bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenetic, Clinical, and Demographic Characterization of Childhood Type I Diabetes in New Zealand
Authors: Forbes Louisa V , Scott Russell S , Brown Laurie J , Darlow Brian A
Published: March 2007

OBJECTIVE

To examine the relationship between genetic susceptibility alleles and islet cell antibodies (ICAs) in type I diabetes.

RESEARCH DESIGN AND METHODS

The human leukocyte antigen (HLA)-DQB1 alleles and ICA levels of all incident type I diabetic cases in patients < 20 years of age diagnosed in 1990 and 1991 in Canterbury, New Zealand, were determined.

RESULTS

The mean annual incidence rate for type I diabetes over the 24 months was 19.0/100,000 patient-years (95% confidence interval [CI] 13.5−26.0/100,000), which was considerably higher than rates observed between 1982 and 1989 (11.7/100,000; 95% CI 9.6−14.3/100,000). ICAs ≥ 10 Juvenile Diabetes Foundation units (JDF U) were present in 84.6% of the subjects, but there was a higher prevalence of ICA-negative (ICA−) subjects among those diagnosed during the winter months. The frequencies of the susceptibility allele DQB1*0302 and susceptibility genotype 0302/0201 were 71.8% and 43.5%, respectively. Subjects with 0302 tended to be younger (mean age 8.3 ± 5.1 years) than those with nonsusceptibility types (mean age 11.8 ± 4.7 years, P = 0.056). The probability of being ICA positive (ICA+) was not significantly different between subjects with allele 0302 (85.7%) and those without it (81.8%). All seven patients negative for ICA were homozygous for DQB1 nonaspartate-57. There was no clustering of the immunogenetic markers with demographic and clinical characteristics apart from age at diagnosis.

CONCLUSIONS

No direct relationship was observed between DQB1-defined genetic susceptibility and ICA at diagnosis, suggesting that variations at the DQB1 locus are not linked to the expression of this autoimmune marker of β-cell destruction.
Nutrition Principles and Diabetes: A role for “lente carbohydrate”?
Authors: Jenkins David J A , Jenkins Alexandra L
Published: March 2007

The current nutrition recommendations of the American Diabetes Association (ADA) represent a thoughtful synthesis of much current data. They depart from tradition by not advocating specific figures for total fat and carbohydrate intake. Rather, since many issues are still topics of scientific debate, they endorse the principle of individualization and set guidelines accordingly. One topic that may be worthy of further debate is the principle of “spreading the nutrient load,” or lengthening the absorption time. This principle covers the effects of altered meal frequency, viscous dietary fibers, low-glycemic index foods, and inhibitors of carbohydrate absorption. In its simplest form it is illustrated by studies of altered meal frequency (“nibbling versus gorging”). Reducing the size and increasing the frequency of meals has been shown acutely to result in lower mean blood glucose and insulin levels over the day in type II diabetes and to result in reduced 24-h urinary C-peptide losses. In the longer term in nondiabetic subjects, total and low-density lipoprotein cholesterol levels are reduced, together with fasting apolipoprotein B and serum uric acid levels, as additional risk factors for coronary heart disease. These and other physiological effects make slowing carbohydrate absorption (“lente carbohydrate”) a potentially useful therapeutic modality. However, of the possible ways of slowing absorption, only alteration in meal frequency was of general interest in the current ADA nutrition recommendations. Nevertheless, the effects of slowing carbohydrate absorption by various means may have beneficial metabolic effects in diabetes and may support the use of ethnic foods in diets compatible with further modifications identified more favorably in the current nutrition recommendations (e.g., increased use of monounsaturated fat).
Impaired Retinal Artery Blood Flow in IDDM Patients Before Clinical Manifestations of Diabetic Retinopathy
Authors: Kawagishi Takahiko , Nishizawa Yoshiki , Emoto Masanori , Konishi Toshiaki , Maekawa Kiyoshi , Hagiwara Satoshi , Okuno Yasuhisa , Inada Hiroshi , Isshiki Gen , Morii Hirotoshi
Published: March 2007

OBJECTIVE

To determine whether hemodynamic changes in retinal arteries precede clinical manifestations of diabetic retinopathy and to examine the effects of control of hyperglycemia on retinal artery blood flow.

RESEARCH DESIGN AND METHODS

We assessed blood flow in bilateral central retinal arteries in 50 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 20 sex- and age-matched control subjects using duplex Doppler sonography. We determined the peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged velocity (TAV), resistance index (RI), and pulsatility index (PI).

RESULTS

PSV, EDV, and TAV were significantly lower in IDDM patients than in control subjects (P < 0.05, P < 0.01, and P < 0.01, respectively). The RI was significantly higher in IDDM patients than in control subjects (P < 0.01) and was significantly correlated with plasma levels of glucose in IDDM patients (r = 0.0.310, P = 0.0248). Multiple regression analysis identified the plasma levels of glucose as a significant determination of RI in IDDM patients. After 14 days of intensive insulin therapy in 7 IDDM patients, the RI and plasma levels of glucose showed significant decreases (P = 0.018, P = 0.001, respectively).

