bluuebunny/crossref_metadata_2025 huggingface dataset:
Postabsorptive and Insulin-Stimulated Energy Homeostasis and Leucine Turnover in Offspring of Type 2 Diabetic Patients
Authors: Lattuada Guido , Sereni Lucia Piceni , Ruggieri Dora , Scollo Antonella , Benedini Stefano , Ragogna Francesca , Costantino Federica , Battezzati Alberto , Luzi Livio , Perseghin Gianluca
Published: March 2007

OBJECTIVE—This study was performed to ascertain whether insulin resistance with respect to protein metabolism is an additional primary metabolic abnormality affecting insulin-resistant offspring of type 2 diabetic parents, along with insulin resistance with respect to glucose and lipid metabolism.

RESEARCH DESIGN AND METHODS—We studied 18 young, nonobese offspring of type 2 diabetic parents and 27 healthy matched (by means of dual-energy X-ray absorption) individuals with the bolus plus continuous infusion of [6,6-2H2]glucose and [1-13C]leucine in combination with the insulin clamp (40 mU · m–2 · min−1).

RESULTS—Fasting plasma leucine, phenylalanine, alanine, and glutamine concentrations, as well as the glucose and leucine turnover (reciprocal pool model: 155 ± 10 vs. 165 ± 5 μmol · kg lean body mass–1 · h−1 in offspring of type 2 diabetic patients and healthy matched individuals, respectively), were also not different. During the clamp, glucose turnover rates were significantly reduced in offspring of type 2 diabetic patients (7.1 ± 0.5) in comparison with healthy matched individuals (9.9 ± 0.6 mg · kg lean body mass–1 · min−1; P < 0.01). Also, the suppression of leucine turnover was impaired in offspring of type 2 diabetic patients (12 ± 1%) in comparison with healthy matched individuals (17 ± 1%; P = 0.04) and correlated with the degree of the impairment of insulin-stimulated glucose metabolism (R2 = 0.13; P = 0.02).

CONCLUSIONS—Nonobese, nondiabetic, insulin-resistant offspring of type 2 diabetic patients were characterized by an impairment of insulin-dependent suppression of protein breakdown, which was proportional to the impairment of glucose metabolism. These results demonstrate that in humans, a primary in vivo impairment of insulin action affects glucose and fatty acid metabolism as previously shown and also protein/amino acid metabolism.
Including Walnuts in a Low-Fat/Modified-Fat Diet Improves HDL Cholesterol-to-Total Cholesterol Ratios in Patients With Type 2 Diabetes
Authors: Tapsell Linda C. , Gillen Lynda J. , Patch Craig S. , Batterham Marijka , Owen Alice , Baré Marian , Kennedy Meredith
Published: March 2007

OBJECTIVE—The aim of this study was to examine the effect of a moderate-fat diet inclusive of walnuts on blood lipid profiles in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—This was a parallel randomized controlled trial comparing three dietary advice groups each with 30% energy as fat: low fat, modified low fat, and modified low fat inclusive of 30 g of walnuts per day. Fifty-eight men and women, mean age 59.3 ± 8.1 years, started the trial. Dietary advice was given at baseline with monthly follow-up and fortnightly phone calls for support. Body weight, percent body fat, blood lipids, HbA1c, total antioxidant capacity, and erythrocyte fatty acid levels were measured at 0, 3, and 6 months. Data were assessed by repeated-measures ANOVA with an intention-to-treat model.

RESULTS—The walnut group achieved a significantly greater increase in HDL cholesterol–to–total cholesterol ratio (P = 0.049) and HDL (P = 0.046) than the two other treatment groups. A 10% reduction in LDL cholesterol was also achieved in the walnut group, reflecting a significant effect by group (P = 0.032) and time (P = 0.036). There were no significant differences between groups for changes in body weight, percent body fat, total antioxidant capacity, or HbA1c levels. The higher dietary polyunsaturated fat–to–saturated fat ratio and intakes of ω-3 fatty acids in the walnut group were confirmed by erythrocyte biomarkers of dietary intake.

CONCLUSIONS—Structured “whole of diet” advice that included 30 g of walnuts/day delivering substantial amounts of polyunsaturated fatty acid improved the lipid profile of patients with type 2 diabetes.
Outcomes in Type 1 Diabetic Pregnancies
Authors: Jensen Dorte M. , Damm Peter , Moelsted-Pedersen Lars , Ovesen Per , Westergaard Jes G. , Moeller Margrethe , Beck-Nielsen Henning
Published: March 2007

OBJECTIVE—The aim of this study was to compare pregnancy outcomes in type 1 diabetic pregnancies with the background population.

RESEARCH DESIGN AND METHODS—This nationwide prospective multicenter study took place in eight Danish centers treating pregnant women with type 1 diabetes during 1993–1999. A total of 990 women with 1,218 pregnancies and delivery after 24 weeks (n = 1,215) or early termination due to severe congenital malformations (n = 3) were included. Data were collected prospectively by one to three caregivers in each center and reported to a central registry.

RESULTS—The perinatal mortality rate was 3.1% in type 1 diabetic pregnancies compared with 0.75% in the background population (RR 4.1 [95% CI 2.9–5.6]), and the stillbirth rate was 2.1% compared with 0.45 (4.7 [3.2–7.0]). The congenital malformation rate was 5.0% in the study population and 2.8% (1.7 [1.3–2.2]) in the background population. Six of the perinatal deaths (16%) were related to congenital malformations. Only 34% of women performed daily home monitoring of blood glucose at conception, and 58% received preconceptional guidance. Pregnancies with serious adverse outcomes (perinatal death and/or congenital malformations) were characterized by higher HbA1c values before and during pregnancy and a lesser degree of maternal self-care and preconceptional guidance. Women who performed daily self-monitoring of blood glucose at any time during pregnancy had lower HbA1c values than women who did not measure their daily profile. Likewise, daily self-monitoring was associated with a reduction in serious adverse outcomes. The caesarean section rate was 55.9 and 12.6%, respectively, and the risk of preterm delivery was 41.7 and 6.0%, respectively.

