bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case-Control Study of Diet in Newly Diagnosed NIDDM in the Wanigela People of Papua New Guinea
Authors: Hodge Allison M , Montgomery Janice , Dowse Gary K , Mavo Barnabas , Watt Tahlia , Zimmet Paul Z
Published: March 2007

OBJECTIVE

To study the association between diet and newly diagnosed NIDDM in the Wanigela people of Papua New Guinea, a population with an extraordinary susceptibility for NIDDM.

RESEARCH DESIGN AND METHODS

We performed a case-control study of Wanigela people from an urban settlement (Koki). Case patients (n = 145) were asymptomatic subjects in whom NIDDM was newly diagnosed using a 2-h 75-g oral glucose tolerance test. Control subjects with glucose tolerance (n = 140) were group-matched on the basis of age and sex. A detailed food frequency questionnaire was used to determine energy and nutrient intakes. Nutrient intakes were compared directly and after calculation of residuals to correct for energy intake. Odds ratios for NIDDM were computed in relation to total energy and specific nutrient intakes, adjusting for age, sex, BMI, waist-to-hip ratio, and physical activity.

RESULTS

There were no differences between case patients and control subjects in mean values of total energy-adjusted nutrient intakes. In logistic regression models, neither total energy nor any specific nutrients were associated with increased risk of NIDDM. When models were repeated with nutrients categorized by textiles, there were marginally significant associations with intakes of fiber (positive) and cholesterol, protein, and sugar (negative).

CONCLUSIONS

This study does not support the hypothesis that saturated fat is an independent risk factor for NIDDM. The weak associations of intakes of fiber and cholesterol with newly diagnosed NIDDM were in the opposite directions to those expected and are probably due to chance. Relative homogeneity of diet within a community, such as that found in Koki, makes it difficult to demonstrate risk factor-disease associations. However, changes in diet and reduced levels of physical activity accompanying urbanization undoubtedly contribute to the high prevalence of obesity observed in this community, and hence diet is likely to contribute to NIDDM risk at least by indirect means.
The Prevalence of Diabetes in Rio de Janeiro, Brazil
Authors: Oliveira Jose Egídio P , Milech Adolpho , Franco Laercio J ,   The Cooperative Group for the Study of Diabetes Prevalence in Rio De Janeiro
Published: March 2007

OBJECTIVE

To assess the prevalence of diabetes and impaired glucose tolerance (IGT) in the adult population of Rio de Janeiro, a two-stage cross-sectional survey was carried out in a random sample of 2,051 individuals aged 30–69 years from Rio de Janeiro city in Brazil.

RESEARCH DESIGN AND METHODS

Subjects were first screened by fasting capillary glycemia (FCG). All individuals who screened positive (FCG > 5.6 mmol/l) and every sixth consecutive person who screened negative (FCG < 5.6 mmol/l) were subjected to a 75-g glucose load. Diagnoses of diabetes and IGT were based on World Health Organization criteria.

RESULTS

Results from every sixth individual who screened negative were extrapolated to all individuals who screened negative after adjustment for some potential bias in the subsample. Age-adjusted prevalence rates for diabetes and IGT were 7.1 and 9.0%, respectively. The rates were higher (P < 0.01) among women than among men (8.7 vs. 5.2% for diabetes and 11.7 vs. 5.8% for IGT), among obese individuals than among nonobese individuals (7.9 vs. 6.2% for diabetes and 11.4 vs. 7.3% for IGT), and among those with family history of diabetes than among those without family history of diabetes (12.4 vs. 4.8% for diabetes and 13.8 vs. 6.7% for IGT). The rates for diabetes and IGT increased with age, being 1.7 and 4.5%, respectively, for the age-group of 30–39 years, 3.9 and 8.5% for the age-group of 40–49 years, 13.6 and 13% for the age-group of 50–59 years, and 17.3 and 15.3% for the age-group of 60–69 years (P < 0.01). The prevalence of diabetes was higher among individuals with low educational levels than among those with high educational levels (7.3 vs 4.2%). For IGT, the rates increased from the group with intermediate level of education (8.3%) to the low- (11.3%) and high-education group (12.6%). Differences in the rates for whites and non-whites (6.9 vs. 7.1% for diabetes and 8.8 vs. 9.6% for IGT) were not statistically significant. Among those with confirmed diabetes in the survey, 27.6% did not know of their diabetic condition. Among previously diagnosed diabetes (self-reported diabetes), 19.5% were not being treated, 31.8% were on diet only, 40.7% were on oral hypoglycemic drugs, and 8.0% were on insulin. Self-reported prevalence of diabetes was 0.1% for the population < 30 years of age, 4.3% for the 30–69 year old age-group, and 16.6% for those > 70 years of age.

CONCLUSIONS

The numbers found for Rio de Janeiro are similar to those for more developed countries and lead us to conclude that the impact of diabetes on public health is the same as in those countries where this disease is considered an important health problem.
A Prevalence Survey of Diabetes in Mauritania
Authors: Ducorps Michel , Baleynaud Serge , Mayaudon Herve , Castagne Christian , Bauduceau Bernard
Published: March 2007

OBJECTIVE

To perform an epidemiological study of the prevalence of diabetes in Mauritania, West Africa, with little data available on diabetes in West Africa.

RESEARCH DESIGN AND METHODS

The study was performed with a representative sample of the Mauritanian population. A random selection of the study population (n = 744) was drawn by a cluster sampling method. Screening for diabetes was made by capillary blood glucose (CBG) measurement, using strips analyzed by reflectance meter. Criteria for the diagnosis of diabetes were those of the World Health Organization (WHO).