CONCLUSIONS

Our results showed that changes in retinal hemodynamics were present before the clinical detection of overt diabetic retinopathy and suggest that the presence of short-term hyperglycemia partly contributes to impaired retinal circulation.
Muscle Sympathetic Nerve Activity Is Higher in Intensively versus Conventionally Treated IDDM Subjects
Authors: Hoffman Robert P , Sinkey Christine A , Anderson Erling A
Published: March 2007

OBJECTIVE

To determine whether poor long–term glycemie control may play a role in the lower muscle sympathetic nerve activity (MSNA) levels in insulindependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

Intraneural electrodes were used to record MSNA from the peroneal nerve at baseline and during euglycemic insulin infusion (120 mU · m−2 · min−1) in 16 IDDM subjects enrolled in the Diabetes Control and Complications Trial (DCCT), 8 intensively treated (HbAlc 7.1 ± 1.2%) and 8 conventionally treated (HbA1c 9.0 ± 1.5%; P < 0.05).

RESULTS

Fasting plasma glucose levels tended to be higher at baseline in the conventionally treated group (11.3 ± 1.7 mmol/l) than in the intensively treated group (7.4 ±1.1 mmol/l, P < 0.1), but did not differ during insulin infusion (conventional, 5.0 ± 0.3 mmol/l; intensive, 5.1 ± 0.4 mmol/l). Plasma free insulin levels did not differ between groups either before or during insulin infusion. The intensively treated group had significantly higher MSNA levels than the conventionally treated group both in the fasting state (16.2 ± 2.7 vs. 10.5 ± 4.4 bursts/min, P < 0.05) and during insulin infusion with euglycemia (27.8 ± 2.1 vs. 17.5 ± 5.2 bursts/min).

CONCLUSIONS

MSNA levels in intensively treated IDDM subjects are higher than in conventionally treated subjects. These results suggest that improved long-term glycemie control is associated with increased sympathetic neural outflow to muscle. The mechanism for this effect remains unclear.
Trial of Pentoxifylline for Diabetic Impotence
Authors: Georgitis William J , Merenich John A
Published: March 2007

OBJECTIVE

To test the effectiveness of pentoxifylline as a therapy for diabetic impotence.

RESEARCH DESIGN AND METHODS

A 3-month placebo-controlled double-blind treatment study was conducted at a single center. Therapeutic response was assessed subjectively by serial self-appraisals of erectile function and objectively by nocturnal penile tumescence (NPT) monitoring.

RESULTS

This cohort of impotent diabetic men displayed substantial neurological and penile vascular dysfunction. Age, body mass index, duration of diabetes, duration of impotence, glycemie control, mode of therapy for non-insulin-dependent diabetes, mean testosterone, mean prolactin, and penile brachial indexes were similar in the treatment (n = 34) and placebo groups (n = 26). NPT monitoring revealed infrequent erectile events, diminished average rigidity, and decreased tumescence. Pentoxifylline did not alter overall glycemie control and did not improve neurological, vascular, or erectile function. In fact, a slight decrease in average percent rigidity from 22 ± 3 to 17 ± 2% (mean ± SE, P < 0.05) was observed in the pentoxifylline-treated group. Although eight (24%) pentoxifylline-treated and five (19%) placebo-treated men reported benefit, no objective improvement was observed in nocturnal tumescence.

CONCLUSIONS

Pentoxifylline is not an effective treatment for diabetic erectile dysfunction.
Implementation of Treatment Protocols in the Diabetes Control and Complications Trial
Authors:   Diabetes Control and Complications Trial Research Group
Published: March 2007

OBJECTIVE

To describe the methods used to implement intensive and conventional therapies in the Diabetes Control and Complications Trial (DCCT) and the metabolic results that occurred with the different treatment regimens.

RESEARCH DESIGN AND METHODS

The DCCT was a controlled clinical trial that demonstrated the beneficial effect of intensive therapy on the long-term complications of insulin-dependent diabetes mellitus (IDDM). A total of 1,441 volunteers with IDDM, aged 13–39, from 29 centers in the U.S. and Canada, were randomly assigned to conventional or intensive diabetes therapy. Intensive therapy, which used multiple daily injections (MDI) of insulin (≥3 injections/day) or continuous subcutaneous insulin infusion (CSI1), was implemented by a team that included diabetes nurses, dietitians, behavioral experts, and diabetologists. Volunteers in the intensive treatment group could use MDI or CSII, based on patient and clinic preference, and could switch between therapies over the course of the study. The volunteers were followed for a mean of 6.5 years (range 3–9 years).

RESULTS

A detailed analysis of implementation of the two treatments indicates that intensive and conventional treatment subjects adhered to their respective insulin injection regimens >97% of the time. Adherence to other elements of intensive treatment was similarly high and resulted in median HbAlc values between 6.7 and 7.2, compared with 8.7–9.2 with conventional therapy, over the course of the study. Severe hypoglycemia occurred three times more often in intensively treated subjects. Although subjects on intensive treatment were not randomly assigned to MDI or CSII, we compared those subjects who used either of these methods for >90% of the study time. CSIIy-treated patients maintained a mean HbAlc of 6.8 vs. 7.0 in MDI-treated subjects during the trial (P < 0.05). The frequency of hypoglycemia with coma and seizure and diabetic ketoacidosis was modestly higher with CSII than with MDI.

