bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensive Insulin Therapy With Insulin Lispro
Authors: Tsui Elaine , Barnie Annette , Ross Sue , Parkes Robert , Zinman Bernard
Published: March 2007

OBJECTIVE—To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin.

RESEARCH DESIGN AND METHODS—This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA1c level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire.

RESULTS—A significant decrease in HbA1c from baseline was shown for both groups. However, the overall treatment effect (CSII − MDI) for HbA1c was +0.08% (95% CI −0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of ±0.5% (P = 0.004). The relative treatment effect ([CSII − MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI −37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales.

CONCLUSIONS—No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than ±0.5% HbA1c between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.
Impaired Autonomic Function Is Associated With Increased Mortality, Especially in Subjects With Diabetes, Hypertension, or a History of Cardiovascular Disease
Authors: Gerritsen Jeanet , Dekker Jacqueline M. , TenVoorde Ben J. , Kostense Piet J. , Heine Robert J. , Bouter Lex M. , Heethaar Rob M. , Stehouwer Coen D.A.
Published: March 2007

OBJECTIVE—Measures of baroreflex sensitivity, heart rate variability (HRV), and the classical Ewing test parameters are currently used for the diagnosis of diabetic autonomic neuropathy and for mortality risk stratification after myocardial infarction. However, the strengths of the associations of these measures of autonomic function with risk of mortality have never been compared in one study population. Furthermore, no evidence is available on the possible effect of glucose tolerance on these associations.

RESEARCH DESIGN AND METHODS—The study population (n = 605) consisted of a glucose tolerance–stratified sample from a general population (50–75 years of age). Cardiac cycle duration and continuous finger arterial pressure were measured under two conditions: at rest and on metronome breathing. From these readings, seven parameters of autonomic function were assessed (one Ewing, five HRV, and one baroreflex sensitivity).

RESULTS—During 9 years of follow-up, 101 individuals died, 43 from cardiovascular causes. Subjects with diabetes and low levels of the autonomic function parameters, indicating impaired autonomic function, had an approximately doubled risk of mortality. This association was consistent, though not statistically significant, for all parameters. The elevated risk was not observed in subjects without diabetes, hypertension, or prevalent cardiovascular disease.

CONCLUSIONS—Impaired autonomic function is associated with all-cause and cardiovascular mortality. Moreover, the results of the present study suggest that cardiac autonomic dysfunction in patients already at risk (diabetes, hypertension, or history of cardiovascular disease) may be especially hazardous.
Good Metabolic Control Is Associated With Better Quality of Life in 2,101 Adolescents With Type 1 Diabetes
Authors: Hoey Hilary , Aanstoot Henk-Jan , Chiarelli Francesco , Daneman Denis , Danne Thomas , Dorchy Harry , Fitzgerald Michael , Garandeau Patrick , Greene Stephen , Holl Reinhard , Hougaard Philip , Kaprio Eero , Kocova Mirjana , Lynggaard Helle , Martul Pedro , Matsuura Nobuo , McGee Hannah M. , Mortensen Henrik B. , Robertson Kenneth , Schoenle Eugen , Sovik Oddmund , Swift Peter , Tsou Rosa Maria , Vanelli Maurizio , Åman Jan ,   For the Hvidøre Study Group on Childhood Diabetes
Published: March 2007

OBJECTIVE—It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families.

RESEARCH DESIGN AND METHODS—The study involved 2,101 adolescents, aged 10–18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA1c was analyzed centrally (normal range 4.4–6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires.

RESULTS—Mean HbA1c was 8.7% (range 4.8–17.4). Lower HbA1c was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores.

CONCLUSIONS—In a multiple regression model, lower HbA1c was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.
Screening Mammogram Utilization in Women With Diabetes
Authors: Beckman Thomas J. , Cuddihy Robert M. , Scheitel Sidna M. , Naessens James M. , Killian Jill M. , Pankratz V. Shane
Published: March 2007

OBJECTIVE—To determine whether women with diabetes undergo fewer screening mammograms than matched control subjects.

RESEARCH DESIGN AND METHODS—A total of 424 women with diabetes aged 50–75 years who received their primary care from general internists at a large Midwestern multispecialty group practice were retrospectively studied for frequency of mammography from August 1997 to January 2000. Two control subjects without diabetes (n = 845) were matched to each case by age, sex, provider, and date of visit. The main outcome measure was the percentage of subjects undergoing mammography 1 year before and 30 days after an index date, defined as the most recent health care visit after August 1997 and before January 2000.

RESULTS—Analysis by conditional logistic regression demonstrated that women with diabetes had significantly lower rates of mammograms than control subjects (78.1 vs. 84.9%, respectively; odds ratio 0.63, P = 0.002). After adjusting for insurance status and race, women with diabetes continued to have significantly lower rates of mammography (odds ratio 0.70, P = 0.027).

