bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic Variation of Lower-Extremity Major Amputation in Individuals With and Without Diabetes in the Medicare Population
Authors: Wrobel James S. , Mayfield Jennifer A. , Reiber Gayle E.
Published: March 2007

OBJECTIVE—To describe geographic variation in rates of lower-limb major amputation in Medicare patients with and without diabetes.

RESEARCH DESIGN AND METHODS—This cross-sectional population-based study used national fee-for-service Medicare claims from 1996 through 1997. The unit of analysis was 306 hospital referral regions (HRRs) representing health care markets for their respective tertiary medical centers. Numerators were calculated using nontraumatic major amputations and the diabetes code (250.x) for individuals with diabetes. Denominators for individuals with diabetes were created by multiplying the regional prevalence of diabetes (as determined using a 5% sample of Medicare Part B data identifying at least two visits with a diabetes code for 1995–1996) by the regional Medicare population. Denominators for individuals without diabetes were the remaining Medicare beneficiaries. Rates of major amputations were adjusted for age, sex, and race.

RESULTS—Rates of major amputations per year were 3.83 per 1,000 (95% CI 3.60–4.06) individuals with diabetes compared with 0.38 per 1,000 (95% CI 0.35–0.41) individuals without diabetes. Marked geographic variation was observed for individuals with and without diabetes; however, patterns were distinct between the two populations. Rates were high in the Southern and Atlantic states for individuals without diabetes. In contrast, rates for individuals with diabetes were widely varied. Variation across HRRs for individuals with diabetes was 8.6-fold compared with 6.7-fold in individuals without diabetes for major amputations.

CONCLUSIONS—Diabetes-related amputation rates exhibit high regional variation, even after age, sex, and race adjustment. Future work should be directed to exploring sources of this variation.
Idiopathic Type 1 Diabetes in Dallas, Texas
Authors: Piñero-Piloña Antonio , Litonjua Patrick , Aviles-Santa Larissa , Raskin Philip
Published: March 2007

OBJECTIVE—To describe the clinical course of individuals with idiopathic type 1 diabetes after a mean of 5 years from diagnosis and to compare glycemic control between those treated with diet and/or oral agents and those treated with insulin at follow-up.

RESEARCH DESIGN AND METHODS—Medical records of patients with new-onset diabetes, who presented with unprovoked diabetic ketoacidosis, were reviewed. A total of 54 of these individuals were traceable and had relevant data collected within the past 2 years. All patients had nonsusceptibility HLA haplotypes and no serological evidence of autoimmune type 1 diabetes. Most of these patients were male (41 men and 13 women), were non-Caucasian, were obese at the time of diagnosis (BMI 31.6 ± 6.3 kg/m2), reported weight loss (12.8 ± 9.8 kg), had a family history of type 2 diabetes, and had acanthosis nigricans. At follow-up, 33 patients were still taking insulin and 21 were on diet and/or oral-agent therapy.

RESULTS—Both treatment groups were similar in clinical presentation and demographics at diagnosis. After 4.8 ± 1.6 years of follow-up, the 33 patients that were receiving insulin had a lower HbA1c than the 21 patients who were using therapies other than insulin (7.8 ± 2.4 vs. 11.1 ± 3.5%, P = 0.009; 95% CI 1.0–6.5%). There was a high correlation between change in weight and change in HbA1c at follow-up (r = 0.45, P < 0.001, n = 54). There were no differences in the rate of diabetes complications or in the episodes of recurrent diabetic ketoacidosis.

CONCLUSIONS—Idiopathic type 1 diabetes occurs more frequently in male African-American patients but also occurs in other ethnic groups. Patients with idiopathic type 1 diabetes who continued to use insulin had better glycemic control than patients using therapies other than insulin. Regained weight is a good clinical marker for improvement in glycemic control. Individuals with this type of diabetes should not be switched to therapies other than insulin.
Polychlorinated Biphenyl Serum Levels in Pregnant Subjects With Diabetes
Authors: Longnecker Matthew P. , Klebanoff Mark A. , Brock John W. , Zhou Haibo
Published: March 2007

OBJECTIVE—Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain; detectable amounts are in the blood of nearly everyone. Their effect on humans at background levels of exposure is an area of active investigation. Increased blood levels of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a PCB-like compound, have recently been reported among subjects with diabetes, suggesting that PCB levels could be similarly elevated. To test this hypothesis, we examined a group of pregnant women whose serum PCB levels had been measured and whose diabetes status had been previously recorded.

RESEARCH DESIGN AND METHODS—Using stored serum from a large birth cohort study, we conducted a cross-sectional study of 2,245 pregnant women, of whom 44 had diabetes (primarily type 1) and 2,201 were control subjects.

RESULTS—The adjusted mean serum level of PCBs among the subjects with diabetes was 30% higher than in the control subjects (P = 0.0002), and the relationship of PCB level to adjusted odds of diabetes was linear.

