bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Activity May Precede Diabetic Foot Ulceration
Authors: Armstrong David G. , Lavery Lawrence A. , Holtz-Neiderer Katherine , Mohler Martha J. , Wendel Christopher S. , Nixon Brent P. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—To evaluate the role of activity in the development of neuropathic foot ulceration in individuals with diabetes.

RESEARCH DESIGN AND METHODS—We evaluated the first 100 consecutive individuals with diabetes (95.0% male, aged 68.5 ± 10.0 years with concomitant neuropathy, deformity, and/or a history of lower-extremity ulceration/partial foot amputation) enrolled in an ongoing prospective longitudinal activity study. Subjects used a high-capacity continuous computerized activity monitor. Data were collected continuously over a minimum of 25 weeks (or until ulceration) with daily activity units expressed as means ± SD.

RESULTS—Eight subjects ulcerated during the evaluation period of 37.1 ± 12.3 weeks. The average daily activity was significantly lower in individuals who ulcerated compared with individuals who did not ulcerate (809.0 ± 612.2 vs. 1,394.5 ± 868.5, P = 0.03). Furthermore, there was a large difference in variability between groups. The coefficient of variation was significantly greater in the ulceration group compared with the no ulceration group (96.4 ± 50.3 vs. 44.7 ± 15.4%, P = 0.0001). In the 2 weeks preceding the ulcerative event, the coefficient of variation increased even further (115.4 ± 43.0%, P = 0.02), but there was no significant difference in average daily activity during that period (P = 0.5).

CONCLUSIONS—The results of this study suggest that individuals with diabetes who develop ulceration may actually have a lower overall activity than their counterparts with no ulceration, but the quality of that activity may be more variable. Perhaps modulating the “peaks and valleys” of activity in this population through some form of feedback might prove to reduce risk for ulceration in this very-high-risk population.
Aldose Reductase Gene Polymorphisms and Peripheral Nerve Function in Patients With Type 2 Diabetes
Authors: Sivenius Katariina , Pihlajamäki Jussi , Partanen Juhani , Niskanen Leo , Laakso Markku , Uusitupa Matti
Published: March 2007

OBJECTIVE—We screened the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic subjects and investigated whether the previously reported and novel polymorphisms were associated with neurophysiologic deterioration and clinical peripheral neuropathy.

RESEARCH DESIGN AND METHODS—The study population included 85 Finnish type 2 diabetic and 126 nondiabetic subjects. The genetic analyses were performed using the PCR, single-strand conformation polymorphism, restriction fragment-length polymorphism, and automated laser fluorescence scanning analyses. A detailed neurologic examination and neurophysiologic analyses were performed at the time of diagnosis and at the 10-year examination.

RESULTS—The genetic screening identified four polymorphisms: C-106T, C-11G, A11370G, and C19739A. The C and Z-2 alleles of the C-106T polymorphism and the previously reported (CA)n repeat marker were more frequent in type 2 diabetic subjects than in nondiabetic subjects. At baseline, the diabetic subjects with the T allele of the C-106T polymorphism had lower sensory response amplitude values in the peroneal (P = 0.025), sural (P = 0.007), and radial (P = 0.057) nerves and, during follow-up, a greater decrease in the conduction velocity of the motor peroneal nerve than those with the C-106C genotype. No associations were found between the polymorphisms examined and clinical polyneuropathy.

CONCLUSIONS—The C-106T polymorphism of the ALR gene may contribute to an early development of neurophysiologic deterioration in type 2 diabetic patients.
Rates of Glucose Change Measured by Blood Glucose Meter and the GlucoWatch Biographer During Day, Night, and Around Mealtimes
Authors: Dunn Timothy C. , Eastman Richard C. , Tamada Janet A.
Published: March 2007

OBJECTIVE—The purpose of this study was to characterize the distribution of the rate of change of blood glucose for a diabetic population.

RESEARCH DESIGN AND METHODS—The study population consisted of 124 adults with type 1 or type 2 diabetes requiring insulin. Study participants applied a GlucoWatch Biographer during the day at home for 5 consecutive days and took finger-prick blood glucose measurements hourly. Subjects kept a diary of meals. The Biographer frequently and automatically measured glucose up to three times per hour for up 12 h. Rates of glucose change were calculated for both Biographer and blood glucose measurements. Rates of glucose change during a separate study of 134 subjects were determined for daytime and nighttime use.

RESULTS—Mean (±SD) rates of change of glucose of −0.36 ± 0.95 and 0.36 ± 0.99 mg · dl−1 · min−1 were found before and after lunch using blood glucose data and −0.31 ± 1.23 and 0.43 ± 1.26 using Biographer data. For both types of diabetes, rates of glucose change exceeded 2 mg · dl−1 · min−1 before and after meals ∼10% of the time. Periprandial glucose patterns showed some significant differences between type 1 and type 2 diabetic subjects. Glucose levels changed more gradually at night than during the day.

CONCLUSIONS—Glucose values were almost equally unstable before and after meals. Glycemic instability around dinner was different in type 1 and type 2 diabetes. The GlucoWatch Biographer was found to be effective in tracking trends in glucose levels and yielded similar results as obtained by finger-prick blood samples.
Data Resources in the Department of Veterans Affairs
Authors: Maynard Charles , Chapko Michael K.
Published: March 2007

OBJECTIVE—To provide an overview of databases that are maintained by the Department of Veterans Affairs (VA) and are of relevance to investigators involved in epidemiologic, clinical, and health services research.

