytes were not detected in the remaining 32 patients or in the 30 healthy control subjects. Diabetic patients positive for urinary podocytes were divided into 2 treatment groups: a dilazep dihydrochloride treatment group (300 mg/day; n = 9, group A) and a placebo group (n = 9, group B). Treatments were continued for 6 months. In group A, microalbuminuria decreased significantly from 146 +/- 42 to 86 +/- 28 microg/min (P < 0.01) and urinary podocytes also decreased from 1.3 +/- 0.8 to 0.4 +/- 0.2 cells/ml (P < 0.01). However, in group B, microalbuminuria and urinary podocytes changed little over the study period. CONCLUSIONS: Podocyte injury may occur in patients with early diabetic nephropathy, and dilazep dihydrochloride may be useful for preventing glomerular injury.
Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection.
Authors: Betterle C , Fabris P , Zanchetta R , Pedini B , Tositti G , Bosi E , de Lalla F
Published: March 2007

OBJECTIVE: The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-alpha (IFN-alpha). RESEARCH DESIGN AND METHODS: The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test. RESULTS: None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA+ patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment. CONCLUSIONS: We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.
Type 2 diabetes and maternal family history: an impact beyond slow glucose removal rate and fasting hyperglycemia in low-risk individuals? Results from 22.5 years of follow-up of healthy nondiabetic men.
Authors: Bjørnholt J V , Erikssen G , Liestøl K , Jervell J , Thaulow E , Erikssen J
Published: March 2007

OBJECTIVE: Although an excess transmission of type 2 diabetes from mothers has been documented, whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be elucidated. The objective of this study was to investigate the prevalence of and the possible prospective effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men. RESEARCH DESIGN AND METHODS: A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose (FBG) levels <110 mg/dl at baseline, in whom an intravenous glucose tolerance test (IVGTT) was administered and several conventional risk factors were measured, were followed for 22.5 years. Family history data were obtained at the baseline examination, and morbidity data were obtained from repeated investigations, hospital records, and death certificates. RESULTS: A total of 131 men reported maternal diabetes family history only, 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history. Among the 1,947 men, 143 cases of type 2 diabetes developed during 22.5 years of observation. Maternal family history and combined maternal and paternal family history predisposed to future type 2 diabetes both in univariate Cox analysis and in multivariate Cox regression analysis after adjusting for glucose disappearance rate (Rd) during an IVGTT, FBG level, BMI, physical fitness, triglyceride level, and age. Maternal family history showed a relative risk (RR) of 2.51 (95% CI 1.55-4.07), combined maternal and paternal family history showed an RR of 3.96 (1.22-12.9), and paternal family history showed an RR of 1.41 (0.657-3.05) in multivariate analysis. CONCLUSIONS: Maternal family history appears to be an important risk factor for type 2 diabetes independent of prediabetic Rd, FBG, BMI, and physical fitness levels.
Diabetes and physical disability among older U.S. adults.
Authors: Gregg E W , Beckles G L , Williamson D F , Leveille S G , Langlois J A , Engelgau M M , Narayan K M
Published: March 2007

OBJECTIVE: To estimate the prevalence of physical disability associated with diabetes among U.S. adults > or =60 years of age. RESEARCH DESIGN AND METHODS: We analyzed data from a nationally representative sample of 6,588 community-dwelling men and women > or =60 years of age who participated in the Third National Health and Nutrition Examination Survey. Diabetes and comorbidities (coronary heart disease, intermittent claudication, stroke, arthritis, and visual impairment) were assessed by questionnaire. Physical disability was assessed by self-reported ability to walk one-fourth of a mile, climb 10 steps, and do housework. Walking speed, lower-extremity function, and balance were assessed using physical performance tests. RESULTS: Among subjects > or =60 years of age with diabetes, 32% of women and 15% of men reported an inability to walk one-fourth of a mile, climb stairs, or do housework compared with 14% of women and 8% of men without diabetes. Diabetes was associated with a 2- to 3-fold increased odds of not being able to do each task among both men and women and up to a 3.6-fold increased risk of not being able to do all 3 tasks. Among women, diabetes was also associated with slower walking speed, inferior lower-extremity function, decreased balance, and an increased risk of falling. Of the >5 million U.S. adults > or =60 years of age with diabetes, 1.2 million are unable to do major physical tasks. CONCLUSIONS: Diabetes is associated with a major burden of physical disability in older U.S. adults, and these disabilities are likely to substantially impair their quality of life.
Diabetes-related emotional distress in Dutch and U.S. diabetic patients: cross-cultural validity of the problem areas in diabetes scale.
Authors: Snoek F J , Pouwer F , Welch G W , Polonsky W H
Published: March 2007

OBJECTIVE: To examine the cross-cultural validity of the Problem Areas in Diabetes Scale (PAID) in Dutch and U.S. diabetic patients. RESEARCH DESIGN AND METHODS: A total of 1,472 Dutch people with diabetes completed the PAID along with other self-report measures of affect. Statistics covered Cronbach's alpha, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA), Pearson's product-moment correlation, and t tests. Psychometric properties of PAID were compared for Dutch and U.S. diabetic patients. RESULTS: Internal consistency of the Dutch PAID was high and stable across sex and type of diabetes. Test-retest reliability was high. Principal component analyses confirmed 1 general 20-item factor, whereas EFA identified 4 new subdimensions: negative emotions, treatment problems, food-related problems, and lack of social support. These dimensions were confirmed with CFA and were replicated in the U.S. sample. The PAID and its subscales demonstrated moderate to high associations in the expected direction with other measures of affect. Dutch and U.S. subjects reported having the same problem areas, with U.S. patients reporting higher emotional distress levels both in type 1 and type 2 diabetes. CONCLUSIONS: The Dutch and U.S. 20-item PAID appeared to be psychometrically equivalent, which allowed for cross-cultural comparisons.
Personality correlates of glycemic control in type 2 diabetes.
Authors: Lane J D , McCaskill C C , Williams P G , Parekh P I , Feinglos M N , Surwit R S
Published: March 2007

