bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibratory and Cooling Detection Thresholds Compared With Other Tests in Diagnosing and Staging Diabetic Neuropathy
Authors: Dyck Peter James , Bushek Wilfred , Spring Eileen M , Karnes Jeannine L , Litchy William J , O'Brien Peter C , Service F John
Published: March 2007

Increasingly more tests are being used to detect and characterize diabetic polyneuropathy, but their value in setting minimal criteria for the diagnosis of neuropathy and for staging severity remains inadequately studied. In 180 diabetics, we compared the percentage of patients with test abnormalities and associations among test results, evaluating neuropathic symptoms [neuropathy symptom score (NSS) and neuropathy scale of neuropathy symptom profile (NNSP)], deficits [neurologic disability score (NDS) and vibratory (VDT) and cooling (CDT) detection thresholds], or nerve dysfunction [nerve conduction (NC)]. The percentage of patients that were abnormal varied considerably depending on criteria for abnormality and the tests used. Abnormality (≥ 3 SD of 1 or more parameters) of NC of one or more of four nerves occurred in 80%, of two or more in 69%, of three or more in 46%, and of four in 21%. Similarly, for other tests, the rate of abnormality decreased with use of increasingly stringent criteria. Setting the criteria for abnormal NC at abnormality of two or more nerves, NSS at ≥ 1, NDS at > 6, NNSP at ≥ 97.5th percentile, and at ≥ 95th percentile for the other tests, NC was abnormal in 69%, NSS in 54%, NDS in 48%, NNSP in 47%, VDT in 44%, and CDT in 35%. Abnormality of any two or more of the six tests evaluated occurred in 64% of patients. We estimated that at least 16% of patients without abnormal NC (<2 abnormal nerves) had other findings indicative of neuropathy. By regression analysis, results of one test were in almost all cases associated with those of another test, but the association was not close enough to be predictive. Therefore, although NC provides objective and repeatable results, symptoms and deficits must be measured independently. Assuming no differences between groups of patients, the standardized and validated test (NNSP, VDT, or CDT) should provide the same results at different medical centers. By contrast, the results of NSS or NDS tests, with less standardized approaches and based on the judgment of physicians, might not provide the same results at different medical centers. Tests such as the ones described here may be used to define minimal criteria for the diagnosis of polyneuropathy and for staging its severity.
Glyburide Decreases Insulin Requirement, Increases (β-Cell Response to Mixed Meal, and Does Not Affect Insulin Sensitivity: Effects of Short- and Long-Term Combined Treatment in Secondary Failure to Sulfonylurea
Authors: Gutniak Mark , Karlander Sven-Gunnar , Efendić Suad
Published: March 2007

In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1–18 and 78–85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long-lasting improvement of metabolic control: HbA1c decreased from 11.1 ± 0.3% on day 3 to 8.3 ± 0.4% (P < .001) on day 78 and 9.1 ± 0.5% (P < .001) on day 325. In subjects on IP, the corresponding values were 10.3 ± 0.5, 8.4 ± 0.4 (P < .001), and 8.9 ± 0.5% (P < .05). Body weight increased by 6.0 ± 1.5 kg (P < .005) on IG and 2.9 ± 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 ± 12.9 U/day on day 7 to 33.5 ± 8.8 U/ day on day 83 and 34.6 ± 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 ± 10.7 U/day on day 7, 55.5 ± 7.7 U/day on day 83, and 54.7 ± 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin ≈130 μU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal- but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented.
Evaluating Clinical Accuracy of Systems for Self-Monitoring of Blood Glucose
Authors: Clarke William L , Cox Daniel , Gonder-Frederick Linda A , Carter William , Pohl Stephen L
Published: March 2007

Although the scientific literature contains numerous reports of the statistical accuracy of systems for self-monitoring of blood glucose (SMBG), most of these studies determine accuracy in ways that may not be clinically useful. We have developed an error grid analysis (EGA), which describes the clinical accuracy of SMBG systems over the entire range of blood glucose values, taking into account 1) the absolute value of the system-generated glucose value, 2) the absolute value of the reference blood glucose value, 3) the relative difference between these two values, and 4) the clinical significance of this difference. The EGA of accuracy of five different reflectance meters (Eyetone, Dextrometer, Glucometer I, Glucometer II, Memory Glucometer II), a visually interpretable glucose reagent strip (Glucostix), and filter-paper spot glucose determinations is presented. In addition, reanalyses of a laboratory comparison of three reflectance meters (Accucheck II, Glucometer II, Glucoscan 9000) and of two previously published studies comparing the accuracy of five different reflectance meters with EGA is described. EGA provides the practitioner and the researcher with a clinically meaningful method for evaluating the accuracy of blood glucose values generated with various monitoring systems and for analyzing the clinical implications of previously published data.
Fingerstick Glycosylated Hemoglobin, Plasma Protein, and Albumin
Authors: Rendell Marc , Brannan Carol , Nierenberg Julia , Rasbold Kathy , Hestorff Tim
Published: March 2007

We have developed techniques that permit the affinity-chromatographic determination of glycosylated hemoglobin, plasma protein, and albumin on fingerstick samples of whole blood. The fingerstick glycohemoglobin technique takes advantage of the high sensitivity of measurement of hemoglobin by absorbance at 414 nm. The glycosylated plasma protein is assayed by a highly sensitive method based on binding of Coomassie blue. An enzyme-linked immunosorbent assay is used to measure albumin in the bound and nonbound fractions of an aminophenylboronic acid chromatographic separation. The fingerstick method for assay of glycosylated plasma albumin gives results that are ∼40% higher than comparable values obtained on the same patient with a 1-ml plasma sample determined with the bromcresol green technique. There is good correlation of fingerstick glycoalbumins with fingerstick glycohemoglobins and glycosylated plasma protein values. These procedures should be useful for children and for large-scale ambulatory screening for diabetes mellitus.
Glyburide and Glipizide in Treatment of Diabetic Patients With Secondary Failures to Tolazamide or Chlorpropamid
Authors: Lev Jeffrey D , Zeidler Adina , Kumar Dinesh
Published: March 2007

We evaluated therapeutic usefulness of the second-generation sulfonylurea agents glyburide and glipizide in non-insulin-dependent diabetic patients who were secondary failures on chlorpropamide or tolazamide. Twenty patients were treated with glyburide, and 10 of them were subsequently treated with glipizide. Fasting and postprandial serum glucose, insulin, C-peptide, glycosylated hemoglobin, urinary C-peptide, and glucose levels all failed to show significant improvement. We conclude that both glyburide and glipizide proved ineffective in the treatment of secondary failures to first-generation sulfonylureas.
Early Loss of Blue-Sensitive Color Vision in Patients With Type I Diabetes
Authors: Daley Michael L , Watzke Robert C , Riddle Matthew C
Published: March 2007

Existing methods for early detection of ocular injury from diabetes have serious limitations. We describe a new method, measuring visual flicker discrimination of the blue-sensitive mechanism of vision. This method is noninvasive, quantitative, and capable of distinguishing two types of impairment. Blueflicker discrimination was measured in 10 adults with type I (insulin-dependent) diabetes for <5 yr. Although no evidence of diabetic changes was detected by careful ophthalmic examination by an experienced ophthalmologist, 12 of 19 eyes (63%) had flicker discrimination scores considered abnormal in comparison with those of a control group, and 8 of 10 subjects (80%) had at least 1 eye with abnormal performance. In all but 2 abnormal eyes the deficit of blue-flicker discrimination was of the “absorptive” type, suggesting increased absorbance or scattering of blue light in the optical media. These data show that a functional impairment of vision can be measured very early in the course of type I diabetes, before visible retinopathy is present, and suggest this test procedure may have both investigative and clinical applications.
Chronic and Remitting Painful Diabetic Polyneuropathy: Correlations With Clinical Features and Subsequent Changes in Neurophysiology
Authors: Young Robert J , Ewing David J , Clarke Basil F
Published: March 2007

Twenty-nine diabetic patients (19 men, 10 women) aged 19–71 yr with newly developed painful polyneuropathy were studied prospectively for 12–18 mo. Pain remitted completely in 16 patients within 12 mo, but continued in the other 13 patients. At presentation, no differences were found in the type or prevalence of symptoms or neurophysiological measurements (electrophysiology and cardiovascular autonomic function tests) between the patients whose pain remitted and those whose pain continued. Most electrophysiological measurements improved slightly in remitting patients but deteriorated slightly in those whose pain continued to reveal a significant difference (P < .05) between the groups on final review. Similarly, abnormal autonomic nerve function improved slightly when pain remitted but worsened or persisted in patients whose pain continued, again revealing a significant difference between the groups (P < .05) on final review. We also observed that pain remission usually occurred if the onset of symptoms shortly followed some sudden metabolic change (e.g., rapid improvement in glycemic control, ketoacidosis, anorexia nervosa) when the duration of diabetes was relatively short or when considerable weight loss preceded the onset of pain. We suggest that remitting and chronic painful diabetic polyneuropathy have distinctive clinical features at presentation and detectable neurophysiological differences during their symptomatic evolution.
Perioperative Management of Diabetic Subjects: Subcutaneous Versus Intravenous Insulin Administration During Glucose-Potassium Infusion
Authors: Pezzarossa Antonio , Taddei Francesco , Cimicchi M Cristina , Rossini Elisabetta , Contini Sandro , Bonora Enzo , Gnudi Angelo , Uggeri Enzo
Published: March 2007

The purpose of this study was to validate methods for the perioperative management of diabetic patients that meet the prerequisites of simplicity, applicability in the absence of a diabetologist, and flexibility, to rapidly meet changing metabolic requirements. The patients were divided into two groups that were comparable for age, sex distribution, type of diabetes, and type of surgical procedures. The results show that intravenous insulin administration achieved better glycemic control during the intraoperative period, whereas it did not offer advantages over the subcutaneous route during the pre- and postoperative periods. The satisfactory degree of steady glycemic control achieved and the absence of hypoglycemic episodes indicate that the separate administration of insulin and glucose plus electrolytes is an effective and safe management modality for diabetic patients undergoing major surgery.
Etiology and Prevalence of Hypertension in Diabetic Patients
Authors: Simonson Donald C
Published: March 2007

Data from several epidemiologic studies have suggested that the prevalence of hypertension in patients with diabetes mellitus is ∼1.5–2.0 times greater than in an appropriately matched nondiabetic population. In patients with insulin-dependent diabetes mellitus (IDDM), hypertension is generally not present at the time of diagnosis. As renal insufficiency develops, blood pressure rises and may exacerbate the progression to end-stage renal failure. In non-insulin-dependent diabetes mellitus (NIDDM), many patients are hypertensive at the time of diagnosis. The incidence of hypertension in NIDDM is related to the degree of obesity, advanced age, and extensive atherosclerosis that is typically present, and it probably includes many patients with essential hypertension. Several other pathophysiologic mechanisms also contribute to the genesis and maintenance of hypertension in the patient with diabetes. Hyperglycemia and increases in totalbody exchangeable sodium may lead to extracellular fluid accumulation and expansion of the plasma volume. In some patients, alterations in the function of the renin-angiotensin-aldosterone system and vascular sensitivity to vasoactive hormones may also play a role. It has recently been suggested that hyperinsulinemia and insulin resistance may also contribute to the maintenance of an elevated blood pressure because insulin is known to promote sodium retention and enhance sympathetic nervous system activity. The evidence for these hypotheses and their respective contributions to the etiology of hypertension in IDDM and NIDDM are discussed.
Treatment of Hypertensive Diabetic Patients
Authors: Tuck Michael
Published: March 2007

This article briefly reviews the literature on the incidence of hypertension in the diabetic population, the risks associated with this combination of conditions, and the nonpharmacologic and other therapies available to lower blood pressure in these patients. Although several studies of nonpharmacologic therapies and diuretics are considered, the emphasis is on the reported advantages and disadvantages of β-blockers, centrally acting agents, α-adrenergic-blocking agents, calcium-channel blockers, and angiotensin-converting enzyme inhibitors.
Use of Alternative Sweeteners in Diabetic Diet
Authors: Crapo Phyllis A
Published: March 2007

Alternative sweeteners are widely advocated and used. However, there is insufficient scientific information to determine whether alternative sweeteners are of value in the management of diabetes, either in improving dietary adherance or in contributing to the achievement or maintenance of a lower body weight. Each of the available sweeteners has advantages and disadvantages; no one is preferred. Recommendations about alternative-sweetener use should be tailored to the specific dietary and life-style patterns of the individual.
Role and Management of Exercise in Diabetes Mellitus
Authors: Horton Edward S
Published: March 2007

Asmore is understood about the physiology of exercise, in both normal and diabetic subjects, its role in the treatment of diabetes is becoming better defined. Whereas people with diabetes may derive many benefits from regular physical exercise, there are also several hazards that make exercise difficult to manage. In type I (insulin-dependent) diabetes, there are risks of hypoglycemia during or after exercise or of worsening metabolic control if insulin deficiency is present. Type II (non-insulin-dependent) diabetic patients treated with sulfonylureas are also at some increased risk of developing hypoglycemia during or after exercise, although this poses less of a problem than with insulin treatment. In individuals treated by diet alone, regulation of blood glucose during exercise is usually not a significant problem and exercise can be used as an adjunct to diet to achieve weight loss and improved insulin sensitivity. When obese type II diabetic patients are treated with very low calorie diets, adequate amounts of carbohydrate must be provided to ensure maintenance of normal muscle glycogen content, particularly if individuals wish to participate in highintensity exercise that places a heavy workload on specific muscle groups. On the other hand, moderateintensity exercise such as vigorous walking can be tolerated by individuals on very low calorie, carbohydrate-restricted diets after an appropriate period of adaptation. A number of strategies can be employed to avoid hypoglycemia in type I diabetic patients, and both type I and II diabetic patients should be examined carefully for long-term complications of their disease, which may be made worse by exercise. These considerations have led many diabetologists to consider exercise beneficial in the management of diabetes for some individuals but not recommended for everyone as a necessary part of diabetes treatment as in the past. The goals should be to teach patients to incorporate exercise into their daily lives if they wish and to develop strategies to avoid the complications of exercise. The rationale for the use of exercise as part of the treatment program in type II diabetes is much more clear than for type I diabetes; regular exercise may be prescribed as an adjunct to caloric restriction for weight reduction and as a means to improve insulin sensitivity in the obese insulin-resistant individual.
Glucose Intolerance as Contributor to Noncommunicable Disease Morbidity and Mortality: WHO Integrated Program for Community Health in Noncommunicable Diseases
Authors: Grabauskas VJ
Published: March 2007

The World Health Organization (WHO) has considerable evidence that several interrelated factors (e.g., smoking, hypertension, cholesterol, and obesity) contribute to total mortality. Data are presented documenting that glucose intolerance is also a risk factor for total mortality, as well as for cancer and cardiovascular mortality. The Kaunas-Rotterdam Intervention Study, which documented glucose tolerance and mortality in a cohort of men, shows a linear increase in total mortality with increasing blood glucose levels. By use of multiple logistic regressions, glucose was shown to be a significant risk factor (c = .2534, t = 4. 0) for total mortality. A paradigm is presented in which diabetes is placed as a disease and glucose intolerance as a risk factor within the total scheme for the development of noncommunicable diseases. The WHO action plan for integrated programs in noncommunicable diseases is discussed. The program expands on the experience gained by WHO investigators in community programs and proposes a cooperative effort globally in community-based programming.
Stability of Reacted Chemstrip bG
Authors: Cox Daniel , Herrman Jana , Snyder Andrea , Gonder-Frederick Linda , Reschke Jill , Clarke William
Published: March 2007

Reacted Chemstrip bG glucose reagent strips have been reported to retain their color changes for up to 7 days. Thus, patients could theoretically measure their blood glucose and mail their reacted test strips to their physicians for reanalysis. To test the stability of reacted Chemstrip bG blood glucose measurements, 268 Chemstrip bG test strips were reacted with blood obtained from 67 insulin-dependent diabetic patients, stored in desiccator vials, and read daily for 5 consecutive days with an Accu-Chek II blood glucose meter. Although Chemstrip bG blood glucose values significantly correlated with initial reference Beckman glucose analyzer glucose determinations for all 5 days, a steady significant decay in blood glucose readings over time was observed, and clinically accurate strip readings declined from 94% to 68%. Because this decay appeared consistent, correction factors were calculated with regression analyses. The correction factor for day 5 Accu-Chek II readings reduced measurement error by 77%. When applied to a different validation sample, this correction factor decreased day 5 error by 73%. Hence, it seems that correction factors may be applied to delayed readings of Chemstrips obtained with Accu- Chek II that would correct for the observed reduction in blood glucose readings. From these results, we conclude that delayed readings of Chemstrip bG test strips with the Accu-Chek II are not sufficiently accurate for clinical decision making or research purposes unless mathematically corrected.
Significance of High HbA1 Levels in Normal Glucose Tolerance
Authors: Modan Michaela , Meytes Dina , Rozeman Paul , Yosef Shaul Ben , Sehayek Ephraim , Yosef Nurit Ben , Lusky Ayala , Halkin Hillel
Published: March 2007

The significance of high hemoglobin A1 (HbA1) levels (≥8.0%) found in 12.1% of 648 individuals with normal glucose tolerance constituting a part of a representative population sample was examined. Measurement error in HbA1 and/or glucose-tolerance levels was precluded by HbA1 remaining in the same range over 3.5 yr in 89.7% of 29 individuals with initially high and 68.1% of 22 individuals with initially low (<6.5%) HbA1. Rate of deterioration to glucose intolerance (6.9%) in the high group during that period resembled the rate (11.8%) in a control group (n = 279). Fasting plasma glucose significantly accounted for only 2.4% of total HbA1 - population variance. No correlation of HbA1 was found with other correlates of glucose tolerance or with daily caloric intake and physical activity. A small but significant increment in HbA1 was associated with smoking (7.1 vs. 6.8%, P < .01) and with clinically overt atherosclerosis (7.3 vs. 6.9%, P < .01). We conclude that factors unrelated to glucose metabolism are the main determinants of HbA1 level in normal glucose tolerance and play an important role in diabetes as well. These factors have bearing on evaluation of diabetic control by HbA1 and possibly on risk for diabetic complications.
Specific Assessments of Warm and Cool Sensitivities in Adult Diabetic Patients
Authors: Sosenko Jay M , Kato Marta , Soto Ramon A , Gadia Maria T , Ayyar D Ram
Published: March 2007

We have specifically examined warm and cool sensitivities in 60 diabetic and 43 nondiabetic individuals. Diabetic patients tended to have less warm and cool sensitivity than the control subjects (P < .001 for age <50 yr and P <.05 for age ≥50 yr). Both patients asymptomatic for neuropathy and patients with symptoms had impairment of warm and cool sensitivity (P < .05 for comparisons with control subjects). These differences persisted (P < .05) in covariance analyses with age included as a covariate. There was a nonlinear association between warm sensitivity and hemoglobin A1c. Warm-sensitivity values in the lowest and middle tertiles of the hemoglobin A1c distribution were similar; however, warm-sensitivity values of patientsin the highest tertile were markedly increased (P < .05 for the comparison of the highest tertile with the lowest and middle tertiles combined)There tended to be more warm insensitivity than cool insensitivity among the diabetic patients, and this difference increased with worsening glycemia. These data indicate that both warm and cool sensations are markedly impaired in asymptomatic adult diabetic patients. They also suggest that warm sensitivity is more impaired than cool sensitivity, and that this is the result of a stronger association between warm sensitivity and metabolic factors.
Potent Mental Stress and Insulin Absorption in Normal Subjects
Authors: Fernqvist Eva , Linde Birgitta
Published: March 2007

Effects of mental stress (a 20-min modified Stroop's color-word conflict test; CWT) on the absorption of 12Sl-labeled soluble human insulin (10 U s.c. in the thigh 60 min before CWT) and on subcutaneous adipose tissue blood flow (ATBF; 133Xe clearance); heart rate (HR); arterial blood pressure (BP); and arterial levels of epinephrine (Epi), norepinephrine (NE), and glycerol were studied in 11 healthy subjects. Insulin absorption was measured as elimination of radioactivity (external ycounting) and as appearance of plasma immunoreactive insulin (IRI). The glucose-clamp technique was used to maintain normoglycemia. Identical measurements were performed during a control day without CWT. HR and mean BP increased markedly (35 ± 5 beats/min and 30 ± 3 mmHg) during CWT despite only minor elevations in plasma catecholamines. Thus, arterial plasma Epi rose from 0.18 ± 0.03 to 0.82 ± 0.17 nM (P < .01) and NE from 0.94 ± 0.09 to 1.69 ± 0.18 nM (P < .001). ATBF showed a biphasic response, with a 100% elevation during CWT followed by a decrease and a second peak of similar magnitude ∼0.5 to 1 h after CWT. Blood glycerol was approximately doubled during CWT and remained elevated during recovery. Despite these changes, insulin absorption was unaltered during and after stress. Thus, elimination rates of 125I, plasma IRI levels, and amounts of glucose needed to maintain normoglycemia were all similar during the stress and control days. These results suggest that absorption of soluble insulin from subcutaneous injection sites in the thigh is unaltered during potent mental stress in healthy subjects despite a considerable and prolonged increase in ATBF.
Major malformations in Infants of IDDM Women: Vasculopathy and Early First-Trimester Poor Glycemic Control
Authors: Miodovnik Menachem , Mimouni Francis , Dignan Peter St John , Berk Michael A , Ballard Jeanne L , Siddiqi Tariq A , Khoury Jane , Tsang Reginald C
Published: March 2007

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of <100 mg/dl and a 90-min postprandial blood glucose of <140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%). By both univariate and multivariate analyses, the following two factors were significantly associated with major CMs: preexisting vasculopathy (retinopathy and/or nephropathy; 54 vs. 25% in the CM and non-CM groups, respectively; P < .05) and increased maternal HbA, at 9 wk gestation (P < .001). CMs were not associated with White class, insulin requirements, and frequency of maternal hypoglycemia as assessed clinically. There was no significant interaction between maternal HbA, and the presence of vasculopathy. We conclude that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal clinical hypoglycemia or insulin therapy per se are independent factors associated with major CMs in IDMs. We suggest, based on these data, that in addition to establishment of meticulous glycemic control, IDDM women be assessed for vasculopathy before pregnancy and given appropriate counseling regarding risk of CMs.
Anti-Sympathetic Ganglia Antibodies and Postural Blood Pressure in IDDM Subjects of Varying Duration and Patients at High Risk of Developing IDDM
Authors: Rabinowe Steven L , Brown Florence M , Watts Michael , Kadrofske Mark M , Vinik Aaron I
Published: March 2007

We examined the sera of 94 subjects with insulindependent diabetes mellitus (IDDM) for the presence of complement-fixing sympathetic ganglia (CF-SG) antibodies. In a cross-sectional analysis (duration 0–43 yr), 22% had detectable CF-SG antibodies. Subjects at high risk for IDDM were also studied. Four groups were studied: group 1 (aged 4–64 yr) islet cell antibodypositive (ICA+) prediabetic subjects, 10 of 19 (53%) were CF-SG+ ; group 2 (aged 6–14 yr) ICA− prediabetic subjects (first-degree relatives of IDDM subjects with either transient hyperglycemia, impaired oral glucose tolerance, and/or first-phase insulin release after intravenous glucose tolerance testing), 4 of 9 (44%) were CF-SG+ (2 of the 4 ICA− CF-SG+ subjects have progressed to IDDM); group 3 (aged 1.5-43 yr) ICA+ IDDM subjects (≤1 yr duration) 6 of 10 (60%) were CF-SG+; and group 4 (aged 8–59 yr) ICA IDDM subjects (≤1 yr duration), 2 of 11 (18%) were CF-SG+. All groups had increased CF-SG compared with controls. Postural blood pressure and simultaneous CF-SG antibody measurements were performed in 28 IDDM subjects. The drop in systolic blood pressure was greater in the CF-SG+ subjects (P < .05), and the frequency of CF-SG was greater in the mean to – 2SD group (P < .03) when data were analyzed within mean ± 2SD of the normal blood pressure response.
Postprandial Oscillatory Patterns of Blood Glucose and Insulin in NIDDM: Abnormal Diurnal Insulin Secretion Patterns and Glucose Homeostasis Independent of Obesity
Authors: Calles-Escandon Jorge , Jaspan Jonathan , Robbins David C
Published: March 2007

Compared with control subjects, non-insulin-dependent diabetes mellitus (NIDDM) subjects had both quantitative and qualitative abnormalities in blood insulin and glucose concentrations. The purpose of this study was to determine whether and to what extent normally observed multiphasic patterns of insulin and glucose responses to mixed meals are deranged in NIDDM. A total of 24 volunteers were studied while eating three meals of identical composition at 0745, 1145, and 1645. Twelve had NIDDM, and the remainder were healthy nondiabetic age- and weight-matched control subjects. Blood was withdrawn every 10 min from 0630 to 1930 for measurement of C-peptide, insulin, and glucose concentrations. Peaks were analyzed by computer-based algorithms. Diabetic volunteers displayed several differences from control subjects. First, although the number of insulin peaks was similar, there was aconsistent delay of 20-30 min in the appearance of the first postprandial peak. Second, insulin concentrations after lunch were higher than after breakfast, whereas the reverse pattern occurred in control subjects. Third, integrated glycemia was greater after breakfast than after lunch. Fourth, glucose concentrations decreased during the first 30 min after lunch, suggesting accelerated glucose disposal and/or enhanced suppression of endogenous glucose production at this time of day. These data demonstrate that insulin secretion and action and glucose homeostasis in NIDDM are more complex than commonly appreciated. This dynamic state is undetected unless there is frequent blood sampling for measurement of insulin and glucose. The quantitative and qualitative abnormalities that we observed in these parameters are independent of obesity and suggest the need to expand the pathophysiological definition of NIDDM.
Pancreatic Nesidioblastosis in Adults
Authors: Fong Tse-Ling , Warner Nancy E , Kumar Dinesh
Published: March 2007

Nesidioblastosis, a condition characterized by diffuse islet cell hyperplasia arising from the ductal epithelium, is often associated with hyperinsulinemic hypoglycemia. This is a childhood disease and is rarely found in adults. Only 10 histologically proven cases have been recorded, including 3 new cases described in this article. Most clinical and biochemical features are identical to those of an insulinoma, except the proinsulin-like component of circulating immunoreactive insulin, which is usually within the normal range in nesidioblastosis. Limited observations show that some patients may be managed medically with diazoxide. Patients who remain hypoglycemic despite medical therapy require pancreatectomy, although >90% resection frequently results in insulin dependency and permanent diabetes.
Relationship of Skin Thickness to Duration of Diabetes, Glycemic Control, and Diabetic Complications in Male IDDM Patients
Authors: Collier Andrew , Patrick Alan W , Bell Derek , Matthews David M , Maclntyre Cecilia C A , Ewing David J , Clarke Basil F
Published: March 2007

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24–38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P < .001), previous glycemic control (P < .001), retinopathy (P < .001), cheiroarthropathy (P < .001), and vibrationperception threshold (P < .05). There was a negative correlation between forced expiratory volume at 1 s (P < .05) and vital capacity (P < .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P < .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.
Systematic Approach to Diagnosis and Management of Biphasic Insulin Allergy with Local Anti-Inflammatory Agents
Authors: Loeb Jeffrey A , Herold Kevan C , Barton Kevin P , Robinson Lucia E , Jaspan Jonathan B
Published: March 2007

In this report, we present a patient with a rarely encountered form of biphasic insulin allergy refractory to a conventional desensitization procedure. We describe a systematic approach to this clinical problem with a set of insulin preparations containing antihistamine and/or corticosteroid to verify the type of hypersensitivity reaction and identify treatment options.The approach taken here may be of use for patients with similar conditions who require insulin for adequate diabetic management but who would otherwise be forced to discontinue insulin because of allergic reactions.
Adrenal Medullary Fibrosis in IDDM of Long Duration
Authors: Brown Florence M , Zuckerman Mark , Longway Sharon , Rabinowe Steven L
Published: March 2007

We conducted a retrospective pathology study to determine whether subjects with long-standing insulindependent diabetes mellitus (IDDM) have abnormalities of the adrenal medulla compared with subjects with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic individuals. Slides were scored from 0 (no fibrosis) to 3+ (complete fibrosis). Nineteen IDDM subjects aged 30–60 yr (mean ± SE 44.9 ± 2.5 yr) at autopsy and with duration of diabetes 13–45 yr (26.8 ± 1.8 yr) were studied. Twelve NIDDM subjects aged 61–84 yr (73.3 ± 2.5 yr) with duration of diabetes 17–33 yr (22.8 ± 1. 9 yr) were studied. Twenty-two nondiabetic subjects aged 32–77 yr (53.7 ± 2.9 yr) were studied. Four of 19 (27%) IDDM subjects had moderate to severe fibrosis compared to 1 of 12 (8.3%) NIDDM subjects and 1 of 22 (4.5%) control subjects. Thirteen of 19 (68%) IDDM subjects had a score of 1, 2, or 3 compared to 3 of 22 (13.6%) control subjects (P < .0005). There was an association between duration of IDDM and fibrosis score (r = .46, P < .05) and between age and fibrosis score among IDDM subjects (r = .57, P = .01). No association between age or duration of diabetes and /ibrosis score was observed for NIDDM or control subjects. Adrenal medullary fibrosis may be an anatomical correlate of the diminished epinephrine secretion that occurs in response to insulin-induced hypoglycemia in some IDDM subjects.
Evaluation of New Rapid Office Test for Microalbuminuria and Its Comparison to Fully Quantitative Radioimmunoassay
Authors: Neuman R Glenn , Bonomini Luigi V , Braunstein Seth N
Published: March 2007

A novel enzyme-linked immunosorbent assay (ELISA [Dialbumin]) for rapid office measurement of microalbuminuria was evaluated and its performance compared with that of a commercially available radioimmunoassay (double-antibody albumin). Urine samples containing between 0.75 and 1800 μg/ml of albumin were obtained from 31 diabetic patients and assayed by both methods. A comparison of the paired values obtained from the two methods gave a correlation coefficient of >0.99. The Dialbumin assay, which used detachable eight-well strips (1 strip/sample), 10-min incubation, tap water wash, and a 2-min color development step, was read on both an ELISA reader and a hand-held analytical device (Acc-U-Dial) designed specifically for this test. The findings of this study indicate that the Dialbumin assay, usedin conjunction with the Acc-U-Dial device, affords a rapid, convenient, and sensitive method for quantitative determination of a broad range (0.3–1280 μg/ml) of urinary albumin levels in the office setting.
Obesity and Diabetes in Blacks
Authors: Pi-Sunyer F Xavier
Published: March 2007

Diabetes mellitus is more prevalent in the American Black population than in the White population. The prevalence is increasing in Blacks, and there is evidence that it is accompanied by a greater severity of diabetic complications. In addition, mortality figures are higher in Blacks, and Black women are more seriously affected than Black men. Although the reasons for this are unclear, some factors stand out as important. These include obesity, socioeconomic status, and genetics. Obesity is a severe problem in Blacks, particularly in women. Both the degree and the distribution of fat may contribute greatly to the prevalence of diabetes in Blacks. Although the prevalence of obesity is higher in the poor economic groups, multivariate analysis suggests that poverty cannot explain all of the excess obesity that occurs in the Black population. More research is needed into a possible genetic predisposition of Blacks to obesity and diabetes and into the interrelationship between the two conditions in this racial group.
Insulin-Receptor Approaches to Studying Protein Kinase Domain
Authors: Wente Susan R , Rosen Ora M
Published: March 2007

Protein tyrosine kinase activity found in the β-subunit of the insulin receptor provides a mechanism by which insulin binding on the outside of the cell transmits its signal across the plasma membrane into the cytosol. The autophosphorylation of the insulin receptor on tyrosyl residues activates the intrinsic tyrosine kinase of the receptor; rendering its ligand independent. Evidence suggests that phosphorylation of tyrosyl residues 1146, 1150, and 1151 in the kinase domain of the β-subunit play a role in activation. Point mutations in the cytoplasmic portion of the β-subunit confirm the above suggestions and indicate that additional sites are important for receptor function. We present methodology for overproducing the cytoplasmic domain of the receptor in the Baculovirus expression system. The protein, produced in insect cells and larvae, is soluble and fully active on autophosphorylation. Like the intact receptor, its autophosphorylation is intramolecular. Because >10 mg of pure protein can be isolated from 1010 insect cells infected with the recombinant Baculovirus encoding the human insulinreceptor kinase domain, sufficient enzyme is available for various studies, including physicochemical analysis. Isolation of β-subunit defects found in the receptors of patients with various forms of diabetes mellitus also implicates the insulin-receptor kinase in insulin action. Finally, α potential model system for the genetic analysis of the insulin-insulin-receptor system with Drosophila melanogaster is noted. Conservation of the deduced amino acid sequence for both α- and β-subunit sequences between humans and insects highlights the significance of this manner of signal transduction throughout nearly 1 billion years of evolution.
Lack of Relationship Between Glucose Tolerance and Complications of Pregnancy in Nondiabetic Women
Authors: Little Randie R , McKenzie Edith M , Shyken Jaye M , Winkelmann Susan E , Ramsey Linda M , Madsen Richard W , Goldstein David E
Published: March 2007

Recent studies suggest that gestational diabetes mellitus (GDM) is underdiagnosed. To test this hypothesis, we examined the relationship of perinatal complications to glucose tolerance during the third trimester. Our population consisted of 287 women evaluated at ∼28 wk gestation who had normal fasting (<5.9 mM) and 2-h (<9.2 mM plasma glucose) levels after a 100-g glucose load. Glycosylated hemoglobin and glycosylated plasma protein were also measured. Study subjects were stratified into three groups based on 2-h plasma glucose values: group 1 (n = 59) <5.6 mM, group 2 (n = 112) 5.6–6.0 mM, and group 3 (n = 116) 6.7–9.2 mM. There were statistically significant but low correlations (r < 0.20) between 2-h plasma glucose levels and mother's age, body mass index, infant weights, and Apgar scores. There was a significant increasing trend in the proportion of overweight and obese women from groups 1 to 3 (P < 0.02). There was also a significant trend toward higher birth weights (P = 0.013) and larger proportions of large for gestational age (LGA) babies (P = 0.02) from groups 1 to 3, and women with LGA infants showed higher fasting and 2-h plasma glucose levels than women with non-LGA infants (P = 0.032). However, there was no significant difference in perinatal complications or infant morbidity or mortality between groups. Percentage of glycosylated hemoglobin or glycosylated plasma protein did not differ between groups. In conclusion, mother and infant size are significantly related to 2-h plasma glucose, but we found no increased risk of perinatal complications with increased 2-h plasma glucose if <9.2 mM, suggesting that the current criteria for GDM are adequate for detecting women at risk for complications in our patient population.
Pathways to Diabetic Limb Amputation: Basis for Prevention
Authors: Pecoraro Roger E , Reiber Gayle E , Burgess Ernest M
Published: March 2007

We defined the causal pathways responsible for 80 consecutive initial lower-extremity amputations to an extremity in diabetic patients at the Seattle Veterans Affairs Medical Center over a 30-mo interval from 1984 to 1987. Causal pathways, either unitary or composed of various combinations of seven potential causes (i.e., ischemia, infection, neuropathy, faulty wound healing, minor trauma, cutaneous ulceration, gangrene), were determined empirically after a synthesis by the investigators of various objective and subjective data. Estimates of the proportion of amputations that could be ascribed to each component cause were calculated. Twenty-three unique causal pathways to diabetic limb amputation were identified. Eight frequent constellations of component causes resulted in 73% of the amputations. Most pathways were composed of multiple causes, with only critical ischemia from acute arterial occlusions responsible for amputations as a singular cause. The causal sequence of minor trauma, cutaneous ulceration, and wound-healing failure applied to 72% of the amputations, often with the additional association of infection and gangrene. We specified precise criteria in the definition of causal pathway to permit estimation of the cumulative proportion of amputations due to various causes. Forty-six percent of the amputations were attributed to ischemia, 59% to infection, 61% to neuropathy, 81% to faulty wound healing, 84% to ulceration, 55% to gangrene, and 81% to initial minor trauma. An identifiable and potentially preventable pivotal event, in most cases an episode involving minor trauma that caused cutaneous injury, preceded 69 of 80 amputations. Defining causal pathways that predispose to diabetic limb amputation suggests practical interventions that may be effective in preventing diabetic limb loss.
Validation of Scale Measuring Environmental Barriers to Diabetes-Regimen Adherence
Authors: Irvine Audrey A , Saunders J Terry , Blank Michael B , Carter William R
Published: March 2007

This study reports on the validation of a diabetesspecific measure of environmental barriers to regimen adherence. The reliability and validity of the environmental barriers to adherence scale (EBAS) were determined for a sample of 214 insulin-dependent and non-insulin-dependent diabetic patients. The scale was shown to be a valid measure of barriers to adherence as assessed by its relationship to the barriers to adherence questionnaire and the barriers to adherence portion of the diabetes-care profile. The medication, testing, exercise, and diet subscales of the EBAS were correlated with four corresponding and three noncorresponding measures of self-care behavior from the diabetes selfcare behaviors scale. Each subscale correlated well with its corresponding self-care behavior and less well with noncorresponding self-care behavior. The internal consistency of the scale and the test-retest reliability were found to be good. The results suggest that the EBAS scale is a valid, reliable measure of barriers to diabetes-regimen adherence.