CONCLUSIONS—Women with diabetes were significantly less likely to undergo screening mammography than control subjects. Considering the increasing incidence of diabetes and the equal incidence of malignancy in women with and without diabetes, it would be beneficial to improve breast cancer screening in this population.
Is One 60° Fundus Photograph Sufficient for Screening of Proliferative Diabetic Retinopathy?
Authors: Møller Flemming , Hansen Merete , Sjølie Anne Katrin
Published: March 2007

OBJECTIVE—To compare one 60° fundus photograph to seven field stereo fundus photographs in identifying proliferative diabetic retinopathy.

RESEARCH DESIGN AND METHODS—A total of 44 eyes in 23 patients with moderate/severe nonproliferative diabetic retinopathy were included. Evaluation of each eye was based on one 60° fundus photograph. Eyes were re-examined using seven field 30° stereo fundus photographs according to the protocol of the Early Treatment Diabetic Retinopathy Study, and the photographs were examined independently by three ophthalmologists to identify retinal neovascular lesions. In addition, fluorescein angiography was performed in all patients to verify the presence of the lesions.

RESULTS—In four eyes of three patients (11.1% of eyes) evaluated based on seven field stereo photographs, retinal neovascularization was found. This condition was not found on examination of 60° fundus photographs.

CONCLUSIONS—Examination of one 60° fundus photograph was found to be insufficient as a screening procedure in patients with moderate/severe nonproliferative diabetic retinopathy.
Beneficial Effects of a Soy-Based Dietary Supplement on Lipid Levels and Cardiovascular Risk Markers in Type 2 Diabetic Subjects
Authors: Hermansen Kjeld , Søndergaard Mette , Høie Lars , Carstensen Marius , Brock Birgitte
Published: March 2007

OBJECTIVE— Consumption of soy protein has recently been shown to improve the blood lipid levels in nondiabetic subjects. The purpose of this study was to evaluate if a dietary supplement of soy protein, isoflavones, and cotyledon fiber (Abalon) affects cardiovascular risk markers, blood glucose,and insulin levels in type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS— Twenty type 2 diabetic subjects participated in a crossover trial. They were randomized to double-blind supplementation for 6 weeks with Abalon (soy protein [50 g/day] with high levels of isoflavones [minimum 165 mg/day] and cotyledon fiber [20 g/day]) or placebo (casein [50 g/day] and cellulose [20 g/day]), separated by a 3-week wash-out period.

RESULTS— The results are expressed as means ± SD. The percentage mean treatment difference between Abalon and placebo demonstrated significantly lower mean values after Abalon for LDL cholesterol (10 ±15%, P < 0.05), LDL/HDL ratio (12 ± 18%, P <0.05), apolipoprotein (apo) B100 (30 ± 38%, P < 0.01),triglycerides (22 ± 10%, P < 0.05), and homocysteine (14± 21%, P < 0.01), whereas the total cholesterol value tended to be less significant but still lower (8 ± 15%, P <0.08). No change occurred in HDL cholesterol, apo B100/apo A1 ratio,plasminogen activator inhibitor 1, factor VIIc, von Willebrand factor,fibrinogen, lipoprotein(a), glucose, HbAlc, or 24-h blood pressure.

CONCLUSIONS— These results indicate beneficial effects of dietary supplementation with Abalon on cardiovascular risk markers in type 2 diabetic subjects. This improvement is seen even in individuals with near-normal lipid values.
Differential Influence of LDL Cholesterol and Triglycerides on Lipoprotein(a) Concentrations in Diabetic Patients
Authors: Hernández Cristina , Chacón Pilar , García-Pascual Luis , Simó Rafael
Published: March 2007

OBJECTIVE— To evaluate the relationship between plasma lipid profiles and lipoprotein(a) [Lp(a)] concentrations in diabetic patients,taking into account the Lp(a) phenotype.

RESEARCH DESIGN AND METHODS— We included 191 consecutive diabetic outpatients (69 type 1 and 122 type 2 diabetic patients) in a cross-sectional study. Serum Lp(a) was determined by enzyme-linked immunosorbent assay, and Lp(a) phenotypes were assessed by SDS-PAGE followed by immunoblotting. The statistical methods included a stepwise multiple regression analysis using the Lp(a) serum concentration as the dependent variable. The lipid profile consisted of total cholesterol, HDL cholesterol,LDL cholesterol, corrected LDL cholesterol, triglycerides, and apolipoproteins AI and B.

RESULTS— In the multiple regression analysis, LDL cholesterol(positively) and triglycerides (negatively) were independently related to the Lp(a) concentration, and they explained the 6.6 and 7.8% of the Lp(a)variation, respectively. After correcting LDL cholesterol, the two variables explained 3.8 and 6.4% of the Lp(a) variation, respectively. In addition, we observed that serum Lp(a) concentrations were significantly lower in patients with type IV hyperlipidemia (mean 1.0 mg/dl [range 0.5-17], n = 16)than in normolipidemic patients (6.5 mg/dl [0.5-33.5], n = 117) and in type II hyperlipidemic patients (IIa 15.5 mg/dl [3.5-75], n = 13;IIb 9 mg/dl [1-80], n = 45); P < 0.001 by analysis of variance.