CONCLUSIONS—Type 1 diabetic pregnancies are still complicated by considerably higher rates of severe perinatal complications compared with the background population, and women with poor self-care are at the highest risk. Adequate glycemic control using daily glucose monitoring before and during pregnancy is a crucial step toward reaching the goals of the St. Vincent declaration.
Association Between Urinary Albumin Excretion and Serum Dehydroepiandrosterone Sulfate Concentration in Male Patients With Type 2 Diabetes
Authors: Fukui Michiaki , Kitagawa Yoshihiro , Nakamura Naoto , Kadono Mayuko , Hasegawa Goji , Yoshikawa Toshikazu
Published: March 2007

OBJECTIVE—Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes. Both elevated urinary albumin excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are associated with increased CVD mortality. This raises the possibility of DHEA as a causal intermediate linking urinary albumin excretion to CVD.

RESEARCH DESIGN AND METHODS—Relationships of urinary albumin excretion to serum DHEA sulfate (DHEA-S) concentration and to major cardiovascular risk factors, including blood pressure, serum lipid concentration, glycemic control (HbA1c), and BMI, were investigated in 357 consecutive men with type 2 diabetes.

RESULTS—Serum DHEA-S concentrations were lower in patients with macroalbuminuria (866.5 ± 523.8 ng/ml, P < 0.0001) and in those with microalbuminuria (1,014.4 ± 525.3 ng/ml, P = 0.0006) than in patients with normoalbuminuria (1,232.6 ± 542.4 ng/ml). Serum DHEA-S concentration correlated inversely with log (urinary albumin excretion) (r = −0.227, P < 0.0001). Multiple regression analysis demonstrated that duration of diabetes (β = 0.147, P = 0.0075), HbA1c (β = 0.156, P = 0.0048), BMI (β = 0.194, P = 0.0007), systolic blood pressure (β = 0.195, P = 0.0005), and serum DHEA-S concentration (β = −0.192, P = 0.0010) were independent determinants of log (urinary albumin excretion).

CONCLUSIONS—Serum DHEA-S concentration, which correlated inversely with degree of urinary albumin excretion, may contribute to the link between elevated urinary albumin excretion and higher CVD mortality in male patients with type 2 diabetes.
Radial Artery Tonometry Demonstrates Arterial Stiffness in Children With Type 1 Diabetes
Authors: Haller Michael J. , Samyn Margaret , Nichols Wilmer W. , Brusko Todd , Wasserfall Clive , Schwartz R. Fletcher , Atkinson Mark , Shuster Jonathan J. , Pierce Gary L. , Silverstein Janet H.
Published: March 2007

OBJECTIVE—To determine if children with type 1 diabetes have increased arterial stiffness by estimating augmentation index with the simple noninvasive technique of radial artery tonometry.

RESEARCH DESIGN AND METHODS—We studied 98 type 1 diabetic children and 57 healthy control subjects, ages 10–18 years, matched for age, sex, race, and BMI, generating 43 matched pairs. Radial artery tonometry was performed, and blood was collected for analysis of fasting lipids, HbA1c, glucose, and cytokines in all children.

RESULTS—Children with diabetes had a significantly higher augmentation index corrected to a heart rate of 75 (AI75) than their matched control subjects. Mean AI75 in type 1 diabetic subjects was 1.11 ± 10.15 versus −3.32 ± 10.36 in control subjects. The case-control difference was 5.20 ± 11.02 (P = 0.0031).

CONCLUSIONS—Children with type 1 diabetes have increased arterial stiffness compared with healthy control subjects. Radial artery tonometry is a simple noninvasive technique that could be added to the armamentarium of tests used to provide cardiovascular risk stratification in children with type 1 diabetes.
The LDIflare
Authors: Krishnan Singhan T.M. , Rayman Gerry
Published: March 2007

OBJECTIVE—The aim of this study was to evaluate a novel method for assessing the axon reflex and to determine its value in detecting neuropathy in type 2 diabetes.

RESEARCH DESIGN AND METHODS—The neurogenic flare response to nociceptive stimuli is mediated by an axon reflex involving small unmyelinated C-fibers. We developed a method to assess this reflex involving skin heating to 44°C to evoke the flare followed by scanning the site using a laser Doppler imager (LDI) to measure the area; we termed this method LDIflare. To confirm its neurogenic nature, we examined the LDIflare in eight healthy subjects before and after topical administration of anesthesia. We used this technique to detect C-fiber neuropathy in people with type 2 diabetes. A total of 36 subjects were studied: 12 subjects with neuropathy (group DN), 12 subjects without neuropathy (group DC), and 12 age- and sex-matched control subjects (group NC). For comparison, small-fiber function was also assessed using the Computer Aided Sensory Evaluator–IV (CASE IV) (WR Medical Electronics, Stillwater, MN).