RESULTS

The survey performed a screening of 744 subjects whose sex distribution was 307 men and 437 women. Their mean age was 34.6 ± 15.2 years, and their mean BMI was 22.7 ± 5.1 kg/m2, with a significant difference for BMI between men (20.0 ± 2.9 kg/m2) and women (24.3 ± 5.5 kg/m2). According to the study criteria, we found 14 diabetic patients (4 men, 10 women). The crude prevalence of diabetes was 1.88% (95% CI 0.90–2.86). The difference in prevalence by sex was 1.30% (95% CI 0.00–2.60) for men and 2.29% (95% CI 0.89–3.43) for women. For the truncated 30- to 64-year-old age-group, the crude prevalence was 2.84%; the age-adjusted prevalence for the same 30- to 64-year-old age-group, using the standardized age distribution of Segi (10), was 2.61%.

CONCLUSIONS

With a crude prevalence of diabetes of 1.88% and an age-adjusted prevalence of 2.61%, Mauritania may be classified among the countries with a low prevalence of diabetes, a finding which is not surprising, considering the low level of development of this region of Africa.
Potential Therapeutic Levels of Glucagon-Like Peptide I Achieved in Humans by a Buccal Tablet
Authors: Gutniak Mark K , Larsson Hillevi , Heiber Sonia J , Juneskans Olof T , Holst Jens J , Ahrén Bo
Published: March 2007

OBJECTIVE

Glucagon-like peptide I(7–36) (GLP-I) amide, an endogenous incretin, has been identified as a potential adjunct to the treatment of NIDDM and has been studied following intravenous and subcutaneous injection. A mucoadhesive buccal GLP-I tablet containing 119 nmol has been developed to provide transmucosal absorption as a possible alternative to injection treatment.

RESEARCH DESIGN AND METHODS

Eight healthy volunteers received a single tablet under fasting conditions in this randomized double-blind placebo-controlled study. A total GLP-I immunoreactivity was measured using COOH-terminal radioimmunoassay (RIA) (total peptide activity) and NH2-terminal RIA (active, nondegraded peptide).

RESULTS

The mean (± SE) peak GLP-I concentration was 117 ± 19 pmol/l and occurred 30 ± 4 min after application. The mean placebo-adjusted area under curve was 8,145 ± 873 pmol · min−1 · l−1, consistent with a relative bioavailability of 7% versus intravenous injection and 47% versus subcutaneous injection. The levels of active peptide increased in parallel with total GLP-I. Half-life of peptide activity after buccal administration was 27 and 24 min measured with COOH-terminal and NH2-terminal RIA, respectively. Placebo adjusted insulin concentrations increased to a peak of 252 ± 57 pmol/l, glucose decreased 1.4 ± 0.2 mmo/l, and glucagon decreased 17 ± 3 ng/l, consistent with the increase in plasma GLP-I concentrations.

CONCLUSIONS

Therapeutic plasma levels of GLP-I in humans were achieved after a single buccal tablet. No increased degradation of GLP-I was found in the buccal mucosa compared to subcutaneous tissue. This alternative treatment form may be feasible in in the future for NIDDM.
How Have Patients Reacted to the Implications of the DCCT?
Authors: Thompson Chris J , Cummings J Fraser , Chalmers John , Gould Craig , Newton Ray W
Published: March 2007

OBJECTIVES

To assess the reactions of people with insulin-treated diabetes (ITD) to the results of the Diabetes Control and Complications Trial (DCCT).

RESEARCH DESIGN AND METHODS

A leaflet documenting the purpose and results of the DCCT was circulated to all 771 patients ages 15–60 years with ITD attending our clinic. Patients were invited to complete and return a questionnaire on their responses.

RESULTS

Of 550 respondents, 330 felt encouraged to improve glycemic control. Female respondents (P = 0.003) and younger age-groups (15–25 years, P = 0.001) were most likely to want to improve control. Patients with long duration of diabetes (> 20 years, P = 0.00001), hypoglycemia unawareness (P = 0.0001), or previous severe hypoglycemia (P = 0.001) were less likely to want to improve their control. Fear of hypoglycemia concerned all age-groups, whereas female respondents were most likely to be worried about the potential for weight gain (P = 0.00006).

CONCLUSIONS

Knowledge of the results of the DCCT encourages significant numbers of patients to want to improve glycemic control. Fear of hypoglycemia and, in women, weight gain may prove significant impediments to the clinical implementation of the results of the DCCT.
Prevalence of Major Vascular Complications at the Initial Visit Among Japanese Diabetic Patients
Authors: Miki Eishi , Akanuma Yasuo , Kanazawa Yasunori , Sando Hiroyuki , Kikuchi Masatoshi , Kawazu Shoji , Kosaka Kinori
Published: March 2007

The frequencies of retinopathy, proteinuria, hypertension, and electrocardiographic (ECG) abnormalities in 2025 diabetic subjects new to our clinic in Tokyo were analyzed in relation to status at initial visit with respect to age, estimated duration of diabetes, and fasting blood glucose. Frequency and severity of retinopathy increased markedly with duration of diabetes. A relationship was found between retinopathy at first visit and level of blood glucose at that time. Proteinuria also clearly increased with duration; its frequency was generally higher in older age groups. Frequency of hypertension increased with age up to 60 yr, but there was no association between prevalence of hypertension and duration of diabetes. ECG abnormalities also increased with age, although serious abnormalities were rare even in older subjects. Hypertension and ECG abnormalities were not more common in those with higher initial blood glucose values, and the frequencies of these aberrations did not increase with the duration of diabetes. ECG abnormalities were more common among hypertensives, especially in younger age groups. Despite the clear effect of degree and duration of hyperglycemia on microvascular complications, there was no evidence of a direct effect of hyperglycemia on macrovascular abnormalities in this study.
Plasma Insulin and C-Peptide Levels During Continuous Subcutaneous Insulin Infusion
Authors: Slama Gerard , Phuoc Buu Kim Nguyen , Tchobroutsky Georges , Delage Anne , Desplanque Nelly
Published: March 2007

