bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of Glyburide and Glipizide Into Breast Milk
Authors: Feig Denice S. , Briggs Gerald G. , Kraemer Jennifer M. , Ambrose Peter J. , Moskovitz David N. , Nageotte Michael , Donat Diane J. , Padilla Guadalupe , Wan Stephanie , Klein Julia , Koren Gideon
Published: March 2007

OBJECTIVE—To determine if glyburide and glipizide are excreted into breast milk and if breast-feeding from women taking these drugs causes infant hypoglycemia.

RESEARCH DESIGN AND METHODS—We studied eight women who had received a single oral dose of 5 or 10 mg glyburide. Drug concentrations were measured in maternal blood and milk for 8 h after the dose. In a separate study, five women were given a daily dosage (5 mg/day) of glyburide or glipizide, starting on the first postpartum day. Maternal blood and milk drug concentrations and infant blood glucose were measured 5–16 days after delivery.

RESULTS—In the single-dose glyburide study, the mean maximum theoretical infant dose (MTID) as a percent of the weight-adjusted maternal dose (WAMD) was <1.5 and <0.7% for the 5- and 10-mg doses, respectively. For the five women taking daily dosages, the mean MTID as a percent of the WAMD was <28% for glyburide and <27% for glipizide. The high estimates were due to the insensitivity of the assay. Neither glyburide nor glipizide were detected in breast milk in either study and blood glucose was normal in the three infants (one glyburide and two glipizide) who were wholly breast-fed when the drug concentrations were at steady state.

CONCLUSIONS—Neither glyburide nor glipizide were detected in breast milk, and hypoglycemia was not observed in the three nursing infants. Both agents, at the doses tested, appear to be compatible with breast-feeding.
Family History of Type 2 Diabetes Is Associated With Increased Carotid Artery Intimal-Medial Thickness in Mexican Americans
Authors: Kao W.H. Linda , Hsueh Wen-Chi , Rainwater David L. , O’Leary Daniel H. , Imumorin Ikhide G. , Stern Michael P. , Mitchell Braxton D.
Published: March 2007

OBJECTIVE—To evaluate whether the joint risk of diabetes and atherosclerosis tracked within families, we assessed the correlation between a family history of diabetes and intimal-medial thickness (IMT) of the common carotid artery (CCA).

RESEARCH DESIGN AND METHODS—Study subjects included 620 nondiabetic individuals from 24 families enrolled in the San Antonio Family Heart Study. The thickness of the far walls of the CCA was measured by B-mode ultrasonography. Statistical analyses included familial correlations to account for the nonindependence of family data.

RESULTS—After adjusting for sex, age, and IMT reader effects, the heritability of IMT in this population was 16% (P = 0.009). Using a more comprehensive family history score that accounted for diabetes status of the individual’s parents and older siblings, we observed a significant correlation between family history score and increased CCA IMT (0.006 mm increase in CCA IMT for every point increase of diabetes family history score, P = 0.016). This association remained even after further adjustment for BMI, smoking, and fasting insulin and glucose levels. After adjusting for several cardiovascular risk factors, the mean CCA IMT in those with high family history scores for diabetes was still 0.037 mm thicker than those with low family history scores for diabetes (P = 0.040).

CONCLUSIONS—These results suggest that the genetic contribution to CCA IMT variability is modest. Also, the small increase in subclinical atherosclerosis observed even among nondiabetic Mexican Americans with a positive family history of diabetes is probably transmitted along with the risk of diabetes through shared etiologic risk factors between diabetes and cardiovascular disease.
Randomized Trial of Quality Improvement Intervention to Improve Diabetes Care in Primary Care Settings
Authors: O’Connor Patrick J. , Desai Jay , Solberg Leif I. , Reger Laurel A. , Crain A. Lauren , Asche Stephen E. , Pearson Teresa L. , Clark Cynthia K. , Rush William A. , Cherney Linda M. , Sperl-Hillen JoAnn M. , Bishop Donald B.
Published: March 2007

OBJECTIVE—To assess the impact of a quality improvement (QI) intervention on the quality of diabetes care at primary care clinics.

RESEARCH DESIGN AND METHODS—Twelve primary care medical practices were matched by size and location and randomized to intervention or control conditions. Intervention clinic staff were trained in a seven-step QI change process to improve diabetes care. Surveys and medical record reviews of 754 patients, surveys of 329 clinic staff, interviews with clinic leaders, and analysis of training session videotapes evaluated compliance with and impact of the intervention. Mixed-model nested analyses compared differences in the quality of diabetes care before and after intervention.

RESULTS—All intervention clinics completed at least six steps of the seven-step QI change process in an 18-month period and, compared with control clinics, had broader staff participation in QI activities (P = 0.04), used patient registries more often (P = 0.03), and had better test rates for HbA1c (A1C), LDL, and blood pressure (P = 0.02). Other processes of diabetes care were unchanged. The intervention did not improve A1C (P = 0.54), LDL (P = 0.46), or blood pressure (P = 0.69) levels or a composite of these outcomes (P = 0.35).

CONCLUSIONS—This QI change process was successfully implemented but failed to improve A1C, LDL, or blood pressure levels. Data suggest that to be successful, such a QI change process should direct more attention to specific clinical actions, such as drug intensification and patient activation.
Depressive Symptoms in Mothers of Infants Identified as Genetically at Risk for Type 1 Diabetes
Authors: Hood Korey K. , Bennett Johnson Suzanne , Carmichael Stacy K. , Laffel Lori M.B. , She Jin-Xiong , Schatz Desmond A.
Published: March 2007

OBJECTIVE—This study describes maternal depression associated with newborn genetic screening for type 1 diabetes after risk notification.