RESEARCH DESIGN AND METHODS—We reviewed both national and local VA databases and identified their strengths and limitations. We also referenced specific studies that have assessed the validity and reliability of VA databases.

RESULTS—There are numerous national databases housed at the Austin Automation Center in Austin, Texas. These include the Patient Treatment File (hospital abstracts), the Outpatient Care File, the Beneficiary Identification Record Locator System death file for assessing vital status, and the Decision Support System, which provides integrated clinical and financial information for managerial decision making. The major limitation of these databases is that clinical detail below the level of ICD-9-CM diagnosis and procedure codes is not uniformly available nationally. These databases offer an excellent opportunity to monitor the health of veterans over time because they track all inpatient and outpatient utilization in the VA. However, at the local or medical center level, the Veterans Health Information and Systems and Technology Architecture contains extensive clinical information, but has fewer patients, varies in format across medical centers, and poses difficulties with data extraction for statistical analysis.

CONCLUSIONS—Both local and national VA databases are valuable resources for investigators who have interests in a wide array of research topics, including diabetes. The potential for investigating important scientific questions with VA databases becomes greater as communications and database management technologies improve.
Diabetes and Renal Disease in Veterans
Authors: Young Bessie A. , Pugh Jacqueline A. , Maynard Charles , Reiber Gayle
Published: March 2007

OBJECTIVE—To describe the frequency and sequelae of diabetic renal disease in veterans who receive health care from the Veterans Administration (VA).

RESEARCH DESIGN AND METHODS—Veterans with a diagnosis of diabetes, diabetic nephropathy, other kidney diseases, and end-stage renal disease (ESRD) were identified by diagnosis codes from national VA databases for FY1998. Data were obtained and analyzed for prevalence of renal disease, comorbid conditions, and 1-year mortality.

RESULTS—A total of 44,671 (10.7%) of the 415,910 veterans with diabetes had a concomitant diagnosis of any renal disease. The average age was 67 years; 98% were male and 60% were white. The prevalence of diabetic nephropathy was 6.0% (n = 25,263). ESRD secondary to diabetes was present in 4.2% (17,636) of subjects. The age-standardized prevalence of diabetes and any renal disease was 72.6/1,000 persons and differed by race (white 76.1/1,000, black 103.4/1,000 persons). Diabetes-associated ESRD prevalence was higher among black versus white veterans and male versus female veterans. One-year age-standardized mortality was 10.7%.

CONCLUSIONS—Nephropathy is prevalent in veterans with diabetes. Greater mortality is observed among those with renal disease compared with those without renal disease. Additional surveillance is needed to identify persons likely to progress to diabetic nephropathy and to plan for appropriate and timely health care for these individuals.
Pharmacy Costs and Glycemic Control in the Department of Veterans Affairs
Authors: Weinstock Ruth S. , Hawley Gerald , Repke Denis , Feuerstein Barbara L. , Sawin Clark T. , Pogach Leonard M.
Published: March 2007

OBJECTIVE—To determine pharmacy costs for glycemic treatment and its relationship to glycemic control in the Department of Veterans Affairs (VA) between 1994 and 2000.

RESEARCH DESIGN AND METHODS—Patients with diabetes in the VA in FY1994, FY1996, FY1998, and FY2000 were identified using an ambulatory care pharmacy-derived database. Total drug acquisition costs, as well as expenditures for insulin, oral glycemic control agents, and self–blood glucose monitoring strips, were determined for these veterans. HbA1c levels for the corresponding time periods were also obtained. Pharmacy costs (medications and monitoring) were examined by glycemic control treatment type.

RESULTS—In FY2000, 18% (n = 535,016) of all VA pharmacy patients were identified as having diabetes, and they received 30% of all pharmacy prescriptions. Overall, 23% of pharmacy expenditures for these patients were related to glycemic control medications and monitoring supplies. Annual pharmacy costs increased from FY1994 to FY2000. The greatest change was the higher expenditure for monitoring supplies through FY1998, which then decreased in FY2000. Increased pharmacy costs were associated with improved glycemic control. In FY2000, the mean last HbA1c level (n = 446,384) fell to 7.6% from 7.8% in FY1998 (n = 204,136) and 8.4% in 1996 (n = 53,348).

CONCLUSIONS—Diabetes was associated with high pharmacy costs. Increasing medication expenditures were associated with improved HbA1c levels at the aggregated national level. Policies concerning dispensing monitoring supplies and several diabetes quality improvement projects were initiated during this interval. Future challenges include initiatives to further optimize care while controlling costs.
Randomized Controlled Clinical Trial of Glargine Versus Ultralente Insulin in the Treatment of Type 1 Diabetes
Authors: Kudva Yogish C. , Basu Ananda , Jenkins Gregory D. , Pons Guillermo M. , Quandt Lori L. , Gebel Julie A. , Vogelsang Debra A. , Smith Steven A. , Rizza Robert A. , Isley William L.
Published: March 2007

OBJECTIVE—Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia. We conducted a randomized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes.

RESEARCH DESIGN AND METHODS—To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin, 22 individuals (aged 44 ± 14 years [±SD], 55% men) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of <7.8% were randomized in a crossover design to receive either glargine or ultralente as the basal insulin for 4 months. Aspart insulin was used as the prandial insulin. Physicians providing insulin dose adjustment advice were masked to the type of basal insulin.