A study was performed to estimate the absorption kinetics of insulin infused subcutaneously. Four insulin-dependent diabetic subjects had their insulin pumped through a subcutaneously implanted fine polyethylene catheter at a constant rate of 5.0 ± 0.3 ml/h but at two different insulin concentrations: 218 mU/ml between meals, and 2400 mU/ml at the start of breakfast, lunch, and dinner (lasting 20, 30, and 30 min, respectively). The amount (40 U/day) and distribution of insulin delivered was identical in the four patients in order to facilitate comparison between the subjects. No attempt was made to normalize their blood glucose during the study period. A study of the kinetics of insulin absorption was made by assaying plasma insulin levels; lack of plasma anti-insulin antibodies was verified; plasma C-peptide levels were measured and were far below values observed in the fed state in nondiabetic patients. The mean maximum insulin level reached after switching from low to high concentration insulin was observed 87 ± 2 min after breakfast, 117 ± 22 min after lunch, and 125 ± 20 min after dinner. Differences observed are not significant. These values are similar to those observed after subcutaneous injection of 40 U/ml Regular insulin as a single bolus. After switching from high to low concentration, plasma insulin levels did not return to their basal values before the third or fourth hour. Subcutaneous insulin infusion could be a safe and easy way of insulin administration in an open-loop system; however, this method does not seem to be suitable for a closed-loop system.
Long-Term Therapy of IDDM With an Implantable Insulin Pump
Authors: Dunn Fredrick L , Nathan David M , Scavini Marina , Selam Jean-Louis L , Wingrove Theresa G ,   The Implantable Insulin Pump Trial Study Group
Published: March 2007

OBJECTIVE

To examine the long-term benefits and risks of treatment of IDDM with an implantable programmable insulin pump.

RESEARCH DESIGN AND METHODS

Seventy-six patients with IDDM were studied at nine clinical centers. After 3–4 months of intensive subcutaneous therapy, the Infusaid Model 1000 pump was implanted, and insulin was delivered either intraperitoneally or intravenously for an average of 39.6 ± 10 months (251 patient-years). Data was collected for glycemic control, lipid levels, weight gain, insulin requirements, adverse events, and quality of life. Sixty-three patients were also followed for 8.5 ± 6.3 months (45 patient-years) after pump therapy was discontinued.

RESULTS

Mean quarterly HbA1c fell with subcutaneous intensive therapy and remained stable on implantable pump therapy between 6.9 and 7.5%. Severe hypoglycemia was relatively rare, with only 4 episodes/100 patient-years of implantable pump therapy. This rate was significantly less than with subcutaneous intensive therapy before implantable pump initiation (33 episodes/100 patient-years) or after discontinuation of implantable pump therapy (36/100 patient-years) (P < 0.003). Weight did not increase significantly in the 1st year of therapy, but increased by 2.0 ± 4.3 kg after 3 years of therapy. There were no significant differences in metabolic control or adverse events between intraperitoneal and intravenous insulin therapy except for minor differences in lipid levels and the more frequent development of catheter obstruction with intravenous delivery. Most pump slow-downs and catheter occlusions were corrected noninvasively. Quality of life, as measured by the Diabetes Control and Complications Trial instrument, showed high satisfaction and improved impact scores.

CONCLUSIONS

Long-term implantable pump therapy maintained HbA1c in a range similar to intensive subcutaneous therapy, but with fewer episodes of severe hypoglycemia. Although pump and catheter occlusions remain a limitation, patient satisfaction with implantable pump therapy remains high.
The PATHWAYS Church-Based Weight Loss Program for Urban African-American Women at Risk for Diabetes
Authors: McNabb Wylie , Quinn Michael , Kerver Jean , Cook Sandy , Karrison Theodore
Published: March 2007

OBJECTIVE

This study was carried out to test the effectiveness of PATHWAYS, a weight loss program designed specifically for urban African-American women, when administered in urban churches by trained lay facilitators.

RESEARCH DESIGN AND METHODS

Thirty-nine obese women were recruited from three urban African-American churches. After randomization and the collection of baseline data on weight and lifestyle practices, subjects in the experimental group (n = 19) were assigned to receive a 14-week weight loss program (PATHWAYS) conducted by trained lay volunteers; control group subjects (n = 20) were put on a waiting list to receive the program at the conclusion of the study period.

RESULTS

Of the 39 women enrolled, 15 experimental group subjects and 18 control group subjects were available for posttreatment data collection. After completing the program, PATHWAYS participants lost an average of 10.0 lb, and the control group subjects gained an average of 1.9 lb. Posttreatment difference in weight loss between the groups was statistically significant (P < 0.0001). Waist circumference among PATHWAYS participants decreased 2.5 inches, while waist circumference among control group subjects remained relatively the same. This difference between the groups was statistically significant (P < 0.05).