CONCLUSIONS— Lp(a) concentrations were directly correlated with LDL cholesterol and negatively correlated with triglyceride levels in diabetic patients. Therefore, our results suggest that the treatment of diabetic dyslipemia may indirectly affect Lp(a) concentrations.
Relationships of Upper Gastrointestinal Motor and Sensory Function With Glycemic Control
Authors: Rayner Christopher K. , Samsom Melvin , Jones Karen L. , Horowitz Michael
Published: March 2007

Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may, accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.
The Relationship Between Physicians’ Self-Reported Target Fasting Blood Glucose Levels and Metabolic Control in Type 2 Diabetes
Authors:   The QuED Study Group Writing Committee Coordinating Center:, Belfiglio Maurizio , De Berardis Giorgia , Franciosi Monica , Cavaliere Donatella , Di Nardo Barbara , Greenfield Sheldon , Kaplan Sherrie H. , Pellegrini Fabio , Sacco Michele , Tognoni Gianni , Valentini Miriam , Nicolucci Antonio ,   Scientific Committee:, Caimi Vittorio , Capani Fabio , Corsi Andrea , Della Vedova Roberto , Massi Benedetti Massimo , Nicolucci Antonio , Taboga Claudio , Tombesi Massimo , Vespasiani Giacomo
Published: March 2007

OBJECTIVE—To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients.

RESEARCH DESIGN AND METHODS—Physicians’ beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. ≥65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians.

RESULTS—Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels ≤6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 ± 1.6 for patients in the charge of physicians pursuing FBG levels ≤6.1 mmol/l and 7.8 ± 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients’ and physicians’ characteristics, the risk of having HbA1c values >7.0% was highly correlated with physicians’ beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy.

CONCLUSIONS—Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed.
Hospitalization Among Diabetic Children and Adolescents and the General Population in Germany
Authors: Icks Andrea , Rosenbauer Joachim , Holl Reinhard W. , Grabert Matthias , Rathmann Wolfgang , Giani Guido ,   On behalf of the German Working Group for Pediatric Diabetology
Published: March 2007

OBJECTIVE—To compare hospitalization in a multicenter-based cohort of diabetic children and adolescents (aged 1–19 years) in Germany with that of the general population.

RESEARCH DESIGN AND METHODS—Based on standardized documentation, hospital stays after manifestation were ascertained in diabetic subjects 1–19 years of age in 1997. Hospitalization data in the general German population were derived from official statistics. Incidence rates and numbers of hospital days were estimated. Ratios of hospitalization incidences and numbers of hospital days between the diabetic and the general population were calculated. Costs for hospital care in the German diabetic population in 1997 were determined.

RESULTS—A total of 5,874 patients came from 61 pediatric centers (52% male, age [mean ± SD] 12.2 ± 4.3 years, diabetes duration 4.6 ± 4.4 years). Hospitalization incidence rates and hospital days per person-year (95% CI) were 0.27 (0.25–0.29) and 1.80 (1.75–1.84) in the diabetic population and 0.0948 (0.0946–0.0949) and 0.6416 (0.6412–0.6420) in the general population. The standardized ratio of hospital incidences was 3.1 (2.9–3.2), and the ratio of numbers of hospital days was 2.8 (2.7–2.9). Costs for hospital care after manifestation were estimated to be $506 (U.S. dollars) per person-year and $12.4 million in the whole German diabetic population aged 1–19 years in 1997; including hospital stays at diabetes onset, total annual costs were $24 million ($970 per person-year).

CONCLUSIONS—Diabetic children and adolescents in Germany had an approximately three times higher hospitalization risk and three times more hospital days than the age-matched general population. Including hospitalization at diabetes onset, the annual costs of hospital care for the German diabetic population aged 1–19 years amounted to ∼1% of all costs for hospital care in this age-group. Thus, costs were largely overproportional (diabetes prevalence 0.1%).
Effectiveness of Platelet Releasate for the Treatment of Diabetic Neuropathic Foot Ulcers
Authors: Margolis David J. , Kantor Jonathan , Santanna Jill , Strom Brian L. , Berlin Jesse A.
Published: March 2007

OBJECTIVE—The goal of this study was to specifically estimate the effectiveness of platelet releasate, a widely available treatment administered by a proprietary group of wound care centers (WCCs) for the treatment of diabetic neuropathic foot ulceration.

RESEARCH DESIGN AND METHODS—Treatment effectiveness was estimated in a retrospective cohort study controlling for treatment selection bias using logistic regression–derived propensity scores.