RESULTS—In the eight healthy control subjects, LDIflare was markedly reduced after topical administration of anesthesia (1.62 [1.45–1.72] vs. 5.2 cm2 [3.9–5.9], P < 0.0001), confirming its neurogenic nature. Similarly, in neuropathic subjects, LDIflare was significantly smaller compared with normal and diabetic control subjects (LDIflare area: DN 1.3 cm2 [0.9–1.8], NC 5.5 cm2 [3.9–5.8], and DC 2.8 cm2 [2.5–3.8]; P < 0.0001 and P = 0.01, respectively). The group without neuropathy (DC) also demonstrated a reduced flare compared with the NC group (P = 0.01). In contrast, C-fiber function assessed by evaluating the quantitative thermal thresholds (CASE IV) did not detect a difference between the latter two groups.

CONCLUSIONS—This study confirms the neurogenic nature of the LDIflare and clearly demonstrates loss of C-fiber function in neuropathic subjects with type 2 diabetes. Moreover, it demonstrates C-fiber dysfunction before its detection by other currently available methods, including CASE IV. The LDIflare seems to be a simple objective method to detect early neuropathy and may be of value in assessing therapeutic interventions aimed at preventing or reversing C-fiber dysfunction.
Visceral and Central Abdominal Fat and Anthropometry in Relation to Diabetes in Asian Indians
Authors: Anjana Mohan , Sandeep Sreedharan , Deepa Raj , Vimaleswaran Karani Santhanakrishnan , Farooq Syed , Mohan Viswanathan
Published: March 2007

OBJECTIVE—The objective of the study was to examine body fat distribution using computed tomography (CT), dual-energy X-ray absorptiometry (DEXA), and anthropometry in relation to type 2 diabetes in urban Asian Indians.

RESEARCH DESIGN AND METHODS—This is a case-control study of 82 type 2 diabetic and 82 age- and sex-matched nondiabetic subjects from the Chennai Urban Rural Epidemiology Study, an ongoing epidemiological study in southern India. Visceral, subcutaneous, and total abdominal fat were measured using CT, while DEXA was used to measure central abdominal and total body fat. Anthropometric measures included BMI, waist circumference, sagittal abdominal diameter (SAD), and waist-to-hip ratio.

RESULTS—Visceral and central abdominal fat showed a strong correlation with each other (P < 0.0001), and κ analysis revealed a fairly good agreement between tertiles of visceral and central abdominal fat (κ = 0.44, P < 0.0001). Diabetic subjects had significantly higher visceral (P = 0.005) and central abdominal (P = 0.011) fat compared with nondiabetic subjects. Waist circumference and SAD showed a strong correlation with visceral (P < 0.01) and central abdominal (P < 0.0001) fat in both diabetic and nondiabetic subjects. Logistic regression analysis revealed visceral (odds ratio [OR] 1.011, P = 0.004) and central abdominal (OR 1.001, P = 0.013) fat to be associated with diabetes, even after adjusting for age and sex.

CONCLUSIONS—Visceral and central abdominal fat showed a strong association with type 2 diabetes. Both measures correlated well with each other and with waist circumference and SAD in diabetic and nondiabetic urban Asian Indians.
A Prospective Study of Glycemic Control During Holiday Time in Type 2 Diabetic Patients
Authors: Chen Harn-Shen , Jap Tjin-Shing , Chen Ru-Lin , Lin Hong-Da
Published: March 2007

OBJECTIVE—In the U.K. Prospective Diabetes Study, A1C increased from 1.2 to 1.7% and fasting plasma glucose from 1.0 to 2.8 mmol/l over 10 years in type 2 diabetic patients. It is not known whether the blood glucose increase observed in long-term studies of type 2 diabetes results from small, steady increases throughout the year or from increases during discrete periods.

RESEARCH DESIGN AND METHODS—To estimate the variation of actual glycemic control and its relation to holiday times, we measured A1C and fructosamine in 110 patients with type 2 diabetes. These measurements were performed four times at intervals of 4–6 weeks; therefore, glycemic change was determined for three periods: preholiday period (from between November 13 and December 20 to between December 20 and January 20), holiday period (from between December 20 and January 20 to between January 28 and February 28), and postholiday period (from between January 28 and February 28 to between March 1 and April 10). A final measurement of A1C was obtained from 90 subjects in the following December or January.

RESULTS—The mean A1C increased, but not significantly, during the preholiday (increase 0.135 ± 0.723%, P = 0.055) and holiday (increase 0.094 ± 0.828%, P = 0.239) periods. The mean A1C decreased, but not significantly, during the postholiday period (decrease 0.022 ± 0.588%, P = 0.695). Altogether, the A1C change during these three periods increased significantly (increase 0.207 ± 0.943%, P = 0.024). The mean fructosamine increased significantly during the preholiday period (increase 0.151 ± 0.460 mmol/l, P = 0.001), but there was no significant change during the holiday period (increase 0.057 ± 0.593 mmol/l, P = 0.321). However, fructosamine decreased significantly during the postholiday period (decrease 0.178 ± 0.448 mmol/l, P < 0.001). Altogether, the fructosamine changes during the study periods showed no significant difference (increase 0.030 ± 0.566 mmol/l, P = 0.579). Between March or early April and the following December or January, there was no additional change in A1C (decrease 0.009 ± 1.039%, P = 0.935) for the 90 participants who returned for follow-up treatment.

CONCLUSIONS—The present study demonstrates an influence of winter holidays on the glycemic control of patients who have type 2 diabetes, and this poor glycemic control might not be reversed during the summer and autumn months. Therefore, the cumulative effects of the yearly A1C gain during the winter holidays are likely to contribute to the substantial increase in A1C that occurs every year among type 2 diabetic individuals.
Problems Paying Out-of-Pocket Medication Costs Among Older Adults With Diabetes
Authors: Piette John D. , Heisler Michele , Wagner Todd H.
Published: March 2007

OBJECTIVE—To identify problems faced by older adults with diabetes due to out-of-pocket medication costs.