RESULTS—Treatment with glargine resulted in lower mean HbA1c (6.82 ± 0.13 vs. 7.02 ± 0.13, difference: 0.2 ± 0.08, P = 0.026), less nocturnal variability (plasma glucose 49.06 ± 4.74 vs. 62.36 ± 5.21 mg/dl, P = 0.04), and less hypoglycemia (24.5 ± 2.99 vs. 31.3 ± 4.04 events, P = 0.05), primarily due to less daytime hypoglycemia (P = 0.002). On the other hand, serious hypoglycemia and average glucose concentration measured with continuous subcutaneous glucose monitoring did not differ.

CONCLUSIONS—We conclude that while use of either ultralente or glargine as a basal insulin can result in excellent glycemic control, treatment with glargine is associated with slightly but significantly lower HbA1c and less nocturnal glycemic variability and hypoglycemia.
Strategies to Identify Adults at High Risk for Type 2 Diabetes
Authors:   The Diabetes Prevention Program Research Group
Published: March 2007

OBJECTIVE—The Diabetes Prevention Program (DPP) was a large, multicenter, randomized clinical trial testing interventions to prevent or delay type 2 diabetes. A major challenge was to identify eligible high-risk adults, defined by DPP as having both impaired glucose tolerance (IGT) (2-h glucose 140–199 mg/dl) and elevated fasting plasma glucose (EFG) (95–125 mg/dl).

RESEARCH DESIGN AND METHODS—We analyzed how screening yields would be affected by the presence of established risk factors such as age, sex, ethnicity, BMI, and family history of diabetes, and how much yields would be enhanced by preselecting individuals with elevated capillary blood glucose levels. Of 158,177 contacted adults, 79,190 were potentially eligible (no history of diabetes, age 25 years and older, BMI ≥24 kg/m2). We focus on the 30,383 participants who completed an oral glucose tolerance test (OGTT).

RESULTS—Based on OGTT, 27% had IGT with EFG, meeting DPP eligibility criteria for being at high risk of diabetes, and 13% had previously undiagnosed diabetes based on OGTT. Older age and higher BMI increased yield of high-risk individuals and those with newly discovered diabetes in most ethnic groups (whites, African Americans, Hispanics, and American Indians). In Asian Americans, age but not BMI predicted high risk and diabetes. Independent of age and BMI, the preliminary fasting capillary glucose predicted screening yield in all ethnic groups, with an inverted-U pattern defining DPP eligibility alone (IGT-EFG) and a steep curvilinear pattern defining either IGT-EFG or newly discovered diabetes. Fasting capillary glucose did not attenuate the affects of other participant characteristics in predicting IGT-EFG or the combination of IGT-EFG and newly discovered diabetes.

CONCLUSIONS—The DPP screening approach identified adults with or at high risk for type 2 diabetes across various ethnic groups and provided guidance to more efficient use of OGTTs. Fasting capillary glucose is a useful adjunct in screening programs combined with data on age and adiposity.
Home-Based Resistance Training Is Not Sufficient to Maintain Improved Glycemic Control Following Supervised Training in Older Individuals With Type 2 Diabetes
Authors: Dunstan David W. , Daly Robin M. , Owen Neville , Jolley Damien , Vulikh Elena , Shaw Jonathan , Zimmet Paul
Published: March 2007

OBJECTIVE—To examine whether improvements in glycemic control and body composition resulting from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training.

RESEARCH DESIGN AND METHODS—We performed a 12-month randomized controlled trial in 36 sedentary, overweight men and women with type 2 diabetes (aged 60–80 years) who were randomly assigned to moderate weight loss plus high-intensity progressive resistance training (RT&WL group) or moderate weight loss plus a control program (WL group). Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. Glycemic control (HbA1c), body composition, muscle strength, and metabolic syndrome abnormalities were assessed at 0, 3, 6, 9, and 12 months.

RESULTS—Compared with the WL group, HbA1c decreased significantly more in the RT&WL group (−0.8%) during 6 months of supervised gymnasium-based training; however, this effect was not maintained after an additional 6 months of home-based training. In contrast, the greater increase in lean body mass (LBM) observed in the RT&WL group compared with the WL group (0.9 kg, P < 0.05) after the gymnasium-based training tended to be maintained after the home-based training (0.8 kg, P = 0.08). Similarly, the gymnasium-based increases in upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months (P < 0.001). There were no between-group differences for changes in body weight, fat mass, fasting glucose, or insulin at 6 or 12 months.

CONCLUSIONS—In older adults with type 2 diabetes, home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control. Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control.
Specialist Nurse–Led Clinics to Improve Control of Hypertension and Hyperlipidemia in Diabetes
Authors: Mason James M. , Freemantle Nick , Gibson J. Martin , New John P.
Published: March 2007

OBJECTIVE—To determine the cost-effectiveness of specialist nurse–led clinics provided to improve lipid and blood pressure control in diabetic patients receiving hospital-based care.

RESEARCH DESIGN AND METHODS—A policy of targeting improved care through specialist nurse–led clinics is evaluated using a novel method, linking the cost-effectiveness of antihypertensive and lipid-lowering treatments with the cost and level of behavioral change achieved by the specialist nurse–led clinics. Treatment cost-effectiveness is modeled from the U.K. Prospective Diabetes Study and Heart Protection Study treatment trials, whereas specialist nurse–led clinics are evaluated using the Specialist Nurse–Led Clinics to Improve Control of Hypertension and Hyperlipidemia in Diabetes (SPLINT) trial.