RESULTS—Platelet releasate was more effective than standard care. The relative risk for a wound to heal after treatment with platelet releasate compared with standard care at a WCC varied from 1.14 (95% CI 1.03–1.27) to 1.59 (1.49–1.70). The effect was greatest in those with the most severe wounds, i.e., large wounds that affect deeper anatomical structures.

CONCLUSIONS—Within the limitations of the ability of propensity score analysis to control for selection bias, platelet releasate is more effective than standard therapy. This effect is more pronounced in more severe wounds. Unfortunately, severe wounds have not been evaluated in randomized clinical trials of new interventions. We encourage the inclusion of these patients in future trials.
Familial Early-Onset Type 2 Diabetes in Chinese Patients
Authors: Ng Maggie C.Y. , Lee Shao-Chin , Ko Gary T.C. , Li June K.Y. , So Wing-Yee , Hashim Yasmeen , Barnett Anthony H. , Mackay Ian R. , Critchley Julian A.J.H. , Cockram Clive S. , Chan Juliana C.N.
Published: March 2007

OBJECTIVE—We examined the prevalence of different forms of diabetes in Hong Kong Chinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 145 young patients with early-onset diabetes (age and age at diagnosis ≤40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4α, and HNF-1α. The mitochondrial DNA A→G at nucleotide 3243 (mt3243) and amylin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined.

RESULTS—The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4α, 5% for HNF-1α, 3% for mt3243, 2% for amylin S20G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria.

CONCLUSIONS—Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined.
Glycemic Control Is Related to the Morphological Severity of Diabetic Sensorimotor Polyneuropathy
Authors: Perkins Bruce A. , Greene Douglas A. , Bril Vera
Published: March 2007

OBJECTIVE—The aim of the current study was to determine the independent clinical risk factors for predicting morphological severity of distal diabetic sensorimotor polyneuropathy (DSP) as determined by fiber density (FD) on sural nerve biopsy.

RESEARCH DESIGN AND METHODS—A total of 89 patients with both type 1 and type 2 diabetes, ascertained from a large therapeutic randomized clinical trial, were included in this observational cohort study. Morphological severity of DSP was expressed as the myelinated FD in the sural nerve biopsy. General linear models were used to assess the relationship between the morphological severity of DSP and various clinical risk factors.

RESULTS—Glycated hemoglobin (GHb) was significantly related to FD in univariate and multivariate regression analyses. This relationship was present in models in which GHb was handled either as a continuous variable or as a categorical variable with the highest significance level, with a GHb cutoff level of 9%. After dividing patients into groups with optimal to moderate (GHb ≤9%) and suboptimal (GHb >9%) glycemic control, the difference in FD between the two groups ranged between 3,461 and 2,334 per mm2. FD was also significantly related to duration of diabetes and age of the patient.

CONCLUSIONS—The severity of peripheral DSP expressed by morphological criteria was significantly related to glycemic control in type 1 and type 2 diabetic patients. Inconsistent with previously published electrophysiological data demonstrating a correlation between height and conduction velocity, increasing height is not associated with morphological severity. Based on the results of the present study, it might be hypothesized that improving glycemic control will lessen severity of DSP in terms of FD loss in subjects with diabetes.
Peripheral Blood Mitochondrial DNA Content Is Related to Insulin Sensitivity in Offspring of Type 2 Diabetic Patients
Authors: Song Jihyun , Oh Jee Young , Sung Yeon-Ah , Pak Youngmi Kim , Park Kyong Soo , Lee Hong Kyu
Published: March 2007

OBJECTIVE—To investigate whether the peripheral blood mtDNA (pb-mtDNA) content is decreased and linked to insulin resistance in the offspring of type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 82 offspring of type 2 diabetic patients and 52 age-, sex-, and BMI-matched normal subjects from the Mokdong, Korea, population were selected for this study by stratified, randomized sampling. Of the offspring of diabetic patients, 52 had normal glucose tolerance (NGT), 21 had impaired glucose tolerance (IGT), and 9 had newly diagnosed type 2 diabetes. The pb-mtDNA content was measured by real-time polymerase chain reaction with a mitochondria-specific fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene. The associations between pb-mtDNA content and several parameters of insulin resistance were studied.

RESULTS—The pb-mtDNA contents tended to be lower in the 82 offspring of type 2 diabetic patients (1,084.7 ± 62.6 vs. 1,304.0 ± 99.2 in the offspring and control subjects, respectively, P = 0.051) and was significantly lower in the combined NGT and IGT offspring group (NGT+IGT, 1,068.0 ± 67.8, P < 0.05) than in the control subjects. In NGT+IGT offspring, the pb-mtDNA content was significantly correlated with logarithmically transformed insulin sensitivity (r = 0.253, P < 0.05) and was the main predictor of insulin sensitivity.