RESEARCH DESIGN AND METHODS—In this cross-sectional national survey of 875 adults with diabetes treated with hypoglycemic medication, respondents reported whether they had underused prescription medications due to cost pressures or had experienced other financial problems associated with medication costs such as forgoing basic necessities. Respondents also described their interactions with clinicians about medication costs.

RESULTS—A total of 19% of respondents reported cutting back on medication use in the prior year due to cost, 11% reported cutting back on their diabetes medications, and 7% reported cutting back on their diabetes medications at least once per month. Moreover, 28% reported forgoing food or other essentials to pay medication costs, 14% increased their credit card debt, and 10% borrowed money from family or friends to pay for their prescriptions. Medication cost problems were especially common among respondents who were younger, had higher monthly out-of-pocket costs, and had no prescription drug coverage. In general, few respondents, including those reporting medication cost problems, reported that their health care providers had given them information or other assistance to address medication cost pressures.

CONCLUSIONS—Out-of-pocket medication costs pose a significant burden to many adults with diabetes and contribute to decreased treatment adherence. Clinicians should actively identify patients with diabetes who are facing medication cost pressures and assist them by modifying their medication regimens, helping them understand the importance of each prescribed medication, providing information on sources of low-cost drugs, and linking patients with coverage programs.
Maternal Anxiety Associated With Newborn Genetic Screening for Type 1 Diabetes
Authors: Bennett Johnson Suzanne , Baughcum Amy E. , Carmichael Stacy K. , She Jin-Xiong , Schatz Desmond A.
Published: March 2007

OBJECTIVE—To describe maternal anxiety associated with newborn genetic screening for type 1 diabetes during the first year after risk notification.

RESEARCH DESIGN AND METHODS—Mothers of at-risk infants (n = 435), identified through newborn genetic screening as part of the Prospective Assessment of Newborn for Diabetes Autoimmunity (PANDA) study, were administered a short form of the State Trait Anxiety Inventory (STAI) during telephone interviews ∼3.5 weeks, 4 months, and 1 year after risk notification. Statistical analyses were conducted to examine predictors of maternal anxiety at each interview as well as changes in anxiety over time.

RESULTS—For the total sample, initial state STAI scores were not elevated and declined further over time. However, Hispanic mothers, those with low levels of education, those who overestimated the child’s risk for diabetes, and mothers of infants in the highest risk group exhibited significantly elevated initial state STAI scores. At 4 months, higher state STAI scores were associated with higher initial state STAI scores, single parent status, having an infant with a first-degree relative with diabetes, and overestimation of the child’s actual risk. Initial and 4-month STAI scores remained predictive of STAI scores at 1 year. In addition, single mothers and mothers of female children reported higher STAI state scores 1 year after risk notification.

CONCLUSIONS—For most mothers, newborn genetic screening to identify infants at increased risk for type 1 diabetes is not associated with significantly elevated maternal anxiety; anxiety further dissipates over time. However, anxiety levels vary considerably as a function of maternal ethnic status, education, marital status, maternal estimation of infant risk, and sex of the child and may be significantly elevated in some women.
Quality of Care and Outcomes in Type 2 Diabetic Patients
Authors: De Berardis Giorgia , Pellegrini Fabio , Franciosi Monica , Belfiglio Maurizio , Di Nardo Barbara , Greenfield Sheldon , Kaplan Sherrie H. , Rossi Marie C.E. , Sacco Michele , Tognoni Gianni , Valentini Miriam , Nicolucci Antonio ,   on behalf of the QuED Study Group
Published: March 2007

OBJECTIVE—The role of general practice and diabetes clinics in the management of diabetes is still a matter of debate. Methodological flaws in previous studies may have led to inaccurate conclusions when comparing the care provided in these different settings. We compared the care provided to type 2 diabetic patients attending diabetes outpatient clinics (DOCs) or being treated by a general practitioner (GP) using appropriate statistical methods to adjust for patient case mix and physician-level clustering.

RESEARCH DESIGN AND METHODS—We prospectively evaluated the process and intermediate outcome measures over 2 years in a sample of 3,437 patients recruited by 212 physicians with different specialties practicing in 125 DOCs and 103 general practice offices. Process measures included frequency of HbA1c, lipids, microalbuminuria, and serum creatinine measurements and frequency of foot and eye examinations. Outcome measures included HbA1c, blood pressure, and total and LDL cholesterol levels.

RESULTS—Differences for most process measures were statistically significantly in favor of DOCs. The differences were more marked for patients who were always treated by the same physician within a DOC and if that physician had a specialty in diabetology. Less consistent differences in process measures were detected when patients followed by GPs were compared with those followed by physicians with a specialty other than diabetology. As for the outcomes considered, patients attending DOCs attained better total cholesterol levels, whereas no major differences emerged in terms of metabolic control and blood pressure levels between DOCs and GPs. Physicians’ specialties were not independently related to patient outcomes.

CONCLUSIONS—Being followed always by the same physician in a DOC, particularly if the physician had a specialty in diabetes, ensured better quality of care in terms of process measures. In the short term, care provided by DOCs was also associated with better intermediate outcome measures, such as total cholesterol levels.
Depressive Symptoms and the Risk of Type 2 Diabetes
Authors: Golden Sherita Hill , Williams Janice E. , Ford Daniel E. , Yeh Hsin-Chieh , Paton Sanford Catherine , Nieto F. Javier , Brancati Frederick L.
Published: March 2007

OBJECTIVE—The goal of this study was to determine whether depressive symptoms predict type 2 diabetes.

