bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Peer-Group Intervention on Metabolic Control of Adolescents With IDDM: Randomized Outpatient Study
Authors: Anderson Barbara J , Wolf Fredric M , Burkhart Mary T , Cornell Richard G , Bacon George E
Published: March 2007

In children with insulin-dependent diabetes mellitus (IDDM), deterioration in metabolic control frequently occurs during early adolescence. To prevent this predictable increase in blood glucose levels, we randomly assigned young adolescents with IDDM to an intervention based on problem solving with self-monitoring of blood glucose (SMBG) integrated into standard outpatient care or to standard care only for an 18-mo period. At follow-up, 50% of the standard-care adolescents exhibited > 1% increase in glycosylated hemoglobin (HbA1) levels over baseline values, indicating a deterioration in metabolic control, compared to only 23% of the intervention group. Follow-up HbA1 means ± SD were 10.10 ± 2.00% for intervention and 11.04 ± 2.28% for standard-care adolescents, indicating a significantly lower value in the intervention group (P = .04). At follow-up, a greater percentage of intervention than standard-care adolescents reported using SMBG information when they exercised (60.0 vs. 33.3%, X2 = 4.29, P = .04). Our data suggest that clinic-based problem-solving groups can be more effective with young adolescents with IDDM than conventional treatment in preventing the expected deterioration in blood glucose.
Symptomatic Hypoglycemia in NIDDM Patients Treated With Oral Hypoglycemic Agents
Authors: Jennings Adrian M , Wilson R Malcolm , Ward John D
Published: March 2007

We assessed the prevalence of hypoglycemic symptoms in patients (aged 40–65 yr) treated with oral hypoglycemic agents (OHAs) attending routine diabetes clinics at our hospital. Symptoms were experienced during the previous 6 mo in 41 of 203 (20.2%) patients treated with sulfonylureas but in none of the 16 patients treated with metformin alone. Hypoglycemic symptoms were experienced at least monthly in 5.9% and less frequently in 14.3% of patients. The prevalence of symptoms decreased with increasing duration of sulfonylurea administration (P < .01). Mean glycosylated hemoglobin and postprandial plasma glucose were significantly lower in patients reporting hypoglycemic symptoms than in those without symptoms (P < .001). The prevalence of hypoglycemic symptoms was significantly higher in patients treated with glyburide than in patients treated with gliclazide (P < .01) or chlorpropamide (P < .05). The prevalence of symptoms was higher in patients taking medications in addition to OHAs (P < .01). Ten (24%) of the patients who experienced hypoglycemic symptoms were taking drugs that may potentiate sulfonylureas.
Case-Control Study of IDDM
Authors: Siemiatycki Jack , Colle Eleanor , Campbell Sally , Dewar Ron A D , Belmonte Mimi M
Published: March 2007

Insulin-dependent diabetes mellitus (IDDM) may be caused by a combination of genetic predisposition and environmental insults. However, there are few solid leads concerning human diabetogenic environmental agents. A case-control study was carried out to investigate the possible relationships between IDDM and various biological, chemical, and psychological factors. All 161 cases of IDDM among children aged 0–17 yr occurring in Montreal from 1983 to 1986 were included. The parent of each newly diagnosed diabetic subject was asked to provide the names of two of the child's friends or neighbors who would be age and sex matched to serve as controls. For those unable to do so, matched controls were selected from a hospital emergency room. Parents of cases and controls were interviewed concerning many factors. There was little or no difference between cases and controls with regard to parental smoking habits, exposure to pets, and consumption of meat products high in nitrosamines. In univariate analyses, there was some indication of elevated risk for children who had not been breast-fed, who attended day care or nursery before age 5 yr, who lived in a crowded household at age 3 yr, or who had a history of asthma or eczema, although in multivariate analyses the only variables that had any effect were crowding and day-care attendance. In univariate and multivariate analyses, there was high risk of IDDM among children who had experienced selected stressful life events during the 12 mo preceding onset of IDDM or who had exhibited symptoms of social or psychological dysfunction during that time. Some of these apparent effects may have been due, in part, to biases induced by the method of selecting controls and to the interview process.
Effects and Correlates of Blood Glucose Awareness Training Among Patients With IDDM
Authors: Cox Daniel J , Gonder-Frederick Linda A , Lee Jana H , Julian Diana M , Carter William R , Clarke William L
Published: March 2007

Whereas self-monitoring of blood glucose (SMBG) is the recommended source of information on which to make self-care decisions, patients frequently use estimates of their own blood glucose (BG). This study evaluated whether patients with insulin-dependent diabetes mellitus (IDDM) could learn to improve accuracy of BG estimations and whether this would lead to improved metabolic control. Subjects in BG awareness training improved both their BG-estimation accuracy and glycosylated hemoglobin (HbA1) compared with the control group. Initial BG-estimation accuracy was marginally associated with pretreatment HbA1 and months of previous SMBG experience. Posttreatment improvement was associated with pretreatment BGestimation accuracy and the ability to counterregulate to insulin-induced hypoglycemia.
Quantitative Relationship Between Plasma Lipids and Glycohemoglobin in Type I Patients: Longitudinal Study of 212 Patients
Authors: Ostlund Richard E , Semenkovich Clay F , Schechtman Kenneth B
Published: March 2007