RESEARCH DESIGN AND METHODS—Mothers of at-risk infants (n = 192), identified through newborn genetic screening as part of the Prospective Assessment of Newborns for Diabetes Autoimmunity study, were administered a structured telephone interview assessing maternal depressive symptoms 1 and 3.5 months after risk notification. Statistical analyses were conducted to examine predictors and correlates of maternal depressive symptoms.

RESULTS—For the total sample, maternal depressive symptoms in response to infant risk status were not elevated at 1 and 3.5 months after risk notification. However, at the first interview, mothers from ethnic minority backgrounds (P < 0.002), with limited education (P < 0.001), and with postpartum depression symptomatology (P < 0.001) reported significantly more depressive symptoms in response to risk notification (r2 = 0.354). At the second interview, postpartum depression symptomatology remained a powerful predictor of depressive symptoms in response to risk notification (P < 0.001). In addition, certain coping styles (wishful thinking, self-blame, and seeking social support) were associated with increased depressive symptoms. A history of major depression was a correlate of both postpartum depressive symptomatology (r = 0.26) and maternal depressive response to risk notification (r = 0.21).

CONCLUSIONS—For the most part, mothers of infants genetically at risk for type 1 diabetes do not appear to evidence elevated depressive symptoms. This suggests that most mothers are resilient when notified of infant risk. However, certain maternal characteristics such as ethnic minority status, less than a high school education, postpartum depression symptomatology, a history of major depression, and certain coping strategies (wishful thinking, self-blame, and seeking social support) appear to be associated with a more difficult maternal response to the news of an infant’s increased genetic risk for type 1 diabetes.
Joint Distribution of Non-HDL and LDL Cholesterol and Coronary Heart Disease Risk Prediction Among Individuals With and Without Diabetes
Authors: Liu Jian , Sempos Christopher , Donahue Richard P. , Dorn Joan , Trevisan Maurizio , Grundy Scott M.
Published: March 2007

OBJECTIVE—To assess coronary heart disease (CHD) risk within levels of the joint distribution of non-HDL and LDL cholesterol among individuals with and without diabetes.

RESEARCH DESIGN AND METHODS—We used four publicly available data sets for this pooled post hoc analysis and confined the eligible subjects to white individuals aged ≥30 years and free of CHD at baseline (12,660 men and 6,721 women). Diabetes status was defined as either “reported by physician-diagnosed and on medication” or having a fasting glucose level ≥126 mg/dl at the baseline examination. The primary end point was CHD death. Within diabetes categories, risk was assessed based on lipid levels (in mg/dl): non-HDL <130 and LDL <100 (group 1); non-HDL <130 and LDL ≥100 (group 2); non-HDL ≥130 and LDL <100 (group 3); and non-HDL ≥130 and LDL ≥100 (group 4). Group 1 within those without diabetes was the overall reference group.

RESULTS—Of the subjects studied, ∼6% of men and 4% of women were defined as having diabetes. A total of 773 CHD deaths occurred during the average 13 years of follow-up time. A Cox proportional hazard model was used to estimate the relative risk (RR) of CHD death. Those with diabetes had a 200% higher RR than those without diabetes. In a multivariate model, CHD risk in those with diabetes did not increase with increasing LDL, whereas it did increase with increasing non-HDL: RR (95% confidence interval) for group 1: 5.7 (2.0–16.8); group 2: 5.7 (1.6–20.7); group 3: 7.2 (2.6–19.8); and group 4: 7.1 (3.7–13.6).

CONCLUSIONS—Non-HDL is a stronger predictor of CHD death among those with diabetes than LDL and should be given more consideration in the clinical approach to risk reduction among diabetic patients.
Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals With Diabetes
Authors: Selvin Elizabeth , Coresh Josef , Golden Sherita H. , Boland Lori L. , Brancati Frederick L. , Steffes Michael W.
Published: March 2007

OBJECTIVE—Glycemic control (HbA1c [A1C]) is strongly associated with microvascular disease in individuals with diabetes, but its relation to macrovascular disease and atherosclerosis is less clear. This study examines the relationship between A1C, carotid intima-media thickness (IMT), and traditional cardiovascular risk factors in individuals with diabetes.

RESEARCH DESIGN AND METHODS—A cross-sectional study of 2,060 people with diagnosed and undiagnosed (unrecognized) diabetes in the Atherosclerosis Risk in Communities study was performed.

RESULTS—LDL and HDL cholesterol, plasma triglycerides, and waist-to-hip ratio were significantly associated with A1C after multivariable adjustment. African Americans with undiagnosed and diagnosed diabetes had significantly elevated A1C values compared with whites, even after adjustment for potentially confounding factors. There was a graded association between A1C and carotid IMT. In a fully adjusted model in individuals with undiagnosed diabetes, the odds ratio (OR) of being in the highest quartile of IMT versus the lowest was 2.46 (95% CI 1.16–5.03, comparing the highest quartile of A1C to the lowest). In people with diagnosed diabetes, the comparable OR was 2.62 (1.36–5.06).