CONCLUSIONS

A weight loss program administered by trained lay volunteers was effective in producing significant and clinically meaningful weight loss among African-American women who often do not benefit from typical weight loss programs. Ongoing research is focusing on whether the weight loss can be maintained or enhanced through monthly reinforcement sessions.
Disparity in Glycemic Control and Adherence Between African-American and Caucasian Youths With Diabetes: Family and community contexts
Authors: Auslander Wendy F , Thompson Sanna , Dreitzer Daniele , White Neil H , Santiago Julio V
Published: March 2007

OBJECTIVE

To describe sociodemographic, family, and community factors that contribute to the glycemic control of African-American and Caucasian youths with diabetes, we investigated two questions: 1) Is there a disparity in glycemic control between African-American and Caucasian youths with diabetes, and if so, what sociodemographic, family, and community factors explain the disparity? and 2) Is there a difference in the adherence to treatment between African-American and Caucasian youths with diabetes, and if so, what sociodemographic, family, and community factors explain the difference?

RESEARCH DESIGN AND METHODS

This cross-sectional study included 146 youths with diabetes (95 Caucasians and 51 African-Americans) and their mothers. The youths were invited to participate if they had been diagnosed with diabetes at least 1 year before the study, did not have another chronic illness, and were < 18 years of age.

RESULTS

The findings indicate that African-American youths with diabetes are in significantly poorer metabolic control than their Caucasian counterparts (1.5% difference in HbA1c levels). Single-parent household status and lower levels of adherence partially account for the poorer glycemic control. Examination of the adherence subscales indicates that African-Americans report significantly lower adherence to diet and glucose testing than Caucasian youths.

CONCLUSIONS

This study suggests that African-American youths with diabetes may be at greater risk for poor glycemic control due to the higher prevalence of single parenting and lower levels of adherence found in this population.
Factors Related to Glycemic Control in IDDM and Insulin-Treated NIDDM Patients in Current Practice: A comparison of care policies
Authors: Garancini Maria Paola , Gallus Giuseppe , Cucinotta Domenico , Rossi Andrea , Riccardi Gabriele ,   Siemtic Group
Published: March 2007

OBJECTIVE

To evaluate, under routine conditions, the relation between different diabetes care policies and glycemic control through a by-center analysis procedure aimed at reducing some drawbacks of cross-sectional data.

RESEARCH DESIGN AND METHODS

A survey on insulin-treated diabetes care management (IDDM and NIDDM) involved 16 Italian randomly selected diabetes outpatient clinics. A total of 2,142 representative patients were investigated. The standardized HbA1c average value of each center was related, by regression models, to some indicators of center care policy (average number of injections, average BMI, proportion of cases with recent fundus oculi examinations, or frequent visits) as well as to patients' average social levels (employment type). Homogeneity in patient admission criteria is assumed among the investigated centers as a basic condition for the procedure validity. Some known imbalance were controlled for both design and analysis.

RESULTS

HbA1c showed a univariate inverse relation with daily number of injections in IDDM (P = 0.0009, r2 = 0.56) but not in NIDDM (P = 0.33). It was inversely related to both fundus examination (IDDM P = 0.04; NIDDM P = 0.099) and qualified employment (IDDM P = 0.06; NIDDM P = 0.026). A stepwise regression analysis left in the model insulin injections (P = 0.0002) in IDDM (total r2 = 0.68) and qualified employment (P = 0.016) and fundus examination (P = 0.14) in NIDDM (total r2 = 0.53), after controlling for age, sex, disease duration, insulin therapy starting delay, and insulin dose per kilogram.

CONCLUSIONS

These results suggest that the confirmed benefits of a multiple-injection regimen in IDDM cannot be simply extrapolated to NIDDM, where patients' awareness and medical attention to complications proved to be the most important factors in current practice.
Reducing Plantar Pressure in the Neuropathic Foot: A comparison of footwear
Authors: Lavery Lawrence A , Vela Steven A , Fleischli John G , Armstrong David G , Lavery David C
Published: March 2007

OBJECTIVE

To compare the effectiveness of therapeutic, comfort, and athletic shoes with and without viscoelastic insoles.

RESEARCH DESIGN AND METHODS

We compared pressure reduction at ulcer sites under the hallux (n = 10), first metatarsal (n = 10), and lesser metatarsals (n = 12), using extra-depth, athletic, and comfort shoes with and without viscoelastic insoles. A rubber-soled canvas oxford was used to establish baseline pressure values.

RESULTS

When used in conjunction with a viscoelastic insole, all shoe types reduced mean peak plantar pressure better than their non-insoled counterparts (P < 0.05). Consistently, comfort shoes reduced pressure significantly better than both the cross trainers and extra-depth shoes for ulcers under the first and lesser metatarsals (P < 0.05). For each shoe type, the addition of the viscoelastic insole provided a significant reduction in mean peak pressure (P < 0.05). Compared with stock insoles, viscoelastic insoles reduced pressures an additional 5.4-20.1% at ulcer sites. The same trend was also observed at regions of the foot not associated with an ulceration.

CONCLUSIONS

When used in conjunction with a viscoelastic insole, both the comfort and athletic cross-trainer shoes studied were as, if not more, effective than commonly prescribed therapeutic shoes in reducing mean peak first and lesser metatarsal pressures. Furthermore, comfort shoes were as effective as therapeutic shoes in reducing pressure under the great toe. Both of these shoe types may be viable options to prevent the development or recurrence of foot ulcers.
A Prospective Study of Oral Contraceptives and NIDDM Among U.S. Women
Authors: Chasan-Taber Lisa , Willett Walter C , Stampfer Meir J , Hunter David J , Colditz Graham A , Spiegelman Donna , Manson Joann E
Published: March 2007

OBJECTIVE

To examine prospectively the association between modern oral contraceptives with low doses of estrogen and progestin and subsequent incidence of NIDDM.