OBJECTIVE: To determine whether traits of normal personality are associated with variations in glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A longitudinal cohort study was conducted using data from 105 type 2 diabetic patients in a clinical trial of a stress management intervention. Before treatment assignment, patients completed the NEO Personality Inventory, Revised, which is a questionnaire inventory measuring 5 major domains of normal personality and 30 important traits that define these domains. Glycemic control was assessed by measures of HbA1c and average blood glucose levels based on 7 days of self-monitoring at baseline and at 6 and 12 months. Relationships between personality traits and measures of glycemic control were examined by correlation and linear regression models that were adjusted for age, sex, race, duration of diabetes, medication status, and experimental treatment. RESULTS: Lower average blood glucose values at baseline were associated with higher scores for the personality domain of neuroticism and several specific traits including anxiety, angry hostility depression, self-consciousness, and vulnerability but were associated with lower scores for the trait of altruism. Results were similar for HbA1c but were not as strong. Follow-up results were similar but were less consistent. CONCLUSIONS: Personality traits may offer new insights into variations in glycemic control in patients with type 2 diabetes undergoing standard management. The relative tendency to experience fewer negative emotions and to focus on the needs of others instead of oneself could prove to be a risk factor for poor glycemic control.
Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes.
Authors: Sabbah E , Savola K , Ebeling T , Kulmala P , Vähäsalo P , Ilonen J , Salmela P I , Knip M
Published: March 2007

OBJECTIVE: To assess whether there are any differences in genetic, autoimmune, or clinical features between type 1 diabetes presenting in childhood and that diagnosed later. RESEARCH DESIGN AND METHODS: We studied 352 individuals (252 children and adolescents <20 years of age and 100 adults > or =20 years of age) manifesting clinical signs of type 1 diabetes over a period of 7.5 years at a university hospital in northern Finland with a primary catchment area population of approximately 300,000. The patients were analyzed for susceptible and protective HLA-DQB1 alleles (*02, *0302, *0301, *0602, *0603, and *0604), islet cell antibodies (ICA), insulin autoantibodies, and antibodies to GAD and IA-2 (IA-2A). Their clinical symptoms and signs were recorded at diagnosis. RESULTS: The adult patients carried the high-risk DQB1*02/0302 genotype less frequently than the children and more often had protective genotypes. They also had a decreased frequency of all 4 single autoantibody specificities and of multiple (> or =3) autoantibodies. The proportion of patients testing negative for all autoantibodies was lower among the children than among the adults. IA-2A were associated with the DQB1*0302/x genotype in both the children and adults, and the same held true for ICA among the adults. The adults were characterized by a higher proportion of males, a longer duration of symptoms, and a lower frequency of infections during the preceding 3 months. In addition, they had a higher relative body weight on admission and milder signs of metabolic decompensation (higher pH, base excess, and bicarbonate concentrations) and a lower glycated hemoglobin level at diagnosis than the children. CONCLUSIONS: Clinical manifestation of type 1 diabetes before the age of 20 years is associated with a strong HLA-defined genetic disease susceptibility, an intensive humoral immune response to various beta-cell antigens, a higher frequency of preceding infections, and a shorter duration of symptoms and more severe metabolic decompensation at diagnosis. Taken together, these observations suggest that the age at clinical onset of type 1 diabetes is determined by the intensity of the beta-cell-destructive process, which is modulated by both genetic and environmental factors.
Effectiveness of a comprehensive diabetes lower-extremity amputation prevention program in a predominantly low-income African-American population.
Authors: Patout C A , Birke J A , Horswell R , Williams D , Cerise F P
Published: March 2007

OBJECTIVE: To compare patient outcomes 1 year before and 1 year after enrollment in a comprehensive diabetes lower-extremity amputation prevention program. RESEARCH DESIGN AND METHODS: Outcome data were obtained on 197 patients enrolled in the Louisiana State University Health Sciences Center Diabetes Foot Program, which provides foot care to a predominantly low-income African-American population in Louisiana. Data were obtained using a structured interview administered by a registered nurse. Recordings were made of number of days with an open foot ulcer, number of times hospitalized for a foot problem, number of days spent in the hospital for a foot problem, number of visits to the emergency room for a foot problem, number of times an antibiotic was prescribed for a foot problem, number of all foot operations, number of lower-extremity amputations, and number of missed workdays for a foot problem. Data were obtained on all patients at the initial visit and at the 1-year follow-up. RESULTS: Analysis of data showed a reduction in foot-related ulcer days (-49%), hospitalizations, (-89%), hospital days (-90%), emergency room visits (-81%), antibiotic prescriptions, (-57%), foot operations (-87%), lower-extremity amputations (-79%), and missed workdays (-70%) after 1 year of comprehensive foot care compared with the 1-year period before treatment. CONCLUSIONS: This single cohort outcome study showed a large reduction in foot-related complications after the first year of comprehensive preventive foot care.
Fish oil supplementation in type 2 diabetes: a quantitative systematic review.
Authors: Montori V M , Farmer A , Wollan P C , Dinneen S F
Published: March 2007

OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.