CONCLUSIONS—This study identified several important associations between A1C and known risk factors for cardiovascular disease and suggested that A1C is independently related to carotid IMT. Chronically elevated glucose levels may contribute to the development of atherosclerosis in people with diabetes, independent of other risk factors.
Discordant Trends in Microvascular Complications in Adolescents With Type 1 Diabetes From 1990 to 2002
Authors: Mohsin Fauzia , Craig Maria E , Cusumano Janine , Chan Albert K.F. , Hing Stephen , Lee Jennifer W. , Silink Martin , Howard Neville J. , Donaghue Kim C.
Published: March 2007

OBJECTIVE—Since the Diabetes Control and Complications Trial, diabetes management goals have changed. The aims of the present study were to assess complication rates, including nerve abnormalities, in adolescents from 1990 to 2002 and to investigate associated risk factors.

RESEARCH DESIGN AND METHODS—Cross-sectional analysis of complications was assessed in three study periods (1990–1994 [T1], 1995–1998 [T2], and 1999–2002 [T3]) in adolescents matched for age and diabetes duration (n = 878, median age 14.6 years, median duration 7.5 years). Retinopathy was assessed by seven-field stereoscopic fundal photography, albumin excretion rate (AER) from three consecutive timed overnight urine collections, peripheral nerve function by thermal and vibration thresholds, and autonomic nerve function by cardiovascular reflexes.

RESULTS—Retinopathy declined significantly (T1, 49%; T2, 31%; and T3, 24%; P < 0.0001), early elevation of AER (≥7.5 μg/min) declined (38, 30, and 25%, respectively, P = 0.022), and microalbuminuria (AER ≥20 μg/min) declined (7, 3, and 3%, respectively; P = 0.017, T1 vs. T2 and T3). Autonomic nerve abnormalities were unchanged (18, 21, and 18%, respectively; P = 0.60), but peripheral nerve abnormalities increased (12, 19, and 24%, respectively; P = 0.0017). More patients were treated with three or more injections per day (12, 46, and 67%, respectively; P < 0.0001) and insulin dose increased (1.08, 1.17, and 1.22 units · kg−1 · day−1, respectively; P < 0.0001), but median HbA1c (A1C) was unchanged (8.5, 8.5, and 8.4%, respectively). BMI and height SD score increased: BMI 0.46, 0.67, and 0.79, respectively (P < 0.0001), and height −0.09, 0.05, and 0.27, respectively (P < 0.0001).

CONCLUSIONS—Retinopathy and microalbuminuria declined over time in this cohort, but the increased rate of peripheral nerve abnormalities is of concern. Despite intensified management (higher insulin dose and more injections), A1C has not changed and remains well above the recommended targets for adolescents.
Relationship Between HbA1c Level and Peripheral Arterial Disease
Authors: Muntner Paul , Wildman Rachel P. , Reynolds Kristi , DeSalvo Karen B. , Chen Jing , Fonseca Vivian
Published: March 2007

OBJECTIVE—Homeostatic glucose control may play an important role in the development of peripheral arterial disease among individuals without diabetes. We sought to evaluate the association of HbA1c (A1C) with peripheral arterial disease in a representative sample of the U.S. population with and without diabetes.

RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted among 4,526 National Health and Nutrition Examination Survey 1999–2002 participants ≥40 years of age. Peripheral arterial disease was defined as an ankle-brachial index <0.9 (n = 327).

RESULTS—Among nondiabetic subjects, the age-standardized prevalence of peripheral arterial disease was 3.1, 4.8, 4.7, and 6.4% for participants with an A1C <5.3, 5.3–5.4, 5.5–5.6, and 5.7–6.0%, respectively (P trend <0.001). The prevalence of peripheral arterial disease was 7.5 and 8.8% for diabetic participants with A1C <7 and ≥7%, respectively. After multivariable adjustment and compared with nondiabetic participants with A1C <5.3%, the odds ratio (95% CI) of peripheral arterial disease for nondiabetic participants with an A1C of 5.3–5.4, 5.5–5.6, and 5.7–6.0% was 1.41 (0.85–2.32), 1.39 (0.70–2.75), and 1.57 (1.02–2.47), respectively, and it was 2.33 (1.15–4.70) and 2.74 (1.25–6.02) for diabetic participants with A1C <7 and ≥7%, respectively.

CONCLUSIONS—An association exists between higher levels of A1C and peripheral arterial disease, even among patients without diabetes. Individuals with A1C levels ≥5.3% should be targeted for aggressive risk factor reduction, which may reduce the burden of subclinical cardiovascular disease even among those without diabetes.
C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance
Authors: Cardellini Marina , Perego Lucia , D’Adamo Monica , Marini Maria Adelaide , Procopio Cristina , Hribal Marta Letizia , Andreozzi Francesco , Frontoni Simona , Giacomelli Maurizio , Paganelli Michele , Pontiroli Antonio E. , Lauro Renato , Folli Franco , Sesti Giorgio
Published: March 2007

OBJECTIVE—The C-174G promoter polymorphism of the interleukin (IL)-6 gene was found to influence transcriptional activity and plasma IL-6 levels in humans. We addressed the question of whether the C-174G IL-6 polymorphism contributes to variation of insulin sensitivity.

RESEARCH DESIGN AND METHODS—Two cohorts of subjects were genotyped. Cohort 1 includes 275 nondiabetic subjects who underwent a euglycemic-hyperinsulinemic clamp. Cohort 2 includes 77 patients with morbid obesity who underwent laparoscopic adjustable gastric banding (LAGB).