RESEARCH DESIGN AND METHODS—We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48–67 years, who were subsequently followed for 6 years for the development of type 2 diabetes.

RESULTS—At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P < 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard [RH] 1.63, 95% CI 1.31–2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02–1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10–1.73).

CONCLUSIONS—In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements.
Comparison of the [13C]Glucose Breath Test to the Hyperinsulinemic-Euglycemic Clamp When Determining Insulin Resistance
Authors: Lewanczuk Richard Z. , Paty Breay W. , Toth Ellen L.
Published: March 2007

OBJECTIVE—With increasing emphasis on the recognition of the metabolic syndrome and early type 2 diabetes, a clinically useful measure of insulin resistance is desirable. The purpose of this study was to evaluate whether an index of glucose metabolism, as measured by 13CO2 generation from ingested [13C]glucose, would correlate with indexes from the hyperinsulinemic-euglycemic clamp.

RESEARCH DESIGN AND METHODS—A total of 26 subjects with varying degrees of insulin sensitivity underwent both the [13C]glucose breath test and the hyperinsulinemic-euglycemic clamp. Results from the [13C]glucose breath test were compared with measures of insulin sensitivity from the glucose clamp as well as with other commonly used indexes of insulin sensitivity.

RESULTS—There was a strong correlation between the [13C]glucose breath test result and the glucose disposal rate (r = 0.69, P < 0.0001) and insulin sensitivity index (r = 0.69, P < 0.0001) from the insulin clamp. The magnitude of these correlations compared favorably with QUICKI and were superior to the homeostasis model assessment.

CONCLUSIONS—The [13C]glucose breath test may provide a useful noninvasive assessment of insulin sensitivity.
Implementation of a Safe and Effective Insulin Infusion Protocol in a Medical Intensive Care Unit
Authors: Goldberg Philip A. , Siegel Mark D. , Sherwin Robert S. , Halickman Joshua I. , Lee Michelle , Bailey Valerie A. , Lee Sandy L. , Dziura James D. , Inzucchi Silvio E.
Published: March 2007

OBJECTIVE—In a recent randomized controlled trial, lowering blood glucose levels to 80–110 mg/dl improved clinical outcomes in critically ill patients. In that study, the insulin infusion protocol (IIP) used to normalize blood glucose levels provided valuable guidelines for adjusting insulin therapy. In our hands, however, ongoing expert supervision was required to effectively manage the insulin infusions. This work describes our early experience with a safe, effective, nurse-implemented IIP that provides detailed insulin dosing instructions and requires minimal physician input.

RESEARCH DESIGN AND METHODS—We collected data from 52 medical intensive care unit (MICU) patients who were placed on the IIP. Blood glucose levels were the primary outcome measurement. Relevant clinical variables and insulin requirements were also recorded. MICU nurses were surveyed regarding their experience with the IIP.

RESULTS—To date, our IIP has been employed 69 times in 52 patients admitted to an MICU. Using the IIP, the median time to reach target blood glucose levels (100–139 mg/dl) was 9 h. Once blood glucose levels fell below 140 mg/dl, 52% of 5,808 subsequent hourly blood glucose values fell within our narrow target range; 66% within a “clinically desirable” range of 80–139 mg/dl; and 93% within a “clinically acceptable” range of 80–199 mg/dl. Only 20 (0.3%) blood glucose values were <60 mg/dl, none of which resulted in clinically significant adverse events. In general, the IIP was readily accepted by our MICU nursing staff, most of whom rated the protocol as both clinically effective and easy to use.

CONCLUSIONS—Our nurse-implemented IIP is safe and effective in improving glycemic control in critically ill patients.
Effectiveness of Different Types of Footwear Insoles for the Diabetic Neuropathic Foot
Authors: Viswanathan Vijay , Madhavan Sivagami , Gnanasundaram Saraswathy , Gopalakrishna Gautham , Das Bhabendra Nath , Rajasekar Seena , Ramachandran Ambady
Published: March 2007

OBJECTIVE—To compare the effectiveness of different types of footwear insoles in the diabetic neuropathic foot.

RESEARCH DESIGN AND METHODS—A sample of 241 consecutive diabetic patients (158 men and 83 women, age 57.5 ± 9.6 years [mean ± SD], and mean duration of diabetes 12.3 ± 7.2 years) attending the foot clinic with previous foot ulceration and those considered at high risk of foot ulceration were included in the study. The study groups consisted of group 1, patients provided with sandals with insoles made with microcellular rubber (n = 100); group 2, with sandals with polyurethane foam (n = 59); group 3, with molded insoles (n = 32); and group 4, with their own footwear containing leather board insoles (n = 50). Neuropathy status was assessed using a biothesiometer. Plantar pressure was measured using the RS Scan inshoe pressure measurement system. Data obtained from the metatarsal heads were used as the peak pressure. The state of the sandals was assessed after 9 months. The patients were considered to have had an ulcer relapse when either a new ulcer appeared at the site of a previous one or a new foot ulcer appeared in a different area.

RESULTS—Patients who were using therapeutic footwear showed lower foot pressure (group 1, 6.9 ± 3.6; group 2, 6.2 ± 3.9; and group 3, 6.8 ± 6.1 kPa; P = 0.0001), while those who used the nontherapeutic footwear showed an increased foot pressure (group 4, 40.7 ± 20.5 kPa; P = 0.008). The occurrence of new lesions was significantly higher in patients in group 4 (33%) when compared with that of all other groups (4%).

