bluuebunny/crossref_metadata_2025 huggingface dataset:
High cardiovascular disease mortality in subjects with visual impairment caused by diabetic retinopathy.
Authors: Rajala U , Pajunpää H , Koskela P , Keinänen-Kiukaanniemi S
Published: March 2007

OBJECTIVE: The aim of this study was to assess mortality and causes of death in subjects with visual impairment caused by diabetic retinopathy (DR). Only limited data are available concerning the mortality of subjects with DR, and to our knowledge, no data so far have been published on the mortality of subjects with visual impairment caused by DR. RESEARCH DESIGN AND METHODS: We identified 34 men and 73 women living in northern Finland with visual impairment caused by DR on 31 December 1993. The median age of the subjects was 71 years (range 27-88). The mortality of these 107 diabetic subjects was followed up for 4 years, until 31 December 1997, and compared with the mortality rates of 3 age- and sex-matched control groups. The first control group consisted of subjects treated for DR by laser coagulation from 1990 to 1993. The second control group consisted of diabetic subjects who had had fundus photographs taken from 1991 to 1992. The third control group comprised nondiabetic subjects selected from the population register. Information on deaths was obtained from official death certificates. RESULTS: A total of 91 diabetic and 10 nondiabetic subjects died during the follow-up. Of the deaths, 51 occurred in the subjects with visual impairment caused by DR, with a 4-year mortality rate of 477/1,000 (95% CI 382-571/1,000). Mortality rates were 224/1,000 (145-303/1,000) for the diabetic subjects with retinopathy treated by laser coagulation; 150/1,000 (82-217/1,000) for the diabetic subjects who had undergone fundus photography; and 94/1,000 (46-165/1,000) for the nondiabetic subjects. Cardiovascular diseases were the underlying cause of death in 55% of the subjects with visual impairment. Nephropathy was mentioned as the immediate cause of death for only 10% of the subjects. Compared with the nondiabetic control subjects, the odds ratios (ORs) for all-cause mortality were 5.1 (2.6-11) in the diabetic subjects with visual impairment caused by DR, and 5.6 (2.1-19) for mortality caused by diseases of the circulatory system. The ORs for all-cause mortality were 2.4 (1.1-5.6) in the diabetic subjects with retinopathy treated by laser coagulation and 1.6 (0.68-4.0) in the diabetic subjects with fundus photographs taken. CONCLUSIONS: The survival of diabetic subjects with visual impairment caused by DR was poor. The high mortality rate was attributed mainly to cardiovascular diseases. Therefore, severe retinopathy proves to be a risk marker of cardiovascular death in diabetic patients.
Differences in the performance of commercially available 10-g monofilaments.
Authors: Booth J , Young M J
Published: March 2007

OBJECTIVE: This independent study was designed to determine the accuracy of 10-g monofilaments manufactured and supplied by popular commercial companies. RESEARCH DESIGN AND METHODS: A total of 160 new 10-g monofilaments (30 Semmes-Weinstein monofilaments [North Coast Medical], 30 Timesco/Sensory Testing Systems monofilaments, 50 Owen Mumford Neuropens, and 50 Bailey Instruments monofilaments) were tested using a calibrated load cell. Each monofilament was subjected to 10 mechanical bucklings of 10 mm while the load cell detected the maximum buckling force. Longevity testing was performed on a subset of the monofilaments by subjecting them to continuous compressions until the buckling force was <9 g. RESULTS: The accuracy of monofilaments to produce a buckling force of 10 g varies among manufacturers. Bailey Instruments and Owen Mumford filaments were the most accurate with 100% buckling within +/-1.0 g of 10 g. Only 70% of the Semmes-Weinstein monofilaments from North Coast Medical buckled within +/-1.0 g of 10 g. A total of 80% of Timesco filaments buckled at <8 g. Longevity tests on Bailey Instruments and Owen Mumford monofilaments demonstrated that 80% continued to buckle within 10% of 10 g after 100 compressions, but only 50% were within this range after 200 compressions. The maximum amount of recovery achieved in any monofilament occurred within 24 h. CONCLUSIONS: Monofilaments made by either Bailey Instruments or Owen Mumford are recommended for use in clinical practice. North Coast Medical monofilaments may operate differently in the U.S. because of different environmental conditions such as differences in humidity. Timesco/Sensory Testing Systems monofilaments were neither accurate enough nor Conformity European marked to recommend their use in the U.K. Longevity and recovery testing suggest that each monofilament will survive usage on approximately 10 patients before needing a recovery time of 24 h before further use.
Diabetes duration and cause-specific mortality in the Verona Diabetes Study.
Authors: Brun E , Nelson R G , Bennett P H , Imperatore G , Zoppini G , Verlato G , Muggeo M ,   Verona Diabetes Study
Published: March 2007