RESULTS—The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In cohort 1, insulin sensitivity was reduced in carriers of the −174G/G genotype as compared with subjects carrying the C allele (P = 0.004). Carriers of −174G/G displayed significantly higher plasma IL-6 levels in comparison with carriers of the C allele. In a stepwise linear regression analysis, the C-174G polymorphism was independently associated with insulin sensitivity; however, after inclusion of plasma IL-6 concentrations, the polymorphism was excluded from the model explaining insulin sensitivity variability, thus suggesting that the polymorphism was affecting insulin sensitivity by regulating IL-6 plasma levels. IL-6 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from obese patients of cohort 2 during LAGB. Carriers of −174G/G showed increased IL-6 expression compared with subjects carrying the C allele (P = 0.04). There was a significant correlation between adipose IL-6 mRNA expression and insulin resistance assessed by homeostasis model assessment (ρ = 0.28, P = 0.014).

CONCLUSIONS—These results indicate that the −174G/G genotype of the IL-6 gene may contribute to variations in insulin sensitivity.
Metabolic Syndrome in Type 1 Diabetes
Authors: Thorn Lena M. , Forsblom Carol , Fagerudd Johan , Thomas Merlin C. , Pettersson-Fernholm Kim , Saraheimo Markku , Wadén Johan , Rönnback Mats , Rosengård-Bärlund Milla , Björkesten Clas-Göran af , Taskinen Marja-Riitta , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: March 2007

OBJECTIVE—The aim of this study was to estimate the prevalence of the metabolic syndrome in Finnish type 1 diabetic patients and to assess whether it is associated with diabetic nephropathy or poor glycemic control.

RESEARCH DESIGN AND METHODS—In all, 2,415 type 1 diabetic patients (51% men, mean age 37 years, duration of diabetes 22 years) participating in the nationwide, multicenter Finnish Diabetic Nephropathy (FinnDiane) study were included. Metabolic syndrome was defined according to the National Cholesterol Education Program diagnostic criteria. Patients were classified as having normal albumin excretion rate (AER) (n = 1,261), microalbuminuria (n = 326), macroalbuminuria (n = 383), or end-stage renal disease (ESRD) (n = 164). Glycemic control was classified as good (HbA1c <7.5%), intermediate (7.5–9.0%), or poor (>9.0%). Creatinine clearance was estimated with the Cockcroft-Gault formula.

RESULTS—The overall prevalence of metabolic syndrome was 38% in men and 40% in women. The prevalence was 28% in those with normal AER, 44% in microalbuminuric patients, 62% in macroalbuminuric patients, and 68% in patients with ESRD (P < 0.001). Patients with metabolic syndrome had a 3.75-fold odds ratio for diabetic nephropathy (95% CI 2.89–4.85), and all of the separate components of the syndrome were independently associated with diabetic nephropathy. The prevalence of metabolic syndrome was 31% in patients with good glycemic control, 36% in patients with intermediate glycemic control, and 51% in patients with poor glycemic control (P < 0.001). Similarly, metabolic syndrome increased with worsening creatinine clearance.

CONCLUSIONS—The metabolic syndrome is a frequent finding in type 1 diabetes and increases with advanced diabetic nephropathy and worse glycemic control.
Gestational Weight Gain and Pregnancy Outcomes in 481 Obese Glucose-Tolerant Women
Authors: Jensen Dorte M. , Ovesen Per , Beck-Nielsen Henning , Mølsted-Pedersen Lars , Sørensen Bente , Vinter Christina , Damm Peter
Published: March 2007

OBJECTIVE—To investigate the effect of gestational weight gain in obese glucose-tolerant women.

RESEARCH DESIGN AND METHODS—We performed a historical cohort study of 481 women with prepregnancy BMI ≥30 kg/m2 and a normal 2-h 75-g oral glucose tolerance test (OGTT) during the third trimester (according to World Health Organization criteria). Data on OGTT results and clinical outcomes were collected from medical records. Four groups were defined according to weight gain: group 1, <5.0 kg (n = 93); group 2, 5.0–9.9 kg (n = 134); group 3, 10.0–14.9 kg (n = 132); and group 4, ≥15.0 kg (n = 122).

RESULTS—Birth weight increased significantly with increasing weight gain (mean grams ± SD): group 1, 3,456 ± 620; group 2, 3,624 ± 675; group 3, 3,757 ± 582; and group 4, 3,784 ± 597 (P < 0.001). The birth weight in group 1 was similar to that of the background population of primarily normal-weight women (3,478 g). In multivariate analyses, increasing weight gain was associated with significantly higher rates of hypertension (OR 4.8 [95% CI for group 4 vs. group 1: 1.7–13.1]), cesarean section (3.5 [1.6–7.8]), induction of labor (3.7 [1.7–8.0]), and large-for-gestational-age infants (4.7 [2.0–11.0]). There was no difference in rates of small-for-gestational-age infants. Significant predictors for birth weight (determined by multiple linear regression) were gestational weight gain, 2-h OGTT result, pregestational BMI, maternal age, gestational age, and smoking.

CONCLUSIONS—Increasing weight gain in obese women is associated with increasing pregnancy complications. Our data suggest that minimal gestational weight gain might normalize birth weight. Prospective studies should be performed to clarify the safety of recommending limited gestational weight gain.
The Burden of Mortality Attributable to Diabetes
Authors: Roglic Gojka , Unwin Nigel , Bennett Peter H. , Mathers Colin , Tuomilehto Jaakko , Nag Satyajit , Connolly Vincent , King Hilary
Published: March 2007

OBJECTIVE—To estimate the global number of excess deaths due to diabetes in the year 2000.