CONCLUSION—Therapeutic footwear is useful to reduce new ulceration and consequently the amputation rate in the diabetic population.
In Type 2 Diabetes, Rosiglitazone Therapy for Insulin Resistance Ameliorates Endothelial Dysfunction Independent of Glucose Control
Authors: Pistrosch Frank , Passauer Jens , Fischer Sabine , Fuecker Katja , Hanefeld Markolf , Gross Peter
Published: March 2007

OBJECTIVE—Insulin resistance is an independent risk factor for arteriosclerosis and cardiovascular mortality. However, the mechanism by which insulin resistance contributes to arteriosclerosis is unknown. Conceivably, endothelial dysfunction could be involved. Therefore, we asked whether therapy for insulin resistance ameliorates any endothelial dysfunction.

RESEARCH DESIGN AND METHODS—We performed a double-blind cross-over trial of 12 patients with recently diagnosed type 2 diabetes. They received rosiglitazone 4 mg b.i.d. for 12 weeks and nateglinide 60 mg b.i.d. for the same number of weeks in random order. To assess the degree of endothelial dysfunction, we used venous occlusion plethysmography. We studied vasodilation in response to acetylcholine (ACh) with and without exogenous insulin. The agents were infused into the brachial artery. Furthermore, we determined insulin resistance by euglycemic clamp.

RESULTS—Glycemic control was comparable under rosiglitazone and nateglinide. Rosiglitazone ameliorated insulin resistance by 60% compared with nateglinide. ACh response was significantly increased after rosiglitazone treatment (maximum forearm blood flow 12.8 ± 1.3 vs. 8.8 ± 1.3 ml/100 ml after rosiglitazone and nateglinide, respectively; P < 0.05) but did not attain the level of healthy control subjects (14.0 ± 0.7 ml/100 ml). Coinfusion of exogenous insulin increased ACh response further in the rosiglitazone group. N-monomethyl-l-arginine-acetate (l-NMMA), an antagonist of nitric oxide synthase, largely prevented the increased vasodilation after rosiglitazone, regardless of the presence or absence of insulin. Insulin sensitivity and blood flow response were found to be correlated (P < 0.01).

CONCLUSIONS—Insulin resistance is a major contributor toward endothelial dysfunction in type 2 diabetes. Both endothelial dysfunction and insulin resistance are amenable to treatment by rosiglitazone.
Is Presence of Islet Autoantibodies at Birth Associated With Development of Persistent Islet Autoimmunity?
Authors: Stanley Heather M. , Norris Jill M. , Barriga Katherine , Hoffman Michelle , Yu Liping , Miao Dongmei , Erlich Henry A. , Eisenbarth George S. , Rewers Marian
Published: March 2007

OBJECTIVE—To determine whether the presence of islet autoantibodies in the umbilical cord blood is predictive of subsequent development of islet autoimmunity.

RESEARCH DESIGN AND METHODS—Cord blood sera from 1,118 subjects from the Diabetes Autoimmunity Study in the Young (DAISY) cohort, as well as their venous blood samples taken at follow-up clinic visits, were tested for GAD65 autoantibodies (GAAs), insulin autoantibodies (IAAs), and IA-2 autoantibodies (IA-2As). Venous blood samples taken from mothers of cord blood autoantibody–positive children were analyzed for the same autoantibodies.

RESULTS—At least one of three islet autoantibodies was present in 42 (3.7%) of the cord blood samples tested. The presence of cord blood autoantibodies did not predict the subsequent development of islet autoimmunity (adjusted hazard ratio = 0.73 [0.09, 5.88]). Discordance between cord blood and corresponding maternal autoantibodies was seen in 3 of 36 infants. A strong correlation between levels of autoantibody in cord blood and maternal circulation was found for GAA (r2 = 0.93, P < 0.001) and IAA (r2 = 0.89, P < 0.001) but not IA-2A (r2 = 0.05, P = 0.19). Cord blood autoantibodies in all but one subject disappeared by 9 months of age.

CONCLUSIONS—The presence of cord blood autoantibodies is not predictive of subsequent development of islet autoimmunity. The majority of cord blood autoantibodies appear to result from maternal transmission.
Lipoprotein(a) Is an Independent Risk Factor for Peripheral Arterial Disease in Chinese Type 2 Diabetic Patients in Taiwan
Authors: Tseng Chin-Hsiao
Published: March 2007

OBJECTIVE—To examine the association between lipoprotein(a) [Lp(a)] and peripheral arterial disease (PAD) and determine the optimal cutoff in Chinese type 2 diabetic patients in Taiwan.

RESEARCH DESIGN AND METHODS—Serum Lp(a) was determined in 557 type 2 diabetic patients (243 men and 314 women) recruited consecutively from a diabetes clinic at the National Taiwan University Hospital. Ankle-brachial index (ABI) <0.9 was diagnosed as PAD (n = 45) and <0.8 as severe PAD (n = 20). Potential confounders included age, sex, BMI, waist-to-hip ratio (WHR), diabetes duration, insulin usage, smoking, hypertension, systolic and diastolic blood pressure, fasting plasma glucose (FPG), total cholesterol, triglycerides, and HDL and LDL cholesterol.

RESULTS—The distribution of Lp(a) was right skewed and no significant differences for sex, WHR, insulin usage, smoking, hypertension, and systolic and diastolic blood pressure were observed. In men, log[Lp(a)] was correlated positively with age, duration, and total and LDL cholesterol (borderline significant, P < 0.1) and negatively with BMI, triglycerides, and FPG (P < 0.1). In women, log[Lp(a)] was correlated positively with total and LDL cholesterol and negatively with triglycerides and BMI (P < 0.1). ABI was significantly correlated with log[Lp(a)], especially in men or in patients with PAD. The optimal cutoff determined by discriminant analysis was 13.3 mg/dl. Patients with Lp(a) above this value had a 2.7-fold higher risk of PAD after multivariate adjustment. Lp(a) also significantly increased from no PAD to mild and severe PAD (17.1 ± 14.4, 23.7 ± 20.3, and 36.9 ± 22.8 mg/dl, respectively, P < 0.001).