OBJECTIVE: To examine the 10-year mortality and effect of diabetes duration on overall and cause-specific mortality in diabetic subjects in the Verona Diabetes Study (VDS). RESEARCH DESIGN AND METHODS: Records from diabetes clinics, family physicians, and a drug consumption database were used to identify 5,818 subjects > or =45 years of age with type 2 diabetes who were alive and residing in Verona, Italy on 31 December 1986. Vital status of each subject was ascertained on 31 December 1996. Underlying causes of death were determined from death certificates. Death rates and death rate ratios (DRRs) were computed and standardized to the population of Verona in 1991. RESULTS: During the study, 2,328 subjects died; 974 deaths were attributable to cardiovascular disease, 517 to neoplasms, 324 to diabetes-related diseases, 134 to digestive diseases, 250 to other natural causes, and 48 to external causes. There were 81 subjects who died of unknown causes. Death rates from natural causes were higher in men than in women (DRR 1.4, 95% CI 1.2-1.5) and rose in both sexes with increasing duration of diabetes (P = 0.001). Among the natural causes of death, those for diabetes-related diseases were strongly related to diabetes duration (P = 0.001). a modest relationship with duration was also found for ischemic heart disease in men (P = 0.07). CONCLUSIONS: Cardiovascular disease was the principal cause of death among people with type 2 diabetes in the VDS. Rates for natural causes of death rose with increasing duration of diabetes. Deaths from diabetes-related diseases in both sexes and from ischemic heart disease in men were largely responsible for this increase.
Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group.
Authors: Rosenstock J , Park G , Zimmerman J ,   U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group
Published: March 2007

OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose. RESULTS: At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin. CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.
Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes.
Authors: Vuksan V , Stavro M P , Sievenpiper J L , Beljan-Zdravkovic U , Leiter L A , Josse R G , Xu Z
Published: March 2007

OBJECTIVE: We previously demonstrated that 3 g American ginseng (AG) reduced postprandial glycemia (PPG) in type 2 diabetic individuals. We investigated whether further reductions can be achieved with escalation of dose and time of AG administration. RESEARCH DESIGN AND METHODS: Ten type 2 diabetic patients (6 men, 4 women; age 63+/-2 years; BMI 27.7+/-1.5 kg/m2; HbA1c 7.3+/-0.3%) were randomly administered 0 g (placebo) or 3, 6, or 9 g ground AG root in capsules at 120, 80, 40, or 0 min before a 25-g oral glucose challenge. Capillary blood glucose was measured before ingestion of AG or placebo and at 0, 15, 30, 45, 60, 90, and 120 min from the start of the glucose challenge. RESULTS: Two-way analysis of variance (ANOVA) demonstrated that treatment (0, 3, 6, and 9 g AG) but not time of administration (120, 80, 40, or 0 min before the challenge) significantly affected PPG (P<0.05), with significant (P = 0.037) interaction for area under the curve (AUC). Pairwise comparisons showed that compared with 0 g (placebo), 3, 6, or 9 g significantly (P<0.05) reduced AUC (19.7, 15.3, and 15.9%, respectively) and incremental glycemia at 30 min (16.3, 18.4, and 18.4%, respectively), 45 min (12.5, 14.3, and 14.3%, respectively), and 120 min (59.1, 40.9, and 45.5%, respectively). However, pairwise comparisons showed no differences between the 3-, 6-, or 9-g doses and any of the times of administration. CONCLUSIONS: AG reduced PPG irrespective of dose and time of administration. No more than 3 g AG was required at any time in relation to the challenge to achieve reductions. Because these reductions included glycemia at the 2-h diagnostic end point, there may be implications for diabetes diagnosis and treatment.
Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin.
Authors: Bauman W A , Shaw S , Jayatilleke E , Spungen A M , Herbert V
Published: March 2007

OBJECTIVE: Of patients who are prescribed metformin, 10-30% have evidence of reduced vitamin B12 absorption. B12-intrinsic factor complex uptake by ileal cell surface receptors is known to be a process dependent on calcium availability Metformin affects calcium-dependent membrane action. The objective of this study was to determine the magnitude and mechanism of the reduction in serum vitamin B12 after metformin administration. RESEARCH DESIGN AND METHODS: A comparative study design was employed using 2 groups (metformin and control). A total of 21 patients with type 2 diabetes received sulfonylurea therapy; 14 of these 21 patients were switched to metformin. Monthly serum total vitamin B12 measurements and holotranscobalamin (holoTCII) (B12-TCII) were performed. After 3 months of metformin therapy, oral calcium supplementation was administered. RESULTS: Serial serum vitamin B12 determinations revealed a similar decline in vitamin B12 and holoTCII. Oral calcium supplementation reversed the metformin-induced serum holoTCII depression. CONCLUSIONS: Patients receiving metformin have diminished B12 absorption and low serum total vitamin B12 and TCII-B12 levels because of a calcium-dependent ileal membrane antagonism, an effect reversed with supplemental calcium.
Targets and reality: a comparison of health care indicators in the U.S. (Pittsburgh Epidemiology of Diabetes Complications Study) and Hungary (DiabCare Hungary).
Authors: Tabák A G , Tamás G , Zgibor J , Wilson R , Becker D , Kerényi Z , Orchard T J
Published: March 2007

OBJECTIVE: In the U.S., both primary care and specialist physicians share in the care of type 1 diabetic patients, often in an informal collaboration. In Hungary, however, type 1 diabetic patients are generally managed in special centralized diabetes units. These different treatment settings may lead to different health care practices and outcomes. To determine if this is true, diabetes care indicators and complications were compared across representative study populations from the 2 countries. RESEARCH DESIGN AND METHODS: The Pittsburgh Epidemiology of Diabetes Complications Study (EDC) is a prospective cohort of childhood-onset type 1 diabetic patients. DiabCare Hungary, a multicenter cross-sectional study, was developed for quality control purposes and provides a nationwide data set of diabetic patients. We identified 2 comparable populations (EDC, n = 416; DiabCare, n = 405) in terms of age (> or =14 years) and age at onset (<17 years). RESULTS: EDC patients were less likely to receive diabetes education (P<0.0001), see an ophthalmologist (P<0.0001), be treated by diabetologists (P<0.0001), or perform self-monitoring of blood glucose (P<0.0001). They were more likely to use conservative insulin regimens (i.e., 1-2 injections/day, P<0.0001) and have a higher glycated hemoglobin (P< 0.0001). DiabCare patients more often experienced severe hypoglycemia (P<0.01) and had a lower prevalence of proliferative retinopathy (P<0.0001), legal blindness (P<0.05), and albuminuria (> or =30 mg/day P<0.01). No significant differences in macrovascular complications were seen, although rates were generally low CONCLUSIONS: These data suggest that the 2 populations differ by their diabetes care practices, degree of glycemic control, and microvascular complication status.
Increased plasma levels of endothelin 1 and von Willebrand factor in patients with type 2 diabetes and dyslipidemia.
Authors: Seligman B G , Biolo A , Polanczyk C A , Gross J L , Clausell N
Published: March 2007

OBJECTIVE: Endothelial markers endothelin 1 (ET-1) and von Willebrand factor (vWF) were assessed in patients with type 2 diabetes and dyslipidemia and in patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS: In this case-control study, plasma ET-and vWF levels were measured by enzyme-linked immunosorbent assay in 35 normoalbuminuric type 2 diabetic patients with dyslipidemia (56+/-5 years), in 21 nondiabetic patients with hypercholesterolemia (52+/-7 years), and in 19 healthy control subjects (45+/-4 years). All of the individuals were normotensive and nonsmokers. Urinary albumin was measured by immunoturbidimetry. RESULTS: ET-1 levels were higher (P<0.0001) in type 2 diabetic dyslipidemic patients (1.62+/-0.73 pg/ml) than in both nondiabetic hypercholesterolemic patients (0.91+/-0.73 pg/ml) and control subjects (0.69+/-0.25 pg/ml). vWF levels were significantly increased (P = 0.02) in type 2 diabetic (185.49+/-72.1%) and hypercholesterolemic (163.29+/-50.7%) patients compared with control subjects (129.70+/-35.2%). In the multiple linear regression analysis. ET-1 was significantly associated (adjusted r2 = 0.42) with serum triglyceride levels (P<0.001), age (P<0.01), insulin sensitivity index (P<0.02), and albuminuria levels (P<0.04). vWF levels were associated (adjusted r2 = 0.22) with albuminuria (P<0.001), fibrinogen levels (P<0.02), and BMI (P<0.03). CONCLUSIONS: Compared with hypercholesterolemic patients, type 2 diabetic patients with dyslipidemia have increased levels of ET-1 and vWF which may indicate more pronounced endothelial injury. These findings appear to be related to components of the insulin resistance syndrome.
Relationship Between Electroneurographic Changes and Serum Ubiquitin Levels in Patients With Type 2 Diabetes
Authors: Akarsu Ersin , Pirim Ibrahim , Çapoğlu Ilyas , Deniz Orhan , Akçay Güngör , Ünüvar Necdet
Published: March 2007

OBJECTIVE— The aim of the present study was to investigate any relationship between serum ubiquitin levels and electroneurographic changes in peripheral nerves for patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS— The study involved 34 patients(19 men, 15 women; mean age 46 ± 13 years) with type 2 diabetes. Serum ubiquitin values were measured by sandwich enzyme-linked immunosorbent assay. Measurement of nerve conduction velocity (NCV) was performed on three motor(median, tibial, and peroneal) and three sensory (median, ulnar, and sural)nerves. The value of motor compound muscle action potential (CMAP) was obtained from the sum of median, tibial, and peroneal motor nerve amplitudes,and sensory compound nerve action potential (CNAP) was computed as the sum of median and ulnar sensory nerve amplitudes.

RESULTS— Patients with diabetes were divided into three groups: group 1 (n = 8) had normal electroneurography results, group 2 (n = 8) had slowed NCV, and group 3 (n = 18) had low values of motor CMAP and/or sensory CNAP as well as slowed NCV. Mean ubiquitin level in group 3 (20.4 ± 2.9 ng/dl) was significantly higher than that in group 1 (11.2 ± 1.1 ng/dl, t = 11.5, P <0.0001) and group 2 (13.2 ± 2.7 ng/dl, t = 5.9, P< 0.0001). Serum ubiquitin levels were inversely correlated with motor CMAP(r = -0.68) and sensory CNAP (r = -0.61) values.

CONCLUSIONS— The results of this study indicate that there could be a relationship between the diminished amplitudes of axons of the peripheral nerve and the increase in serum ubiquitin levels in patients with type 2 diabetes. Further studies are required to confirm this relationship.
Report of the Health Care Delivery Work Group
Authors: Glasgow Russell E. , Hiss Roland G. , Anderson Robert M. , Friedman Neal M. , Hayward Rodney A. , Marrero David G. , Taylor C. Barr , Vinicor Frank
Published: March 2007

As one of four work groups for the November 1999 conference on Behavioral Science Research in Diabetes, sponsored by the National Institute on Diabetes and Digestive and Kidney Diseases, the health care delivery work group evaluated the status of research on quality of care, patient-provider interactions, and health care systems' innovations related to improved diabetes outcomes. In addition, we made recommendations for future research. In this article, which was developed and modified at the November conference by experts in health care delivery, diabetes and behavioral science, we summarize the literature on patient-provider interactions, diabetes care and self-management support among underserved and minority populations, and implementation of chronic care management systems for diabetes. We conclude that, although the quality of care provided to the vast majority of diabetic patients is problematic, this is principally not the fault of either individual patients or health care professionals. Rather, it is a systems issue emanating from the acute illness model of care, which still predominates. Examples of proactive population-based chronic care management programs incorporating behavioral principles are discussed. The article concludes by identifying barriers to the establishment of a chronic care model(e.g., lack of supportive policies, understanding of population-based management, and information systems) and priorities for future research in this area needed to overcome these barriers.
Mealtime Glucose Regulation With Nateglinide in Healthy Volunteers
Authors: Kalbag Jyoti B. , Walter Yulia H. , Nedelman Jerry R. , McLeod James F.
Published: March 2007

OBJECTIVE— This study was designed to compare the pharmacodynamic effects of single doses of nateglinide (A-4166), repaglinide,and placebo on mealtime insulin secretion and glycemic control in healthy subjects.

RESEARCH DESIGN AND METHODS— Fifteen healthy volunteers participated in this open-label five-period crossover study. They received single 10-min preprandial doses of 120 mg nateglinide, 0.5 or 2 mg repaglinide, or placebo or 1 min preprandially of 2 mg repaglinide. Subjects received each dose only once, 48 h apart. Pharmacodynamic and pharmacokinetic assessments were performed from 0 to 12 h postdose.

RESULTS— Nateglinide induced insulin secretion more rapidly than 2 and 0.5 mg repaglinide and placebo (10 min preprandial), with mean rates of insulin rise of 2.3, 1.3, 1.15, and 0.8 μU ·ml-1 · min-1, respectively, over the 0- to 30-min postmeal interval. After peaking, insulin concentrations decreased rapidly in the nateglinide-treated group and were similar to placebo within 2 h postdose. After 2 mg repaglinide, peak insulin concentrations were delayed and returned to baseline more slowly than with nateglinide treatment. Nateglinide treatment produced lower average plasma glucose concentrations in the 0- to 2-h postdose interval than either dose of repaglinide and placebo (P < 0.05 vs. 0.5 mg repaglinide and placebo). Plasma glucose concentrations returned more rapidly to predose levels with nateglinide treatment than with either dose of repaglinide. Treatment with repaglinide produced a sustained hypoglycemic effect up to 6 h postdose.

CONCLUSIONS— In this single-dose study in nondiabetic volunteers, nateglinide provided a more rapid and shorter-lived stimulation of insulin secretion than repaglinide, resulting in lower meal-related glucose excursions. If similar results are observed in diabetes, nateglinide may produce a more physiological insulin secretory response with the potential for a reduced risk of postabsorptive hypoglycemia.
A Comparison of Two Diabetic Foot Ulcer Classification Systems
Authors: Oyibo Samson O. , Jude Edward B. , Tarawneh Ibrahim , Nguyen Hienvu C. , Harkless Lawrence B. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE— In this study, the following two ulcer classification systems were applied to new foot ulcers to compare them as predictors of outcome: the Wagner (grade) and the University of Texas (UT)(grade and stage) wound classification systems.

RESEARCH DESIGN AND METHODS— Ulcer size, appearance, clinical evidence of infection, ischemia, and neuropathy at presentation were recorded,and patients were followed up until healing or for 6 months.

RESULTS— Of 194 patients with new foot ulcers, 67.0% were neuropathic, 26.3% were neuroischemic, 1.0% were ischemic, and 5.7% had no identified underlying factors. Median (interquartile range [IQR]) ulcer size at presentation was 1.5 cm2 (0.6-4.0). Lower-limb amputations were performed for 15% of ulcers, whereas 65% healed [median (IQR) healing time 5(3-10) weeks] and 16% were not healed at study termination; 4% of patients died. Wagner grade (P < 0.0001), and UT grade (P <0.0001) and stage (P < 0.001) showed positive trends with increased number of amputations. For UT stage, the risk of amputation increased with infection both alone (odds ratio [OR] = 11.1, P <0.0001) and in combination with ischemia (OR = 14.7, P < 0.0001),but not significantly with ischemia alone (OR = 4.6, P = 0.09). Healing times were not significantly different for each grade of the Wagner(P = 0.1) or the UT system (P = 0.07), but there was a significant stepwise increase in healing time with each stage of the UT system(P < 0.05), and stage predicted healing (P <0.05).

CONCLUSIONS— Increasing stage, regardless of grade, is associated with increased risk of amputation and prolonged ulcer healing time. The UT system's inclusion of stage makes it a better predictor of outcome.
Evidence-Based Guidelines Meet the Real World
Authors: Larme Anne C. , Pugh Jacqueline A.
Published: March 2007

OBJECTIVE—Improving diabetes care in the U.S. is critical because diabetes rates are increasing dramatically, particularly among minority and low-income populations. Although evidence-based practice guidelines for diabetes have been widely disseminated, many physicians fail to implement them. The objective of this study was to explore what happens to diabetes practice guidelines in real-world clinical settings.

RESEARCH DESIGN AND METHODS—A qualitative research design was used. Open-ended semistructured interviews lasting 1–2 h were conducted with 32 key informants (physicians, certified diabetes educators, researchers, and agency personnel) selected for their knowledge of diabetes care in South Texas, an area with a high diabetes prevalence and a large proportion of minority and low-income patients.

RESULTS—Health professionals stress that contextual factors are more important barriers to optimal diabetes care than physician knowledge and attitudes. Barriers exist at multiple levels and are interrelated in a complex manner. Examples include the following: time constraints and practice economics in the private practice setting; the need to maintain referral relationships and maldistribution of professionals in the practice community; low awareness and low socioeconomic status among patients; and lack of access for low-income patients, low reimbursement, and insufficient focus on prevention in the U.S. health care system.

CONCLUSIONS—Contextual barriers must be addressed in order for diabetes practice guidelines to be implemented in real-world clinical practice. Suggested changes include an increased focus on prevention, improvements in health care delivery for chronic diseases, and increased attention to the special needs of minority and low-income populations.
Acute Hypoglycemia in Humans Causes Attentional Dysfunction While Nonverbal Intelligence Is Preserved
Authors: McAulay Vincent , Deary Ian J. , Ferguson Stewart C. , Frier Brian M.
Published: March 2007

OBJECTIVE—Experimentally induced hypoglycemia in humans causes progressive but reversible cognitive dysfunction, but it is not known to what extent neuropsychological tests index abilities of cognitive functioning that are important in everyday life. This study examines the effects of acute insulin-induced hypoglycemia on attention and intelligence in nondiabetic humans.

RESEARCH DESIGN AND METHODS—A hyperinsulinemic glucose clamp was used to achieve controlled euglycemia (4.50 [0.22] mmol/l) and hypoglycemia (blood glucose 2.59 [0.19] mmol/l) in 20 healthy volunteers. Subjects were studied on two occasions in a counterbalanced order. During each study condition, subjects completed parallel tests of cognitive function. Cognitive function was assessed by the Test of Everyday Attention and Raven’s Progressive Matrices.

RESULTS—Hypoglycemia induced a significant deterioration in tests sensitive to both visual and auditory selective attention. During hypoglycemia, attentional flexibility deteriorated and speed of information processing was delayed. Sustained attention was preserved and intelligence scores did not deteriorate during hypoglycemia.

CONCLUSIONS—During hypoglycemia, a significant deterioration occurs in attentional abilities, whereas fluid intelligence is preserved. On the basis of these results, it can be surmised that many complex attention tasks relevant to everyday life are impaired during moderate hypoglycemia.
Do Different Dimensions of the Metabolic Syndrome Change Together Over Time?
Authors: Maison Patrick , Byrne Christopher D. , Hales C. Nicholas , Day Nicholas E. , Wareham Nicholas J.
Published: March 2007

OBJECTIVE—The metabolic syndrome is a loosely defined cluster of cardiovascular risk factors including low HDL cholesterol, hypertriglyceridemia, glucose intolerance, and hypertension. Evidence for inclusion of these features in the syndrome has mostly come from cross-sectional studies, and a few studies have examined how the various factors change together over time.

RESEARCH DESIGN AND METHODS—We conducted a prospective population-based cohort study of 937 individuals aged 40–65 years who underwent oral glucose tolerance testing on two occasions at 4.5-year intervals. Changes in the components of the metabolic syndrome were analyzed by principal component analysis in the entire population and in a subgroup of 471 individuals who did not receive pharmaceutical therapy for hypertension and dyslipidemia.

RESULTS—Principal component analysis identified three independent factors in men: a blood pressure factor (systolic and diastolic blood pressure and BMI), a glucose factor (fasting and 120-min postload glucose, BMI, waist-to-hip ratio [WHR], and fasting insulin level), and a lipid factor (triglycerides and HDL cholesterol, BMI, WHR, and fasting insulin level). In women, an additional factor was identified, which included BMI, WHR, fasting insulin, and triglycerides. Analysis of the contribution of these variables to the different subdimensions indicated that BMI was the central feature of the syndrome in both sexes.

CONCLUSIONS—This analysis of change in the features of the metabolic syndrome over time provides evidence of the fundamental importance of obesity in the origin of this disorder.
Orthostatic Hypertension in Patients With Type 2 Diabetes
Authors: Yoshinari Mototaka , Wakisaka Masanori , Nakamura Udai , Yoshioka Maki , Uchizono Yuji , Iwase Masanori
Published: March 2007

OBJECTIVE—The prevalence and clinical importance of orthostatic hypertension (OHT) in diabetic patients has not been elucidated, in contrast to orthostatic hypotension, which is occasionally found in diabetic patients with autonomic neuropathy.

RESEARCH DESIGN AND METHODS—The prevalence and severity of orthostatic hypertension was investigated in 277 Japanese male patients with type 2 diabetes, including 90 hypertensive patients and 128 nondiabetic age-matched male subjects. Patients treated with antihypertensive drugs were excluded from the study. OHT was defined as an increase in diastolic blood pressure (DBP) from <90 to ≥90 mmHg and/or an increase in systolic blood pressure (SBP) from <140 to ≥140 mmHg after standing from supine position. Clinical profiles and several serum biochemical parameters were determined in addition to chest X-rays and electrocardiograms.

RESULTS—The prevalence of OHT in normotensive and hypertensive diabetic patients was significantly higher than in control subjects (12.8 vs. 1.8%, P < 0.01, for normotensive patients; 12.6 vs. 11.1%, not significant, for hypertensive patients). Orthostasis induced a mean increase of 6.8 ± 11.4 mmHg in SBP and 9.1 ± 5.2 mmHg in DBP in diabetic patients with OHT compared with those without OHT (−1.0 ± 9.0 and 3.8 ± 6.6 mmHg, respectively). Vibration sensation in the lower limb was reduced in diabetic patients with OHT, but the percent coefficient of variation of RR interval, cardio-to-thoracic ratio on chest X-ray, and serum triglyceride levels were higher in these patients compared with normotensive diabetic patients without OHT.

CONCLUSIONS—Orthostatic hypertension is a novel complication in normotensive diabetic patients and may associate with early stage neuropathy and development of sustained hypertension.
Functional Status of Persons With Diabetes-Related Lower-Extremity Amputations
Authors: Peters Edgar J.G. , Childs Michael R. , Wunderlich Robert P. , Harkless Lawrence B. , Armstrong David G. , Lavery Lawrence A.
Published: March 2007

OBJECTIVE—It is reasonable to predict that diabetes-related lower-extremity amputations have a detrimental impact on quality of life. However, we are unaware of any study in the medical literature describing the functional level of diabetic patients with amputations. The objective of this study was to evaluate amputations among diabetic patients and to determine the functional level of these patients with the Sickness Impact Profile (SIP).

RESEARCH DESIGN AND METHODS—We enrolled 124 patients with diabetes. Case subjects (n = 35) were defined as patients who had undergone amputation of the lower-extremity, and control subjects (n = 89) were defined as patients who had not undergone amputation. Study participants received a standard history and physical examination.

RESULTS—Both the physical dimension scores (33.5 ± 14.9 vs. 22.3 ± 14.7, P < 0.001) and the total SIP scores (27.6 ± 9.9 vs. 22.5 ± 10.3, P = 0.013) were significantly higher for amputees. However, the psychosocial dimension scores were not significantly different between case and control subjects (14.9 ± 8.9 vs. 15.2 ± 10.0, P > 0.05). Post hoc analysis showed that the group of patients who had undergone transtibial amputation had a significantly higher total impairment score than patients who had not undergone amputation (P = 0.039). This is in contrast to patients with toe or midfoot amputations, for whom total impairment scores were not significantly higher than those for the control subjects. Interestingly, bilateral amputees did not have significantly higher scores on either SIP dimension compared with unilateral amputees.

CONCLUSIONS—These findings exemplify the detrimental physical and psychosocial health status of patients with diabetes-related lower-extremity amputation.
Performance of Recommended Screening Tests for Undiagnosed Diabetes and Dysglycemia
Authors: Rolka Deborah B. , Narayan K. M. Venkat , Thompson Theodore J. , Goldman Dona , Lindenmayer Joann , Alich Kate , Bacall Darcy , Benjamin Evan M. , Lamb Betty , Stuart Dennis O. , Engelgau Michael M.
Published: March 2007

OBJECTIVE—To evaluate the performance, in settings typical of opportunistic and community screening programs, of screening tests currently recommended by the American Diabetes Association (ADA) for detecting undiagnosed diabetes.

RESEARCH DESIGN AND METHODS—Volunteers aged ≥20 years without previously diagnosed diabetes (n = 1,471) completed a brief questionnaire and underwent recording of postprandial time and measurement of capillary blood glucose (CBG) with a portable sensor. Participants subsequently underwent a 75-g oral glucose tolerance test; fasting serum glucose (FSG) and 2-h postload serum glucose (2-h SG) concentrations were measured. The screening tests we studied included the ADA risk assessment questionnaire, the recommended CBG cut point of 140 mg/dl, and an alternative CBG cut point of 120 mg/dl. Each screening test was evaluated against several diagnostic criteria for diabetes (FSG ≥126 mg/dl, 2-h SG ≥200 mg/dl, or either) and dysglycemia (FSG ≥110 mg/dl, 2-h SG ≥140 mg/dl, or either).

RESULTS—Among all participants, 10.7% had undiagnosed diabetes (FSG ≥126 or 2-h SG ≥200 mg/dl), 52.1% had a positive result on the questionnaire, 9.5% had CBG ≥140 mg/dl, and 18.4% had CBG ≥120 mg/dl. The questionnaire was 72–78% sensitive and 50–51% specific for the three diabetes diagnostic criteria; CBG ≥140 mg/dl was 56–65% sensitive and 95–96% specific, and CBG ≥120 mg/dl was 75–84% sensitive and 86–90% specific. CBG ≥120 mg/dl was 44–62% sensitive and 89–90% specific for dysglycemia.

CONCLUSIONS—Low specificity may limit the usefulness of the ADA questionnaire. Lowering the cut point for a casual CBG test (e.g., to 120 mg/dl) may improve sensitivity and still provide adequate specificity.
Monitoring of Psychological Well-Being in Outpatients With Diabetes
Authors: Pouwer François , Snoek Frank J. , van der Ploeg Henk M. , Adèr Herman J. , Heine Robert J.
Published: March 2007

OBJECTIVE—To investigate whether monitoring and discussing psychological well-being in outpatients with diabetes improves mood, glycemic control, and the patient’s evaluation of the quality of diabetes care.

RESEARCH DESIGN AND METHODS—This study was a randomized controlled trial of 461 outpatients with diabetes who were randomly assigned to standard care or to the monitoring condition. In the latter group, the diabetes nurse specialist assessed and discussed psychological well-being with the patient (with an interval of 6 months) in addition to standard care. The computerized Well-being Questionnaire was used for this purpose. Primary outcomes were mood, HbA1c, and the patient’s evaluation of the quality of diabetes care at 1-year follow-up. The number of referrals to the psychologist was analyzed as a secondary outcome. Intention-to-treat analysis was used.

RESULTS—The monitoring group reported better mood compared with the standard care group, as indicated by significantly lower negative well-being and significantly higher levels of energy, higher general well-being, better mental health, and a more positive evaluation of the quality of the emotional support received from the diabetes nurse. The two groups did not differ for HbA1c or in their overall evaluation of the quality of diabetes care. In the monitoring condition, significantly more subjects were referred to the psychologist.

CONCLUSIONS—Monitoring and discussing psychological well-being as part of routine diabetes outpatient care had favorable effects on the mood of patients but did not affect their HbA1c. Our results support the recommendation to monitor psychological well-being in patients with diabetes.
Relation Between Soluble Adhesion Molecules and Insulin Sensitivity in Type 2 Diabetic Individuals
Authors: Targher Giovanni , Bonadonna Riccardo C. , Alberiche Maria , Zenere Marina B. , Muggeo Michele , Bonora Enzo
Published: March 2007

OBJECTIVE—The purpose of this study was to explore the relation between insulin resistance and plasma levels of soluble adhesion molecules and to examine the effects of acute hyperinsulinemia on these molecules in type 2 diabetic individuals.

RESEARCH DESIGN AND METHODS—Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E- and P-selectin plasma concentrations were measured in 36 nonobese type 2 diabetic patients without cardiovascular disease and in 7 healthy subjects. Insulin sensitivity was assessed by a 4-h euglycemic (∼5 mmol/l)-hyperinsulinemic (∼300 pmol/l) clamp performed in combination with [3H]3-d-glucose infusion.

RESULTS—Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than control subjects. In diabetic subjects, plasma ICAM-1 and E-selectin were negatively correlated with total glucose disposal during the insulin clamp (r = −0.432, P < 0.01; and r = −0.375, P < 0.05, respectively), whereas plasma VCAM-1 and P-selectin were not. Plasma ICAM-1 as well as E- and P-selectin were positively correlated with BMI, total body fat (TBF), and waist girth (P < 0.05–0.001). In multiple regression analyses, the relation of plasma ICAM-1 and E-selectin with insulin sensitivity was lost after adjustment for potential confounders, including HbA1c, blood pressure, and/or LDL cholesterol. In these analyses, BMI was the only independent predictor of plasma ICAM-1 (R2 = 0.244, P < 0.002), whereas TBF was the only independent predictor of plasma E-selectin (R2 = 0.202, P = 0.01). The 4-h insulin infusion during the glucose clamp did not significantly change plasma levels of adhesion molecules.

CONCLUSIONS—Overall adiposity, rather than insulin resistance, may be a determinant of plasma levels of ICAM-1 and E-selectin in type 2 diabetic individuals. In these patients, acute hyperinsulinemia does not exert any significant effect on plasma adhesion molecules. These findings support the possibility that adipose tissue releases one or more factors that may adversely affect endothelial function on one hand and insulin sensitivity on the other.
Effects of Low Birth Weight on Insulin Resistance Syndrome in Caucasian and African-American Children
Authors: Li Chaoyang , Johnson Maria S. , Goran Michael I.
Published: March 2007

OBJECTIVE—To examine the effects of low birth weight (LBW) on the components of insulin resistance syndrome (IRS) in Caucasian and African-American children aged 4–14 years (n = 560 observations among 139 subjects).

RESEARCH DESIGN AND METHODS—A linear random-effects modeling analysis with repeated measures (average four annual visits per child) was conducted to examine the associations between LBW and the components of IRS and their developmental trends over age. Fasting glucose, insulin, and lipids were assessed after an overnight fast; insulin action and secretion were determined by the tolbutamide-modified frequently sampled intravenous glucose tolerance test; and body composition was assessed by dual energy X-ray absorptiometry and computed tomography.

RESULTS—LBW was significantly associated with increased fasting insulin concentration and visceral fat mass, decreased acute insulin response, β-cell function, and HDL cholesterol among African-American children. Among children with LBW, there were significant differences in fasting insulin, insulin sensitivity, acute insulin response, and HDL cholesterol between Caucasians and African-Americans. LBW was significantly associated with faster decrease in acute insulin response and increase in triglycerides with regard to age. The hyperbolic function between insulin sensitivity and β-cell function was retarded among children with LBW (P = 0.04). In addition, there was a significant interaction between LBW and ethnicity in relation to fasting insulin (P < 0.05) and visceral fat (P = 0.05).

CONCLUSIONS—LBW may predict the risk of the IRS and its progression over age in childhood, and this effect may be more pronounced among African-American children.
Differing Associations of Lipid and Lipoprotein Disturbances With the Macrovascular and Microvascular Complications of Type 1 Diabetes
Authors: Chaturvedi Nish , Fuller John H. , Taskinen Marja-Riitta ,   On behalf of the EURODIAB PCS Group
Published: March 2007

OBJECTIVE—Cardiovascular disease (CVD) is increased in patients with type 1 diabetes, but lipid and lipoprotein patterns remain favorable. In contrast, nephropathy is associated with an adverse distribution. We compared the associations and predictive power of lipid and lipoprotein disturbances with these complications.

RESEARCH DESIGN AND METHODS—A nested case-control study from the EURODIAB cohort of 140 case subjects with evidence of at least one complication and 84 control subjects with no complications were analyzed. Conventional and unconventional lipid and lipoprotein fractions, including apolipoprotein (apo)-A1, lipoprotein (Lp)-A1, LpA1/A2, apoB, and LDL particle size were measured centrally.

RESULTS—CVD was only associated with increased LDL cholesterol (3.6 vs. 3.0 mmol/l, P = 0.02). In contrast, albuminuria was associated with elevated cholesterol, triglyceride, LDL, and apoB and with diminished LDL particle size. No disturbances in HDL and related lipoproteins were noted. In normoalbuminuric patients, CVD was not associated with any significant changes in lipids. CVD in macroalbuminuric patients was associated with increased triglyceride level (2.37 vs. 1.07 mmol/l, P = 0.001; P = 0.02 for CVD/albuminuria interaction) and LDL cholesterol (5.4 vs. 3.3 mmol/l, P = 0.005; P = 0.004 for interaction). Independent associations were observed for total cholesterol and for LDL particle size and albuminuria.

CONCLUSIONS—Abnormalities in lipid and lipoprotein disturbances are more closely related to albuminuria than to CVD in patients with type 1 diabetes. Measurement of conventional parameters provide sufficient risk information. ApoB and LDL particle size offer limited extra information. HDL metabolism remains undisturbed in the presence of complications. These changes reflect associations with glycemic control, which is the key to understanding lipid and lipoprotein disturbances.
Use of Insulin Pumps in Pregnancies Complicated by Type 2 Diabetes and Gestational Diabetes in a Multiethnic Community
Authors: Simmons David , Thompson Colin F. , Conroy Caroline , Scott David J.
Published: March 2007

OBJECTIVE—To describe the use of insulin pump therapy in women with gestational diabetes mellitus (GDM) or type 2 diabetes in pregnancy and persistent hyperglycemia despite multiple injections of subcutaneous insulin.

RESEARCH DESIGN AND METHODS—As part of a service audit, deliveries to women with diabetes at a single South Auckland hospital were reviewed from 1991 through 1994. Glycemic control was estimated by the mean of self-recorded and laboratory postprandial glucose concentrations. In a nested case-control study, pregnancies complicated by GDM/type 2 diabetes with use of an insulin pump were compared with those without insulin pump therapy and peak insulin requirements of 100–199 units/ day, matched for ethnicity and type of diabetes.

RESULTS—A total of 30 of 251 Polynesian, European, and South Asian women with singleton pregnancies complicated by insulin-requiring GDM/type 2 diabetes used an insulin pump. An additional two women with high insulin requirements discontinued pump therapy. None of the women with GDM/type 2 diabetes experienced severe hypoglycemia, whereas 79% of the women had improved glycemic control within 1–4 weeks. Mothers using a pump had greater insulin requirements (median maximum 246 vs. 130 units per day) and greater weight gain (10.6 vs. 5.0 kg). Their babies were more likely to be admitted to the Special Care Baby Unit but were neither significantly heavier nor experienced greater hypoglycemia than control subjects.

CONCLUSIONS—Insulin pump therapy seems to be safe and effective for maintaining glycemic control in pregnancies complicated by GDM/type 2 diabetes and requiring large doses of insulin.
Two-Field Photography Can Identify Patients With Vision-Threatening Diabetic Retinopathy
Authors: Stellingwerf Catharina , Hardus Peter L.L.J. , Hooymans Johanna M.M.
Published: March 2007

OBJECTIVE—To compare the effectiveness of two 45° photographic fields per eye in the screening for diabetic retinopathy with the routine ophthalmologist’s examination and to study the effectiveness of visual acuity measurement in the detection of diabetic macular edema.

RESEARCH DESIGN AND METHODS—Type 1 and 2 diabetic patients without a known history of more than minimal retinopathy (n = 469) had a routine examination by an ophthalmologist, including visual acuity measurement, indirect retinoscopy, and biomicroscopy. At the same time, two-field nonstereoscopic retinal photographs were made of both eyes and assessed in a masked fashion by a retinal specialist. The results were compared.

RESULTS—The prevalence was 4.3% for vision-threatening retinopathy and 24% for any retinopathy. The sensitivity of two-field photography in identifying diabetic patients with sight-threatening retinopathy was 95% (specificity 99%) and sensitivity for detecting any retinopathy was 83% (specificity 88%). The percentage of referrals to an ophthalmologist was 6.2%. All patients with macular edema detected by biomicroscopy were classified as having vision-threatening retinopathy on the photographs.

CONCLUSIONS—Two-field retinal photography is a promising alternative to the routine ophthalmologist’s examination in the screening for diabetic retinopathy. Visual acuity measurement is not a sensitive tool for the detection of macular edema. Screening for diabetic retinopathy using two-field retinal photography is feasible in a primary care setting and can substantially lower the number of ophthalmic referrals.