RESEARCH DESIGN AND METHODS—We used a computerized generic formal disease model (DisMod II), used by the World Health Organization to assess disease burden through modeling the relationships between incidence, prevalence, and disease-specific mortality. Baseline input data included population structure, age- and sex-specific estimates of diabetes prevalence, and available published estimates of relative risk of death for people with diabetes compared with people without diabetes. The results were validated with population-based observations and independent estimates of relative risk of death.

RESULTS—The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths. Excess mortality attributable to diabetes accounted for 2–3% of deaths in poorest countries and over 8% in the U.S., Canada, and the Middle East. In people 35–64 years old, 6–27% of deaths were attributable to diabetes.

CONCLUSIONS—These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death.
Access to Care for Patients With Insulin-Requiring Diabetes in Developing Countries
Authors: Beran David , Yudkin John S. , de Courten Maximilian
Published: March 2007

OBJECTIVE—The objective of this study was to assess the barriers to care for patients with insulin-requiring diabetes in Mozambique and Zambia.

RESEARCH DESIGN AND METHODS—We used the Rapid Assessment Protocol for Insulin Access to collect information through interviews, discussions, site visits, and document reviews. Government organizations, health facilities, care givers, and patients were asked about care for people with insulin-requiring diabetes. Between 100 and 200 interviews/discussions per country were undertaken in and around the capital city and the regional capital and in a rural area.

RESULTS—Insulin was present in both countries in sufficient quantities, although the financial burden for health services and patients meant that problems with supply exist. There are problems with quantification of needs and equitable distribution of insulin. Problems with availability of syringes and testing equipment were noted, particularly in Mozambique. This lack of tools and infrastructure for diagnosis and follow-up coupled with low levels of health care worker training and lack of diagnostic reagents resulted in a substantial risk of misdiagnosis or failure to detect diabetes. The estimated prevalence of insulin-requiring diabetes differs more than 10-fold between urban and rural areas in Mozambique and 4-fold between Mozambique and Zambia, suggesting that problems in diagnosis and care result in substantial worsening of prognosis for such patients.

CONCLUSIONS—Insulin is necessary but not sufficient to improve prognosis for diabetic patients. A Rapid Assessment Protocol methodology can be used to define problems in health care delivery for diabetes. Proper care for insulin-requiring diabetes necessitates health systems able to provide trained personnel, medicines in sufficient quantity, and diagnostic and monitoring facilities.
Biofeedback-Assisted Relaxation in Type 2 Diabetes
Authors: McGinnis Ronald A. , McGrady Angele , Cox Stephen A. , Grower-Dowling Kimber A.
Published: March 2007

OBJECTIVE—The objective of this randomized controlled study was to determine the effects of biofeedback and relaxation on blood glucose and HbA1c (A1C) in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes were randomized to either 10 sessions of biofeedback (electromyograph and thermal) and relaxation or 3 sessions of education. All sessions were individual. A total of 39 participants were entered, and 30 completed the 3-month protocol. Average blood glucose, A1C, forehead muscle tension, and peripheral skin temperature were assessed, and inventories measuring depression and anxiety were administered prerandomization and after completion of treatment/control.

RESULTS—Biofeedback and relaxation were associated with significant decreases in average blood glucose, A1C, and muscle tension compared with the control group. At 3-month follow-up, the treatment group continued to demonstrate lower blood glucose and A1C. Both groups decreased scores on the depression and anxiety inventories. Patients with depression had higher blood glucose levels and tended to drop out of the study.

CONCLUSIONS—This study supports the use of biofeedback and relaxation in patients with type 2 diabetes for up to 3 months after treatment. Further research is necessary to determine the long-term effects of biofeedback and the effects of mood on patients’ responses to treatment.
Enteral Nutritional Support and Use of Diabetes-Specific Formulas for Patients With Diabetes
Authors: Elia Marinos , Ceriello Antonio , Laube Heiner , Sinclair Alan J. , Engfer Meike , Stratton Rebecca J.
Published: March 2007

OBJECTIVE—The aim of this systematic review was to determine the benefits of nutritional support in patients with type 1 or type 2 diabetes.

RESEARCH DESIGN AND METHODS—Studies utilizing an enteral nutritional support intervention (oral supplements or tube feeding) were identified using electronic databases and bibliography searches. Comparisons of interest were nutritional support versus routine care and standard versus diabetes-specific formulas (containing high proportions of monounsaturated fatty acids, fructose, and fiber). Outcomes of interest were measures of glycemia and lipid status, medication requirements, nutritional status, quality of life, complications, and mortality. Meta-analyses were performed where possible.

RESULTS—A total of 23 studies (comprising 784 patients) of oral supplements (16 studies) and tube feeding (7 studies) were included in the review, and the majority compared diabetes-specific with standard formulas. Compared with standard formulas, diabetes-specific formulas significantly reduced postprandial rise in blood glucose (by 1.03 mmol/l [95% CI 0.58–1.47]; six randomized controlled trials [RCTs]), peak blood glucose concentration (by 1.59 mmol/l [86–2.32]; two RCTs), and glucose area under curve (by 7.96 mmol · l−1 · min−1 [2.25–13.66]; four RCTs, i.e., by 35%) with no significant effect on HDL, total cholesterol, or triglyceride concentrations. In addition, individual studies reported a reduced requirement for insulin (26–71% lower) and fewer complications with diabetes-specific compared with standard nutritional formulas.