CONCLUSIONS—The possibility exists that PCBs and diabetes are causality related; alternatively, the pharmacokinetics of PCBs could be altered among patients with diabetes. At any event, if the association is replicated in other studies, increased serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment.
Importance of Early Insulin Secretion
Authors: Hollander Priscilla A. , Schwartz Sherwyn L. , Gatlin Marjorie R. , Haas Stephen J. , Zheng Hongjie , Foley James E. , Dunning Beth E.
Published: March 2007

OBJECTIVE—This study compared the effects of nateglinide, glyburide, and placebo on postmeal glucose excursions and insulin secretion in previously diet-treated patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—This randomized, double-blind, placebo-controlled multicenter study was conducted in 152 patients who received either nateglinide (120 mg before three meals daily, n = 51), glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n = 50), or placebo (n = 51) for 8 weeks. Glucose, insulin, and C-peptide profiles during liquid meal challenges were measured at weeks 0 and 8. At weeks −1 and 7, 19-point daytime glucose and insulin profiles, comprising three solid meals, were measured.

RESULTS—During the liquid-meal challenge, nateglinide reduced the incremental glucose area under the curve (AUC) more effectively than glyburide (Δ = −4.94 vs. −2.71 mmol · h/l, P < 0.05), whereas glyburide reduced fasting plasma glucose more effectively than nateglinide (Δ = −2.9 vs. −1.0 mmol/l, respectively, P < 0.001). In contrast, C-peptide induced by glyburide was greater than that induced by nateglinide (Δ = +1.83 vs. +0.95 nmol · h/l, P < 0.01), and only glyburide increased fasting insulin levels. During the solid meal challenges, nateglinide and glyburide elicited similar overall glucose control (Δ 12-h incremental AUC = −13.2 vs. −15.3 mmol · h/l), but the insulin AUC induced by nateglinide was significantly less than that induced by glyburide (Δ 12-h AUC = +866 vs. +1,702 pmol · h/l, P = 0.01).

CONCLUSIONS—This study demonstrated that nateglinide selectively enhanced early insulin release and provided better mealtime glucose control with less total insulin exposure than glyburide.
Role of Hemochromatosis C282Y and H63D Mutations in HFE Gene in Development of Type 2 Diabetes and Diabetic Nephropathy
Authors: Moczulski Dariusz K. , Grzeszczak Wladyslaw , Gawlik Barbara
Published: March 2007

OBJECTIVE—In patients with clinical hemochromatosis, the frequency of diabetes ranges from 20 to 50%, and the heterozygosity for the C282Y mutation in the HFE gene might be associated with an increased risk for diabetes. There are also some reports that suggest that iron overload might cause diabetic nephropathy.

RESEARCH DESIGN AND METHODS—We performed an association study to assess the role of the C282Y and H63D mutations in the HFE gene as a risk factor for type 2 diabetes and diabetic nephropathy. Altogether, 563 patients with type 2 diabetes were included in the study. In the analyzed group, 108 patients had overt proteinuria, 154 had microalbuminuria, and 301 had normoalbuminuria. Among the patients with normoalbuminuria, only those with known diabetes duration ≥10 years were considered normoalbuminuric (n = 162). A total of 196 unrelated healthy subjects were used as a control group. All subjects were genotyped for C282Y and H63D using the polymerase chain reaction–based protocol.

RESULTS—There was an increased frequency of 282Y allele carriers among patients with type 2 diabetes versus healthy control subjects (OR 5.3, 95% CI 1.6–17.3). We observed an increased frequency of the 63D allele carriers among patients with diabetic nephropathy (1.8, 1.2–2.8).

CONCLUSIONS—In conclusion, our study is the first to indicate that being a carrier of the H63D hemochromatosis mutation is a risk factor for nephropathy in type 2 diabetic patients. We also confirmed previous observations that the frequency of the 282Y mutation was higher in patients with type 2 diabetes than it was in the general population of healthy subjects.
Use of an Automated Device for Alternative Site Blood Glucose Monitoring
Authors: Fineberg S. Edwin , Bergenstal Richard M. , Bernstein Robert M. , Laffel Lori M. , Schwartz Sherwyn L.
Published: March 2007

OBJECTIVE—To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site.

RESEARCH DESIGN AND METHODS—These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device.

RESULTS—Blood glucose results in samples obtained from the arm with the automated device agreed well with finger-stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was “painless;” another 31% of the patients stated that it was “much less painful,” and 6% of patients considered using the device “less painful” than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5.

CONCLUSIONS—The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing.
Body Fatness and Fat Distribution as Predictors of Metabolic Abnormalities and Early Carotid Atherosclerosis
Authors: Takami Rieko , Takeda Noriyuki , Hayashi Makoto , Sasaki Akihiko , Kawachi Shinichi , Yoshino Koji , Takami Kazuhisa , Nakashima Kazuya , Akai Akifumi , Yamakita Noriyoshi , Yasuda Keigo
Published: March 2007

OBJECTIVE—To test the hypothesis that intra-abdominal fat plays a primary role over general adiposity for metabolic abnormalities and atherosclerosis.

RESEARCH DESIGN AND METHODS—We cross-sectionally studied 849 Japanese men aged 50.3 ± 8.5 years (range 20–78) with BMI 23.5 ± 2.9 kg/m2. Intimal-medial thickness (IMT) of the carotid artery was measured by ultrasound. General adiposity was assessed by BMI. Waist circumference and waist-to-hip ratio (WHR) were used as a surrogate measure for abdominal fat. Abdominal subcutaneous fat area (ASF) and intra-abdominal fat area (IAF) were measured by computed tomography. Correlations between these measures and carotid IMT were analyzed. The interaction of generalized adiposity (BMI) and IAF in relation to metabolic variables, such as glucose tolerance, insulin resistance, and serum lipids, was also evaluated.

RESULTS—BMI, waist circumference, WHR, ASF, and IAF were all correlated with carotid IMT. Adjustment for BMI eliminated the associations between IMT and waist circumference, ASF, and IAF. In contrast, WHR retained a significant correlation with IMT. BMI and IAF were associated with insulin resistance, glucose tolerance, HDL cholesterol, and blood pressure independently of each other. IAF was an independent correlate for serum triglyceride, but BMI was not.

CONCLUSIONS—The primary importance of IAF over general adiposity for carotid atherosclerosis was not confirmed. Caution is recommended when using WHR as a measure of abdominal fat. The roles of IAF for metabolic abnormalities may be more limited than conventionally thought. BMI and WHR are simple and better clinical predictors for carotid atherosclerosis versus IAF.
Predictors of Delayed Gastric Emptying in Diabetes
Authors: Jones Karen L. , Russo Antonietta , Stevens Julie E. , Wishart Judith M. , Berry Melanie K. , Horowitz Michael
Published: March 2007

OBJECTIVE—To define the predictors of the rate of gastric emptying in patients with diabetes.

RESEARCH DESIGN AND METHODS—A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes).

RESULTS—The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 ± 3.2 vs. 50.2 ± 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 ± 1.7 vs. 16.0 ± 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids.

CONCLUSIONS—We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.
Is Diabetes Treated as an Acute or Chronic Illness in Community Family Practice?
Authors: Yawn Barbara , Zyzanski Stephen J. , Goodwin Meredith A. , Gotler Robin S. , Stange Kurt C.
Published: March 2007

OBJECTIVE—Poor quality of diabetes care has been ascribed to the acute care focus of primary care practice. A better understanding of how time is spent during outpatient visits for diabetes compared with visits for acute conditions and other chronic diseases may facilitate the design of programs to enhance diabetes care.

RESEARCH DESIGN AND METHODS—Research nurses directly observed consecutive outpatient visits during two separate days in 138 community family physician offices. Time use was categorized into 20 different behaviors using the Davis Observation Code (DOC). Time use was compared for visits for diabetes, other chronic conditions, and acute illnesses during 1,867 visits by patients ≥40 years of age.

RESULTS—Of 20 DOC behavioral categories, 10 exhibited differences among the three groups. Discriminant analysis identified two distinct factors that distinguished visits for chronic disease from visits for acute illness and visits for diabetes from those for other chronic diseases. Compared with visits for other chronic diseases, visits for diabetes devoted a greater proportion of time to nutrition counseling, health education, and feedback on results and less time to chatting. Compared with visits for acute illness, visits for diabetes were longer and involved a higher proportion of dietary advice, negotiation, and assessment of compliance.

CONCLUSIONS—Visits for diabetes are distinct from visits for other chronic diseases and acute illnesses in ways that may facilitate patient self-management. Novel quality-improvement interventions could support and expand existing differences between family physicians’ current approaches to care of diabetes and other chronic and acute illnesses.
Effectiveness of the Diabetic Foot Risk Classification System of the International Working Group on the Diabetic Foot
Authors: Peters Edgar J.G. , Lavery Lawrence A.
Published: March 2007

OBJECTIVE—To evaluate the effectiveness of a diabetic foot risk classification system by the International Working Group on the Diabetic Foot to predict clinical outcomes.

RESEARCH DESIGN AND METHODS—A total of 225 diabetic patients were initially evaluated as part of a prospective case-control study at the University of Texas Health Science Center at San Antonio. Complete records were available for 213 patients for follow-up evaluation after 29 months. Upon enrollment, subjects were stratified into four risk groups based on the presence of risk factors according to the consensus of the International Working Group on the Diabetic Foot. Group 0 consisted of subjects without neuropathy, group 1 consisted of patients with neuropathy but without deformity or peripheral vascular disease (PVD), group 2 consisted of subjects with neuropathy and deformity or PVD, and group 3 consisted of patients with a history of foot ulceration or a lower-extremity amputation.

RESULTS—Upon enrollment, patients in higher-risk groups had longer duration of diabetes, worse glycemic control, vascular and neuropathic variables, and more systemic complications of diabetes. During 3 years of follow-up, ulceration occurred in 5.1, 14.3, 18.8, and 55.8% of the patients in groups 0, 1, 2, and 3, respectively (linear-by-linear association, P < 0.001). All amputations were found in Groups 2 and 3 (3.1 and 20.9%, P < 0.001).

CONCLUSIONS—The foot risk classification of the International Working Group on the Diabetic Foot predicts ulceration and amputation and can function as a tool to prevent lower-extremity complications of diabetes.
Parental History of Diabetes Modifies the Association Between Abdominal Adiposity and Hyperglycemia
Authors: van Dam Rob M. , Boer Jolanda M.A. , Feskens Edith J.M. , Seidell Jaap C.
Published: March 2007

OBJECTIVE—To examine whether the association between abdominal obesity and hyperglycemia differs according to the presence of a parental history of diabetes.

RESEARCH DESIGN AND METHODS—We conducted a cross-sectional study of 3,068 men and women, aged 20–65 years, without known diabetes who were fasting participants of a population-based study in three Dutch towns. Hyperglycemia was defined as a fasting plasma glucose concentration of 6.1 mmol/l (American Diabetes Association criterion). Waist circumference was categorized according to previously defined waist action levels. All estimates were adjusted for age and town.

RESULTS—The regression coefficients for the association between waist circumference and fasting plasma glucose were larger in participants who had a parental history of diabetes than in those who did not (men β = 0.31 vs. 0.16 mmol/SD, P [for interaction] = 0.003; women β = 0.24 vs. 0.11 mmol/SD, P = 0.002). Furthermore, larger waist circumference (men ≥94 vs. <94 cm, women ≥88 vs. <80 cm) was associated with a greater excess prevalence of hyperglycemia in participants who had a parental history of diabetes than in those who did not (men 12.4 vs. 2.0%, P = 0.03; women 13.6 vs. 5.9%, P = 0.05). Adjustment for physical activity, alcohol intake, smoking, and educational level did not materially change the results.

CONCLUSIONS—These findings indicate that the association between abdominal obesity and hyperglycemia is stronger in the presence of a parental history of diabetes. Blood glucose screening may be warranted at lower levels of waist circumference in individuals with a parental history of diabetes.
Platelet Dysfunction in Type 2 Diabetes
Authors: Vinik Aaron I. , Erbas Tomris , Park Tae Sun , Nolan Roger , Pittenger Gary L.
Published: March 2007

Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI2) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI2 and enhances endothelial generation of PGI2 and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.
Neuropsychological Profiles of Children With Type 1 Diabetes 6 Years After Disease Onset
Authors: Northam Elisabeth A. , Anderson Peter J. , Jacobs Rani , Hughes Matthew , Warne Garry L , Werther George A.
Published: March 2007

OBJECTIVE—To describe neuropsychological profiles and their relationship to metabolic control in children with type 1 diabetes 6 years after the onset of disease.

RESEARCH DESIGN AND METHODS—Children with type 1 diabetes (n = 90), aged 6–17 years, who had previously been assessed soon after diagnosis and 2 years later, were reevaluated 6 years after the onset of disease. Their neuropsychological profiles were compared with those of individuals in a community control group (n = 84), who had been assessed at similar intervals. Relationships between illness variables, such as age at the onset of disease and metabolic control history, and neuropsychological status were also examined.

RESULTS—Six years after onset of disease, children with type 1 diabetes performed more poorly than control subjects on measures of intelligence, attention, processing speed, long-term memory, and executive skills. Attention, processing speed, and executive skills were particularly affected in children with onset of disease before 4 years of age, whereas severe hypoglycemia was associated with lower verbal and full-scale intelligence quotient scores.

CONCLUSIONS—Neuropsychological profiles of children with type 1 diabetes 6 years after the onset of disease are consistent with subtle compromise of anterior and medial temporal brain regions. Severe hypoglycemia, particularly in very young children, is the most plausible explanation for neuropsychological deficits, but the contributory role of chronic hyperglycemia warrants further exploration.
Advanced Glycation End Products in Nondiabetic Patients With Coronary Artery Disease
Authors: Kanauchi Masao , Tsujimoto Nobuhiro , Hashimoto Toshio
Published: March 2007

OBJECTIVE—To investigate whether advanced glycation end products (AGEs) participate in the development of coronary artery disease (CAD) in nondiabetic and diabetic subjects.

RESEARCH DESIGN AND METHODS—Serum concentrations of AGEs were measured using a newly established enzyme-linked immunosorbent assay in 48 nondiabetic patients (normal glucose tolerance, n = 20; impaired glucose tolerance, n = 28) who received coronary angiography for the study of chest pain or suspected CAD. Insulin sensitivity was examined by the euglycemic-hyperinsulinemic glucose clamp technique and was estimated as the mean glucose infusion rate during the last 30 min of clamp time (M value).

RESULTS—Patients were classified into four groups based on the number of significantly stenosed vessels, defined as 0-, 1-, 2-, or 3-vessel disease. Serum concentrations of AGEs were significantly higher in nondiabetic subjects with CAD than in control subjects (2.42 ± 0.65 vs. 1.96 ± 0.40 mU/ml, P < 0.01) and significantly correlated with the number of significantly stenosed vessels (r = 0.678, P < 0.001). M values significantly inversely correlated with serum concentrations of AGEs (r = −0.490, P < 0.05). In multiple regression analysis, with the number of significantly stenosed vessels as the dependent variable, serum concentrations of AGEs, 2-h plasma glucose, and areas under the plasma glucose response curve were independently associated.

CONCLUSIONS—This pilot study indicates the relation between AGEs and the severity of CAD in nondiabetic patients. The measurement of serum AGE concentrations may be predictive of vascular damage.
Variations of Ambulatory Blood Pressure With Position in Patients With Type 1 Diabetes
Authors: Benhamou Pierre Y. , Mouret Sandrine , Quesada Jean L. , Boizel Robert , Baguet Jean P. , Halimi Serge , Mallion Jean M.
Published: March 2007

OBJECTIVE—To study the influence of position changes on 24-h ambulatory blood pressure (ABP) in normotensive or mildly hypertensive normoalbuminuric patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—A cross-sectional evaluation of patients was staged according to the duration of diabetes (DD) and the presence of microangiopathy. We recruited 37 patients (30 men and 7 women), aged 38 ± 12 years, who were normotensive or mildly hypertensive (diastolic blood pressure [DBP] <105 mmHg) and free of antihypertensive treatment and microalbuminuria. They were included according to DD (group 1, <5 years; group 2, ≥10 years). An additional group of seven diabetic patients with microalbuminuria and mild untreated hypertension was also investigated. We recorded 24-h ambulatory blood pressure every 15 min with a position sensor, which allowed for the discrimination between standing or supine/sitting position in the patient.

RESULTS—Mean daytime (10:00 a.m. to 8:00 p.m.) ABP in supine/sitting position did not significantly differ between groups 1 and 2. However, standing ambulatory systolic blood pressure (ASBP) and ambulatory DBP (ADBP) were significantly higher than supine/sitting ASBP and ADBP in group 1 (ΔSBP 4 ± 5, ΔDPB 4 ± 6 mmHg, P < 0.01) but not in group 2 (ΔSBP 2 ± 8, ΔDBP 2 ± 4 mmHg, P = NS). Patients free of microangiopathy presented with significantly higher ABP in standing position than in sitting/lying position, whereas patients with retinopathy and/or nephropathy exhibited no significant increase of ABP during standing.

CONCLUSION—The monitoring of position during ambulatory measurement of blood pressure in type 1 diabetic patients shows different patterns in relation to disease duration and the presence of microangiopathy.
Repaglinide Versus Metformin in Combination With Bedtime NPH Insulin in Patients With Type 2 Diabetes Established on Insulin/Metformin Combination Therapy
Authors: Furlong Niall J. , Hulme Shirley A. , O’Brien Sarah V. , Hardy Kevin J.
Published: March 2007

OBJECTIVE—To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician’s discretion, aiming for a fasting blood glucose (FBG) ≤6.0 mmol/l.

RESULTS—Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA1c (Diabetes Control and Complications Trial–aligned assay, normal range 4.6–6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 ± 0.4 kg (means ± SE) (P = 0.01) versus 2.7 ± 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 ± 0.8 to 34.1 ± 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 ± 0.9 to 29.1 ± 1.3 (P < 0.002) with insulin/repaglinide.

CONCLUSIONS—Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.
Comparison of Insulin Monotherapy and Combination Therapy With Insulin and Metformin or Insulin and Troglitazone in Type 2 Diabetes
Authors: Strowig Suzanne M. , Avilés-Santa M. Larissa , Raskin Philip
Published: March 2007

OBJECTIVE—To evaluate the safety and efficacy of treatment with insulin alone, insulin plus metformin, or insulin plus troglitazone in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 88 type 2 diabetic subjects using insulin monotherapy (baseline HbAlc 8.7%) were randomly assigned to insulin alone (n = 31), insulin plus metformin (n = 27), or insulin plus troglitazone (n = 30) for 4 months. The insulin dose was increased only in the insulin group. Metformin was titrated to a maximum dose of 2,000 mg and troglitazone to 600 mg.

RESULTS—HbAlc levels decreased in all groups, the lowest level occurring in the insulin plus troglitazone group (insulin alone to 7.0%, insulin plus metformin to 7.1%, and insulin plus troglitazone to 6.4%, P < 0.0001). The dose of insulin increased by 55 units/day in the insulin alone group (P < 0.0001) and decreased by 1.4 units/day in the insulin plus metformin group and 12.8 units/day in the insulin plus troglitazone group (insulin plus metformin versus insulin plus troglitazone, P = 0.004). Body weight increased by 0.5 kg in the insulin plus metformin group, whereas the other two groups gained 4.4 kg (P < 0.0001 vs. baseline). Triglyceride and VLDL triglyceride levels significantly improved only in the insulin plus troglitazone group. Subjects taking metformin experienced significantly more gastrointestinal side effects and less hypoglycemia.

CONCLUSIONS—Aggressive insulin therapy significantly improved glycemic control in type 2 diabetic subjects to levels comparable with those achieved by adding metformin to insulin therapy. Troglitazone was the most effective in lowering HbAlc, total daily insulin dose, and triglyceride levels. However, treatment with insulin plus metformin was advantageous in avoiding weight gain and hypoglycemia.
Treatment of Chronic Painful Diabetic Neuropathy With Isosorbide Dinitrate Spray
Authors: Yuen Kevin C.J. , Baker Neil R. , Rayman Gerry
Published: March 2007

OBJECTIVE—Considerable evidence implicates impaired nitric oxide (NO) generation in the pathogenesis of diabetic neuropathic pain. We therefore conducted a pilot study to examine the effects of isosorbide dinitrate (ISDN), a NO donor with local vasodilating properties, in spray form in the management of chronic neuropathic pain.

RESEARCH DESIGN AND METHODS—The study was of double-blind, randomized, placebo-controlled, and two-period cross-over design. After a 2-week run-in period, 22 diabetic patients (13 men, 20 with type 2 diabetes, age [mean ± SE] 63.7 ± 1.8 years, duration of diabetes 9.1 ± 1.5 years, duration of painful neuropathy 2.6 ± 0.4 years) were randomized to receive ISDN or placebo sprays for 4 weeks, exchanging their treatment for a further 4 weeks after a 2-week wash-out period. The patients administered the spray to both feet before bedtime. Biweekly pain and other sensory symptoms were assessed using a visual analog scale (VAS) and the Lickert scale, respectively.

RESULTS—ISDN spray reduced overall neuropathic pain (P = 0.02) and burning sensation (P = 0.006). No treatment difference was observed with other sensory modalities (hot/cold sensation, tingling, numbness, hyperesthesia, and jabbing-like sensation). At study completion, 11 patients (50%) reported benefit and wished to continue using the ISDN spray, 4 (18%) preferred the placebo spray, and the remaining 7 (32%) were undecided.

CONCLUSIONS—ISDN spray offers an alternative and effective pharmacological option in relieving overall pain and burning sensation in the management of painful diabetic neuropathy. The potential of ISDN spray in alleviating other specific sensory symptoms associated with diabetic peripheral neuropathy merits further study.
Diet and Exercise Among Adults With Type 2 Diabetes
Authors: Nelson Karin M. , Reiber Gayle , Boyko Edward J.
Published: March 2007

OBJECTIVE—To describe diet and exercise practices from a nationally representative sample of U.S. adults with type 2 diabetes.

METHODS—We analyzed data from 1,480 adults older than 17 years with a self-reported diagnosis of type 2 diabetes in the Third National Health and Nutrition Examination Survey (NHANES III). Fruit and vegetable consumption was obtained from a food frequency questionnaire; the percentages of total calories from fat and saturated fat were obtained from a 24-h food recall. Physical activity was based on self report during the month before the survey.

RESULTS—Of individuals with type 2 diabetes, 31% reported no regular physical activity and another 38% reported less than recommended levels of physical activity. Sixty-two percent of respondents ate fewer than five servings of fruits and vegetables per day. Almost two thirds of the respondents consumed >30% of their daily calories from fat and >10% of total calories from saturated fat. Mexican Americans and individuals over the age of 65 years ate a higher number of fruits and vegetables and a lower percentage of total calories from fat. Lower income and increasing age were associated with physical inactivity. Thirty-six percent of the sample were overweight and another 46% were obese.

CONCLUSIONS—The majority of individuals with type 2 diabetes were overweight, did not engage in recommended levels of physical activity, and did not follow dietary guidelines for fat and fruit and vegetable consumption. Additional measures are needed to encourage regular physical activity and improve dietary habits in this population.
Reduced IGFBP-1 Is Associated With Thickening of the Carotid Wall in Type 2 Diabetes
Authors: Leinonen Eeva S. , Salonen Jukka T. , Salonen Riitta M. , Koistinen Riitta A. , Leinonen Pekka J. , Sarna Seppo S. , Taskinen Marja-Riitta
Published: March 2007

OBJECTIVE—The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50–75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA1c, and C-peptide were measured in fasting samples. Patients were divided in groups without (n = 168) and with (n = 71) clinical cardiovascular disease (CVD).

RESULTS—Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide (r = −0. 24, P = 0.018) and with maximal IMT (r = −0.42, P < 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD.

CONCLUSIONS—In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes.
Projected Impact of Implementing the Results of the Diabetes Prevention Program in the U.S. Population
Authors: Saydah Sharon H. , Byrd-Holt Danita , Harris Maureen I.
Published: March 2007

OBJECTIVE—To determine the feasibility of using either fasting plasma glucose or HbA1c to identify individuals in the U.S. population who meet the Diabetes Prevention Program (DPP) criteria for intervention, defined as BMI ≥24 kg/m2, fasting plasma glucose level 96–125 mg/dl, and 2-h glucose level 140–199 mg/dl in an oral glucose tolerance test (OGTT).

RESEARCH DESIGN AND METHODS—Analysis of a representative sample of U.S. adults aged 40–74 years with no medical history of diabetes for whom data on height, weight, fasting plasma glucose, HbA1c, and 2-h plasma glucose during an OGTT were obtained. Sensitivity, specificity, positive predictive value (PPV), and receiver operator characteristic (ROC) curves for fasting glucose and HbA1c were determined.

RESULTS—Using BMI <24 kg/m2 as an initial criterion eliminated 27.2% of U.S. adults from further testing. Of the remaining group, 41.1% did not have to be considered for an OGTT because their fasting glucose level was below or above 96–125 mg/dl. Overall, 10.6% of adults aged 40–74 years without medical history of diabetes met the DPP eligibility criteria for intervention. Among individuals with BMI ≥24 kg/m2 and fasting glucose level 96–125 mg/dl, applying a fasting plasma glucose cutoff of ≥105 mg/dl excluded 62.5% of this group and resulted in 56.0% of those with 2-h glucose level 140–199 mg/dl in this group being identified, with a specificity of 72.0% and a PPV of 17.1%. Similar values were obtained for an HbA1c cutoff value of ≥5.5%.

CONCLUSIONS—Using data on BMI and setting cutoff values for fasting glucose and HbA1c would greatly reduce the number of individuals who would need to undergo an OGTT while achieving adequate sensitivity, specificity, and PPV.
Prospective Study of C-Reactive Protein in Relation to the Development of Diabetes and Metabolic Syndrome in the Mexico City Diabetes Study
Authors: Han Thang S. , Sattar Naveed , Williams Ken , Gonzalez-Villalpando Clicerio , Lean Michael E.J. , Haffner Steven M.
Published: March 2007

OBJECTIVE—Recent evidence suggests that C-reactive protein (CRP) may predict development of diabetes in Caucasian populations. We evaluated CRP as a possible risk factor of the development of diabetes and metabolic syndrome in a 6-year study of 515 men and 729 women from the Mexico City Diabetes Study.

RESEARCH DESIGN AND METHODS—Baseline CRP, indexes of adiposity, and insulin resistance (homeostasis model assessment [HOMA-IR]) were used to predict development of the metabolic syndrome, defined as including two or more of the following: 1) dyslipidemia (triglyceride ≥2.26 mmol/l or HDL cholesterol ≤0.91 mmol/l in men and ≤1.17 mmol/l in women; <35 and 40 mg/dl for men and women); 2) hypertension (blood pressure >140/90 mmHg or on hypertensive medication); or 3) diabetes (1999 World Health Organization criteria).

RESULTS—At baseline, CRP correlated significantly (P < 0.001) with all metabolic indexes in women, but less so in men. After 6 years, 14.2% of men and 16.0% of women developed the metabolic syndrome. Compared with tertile 1, women with CRP in the highest tertile had an increased relative risk of developing the metabolic syndrome by 4.0 (95% CI 2.0–7.9) and diabetes by 5.5 (2.2–13.5); these risks changed minimally after adjusting for BMI or HOMA-IR. The area under receiver-operating characteristic (ROC) curve for the prediction of the development of the syndrome was 0.684 for CRP, increasing to 0.706 when combined with BMI and to 0.710 for a complex model of CRP, BMI, and HOMA-IR.

CONCLUSIONS—CRP was not a significant predictor of the development of the metabolic syndrome in men. Our data strongly support the notion that inflammation is important in the pathogenesis of diabetes and metabolic disorders in women.
Concomitance of Diabetic Retinopathy and Proteinuria Accelerates the Rate of Decline of Kidney Function in Type 2 Diabetic Patients
Authors: Trevisan Roberto , Vedovato Monica , Mazzon Cinzia , Coracina Anna , Iori Elisabetta , Tiengo Antonio , Del Prato Stefano
Published: March 2007

OBJECTIVE—To evaluate the rate of progression of renal disease in proteinuric type 2 diabetic patients with and without retinopathy.

RESEARCH DESIGN AND METHODS—Thirty-eight proteinuric type 2 diabetic patients with diabetic retinopathy and 27 without were enrolled in an observational study for the evaluation of rate of glomerular filtration rate (GFR) decline and followed up for a median period of 6 years. GFR was determined at least once per year, and blood pressure, glycated hemoglobin, and proteinuria were determined every 4 months.

RESULTS—Although the two groups had comparable GFR, albuminuria, blood pressure, and HbA1c at entry of the study, the rate of decline of GFR was higher in type 2 diabetic patients with retinopathy (−6.5 ± 4.4 ml/year) than in those without (−1.8 ± 4.8 ml/year; P < 0.0001). Protein and albumin excretion rate increased significantly in patients with retinopathy, while they did not change in those without. Mean blood pressure between the two groups of patients were similar both at entry and during the follow-up, although the proportion of patients treated with at least two antihypertensive drugs was higher in patients with retinopathy. On a multiple regression analysis, only mean blood pressure and proteinuria were significant determinants of progression of renal disease in type 2 diabetic patients with retinopathy.

CONCLUSIONS—The rate of progression of renal disease in proteinuric type 2 diabetic patients with retinopathy is faster than that observed in those without retinopathy. The screening for retinopathy identifies patients at high risk for rapid deterioration of kidney function.
Validation of the Toronto Clinical Scoring System for Diabetic Polyneuropathy
Authors: Bril Vera , Perkins Bruce A.
Published: March 2007

OBJECTIVE—The aim of the current study was to determine the validity of the Toronto Clinical Scoring System (CSS) in reflecting the presence and severity of diabetic peripheral sensorimotor polyneuropathy (DSP) as determined by myelinated fiber density (FD) on sural nerve biopsy.

RESEARCH DESIGN AND METHODS—Eighty-nine patients with both type 1 and type 2 diabetes, ascertained from a large therapeutic randomized controlled trial, were included in this cross-sectional, observational cohort study. Morphological severity of DSP was expressed as the FD in the sural nerve biopsy. The Toronto CSS was applied to all patients to determine a clinical neuropathy score. General linear regression models were used to assess the relationship between the morphological severity of DSP and the Toronto CSS.

RESULTS—The Toronto CSS showed a significant negative correlation with sural nerve FD (R2 = 0.256, P < 0.0001). The Toronto CSS was lower in those with better glycemic control (HbA1c ≤8%). Sural nerve FD and the Toronto CSS showed strong correlations with electrophysiology, by both summed amplitude and summed conduction velocity values.

CONCLUSIONS—The Toronto CSS is a valid instrument to reflect the presence and severity of DSP as measured by sural nerve morphology and electrophysiology. The results of the current study underscore the interrelationships between clinical deficits, electrophysiological findings, and morphological changes in DSP. This evidence suggests that the Toronto CSS may prove useful in documenting and monitoring DSP in the clinic and in clinical research trials.
Indices of Insulin Action, Disposal, and Secretion Derived From Fasting Samples and Clamps in Normal Glucose-Tolerant Black and White Children
Authors: Uwaifo Gabriel I. , Fallon Erica M. , Chin Jeff , Elberg Jane , Parikh Shamik J. , Yanovski Jack A.
Published: March 2007

OBJECTIVE—To validate fasting indices of insulin sensitivity and secretion in a diverse pediatric population against gold standard estimates from euglycemic and hyperglycemic clamps.

RESEARCH DESIGN AND METHODS—A total of 31 children (mean BMI 25.1 ± 4.9 kg/m2, mean age 8.7 ± 1.4 years, 15 girls and 16 boys, 12 black and 19 white) underwent euglycemic and hyperglycemic clamps 2–6 weeks apart to derive insulin sensitivity indices (SI Eug clamp and SI Hyper clamp). Fasting samples were used to derive the homeostasis model assessment of insulin resistance index (HOMA-IR), HOMA of percent β-cell function (HOMA-B%), quantitative insulin sensitivity check index (QUICKI), insulinogenic index, antilipolytic insulin sensitivity index (ISI-FFA), and C-peptide–to–insulin ratio.

RESULTS—The QUICKI correlated best with SI Eug clamp (r = 0.69, P < 0.05) and had greater correlations to SI Eug clamp than did either SI Hyper clamp (r = 0.45, P < 0.05) or the HOMA-IR (r = −0.51, P < 0.05). Both fasting insulin and the insulinogenic index correlated well with first- and steady-phase insulin secretion (r’s from 0.79 to 0.86, P < 0.05). HOMA-B% was not as highly correlated (r = 0.69–0.72, P < 0.05). Fasting C-peptide–to–insulin ratio was not significantly correlated with clamp-derived metabolic clearance rate of insulin. ISI-FFA was not correlated with the degree of free fatty acid suppression obtained from the clamps.

CONCLUSIONS—The QUICKI, fasting insulin, and the insulinogenic index all closely correlate with corresponding clamp-derived indices of insulin sensitivity and secretion in this diverse pediatric cohort. These results, if replicated in similarly diverse populations, suggest that estimates based on fasting samples can be used to rank order insulin secretion and sensitivity in pediatric cohorts.
The Diabetes Prevention Program (DPP)
Authors:   The Diabetes Prevention Program (DPP) Research Group
Published: March 2007

The purpose of the present article is to provide a detailed description of the highly successful lifestyle intervention administered to 1,079 participants, which included 45% racial and ethnic minorities and resulted in a 58% reduction in the incidence rate of diabetes (2). The two major goals of the Diabetes Prevention Program (DPP) lifestyle intervention were a minimum of 7% weight loss/weight maintenance and a minimum of 150 min of physical activity similar in intensity to brisk walking. Both goals were hypothesized to be feasible, safe, and effective based on previous clinical trials in other countries (3–7). The methods used to achieve these lifestyle goals include the following key features: 1) individual case managers or “lifestyle coaches;” 2) frequent contact with participants; 3) a structured, state-of-the-art, 16-session core-curriculum that taught behavioral self-management strategies for weight loss and physical activity; 4) supervised physical activity sessions; 5) a more flexible maintenance intervention, combining group and individual approaches, motivational campaigns, and “restarts;” 6) individualization through a “toolbox” of adherence strategies; 7) tailoring of materials and strategies to address ethnic diversity; and finally 8) an extensive network of training, feedback, and clinical support.