RESULTS—Good lipid and blood pressure control are cost-effective treatment goals for patients with diabetes. Modeling findings from treatment trials, blood pressure lowering is estimated to be cost saving and life prolonging (−$1,400/quality-adjusted life-year [QALY]), whereas lipid-lowering is estimated to be highly cost-effective ($8,230/QALY). Investing in nurse-led clinics to help achieve these benefits imposes an addition on treatment cost-effectiveness leading to higher estimates: $4,020/QALY and $19,950/QALY, respectively. For both clinics combined, the estimated cost-effectiveness is $9,070/QALY. Using an acceptability threshold of $50,000/QALY, the likelihood that blood pressure–lowering clinics are cost-effective is 77%, lipid clinics 99%, and combined clinics 83%.

CONCLUSIONS—A method is described for evaluating the cost-effectiveness of policies to change patient uptake of health care. Such policies are less attractive than treatment cost-effectiveness (which implies cost-less self-implementation). However, specialist nurse–led clinics, as an adjunct to hospital-based diabetic care, combining both lipid and blood pressure control, appear effective and likely to provide excellent value for money.
Predictors of Health Care Costs in Adults With Diabetes
Authors: Gilmer Todd P. , O’Connor Patrick J. , Rush William A. , Crain A. Lauren , Whitebird Robin R. , Hanson Ann M. , Solberg Leif I.
Published: March 2007

OBJECTIVE—The purpose of this study was to assess the impact of baseline A1c, cardiovascular disease, and depression on subsequent health care costs among adults with diabetes.

RESEARCH DESIGN AND METHODS—A prospective analysis was performed of data from a patient survey and medical record review merged with 3 years of medical claims. Costs were estimated using detailed data on resource use and Medicare payment methodologies. Generalized linear models were used to analyze costs related to clinical predictors after adjusting for demographic and socioeconomic factors.

RESULTS—In multivariate analysis of 1,694 adults with diabetes, 3-year costs in those with coronary heart disease (CHD) and hypertension were over 300% of those with diabetes only ($46,879 vs. $14,233; P < 0.05). Depression was associated with a 50% increase in costs ($31,967 vs. $21,609; P < 0.05). Relative to those with a baseline A1c of 6%, those with an A1c of 10% had 3-year costs that were 11% higher ($26,408 vs. $23,873; P < 0.05). Higher A1c predicted higher costs only for those with baseline A1c >7.5% (P = 0.015).

CONCLUSIONS—In adults with diabetes, CHD, hypertension, and depression spectrum disorders more strongly predicted future costs than the A1c level. Concurrent with aggressive efforts to control glucose, greater efforts to prevent or control CHD, hypertension, and depression are necessary to control health care costs in adults with diabetes.
Acetyl-l-Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy
Authors: Sima Anders A.F. , Calvani Menotti , Mehra Munish , Amato Antonino ,   for the Acetyl-l-Carnitine Study Group
Published: March 2007

OBJECTIVE—We evaluated frozen databases from two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine (ALC): 500 and 1,000 mg/day t.i.d.

RESEARCH DESIGN AND METHODS—Intention-to-treat patients amounted to 1,257 or 93% of enrolled patients. Efficacy end points were sural nerve morphometry, nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined.

RESULTS—Data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg ALC.

CONCLUSIONS—These studies demonstrate that ALC treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.
A Prognostic Role of Mean 24-h Pulse Pressure Level for Cardiovascular Events in Type 2 Diabetic Subjects Under 60 Years of Age
Authors: Nakano Shigeru , Konishi Kazunori , Furuya Keisuke , Uehara Keigo , Nishizawa Makoto , Nakagawa Atsushi , Kigoshi Toshikazu , Uchida Kenzo
Published: March 2007

OBJECTIVE—To assess the prognostic role of ambulatory 24-h pulse pressure (PP) on various vascular events in relatively young type 2 diabetic subjects under 60 years of age.

RESEARCH DESIGN AND METHODS—In this prospective study, 237 type 2 diabetic subjects without any history of vascular complications were analyzed. After excluding 9 dropout subjects, 228 subjects (mean age, 46 years; 69% men; mean follow-up period, 100 months) entered the study.

RESULTS—Distribution of 24-h PP for all subjects showed left skewed data, indicating that there may be a diabetic subgroup that had a wide PP. Therefore, further analysis was performed by stratifying the diabetic subjects by quartile of 24-h PP. Outcomes for the widest quartile (n = 58; cut point = 53.3 mmHg) was then compared with those from the other narrower quartiles (n = 170). In the diabetic subjects with a wide PP, cardiovascular events occurred more frequently than those in the diabetic subjects with a narrow one (20.7 vs. 4.1%; P < 0.001), resulting in the significant difference in the cumulative incidence of cardiovascular events (P < 0.001, log-rank test), but not cerebrovascular events, between the two subgroups. The Cox model revealed that a wide 24-h PP at baseline independently predicted subsequent cardiovascular events but not cerebrovascular events. By contrast, only duration of diabetes was the risk factor for cerebrovascular events.

CONCLUSIONS—This study showed that a wide 24-h PP is predictive for cardiovascular events in relatively young diabetic subjects.
Differences in Cardiovascular Risk Factors, Insulin Resistance, and Insulin Secretion in Individuals With Normal Glucose Tolerance and in Subjects With Impaired Glucose Regulation
Authors: Nóvoa Francisco J. , Boronat Mauro , Saavedra Pedro , Díaz-Cremades Juan M. , Varillas Valois F. , La Roche Fátima , Alberiche María P. , Carrillo Armando
Published: March 2007

OBJECTIVE—To assess the cardiovascular risk profile, the degree of insulin resistance, and β-cell secretion in a cohort of subjects with different categories of impaired glucose regulation (IGR): impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT.