CONCLUSIONS—This systematic review shows that short- and long-term use of diabetes-specific formulas as oral supplements and tube feeds are associated with improved glycemic control compared with standard formulas. If such nutritional support is given long term, this may have implications for reducing chronic complications of diabetes, such as cardiovascular events.
Self-Management, Patient Compliance, and the Physician
Authors: Krosnick Arthur
Published: March 2007

Two-hundred ambulatory private office patients with IDDM were surveyed to determine the acceptability of home blood glucose testing, and the factors which permit the physician to predict which patients will use this adjuvant to self-management. The method proved acceptable to 80% of those with GODM and 63% of the MODM patients. Predictability factors, a contingency patient-physician contract, and a protocol for urine and blood testing in conjunction with a treatment algorithm are discussed.
Teaching Diabetic Patients About Self-Management
Authors: Judd Sue , Sönksen P H
Published: March 2007

It takes approximately 20 min to teach a patient how to use Dextrostix reagent strips in conjunction with an Eyetone reflectance meter (or the more recently introduced Glucochek). Blood glucose monitoring is no more difficult or time consuming than conventional urine testing and can be learned and executed by patients of various levels of intelligence. It is important to emphasize the need for an adequate drop of blood and the use of Monolet blood lancets has greatly facilitated this. Emphasis is put on the most useful times to make recordings and the importance of good record-keeping. The more intelligent patients readily learn how to adjust their insulin to improve their blood glucose readings while the less intelligent need help and advice. Experience has shown that no only are blood glucose levels improved but also hypoglycemic episodes are less commmon.
A Program for Normal Glycemic Control of Insulin-dependent Diabetes
Authors: Williams John R , Alling Katharine
Published: March 2007

A method of instruction enabling patients to control their diabetes is described. The patients learn through home glucose monitoring how their blood sugar levels vary with changes in diet, exercise, and insulin. They learn to chart accurately all the factors influencing their control in a manner that enables them, as well as the physician, to analyze them quickly. From this information they learn to anticipate the results of various changes in life-style and, thus, to live beyond the customary constraints of the disease without loss of glycemic control. Significant improvements in neuritis, impotence, and creatinine clearance rates are reported.
Provocation of Postural Hypotension by Nitroglycerin in Diabetic Autonomic Neuropathy?
Authors: Hume L , Ewing D J , Campbell I W , Reuben S R , Clarke B F
Published: March 2007

The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy.
Characteristics of Glycemic Stability
Authors: Service F John , Nelson Roger L
Published: March 2007

Glucose homeostasis in healthy subjects is characterized by postmeal glucose increases of about 40 mg/dl, peaks at about 45 min, decreases close to antecibal levels 1 h after the peak, and no spontaneous oscillations until the next meal. Diabetes is characterized by progressive loss of glucose homeostasis from stable to unstable, which is directly proportional to loss of insulin secretory reserve. Degree of instability of diabetes in ambulatory subjects within a 24-h period can be expressed as mean amplitude of glycemic excursion of M-value and between two successive 24-h periods as mean of daily differences of blood glucose. Stable diabetic persons have lower values, which are closest to those of nondiabetic persons, and unstable diabetic persons have higher values. The mean diurnal blood glucose level is a measure of glycemic control. The failure to restore glycemic patterns of diabetic to those of nondiabetic persons is largely due to the failure of subcutaneously administered insulin to mimic the pattern of insulinemia of healthy subjects.
Peripheral Vascular Disease in Diabetes Mellitus and Its Relation to Cardiovascular Risk Factors: Screening with the Doppler Ultrasonic Technique
Authors: Janka Hans U , Standl Eberhard , Mehnert Hellmut
Published: March 2007

Data of 623 nonselected diabetic outpatients are presented who were screened for peripheral vascular disease (PVD) and for cardiovascular risk factors. PVD was diagnosed in 15.9% of the diabetic patients (14.4% women and 18.0% men). Nine percent of the patients had signs of marked mediasclerosis at the ankle level. Multivariate statistical analysis revealed that PVD was closely associated with systolic hypertension and also with the duration of diabetes, a relationship that was highly significant (P < 0.001) for the peripheral type (below the knee) of PVD. Diabetic patients with arterial disease at the pelvic or femoral site exhibited a higher number of cardiovascular risk factors. In contrast, in patients with the peripheral type, significantly higher blood glucose values were found. Therefore, the quality of metabolic control may play an important part in the development of this form of diabetic macroangiopathy.
Absence of a Relationship Between Smoking and Diabetic Microangiopathy
Authors: West Kelly M , Erdreich Linda S , Stober Judy A
Published: March 2007

The relationship between cigarette smoking and retinopathy and proteinuria was examined in a group of 973 subjects with diabetes. Other variables known to influence the risk of microangiopathy were also measured in a standardized fashion (e.g., duration of diabetes, blood glucose, blood pressure). The characteristics of smokers and nonsmokers were studied in detail. It was therefore possible to take into account the effects of confounding variables on the relationship between smoking and risk of microangiopathy. Associations between smoking and risk of microangiopathies, previously reported in some of the smaller studies, were not confirmed in this larger study.
Hyperinsulinism Complicating Control of Diabetes Mellitus by an Artificial Beta-Cell
Authors: Horwitz David L , Zeidler Adina , Gonen Boas , Jaspan Jonathan B
Published: March 2007