CONCLUSIONS—Lp(a) is an independent risk factor for PAD in type 2 diabetic patients in Taiwan. The optimal cutoff is 13.3 mg/dl.
Carbohydrate Nutrition, Insulin Resistance, and the Prevalence of the Metabolic Syndrome in the Framingham Offspring Cohort
Authors: McKeown Nicola M. , Meigs James B. , Liu Simin , Saltzman Edward , Wilson Peter W.F. , Jacques Paul F.
Published: March 2007

OBJECTIVE—The aim of this study was to examine the relation between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort.

RESEARCH DESIGN AND METHODS—We examined cross-sectional associations between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in 2,834 subjects at the fifth examination (1991–1995) of the Framingham Offspring Study. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the following formula (fasting plasma insulin × plasma glucose)/22.5. The metabolic syndrome was defined using the National Cholesterol Education Program criteria.

RESULTS—After adjustment for potential confounding variables, intakes of total dietary fiber, cereal fiber, fruit fiber, and whole grains were inversely associated, whereas glycemic index and glycemic load were positively associated with HOMA-IR. The prevalence of the metabolic syndrome was significantly lower among those in the highest quintile of cereal fiber (odds ratio [OR] 0.62; 95% CI 0.45–0.86) and whole-grain (0.67; 0.48–0.91) intakes relative to those in the lowest quintile category after adjustment for confounding lifestyle and dietary factors. Conversely, the prevalence of the metabolic syndrome was significantly higher among individuals in the highest relative to the lowest quintile category of glycemic index (1.41; 1.04–1.91). Total carbohydrate, dietary fiber, fruit fiber, vegetable fiber, legume fiber, glycemic load, and refined grain intakes were not associated with prevalence of the metabolic syndrome.

CONCLUSIONS—Whole-grain intake, largely attributed to the cereal fiber, is inversely associated with HOMA-IR and a lower prevalence of the metabolic syndrome. Dietary glycemic index is positively associated with HOMA-IR and prevalence of the metabolic syndrome. Given that both a high cereal fiber content and lower glycemic index are attributes of whole-grain foods, recommendation to increase whole-grain intake may reduce the risk of developing the metabolic syndrome.
Trying to Lose Weight, Losing Weight, and 9-Year Mortality in Overweight U.S. Adults With Diabetes
Authors: Gregg Edward W. , Gerzoff Robert B. , Thompson Theodore J. , Williamson David F.
Published: March 2007

OBJECTIVE—The aim of this study was to examine the relationships between intention to lose weight, actual weight loss, and all-cause mortality among overweight individuals with diabetes.

RESEARCH DESIGN AND METHODS— We performed a prospective analysis among 1,401 overweight diabetic adults aged ≥35 years sampled in the National Health Interview Survey. The previous year intention to lose weight and weight change were assessed by self-report. Nine-year mortality rates were examined according to intent to lose weight and weight loss, which were adjusted for age, sex, education, ethnicity, smoking, initial body weight, and diabetes complications.

RESULTS—Individuals trying to lose weight had a 23% lower mortality rate (hazard rate ratio [HRR] 0.77, 95% CI 0.61–0.99) than those who reported not trying to lose weight. This association was as strong for those who failed to lose weight (0.72, 0.55–0.96) as for those who succeeded in losing weight (0.83, 0.63–1.08). Trying to lose weight was beneficial for overweight (BMI 25–30 kg/m2) individuals (0.62, 0.46–0.83) but not for obese (BMI >30) individuals (1.17, 0.72–1.92). Overall weight loss, without regard to intent, was associated with an increase of 22% (1.22, 0.99–1.50) in the mortality rate. This increase was largely explained by unintentional weight loss, which was associated with a 58% (1.58, 1.08–2.31) higher mortality rate.

CONCLUSIONS—Overweight diabetic adults trying to lose weight have a reduced risk of all-cause mortality, independent of whether they lose weight. Actual weight loss is associated with increased mortality only if the weight loss is unintentional.
Accuracy of the GlucoWatch G2 Biographer and the Continuous Glucose Monitoring System During Hypoglycemia
Authors:   *The Diabetes Research in Children Network (DirecNet) Study Group
Published: March 2007

OBJECTIVE—The goal of this study was to assess the accuracy of the GlucoWatch G2 Biographer (GW2B) and the continuous glucose monitoring system (CGMS) during hypoglycemia in children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—During a 24-h clinical research center stay, 91 children and adolescents with type 1 diabetes (aged 3.5–17.7 years) wore one or two CGMSs, and 89 of these subjects wore one or two GW2Bs. Frequent serum glucose determinations were made during the day, overnight, and during insulin-induced hypoglycemia resulting in 192 GW2B reference pairs and 401 CGMS reference pairs during hypoglycemia (reference glucose ≤60 mg/dl).

RESULTS—During hypoglycemia, the median absolute difference between the 192 GW2B reference glucose pairs was 26 mg/dl and between the 401 CGMS reference glucose pairs was 19 mg/dl with 31 and 42%, respectively, of the sensor values within 15 mg/dl of the reference glucose. Sensitivity to detect hypoglycemia when the GW2B alarm level was set to 60 mg/dl was 23% with a false-alarm rate of 51%. Analyses suggested that modified CGMS sensors that became available in November 2002 might be more accurate than the original CGMS sensors (median absolute difference 15 vs. 20 mg/dl).

CONCLUSIONS—These data show that the GW2B and the CGMS do not reliably detect hypoglycemia. Both of these devices perform better at higher glucose levels, suggesting they may be more useful in reducing HbA1c levels than in detecting hypoglycemia.
Improved Glucose Excursions Using an Implantable Real-Time Continuous Glucose Sensor in Adults With Type 1 Diabetes
Authors: Garg Satish K. , Schwartz Sherwyn , Edelman Steven V.
Published: March 2007

OBJECTIVE—The capability of emerging glucose sensor technology to continuously monitor glucose levels may provide ways to achieve glycemic targets while reducing hypoglycemia.

RESEARCH DESIGN AND METHODS—A first-generation, long-term continuous glucose sensor (DexCom, San Diego, CA) was implanted subcutaneously in 15 patients with type 1 diabetes. Safety, efficacy, and potential benefits were evaluated during a blinded control period and in a study period during which patients had real-time access to the glucose data.

RESULTS—The bias differences between self-monitored blood glucose (SMBG) and sensor data were <15% at 2.8, 4.4, 5.6, 8.3, and 11.1 mmol/l. No procedure or device-related adverse events were observed. Of 15 patients, 13 (87%) had functional sensors during the 12-h simulated home use study with 96% of points in the A and B regions of the Clarke error grid, an R value of 0.88, and a mean absolute relative difference of 16% when retrospectively compared with SMBG. In actual home use, during the blinded control period (50 ± 16 days) data were not displayed to the patient, whereas during the unblinded study period (44 ± 17 days) the data were presented to the patient, and alerts were set at 3.1, 5.6, and 11.1 mmol/l. Patients spent a median of 47% less time below 3.1 mmol/l (P < 0.05) and 25% less time above 13.3 mmol/l (P < 0.05) during the nonblinded study period compared with the blinded control period.

CONCLUSIONS—The availability of real-time continuous glucose values may help patients reduce their hyperglycemic excursions and lower the risk of hypoglycemia.
Use of Arterial Transfer Functions for the Derivation of Central Aortic Waveform Characteristics in Subjects With Type 2 Diabetes and Cardiovascular Disease
Authors: Hope Sarah A. , Tay David B. , Meredith Ian T. , Cameron James D.
Published: March 2007

OBJECTIVE—Optimal blood pressure control in subjects with diabetes reduces cardiovascular complications. There is theoretical benefit in the assessment of central aortic waveforms including the augmentation index, which is taken as a putative index of stiffness. Transfer functions may be used to reconstruct aortic from radial pressure waveforms; however, a single generalized transfer function may not be appropriate for all patients. We aimed to evaluate the technique in subjects with diabetes.

RESEARCH DESIGN AND METHODS—Simultaneous invasive central aortic and noninvasive radial waveforms were acquired in 19 subjects with type 2 diabetes, and a diabetes-specific transfer function was derived. Similar data were acquired from 38 age- and sex-matched subjects without diabetes. Central waveforms were reconstructed using a generalized transfer function in all patients and the diabetes-specific transfer function in individuals with diabetes.

RESULTS—There was no difference between groups in measured central pressures. The error in generalized transfer function-derived systolic pressure was greater in individuals with diabetes (6 ± 7 mmHg) (mean ± SD) than without diabetes (2 ± 8 mmHg) (P < 0.05). Errors in other parameters were no different. The diabetes-specific transfer function reduced the error in derived systolic pressure to 0 ± 7 mmHg in individuals with diabetes—no different than that with the generalized transfer function in individuals without diabetes. The central augmentation index reconstructed by either transfer function was unrelated to that directly measured.

CONCLUSIONS—A generalized transfer function is inappropriate for the derivation of central waveforms in subjects with type 2 diabetes. Errors in subjects with diabetes might be reduced with a diabetes-specific transfer function.
Glycemic Exposure Is Associated With Reduced Pulmonary Function in Type 2 Diabetes
Authors: Davis Wendy A. , Knuiman Matthew , Kendall Peter , Grange Valerie , Davis Timothy M.E.
Published: March 2007

OBJECTIVE—To examine prospectively the relationship between diabetes, glycemic control, and spirometric measures.

RESEARCH DESIGN AND METHODS—From a community-based cohort, 495 Europid (i.e., of European descent) patients with type 2 diabetes who had no history of pulmonary disease underwent baseline spirometry between 1993 and 1994. A subset of 125 patients was restudied a mean of 7.0 years later. The main outcome measures included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC), and peak expiratory flow (PEF) corrected for body temperature, air pressure, and water saturation and were expressed either in absolute terms or as percentage-predicted value for age, sex, and height.

RESULTS—Mean percentage-predicted values of each spirometric measure were decreased >10% in the whole cohort at baseline and absolute measures continued to decline at an annual rate of 68, 71, and 84 ml/year and 17 l/min for FVC, FEV1, VC, and PEF, respectively, in the 125 prospectively studied patients. Declining lung function measures were consistently predicted by poor glycemic control in the form of a higher updated mean HbA1c, follow-up HbA1c, or follow-up fasting plasma glucose. In a Cox proportional hazards model, decreased FEV1 percentage-predicted value was an independent predictor of all-cause mortality.

CONCLUSIONS—Reduced lung volumes and airflow limitation are likely to be chronic complications of type 2 diabetes, the severity of which relates to glycemic exposure. Airflow limitation is a predictor of death in type 2 diabetes after adjusting for other recognized risk factors.