Plasma cholesterol, triglycerides, glycohemoglobin, and other covariates were measured in 212 type I (insulindependent) diabetic subjects on entry into a longitudinal study of diabetes and again after an average interval of 3.7 yr. Changes in individual cholesterol and triglyceride values over time were significantly correlated with changes in glycohemoglobin. After adjustment for potentially confounding covariates, plasma cholesterol declined by 2.2% (0.1 mM) for each percentage-point reduction in glycohemoglobin and plasma triglycerides declined by 8% (0.08 mM) per percentage point glycohemoglobin. Increased insulin dose was independently associated with increased plasma triglycerides, after adjusting for glycohemoglobin level and other covariates. However, insulin dose was not related to plasma cholesterol. Improved diabetic metabolic control, measured as declining glycohemoglobin, is the variable most closely associated with reduced plasma lipids in a population of typical type I diabetic patients.
Total Contact Casting in Treatment of Diabetic Plantar Ulcers: Controlled Clinical Trial
Authors: Mueller Michael J , Diamond Jay E , Sinacore David R , Delitto Anthony , Blair Vilray P , Drury Dolores A , Rose Steven J
Published: March 2007

This study compared the treatment of total contact casting (TCC) with traditional dressing treatment (TDT) in the management of diabetic plantar ulcers. Forty patients with diabetes mellitus and a plantar ulcer but with nogross infection, osteomyelitis, or gangrene were randomly assigned to the TCC group (n = 21) or TDT group (n = 19). Age, sex, ratio of insulin-dependent diabetes mellitus to non-insulin-dependent diabetes mellitus, duration of diabetes mellitus, vascular status, size and duration of ulcer, and sensation were not significantly different between groups (P > .05). In the experimental group, TCC was applied on the initial visit, and subjects were instructed to limit ambulation to ∼33% of their usual activity. Subjects in the control group were prescribed dressing changes and accommodative footwear and were instructed to avoid bearing weight on the involved extremity. Ulcers were considered healed if they showed complete skin closure with no drainage. Ulcers were considered not healed if they showed no decrease in size by 6 wk or if infection developed that required hospitalization. In the TCC group, 19 of 21 ulcers healed in 42 ± 29 days; in the TDT group, 6 of 19 ulcers healed in 65 ± 29 days. Significantly more ulcers healed (χ2 = 12.4, P < .05) and fewer infections developed (χ2 = 4.1, P < .05) in the TCC group. We conclude TCC is a successful method of treating diabetic plantar ulcers but requires careful application, close follow-up, and patient compliance with scheduled appointments to minimize complications.
Physiological and Clinical Correlates of Cardiorespiratory Reflexes in Diabetes Mellitus
Authors: Kennedy William R , Navarro Xavier , Sakuta Manabu , Mandell Howard , Knox Charles K , Sutherland David E R
Published: March 2007

Cardiorespiratory reflexes (CRRs) were studied by measuring heart-rate (HR) variation during 6 breaths/min respiration (ΔR6) and Valsalva maneuver (VR) in 145 healthy and 417 type I (insulin-dependent) diabetic subjects. HR variation with breathing at 12 breaths/min and ventilatory response to hypercapnia/hypoxia were measured in fewer subjects. CRR results were compared with symptoms of autonomic dysfunction, the neurological examination, nerve conduction studies, and quantitative sweat testing. The objective was to compare the sensitivity of various methods of characterizing diabetic patients and to use this information when staging patients for clinical therapeutic trials. CRR responses were age dependent in both populations. Either ΔR6 or VR was abnormal in 74% of diabetic patients, Δ R6 being more sensitive. CRRs correlated well with the presence of symptoms of autonomic dysfunction, abnormalities on the neurological examination, results of nerve conduction studies, and sweating activity in the feet of the same patients. However, both CRRs and sweating were abnormal in a high proportion of patients without any clinical manifestations of neuropathy. The ventilatory reflex response to moderate hypercapnia/hypoxia was also measured. It was normal in most of the diabetic patients tested, including many with severe reduction of CRRs. We conclude from the combined results of CRR, ventilatory response, and other studies that the causative factors for abnormal CRR may not be confined to the vagus nerves, and that in most instances, the depressed CRR may be due to a decrease in the efficacy of sensorimotor nerve conduction around the reflex arc.
Effect of Sucrose-Containing Snacks On Blood Glucose Control
Authors: Wise Joyce E , Keim Kathryn S , Huisinga Jacqueline L , Willmann Pamela A
Published: March 2007

To determine whether ingestion of sucrose-containing snacks would affect blood glucose (BG) control, 16 subjects with insulin-dependent diabetes mellitus participated in a 5-day double-blind study at a diabetes camp. Eight subjects in the sucrose group ate sucrose-sweetened snacks twice a day, and 8 subjects in the control group ingested snacks that were sweetened with aspartame. The percentage of total daily calories derived from added sucrose was 7% for the sucrose group and 1% for the control group. Metabolic control was assessed by daily capillary BG measurements obtained before meals and the bedtime snack and by determination of serum fructosamine (F) concentrations on arrival at camp (day 0) and after 5 days on the study protocol (day 5). No significant difference was seen between the groups on day 0 (sucrose group [mean ± SD]: BG 9.9 ± 3.6 mM, F 3.54 ± 0.38 mM; control group: BG 9.1 ± 2.8 mM, F 3.74 ± 0.71 mM) or day 5 (sucrose group: BG 8.8 ± 2.6 mM, F 2.94 ± 0.32 mM; control group: BG 7.4 ± 2.8 mM, F 2.92 ± 0.59 mM). We conclude that ingestion of sucrose, added to snacks in an amount up to 7% of total energy intake, does not adversely affect short-term BG control.
Effect of Raising Injection-Site Skin Temperature on Isophane (NPH) Insulin Crystal Dissociation
Authors: Thow Jonathan C , Johnson Andrew B , Antsiferov Mikhail , Home Philip D
Published: March 2007

In eight healthy subjects, skin temperature at the injection site was raised from mean ± SD 31.7 ± 0.5 to 40.8 ± 0.9°C 180 min after injection of 0.25 U/kg isophane (NPH; Human Insulatard) insulin and maintained for 180 min. On the control day, skin temperature was kept constant. On warming of the injection site, serum insulin concentration rose from mean ±SE 14.4 ± 2.5 to 17.7 ± 3.1 mU/L after 40 min (P < .01) but did not change on the control day over the same period. The change in insulin concentration from the prewarming hour was higher on the warming day than control day in the 1st h (123 ± 8 vs. 93 ± 7%, P < .01), 2nd h (115 ± 14 vs. 83 ± 9%, P < .05), and 3rd h (113 ± 17 vs. 80 ± 10%, P < .05) of warming, providing evidence for both early increased absorption of the free-insulin pool surrounding the protamine-insulin complexes and continuing increased dissociation of the complexes.
Exercise and Posture-Related Changes of Atrial Natriuretic Factor and Cardiac Function in Diabetes
Authors: Donckier Julian E , De Coster Patrick M , Buysschaert Martin , Pieters Denis P , Cauwe Franscisca M , Robert Annie , Brichant Christine M , Berbinschi Adrien C , Ketelslegers Jean-Marie
Published: March 2007

To study whether the release of atrial natriuretic factor (ANF) was altered in diabetic cardiac autonomic neuropathy (CAN), we determined plasma ANF concentrations during exercise and changes of posture in three groups of age- and sex-matched subjects(9 healthy subjects, 7 diabetic patients with CAN, and 7 diabetic patients without CAN). During exercise, plasma ANF concentrations rose threefold (P < .001), and this increase was similar in the three groups. However, heart-rate response to exercise was impaired in the two groups of diabetic patients (P < .004 vs. healthy subjects) but was more severely impaired in patients with CAN (P < .03 vs. patients without CAN). In healthy subjects and patients without CAN, the increases of ANF during exercise correlated significantly with those of heart rate, systolic blood pressure, and rate-pressure product (P < .01). In patients with CAN, the correlation was found exclusively with heart rate (P < .01). An increase of ventricular ejection fraction occurred in all groups (P < .001) but without showing statistical differences between groups. After 30 min of standing, a similar postural drop of plasma ANF concentrations (P < .002) was observed in all subjects, reflecting preserved sympathetic control of vessels. In conclusion, exercise induces an increase of plasma ANF in diabetic patients with CAN. This increase, occurring similarly to healthy subjects, indicates that autonomic activation plays a minor role in ANF release during exercise. Impaired heart-rate response to exercise in patients without CAN suggests early damage of autonomic function, undetected by conventional rest tests.
Relationship of Insulin Autoantibodies to Presentation and Early Course of IDDM in Children
Authors: Sochett Etienne , Daneman Denis
Published: March 2007

Insulin antibodies have been documented before (insulin autoantibodies [IAAs]) and after (insulin antibodies) insulin administration in children with new-onset insulin-dependent diabetes mellitus (IDDM). Whereas the relationship of IAA to various factors at presentation has been studied in some detail, little is known about their relationship to events during the 1st yr after diagnosis. Furthermore, the course and factors affecting insulin-antibody response to human insulin administration in children with newly diagnosed IDDM remain poorly defined. To study these questions, we measured serum glucose, pH, bicarbonate, C-peptide, and IAA at diagnosis in 84 children between 0.5 and 18 yr of age. Basal and peak C-peptide responses to Sustacal ingestion, glycosylated hemoglobin (HbA1c), and IAA were then measured in 33 of these patients at 10 days and 1,3,6, and 12 mo after diagnosis. At presentation, lAAs were absent (binding below the mean + 3SD of the binding of control serums) in 51 patients (61%) and present (binding above the mean + 3SD) in 33 patients (39%). Multiple regression analysis showed a significant nonlinear relationship between lAAs and both age (P < .005) and blood glucose (P < .05) at onset. There was a stepwise increase in median insulin-antibody binding throughout the 1st yr. This increase was most marked during the 1st mo of insulin therapy and showed a statistically significant difference between successive measurements only during this period. Analysis of variance showed no effect of the factors measured at diagnosis (age, blood glucose, C-peptide, pH, bicarbonate, IAA) or those measured during the 1st yr (blood glucose, insulin dose, C-peptide, HbA1c) on the antibody response to insulin. Furthermore, IAA did not correlate with either insulin antibodies or C-peptide at any time during the 1st yr. Because lAAs do not appear to be related to residual insulin secretion and do not predict the insulin-antibody response to human insulin administration, the data failed to define a role for these antibodies in the pathogenesis of this disorder. This suggests that lAAs may be markers of the immune confrontation with the β-cell rather than active participants in its destruction. Furthermore, insulinantibody response after human insulin administration appears to have no effect on residual insulin secretion, insulin requirement, or metabolic control during the 1st yr after diagnosis.
Effects of 8-Wk α-Glucosidase Inhibition on Metabolic Control, C-Peptide Secretion, Hepatic Glucose Output, and Peripheral Insulin Sensitivity in Poorly Controlled Type II Diabetic Patients
Authors: Schnack Christoph , Prager Rudolf JF , Winkler Johanna , Klauser Renate M , Schneider Barbara G , Schernthaner Guntram
Published: March 2007

Miglitol (BAYm 1099), an α-glucosidase inhibitor, reduces the postprandial increase of blood glucose and serum insulin levels in type II (non-insulin-dependent) diabetes mellitus, as shown in short-term studies. In this study, the effects of long-term miglitol treatment on metabolic control, C-peptide secretion, hepatic glucose output, and peripheral insulin sensitivity (euglycemic clamp) were tested in 15 type II diabetic patients (8 receiving insulin, 7 receiving oral hypoglycemic agents). For 8 wk they received either miglitol (300 mg/day) or placebo with a double-blind crossover design that had a 4-wk washout period between treatments. Miglitol therapy induced a reduction of postprandial blood glucose levels (miglitol compared with placebo; areas under the curve; P > .002), whereas fasting blood glucose levels were not influenced. Miglitol caused a slight reduction of glycosylated hemoglobin levels (mean ± SE miglitol and placebo 9.50 ± 0.3 and 10.0 ± 0.4%, respectively; P > .05), which was more pronounced in insulin-treated patients. Miglitol caused a reduction of postprandial C-peptide increase (P > .03). Hepatic glucose output (both in the basal state and during euglycemic clamp conditions) and peripheral insulin sensitivity were not influenced by miglitol therapy. Specific side effects were observed in 11 patients; in 6 patients only to a moderate degree.- Long-term miglitol treatment induces a persistent reduction of postprandial blood glucose increase. This effect is more pronounced in type II diabetic patients on insulin therapy, which can cause a moderate improvement of overall metabolic control.
Binge Eating and Purging in Young Women With IDDM
Authors: Stancin Terry , Link Diane L , Reuter jeanette M
Published: March 2007

Case reports and empirical studies suggest that young women with insulin-dependent diabetes mellitus (IDDM) may be at high risk for developing eating disorders. In this study, self-reports of binge eating and purging from 59 IDDM women (aged 18–30 yr) were obtained. Most participants (58%) reported that they went on eating binges, and 12% met the DSM-III criteria for a diagnosis of bulimia. Nearly 40% admitted to controlling their weight by insulin purging, and 13.5% reported purging by other means. A group of bulimic participants had mean scores on an eating disorder questionnaire in the pathological range. Bulimic symptoms were positively related to reports of hospitalizations, episodes of ketoacidosis, and psychological symptoms. Implications of these results on the medical management of young women with IDDM are discussed.
Stimulation of Prostacyclin Synthesis by Physical Exercise in Type I Diabetes
Authors: Koivisto Veikko A , Jantunen Marja , Sane Timo , Helve Eero , Pelkonen Risto , Viinikka Lasse , Ylikorkala Olavi
Published: March 2007

We examined the effect of short- and long-term exercise on prostacyclin (prostaglandin l2 [PGI2]) and thromboxane A2 (TXA2) synthesis in type I (insulindependent) diabetic patients and healthy control subjects. PGI2 synthesis was assessed by determining the urinary excretion of 6-keto-PGF1α and 2,3-dinor-6-keto- PGF1α and TX synthesis by measuring TXB2 in serum and urine. In the resting state, prostanoid excretion and concentrations were similar in diabetic and control subjects. During 40 min of ergometric cycling exercise, the urinary excretion of 6-keto-PGF1α (a hydration product of vasodilatory PGI2) increased 5.8-fold more in the 12 control subjects than in the 15 diabetic patients (P < .02). Serum TXB2 concentration rose similarly in diabetic patients and control subjects (P < .05). During a 75-km competitive cross-country ski race (7 h, 30 min), urinary excretion of 6-keto-PGF1α rose 1.9-fold in 7 diabetic (P < .05) and 3.3-fold in 10 control (P < .001) subjects, whereas urinary dinor excretion, reflecting vascular PGI2 synthesis more closely, increased only in the control subjects (P < .01). Urinary TXB2 excretion remained unchanged in both groups during long-term exercise. These data suggest that diabetic patients have normal PGI2 and TXA2 synthesis in the resting state but diminished PGI2 response to both acute and prolonged exercise.
Effect of Pregnancy on Progression of Diabetic Retinopathy
Authors: Klein Barbara E K , Moss Scot E , Klein Ronald
Published: March 2007

A prospective study was undertaken to determine the effect of pregnancy on diabetic retinopathy. Insulin-taking diabetic women were enrolled; one group was comprised of pregnant women, the other group was comprised of women who were not pregnant. Women were evaluated on referral and again in the postpartum period. The severity of diabetic retinopathy was based on grading of fundus photographs of seven standard photographic fields. The glycosylated hemoglobin, duration of diabetes, current age, diastolic blood pressure, number of past pregnancies, and current pregnancy status were evaluated as risk factors for progression of diabetic retinopathy. After adjusting for glycosylated hemoglobin, current pregnancy was significantly associated with progression (P < 0.005, adjusted odds ratio 2.3). Diastolic blood pressure had a lesser effect on the probability of progression. The findings from this study indicate that pregnancy and level of glycemia are associated with progression of diabetic retinopathy.
Scope and Heterogeneous Nature of MODY
Authors: Fajans Stefan S
Published: March 2007

This review summarizes aspects of the phenotypic expression, natural history, recognition, pathogenesis, and heterogeneous nature of maturity-onset diabetes of the young (MODY), which is inherited in an autosomal-dominant pattern. There are differences in metabolic, hormonal, and vascular abnormalities in different ethnic groups and even among White pedigrees. In MODY patients with low insulin responses, there are delayed and decreased insulin and C-peptide secretory responses to glucose from childhood or adolescence even before glucose intolerance appears, which may represent the basic genetic defect. When followed for decades, nondiabetic siblings have normal insulin responses. The fasting hyperglycemia of some MODY patients has been treated successfully with sulfonylureas for up to 30 yr. In a few patients, after years or decades of diabetes, the insulin and C-peptide responses to glucose are so low that they resemble those of early insulin-dependent diabetes mellitus. The progression of the insulin secretory defect over time distinguishes between these two types of diabetes. In contrast are patients from families who have very high insulin responses to glucose, despite glucose intolerance and fasting hyperglycemia similar to that seen in patients with low insulin responses. In many of these patients, there is in vivo and in vitro evidence of insulin resistance. Whatever its mechanism, the compensatory insulin responses to nutrients must be insufficient to maintain normal carbohydrate tolerance. This suggests that diabetes occurs only in those patients who have an additional islet cell defect, i.e., insufficient β-cell reserve and secretory capacity. In a few MODY pedigrees with high insulin responses to glucose and lack of evidence of insulin resistance, a structurally abnormal mutant insulin molecule that is biologically ineffective is secreted. No associations have been found between specific HLA antigens and MODY in White, Black, and Asian pedigrees. Linkage studies of the insulin gene, insulin-receptor gene, erythrocyte/HepG2 glucose-transporter locus, and apolipoprotein B locus have shown no association with MODY. Vascular disease may be as prevalent as in conventional non-insulin-dependent diabetes mellitus. Because of autosomal-dominant transmission and penetrance at a young age, MODY is a good model for further investigations of etiologic and pathogenetic factors in non-insulin-dependent diabetes mellitus, including the use of genetic linkage strategies to identify diabetogenic genes.
Corrected Q-T Interval Prolongation as Diagnostic Tool for Assessment of Cardiac Autonomic Neuropathy in Diabetes Mellitus
Authors: Gonin Joyce M , Kadrofske Mark M , Schmaltz Steven , Bastyr Edward J , Vinik Aaron I
Published: March 2007

A simple method for evaluating alterations in cardiac sympathetic innervation may be measurement of the Q-T interval. Seventy-three diabetic patients (46 insulin dependent and 27 non–insulin dependent) were separated into four groups based on the presence and degree of cardiac autonomic neuropathy (CAN) with noninvasive cardiovascular reflexes and blood pressure responses. None of the patients had evidence of ischemic heart disease, kidney disease, or the idiopathic long Q-T–interval syndrome. The corrected Q-T interval (Q-Tc) was determined at rest with Bazett's formula. As a group, diabetic patients with ≥2 abnormalities of cardiac autonomic function had a longer Q-Tc interval than those with no evidence of CAN. Diabetic patients with ≥1 abnormality had a prolonged Q-Tc interval compared with a control group of 96 healthy nondiabetic subjects (mean ± SD 397 ± 18). The frequency of prolonged (>433 ms, normal mean + 2SD) resting Q-Tc intervals increased with the increasing number of abnormalities (0, 1, 2, ≥ 3): 11, 25, 41, and 75%, respectively. Twenty-three of 25 (92%) patients with a Q-Tc >433 ms had evidence of CAN. However, 57% (31 of 54) of the patients with CAN had a normal Q-Tc interval. These data provide further evidence of a relationship between the presence and severity of CAN and degree of Q-Tc interval prolongation. Compared with cardiovascular reflexes and blood pressure tests for CAN, the Q-Tc interval in the group of diabetic patients studied without evidence of heart or kidney disease was an insensitive but specific marker. An abnormal Q-Tc interval may be an additional diagnostic tool for evaluating CAN in patients with diabetes mellitus.
Preservatives in Insulin Preparations Impair Leukocyte Function: In vitro study
Authors: van Faassen Ineke , Verweij-van Vught A Marian JJ , Lomecky-Janousek Mary Z , Razenberg Peter PA , van der Veen Eduard A
Published: March 2007

m-Cresol and methyl p-hydroxybenzoate are preservatives in insulin preparations. As previously reported, in diabetic patients on continuous subcutaneous insulin infusion, users of insulin-containing m-cresol had significantly more inflamed infusion sites than users of insulin with methyl p-hydroxybenzoate. This study assessed the influence of insulin with and without these preservatives on leukocyte function. Leukocyte function was investigated in a killing experiment, expressed as the percentage of bacteria killed after 60 min incubation of bacteria (Staphylococcus aureus), polymorphonuclear leukocytes, serum, and insulin preparations. Because preservative is retained by the infusion device, insulin with preservative was tested before and after 1 and 4 days perfusion with a PVC pump catheter. After perfusion, the amount of preservative was reduced (percentage of original concentration after 1 and 4 days 8 and 30% m-cresol and 42 and 72% methyl p-hydroxybenzoate, respectively). The killing percentage in insulin with m-cresol reduced compared with insulin without preservative (mean ± SE 95.4 ± 0.8%) and the control without insulin (95.8 ± 0.8%), both before and after 1 and 4 days perfusion (74.8 ± 0.7, 80.2 ± 2.8, and 80.6 ± 1.6%, respectively; P < 0.01). The same occurred in insulin with methyl p-hydroxybenzoate (85.0 ± 0.9% before and 88.4 ± 0.9 and 86.2 ± 0.8% after 1 and 4 days perfusion; P < 0.05). All insulin preparations with m-cresol caused lower killing percentages than corresponding insulin preparations with methyl p-hydroxybenzoate (P < 0.05). These results demonstrate that both preservatives impaired leukocyte function, but m-cresol was the most noxious in this respect. This indicates that preservatives in insulin preparations are possibly implicated in the pathogenesis of local infections in continuous subcutaneous insulin infusion.
Variation in Absorption of NPH Insulin Due to Intramuscular Injection
Authors: Vaag Allan , Handberg Aase , Lauritzen Mogens , Henriksen Jan Erik , Pedersen Karen Damgaard , Beck-Nielsen Henning
Published: March 2007

To evaluate the importance of accidental intramuscular injection of NPH insulin, we measured disappearance rates of 125I-labeled NPH insulin (Protaphane) from subcutaneous and intramuscular injection sites in the thighs of 11 insulin-dependent diabetes mellitus patients. Both subcutaneous and intramuscular absorption rates were measured four times in each patient. NPH insulin was absorbed much faster when given intramuscularly than when given subcutaneously (T50% = 5.3 vs. 10.3 h, P < 0.0001). The intrapatient (day-to-day) coefficient of variation (C.V.) of T50% values (C.V. T50%) for subcutaneously injected NPH insulin in this study, where all injections were guided by ultrasound determination of the subcutaneous fat layer, was 18.4%. Intrapatient variation of absorption was significantly lower for subcutaneously than intramuscularly injected NPH insulin (C.V. T50% = 18.4 vs. 29.8%, P < 0.01) and was also lower than interpatient variation for subcutaneously injected insulin (C.V. T50% = 18.4 vs. 50%, P < 0.0001). The faster absorption rate and shorter duration of action, together with the higher day-to-day variation in absorption, led us to conclude that intramuscular injection of NPH insulin should be avoided.
Prevalence of Diabetes and Impaired Glucose Tolerance in Elderly Subjects and Their Association With Obesity and Family History of Diabete
Authors: Mykkänen Leena , Laakso Markku , Uusitupa Matti , Pyörälä Kalevi
Published: March 2007

The goal of this study was to investigate the prevalence of impaired glucose tolerance (IGT) and non-insulindependent diabetes mellitus (NIDDM) in elderly subjects and their association with obesity, central obesity, and a family history of diabetes. A representative population sample of 1300 subjects (471 men, 829 women) aged 65–74 yr participated in the study. The participation rate was 71%. The prevalence rates of previously and newly diagnosed NIDDM and IGT, based on a history of diabetes and an oral glucose tolerance test, were 8.7, 7.0, and 17.8% in men and 11.7, 7.1, and 19.1% in women. Thus, 33.8% of men and 37.9% of women had abnormal glucose tolerance according to World Health Organization criteria. Obesity (body mass index ≥27 kg/m2 in men and ≥25 kg/m2 in women) and central obesity (waist-hip ratio ≥0.98 in men and ≥0.89 in women) doubled the prevalence of IGT or NIDDM. The combination of obesity and a family history of diabetes was associated with a more marked increase in the prevalence of IGT or NIDDM in men than in women. Simultaneous presence of obesity, central obesity, and a family history of diabetes was associated with a threefold increase in the prevalence of IGT or NIDDM (65.4 vs. 24.1% in men, 52.8 vs. 19.6% in women, P < 0.001). The major risk factors for NIDDM, e.g., obesity, central fat distribution, and a family history of diabetes, explained 10% of the variance in 2-h glucose values in multiple regression analysis. In conclusion, the prevalence of IGT and NIDDM was high in elderly subjects. Although obesity, central fat distribution, and a family history of diabetes were significantly associated with the increased prevalence of IGT or NIDDM, they explained only a minor proportion of the variance in 2-h glucose values.
Self-Care Predictors of Metabolic Control in NIDDM Patients
Authors: Rost Kathryn M , Flavin Karen S , Schmidt Lois E , McGill Janet B
Published: March 2007

The objective of this study was to evaluate whether the relationship between self-care behavior and metabolic control is comparable in patients with non-insulindependent diabetes mellitus (NIDDM) on insulin and not on insulin. We studied 84 NIDDM patients hospitalized for an elective admission in Washington University's Model Demonstration Unit. At admission, patients reported the frequency of exercise, blood glucose monitoring, and meal skipping for the previous 2 wk. Metabolic control over the previous 8–12 wk was determined from glycosylated hemoglobin assays. In cross-sectional analysis controlling for patient sociodemographic and health characteristics, glycosylated hemoglobin levels were positively related to meal skipping (P = 0.0008) and negatively related to the frequency of blood glucose monitoring (P = 0.0025). Self-care behaviors explained 26% of the variance in glycosylated hemoglobin levels in NIDDM patients. Multivariate modeling demonstrated no significant interaction effects between insulin treatment and self-care on metabolic control. In conclusion, these findings support the clinical significance of self-care activities for metabolic control in NIDDM patients, particularly meal skipping and blood glucose monitoring.
Genetics of NIDDM
Authors: Permutt M Alan
Published: March 2007

This brief review discusses the current level of understanding of the role of genetic defects in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) and the use of molecular-genetic methods for this study. Evidence for genetic susceptibility is strong, and defects in both insulin production and action are suspect. With restriction-fragment-length polymorphisms and genomic sequencing, various candidate loci are being evaluated. Evidence that multiple genes are involved is only circumstantial. If NIDDM is genetically heterogeneous and also influenced by environmental components, population associations and linkage analyses in families may not be as easily interpreted as for diseases involving single major gene defects.
Exercise in Therapy and Prevention of Type II Diabetes: Implications for Blacks
Authors: Ruderman Neil , Apelian Ara Z , Schneider Stephen H
Published: March 2007

The rationale for the use of exercise in the treatment of type II (non-insulin-dependent) diabetes and its special implications for Blacks are reviewed herein. When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia. In addition, it may be a useful adjunct to diet in producing weight loss. The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity. Benefits are short lived after discontinuing exercise. Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program. For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis. Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution. Type II diabetes is more common in Blacks than in the general population. In most instances, it is associated with cardiovascular risk factors benefited by exercise. Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it.
Diabetic Cardiomyopathy
Authors: Fein Frederick S
Published: March 2007

The purpose of this article was to review the clinical and experimental features of diabetic cardiomyopathy, with particular relevance to the Black population. One hundred thirty-seven studies were identified, of which 57 were selected as references for this article. Diabetes is associated with the development of cardiomyopathy, independent of coronary atherosclerosis. Pathological studies show myocardial hypertrophy and fibrosis; microvascular pathology is also present, but all of these pathological findings have an uncertain relationship to myocardial failure. Hemodynamic findings of both congestive and restrictive cardiomyopathy have been described. Noninvasive studies revealed abnormal systolic and diastolic function in many diabetic subjects, particularly in the presence of diabetic complications and/or hypertension. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. One year of diabetes in dogs resulted in decreased left ventricular compliance and increased interstitial connective tissue. Studies in the diabetic rat showed a marked slowing of contraction and relaxation. Chronic insulin therapy reversed the changes in the rat model. Combining hypertension with diabetes in the rat resulted in increased myocardial and coronary microvascular pathology and greater changes in isolated muscle function, electrophysiology, and contractile protein biochemistry. Many hypertensive diabetic rats died spontaneously, showing signs of congestive heart failure. Diabetic cardiomyopathy is a significant cause of heart failure in diabetic subjects and occurs more frequently in those with microvascular complications and/or hypertension. Clinical studies are needed to clarify the natural history of this disorder, focusing on the benefits of tight control of hyperglycemia and treatment of associated hypertension. Experimental studies will clarify the pathophysiology and contribute to improved therapy. The high prevalence of diabetes and hypertension in Blacks makes these considerations especially relevant to this population.
Treatment of NIDDM With Insulin Agonists or Substitutes
Authors: Galloway John A
Published: March 2007

Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in 3–6% of adults in most western populations. In the United States, 29% of patients with diabetes take insulin; of these, 76% have NIDDM. Insulin therapy is usually required at some time in NIDDM. Insulin therapy improves the abnormalities of NIDDM (reduced β-cell function, increased hepatic glucose production, reduced peripheral glucose disposal, lipid abnormalities). Insulin and sulfonylurea agents have comparable effects on mild forms of NIDDM, but for more severe forms, insulin is usually superior. Combination insulin-sulfonylurea treatment may improve the response to sulfonylureas, although long-term well-controlled trials have not been conducted. Short-term insulin treatment may restore response to sulfonylureas. Other promising treatments (human proinsulin, nasal insulin, somatostatin) have not shown any advantage over conventional insulin therapy. Insulin causes hypoglycemia and peripheral hyperinsulinemia. The hazards of hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and questions about its atherogenic effects remain to be resolved. The effect of glycemic control on macro- and microvascular complications has not been established; however, maintaining fasting blood glucose levels of <6.7 mM may protect against progression of retinopathy, neuropathy, and nephropathy and reduce the severity of ischemic stroke. Dosage algorithms generally use intermediate- or long-acting insulin to control basal glycemia, with regular insulin added before meals if needed to control postprandial glycemia. Effective therapy depends on the patient being informed, cooperative, and willing to self-monitor blood glucose. Insulin treatment intermittency increases the risk for immune complications (resistance and allergy). Overall, patients with NIDDM can benefit from insulin therapy.
Insulin Use in NIDDM
Authors: Genuth Saul
Published: March 2007

The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms for an atherogenic action of insulin exist, current evidence does not prove cause and effect and does not warrant withholding insulin therapy (or compromising on dosage) when it is needed.
Glycemic Index of Foods in Individual Subjects
Authors: Wolever Thomas M S , Jenkins David J A , Vuksan Vladimir , Josse Robert G , Wong Gerald S , Jenkins Alexandra L
Published: March 2007

We studied 12 subjects with diabetes to determine how well the glycemic index (Gl) predicted the ranking of glycemic responses of different foods in individuals. All subjects ate three mixed meals (bread, rice, or spaghetti with GIs of 100, 79, and 61, respectively) four times in a randomized complete block design. The mean glycemic response areas of the different meals ranked according to the predicted Gl in every individual. The observed mean ± SD Gl values of the meals were significantly different from each other (bread 100 ± 7, rice 75 ± 9, spaghetti 54 ± 9), with no significant difference in response between subjects. It is concluded that individuals share common mean Gl values for different foods. Within confidence limits determined by the variability of glycemic responses, the number of repeated tests conducted, and the expected Gl difference, the Gl can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals.
Effect of Coronary Artery Disease on Parasympathetic Cardiovascular Reflexes in NIDDM Patients
Authors: Airaksinen K E Juhani , Koistinen M Juhani , Ikäheimo Markku J , Pirttiaho Heikki , Huikuri Heikki V , Takkunen Juha T
Published: March 2007

To evaluate the effect of coronary artery disease on parasympathetic cardiac reflexes in patients with noninsulin- dependent diabetes mellitus (NIDDM), we studied standard cardiovascular reflexes in 27 NIDDM patients with coronary artery disease (group 1) and in 21 NIDDM patients with no signs of coronary artery disease (group 2). Groups did not differ with respect to age, duration of diabetes, or presence of retinopathy. The mean ± SD heart-rate variation in deep breathing was lower in group 1 than in group 2 (11.6 ± 6.5 vs. 17.1 ± 9.0 beats/min, P < 0.05). Heart-rate variation was more often abnormally low (<10 beats/min) in group 1 than in group 2 (48 vs. 19%, P < 0.05). Thus, the presence of coronary artery disease appears to modify cardiac parasympathetic reflexes in patients with diabetes mellitus and must be kept in mind when interpreting test results.
Psychological Impact of Islet Cell-Antibody Screening: Preliminary Results
Authors: Johnson Suzanne Bennett , Riley William J , Hansen Carolyn Apperson , Nurick Michael Alan
Published: March 2007

The identification of at-risk individuals before the onset of insulin-dependent diabetes mellitus with islet cellantibody (ICA) screening programs could have significant psychological sequelae. We initiated a descriptive study of ICA+ subjects and their family members in which reactions to study participation, anxiety, and coping responses are monitored. Described here are preliminary results from 18 ICA+ youngsters, 6 ICA+ adults, and their family members. ICA+ identification resulted in clinically significant anxiety that dissipated to normal levels over time for all participants. Both ICA+ subjects and family members coped with the news in similar ways, relying primarily on problemfocused and social-support coping strategies. Few blamed themselves for their own or their loved one's ICA+ status. There was some evidence that the ICA+ participants may minimize the potential impact of their at-risk status. Compared with family members, ICA+ subjects used more avoidance coping strategies, and few believed they would ever develop diabetes. In contrast, many family members believed their loved one would ultimately develop diabetes. Although the initial findings support the resiliency of this population, the long-term effects of ICA screening remain to be seen.
Molecular Biology for Nonmolecular Biologists
Authors: Chirgwin John M
Published: March 2007

Molecular biology offers various powerful tools for understanding the etiology of diabetes mellitus. These methods can be understood by nonmolecular biologists. Topics briefly introduced include 1) control of gene expression, 2) cloning of genes, 3) how gene promoters work, 4) transgenic mice, 5) mutagenesis in vitro, 6) human molecular genetics, and 7) the new powerful polymerase chain-reaction technique, which greatly simplifies many of the other methods.