CONCLUSIONS

Intensive therapy was implemented successfully in the DCCT. The detailed description herein will serve to facilitate translation of the DCCT results to the clinical setting.
Glucokinase Gene Variants in Subjects With Late-Onset NIDDM and Impaired Glucose Tolerance
Authors: Laakso Markku , Malkki Mari , Kekäläinen Päivi , Kuusisto Johanna , Mykkänen Leena , Deeb Samir S
Published: March 2007

OBJECTIVE

To investigate the frequency of variants of the glucokinase (GCK) gene in subjects with late-onset non-insulin-dependent diabetes mellitus (NIDDM) and in subjects with late-onset impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

The study population included 36 Finnish patients with late-onset NIDDM who were treated with diet for >8 years or who were newly diagnosed and 40 subjects with late-onset IGT who had low or normal insulin levels when tested by an oral glucose tolerance test. All exons, exon-intron junctions, and islet and liver promotor regions of the GCK gene were amplified with the polymerase chain reaction and screened for mutations using single-strand conformation polymorphism analysis.

RESULTS

A silent third-base substitution (TAC→TAT) in codon 215 of exon 6 was found in 2.8% of NIDDM patients and in 5.0% of IGT subjects. Polymorphisms were found in islet exon 1 at nucleotide 403 (C→G) in 16.7% of NIDDM patients and in 17.5% of IGT subjects and in the noncoding region of the islet promotor at nucleotide -30 (G→A) in 13.9% of NIDDM patients and in 25.0% of IGT subjects. Furthermore, in liver intron 1 a variant (C→T), 12 base pairs upstream from the splice acceptor site, was found in 5.6% of NIDDM patients and in 7.5% of IGT subjects.

CONCLUSIONS

These results indicate that the mutations in the coding region of the GCK gene are not likely to play a major role in the pathogenesis of late-onset NIDDM or IGT in the Finnish population.
Muscarinic Cholinergic Antagonism Does Not Enhance Recovery From Hypoglycemia in IDDM
Authors: Hvidberg Annemarie , Cryer Philip E
Published: March 2007

OBJECTIVE

Because muscarinic cholinergic agonism in the absence of an increase in glucagon secretion inhibits hepatic glucose production, we tested the hypothesis that muscarinic cholinergic antagonism enhances glucose recovery from hypoglycemia in insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

Eight (initially euglycemic) patients with IDDM received overnight infusions of insulin and were studied on three occasions in random order. Hypoglycemia was induced by low-dose insulin infusion (4.0 pmol·kg−1 min−1) from 0 through 80 min; observations were continued through 240 min. At 0 and 80 min, intravenous injections of atropine only (1.0 mg), placebo and then atropine, respectively, or placebo only were administered.

RESULTS

Increments in heart rate (P < 0.001) and prevention of the pancreatic polypeptide response to hypoglycemia (P = 0.042) after atropine administration documented muscarinic cholinergic antagonism. The absent glucagon response to hypoglycemia was unaltered, but the epinephrine response was increased (P = 0.010). Nonetheless, rates of glucose production and utilization and plasma glucose concentrations were unaltered.

CONCLUSIONS

We conclude that muscarinic cholinergic antagonism does not enhance glucose recovery from hypoglycemia in patients with IDDM.
Early Involvement of Central Nervous System in type I Diabetic Patients
Authors: Bax Giuseppe , Lelli Stefania , Grandis Umberto , Cospite Anna Maria , Paolo Negrin , Fedele Domenico
Published: March 2007

OBJECTIVE

To investigate whether the asymptomatic involvement of the central and peripheral nervous systems may be an early complication of diabetes.

RESEARCH DESIGN AND METHODS

We studied early impairment of the central and peripheral nervous system pathways in 15 type I diabetic patients with good metabolic control and short disease duration and in 10 healthy control subjects using a set of neurophysiological tests.

RESULTS

Results in diabetic subjects showed 1) impairment of motor (7% and somatosensory (13%) pathways of the central nervous system, 2) impairment of motor and sensory conduction velocities (40–60%), and 3) normal values of the vibration perception threshold and cardiovascular autonomic tests.

CONCLUSIONS

The damage is more evident in peripheral sites where hyperglycemia and aldose reductase pathways are more active. Instead, several episodes of hypoglycemia, which occur in type I diabetic patients in good metabolic control, may cause alterations of brain nervous cells.
Diabetes and Impaired Glucose Tolerance in Three American Indian Populations Aged 45-74 Years: The Strong Heart Study
Authors: Lee Elisa T , Howard Barbara V , Savage Peter J , Cowan Linda D , Fabsitz Richard R , Oopik Arvo J , Yeh Jeunliang , Go Oscar , Robbins David C , Welty Thomas K
Published: March 2007

OBJECTIVE

To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry.

RESEARCH DESIGN AND METHODS

This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio.

RESULTS

A total of 4,549 eligible participants were examined, and diabetes status was determined for4,304(1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status.

CONCLUSIONS

Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs shoula be expanded to include those with IGT to improve glycemie control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.
A Comparison Between Alternative and Trade Name Glucose Test Strips
Authors: Lenhard M James , Cherney G Stephen De , Maser Raelene E , Patten Bernardine C , Kubik Jennifer
Published: March 2007

OBJECTIVE

To determine the reliability of seven different alternative glucose test strips manufactured for use with three different glucose meters.

RESEARCH DESIGN AND METHODS

Venous blood samples were obtained from volunteers to test trade name glucose test strips on the manufacturers' glucose meters (One Touch II, Glucometer II, and Glucometer III), and the remainder of each sample was used for laboratory determination of blood glucose levels. In addition to the trade name test strips, Quick Check and First Choice test strips were tested on all meters, and Biotel test strips were also tested on the Glucometer III.