RESEARCH DESIGN AND METHODS

In a prospective cohort study, 98,590 U.S. female nurses aged 25 to 42 and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline in 1989 were followed for 4 years. Endpoint was incidence of confirmed NIDDM. Oral contraceptive use was reported on mailed questionnaires.

RESULTS

During 352,067 person-years follow-up, we confirmed 185 incident cases of NIDDM. After adjusting for age, BMI, cigarette smoking, family history of diabetes, parity, physical activity, alcohol intake, ethnicity, history of diagnosis of infertility, elevated cholesterol, and hypertension, women currently using oral contraceptives had a relative risk (RR) of 1.6 (95% CI, 0.9–3.1). For past users, the multivariate RR was 1.2 (95% CI, 0.8–1.8). This association was attenuated after restricting the analysis to symptomatic cases of NIDDM. For current users, RR = 1.3 (95% CI, 0.6–2.8), and for past users, RR = 0.9 (95% CI, 0.6–1.4), suggesting that increased surveillance may explain at least part of any excess risk.

CONCLUSIONS

In this large prospective study, we found no appreciable increase in the 4-year risk of NIDDM among current users of oral contraceptives. There was no apparent increase in risk among past users. The small number of cases reflect the low absolute risk of NIDDM in this population of young women.
Effects of Electrical Stimulation on Wound Healing in Patients With Diabetic Ulcers
Authors: Baker Lucinda L , Chambers Richard , DeMuth Sharon K , Villar Fernando
Published: March 2007

OBJECTIVE

To evaluate the effects of two stimulation waveforms on healing rates in patients with diabetes and open ulcers. The hypothesis was that stimulus waveforms with minimal polar characteristics would provide significant healing for this patient sample.

RESEARCH DESIGN AND METHODS

This was a prospective study that enrolled 80 patients with open ulcers. Patients received stimulation with either an asymmetric biphasic (A) or symmetric biphasic (B) square-wave pulse. Amplitudes were set to activate intact peripheral nerves in the skin. Two other groups received either very low levels of stimulation current (MC), or no electrical stimulation (C). When combined these groups were referred to as the control group. Treatment was carried out daily until the wound healed, the patient withdrew from the study, or the physician changed the overall wound management program. Average healing rates were calculated from weekly measures of the wound perimeter and were used for statistical comparison through a one-way analysis of variance.

RESULTS

Stimulation with the A protocol significantly increased the healing rate, enhancing healing by nearly 60% over the control rate of healing. Stimulation with the B protocol did not increase the healing rate when compared with control subjects.

CONCLUSIONS

Electrical stimulation, given daily with a short pulsed, asymmetric biphasic waveform, was effective for enhancement of healing rates for patients with diabetes and open ulcers.
A Double-Masked Placebo-Controlled Trial Assessing Effects of Various Doses of BTS 67,582, a Novel Insulinotropic Agent, on Fasting Hyperglycemia in NIDDM Patients
Authors: Skillman Carmela A , Raskin Philip
Published: March 2007

OBJECTIVE

To determine the effect over a 4-week period of varying doses of BTS 67,582, a novel nonsulfonylurea insulinotropic agent, on fasting plasma glucose (FPG) levels in sulfonylurea-responsive NIDDM patients.

RESEARCH DESIGN AND METHODS

This was a 12-week multicenter, double-masked, placebo-controlled trial. Patients entered a 4-week stabilization period during which they received their previously prescribed sulfonylurea. Qualified patients (FPG ≤ 10 mmol/l) then entered a 4-week sulfonylurea withdrawal single-masked placebo run-in period. Qualified patients (FPG 8.9–16.7 mmol/l) were randomized to either placebo (n = 14), 50 mg b.i.d. BTS 67,582 (n = 18), 250 mg b.i.d. BTS 67,582 (n = 18), 500 mg b.i.d. BTS 67,582 (n = 15), 100 mg q.d. BTS 67,582 (n = 17), or 500 mg q.d. BTS 67,582 (n = 16). The primary efficacy variables were mean changes from baseline in FPG and fructosamine (FRUC). Additional variables included mean changes from baseline in HbA1c, fasting serum insulin (FSI), and fasting serum C-peptide.

RESULTS

After 4 weeks of treatment, all BTS 67,582 dose groups showed a decrease from baseline in FPG and FRUC compared with the placebo group. The treatment groups of 250 mg b.i.d. (−3.1 ± 0.7 mmol/l), 500 mg b.i.d. (−2.3 ± 0.6 mmol/l), and 500 mg q.d. (−1.2 ± 0.7 mmol/l) had statistically significant (P < 0.05) decreases in FPG compared with placebo (0.7 ± 0.6 mmol/l). Similarly, there were statistically significant (P < 0.05) decreases from baseline in FRUC for the 250 mg b.i.d (−55 ± 10 μumol/l), 500 mg b.i.d. (−40 ± 12 μumol/l), and 500 mg q.d. (−13 ± 9 μumol/l) treatment groups compared with placebo (15 ± 11 μumol/l). Although the treatment period was only 4 weeks in duration, there were also significant differences (P < 0.05) in the HbA1c changes from baseline for the 250 mg b.i.d. (0.0 ± 0.1%) and 500 mg b.i.d. (−0.2 ± 0.1%) treatment groups compared with placebo (0.6 ± 0.2%). There were no significant differences among the treatment groups in the changes from baseline for FSI or C-peptide levels. The most frequently reported side effects were headache, asthenia, infection, and thirst, and the incidence of these events as well as the incidence of study drug discontinuation was comparable in all treatment groups including placebo.