CONCLUSIONS—Quantitative mtDNA status might be a hereditary factor associated with type 2 diabetes and could serve as an indicator for insulin sensitivity.
A Model Educational Program for People With Type 2 Diabetes
Authors: Gagliardino Juan José , Etchegoyen Graciela ,   for the PEDNID-LA Research Group
Published: March 2007

OBJECTIVE—To implement an educational program in 10 Latin American countries and to evaluate its effect on the clinical, biochemical, and therapeutic aspects as well as the economic cost of diabetes.

RESEARCH DESIGN AND METHODS—Educators from each participating country were previously trained to implement the educational model. The patient population included 446 individuals with type 2 diabetes; all patients were <65 years of age, did not require insulin for metabolic control, did not have severe complications of diabetes or life-limiting illnesses, and had not previously participated in diabetes education courses. Clinical and therapeutic data and the cost of their pharmacological treatment were collected 6 months before participation in the educational program (−6 months), on entry into the program (time 0), and at 4, 8, and 12 months after initiation of the program.

RESULTS—All parameters measured had improved significantly (P < 0.001) by 1 year: fasting blood glucose (mean ± SD) 10.6 ± 3.5 vs. 8.7 ± 3.0 mmol/l; HbA1c 9.0 ± 2.0 vs. 7.8 ± 1.6%; body weight 84.6 ± 14.7 vs. 81.2 ± 15.2 kg; systolic blood pressure 149.6 ± 33.6 vs. 142.9 ± 18.8 mmHg; total cholesterol 6.1 ± 1.1 vs. 5.4 ± 1.0 mmol/l; and triglycerides 2.7 ± 1.8 vs. 2.1 ± 1.2 mmol/l. At 12 months, the decrease in pharmacotherapy required for control of diabetes, hypertension, and hyperlipidemia represented a 62% decrease in the annual cost of treatment ($107,939.99 vs. $41,106.30 [U.S.]). After deducting the additional cost of glucosuria monitoring ($30,604), there was still a 34% annual savings.

CONCLUSIONS—The beneficial results of this educational model, implemented in 10 Latin American countries, reinforce the value of patient education as an essential part of diabetes care. They also suggest that an educational approach promoting healthy lifestyle habits and patient empowerment is an effective strategy with the potential to decrease the development of complications related to diabetes as well as the socioeconomic costs of the disease.
Off-Loading the Diabetic Foot Wound
Authors: Armstrong David G. , Nguyen Hienvu C. , Lavery Lawrence A. , van Schie Carine H.M. , Boulton Andrew J.M. , Harkless Lawrence B.
Published: March 2007

OBJECTIVE—To compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes.

RESEARCH DESIGN AND METHODS—In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day).

RESULTS—The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1–26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW (P = 0.033) and half-shoe (P = 0.012). Patients were significantly less active in the TCC (600.1 ± 320.0 daily steps) compared with the half-shoe (1,461.8 ± 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 ± 563.3 daily steps, P = 0.67) or the RCW and the half-shoe (P = 0.15).

CONCLUSIONS—The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe.
Comparison of the Effect of Plasma Glucose Concentrations on Microvascular Disease Between Pima Indian Youths and Adults
Authors: Krakoff Jonathan , Hanson Robert L. , Kobes Sayuko , Knowler William C.
Published: March 2007

OBJECTIVE—To examine whether the current adult guidelines for diagnosis of diabetes are applicable to youth (age <20 years).

RESEARCH DESIGN AND METHODS—We analyzed fasting plasma glucose (FPG) and 2-h plasma glucose (PG) in two groups of Pima Indians, youths aged 5–19 years and adults aged 20–34 years, in relation to the incidence of microvascular disease when subjects were reexamined at ages 25–39 (youths) and 40–54 (adults). Microvascular disease was defined as retinopathy or a urine protein-to-creatinine ratio ≥0.5 g.

RESULTS—An increase in the incidence of microvascular disease occurred at nearly the same level of glycemia in both groups. For youths, this increase occurred at FPG ∼7.3 mmol/l and 2-h PG ∼10.0 mmol/l; for adults, this increase occurred at FPG ∼7.5 mmol/l and 2-h PG ∼10.3 mmol/l. Sensitivity of the adult diagnostic guidelines of FPG ≥7.0 mmol/l and 2-h PG ≥11.1 mmol/l for the detection of microvascular disease was much lower (with higher specificity) in youths than in adults. Receiver operating characteristics (ROC) curve areas were lower for FPG and 2-h PG for youths, suggesting that microvascular disease was less strongly predicted by baseline glucose.