RESULTS

In linear regression analysis, the R2 ranged from 0.84 to 0.97 for the test strips compared with plasma glucose values. The test strips with the highest accuracy and precision at all ranges of blood glucose levels were the One Touch II and Glucometer III trade name strips and the Quick Check and First Choice alternative strips for the One Touch II glucose meter and the First Choice alternative strip for the Glucometer II. Subgroup analysis based on ranges of blood glucose values, however, revealed that the alternative strips were not as accurate as the trade name test strips, with the exception of the First Choice alternative test strip for the Glucometer II. All of the trade name test strips were more precise than the alternative test strips designed for the individual meters.

CONCLUSIONS

Alternative glucose test strips can be used to predict the actual laboratory blood glucose values but are generally not as accurate or precise as the trade name test strips.
Effects of Enalapril and Nitrendipine on the Excretion of Epidermal Growth Factor and Albumin in Hypertensive NIDDM Patients
Authors: Josefsberg Zeev , Ross Stuart A , Lev-Ran Arye , Hwang David L
Published: March 2007

OBJECTIVE

To compare the effect of the antihypertensive drugs nitrendipine and enalapril on the excretion of epidermal growth factor (EGF) and albumin in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) subjects.

RESEARCH DESIGN AND METHODS

After a 4-week washout period, mildly hypertensive (systolic blood pressure [sBP] > 140 mmHg and/or diastolic blood pressure [dBP] >90 mmHg) NIDDM patients with albuminuria (15-200 μg/min) were randomized into an 8-month-long therapy with either nitrendipine (n = 11) or enalapril (n = 10). Blood pressure, EGF, and microalbumin excretion were measured at baseline and throughout the treatment period.

RESULTS

A significant fall in sBP was noticed in the enalapril group and in dBP in the nitrendipine group. In the enalapril group, EGF excretion progressively increased from 188 to 214 nmol/mmol creatinine after 6 weeks and to 274 after 8 months of therapy (P = 0.03). There was a significant fall in albumin excretion while patients were on enalapril, but in the nitrendipine group, neither albuminuria nor EGF excretion changed significantly. There was no correlation of improved EGF excretion with a decrease in albuminuria or BP.

CONCLUSIONS

The angiotensin-converting enzyme inhibitor enalapril has been effective in decreasing albumin and increasing EGF excretion. Measurement of urinary EGF may provide a new valuable index of renal function.
Prevalence and Associated Features of Albuminuria in Koreans with NIDDM
Authors: Lee Ki-Up , Park Joong Y , Kim Sang W , Lee Mee H , Kim Ghi S , Park Su-Kil , Park Jung-Sik
Published: March 2007

OBJECTIVE

To determine the prevalence and the associated features of microalbuminuria and overt proteinuria in Korean subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic.

RESEARCH DESIGN AND METHODS

A total of 631 Korean outpatients with NIDDM were studied cross-sectionally for the presence of albuminuria and other micro- and macrovascular complications. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples. Subjects were divided into three groups: no nephropathy (AER <20 μg/min), microalbuminuria (AER 20–200 μg/min), and overt proteinuria (AER >200 μg/min).

RESULTS

Increased AER was present in 34% of our patients: 20% had microalbuminuria and 14% had overt proteinuria. Of patients with diabetes duration ≥ 15 years, 35% had overt proteinuria. Most (82%) patients with overt proteinuria had retinopathy. Although the prevalence of microalbuminuria as a whole did not differ according to diabetes duration, the prevalence of microalbuminuria in the patients with retinopathy increased with diabetes duration. The microalbuminuric patients without retinopathy (diabetes duration < 5 years) were characterized by higher prevalence of hypertension and previous obesity, higher plasma triglyceride level, and lower plasma high-density lipoprotein cholesterol level.

CONCLUSIONS

The prevalence of overt proteinuria in Korean NIDDM patients with a long diabetes duration was higher than that reported in Caucasians. Our data also suggest that the clinical meaning of microalbuminuria may be different based on the presence or the absence of retinopathy. Microalbuminuria in patients with retinopathy most probably would reflect diabetic nephropathy. In contrast, some recent-onset NIDDM patients with microalbuminuria in the absence of retinopathy had features of syndrome X.
Local Reaction Secondary to Insulin Injection: A potential role for latex antigens in insulin vials and syringes
Authors: Towse Alison , O'Brien Maureen , Twarog Frank J , Braimon Jennifer , Moses Alan C
Published: March 2007

OBJECTIVE

To evaluate the possibility that latex antigens (natural rubber) can contribute to or cause local sensitivity at insulin injection sites.

CASE

A subject with documented local cutaneous allergic reactions at the site of insulin injections and with systemic latex allergy manifested as anaphylaxis was tested with intradermal injections of insulin diluent from two manufacturers and with two brands of insulin syringes.

RESULTS

The subject had high titer anti-latex Ige and elevated total levels of IgE in serum. Anti-insulin IgG and IgE antibodies were absent. Erythema and wheals occurred at the sites of intradermal injection of insulin therapy components (insulin diluent and syringes) that contain natural latex rubber but not at the site of injection of insulin therapy components that do not contain natural latex rubber.

CONCLUSIONS

Small quantities of natural latex rubber antigens in insulin injection materials can be sufficient to produce local cutaneous reactions at the site of insulin injection in individuals highly allergic to natural latex rubber.
Effect of Pregnancy On Renal Function in Patients With Moderate-to-Severe Diabetic Renal Insufficiency
Authors: Purdy Lisa P , Hantsch Christina E , Molitch Mark E , Metzger Boyd E , Phelps Richard L , Dooley Sharon L , Hou Susan H
Published: March 2007

OBJECTIVE

Previous studies of patients with diabetic nephropathy and mild renal impairment have suggested no determination in renal function as a result of pregnancy. The objective of this study was to determine whether pregnancy may permanently worsen renal function in women with diabetic nephropathy and moderate-to-severe renal insufficiency.