Serum free insulin concentrations were measured in diabetic subjects given insulin intravenously by a glucose-controlled insulin infusion system (“closed-loop” artificial beta-cell) in two experimental situations: hourly during the day while given their usual diet and at short intervals after administration of a standardized test meal. Three of four subjects showed sustained hyperinsulinism when compared with matched controls during a day on their usual diet. In two of the subjects, the insulin levels also exceeded those seen in those subjects on their usual dose of subcutaneous insulin. The glucose levels were not completely normalized in the three hyperinsulinemic subjects, and the insulin levels were significantly correlated with plasma glucose levels. After the test meal, all six diabetic subjects studied showed a delayed rise in insulin levels, when compared with six normal subjects, followed by an abrupt rise in insulin levels to peak levels more than seven times those seen in normal subjects. We conclude that significant hyperinsulinism may accompany feedback-controlled intravenous insulin administration. This should be considered in interpreting studies done with such systems, and in design of control algorithms for future systems.
For Insulin Infusion: A Miniature Precision Peristaltic Pump and Silicone Rubber Reservoir
Authors: Jackman W S , Lougheed W , Marliss E B , Zinman B , Albisser A M
Published: March 2007

This paper describes a miniature precision peristaltic pump and a silicone rubber reservoir developed for the infusion of insulin in diabetic subjects. The ability of the 100-ml reservoir to maintain sterility of its contents over 26 refilling cycles (48 days) is demonstrated. Accelerated bench tests on 10 pumps over 30 days indicate an accuracy of ± 1% on flow rate whether measured over 10 min or 24 h and with or without 1 atm of outlet back pressure. Comparison of calibrations made before and after 58 animal and clinical tests of 6–71 days′ duration showed a percentage difference in calibration that varied with a mean ± SD of 0.05 ± 3.09%. Microscopic examination of pump tube samples after 21 days of clinical use indicated redistribution of surface material without evidence of particle spallation. Samples subjected to accelerated wear equivalent to 620 days of clinical use showed extensive luminal surface modification and particulate deposits on downstream filters. These were identified by X-ray spectroscopy as silicon compounds.
Programmable Open-Loop Micropump Insulin Delivery System
Authors: Clemens A H
Published: March 2007

The application of “closed-loop” glucose-controlled insulin infusion in metabolic research and in the management of diabetic patients in acute emergency situations has stimulated the development of portable insulin infusion devices intended for the long-term stabilization of glucose levels. Since in vivo glucose sensors with long-term accuracy and reliability are not yet available, the currently projected portable insulin infusion systems are the “open-loop” type. Such systems should be reliable, safe, programmable, lightweight, and small in size. In addition, the power requirements should be as low as possible to avoid the need for heavy batteries and/or periodic recharging. In turn, these requirements govern the design criteria for the most essential component of such an instrument, the insulin delivery pump. A micropump has been developed in an attempt to meet all desirable design features. Evaluation data are presented.
Fetal Macrosomia—Animal Models
Authors: Schwartz Robert , Susa John
Published: March 2007

Macrosomia is characteristic of the infant whose mother has undiagnosed diabetes mellitus during pregnancy or whose diabetes has been inadequately controlled. Animal models of diabetes have included effects of pancreatectomy or beta-cell destruction by chemical agents. Maternal effects have been variable as have been effects on the fetus. Recent studies by Van Assche indicate that chemically induced diabetes may have genetically transmitted effects through three generations in rats. End-organ effects of hyperinsulinemia have been produced in normal fetal rhesus monkeys without maternal hyperglycemia. In this model, macrosomia and selective organomegaly similar to changes observed in the human infant of the diabetic mother were produced. Hepatic enzyme activities concerned with lipogenesis were increased, while some of those controlling gluconeogenesis were decreased. The primary effects of insulin in utero appear to accelerate growth.
Screening for Abnormalities of Carbohydrate Metabolism in Pregnancy 1966–1977: The Belfast Experience
Authors: Hadden D R
Published: March 2007

Of the 30,300 mothers who attended consecutively at the antenatal clinic during an 11-yr period, 3063 mothers screened positive using clinical criteria for potential diabetes in pregnancy. These 3063 mothers had a glucose tolerance test (GTT), of which 661 were judged abnormal. At different times an oral GTT, cortisone-stressed GTT, or i.v. GTT were used and several changes in the clinical screening criteria and interpretation of the GTT values were made. There was a steady fall in fetal loss in all groups of mothers during the period. Those mothers whose glucose intolerance was between one and three standard deviations above the mean had only slightly more pregnancy complications than those with a normal GTT. Apart from clicnial recognition of this state, no special management of these mothers was necessary. Long-term decompensation of glucose tolerance to frank or symptomatic diabetes was uncommon.
A Pilot Community-Based Screening Program for Gestational Diabetes
Authors: Merkatz Irwin R , Duchon Method A , Yamashita Toyoko S , Houser Harold B
Published: March 2007

A pilot community-based screening program for gestational diabetes has been in operation in Cleveland, Ohio, since April 1, 1977. A socioeconomic and racially heterogeneous group of pregnant women are being routinely tested at approximately 24–28 wk of gestation by a capillary whole blood glucose determination, 2-h after a 75-g oral challenge. The results of the first 2225 screenings are analyzed in terms of the variables of maternal race, age, and stage of gestation. The overall incidence of positive screenings (≥ 120 mg/dl) is shown to be 11.5%, with significantly more positive tests among the whites than the nonwhites. Follow-up oral glucose tolerance testing results in an overall detection rate for abnormal carbohydrate metabolism of 3.1%. The data suggest that a 2-h screening procedure is more efficient than a 1-h procedure in that fewer confirmatory glucose tolerance tests need to be performed in order to yield this rate of detection. It may soon be feasible to introduce such a program on a wider community basis in concert with regionalized perinatal care.
Nesidioblastosis, Islet Cell Hyperplasia, and Adenomatosis in a Case of Metastasizing Insulinoma: Contribution to the Genesis of the Islets of Langerhans
Authors: Leong Anthony S-Y , Slavotinek Anthony H , Higgins Bruce A
Published: March 2007