CONCLUSION—The current adult guidelines for diagnosis of diabetes are applicable to youth, as they identify a population at high risk of microvascular complications.
Autoantibodies to a 38-kDa Glycosylated Islet Cell Membrane–Associated Antigen in (Pre)type 1 Diabetes
Authors: Winnock Frederic , Christie Michael R. , Batstra Manou R. , Aanstoot Henk-Jan , Weets Ilse , Decochez Katelijn , Jopart Philippe , Nicolaij Dany , Gorus Frans K. ,   The Belgian Diabetes Registry
Published: March 2007

OBJECTIVE—To study the association of autoantibodies against a 38-kDa glycated islet cell membrane–associated (GLIMA) protein with (pre)type 1 diabetes, patient characteristics, and other immune and genetic markers of the disease and to evaluate the possible added value of GLIMA antibody determinations for disease prediction and classification.

RESEARCH DESIGN AND METHODS—Recent-onset type 1 diabetic patients (n = 100), prediabetic siblings (n = 23), and nondiabetic control subjects (n = 100) were consecutively recruited by the Belgian Diabetes Registry. GLIMA antibodies were determined by immunoprecipitation of radiolabeled islet cell proteins; islet cell antibodies (ICAs) were determined by indirect immunofluorescence; and insulin autoantibodies (IAAs), insulinoma-associated protein-2 antibodies (IA-2As), and GAD antibodies (GADAs) were determined by radioligand assays.

RESULTS— GLIMA antibodies were detected in 38% of type 1 diabetic patients and 35% of prediabetic siblings (during follow-up) vs. 0% in control subjects (P < 0.001). Their prevalence was lower than that of other antibodies and was significantly associated with high levels of IA-2A and ICA (P < 0.0001). In (pre)diabetes, GLIMA antibodies could only be demonstrated in sera positive for ≥1 other autoantibody.

CONCLUSIONS— GLIMA antibodies are strongly associated with type 1 diabetes and antibody markers of rapid progression to clinical onset but have a lower diagnostic sensitivity for the disease than IAA, ICA, IA-2A, or GADA. In its present form, the GLIMA antibody assay does not provide much additional information for prediction or classification of diabetes, compared with that obtained from the measurement of IA-2As alone or in combination with IAAs, ICAs, and GADAs.
Risk of Type 1 Diabetes Development in Children With Incidental Hyperglycemia
Authors: Lorini Renata , Alibrandi A. , Vitali L. , Klersy C. , Martinetti M. , Betterle C. , d’Annunzio G. , Bonifacio E. ,   Pediatric Italian Study Group of Prediabetes
Published: March 2007

OBJECTIVE—The aim of our study was to determine whether children with incidental hyperglycemia are at an increased risk of developing type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 748 subjects, 1–18 years of age (9.04 ± 3.62, mean ± SD), without family history of type 1 diabetes, without obesity, and not receiving drugs were studied and found to have incidental elevated glycemia defined as fasting plasma glucose >5.6 mmol/l confirmed on two occasions. Subjects were tested for immunological, metabolic, and immunogenetic markers.

RESULTS—Islet cell antibodies >5 Juvenile Diabetes Foundation units were found in 10% of subjects, elevated insulin autoantibody levels in 4.6%, GAD antibody in 4.9%, and anti-tyrosine phosphatase-like protein autoantibodies in 3.9%. First-phase insulin response (FPIR) was <1st centile in 25.6% of subjects. The HLA-DR3/DR3 and HLA-DR4/other alleles were more frequent in hyperglycemic children than in normal control subjects (P = 0.012 and P = 0.005, respectively), and the HLA-DR other/other allele was less frequent than in normal control subjects (P = 0.000027). After a median follow-up of 42 months (range 1 month to 7 years), 16 (2.1%) subjects (11 males and 5 females), 4.1–13.9 years of age, became insulin dependent. All had one or more islet autoantibodies, and the majority had impaired insulin response and genetic susceptibility to type 1 diabetes. Diabetes symptoms were recorded in 11 patients and ketonuria only in 4 patients. The cumulative risk of type 1 diabetes was similar in males and females, and it was also similar in subjects under or over 10 years, whereas the cumulative risk of type 1 diabetes was increased in subjects with one or more autoantibodies and in those with FPIR <1st centile.

CONCLUSIONS—Children with incidental hyperglycemia have a higher-than-normal frequency of immunological, metabolic, or genetic markers for type 1 diabetes and have an increased risk of developing type 1 diabetes.
Serum Type IV Collagen in Diabetic Patients at Risk for Nephropathy
Authors: Cohen Margo P. , Shearman Clyde W. , Lautenslager Gregory T.
Published: March 2007

OBJECTIVE—Whereas increased urinary excretion of type IV collagen, which is believed to reflect renal overproduction of this extracellular matrix protein in early diabetic nephropathy, has been confirmed in several studies, examination of serum concentrations of this analyte has yielded conflicting results. We sought to clarify the relationship between early renal dysfunction in diabetes and circulating type IV collagen concentrations.

RESEARCH DESIGN AND METHODS—We measured serum (human) collagen IV concentrations by immunoassay in 109 patients with type 1 or type 2 diabetes and various amounts of albuminuria extending from the normo- to the macroalbuminuric range, and we examined its relationship to albumin excretion and to serum creatinine levels.