RESEARCH DESIGN AND METHODS

Eleven patients were identified with diabetic nephropathy and moderate-to-severe renal dysfunction (creatinine [Cr] ≥ 124 μmol/l [1.4 mg/dl]) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate were estimated by using linear regression of the reciprocal of Cr over time. An equal number of nonpregnant premenopausal type 1 diabetic women with similar degrees of renal dysfunction served as a comparison group for nonpregnant rate of decline of renal function and potential contributing factors.

RESULTS

Mean serum Cr rose from 159 μmol/l (1.8 mg/dl) prepregnancy to 221 μmol/l (2.5 mg/dl) in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%. Exacerbation of hypertension or preeclampsia occurred in 73%. Seven patients progressed to dialysis 6–57 months postpartum, with 71% (five of seven) of these cases attributed to acceleration of disease during the pregnancy. Student's t tests and repeated-measures analysis of variance support a pregnancy-induced acceleration in the rate of decline of renal function.

CONCLUSIONS

In this series, patients with diabetic nephropathy and moderate-to-severe renal insufficiency were found to have a > 40% chance of accelerated progression of their disease as a result of pregnancy.
The Efficacy of Tolrestat in the Treatment of Diabetic Peripheral Neuropathy: A meta-analysis of individual patient data
Authors: Nicolucci Antonio , Carinci Fabrizio , Graepel Jay G , Hohman Thomas C , Ferris Frederick , Lachin John M
Published: March 2007

OBJECTIVE

The aim of this meta-analysis was to review the existent evidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy.

RESEARCH DESIGN AND METHODS

Individual patient data on 738 subjects from the three randomized clinical trials published on this topic were analyzed using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves investigated included median, ulnar, tibial, and peroneal.

RESULTS

The pooled analysis of NCV taken as a continuous measurement showed a significant treatment effect, the magnitude of this benefit being approximately equal to 1 m/s for all the nerves investigated. When looking at the proportion of patients experiencing a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves investigated, it emerged that treatment reduced by > 40% the risk of such outcomes after adjusting for patients' characteristics. The odds ratios relative to the placebo group were 1.82 (1.30–2.52) and 1.70 (1.15–2.48) for a decrease of 1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk for a loss of nerve function of 1 and 2 m/s, respectively. No statistically significant difference in treatment effect emerged after stratification according to baseline motor NCV and glycated hemoglobin levels.

CONCLUSIONS

After a treatment duration ranging between 24–52 weeks, patients treated with tolrestat had a reduced risk for developing nerve function loss compared with placebo-treated patients. Future long-term trials are needed to evaluate the impact of the treatment on more clinically meaningful endpoints such as the development of foot complications.
Lipoprotein (a) Levels in African-Americans with NIDDM
Authors: Scheer W Douglas , Boudreau Donald A , Cook Curtiss B
Published: March 2007

OBJECTIVE

The purpose of this study was to investigate possible relationships between lipoprotein (a) [Lp(a)] levels and NIDDM in African-Americans. The objectives were to identify associations between Lp(a) levels of subjects with and without NIDDM and to determine the influence of glycemic control, determined by GHb, and of mode of therapy on Lp(a) levels.

RESEARCH DESIGN AND METHODS

We studied 141 African-American subjects, 103 with NIDDM and 38 without NIDDM. Their Lp(a) levels, GHb levels, and apolipoprotein (a) [apo(a)] isoforms were determined. Clinical information, including mode of therapy (sulfonylurea, insulin, or no pharmacological therapy), date of diagnosis, and medical history, was obtained by chart review and patient interview.

RESULTS

There was no significant difference in median Lp(a) levels between the non-NIDDM (25.5 mg/dl) and NIDDM (24.0 mg/dl) study subjects. No statistically significant difference was found in Lp(a) levels when NIDDM patients with GHb < 12.3% were compared to those with GHb ≥ 12.3% (P = 0.096). An inverse relationship was found between apo(a) root-mean-square isoform size and Lp(a) level (r2 = 0.091, P = 0.0035). Analysis of the cases by mode of therapy indicates that there is evidence of an increased median level of Lp(a) in African-Americans with NIDDM on insulin therapy relative to those on sulfonylurea (34.0 vs. 16.0 mg/dl; P = 0.013) and to nondiabetic subjects (34.0 vs. 25.5 mg/dl; P = 0.043).

CONCLUSIONS

We conclude that the level of plasma Lp(a) is higher in African-Americans with NIDDM who are being treated with insulin when compared to those on sulfonylurea therapy and to those who are non-NIDDM subjects, and this does not seem to be due to genetic variance or method bias.
Thrombolytic Therapy in Diabetic Patients with Acute Myocardial Infarction
Authors: Hansen Hans-Henrik T , Kjærgaard Søren C , Bülow Inge , Fog Lars , Christensen Per D
Published: March 2007

OBJECTIVE

To compare the frequency of thrombolytic therapy in diabetic and nondiabetic patients with acute myocardial infarction (MI) and to examine why some diabetic patients do not receive thrombolytic therapy.

RESEARCH DESIGN AND METHODS

Retrospective study of all diabetic patients with acute MI admitted to the coronary care unit of Aalborg Hospital within a 3-year period.

RESULTS

Only 35% (43 of 123) of patients with diabetes compared with 47% (404 of 856) of patients without diabetes received thrombolytic therapy (P < 0.002). There was no difference in the percentage of patients thrombolyzed among patients admitted to the hospital within 12 h after onset of symptoms. Of diabetic patients who were not thrombolyzed, 60% (48 of 80) arrived at the hospital later than 12 h after onset of symptoms. Among patients who arrived late, 63% (35 of 56) had Q wave infarction and 84% (47 of 56) had symptoms typical of acute MI. Mortality was 29% (16 of 56) in this group. Only one patient did not receive thrombolytic therapy due to diabetic retinopathy.

CONCLUSIONS

Significantly fewer diabetic patients received thrombolytic therapy compared with patients without diabetes. The main reason diabetic patients did not receive thrombolytic therapy was late arrival to the hospital.
The Role of Patient Participation in the Doctor Visit: Implications for adherence to diabetes care
Authors: Golin Carol E , DiMatteo M Robin , Gelberg Lillian
Published: March 2007

For patients, treatment of diabetes involves complex changes in basic behaviors and adherence to complicated regimens. Understanding the factors that enable patients to adhere to diabetes treatment is the first step to designing effective interventions. Researchers of diabetes care have postulated that increasing diabetic patients' participation in medical decision making during the doctor visit is likely to improve their adherence to self-care. However, a critical review of the impact of patient participation on diabetic patients adherence to self-care is absent from the literature. We review the subject of patient participation in medical decision making and its effect on adherence to self-care for patients with diabetes. We introduce a model of the determinants of adherence to diabetes self-care that incorporates the effects of patient participation in medical decision making. In this model, we suggest three ways that patient participation can affect adherence to self-care: 1) it may have a direct effect; 2) it may affect adherence to self-care indirectly by affecting patients' understanding of their treatment regimen or the fit of their regimen with their lifestyle; and 3) perceived omissions of participation can affect adherence to self-care indirectly through an effect on patient satisfaction. Research is needed to identify more clearly which components of patient participation affect adherence to self-care and in what ways. Distinguishing patient and physician behaviors that contribute to the process of patient participation would provide a means to develop specific behavioral interventions.
Detection by Competitive Enzyme-Linked Immunosorbent Assay of a Bovine Serum Albumin Peptide (ABBOS) in Infant Formulas Based on Hydrolyzed Cow's Milk Protein
Authors: Van Beresteijn Emerentia C H , Meijer Ron J G M
Published: March 2007

OBJECTIVE

Our aim was to determine whether currently available products based on hydrolyzed milk protein and a small peptide (ABBOS) in bovine serum albumin (BSA) (positions 126–144) share common antigenic sites. The commercial products are primarily developed to reduce cow's milk protein-associated allergenicity, but whether they also could be used in intervention trials to elucidate the role of BSA in the etiology of IDDM is not known.

RESEARCH DESIGN AND METHODS

A sensitive competitive enzyme-linked immunosorbent assay (ELISA) using a rabbit polyclonal antibody raised against the ABBOS peptide in BSA was developed. With this method, we determined cross-reactivity between the ABBOS peptide and commercially available products: four milk protein hydrolysates and eight infant formulas based on hydrolyzed milk protein. The products were further characterized by physicochemical techniques.

RESULTS

Hydrolyzed milk protein products are found to inhibit competitively the binding of ABBOS peptide to antibody. The number of residual reactive sites varied considerably among products and was not strongly related to the degree of hydrolysis (DH) or the molecular mass distribution of the hydrolysates.

CONCLUSIONS

The presence of possible immunoreactive peptides in infant formulas based on hydrolyzed cow's milk protein cannot be adequately predicted by the DH or molecular mass distribution of the hydrolysates. Its specific determination is needed to ensure infant formulas free of cross-reactive ABBOS antibody binding sites for use in ongoing and forthcoming intervention trials to elucidate the role of BSA as a possible environmental triggering agent of IDDM.
Sequential Trends in Overall and Cause-Specific Mortality in Diabetic and Nondiabetic Pima Indians
Authors: Sievers Maurice L , Nelson Robert G , Bennett Peter H
Published: March 2007

OBJECTIVE

To compare sequential trends in overall and cause-specific death rates for diabetic and nondiabetic Pima Indians.

RESEARCH DESIGN AND METHODS

Underlying causes of death in Pimas aged 15 years old were determined for the years 1975–1989 from review of death certificates and medical records. Overall and cause-specific death rates were compared for consecutive intervals.

RESULTS

The all-causes death rate, age- and sex-adjusted, did not change significantly between the first and second halves of the study for diabetic (death rate ratio [DRR] = 0.99, 95% CI 0.70–1.4) or nondiabetic Pimas (DRR = 0.92, 95% CI 0.74–1.1). Among diabetic Pimas, however, the death rate for diabetic nephropathy declined from 2.7 to 1.5/1,000 person-years (DRR = 0.55, 95% CI 0.33–0.93), with ischemic heart disease (IHD) replacing diabetic nephropathy as the leading cause in the second half (DRR = 1.5, 95% CI 0.91–2.6). For diabetic and nondiabetic Pimas combined, the death rate in three consecutive 5-year periods declined progressively for alcoholic liver disease (P = 0.024) and external causes of death (P = 0.016), the largest component of which was automobile accidents.

CONCLUSIONS

The decrease in death rate for diabetic nephropathy may be a result of greater access to and improvements in renal replacement therapy. Because of shared risk factors, however, the IHD death rate increased and largely offset the decrease in diabetic nephropathy deaths. The decline in deaths from alcoholic liver disease and from automobile accidents parallels the national trend.
Acute Effect of Cigarette Smoking on Glucose Tolerance and Other Cardiovascular Risk Factors
Authors: Frati Alberto C , Iniestra Felipe , Ariza C Raul
Published: March 2007

OBJECTIVE

To investigate the acute effect of cigarette smoking on glucose tolerance, insulin sensitivity, serum lipids, blood pressure, and heart rate.

RESEARCH DESIGN AND METHODS

This nonrandomized experimental control trial in a tertiary care center included 20 healthy chronic smokers and 20 age-, sex-, and BMI-matched healthy volunteers. Two oral glucose tolerance tests (OGTTs) were performed on each subject. Three cigarettes were smoked during the first 30 min in one of the tests. Serum glucose, insulin, and C-peptide levels were measured every 30 min; the area under the curve (AUC) and the insulin sensitivity index (ISI) were calculated; serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were measured at 0 and 180 min; and blood pressure and heart rate were recorded every 5 min throughout 180 min.

RESULTS

Smoking acutely impaired glucose tolerance: the AUC for glucose in smokers was 25.5 ± 1.03 mmol/l (mean ± SE) (95% CI 22.9–28) during the smoking OGTT and 21.8 ± 0.85 mmol/l (CI 19.2–24.3) in the control OGTT (P < 0.01); in nonsmokers, it was 19.7 ± 0.3 mmol/l (CI 18.8–20.5) in the smoking OGTT and 18.7 ± 0.35 mmol/l (CI 17.8–19.5) in the control OGTT (P < 0.05). Smoking acutely increased serum insulin and C-peptide levels and decreased ISI only in smokers: ISI in smokers was 55 ± 2.8 (CI 47.4–62.6) in the control OGTT and 43 ± 2.7 (CI 35.4–50.6) in the smoking OGTT (P < 0.05). Smoking acutely caused a rise of serum total cholesterol levels in both groups and increased LDL cholesterol and triglyceride serum levels significantly only in smokers (P < 0.05). A significant rise of blood pressure and heart rate while smoking was present in all the subjects.

CONCLUSIONS

Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate. These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors.
Antibodies to Bovine Serum Albumin in Brazilian Children and Young Adults With IDDM
Authors: Pardini Victor C , Vieira José G H , Miranda Walkíria , Ferreira Sandra Roberta G , Velho Gilberto , Russo Ewaldo M K
Published: March 2007

OBJECTIVE

To evaluate the prevalence of IgG antibodies to bovine serum albumin (BSA) in a cohort of Brazilian children and young adults with IDDM.

RESEARCH DESIGN AND METHODS

Sera from 81 subjects with < 1 year of IDDM (group 1), III subjects with > 1 year of IDDM (group 2), and 207 normoglycemic subjects were tested using an immunofluorimetric assay. A receiver-operating-characteristic curve was used to establish the threshold of anti-BSA antibody titers defining the positivity of the assay.

RESULTS

The distribution of the fluorimetric index (FI) of anti-BSA antibodies did not have a gaussian profile. Rank sum of FI was significantly higher in patients than in control subjects (P < 0.0001). Average logFI values of both IDDM groups were significantly higher than that of the control group (P < 0.005 for both groups). There was a trend toward higher FI levels in group 1 than in group 2 (P = 0.06). A FI cutoff of 0.7 optimized the ratio of true-positive to false-positive of the assay, with the best equilibrium between sensitivity and specificity. The prevalence of anti-BSA antibodies was 52% in group 1, 47% in group 2, and 28% in the control group (P = 0.0001). An independent association between anti-BSA antibodies and IDDM, with an odds ratio of 3.03 (P < 0.0001), was observed in a logistic regression analysis. However anti-BSA antibodies explained only 5% of the variability of IDDM versus NIDDM.

CONCLUSIONS

Our results confirm that the prevalence of anti-BSA antibodies is higher in IDDM subjects than in control subjects, even after 1 year of diabetes. However, a large overlap of antibody titers is observed in patients and control subjects, suggesting that anti-BSA antibodies are neither sensitive nor specific markers of IDDM.
Serum Lipid and Lipoprotein Metabolism After Glucose Ingestion in NIDDM and IGT Patients: Apolipoprotein-containing particles
Authors: Nagai Takashi , Tomizawa Takashi , Minamide Seiki , Nakajima Katsuyuki , Mori Masatomo
Published: March 2007

OBJECTIVE

Through analysis of apolipoprotein-containing particles after glucose ingestion, we determined abnormal lipid metabolism in NIDDM patients and subjects with impaired glucose tolerance (IGT) without obesity or hyperlipidemia.

RESEARCH DESIGN AND METHODS

Apolipoprotein (apo) AI- or B100- containing particles or remnant-like particles (RLPs) were isolated by immunoafnnity columns prepared with monoclonal antibodies. The cholesterol contents in these particles after glucose ingestion (0, 30, 60, and 120 min) were analyzed in 18 nonobese NIDDM patients, 18 nonobese IGT subjects, and 33 normal control subjects.

RESULTS

Changes in cholesterol content in apo B100 particles after oral glucose ingestion decreased significantly in both the NIDDM group and the IGT group; the changes were insignificant in the nondiabetic group. Changes in cholesterol content in the apo AI particles after oral glucose ingestion showed no differences between the three groups. Changes in cholesterol content in RLPs after oral glucose ingestion increased significantly in both the NIDDM group and IGT group; the changes were insignificant in the nondiabetic group. The changes in apo B100 after oral glucose ingestion decreased significantly in the three groups; however, apo AI after oral glucose ingestion showed no change in the three groups.

CONCLUSIONS

The cholesterol content in apo B100 particles might decrease and the cholesterol content in RLPs might increase after oral glucose ingestion in not only NIDDM patients but also IGT subjects. The changes may be partially due to insulin resistance.
No Association Between The Gly971 Arg Variant of the Insulin Receptor Substrate 1 Gene and NIDDM in the Taiwanese Population
Authors: Chuang Lee-Ming , Lai Chuen-Shianf , Yeh Jih-I , Wu Huey-Peir , Tai Tong-Yuan , Lin Boniface J
Published: March 2007

OBJECTIVE

To study the role of the Gly971 Arg variant of the insulin receptor substrate 1 (IRS-1) gene in the development of NIDDM in the Chinese population living in Taiwan.

RESEARCH DESIGN AND METHODS

A total of 82 unrelated normal control subjects, 89 subjects with NIDDM, and 23 multiplex families were recruited in Taiwan. All of them were Han Chinese. Pedigree members without a history of diabetes were studies by the standard 75-g oral glucose tolerance test. Detection of the Gly971 Arg variant of the IRS-1 gene was performed by polymerase chain reaction and restriction fragment-length polymorphism analysis.

RESULTS

The frequency of Gly971 Arg variant of the IRS-1 gene in the normal population was 1.2% which was lower than frequencies reported in white populations. The prevalence of the Gly971 Arg variant was not significantly increased in both the nonselected NIDDM population (1.1%) and the probands of the multiplex families (4.3%). More importantly, the Gly971 Arg variant of the IRS-1 gene did not cosegregate with BMI and NIDDM in these families,

CONCLUSIONS

The Gly971 Arg variant of the IRS-1 gene is an infrequent normal allele among Taiwanese. This variant is neither associated nor cosegregated with NIDDM in the Taiwanese population and families. Gly971 Arg of IRS-1 gene does not play an important role in the development of NIDDM in this population.
Rapid Gastric Emptying of a Solid Pancake Meal in Type II Diabetic Patients
Authors: Schwartz Joyce G , Green Gary M , Guan Difu , McMahan C Alex , Phillips William T
Published: March 2007

OBJECTIVE

To estimate the rate of gastric emptying of a solid pancake carbohydrate meal in recently diagnosed asymptomatic type II diabetic patients compared with nondiabetic control subjects.

RESEARCH DESIGN AND METHODS

Gastric emptying studies using radiolabeled meals were performed on eight recently diagnosed asymptomatic diabetic patients and on eight sex-, BMI- and age-matched nondiabetic control subjects. Although a liquid protein drink was administered along with the pancake meal, the radioactivity was adherent to only the pancake portion of the meal. Plasma glucose and serum insulin levels were measured in fasting and postprandial blood samples collected at 15-min intervals up to 120 min after ingestion of the mixed nutrient meal.

RESULTS

The average gastric half-emptying time (time it takes for one-half of the meal to empty) was significantly more rapid for the diabetic patients (45.3 ± 4.8 min) when compared with the nondiabetic control subjects (60.4 ± 5.1 min; P = 0.05). The serum insulin concentrations were not statistically different between the two groups. Plasma glucose values were significantly higher in the diabetic patients compared with the nondiabetic control subjects.

CONCLUSIONS

Type II diabetic patients with no clinical evidence of neuronal dysfunction have a significantly more rapid rate of gastric emptying of a solid high-carbohydrate meal when compared with nondiabetic control subjects.
Effect of Follow-Up of Women With Gestational Diabetes on the Ratio of IDDM to NIDDM in Pregnancy
Authors: Beischer Norman A , Wein Peter , Sheedy Mary T , Dargaville Richard M
Published: March 2007

OBJECTIVE

We wished to test the hypothesis that the diagnosis of diabetes in women with previous gestational diabetes in our follow-up program had altered the ratio of IDDM to NIDDM in our pregnant population.

RESEARCH DESIGN AND METHODS

We identified all pregnancies managed at the Mercy Hospital for Women in Melbourne, Australia, from 1971 to 1994 that were complicated by prepregnancy diabetes. In these 374 pregnancies, we identified those women who had previously been diagnosed with gestational diabetes mellitus (GDM). The changing prevalences over time of prepregnancy IDDM and NIDDM, as well as the contribution to both of these conditions made by women who had previously had GDM, were calculated.

RESULTS

Over the period of the study, there was an increase in the prevalence of IDDM from 0.15 to 0.44% (χ2 for trend, P < 0.00001) and NIDDM from 0.03 to 0.11% (χ2 for trend, P = 0.0001). The proportion of all women with diabetes with NIDDM did not change significantly (16.7–20%). There was a progressive increase in the proportion of women with NIDDM who had had GDM (from 8.3 to 39.1%), but the trend was not statistically significant (P = 0.059). Women with NIDDM were more likely (20 of 64, 31.3%) to have had gestational diabetes in the past than women with IDDM (12 of 310, 3.9%, odds ratio 11.3, 95% CI 5.16–24.7, P < 0.0001).

CONCLUSIONS

Despite finding relatively young women to have NIDDM, our GDM follow-up clinic has not yet altered significantly the ratio of IDDM to NIDDM in pregnancy.