RESEARCH DESIGN AND METHODS—We studied 902 nondiabetic subjects between 30 and 80 years of age, recruited from a cross-sectional population-based study in Telde, Gran Canaria Island, Spain. Categories of glucose tolerance were defined according to 2003 modified American Diabetes Association criteria. Risk factors for cardiovascular disease, the presence of the metabolic syndrome, and indirect measures of both insulin resistance and β-cell function were analyzed.

RESULTS—A total of 132 (14.6%) participants had isolated IFG, 59 (6.5%) isolated IGT, and 48 (5.3%) combined IFG/IGT. Groups with normal glucose tolerance (NGT) and combined IFG/IGT had, respectively, the most favorable and unfavorable levels of cardiovascular risk factors, metabolic syndrome rates, and measures of insulin resistance. Subjects with IFG and IGT showed an intermediate profile between NGT and IFG/IGT categories. We found no significant differences between IFG and IGT in cardiovascular risk factors, metabolic syndrome prevalence, or insulin resistance. The IFG group exhibited a more impaired insulin secretion than those with IGT or IFG/IGT.

CONCLUSIONS—Individuals with IGR, especially those with IFG/IGT, have increased values of cardiovascular risk factors and higher indexes of insulin resistance. Groups with isolated IFG and isolated IGT present similar cardiovascular risk profiles. Subjects with IFG are characterized by more defective β-cell function than other forms of IGR.
Glucommander
Authors: Davidson Paul C. , Steed R. Dennis , Bode Bruce W.
Published: March 2007

OBJECTIVE—Intravenous insulin is now the recommended method of diabetes management in critically ill persons in the hospital. The published methods for administering the insulin are complex and are usually limited to intensive care units with a low patient-to-nurse ratio.

RESEARCH DESIGN AND METHODS—A computer-directed algorithm for advice on the delivery of intravenous insulin that is flexible in blood glucose timing and advises insulin dosing in a graduated manner has been developed. This software program, known as the Glucommander, has been used extensively by our group. The data were analyzed for this study.

RESULTS—The data from 5,080 intravenous insulin runs over 120,683 h show that blood glucose levels can be safely stabilized in a target range without significant hypoglycemia by nonspecialized nurses working on any unit of a general hospital. The mean glucose level reached <150 mg/dl in 3 h. Only 0.6% of all glucose values were <50 mg/dl. The prevalence of hypoglycemia <40 mg/dl was 2.6% of all runs. No hypoglycemia was severe.

CONCLUSIONS—This computer-directed algorithm is a simple, safe, effective, and robust method for maintaining glycemic control. It has been extensively studied and is applicable in a wide variety of conditions. In contrast to other published intravenous insulin protocols, which have been limited to intensive care units, Glucommander can be used in all units of any hospital.
High Incidence of Glucose Intolerance in Asian-Indian Subjects With Acute Coronary Syndrome
Authors: Ramachandran Ambady , Chamukuttan Snehalatha , Immaneni Sathyamurthy , Shanmugam Ravi Marimuthu , Vishnu Nalini , Viswanathan Vijay , Jaakko Tuomilehto
Published: March 2007

OBJECTIVE—The risk of diabetes and coronary heart disease is high in Asian Indians. In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS.

RESEARCH DESIGN AND METHODS—A total of 146 nondiabetic subjects (121 men, 25 women) with ACS admitted to two hospitals in 1 year were enrolled. Random blood glucose at admission and a standard oral glucose tolerance test within 3 days were done. Glucose tolerance was categorized as normal glucose tolerance, impaired glucose tolerance (IGT) or impaired fasting glucose, and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HbA1c [A1C] >6.0%) or possibly stress diabetes (A1C <6.0%). Subjects not on antidiabetic treatment were reassessed with a glucose tolerance test between 1 and 2 months. Fasting plasma specific insulin, proinsulin, their molar ratios, and insulin resistance (homeostasis model assessment) were estimated at baseline.

RESULTS—Mean age of the cohort was 55 ± 10.6 (SD) years. At baseline, 24 (16.4%) had normal glucose tolerance, 67 (45.9%) had IGT or impaired fasting glucose, and 55 (37%) had diabetes (35 [24%] were undiagnosed and 20 [13.7%] had stress diabetes). At follow-up, 53 of 92 responders (57.6%) continued to have IGT or diabetes. Mean baseline plasma insulin, proinsulin and its ratios, and insulin resistance were higher than normal in all subgroups.

CONCLUSIONS—Nondiabetic Asian Indians showed a high prevalence of hyperglycemia following ACS. ACS was associated with insulin resistance and increased levels of specific insulin, proinsulin, and high proinsulin-to-insulin ratios.
Smoking and Incidence of Diabetes Among U.S. Adults
Authors: Foy Capri Gabrielle , Bell Ronny A. , Farmer Deborah F. , Goff David C. , Wagenknecht Lynne E.
Published: March 2007

OBJECTIVE—The objective of this study was to determine the association between smoking and incident diabetes among U.S. adults.

RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study (IRAS) was a prospective study of the associations of insulin sensitivity and cardiovascular risk factors. We examined the relationship between smoking status categories (never, former, and current) and incident 5-year type 2 diabetes among 906 participants free of diabetes at baseline. We also considered the effect of pack-year categories (never, former <20 pack-years, former ≥20 pack-years, current <20 pack-years, and current ≥20 pack-years) upon diabetes incidence.

RESULTS—Of current smokers, 96 (25%) developed diabetes at 5 years, compared with 60 (14%) never smokers. After multivariable adjustment, current smokers exhibited increased incidence of diabetes compared with never smokers (odds ratio [OR] 2.66, P = 0.001). Similar results were found among current smokers with ≥20 pack-years with normal glucose tolerance (5.66, P = 0.001).

CONCLUSIONS—Smoking shares a robust association with incident diabetes, supporting the current Surgeon General’s warnings against cigarette smoking.
Decreased β-Cell Function in Overweight Latino Children With Impaired Fasting Glucose
Authors: Weigensberg Marc J. , Ball Geoff D.C. , Shaibi Gabriel Q. , Cruz Martha L. , Goran Michael I.
Published: March 2007

OBJECTIVE—To determine whether overweight Latino children with impaired fasting glucose (IFG) (≥100 mg/dl) have increased insulin resistance or decreased β-cell function compared with those with normal fasting glucose (NFG).

RESEARCH DESIGN AND METHODS—We studied 207 healthy overweight Latino children, aged 8–13 years, with a family history of type 2 diabetes. Fasting and 2-h glucose and insulin were assessed by oral glucose tolerance test. Insulin sensitivity (Si), the acute insulin response to glucose (AIRg), and the disposition index (DI; an index of β-cell function) were determined using the insulin-modified intravenous glucose tolerance test and minimal modeling. Body composition was determined by dual-energy X-ray absorptiometry.

RESULTS—There were no differences in body composition between NFG (n = 182) and IFG (n = 25) children. Compared with children with NFG, children with IFG had higher fasting and 2-h glucose values and higher fasting insulin. After adjusting for covariates, children with IFG had no difference in Si but 15% lower DI than NFG children (2,224 ± 210 vs. 2,613 ± 76, P < 0.05). Multivariate linear regression showed that AIRg and DI, but not Si, were significant predictors of fasting blood glucose.

CONCLUSIONS—In overweight Latino adolescents with a family history of type 2 diabetes, IFG is associated with impaired β-cell function and therefore may identify children likely to be at risk for progression to type 2 diabetes. The actual risk of progression of IFG to type 2 diabetes remains to be determined by prospective longitudinal studies.
Women Living Alone Have an Increased Risk to Develop Diabetes, Which Is Explained Mainly by Lifestyle Factors
Authors: Lidfeldt Jonas , Nerbrand Christina , Samsioe Göran , Agardh Carl-David
Published: March 2007

OBJECTIVE— The purpose of this study was to assess the role of household conditions for the progression to diabetes in women with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS— A total of 461 women, aged 50–64 years, with IGT defined by an oral glucose tolerance test, had baseline advice on physical exercise, diet, smoking, and alcohol habits. Physical examination, blood tests, and questionnaires were completed at baseline and after 2.5 years. Household status was categorized into living alone or with a partner, other adults, or children.

RESULTS— Women living alone had a 2.68-fold increased risk (95% CI 1.02–7.05) of developing diabetes after adjustments for biological risk factors. Further stepwise adjustments for education, occupation, subjective mental health, exercise, diet, and alcohol showed remaining significant odds ratios (ORs), decreasing from 3.26 (1.19–8.96) to 3.03 (1.02–8.99). However, when smoking status was added, the OR became nonsignificant, 2.07 (0.62–6.88). More women who lived alone smoked and did not reduce their daily cigarette consumption compared with women in other household conditions. At follow-up, women living alone had reduced their alcohol consumption and were more often abstainers and fewer had healthy dietary habits or had improved their diet. Physical exercise did not differ among the groups. Separate analyses of any other household status did not show any excess risk for development of diabetes.

CONCLUSIONS— Women living alone had a higher risk to progress from IGT to diabetes, mostly explained by smoking, alcohol, and dietary habits. Household conditions should be accounted for when assessing future risk for diabetes.
Association Among Individual Deprivation, Glycemic Control, and Diabetes Complications
Authors: Bihan Hélène , Laurent Silvana , Sass Catherine , Nguyen Gérard , Huot Caroline , Moulin Jean Jacques , Guegen René , Le Toumelin Philippe , Le Clésiau Hervé , La Rosa Emilio , Reach Gérard , Cohen Régis
Published: March 2007

OBJECTIVE—Previous studies have related poor glycemic control and/or some diabetes complications to low socioeconomic status. Some aspects of socioeconomic status have not been assessed in these studies. In the present study, we used an individual index of deprivation, the Evaluation de la Précarité et des Inégalités de santé dans les Centres d’Examens de Santé (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score, to determine the relationship among glycemic control, diabetes complications, and individual conditions of deprivation.

RESEARCH DESIGN AND METHODS—We conducted a cross-sectional prevalence study in 135 consecutive diabetic patients (age 59.41 ± 13.2 years [mean ± SD]) admitted in the hospitalization unit of a French endocrine department. Individual deprivation was assessed by the EPICES score, calculated from 11 socioeconomic questions. Glycemic control, lipid levels, blood pressure, retinopathy, neuropathy, and nephropathy were assessed.

RESULTS—HbA1c level was significantly correlated with the EPICES score (r = 0.366, P < 0.001). The more deprived patients were more likely than the less deprived patients to have poor glycemic control (β = 1.984 [SE 0.477], P < 0.001), neuropathy (odds ratio 2.39 [95% CI 1.05–5.43], P = 0.037), retinopathy (3.66 [1.39–9.64], P = 0.009), and being less often admitted for 1-day hospitalization (0.32 [0.14–0.74], P = 0.008). No significant relationship was observed with either nephropathy or cardiovascular risk factors.

CONCLUSIONS—Deprivation status is associated with poor metabolic control and more frequent microvascular complications, i.e., retinopathy and neuropathy. The medical and economic burden of deprived patients is high.
The Impact of Insulin Resistance on Proinsulin Secretion in Pregnancy
Authors: Retnakaran Ravi , Hanley Anthony J.G. , Sermer Mathew , Zinman Bernard
Published: March 2007

OBJECTIVE—Excessive secretion of the insulin precursor proinsulin, as manifested by an increased serum proinsulin-to-insulin ratio, has been associated with β-cell dysfunction. In women with gestational diabetes mellitus (GDM), previous studies of the proinsulin-to-insulin ratio have yielded conflicting results, despite the presence of β-cell dysfunction. The interpretation of the proinsulin-to-insulin ratio, however, may be confounded by the variable effects of hepatic insulin extraction. Thus, we sought to determine whether GDM is characterized by relative hyperproinsulinemia as measured by the proinsulin–to–C-peptide ratio, an alternate measure of proinsulin secretion that is not affected by hepatic insulin extraction.

RESEARCH DESIGN AND METHODS—Serum proinsulin, C-peptide, and insulin were measured in a cross-sectional study of 180 women undergoing oral glucose tolerance tests (OGTTs) in the late second or early third trimester. Based on the OGTT, participants were stratified into three groups: 1) normal glucose tolerance (NGT; n = 93), 2) impaired glucose tolerance (IGT; n = 39), and 3) GDM (n = 48). Insulin sensitivity (IS) was measured using the ISOGTT index of Matsuda and DeFronzo, which has been previously validated in pregnant women.

RESULTS—There were no significant differences in mean fasting proinsulin–to–C-peptide ratio between the three glucose tolerance groups (NGT, 0.024; IGT, 0.022; GDM, 0.019; P = 0.4). Furthermore, adjustment for age, weeks’ gestation, prepregnancy BMI, ethnicity, previous GDM, and family history of diabetes did not reveal any association between the proinsulin–to–C-peptide ratio and glucose tolerance status. Using Spearman univariate correlation analysis, fasting proinsulin–to–C-peptide ratio was significantly correlated with ISOGTT (r = 0.29, P < 0.0001) and inversely related to the homeostasis model assessment of insulin resistance (r = −0.36, P < 0.0001) and prepregnancy BMI (r = −0.23, P < 0.005). On multiple linear regression analysis, ISOGTT emerged as the strongest independent correlate of the dependent variable proinsulin–to–C-peptide ratio. Furthermore, after adjustment for potential covariates, a stepwise decrease in proinsulin–to–C-peptide ratio was observed per decreasing tertile of ISOGTT (trend P = 0.0019), consistent with enhanced efficiency of proinsulin processing (i.e., reduced proinsulin–to–C-peptide ratio) as insulin resistance increases.

CONCLUSIONS—GDM is not independently associated with hyperproinsulinemia as measured by the proinsulin–to–C-peptide ratio. Instead, in pregnant women, increased insulin resistance is associated with decreased proinsulin–to–C-peptide ratio, independently of glucose tolerance status. These data suggest that relative proinsulin secretion in late pregnancy is primarily related to insulin resistance and does not necessarily reflect β-cell function.
Decreased Endogenous Secretory Advanced Glycation End Product Receptor in Type 1 Diabetic Patients
Authors: Katakami Naoto , Matsuhisa Munehide , Kaneto Hideaki , Matsuoka Taka-aki , Sakamoto Ken’ya , Nakatani Yoshihisa , Ohtoshi Kentaro , Hayaishi-Okano Rieko , Kosugi Keisuke , Hori Masatsugu , Yamasaki Yoshimitsu
Published: March 2007

OBJECTIVE—The binding of advanced glycation end products (AGEs) to their receptor (RAGE) plays an important role in the development of diabetic vascular complications. In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels and the severity of diabetic vascular complications.

RESEARCH DESIGN AND METHODS—Circulating esRAGE levels in serum were examined in 67 Japanese type 1 diabetic patients (22 men and 45 women, age 24.0 ± 4.4 years [means ± SD]) and 23 age-matched healthy nondiabetic subjects (10 men and 13 women aged 24.9 ± 1.4 years). Daily urinary albumin excretion, the presence of retinopathy, and intima-media thickness (IMT) of the carotid artery were also evaluated. We further explored the association between esRAGE levels and severity of diabetic vascular complications.

RESULTS—Circulating esRAGE levels were significantly lower in subjects with type 1 diabetes than in nondiabetic subjects (0.266 ± 0.089 vs. 0.436 ± 0.121 ng/ml, respectively, P < 0.0001) and was inversely correlated with HbA1c (A1C) levels (r = −0.614, P < 0.0001). In addition, multivariate regression analysis demonstrated that A1C was an independent risk factor for a low esRAGE value. Furthermore, circulating esRAGE levels were inversely correlated with carotid IMT (r = −0.325, P = 0.0017) and was one of the independent risk factors for IMT thickening. Furthermore, there was a significant difference (P = 0.0124) in esRAGE levels between patients without retinopathy (0.286 ± 0.092 ng/ml) and those with retinopathy (0.230 ± 0.074 ng/ml).

CONCLUSIONS—Circulating esRAGE levels were significantly lower in type 1 diabetic patients than in nondiabetic subjects and were inversely associated with the severity of some diabetic vascular complications.
Predictive Value of Silent Myocardial Ischemia for Cardiac Events in Diabetic Patients
Authors: Valensi Paul , Pariès Jacques , Brulport-Cerisier Valérie , Torremocha Florence , Sachs Régis-Nessim , Vanzetto Gérald , Cosson Emmanuel , Lormeau Boris , Attali Jean-Raymond , Maréchaud Richard , Estour Bruno , Halimi Serge
Published: March 2007

OBJECTIVE—Silent myocardial ischemia (SMI) in asymptomatic subjects with no history of myocardial infarction or angina is a frequent condition in diabetic patients. The aim of the study was to examine the predictive value of SMI for cardiac events in a multicenter cohort and to determine whether this value is higher in patients with a particular clinical profile.

RESEARCH DESIGN AND METHODS—A total of 370 asymptomatic diabetic patients with at least two additional cardiovascular risk factors was recruited in four departments of diabetology. SMI was assessed by either exercise or dipyridamole single-photon emission–computed tomography myocardial perfusion imaging with thallium-201. If dipyridamole stress was used, an electrocardiogram stress test was performed separately on another day. Follow-up duration was 3–89 months (38 ± 23 months).

RESULTS—There was evidence of SMI in 131 patients (35.4%) on at least one positive noninvasive test. The patients with SMI were significantly older and had significantly higher serum triglycerides and lower HDL cholesterol levels. Cardiac events occurred in 53 patients (14.3%). Major cardiac events (death or myocardial infarction) occurred in 38 patients (10%) and other events (unstable angina, heart failure, or coronary revascularization) occurred in 15 patients. The patients who had cardiac events were older and had higher serum triglyceride levels at baseline. There was a significant association between SMI and cardiac events (hazard ratio 2.79 [95% CI 1.54–5.04]) and in particular major cardiac events (3 [1.53–5.87]). In the patients >60 years of age, the prevalence of SMI was higher (43.4 vs. 30.2% in those <60 years). SMI was associated with a significant risk of cardiac events (2.89 [1.31–6.39]) and in particular major cardiac events (3.66 [1.36–9.87]) for the patients >60 years old but not for those <60 years old.

CONCLUSIONS—In asymptomatic diabetic patients with additional cardiovascular risk factors, SMI is a potent predictor of cardiac events and should be assessed preferably in the patients >60 years of age.
Efficacy of Lifestyle Education to Prevent Type 2 Diabetes
Authors: Yamaoka Kazue , Tango Toshiro
Published: March 2007

OBJECTIVE—To evaluate the efficacy of lifestyle education for preventing type 2 diabetes in individuals at high risk by meta-analysis of randomized controlled trials, as assessed by incidence and a reduced level of plasma glucose 2 h after a 75-g oral glucose load (2-h plasma glucose).

RESEARCH DESIGN AND METHODS—Through an electronic search, 123 studies were identified. A literature search identified eight studies that met strict inclusion criterion of meta-analysis for 2-h plasma glucose and five studies for the incidence of diabetes. All were randomized controlled trials of ≥6 months with lifestyle education that included a dietary intervention. Subjects were adults diagnosed as being at high risk for type 2 diabetes. The difference in mean reduction of 2-h plasma glucose from baseline to the 1-year follow-up and relative risk (RR) of the incidence of diabetes in the lifestyle education group versus the control group were assessed. Overall estimates were calculated using a random-effects model. Those estimates were confirmed by several models, and the possibility of selection bias was examined using a funnel plot.

RESULTS—Lifestyle education intervention reduced 2-h plasma glucose by 0.84 mmol/l (95% CI 0.39–1.29) compared with the control group. The 1-year incidence of diabetes was reduced by ∼50% (RR 0.55, 95% CI 0.44–0.69) compared with the control group. Results were stable and little changed if data were analyzed by subgroups or other statistical models. Funnel plots revealed no selection bias.

CONCLUSIONS—Lifestyle education was effective for reducing both 2-h plasma glucose and RR in high-risk individuals and may be a useful tool in preventing diabetes.
Ischemia Imaging and Plaque Imaging in Diabetes
Authors: Raggi Paolo , Bellasi Antonio , Ratti Carlo
Published: March 2007

Cardiovascular disease is the most frequent cause of death and disability in diabetes, and the morbidity and mortality for coronary artery disease (CAD) in this population is two to four times higher than in nondiabetic subjects. Traditional risk factors do not fully explain the level of cardiovascular risk, and coronary disease events are often silent in diabetic patients. Thus, research has recently focused on improving the risk assessment of an individual patient with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging has proven very helpful in this regard. Traditional methods to assess CAD are based on detection of obstructive luminal disease responsible for myocardial ischemia. However, acute coronary syndromes often occur in the absence of luminal stenoses. Hence, the utilization of imaging methodologies to visualize atherosclerosis in its presymptomatic stages has received mounting attention in recent years. In this article, we review the current literature on the utility of traditional imaging modalities for obstructive CAD (nuclear and echocardiographic stress testing) as well as atherosclerosis plaque imaging with carotid intima-media thickness and coronary artery calcium for risk stratification of diabetic patients.