RESULTS—Serum collagen IV concentrations (mean ± SEM) were not significantly different in normoalbuminuric (219 ± 10 ng/ml), microalbuminuric (209 ± 6 ng/ml), or macroalbuminuric (206 ± 7 ng/ml) diabetic subjects or in nondiabetic normal volunteers (206 ± 10 ng/ml). Collagen IV concentrations showed no significant correlation (P > 0.25) with albumin excretion (r = −0.001), HbA1c (r = 0.030), or serum creatinine (r = −0.161) and were unrelated to urinary excretion of collagen IV in the subset of subjects in whom these data were available.

CONCLUSIONS—The results of this cross-sectional analysis discount the utility of measurement of the serum concentration of collagen IV as an indicator of early renal dysfunction in diabetes. Increased urine excretion of collagen IV without a significant change in the serum concentration is consistent with a renal origin of this analyte in early diabetic nephropathy.
The Effect of Aggressive Versus Standard Lipid Lowering by Atorvastatin on Diabetic Dyslipidemia
Authors:   The Diabetes Atorvastatin Lipid Intervention (DALI) Study Group
Published: March 2007

OBJECTIVE—In patients with type 2 diabetes, intensive glucose regulation, although effective for microangiopathy, has not been shown to have unambiguous preventive effects on the occurrence of cardiovascular disease. Patients with diabetes show a characteristic dyslipidemia (high triglyceride level, low HDL cholesterol level). Aggressive reduction of triglycerides might be an effective method to reduce the cardiovascular risk in these patients.

RESEARCH DESIGN AND METHODS—A double-blind, placebo-controlled, randomized study to assess the effect of 30 weeks of administration of atorvastatin 10 and 80 mg on plasma triglyceride levels in 217 patients with type 2 diabetes and fasting triglyceride levels between 1.5 and 6.0 mmol/l.

RESULTS—Administration of atorvastatin 10 and 80 mg resulted in significant reductions (25 and 35%, respectively) of plasma triglyceride levels (both P < 0.001). The difference between 10 and 80 mg was not statistically significant (P > 0.5). Atorvastatin 10 mg provided significant reductions from baseline in total cholesterol (−30%, P < 0.001), LDL cholesterol (−40%, P < 0.001), and apolipoprotein B (−31%, P < 0.001), and significantly increased HDL cholesterol from baseline by 6% (P < 0.005). Atorvastatin 80 mg had a similar effect on HDL cholesterol (+5.2%, P < 0.005) but significantly decreased total cholesterol (−40%, P < 0.001), LDL cholesterol (−52%, P < 0.001), and apolipoprotein B (−40%, P < 0.001) more than atorvastatin 10 mg (P < 0.005). The side effects of atorvastatin 10 and 80 mg were similar and did not differ from the patients receiving placebo.

CONCLUSIONS—Administration of 10- and 80-mg doses of atorvastatin provides similar, significant reductions from baseline in triglyceride levels in patients with type 2 diabetes. A higher dose of atorvastatin improves cholesterol-related parameters. Both doses were well tolerated in this patient population.
The Effect of Day Care Exposure on the Risk of Developing Type 1 Diabetes
Authors: Kaila Brinderjit , Taback Shayne P.
Published: March 2007

OBJECTIVE—Exposure to infections in infancy or childhood may be important in the pathogenesis of type 1 diabetes, but a protective role has also been suggested. We tested the hypothesis that increased early contact with infectious agents, measured by day care exposure, would decrease the risk of type 1 diabetes in childhood.

RESEARCH DESIGN AND METHODS—We conducted a systematic review of case-control studies. Meta-analysis was performed to combine results, assess for heterogeneity, and explore variation in study design.

RESULTS—Several generally well-designed case-control studies show a statistically significant protective effect of day care on type 1 diabetes. However, meta-analysis revealed too much heterogeneity to accept the overall synthesis results and none of the studies used prerecorded data. Day care does seem to have a protective effect in the subgroup of children who will be diagnosed with type 1 diabetes before the age of 5 years (odds ratio = 0.6, 95% CI 0.5–0.8); however, this result is based on only two studies.

CONCLUSIONS—Recall bias is one alternate explanation for these data; confirmation using prerecorded data is required. Such data could be prospectively measured in cohort studies of children at risk. We also suggest that information about day care attendance be measured in randomized trials of agents for the prevention of type 1 diabetes, as day care exposure could potentially modify the effect of the preventive agent.
High Prevalence of Type 2 Diabetes in All Ethnic Groups, Including Europeans, in a British Inner City
Authors: Riste Lisa , Khan Farida , Cruickshank Kennedy
Published: March 2007

OBJECTIVE—To compare the prevalence of type 2 diabetes in white Europeans and individuals of African-Caribbean and Pakistani descent.