CONCLUSIONS

Four weeks of treatment with BTS 67,582 at doses of 250 mg b.i.d. and 500 mg b.i.d. in NIDDM patients was effective in reducing FPG and FRUC, with significant results also seen for HbA1c. The drug was well tolerated with an incidence of discontinuations and laboratory side-effect safety profiles comparable to placebo. BTS 67,582 is a safe and effective oral treatment for NIDDM patients.
Presence of Anti-Pituitary Antibodies and GAD Antibodies in NIDDM and IDDM
Authors: Kobayashi Takeo , Yabe Shigeki , Kikuchi Takashi , Kanda Tsugiyasu , Kobayashi Isao
Published: March 2007

OBJECTIVE

To evaluate the clinical significance of the presence of anti-pituitary antibodies (APAs) in patients with NIDDM or IDDM and to examine the relationship of APAs to GAD antibodies (GADAs).

RESEARCH DESIGN AND METHODS

Serum samples were obtained from patients with NIDDM and IDDM. APAs, determined by Western blot analysis, and GADAs, determined by radioimmunoassay, were detected in the patients' sera and control sera. Urinary levels of C-peptide (U-CPR) were measured.

RESULTS

The prevalence of APAs was significantly higher in patients with NIDDM (24.2%) or IDDM (56.8%) than in healthy control subjects (6%). In patients with NIDDM, the levels of U-CPR were significantly lower, and the prevalence of insulin deficiency was higher in APA+ patients than in APA− patients.

CONCLUSIONS

This is the first study to demonstrate that the prevalence of APAs is increased in patients with NIDDM and IDDM. The presence of APAs may be related to reduced secretion of insulin in NIDDM patients.
Contraindications to Metformin Therapy in Patients With NIDDM
Authors: Sulkin Thomas V , Bosman Deborah , Krentz Andrew J
Published: March 2007

OBJECTIVE

Treatment with metformin is occasionally associated with the development of severe lactic acidosis. However, this is usually observed in patients with major contraindications to the drug. In this study, we aimed to determine the prevalence of conditions currently regarded as either contraindications or cautions to the use of metformin in patients with NIDDM.

RESEARCH DESIGN AND METHODS

The case notes of metformin-treated NIDDM patients (mean age 62 years) attending a United Kingdom university hospital diabetes clinic over a 3-month period were reviewed according to criteria reflecting a pragmatic view of current prescribing recommendations.

RESULTS

Of 89 consecutive patients whose notes could be evaluated in detail, only 41 (46%) had no contraindications or cautions to metformin whatsoever. Concomitant chronic disorders associated with a potentially increased risk of hyperlactatemia were renal impairment (n = 2; plasma creatinine concentrations 1.7 and 2.3 mg/dl, respectively), cardiac failure (n = 2), and chronic liver disease (n = 2). Other potentially relevant disorders included ischemic heart disease (n = 20), clinical proteinuria (n = 14), peripheral vascular disease (n = 22), and pulmonary disease (n = 7). Multiple conditions (i.e., two, three, or four) were present in eight, five, and one patient(s), respectively.

CONCLUSIONS

More than half the patients in our series had concomitant conditions or complications conventionally regarded as cautions or contraindications to metformin; ∼ 10% had a multiplicity of such conditions. Regular surveillance is necessary to detect the development of complications such as renal impairment. Vigilance is also required in view of the increased risk of major intercurrent illnesses, which may independently disturb lactate metabolism in patients with NIDDM. Metformin should be withdrawn promptly under such circumstances.
Glipizide-GITS Does Not Increase the Hypoglycemic Effect of Mild Exercise During Fasting in NIDDM
Authors: Riddle Matthew C , McDaniel Patricia A , Tive Leslie A
Published: March 2007

OBJECTIVE

This study compared the effect of mild exercise while fasting on plasma glucose concentrations in subjects with NIDDM treated with extended-release glipizide and subjects not taking an oral hypoglycemic agent.

RESEARCH DESIGN AND METHODS

Twenty-five moderately obese subjects with NIDDM were randomized to treatment with extended-release glipizide or placebo. After 9 weeks of treatment, they fasted overnight, took their study drug, omitted breakfast, and exercised on a treadmill for 90 min. Glucose, insulin, and C-peptide concentrations were measured before, during, and after exercise.

RESULTS

On the fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241 mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended-release glipizide group. The decrement of glucose from the fasting baseline was modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms.

CONCLUSIONS

Chronic use of extended-release glipizide does not enhance the hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine lifestyle treatments for NIDDM may be continued during ongoing use of this agent.
Epalrestat, an Aldose Reductase Inhibitor, Improves an Impaired Generation of Oxygen-Derived Free Radicals by Neutrophils From Poorly Controlled NIDDM Patients
Authors: Sato Noriyuki , Kashima Koji , Uehara Yutaka , Ohtani Kenichi , Shimizu Hiroyuki , Mori Masatomo
Published: March 2007

OBJECTIVE

To study the in vivo effect of epalrestat (Epa), an aldose reductase inhibitor, on the generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients (HbA1c > 10%).

RESEARCH DESIGN AND METHODS

A total of 31 diabetic patients were randomly divided into two groups: an Epa(+) group of 16 patients treated with 150 mg/day epalrestat and an Epa(−) group of 15 patients treated without epalrestat. A control group of 20 age- and sex-matched normal healthy subjects also participated. HbA1c, postprandial plasma glucose (PPG), and neutrophil bactericidal function were measured before and at the end of the drug treatment period (4 weeks). Neutrophil bactericidal function was measured as chemilu-minescence amplified by a Cypridina luciferin analog (CLA), which is dependent on O2− generation, and by luminol (L), which is highly dependent on OCl− generation, in response to formyl-methonyl-leucyl-phenylalanine (fMLP).

RESULTS

At the start of the experiment, both CLA-dependent chemiluminescence (CLA-DCL) and L-dependent chemiluminescence (L-DCL) were clearly decreased in diabetic subjects (64 and 54%, respectively; P < 0.05) compared with control subjects (2,182 ± 144 and 3,221 ± 173 kc · min−1 · 10−6 cells, respectively). At the end of the experiment, CLA-DCL and L-DCL in the Epa(+) group were significantly improved by 44 and 46%, respectively; however, these values were still lower than the corresponding results in the control group. HbA1c and PPG in both the Epa(+) and Epa (−) groups were significantly higher than in the control group, and treatment had no effect on either HbA1c or PPG.

CONCLUSIONS

These data suggest that epalrestat may be a useful drug to prevent infection by improving the impaired O2− and OCl− generation by neutrophils from poorly controlled NIDDM patients.
Risk Factors for Diabetic Peripheral Sensory Neuropathy: Results of the Seattle Prospective Diabetic Foot Study
Authors: Adler Amanda I , Boyko Edward J , Ahroni Jessie H , Stensel Victoria , Forsberg Ruby C , Smith Douglas G
Published: March 2007

OBJECTIVE

To identify risk factors for diabetic lower-extremity peripheral sensory neuropathy prospectively in a cohort of U.S. veterans with diabetes.

RESEARCH DESIGN AND METHODS

General medicine clinic outpatients with diabetes were followed prospectively for the development of insensitivity to the 5.07 monofilament on the foot.

RESULTS

Of 775 subjects, 388 (50%) had neuropathy at baseline. Of the 387 subjects without neuropathy at baseline, 288 were followed up, and of these, 58 (20%) developed neuropathy. Multivariate logistic regression modeling of prevalent neuropathy controlling for sex and race revealed independent and significant associations with age, duration of diabetes, glycohemoglobin level, height, history of lower-extremity ulceration, callus, and edema; an independent and inverse correlation was noted with ankle-arm index. Risk factors for incident neuropathy in multivariate logistic regression included age, baseline glycohemoglobin level, height, history of ulcer, and CAGE screening instrument alcohol score; current smoking and albumin level were inversely associated with risk.

CONCLUSIONS

Poorer glycemic control increases the risk of neuropathy and is amenable to intervention. Height and age directly increase risk of neuropathy and may help identify patients at risk. A proportion of neuropathy in diabetic veterans is probably due to or worsened by alcohol ingestion. Neuropathy was less common in current smokers than subjects not currently smoking.
IDDM and Milk Consumption: A case-control study in São Paulo, Brazil
Authors: Gimeno Suely Godoy Agostinho , Souza José Maria Pacheco De
Published: March 2007

OBJECTIVE

To test the hypothesis that breast-feeding is a protective factor against IDDM and that early exposure to cow's milk is a risk factor for the disease.

RESEARCH DESIGN AND METHODS

A case-control study was conducted in São Paulo, Brazil. A total of 346 diabetic children, aged < 18 years, were identified in two institutions in the city of São Paulo. Duration of exclusive breast-feeding and age of introduction to cow's milk products in infant diet were compared with 346 sex-, age-, and neighborhood-matched control children. All comparisons between diabetic and control children were done using paired tests.

RESULTS

Statistically significant differences were found for the duration of exclusive breast-feeding (P = 0.007) and for the age of introduction to cow's milk products (P = 0.047). Control children had a longer time of exclusive breast-feeding and had received cow's milk later in their diet than the case children.

CONCLUSIONS

The results suggest that a shorter duration of exclusive breast-feeding is a risk factor for IDDM (odds ratio [OR] 2.13; 95% CI 1.8–3.55) and that the introduction to cow's milk products before age 8 days is a risk factor for the disease (OR 2.29;95% CI 1.37–3.83).
NIDDM and Blood Pressure as Risk Factors for Poor Cognitive Performance: The Framingham Study
Authors: Elias Penelope K , Elias Merrill F , D'Agostino Ralph B , Cupples L Adrienne , Wilson Peter W , Silbershatz Halit , Wolf Philip A
Published: March 2007

OBJECTIVE

To determine if NIDDM and blood pressure are risk factors for poor cognitive performance and if history and duration of NIDDM and blood pressure interact such that the risk of poor performance is greater for subjects with both NIDDM and hypertension.

RESEARCH DESIGN AND METHODS

We used a large prospective cohort sample with 187 NIDDM subjects and 1,624 nondiabetic subjects who were followed for 28–30 years. Cognitive function was assessed using eight tests of learning, memory, visual organization, verbal fluency attention, concept formation, and abstract reasoning. A composite score was also calculated. Odds ratios were used to estimate the relative risk of performing below the lower 25th percentile of z scores on these tests.

RESULTS

NIDDM and blood pressure interacted such that diagnosis and duration of NIDDM were associated with greater risk of poor performance on tests of visual memory and on the composite score for hypertensive subjects. Duration of NIDDM was associated with increased risk for poor performance on tests of verbal memory and concept formation. Insulin-treated NIDDM subjects were at higher risk for poor cognitive performance than those NIDDM subjects treated with oral agents or diet. Blood pressure level was associated independently with a measure of verbal fluency.

CONCLUSIONS

History and duration of NIDDM and high blood pressure are significant risk factors for poor cognitive performance. Hypertensive people with NIDDM are at greatest risk for poor performance on tests measuring visual organization and memory.
Serum Immunoreactive Leptin Concentrations in a Canadian Aboriginal Population With High Rates of NIDDM
Authors: Hanley Anthony J G , Harris Stewart B , Gao X Joe , Kwan Jeremy , Zinman Bernard
Published: March 2007

OBJECTIVE

To better understand the relationship between leptin and the anthropometric and physiological variables associated with diabetes, we measured this protein in an isolated Canadian aboriginal population with very high rates of NIDDM.

RESEARCH DESIGN AND METHODS

There were 728 individuals aged 10–79 years who participated in a population-based survey to determine the prevalence of NIDDM and its associated risk factors. Fasting blood samples for glucose, insulin, triglyceride, and leptin were collected; a 75-g oral glucose tolerance test was administered and a second blood sample drawn after 120 min. Height, weight, and waist and hip circumference were determined, and percent body fat was estimated using biological impedance analysis. Fitness level was assessed in a subsample of individuals using a validated submaximal step test. The relationship between serum leptin and the other variables was assessed using Spearman's correlation coefficients and multiple linear regression.

RESULTS

Serum leptin concentration was strongly correlated with adiposity, and levels were substantially higher in female subjects in all age-groups. For male subjects, percent body fat, fasting insulin level, and waist circumference were significant independent predictors of log serum leptin concentration in a multiple linear regression model (R2 ; 0.582). For female subjects, these variables plus glucose tolerance status were included in the final model (R2 ; 0.633). Fitness level, when included with the main effects of the above models, was a significant predictor for male subjectsonly.

CONCLUSIONS

In an isolated aboriginal community with high rates of diabetes, we found significant independent relationships between leptin and percent body fat and between leptin and fasting insulin. As documented in other populations, the higher leptin concentration among female subjects may reflect differential leptin production from different adipose tissue beds, or leptin resistance. Independent relationships also existed among leptin and glucose tolerance status in female subjects and fitness level in male subjects.
Glycosylated Hemoglobin Level and Carotid Intimal-Medial Thickening in Nondiabetic Individuals: The Atherosclerosis Risk in Communities Study
Authors: Vitelli Lori L , Shahar Eyal , Heiss Gerardo , McGovern Paul G , Brancati Frederick L , Eckfeldt John H , Folsom Aaron R ,   Atherosclerosis risk in Communities (ARIC) Study Investigators
Published: March 2007

OBJECTIVE

People with diabetes are at increased risk for cardiovascular events. However, questions remain about what role, if any, homeostatic glucose control plays in the development of cardiovascular disease among nondiabetic individuals. We investigated the relationship between HbA1c level and carotid intimal-medial thickening in normoglycemic individuals.

RESEARCH DESIGN AND METHODS

We conducted a case-control study among 208 normoglycemic individuals (fasting glucose ≤ 6.4 mmol/l and no history of diabetes) who had carotid initial-medial thickening (case subjects) and 208 normoglycemic control subjects individually matched for age, sex, race, field center, and date of exam. Subjects were free-living men and women, aged 45–64 years at baseline, who participated in the Atherosclerosis Risk in Communities (ARIC) Study.

RESULTS

HbA1c levels, expressed as percent of total hemoglobin, ranged from 4 to 7% and correlated only modestly with single measurements of fasting glucose (r = 0.16) and fasting insulin (r = 0.14). The mean level of HbA1c was 5.18% among case subjects and 5.07% among control subjects (P = 0.004, paired t test). As compared with the first quartile of HbA1c the matched relative odds of being a case were 1.15, 1.33, and 2.30 for the second, third, and fourth quartiles, respectively (P = 0.005 for linear trend). After multivariate adjustment for age, fasting glucose, fasting insulin, BMI, smoking status, hypertension, LDL cholesterol, HDL cholesterol, fibrinogen, and education level, the respective relative odds estimates were 0.98, 1.07, and 1.8 (P = 0.16 for linear trend). When modeled linearly as a continuous variable and after adjustment for the above-mentioned covariates, a 1% point increment in HbA1c level was associated with 1.77 greater odds of being a case (95% CI, 0.9–3.5).

CONCLUSIONS

These data provide some support to the hypothesis that in the absence of diabetes, homeostatic glycemic control is a risk factor for atherosclerosis.
Longitudinal Study of Carbohydrate Metabolism in Healthy Obese Pregnant Women
Authors: Sivan Eyal , Chen Xinhua , Homko Carol J , Reece E Albert , Boden Guenther
Published: March 2007

OBJECTIVE

To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy.

RESEARCH DESIGN AND METHODS

Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500–600 pmol/l) clamping during the second (22.5 ± 2 weeks [mean ± SD]) and third trimester (36.8 ± 0.9) of pregnancy and again 15.6 ± 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6−2H2]glucose) and oxidation (with indirect calorimetry) were measured.

RESULTS

There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (−28%, P < 0.05, compared with the second trimester and −40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (−46%, P < 0.05, compared with the second trimester and −54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (−39% compared with −79% at the second trimester and −77% postpartum, P < 0.01).

CONCLUSIONS

Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterationswere reversed after delivery and appeared to be adaptive mechanisms to copewith the increased demand for glucose of the growing fetus.