An unusual case of insulinoma is described in a 40-yr-old woman whose resected pancreas showed multiple adenomas with lymph node metastasis, associated hyperplasia of islets, and nesidioblastosis. The association of nesidioblastosis with this continuum of proliferative changes adds further evidence for a ductular origin of islet Cell tumors.
Control of Maturity-Onset Diabetes by Monitoring Fasting Blood Glucose and Body Weight
Authors: Howe-Davies S , Simpson R W , Turner R C
Published: March 2007

The feasibility of reducing the fasting blood glucose (FBG) level to <6 mmol/L has been studied in all 84 maturity-onset diabetic (MOD) patients in three general practices. Only 35 (48%) were initially “well controlled” by this criterion, although 72 (86%) had no postprandial glycosuria. Seventy-one patients were monitored for 6 mo. With additional oral hypoglycemic therapy where necessary, the number of “well controlled” increased from 29 (41%) to 54 (76%), associated with a significant decrease in the hemoglobin A1. The patients were subsequently assessed at two 3-monthly intervals, and a fasting plasma glucose >4 and <6 mmol/L was usually maintained. All but two patients with a fasting glucose level < 6 mmol/L had fasting triglyceride concentrations < 2 mmol/L. The fasting blood glucose can be assayed in general practice with glucose-oxidase strips, and control by this means is simpler, cheaper, and more effective than regular urine glucose monitoring.
Malignant External Otitis: Now a Medical Problem
Authors: Giordano Joseph A , Phillips John
Published: March 2007

A 75-yr-old diabetic woman presented with right ear tenderness and neck pain. Pseudomonas aeruginosa was cultured during surgery from an inflammatory area in the region of the cervical vertebrae. A diagnosis of malignant external otitis was made and parenteral antibiotics were given, which produced a cure. This disease has a high mortality rate, which accounts for the use of the word malignant. Our patient also manifested the jugular foramen syndrome involving multiple cranial nerves. If there is cranial nerve involvement, which is seen in at least one-half of cases, the mortality ranges as high as 80%. We describe here the first case with invasion of the cervical vertebrae.
The Problem of “Cheating” in the Diabetic Child and Adolescent
Authors: Belmonte Mimi M , Gunn Tania , Gonthier Monique
Published: March 2007

The frequency, causes, and consequences of “cheating” in diabetic children and adolescents were studied during summer camp. A philosophical approach is proposed for its understanding and management.
Pathogenesis of Atherosclerosis in Diabetes Mellitus
Authors: Colwell John A , Lopes-Virella Maria , Halushka Perry V
Published: March 2007

Numerous studies have shown that patients with diabetes mellitus have accelerated atherosclerotic vascular disease, and major advances in understanding its pathogenesis have been made. Current suggestions are that endothelial injury may be the initial event in the genesis of atherosclerosis, followed by platelet adhesion and aggregation at the site of injury. In diabetes, evidence of endothelial dysfunction is present. Smooth muscle cell proliferation is an important pathologic finding in atherosclerosis. This process is stimulated by a platelet mitogen, which has been partially characterized. The mitogen has not been studied in diabetes. Lipid accumulation in the area of the atherosclerotic lesion is primarily in the form of intracellular and extracellular esterified cholesterol. In uncontrolled diabetes, elevated plasma low density lipoprotein levels and decreased plasma high density lipoprotein levels favor lipid deposition in large vessels. There is evidence of a thrombotic state in certain diabetic patients. Collectively, these abnormalities of endothelial, platelet, smooth muscle, lipoprotein, and coagulation behavior may be viewed as contributing to the problem of accelerated atherosclerosis in diabetes. A thorough understanding of the pathogenesis of this process aids in designing appropriate preventive therapeutic approaches.
Nutrient Intake in a Partly Westernized Isolated Polynesian Population: The Funafuti Survey
Authors: Wicking Julie , Ringrose Helen , Whitehouse Sunny , Zimmet Paul
Published: March 2007

Dietary data were obtained from 110 adult Polynesians (indigenous Funafutians) during a diabetes epidemiologic survey in Tuvalu. Funafuti (the main island of Tuvalu) was chosen as representative of partly urbanized population that has seen progressive socioeconomic changes in the previous 30 yr. The distribution of calories in the Funafuti diet is almost identical to that reported in the urbanized Micronesian population of Nauru and in Caucasian populations. Prevalence of diabetes was found to be five times higher than that reported in caucasian populations. Similarly, the prevalence of hypertension was 11% (equal to Caucasian figures), whereas hypertension is virtually unknown in traditional-living populations. Prevalence of diabetes, and degree of obesity, is significantly greater in women than in men. It is possible that this Polynesian group may have a genetic susceptibility to diabetes, which may have been unmasked by change from a traditional to western life-style. Marked obesity is now a characteristic of many Polynesian and Micronesian populations, and must rank as a major causative factor for the diabetes and hypertension explosion.