RESEARCH DESIGN AND METHODS—Random sampling of population-based registers in inner-city Manchester, Britain’s third most impoverished area. A total of 1,318 people (25–79 years of age) were screened (minimum response 67%); 533 individuals without known diabetes underwent 2-h glucose tolerance testing, classified by 1999 World Health Organization criteria.

RESULTS—More than 60% of individuals reported household annual income <£10,000 ($15,000) per year. Energetic physical activity was rare and obesity was common. Age-standardized (35–79 years) prevalence (mean 95% CI) of known and newly detected diabetes was 20% (17–24%) in Europeans, 22% (18–26%) in African-Caribbeans, and 33% (25–41%) in Pakistanis. Minimum prevalence (assuming all individuals not tested were normoglycemic) was 11% (8–14%), 19% (15–23%), and 32% (24–40%), respectively. Marked changes in prevalence represent only small shifts in glucose distributions. Regression models showed that greater waist girth, lower height, and older age were independently related to plasma glucose levels, as was physical activity. Substituting BMI and waist-to-hip ratio revealed their powerful contribution.

CONCLUSIONS—A surprisingly high prevalence of diabetes, despite expected increases with new lower criteria, was found in Europeans, as previously established in Caribbeans and Pakistanis. Lower height eliminated ethnic differences in regression models. History and relative poverty, which cosegregate with obesity and physical inactivity, are likely contributors. Whatever the causes, the implications for health services are alarming, although substantial preventive opportunities through small reversals of glucose distributions are the challenge.
Postchallenge Hyperglycemia and Mortality in a National Sample of U.S. Adults
Authors: Saydah Sharon H. , Miret Montserrat , Sung Jennifer , Varas Cristina , Gause Douglas , Brancati Frederick L.
Published: March 2007

OBJECTIVE—Although postchallenge hyperglycemia is a well-established feature of type 2 diabetes, its association with risk of mortality is uncertain. Therefore, the aim of this study was to assess the independent association of fasting and 2-h glucose levels with all-cause and cardiovascular disease (CVD) mortality.

RESEARCH DESIGN AND METHODS—We analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study, a prospective cohort study of U.S. adults examined in the NHANES II, and focused on the 3,092 adults aged 30–74 years who underwent an oral glucose tolerance test at baseline (1976–1980). Deaths were identified from U.S. national mortality files from 1976 to 1992. To account for the complex survey design, we used SUDAAN statistical software for weighted analysis.

RESULTS—Compared with their normoglycemic counterparts (fasting glucose [FG] <7.0 and 2-h glucose <7.8 mmol/l), adults with fasting and postchallenge hyperglycemia (FG ≥7.0 and 2-h glucose ≥11.1 mmol/l) had a twofold higher risk of death after 16 years of follow-up (age- and sex-adjusted relative hazard [RH] 2.1, 95% CI 1.4–3.2). However, adults with isolated postchallenge hyperglycemia (FG <7.0 and 2-h glucose ≥11.1 mmol/l) were also at higher risk of death (1.6, 1.0–2.6). In proportional hazards analysis, FG (fully adjusted RH 1.10 per 1 SD; 95% CI 1.01, 1.22) and 2-h glucose (1.14, 1.00–1.29) showed nearly identical predictive value for mortality. Similar trends were observed for CVD mortality.

CONCLUSIONS—These results suggest that postchallenge hyperglycemia is associated with increased risk of all-cause and CVD mortality independently of other CVD risk factors.
Peripheral Arterial Disease in Diabetic and Nondiabetic Patients
Authors: Jude Edward B. , Oyibo Samson O. , Chalmers Nicholas , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients.

RESEARCH DESIGN AND METHODS—Randomly selected lower-extremity angiograms were examined according to the Bollinger system. Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died.

RESULTS—A total of 136 arteriograms obtained between 1992 and 1996 were analyzed. The age (mean ± SD) of the patients was 64.7 ± 10.8 years. Diabetic patients (43%) and nondiabetic patients were of similar age (63.9 ± 10.4 vs. 65.3 ± 11.1 years, P = 0.43), with a similar history of smoking (81.0 vs. 76.9%, P = 0.26), ischemic heart disease (41.4 vs. 37.2%, P = 0.54), and hypercholesterolemia (24.4 vs. 30.8%, P = 0.48). However, there were a greater proportion of hypertensive patients in the diabetic group (63.8 vs. 39.7%, P = 0.006). Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee (P = 0.02). A greater number of amputations occurred in the diabetic group: diabetic patients were five times more likely to have an amputation (41.4 vs. 11.5%, odds ratio [OR] 5.4, P < 0.0001). Mortality was higher in the diabetic group (51.7 vs. 25.6%, OR 3.1, P = 0.002), and diabetic patients who died were younger at presentation than nondiabetic patients (64.7 ± 11.4 vs. 71.1 ± 8.7 years, P = 0.04).

CONCLUSIONS—In patients with peripheral arterial disease, diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients.