bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of Endothelial Function by Pregnancy
Authors: Ramsay Jane E. , Simms Roslyn J. , Ferrell William R. , Crawford Lynn , Greer Ian A. , Lumsden Mary-Anne , Sattar Naveed
Published: March 2007

OBJECTIVE—Pregnant women with type 1 diabetes have a substantially increased risk of vascular complications. Our aim was to study vascular function and metabolic and inflammatory risk factors during the antenatal and postpartum periods in women with type 1 diabetes compared with healthy control subjects.

RESEARCH DESIGN AND METHODS—A total of 15 women with diabetes and 30 control subjects were recruited in the third trimester of pregnancy. Of these women, 9 case subjects and 16 control subjects were reinvestigated in the postnatal period. Blood samples were collected and microvascular skin perfusion was assessed in vivo using laser Doppler imaging and iontophoretic administration of endothelial-dependent (acetylcholine [ACH]) and endothelial-independent (sodium nitroprusside [SNP]) vasodilators.

RESULTS—Microvascular responses in both control subjects (ACH, P = 0.018; SNP, P = 0.01) and diabetic women (ACH, P = 0.029; SNP, P = 0.105) were better during pregnancy than in the postnatal period, although responses in women with diabetes were significantly inferior to those in control subjects during both periods (all P < 0.001, two-way ANOVA). This dysfunction existed despite similar lipoprotein profiles. The difference in vascular responsivity between case and control subjects was significantly attenuated by adjustment for differences in HbA1c but not C-reactive protein concentrations in the two groups.

CONCLUSIONS—Pregnancy enhances microvascular function, but in women with diabetes, such improvements are insufficient to attain responses seen in healthy nonpregnant women. This suggests a persistent vascular defect in young women with type 1 diabetes that may contribute to adverse pregnancy outcome. Our data suggest a role for the chronic effects of hyperglycemia in the impaired vascular responsiveness in such women.
Renal and Metabolic Effects of Insulin Lispro in Type 2 Diabetic Subjects With Overt Nephropathy
Authors: Ruggenenti Piero , Flores Claudio , Aros Claudio , Ene-Iordache Bogdan , Trevisan Roberto , Ottomano Cosimo , Remuzzi Giuseppe
Published: March 2007

OBJECTIVE—To assess whether the insulin analog lispro may antagonize the renal effects of IGF-1, a mediator of glomerular hyperfiltration involved in the progression of diabetic and nondiabetic chronic nephropathies.

RESEARCH DESIGN AND METHODS—In a randomized crossover study, we compared the renal and metabolic responses to regular or lispro insulin (0.1 units/kg body wt) administered after a euglycemic clamp and 5 and 30 min before a standard meal to 11 type 2 diabetic patients with macroalbuminuria.

RESULTS—Two- and four-hour postprandial changes (vs. preprandial euglycemia) in glomerular filtration rate (GFR) followed a significantly different trend (5.8 ± 5.0 vs. −6.3 ± 4.7, P < 0.05; and 11.0 ± 6.8 vs. 0.7 ± 5.1%, P < 0.05) after regular insulin and lispro injection, respectively. After lispro, postprandial GFR changes were negatively correlated (r = −0.48, P = 0.0001) with plasma insulin concentration. After regular insulin, renal plasma flow increased in parallel with a decrease in renal vascular resistances. Both changes were fully prevented by lispro. Postprandial blood glucose maximum concentration (278 ± 16 vs. 240 ± 16 mg/dl, P < 0.01) and area under the curve (79,381 ± 19,237 vs. 72,810 ± 16,211 mg/dl per min, P < 0,05) were significantly lower after insulin lispro than after regular insulin injection, respectively, despite comparable postprandial insulin profiles. Changes in total and gluconeogenic amino acids followed a similar trend. Changes in blood glucose and plasma amino acids did not correlate with concomitant changes in GFR.

CONCLUSIONS—In overt nephropathy of type 2 diabetes, lispro prevents glomerular hyperfiltration and offsets the renal effects of meal or meal-associated hyperglycemia by mechanisms possibly related to IGF-1 antagonism.
Prospective Analysis of Mortality, Morbidity, and Risk Factors in Elderly Diabetic Subjects
Authors: Katakura Masafumi , Naka Motoji , Kondo Teruki , Nishii Nakako , Komatsu Mitsuhisa , Sato Yoshihiko , Yamauchi Keishi , Hiramatsu Kunihide , Ikeda Mitsuru , Aizawa Toru , Hashizume Kiyoshi
Published: March 2007

OBJECTIVE—To clarify mortality and morbidity of intensively managed elderly diabetic individuals and to explore factors predicting mortality and diabetes-related end points.

RESEARCH DESIGN AND METHODS—A total of 390 elderly (≥65 years of age) outpatients with type 2 diabetes ( 173 men and 217 women, mean age 73.0 years) were analyzed. The mean HbA1c upon entry was 6.8% (332 receiving oral hypoglycemics and/or insulin) and blood pressure upon entry was 136/74 mmHg (219 receiving antihypertensive drugs). The patients have been followed-up for 3 years with HbA1c <7.0% and blood pressure <145/80 mmHg as targets, with mortality and an aggregate of fatal and nonfatal diabetes-related events as end points. Mortality rate and causes of mortality, as well as risk factors for mortality and morbidity, were determined.

RESULTS—The mortality rate, 2.9% per year, was comparable to that of the age- and sex-matched general population. Stroke was a leading cause of mortality after malignancy. By the univariate Cox proportional hazards model, only high serum creatinine and prior stroke were highly significant and strong risks for both end points. In those without prior stroke and receiving antihypertensive agents, the incidence of the diabetes-related end point based on their systolic blood pressure (SBP) quartile was U-shaped, with the nadir at the 3rd (SBP, 137–147 mmHg) and the peak at the 1st (SBP ≤ 125 mmHg) quartile.

CONCLUSIONS—In well-controlled elderly diabetic subjects, there was no excessive mortality compared to the age- and sex-matched general population. Renal dysfunction and prior stroke were independent risks for mortality and morbidity. In those without prior stroke, a risk of too much lowering of blood pressure was suggested.
Comparison of a Clinical Model, the Oral Glucose Tolerance Test, and Fasting Glucose for Prediction of Type 2 Diabetes Risk in Japanese Americans
Authors: McNeely Marguerite J. , Boyko Edward J. , Leonetti Donna L. , Kahn Steven E. , Fujimoto Wilfred Y.
Published: March 2007

OBJECTIVE—To test the validity of a published clinical model for predicting incident diabetes in Japanese Americans.

RESEARCH DESIGN AND METHODS—A total of 465 nondiabetic Japanese Americans (243 men, 222 women), aged 34–75 years, were studied at baseline and at 5–6 years. A total of 412 subjects were studied at 10 years. The clinical model included age, sex, ethnicity, BMI, systolic blood pressure, fasting plasma glucose (FPG), HDL cholesterol, and family history of diabetes at baseline. Diabetes status at 5–6 and 10 years was determined by 75-g oral glucose tolerance test. The clinical model, 2-h glucose, and FPG were compared using receiver-operating characteristic (ROC) curves.

RESULTS—The diabetes risk associated with BMI, sex, and HDL cholesterol differed by age (P ≤ 0.011). At 5–6 years, the clinical model ROC curve area (0.896) was higher than that for FPG (0.776, P = 0.008), but not for 2-h glucose (0.851, P = 0.341), for subjects aged ≤55 years. For older subjects, the clinical model ROC curve area (0.599) was lower than that for 2-h glucose (0.792, P ≤ 0.001), but not for FPG (0.627, P = 0.467). At 10 years, there were no significant differences between the clinical model, FPG, and 2-h glucose ROC curve areas in either age group.

CONCLUSIONS—In Japanese Americans aged ≤55 years, a clinical model was better than FPG for predicting diabetes after 5–6 years but not after 10 years. The model was not useful in older Japanese Americans, whereas 2-h glucose was useful for predicting diabetes risk regardless of age.
β-Cell Function and the Development of Diabetes-Related Complications in the Diabetes Control and Complications Trial
Authors: Steffes Michael W. , Sibley Shalamar , Jackson Melissa , Thomas William
Published: March 2007

In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining β-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual β-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: ≤0.03, 0.04–0.20, 0.21–0.50 nmol/l at entry, and 0.21–0.50 nmol/l at entry and at least 1 year later (sustained C-peptide secretion). Uniformly in the intensive and partially in the conventional DCCT treatment groups, any C-peptide secretion, but especially at higher and sustained levels of stimulated C-peptide, was associated with reduced incidences of retinopathy (both a single three-step change and a repeated three-step change on the Early Treatment of Diabetic Retinopathy Study [ETDRS] scale at the next 6 month visit) and nephropathy (both albuminuria >40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia (∼65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level >0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of ∼30%. Therefore, even modest levels of β-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).
Poor Prognosis of Young Adults With Type 1 Diabetes
Authors: Bryden Kathryn S. , Dunger David B. , Mayou Richard A. , Peveler Robert C. , Neil H. Andrew W.
Published: March 2007

OBJECTIVE—To determine the role of early behavioral and psychological factors on later outcomes in young adults with childhood- or adolescent-onset type 1 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a longitudinal cohort study of patients recruited from the register of the young adult outpatient diabetes clinic, Oxford, U.K. A total of 113 individuals (51 male subjects) aged 17–25 years completed assessments, and 87 (77%) were reinterviewed as older adults (aged 28–37 years). Longitudinal assessments were made of glycemic control (HbA1c) and complications. Psychological state at baseline was assessed using the Present State Examination and self-report Symptom Checklist, with corresponding interview schedules administered at follow-up.

RESULTS—There was no significant improvement between baseline and follow-up in mean HbA1c levels (8.5 vs. 8.6% in men, 9.3 vs. 8.7% in women). The proportion of individuals with serious complications (preproliferative or laser-treated retinopathy, proteinuria or more severe renal disease, peripheral neuropathy, and autonomic neuropathy) increased from 3–37% during the 11-year period. Women were more likely than men to have multiple complications (23 vs. 6%, difference 17%, 95% CI 4–29%, P = 0.02). Psychiatric disorders increased from 16 to 28% (20% in men, 36% in women at follow-up, difference NS), and 8% had psychiatric disorders at both assessments. Baseline psychiatric symptom scores predicted follow-up scores (β = 0.32, SE [β] 0.12, P = 0.008, 95% CI 0.09–0.56) and recurrent admissions with diabetic ketoacidosis (odds ratio 9.1, 95% CI 2.9–28.6, P < 0.0001).

CONCLUSIONS—The clinical and psychiatric outcome in this cohort was poor. Psychiatric symptoms in later adolescence and young adulthood appeared to predict later psychiatric problems.
Rapid A1c Availability Improves Clinical Decision-Making in an Urban Primary Care Clinic
Authors: Miller Christopher D. , Barnes Catherine S. , Phillips Lawrence S. , Ziemer David C. , Gallina Daniel L. , Cook Curtiss B. , Maryman Sandra D. , El-Kebbi Imad M.
Published: March 2007

OBJECTIVE—Failure to meet goals for glycemic control in primary care settings may be due in part to lack of information critical to guide intensification of therapy. Our objective is to determine whether rapid-turnaround A1c availability would improve intensification of diabetes therapy and reduce A1c levels in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—In this prospective controlled trial, A1c was determined on capillary glucose samples and made available to providers, either during (“rapid”) or after (“routine”) the patient visit. Frequency of intensification of pharmacological diabetes therapy in inadequately controlled patients and A1c levels were assessed at baseline and after follow-up.

RESULTS—We recruited 597 subjects. Patients were 79% female and 96% African American, with average age of 61 years, duration of diabetes 10 years, BMI 33 kg/m2, and A1c 8.5%. The rapid and routine groups had similar clinical demographics. Rapid A1c availability resulted in more frequent intensification of therapy when A1c was ≥7.0% at the baseline visit (51 vs. 32% of patients, P = 0.01), particularly when A1c was >8.0% and/or random glucose was in the 8.4–14.4 mmol/l range (151–250 mg/dl). In 275 patients with two follow-up visits, A1c fell significantly in the rapid group (from 8.4 to 8.1%, P = 0.04) but not in the routine group (from 8.1 to 8.0%, P = 0.31).

CONCLUSIONS—Availability of rapid A1c measurements increased the frequency of intensification of therapy and lowered A1c levels in patients with type 2 diabetes in an urban neighborhood health center.
Unrecognized Anemia in Patients With Diabetes
Authors: Thomas Merlin C. , MacIsaac Richard J. , Tsalamandris Con , Power David , Jerums George
Published: March 2007

OBJECTIVE—Anemia is common in diabetes, potentially contributing to the pathogenesis of diabetes complications. This study aims to establish the prevalence and independent predictors of anemia in a cross-sectional survey of 820 patients with diabetes in long-term follow-up in a single clinic.

RESEARCH DESIGN AND METHODS—A full blood count was obtained in addition to routine blood and urine test results for all patients over a 2-year period to encompass all patterns of review. Predictors of the most recent Hb concentration and anemia were identified using multiple and logistic regression analysis.

RESULTS—A total of 190 patients (23%) had unrecognized anemia (Hb <12 g/dl for women and <13 g/dl for men). This prevalence is two to three times higher than for patients with comparable renal impairment and iron stores in the general population. Independent predictors for Hb were transferrin saturation, glomerular filtration rate (GFR), sex, albumin excretion rate, and HbA1c level (all P < 0.0001). Microalbuminuric patients were >2 times (odds ratio [OR] 2.3) and macroalbuminuric patients >10 times (OR 10.1) as likely to have anemia than normoalbuminuric patients with preserved renal function (GFR >80 ml/min).

CONCLUSIONS—Anemia is a common accompaniment to diabetes, particularly in those with albuminuria or reduced renal function. Additional factors present in diabetes may contribute to the development of increased risk for anemia in patients with diabetes.
Detection of Undiagnosed Diabetes and Other Hyperglycemia States
Authors: Schmidt Maria Inês , Duncan Bruce B. , Vigo Alvaro , Pankow James , Ballantyne Christie M. , Couper David , Brancati Frederick , Folsom Aaron R. ,   for the ARIC Investigators
Published: March 2007

OBJECTIVE—To evaluate screening strategies based on fasting plasma glucose (FPG), clinical information, and the oral glucose tolerance test (OGTT) for detection of diabetes or other hyperglycemic states—impaired fasting glucose (IFG) and impaired glucose tolerance—meriting clinical intervention.

RESEARCH DESIGN AND METHODS—We studied 8,286 African-American and white men and women without known diabetes, aged 53–75 years, who received an OGTT during the fourth exam of the Atherosclerosis Risk in Communities Study. Using a split sample technique, we estimated the diagnostic properties of various clinical detection rules derived from logistic regression modeling. Screening strategies utilizing FPG, these detection rules, and/or the OGTT were then compared in terms of both the fraction of hyperglycemia cases detected and the sample fraction receiving different screening tests and identified as screen positive.

RESULTS—Screening based on the IFG cut point (≥6.1 mmol/l), followed by a clinical detection rule for those below this value, detected 86.3% of diabetic case subjects and 66.0% of all hyperglycemia cases, identifying 42% of the sample as screen positive. Applying an OGTT for those positive by the rule provides diagnostic labeling and reduces the fraction that is screen positive to 29%. Another strategy, to apply an OGTT to those with an FPG cut point between 5.6 and 6.1 mmol/l, also identifies 29% of the sample as screen positive, although it detects slightly fewer hyperglycemia cases.

CONCLUSIONS—Screening strategies based on FPG, complemented by clinical detection rules and/or an OGTT, are effective and practical in the detection of hyperglycemic states meriting clinical intervention.
Prevalence of the Metabolic Syndrome Among Omani Adults
Authors: Al-Lawati Jawad A. , Mohammed Ali J. , Al-Hinai Halima Q. , Jousilahti Pekka
Published: March 2007

OBJECTIVE—To estimate the prevalence of the metabolic syndrome by age and sex in the Omani population as defined by the third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) of North America.

RESEARCH DESIGN AND METHODS—We analyzed data from a cross-sectional survey conducted in 2001 containing a probability random sample of 1,419 Omani adults aged ≥20 years living in the city of Nizwa. The metabolic syndrome, defined by the ATP III, was defined as having three or more of the following abnormalities: waist circumference >102 cm in men and >88 cm in women, serum triglycerides ≥150 mg/dl (1.69 mmol/l), HDL cholesterol <40 mg/dl (1.04 mmol/l) in men and <50 mg/dl (1.29 mmol/l) in women, systolic blood pressure ≥130 mmHg and/or diastolic ≥85 mmHg or on treatment for hypertension, and fasting serum glucose ≥110 mg/dl (6.1 mmol/l) or on treatment for diabetes.

RESULTS—The age-adjusted prevalence of the metabolic syndrome was 21.0%. The crude prevalence was slightly lower (17.0%). The age-adjusted prevalence was 19.5% among men and 23.0% among women (P = 0.236). Low HDL cholesterol was the most common component (75.4%) of the metabolic syndrome among the study population followed by abdominal obesity (24.6%). Abdominal obesity was markedly higher in women (44.3%) than in men (4.7%).

CONCLUSIONS—The prevalence of the metabolic syndrome in Oman is similar to that in developed countries. Future prevention and control strategies should not overlook the importance of noncommunicable disease risk factors in rapidly developing countries.
Ulcer Recurrence Following First Ray Amputation in Diabetic Patients
Authors: Dalla Paola Luca , Faglia Ezio , Caminiti Maurizio , Clerici Giacomo , Ninkovic Sasa , Deanesi Valter
Published: March 2007

OBJECTIVE—to evaluate the reulceration and reamputation rates in a cohort of diabetic patients following first ray amputation.

RESEARCH DESIGN AND METHODS—We evaluated a cohort of 89 diabetic patients, 63 men and 26 women, who underwent first ray amputation in the period from January 2000 to December 2001. The first ray lesions were Wagner grade 2 in 3 patients, Wagner grade 3 in 47 patients, and Wagner grade 4 in 39 patients. Following surgical wound healing, all patients wore special footwear with rocker bottom soles and custom molded insoles and were put on an intensive secondary prevention program.

RESULTS—The mean follow-up duration was 16.35 ± 6.76 months (range 7–28). Fifteen patients developed new ulcerations, with 11 lesions occurring ipsilaterally and 4 contralaterally to the first ray amputation. In seven patients, the new lesion was treated and healed with dressing. Eight patients underwent a new surgical procedure: panmetatarsal head resection in four patients, toe amputation in two patients, a transmetatarsal amputation in one patient, and Lisfranc’s amputation in one patient.

CONCLUSIONS—In the population studied, the first ray amputation presented a lower reulceration and reamputation rate with respect to that reported in the literature. This finding should therefore be attributed to the follow-up program, which uses shoes with a rocker bottom sole and custom molded insoles and intensive ambulatory check-ups.
The Association Between Cardiovascular Autonomic Neuropathy and Mortality in Individuals With Diabetes
Authors: Maser Raelene E. , Mitchell Braxton D. , Vinik Aaron I. , Freeman Roy
Published: March 2007

OBJECTIVE—To examine by meta-analysis the relationship between cardiovascular autonomic neuropathy (CAN) and risk of mortality in individuals with diabetes.

RESEARCH DESIGN AND METHODS—We searched Medline for English-language articles published from 1966 to 2001. Fifteen studies having a baseline assessment of cardiovascular autonomic function and mortality follow-up were identified. The analyses were stratified according to whether a single abnormality or two or more measures of cardiovascular autonomic function were used to define CAN. A global measure of association (i.e., relative risk) was generated for each group by pooling estimates across the studies using the Mantel-Haenszel procedure.

RESULTS—CAN was significantly associated with subsequent mortality in both groups, although the magnitude of the association was stronger for those studies for which two or more measures were used to define CAN. The pooled relative risk for studies that defined CAN with the presence of two or more abnormalities was 3.45 (95% CI 2.66–4.47; P < 0.001) compared with 1.20 (1.02–1.41; P = 0.03) for studies that used one measure.

CONCLUSIONS—These results support an association between CAN and increased risk of mortality. The stronger association observed in studies defining CAN by the presence of two or more abnormalities may be due to more severe autonomic dysfunction in these subjects or a higher frequency of other comorbid complications that contributed to their higher mortality risk. Future studies should evaluate whether early identification of subjects with CAN can lead to a reduction in mortality.
A Flexible, Low-Glycemic Index Mexican-Style Diet in Overweight and Obese Subjects With Type 2 Diabetes Improves Metabolic Parameters During a 6-Week Treatment Period
Authors: Jimenez-Cruz Arturo , Bacardi-Gascon Montserrat , Turnbull Wilfred H. , Rosales-Garay Perla , Severino-Lugo Isis
Published: March 2007

OBJECTIVE—The aim of this study was to compare the effects of a flexible lower- and higher-glycemic index (GI) Mexican-style diet on biochemical data and BMI during a 6-week treatment period.

RESEARCH DESIGN AND METHODS—This study was a randomized, crossover design of two 6-week periods with a 6-week washout period between treatments. Subjects with type 2 diabetes (n = 36) with a BMI >25 kg/m2 were selected. Fourteen subjects completed the study with eligible dietary records. Dietary instruction was provided on flexible diets with both a high and low GI. Fasting venous blood samples were taken at the start and finish of each dietary period, and biochemical data were analyzed. Multi- and univariate one-factor repeated-measures ANOVA were used to compare biochemical data.

RESULTS—Glycemic load and GI were lower during the low-GI diet, and dietary fiber was lower during the high-GI diet. The participants in the low-GI period consumed significantly fewer carbohydrates, such as white-wheat bread, white long-grain rice, potatoes, high-GI fruits, and carrots, and more carbohydrates, such as pinto beans, whole-meal wheat bread, and low-GI fruits than did participants in the high-GI period. There were no differences in the amount of carbohydrates consumed, such as corn tortillas and dairy products. At the end of the study periods, A1c was improved on the low- compared with the high-GI diet (P < 0.008).

CONCLUSIONS—We conclude that a low-GI diet, containing Mexican-style foods, may help to improve the metabolic control in type 2 obese diabetic subjects during a 6-week period.
Associations of Dietary Fiber With Glucose Metabolism in Nondiabetic Relatives of Subjects With Type 2 Diabetes
Authors: Ylönen Katriina , Saloranta Carola , Kronberg-Kippilä Carina , Groop Leif , Aro Antti , Virtanen Suvi M. ,   the Botnia Research Group
Published: March 2007

OBJECTIVE—To study cross-sectional associations of dietary fiber intake with insulin resistance, insulin secretion, and glucose tolerance in a population at high risk for type 2 diabetes.

RESEARCH DESIGN AND METHODS—The subjects consisted of 248 male and 304 female adult nondiabetic relatives of patients with type 2 diabetes. Dietary intake was measured by means of two 3-day food records. Associations of total, water-insoluble, and water-soluble fiber with measures of glucose metabolism based on an oral glucose tolerance test, were analyzed by multiple linear regression analysis adjusting for sex, age, length of education, physical activity, BMI, waist-to-hip ratio, systolic blood pressure, and serum triglyceride and HDL cholesterol concentrations. The homeostasis model assessment insulin resistance index, the incremental 30-min serum insulin concentration divided by the incremental 30-min glucose concentration, and fasting and 2-h glucose concentrations were the outcome variables.

RESULTS—The dietary intake of total as well as water-insoluble and water-soluble fiber was inversely associated with insulin resistance: −0.17 (0.07), P = 0.012; −0.15 (0.07), P = 0.024; and −0.14 (0.07), P = 0.049 [regression coefficients (SE)]. Fiber variables were unrelated to insulin secretion and plasma glucose concentrations.

CONCLUSIONS—The results support evidence that a high intake of dietary fiber is associated with enhanced insulin sensitivity and therefore may have a role in the prevention of type 2 diabetes.
Treatment of Patients Over 64 Years of Age With Type 2 Diabetes
Authors: Del Prato Stefano , Heine Robert J. , Keilson Leonard , Guitard Christiane , Shen Sharon G. , Emmons Rebecca P.
Published: March 2007

OBJECTIVE—To evaluate the impact of renal impairment (RI) (estimated creatinine clearance [Clcr] <60 ml/min per 1.73 m2) and low baseline HbA1c (<7.5%) on comorbidity in patients with type 2 diabetes, and to assess the efficacy and safety of nateglinide monotherapy in these patients and in subgroups of patients over age 64 years (elderly) and elderly with RI.

RESEARCH DESIGN AND METHODS—Retrospective subgroup analyses were performed on pooled data from all completed nateglinide studies (12 randomized, double blind trials and 1 open trial) in patients with type 2 diabetes. A total of 3,702 patients with ≥1 postbaseline safety evaluation received monotherapy with nateglinide (n = 2,204), metformin (n = 436), glyburide (n = 293), or placebo (n = 769). Efficacy (HbA1c) was evaluated in pooled data from four studies with similar design using 120 mg nateglinide (n = 544) versus placebo (n = 521). Evaluations were performed in the overall population and subgroups of patients over age 64 years. Specific considerations were given to RI, comorbidity, and baseline HbA1c.

RESULTS—Patients over age 64 years (n = 1,170) represented 31.6% of the study population. Undiagnosed RI was common in the elderly with 83.4% of all patients being in this subgroup. Patients over 64 years with RI had a higher prevalence of cardio- and microvascular comorbidity compared with the overall population and all patients over age 64 years. Statistically significant HbA1c reductions versus placebo were observed with nateglinide in patients over age 64 years and elderly with RI patients at study end point (−0.9% and −1.1% in each subgroup, P < 0.01). Nateglinide was well tolerated with a low incidence of hypoglycemia in all subgroups, including those with RI and low baseline HbA1c.

CONCLUSIONS—RI and comorbidity are common in patients over age 64 years with type 2 diabetes. Nateglinide was effective and well tolerated in all treated patients. In subgroups in which metformin and long-acting sulfonylureas must be used with caution, nateglinide had a low risk of adverse events and hypoglycemia.
Beneficial Effects of Insulin Versus Sulphonylurea on Insulin Secretion and Metabolic Control in Recently Diagnosed Type 2 Diabetic Patients
Authors: Alvarsson Michael , Sundkvist Göran , Lager Ibe , Henricsson Marianne , Berntorp Kerstin , Fernqvist-Forbes Eva , Steen Lars , Westermark Gunilla , Westermark Per , Örn Thomas , Grill Valdemar
Published: March 2007

OBJECTIVE—To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment.

RESEARCH DESIGN AND METHODS—β-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0–2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5–10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2–3 days of temporary withdrawal of treatment.

RESULTS—After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ± 0.08 nmol/l, whereas it was decreased by 0.12 ± 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups; however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02. A questionnaire indicated no difference in well-being related to treatment.

CONCLUSIONS—Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.
C-Reactive Protein Predicts the Deterioration of Glycemia in Chinese Subjects With Impaired Glucose Tolerance
Authors: Tan Kathryn C.B. , Wat Nelson M.S. , Tam Sidney C.F. , Janus Edward D. , Lam T.H. , Lam Karen S.L.
Published: March 2007

OBJECTIVE—Recent studies have shown that C-reactive protein (CRP) predicts future risk of diabetes in healthy Caucasians. We determined whether plasma CRP level was elevated in Chinese subjects with impaired glucose tolerance (IGT) and whether CRP level could be used to predict progression to type 2 diabetes or reversion to normal glucose tolerance (NGT) in these high-risk individuals.

RESEARCH DESIGN AND METHODS—A total of 228 subjects with IGT at baseline from the Hong Kong Cardiovascular Risk Factors Prevalence Study underwent repeat oral glucose tolerance testing after 2 years. Plasma high-sensitivity CRP was measured from their stored baseline samples and from 228 subjects with NGT matched for age and BMI by an immunoturbidimetric assay.

RESULTS—Subjects with IGT at baseline had higher plasma CRP levels than subjects with NGT: 1.18 mg/l (0.52–2.52) vs. 0.87 mg/l (0.37–1.84), median (interquartile range), P = 0.01. At 2 years, 117 subjects with IGT reverted to NGT, 84 remained in IGT, and 21 progressed to diabetes. Individuals who progressed to diabetes had the highest plasma CRP levels at baseline (P < 0.0001). Those with baseline CRP levels in the third and top quartile had a relative risk of remaining in IGT or progressing to diabetes of 2.87 (95% CI 1.06–7.82) and 2.76 (1.06–7.31), respectively, after adjusting for anthropometric measure and lifestyle factors.

CONCLUSIONS—CRP independently predicts the risk of remaining in IGT or progressing to diabetes in Chinese subjects with IGT. CRP might provide an adjunctive measure for identifying subjects with the highest risk of progression to diabetes who would derive the greatest benefits from preventive interventions.
Racial Differences in Diabetic Nephropathy, Cardiovascular Disease, and Mortality in a National Population of Veterans
Authors: Young Bessie A. , Maynard Charles , Boyko Edward J.
Published: March 2007

OBJECTIVE—To determine racial differences in the prevalence of diabetic nephropathy, cardiovascular disease (CVD), and risk of mortality in a national health care system.

RESEARCH DESIGN AND METHODS—A longitudinal cohort study was conducted in 429,918 veterans with diabetes. Racial minority groups were analyzed for baseline differences in prevalence of early diabetic nephropathy, diabetic end-stage renal disease (ESRD) and CVD, and longitudinal risk of mortality compared with Caucasians.

RESULTS—The 429,918 patients identified with diabetes were of the following racial groups: Caucasian (56.2%), African American (15.3%), Asian (0.5%), Native American (0.4%), and unknown race (21.4%). Minority individuals were, on average, younger and less likely to have CVD but were more likely to have renal disease than Caucasians. After adjustment for age, sex, and economic status, African Americans (adjusted odds ratio [OR] = 1.3, 95% CI 1.2–1.4) and Native Americans (1.5, 1.1–2.1) were more likely to have early diabetic nephropathy than Caucasians. Diabetic ESRD was more likely to be present in African Americans (1.9, 1.9–2.0), Hispanics (1.4, 1.3–1.4), Asians (1.8, 1.5–2.1), and Native Americans (1.9, 1.5–2.3) than Caucasians. Concurrently, the adjusted OR of CVD in racial minority groups was 27–49% less than in Caucasians, whereas the 18-month risk of mortality among people from most racial minority groups was 7–12% lower than in Caucasians.

CONCLUSIONS—We conclude that when access to care is comparable, microvascular complications, macrovascular disease, and subsequent death occur with different frequencies among various racial groups.
Acanthocytes in the Urine
Authors: Heine Gunnar H. , Sester Urban , Girndt Matthias , Köhler Hans
Published: March 2007

OBJECTIVE—The presence of hematuria has been suggested to indicate nondiabetic nephropathy in diabetic patients with proteinuria. However, hematuria is frequently found in patients with biopsy-proven diabetic glomerulosclerosis without nondiabetic nephropathy. Urine microscopy allows discrimination of glomerular hematuria, which is defined as acanthocyturia (urinary excretion of acanthocytes, which are dysmorphic erythrocytes with vesicle-like protrusions), from nonglomerular hematuria. We hypothesized that acanthocyturia is an uncommon finding in diabetic nephropathy, which suggests the presence of a nondiabetic nephropathy in diabetic patients with proteinuria.

RESEARCH DESIGN AND METHODS—Urine samples of patients with the clinical diagnosis of diabetic nephropathy (n = 68), of patients with biopsy-proven glomerulonephritis (n = 43), and of age-matched healthy control subjects (n = 20) were examined by phase-contrast microscopy for the presence of hematuria (≥8 erythrocytes/μl) and acanthocyturia. Acanthocyturia of ≥5% (5 acanthocytes among 100 excreted erythrocytes) was classified as glomerular hematuria; acanthocyturia of 2–4% was classified as suspected glomerular hematuria.

RESULTS—Hematuria was found in 62% of patients with the clinical diagnosis of diabetic nephropathy, in 84% of patients with glomerulonephritis, and in 20% of the healthy control subjects upon a single urine examination. In contrast, glomerular hematuria occurred in 4% of patients with diabetic nephropathy and in 40% of patients with glomerulonephritis (P < 0.001).

CONCLUSIONS—In contrast to hematuria, acanthocyturia is uncommon in patients with the clinical diagnosis of diabetic nephropathy. In diabetic patients with proteinuria, the finding of acanthocyturia points to nondiabetic glomerulopathies, and renal biopsy should be considered.
Infections in Diabetic Burn Patients
Authors: Memmel Heidi , Kowal-Vern Areta , Latenser Barbara A.
Published: March 2007

OBJECTIVE— Diabetic burn patients comprise a significant population in burn centers. The purpose of the study was to determine the demographic characteristics of diabetic burn patients and their rate of community-acquired and nosocomial infections.

RESEARCH DESIGN AND METHODS—This was a 46-month retrospective chart and patient registry review comparing diabetic with nondiabetic burn patients. Statistical analysis consisted of means ± SD, descriptive statistics, one-way ANOVA, and χ2 tests.

RESULTS—Of 1,063 adult burn patients (aged 15–54 years), 68 (6%) diabetic burns were compared with burns of 995 adult nondiabetic patients. Of 193, 62 (32%) senior (≥55 years of age) diabetic burns were compared with 131 nondiabetic senior burns. The major mechanism of injury for the diabetic patients was scalding and contact, in contrast to that of nondiabetic patients who were injured mainly by scalding or flame burns. Adult diabetic patients had a significantly increased frequency of foot burns compared with adult nondiabetic patients (32 of 68 [68%] versus 144 of 995 [14%], P = 0.001). Adult diabetic burns had a significant increase in sepsis (P < 0.002) and community-acquired burn wound cellulitis (P < 0.001) compared with adult nondiabetic patients; and senior diabetic patients had a significantly increased frequency of urinary tract infections compared with senior nondiabetic burn patients (P < 0.04). The most common organisms in diabetic burn infections were Streptococcus, Proteus, Pseudomonas, Candida species, and MRSA (methicillin-resistant Staphylococcus aureus). Forty-two percent of the diabetic patients were admitted during the winter months and 25% in the spring. Only 49 of 130 (38%) diabetic burn patients presented for treatment within 48 h after injury compared with 669 of 1,126 (62%) nondiabetic patients (P = 0.001).

CONCLUSIONS—Peripheral neuropathy may have precipitated and delayed medical treatment in lower-extremity burns of diabetic patients. Hospitalized diabetic burn patients were also at an increased risk for nosocomial infections, which prolonged hospitalization. Diabetic patient education must include not only caution about potential burn mishaps but also educate concerning the complications from burns that may ensue.
Prevalence and Trends of a Metabolic Syndrome Phenotype Among U.S. Adolescents, 1999–2000
Authors: Duncan Glen E. , Li Sierra M. , Zhou Xiao-Hua
Published: March 2007

OBJECTIVE—To determine the prevalence of a metabolic syndrome phenotype among U.S. adolescents using the most recent national data and to examine trends in metabolic syndrome prevalence.

RESEARCH DESIGN AND METHODS—Analysis of data on 991 adolescents (aged 12–19 years) who had fasted for at least 6 h, from the National Health and Nutrition Examination Survey (NHANES 1999–2000). The metabolic syndrome was determined using the National Cholesterol Education Program (Adult Treatment Panel III) definition modified for age.

RESULTS—The overall prevalence of a metabolic syndrome phenotype among U.S. adolescents increased from 4.2% in NHANES III (1988–1992) to 6.4% in NHANES 1999–2000 (P < 0.001). The syndrome was more prevalent (P < 0.01) in male than female adolescents (9.1 vs. 3.7%) and was found in 32.1% of overweight adolescents (BMI ≥95th percentile for age and sex), compared with 7.1% of adolescents at risk for overweight (BMI between 85th and 95th percentiles) (P < 0.001). Based on population-weighted estimates, >2 million U.S. adolescents currently have a metabolic syndrome phenotype.

CONCLUSIONS—The prevalence of a metabolic syndrome phenotype has increased significantly over the past decade among U.S. adolescents and is particularly prevalent (>30%) in overweight adolescents. These findings have important implications for public health because of the well-known health risks associated with the metabolic syndrome in adults.
Increasing Prevalence of the Metabolic Syndrome Among U.S. Adults
Authors: Ford Earl S. , Giles Wayne H. , Mokdad Ali H.
Published: March 2007

OBJECTIVE—The prevalence of the metabolic syndrome is high among U.S. adults. Our purpose was to determine whether the prevalence of this syndrome has changed since 1988–1994.

RESEARCH DESIGN AND METHODS—A total of 6,436 men and women aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and 1,677 participants from NHANES 1999–2000 were included in the analyses. We used the definition of the metabolic syndrome developed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.

RESULTS—The unadjusted prevalence of the metabolic syndrome was 23.1% in NHANES III and 26.7% in NHANES 1999–2000 (P = 0.043), and the age-adjusted prevalences were 24.1 and 27.0% (P = 0.088), respectively. The age-adjusted prevalence increased by 23.5% among women (P = 0.021) and 2.2% among men (P = 0.831). Increases in high blood pressure, waist circumference, and hypertriglyceridemia accounted for much of the increase in the prevalence of the metabolic syndrome, particularly among women.

CONCLUSIONS—The increased prevalence of the metabolic syndrome is likely to lead to future increases in diabetes and cardiovascular disease.
IDDM1 and Multiple Family History of Type 1 Diabetes Combine to Identify Neonates at High Risk for Type 1 Diabetes
Authors: Bonifacio Ezio , Hummel Michael , Walter Markus , Schmid Sandra , Ziegler Anette-G.
Published: March 2007

OBJECTIVE—Children of affected probands are at increased risk for type 1 diabetes. The objective of this study was to determine and stratify the risk for islet autoimmunity and childhood diabetes in newborn offspring of affected parents using family history and HLA genetic markers.

RESEARCH DESIGN AND METHODS—Antibodies to islet autoantigens were measured at ages 9 months, 2 years, 5 years, and 8 years in 1,610 offspring of parents with type 1 diabetes participating in the German BABYDIAB study. HLA DR and DQ genetic typing was performed. Family history of type 1 diabetes was obtained from questionnaires.

RESULTS—Extensive family history of type 1 diabetes and HLA DR/DQ genotyping were associated with islet autoantibody and diabetes risks. Significant contributions to the child’s risk for developing islet autoantibodies and type 1 diabetes were conferred by a multiple first-degree family history of type 1 diabetes (two parents or one parent and a sibling; adjusted hazard [HR] ratio, 6.2 for multiple islet autoantibodies and 7.8 for type 1 diabetes), high-risk HLA genotypes (adjusted HR, 11 and 10.9), and moderate-risk HLA genotypes (adjusted HR, 6.3 and 4.3) in a multivariate analysis. Combining these factors stratified the risk for islet autoantibodies from 1 to 46% and for type 1 diabetes from 0 to 19.5% by 5 years of age.

CONCLUSIONS—Risk of childhood diabetes in affected families can be stratified using a combination of genetic and family history markers very early in life.
Diabetes Incidence in 0- to 14-Year Age-Group in Italy
Authors: Carle Flavia , Gesuita Rosaria , Bruno Graziella , Coppa Giovanni V. , Falorni Alberto , Lorini Renata , Martinucci Marco E. , Pozzilli Paolo , Prisco Francesco , Songini Marco , Tenconi Maria T. , Cherubini Valentino ,   for the RIDI Study Group
Published: March 2007

OBJECTIVE—The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990–1999 by nine centers, covering >35% of the Italian population.

RESEARCH DESIGN AND METHODS—Registries were pooled in four geographic macro-areas: north, central, south, and insular. The completeness of registration was assessed by the capture-recapture method. Poisson regression analysis was used to evaluate temporal trend in incidence.

RESULTS—Large variations in incidence were confirmed not only between Sardegna and the mainland but also among peninsular areas. In Sardegna, there was an excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence showed average increases of 3.6% (P < 0.001) and 3.7% (P < 0.001) per year in peninsular Italy and in Sardegna, respectively. Significant increases in incidence rates were found in boys aged 10–14 years (6.7%, 95% CI 0.5–13.3) and in girls aged 5–9 years (6.6%, 0.5–13.1) living in the southern area. The incidence rate also increased in boys aged 10–14 years (5.0%, 0.3–10) and in girls aged 0–4 years (4.9%, 0.8–9.1) living in Sardegna.

CONCLUSIONS—Italy is a country with large geographical variations in incidence rates of type 1 diabetes. However, the rates are evenly increasing both in the mainland and Sardegna, suggesting that similar environmental factors are operating over populations that have different genetic backgrounds.
Dose-Response Effect of a Single Administration of Oral Hexyl-Insulin Monoconjugate 2 in Healthy Nondiabetic Subjects
Authors: Wajcberg Estela , Miyazaki Yoshinori , Triplitt Curtis , Cersosimo Eugenio , DeFronzo Ralph A.
Published: March 2007

OBJECTIVE—1) To evaluate the effect of a single oral dose of hexyl-insulin monoconjugate 2 (HIM2) on the rate of whole-body glucose disposal (Rd) and endogenous glucose production (EGP) in healthy nondiabetic subjects, 2) to examine the reproducibility of HIM2 on glucose metabolism, and 3) to compare the results obtained with HIM2 with those using a bioequivalent dose of subcutaneous lispro insulin.

RESEARCH DESIGN AND METHODS—Six healthy subjects ([means ± SE] aged 31 ± 5 years and BMI 23.1 ± 3.9 kg/m2) participated in four studies performed in random order on separate days. Subjects ingested a single dose of HIM2 (0.125, 0.5, and 0.75 mg/kg) or received subcutaneous lispro insulin (0.1 units/kg). Studies were performed with [3-3H]glucose, and plasma glucose concentration was maintained at basal levels for 4 h with the euglycemic clamp technique. After 6 weeks, subjects participated in two repeat studies to examine the reproducibility of HIM2 (0.5 mg/kg) and lispro insulin (0.1 units/kg).

RESULTS—Fasting plasma insulin (7 μU/ml) increased to a maximum of 102, 321, and 561 μU/ml at 60 min after all three HIM2 doses (0.125, 0.5, and 0.75 mg/kg, respectively). A dose-related decrease in basal EGP was observed as the HIM2 dosage was increased from 0 to 0.125 to 0.5 mg/kg (P < 0.05 vs. each preceding dose). Suppression of EGP was similar with the 0.5- and 0.75-mg/kg HIM2 doses. A dose-related stimulation of basal Rd was observed as the HIM2 dosage was increased from 0 to 0.125 to 0.5 (P < 0.05 vs. each preceding dose) to 0.75 mg/kg (P < 0.10 vs. preceding dose). Rd (0–240 min) was increased by 0.5 mg/kg oral HIM2 to a value similar to 0.1 units/kg lispro insulin. The 0.125-mg/kg HIM2 dose reduced EGP (0–240 min) to a value that was similar to 0.1 units/kg lispro insulin. The variability in the effect of HIM2 and lispro on Rd (25 ± 7 vs. 27 ± 1%, respectively) and on suppression of EGP (19 ± 1 vs. 19 ± 0.7%, respectively) was similar.

CONCLUSIONS—Oral HIM2 suppresses EGP and increases tissue Rd in a dose-dependent manner. The effects of HIM2 on EGP and Rd persisted at 240 min, even though plasma insulin concentration had returned to basal levels. Oral HIM2 may provide an effective and reproducible means of controlling postprandial plasma glucose excursions in diabetic patients.