bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies Toward Improved Control During Insulin Lispro Therapy in IDDM: Importance of basal insulin
Authors: Ebeling Pertti , Jansson Per-Anders , Smith Ule , Lalli Carlo , Bolli Geremia B , Koivisto Veikko A
Published: March 2007

OBJECTIVE

To examine whether overall glycemic control can be improved with insulin lispro by adjustment of the basal insulin regimen without an increased risk of hypoglycemia.

RESEARCH DESIGN AND METHODS

A 5-month open study was performed in 66 IDDM patients after they had been transferred from human regular insulin to insulin lispro as a premeal therapy. The premeal and basal insulin regimens were adjusted according to self-monitoring of blood glucose during the visits at 2-week to 1-month intervals. Diurnal glucose profile, hypoglycemic events, HbA1c, and patient satisfaction were evaluated.

RESULTS

The mean daily glucose level decreased from 9.2 ± 0.2 to 8.4 ± 0.2 mmol/l (P = 0.001) and HbA1c decreased from 8.8 ± 0.1 to 8.0 ± 0.1% (P < 0.001) (mean ± SD). The number of daily NPH injections increased from 1.4 ± 0.1 at baseline to 3.1 ± 0.1 at the end of the study. Total daily insulin dose increased by 3 U (7%) because of an 8-U (43%) rise in basal insulin, whereas premeal insulin dose decreased by 5 U (20%). The number of hypoglycemic episodes did not change during the study. Of the patients, 86% considered insulin lispro equal or better than human regular insulin.

CONCLUSIONS

Although the study was open, the date suggest that the appropriate combination of insulin lispro and basal insulin can improve postmeal hyperglycemia, HbA1c, and treatment satisfaction without increasing the risk of hypoglycemia.
Diabetic Retinopathy, Promoter (4G/5G) Polymorphism of PAI-1 Gene, and PAI-1 Activity in Pima Indians With Type 2 Diabetes
Authors: Nagi Dinesh K , McCormack Lynn J , Mohamed-Ali Vidya , Yudkin John S , Knowler William C , Grant Peter J
Published: March 2007

OBJECTIVE

To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We studied 171 Pima Indians with type 2 diabetes between the ages of 30–70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative.

RESULTS

Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 ± vs. 19.7 ± 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated with duration of diabetes (rs = −0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated with fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi χ2 = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively.

CONCLUSIONS

Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic retinopathy.
Treatment of Diabetic Ketoacidosis Using Normalization of Blood 3-Hydroxybutyrate Concentration as the Endpoint of Emergency Management: A randomized controlled study
Authors: Wiggam M Ivan , O'Kane Maurice J , Harper Roy , Atkinson A Brew , Hadden David R , Trimble Elisabeth R , Bell Patrick M
Published: March 2007

OBJECTIVE

To compare the efficacy of an extended insulin regimen using correction of hyperketonemia as endpoint with a more conventional regimen in the treatment of diabetic ketoacidosis.

RESEARCH DESIGN AND METHODS

A total of 22 patients admitted to a Belfast teaching hospital with clinical and biochemical features of diabetic ketoacidosis (pH < 7.25 and/or bicarbonate < 16 mmol/l) were randomized to either conventional or extended insulin regimens. In the conventional regimen, insulin was administered at 5 U/h until near-normoglycemia (blood glucose ≤ 10 mmol/l) and then administered at a reduced rate until clinical recovery. In the extended regimen, administration of insulin at 5 U/h was continued beyond attainment of normoglycemia, until resolution of hyperketonemia (3-hydroxybutyrate < 0.5 mmol/l). Main outcome measures were 3-hydroxybutyrate and bicarbonate levels during the 24 h after attainment of near-normoglycemia.

RESULTS

After near-normoglycemia, correction of hyperketonemia was achieved earlier with the extended treatment (5.9 ± 0.8 vs. 21.8 ± 3.4 h, P = 0.0004 [mean ± SD]). The area under the curve of 3-hydroxybutyrate against time for 24 h after near-normoglycemia was reduced with the extended treatment (24.9 ± 3.8 vs. 55.9 ± 6.7 mmol·l−1·h−1 P = 0.001). These differences remained statistically significant after adjustment for higher baseline levels of 3-hydroxybutyrate at near-normoglycemia in the extended treatment group. Bicarbonate levels at 6 and 12 h after near-normoglycemia were not significantly different between groups.

CONCLUSIONS

The extended insulin regimen, which was easy to implement at ward level, produced a more rapid resolution of ketosis than the conventional regimen.
Maternal Serum Ferritin and Gestational Impaired Glucose Tolerance
Authors: Lao Terence T , Tam Kar-Fai F
Published: March 2007

OBJECTIVE

To determine if the reported features of decreased iron store in the infant of diabetic mother are related to underlying maternal iron deficiency, a prospective case-control study was performed on a group of low-risk antenatal patients without preexisting anemia or thalassemia trait and before the diagnosis of gestational diabetes mellitus (GDM) in the last trimester.

RESEARCH DESIGN AND METHODS

At the time of routine screening for anemia and GDM at 28–30 weeks of gestation, an additional blood sample was collected for the assay of serum ferritin, iron, and total iron binding capacity (TIBC). Patients with elevated random sugar underwent a 75-g oral glucose tolerance test (OGTT), interpreted by the World Health Organization criteria. For each person diagnosed with GDM, a control subject matched in maternal age and parity was identified, and their iron status and hematological indexes were compared.

RESULTS

There were 60 patients with gestational impaired glucose tolerance (GIGT), and none had frank GDM. There was no difference in the hematological indexes or serum iron and TIBC values, but serum ferritin level was significantly increased in the GIGT group, when compared with control subjects.

CONCLUSIONS

The findings indicate that there was no evidence of preexisting iron deficiency in the third trimester before the diagnosis of GIGT, while serum ferritin was even increased in the GIGT patients, a phenomenon that could have reflected the glucose intolerance. Serum ferritin is probably an unreliable index for maternal iron therapy in these patients, and the role of iron therapy in GIGT patients remains to be established.
Effects of a Behavioral Intervention on Treatment Adherence and Stress Management in Adolescents With IDDM
Authors: Méndez Francisco J , Beléndez Marina
Published: March 2007

OBJECTIVE

To evaluate the effects of a behavioral program to increase treatment adherence and to improve stress management in adolescents with IDDM.

RESEARCH DESIGN AND METHODS

A quasi-experimental pretest-posttest design with a nonequivalent control group was used. Eighteen subjects were assigned to the experimental group, which received the program, while nineteen subjects made up the control group, which received routine medical care. During the 12 intervention sessions with diabetic adolescents, different procedures were applied: instruction, blood glucose discrimination training, role-playing, relaxation exercises, self-instructions, problem-solving strategies, and homework, among others.

RESULTS

The results show significant changes in the experimental group in variables related to diabetes information (patients and their parents), adherence, daily hassles, uneasiness and likelihood of response in social interactions, skills and frequency of glycemic analyses, blood glucose estimate errors, and negative family support (parents). The program had no effect on either dietary and physical exercise or glycemic control. The improvements, which were maintained at a follow-up carried out 13 months after finishing the program, were: patients' information about physiopathology (P = 0.000), diet (P = 0.000), physical exercise (P = 0.048), glucose testing (P = 0.030), and insulin (P = 0.000), barriers to adherence frequency (P = 0.000), severity of daily hassles (P = 0.006), and degree of uneasiness in social interaction (P = 0.000).

CONCLUSIONS

This research introduces the novelty of integrating several behavioral procedures within a wide-ranging package that affects aspects implied in diabetes control such as treatment adherence and stress management. The testing of similar programs on samples of subjects with glycemic control difficulties would be useful.
Excess Costs of Medical Care for Patients With Diabetes in a Managed Care Population
Authors: Selby Joe V , Ray G Thomas , Zhang Danya , Colby Chris J
Published: March 2007

OBJECTIVE

To estimate the excess costs of medical care for patients with diabetes in a managed care population and to determine the proportion of costs spent on treating the complications of diabetes.

RESEARCH DESIGN AND METHODS

A comparison of 1-year (1994) costs of medical care in the 85,209 members of the diabetes registry of Kaiser Permanente, Northern California, and in 85,209 age- and sex-matched nondiabetic control subjects. Costs were obtained from automated program databases. Costs specifically related to treating acute and long-term complications of diabetes were identified, and the excess costs attributable to each complication in individuals with diabetes were calculated.

RESULTS

Excess expenditures in individuals with diabetes totaled $282.7 million, or $3,494 per person. Per person expenditures for members with diabetes were 2.4 times those for matched control subjects. The largest proportion of total excess costs was for hospitalizations within the health maintenance organization (38.5%). Nearly 38% of the total excess was spent treating the long-term complications of diabetes, predominantly coronary heart disease and end-stage renal disease.

CONCLUSIONS

Diabetes is a costly condition by virtue of its high prevalence and high per person costs. A large proportion of these costs are related to treating complications of diabetes. Available evidence indicates that several measures can reduce complication rates. Thus, effective disease management programs that aim to prevent complications could potentially lead to cost savings in managed care settings.
Evaluation of ICA512As in Combination With Other Islet Cell Autoantibodies at the Onset of IDDM
Authors: Feeney Sandra J , Myers Mark A , Mackay Ian R , Zimmet Paul Z , Howard Neville , Verge Charles F , Rowley Merrill J
Published: March 2007

OBJECTIVE

The ICA512 pancreatic islet autoantigen is a putative tyrosine phosphatase that is co-identified with the earlier described 40-kDa autoantigen. We report the frequency of autoantibodies to islet cell antigen 512 (ICA512As) in recent-onset IDDM and compare this with other islet cell autoantibodies, including those to GAD (GADAs), insulin (IAAs), and islet cell cytoplasm (ICAs) identified by immunofluorescence.

RESEARCH DESIGN AND METHODS

Sera from 232 children aged between 9 months and 14.9 years collected within 14 days of diagnosis were tested for ICA512As by a radioimmunoprecipitation assay. The results were compared with previously reported data for GADAs (n = 232), IAAs (n = 167), and ICAs (n = 230).

RESULTS

The frequency of a positive result for ICA512As in children with newly diagnosed IDDM was 60%. The frequency was greater for children with an age of onset between 5 and 10 years (69%) than for children aged < 5 years (49%) and aged between 10 and 15 years (56%). The frequencies for other autoantibody reactivities were 69% for GADAs, 65% for IAAs, and 70% for ICAs. A combination of positive results for ICA512As, GADAs, and IAAs gave a sensitivity for the diagnosis of childhood IDDM of 95%, which was not significantly increased by a positive result for ICAs (96%).

CONCLUSIONS

Our results further establish that positivity in a combination of tests is more valuable for the prediction of IDDM than a result for any single autoantibody and that the age of the patient should be considered when selecting the combination of tests to use.
Evidence That Plasma Leptin and Insulin Levels are Associated With Body Adiposity Via Different Mechanisms
Authors: Schwartz Michael W , Prigeon Ronald L , Kahn Steven E , Nicolson Marjery , Moore Jason , Morawiecki Andrew , Boyko Edward J , Porte Daniel
Published: March 2007

OBJECTIVE

Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM.

RESEARCH DESIGN AND METHODS

We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (S1) was also determined in a subset of nondiabetic subjects (n = 38).

RESULTS

Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to S1 (r = −0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and S1 was not. Conversely, the relationship between plasma leptin and BMI was independent of S1, whereas that between insulin and BMI was dependent on S1. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observedin nondiabetic subjects.

CONCLUSIONS

We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM doesnot influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to bedifferent.
The Efficacy of Self-Monitoring of Blood Glucose in NIDDM subjects: A criteria-based literature review
Authors: Faas A , Schellevis F G , Eijk J T M Van
Published: March 2007

OBJECTIVE

To determine the efficacy of self-monitoring of blood glucose (SMBG) in NIDDM patients from studies published during the years 1976–1996.

RESEARCH DESIGN AND METHODS

A systematic literature search was conducted. The selected studies were assessed for their methodological quality and reviewed on the reported efficacy and on the following topics: characteristics of the study population, follow-up duration, nature of the efficacy measures, use of a therapy decision scheme, nature of the intervention, nature of the SMBG device, patient instruction, type of SMBG regime, assessment of the frequency of self-measurement, and whether feedback was given on the measured glucose levels. Studies with positive conclusions on the efficacy of SMBG were compared with studies with negative conclusions on the basis of the these characteristics to determine which factors could have contributed to the results.

RESULTS

Of the 11 studies identified, only 4 met all quality criteria. Six of the studies were randomized controlled trials, of which only one showed positive conclusions regarding the efficacy of SMBG. Although the studies differed on most topics, no factor could be identified as responsible for the results of the studies.

CONCLUSIONS

The efficacy of SMBG in NIDDM patients is still questionable and should be tested in a rigorous high-quality randomized controlled trial, for which some recommendations are given.
Association of Symptoms of Type 2 Diabetic Patients With Severity of Disease, Obesity, and Blood Pressure
Authors: Bulpitt Christopher J , Palmer Alison J , Battersby Clare , Fletcher Astrid E
Published: March 2007

OBJECTIVE

The symptoms of 430 type 2 diabetic patients were determined by a self-administered questionnaire before entry into the U.K. Prospective Diabetes Study.

RESEARCH DESIGN AND METHODS

Entry into the trial followed 2 months of dietary treatment for newly diagnosed patients with type 2 diabetes. Forty symptoms with five levels of severity were included in the questionnaire. A complaint rate was computed as the sum of symptom scores divided by the number of symptom questions answered.

RESULTS

The complaint rate was independently and positively related to BMI, fasting plasma glucose (FPG), and being a woman. Three symptoms—presence of dry mouth (P < 0.001), thirst (P < 0.01), and stomach pain (P = 0.02)—were related to FPG independent of sex, age, BMI, or blood pressure. Only dry mouth was related to HbA1c (P = 0.05). Complaints of shortness of breath, swollen ankles, headaches, heartburn, sweating, wheezing, nocturia, thirst, and diarrhea increased with BMI independently of other variables. A complaint of cold extremities decreased with BMI. Heartburn, weakness of limbs, and hot flushes were positively related to blood pressure, and unsteadiness was negatively related.

CONCLUSIONS

The symptoms reported by patients with type 2 diabetes increased with FPG and markedly with BMI. The symptoms associated with obesity have been underestimated in the past.
Intact Proinsulin, des 31,32 Proinsulin, and Specific Insulin Concentrations Among Nondiabetic and Diabetic Subjects in Populations at Varying Risk of Type 2 Diabetes
Authors: Nagi Dinesh K , Knowler William C , Mohamed-Ali Vidya , Bennett Peter H , Yudkin John S
Published: March 2007

OBJECTIVE

To examine hyperinsulinemia, insulin secretion, and β-cell function in Pima Indians, South Asians, and whites, populations at varying risk of diabetes.

RESEARCH DESIGN AND METHODS

We investigated 136 Pima Indian, 98 Asian, and 80 white nondiabetic and 172 Pima Indian, 40 Asian, and 49 white diabetic subjects. Highly specific assays for insulin, intact proinsulin, and des 31,32 proinsulin were used. Insulin secretion was assessed using ratio of increment (0 to 30 min) in insulin to glucose concentrations during an oral glucose tolerance test (OGTT).

RESULTS

Nondiabetic Pima Indians were significantly more obese than Asians and whites. Pima Indian subjects had significantly higher (P < 0.01) fasting insulin concentrations (median 109 pmol/l, range 40−250) than Asian (37 pmol/l, range 17−91) and white (30 pmol/l, range 10−82) subjects. These differences remained significant when controlled for obesity. Nondiabetic Pima Indians also had higher fasting C-peptide concentrations and higher early insulin secretion during an OGTT. Fasting concentrations of intact proinsulin and des 31,32 proinsulin were also significantly higher in Pima Indians (P < 0.01). However, the proportion of proinsulin-like molecules was significantly lower (P < 0.01) in Pima Indians (median 7.9% vs. 12.7% for South Asians and 12.2% for whites). Subjects with diabetes from the three ethnic groups showed significantly higher fasting insulin concentrations but lower 30-min insulin and lower ratios of increment (0−30 min) in insulin to glucose concentrations than did nondiabetic subjects. The proportion of proinsulin-like molecules was not significantly different in diabetic subjects from the three ethnic groups.

CONCLUSIONS

These specific assays for insulin indicate that after adjusting for obesity nondiabetic Pima Indians are truly hyperinsulinemic, which is consistent with their insulin resistance as measured by other methods. Hyperinsulinemia in this population with a high risk of diabetes is likely to be due to enhanced insulin secretion. Furthermore, in Pima Indians, the predominant β-cell secretory product is insulin and not its precursors. We conclude that the differences in the risk of diabetes among these three groups are not due to differences in insulin secretion or insulin processing. Subjects with type 2 diabetes have defective early insulin secretion during OGTTs but show fasting hyperinsulinemia even when specific assays for insulin are used.
Development and Progression of Diabetic Retinopathy in Koreans With NIDDM
Authors: Kim Hong-Kyu , Kim Chul-Hee , Kim Sang-Wook , Park Joong-Yeol , Hong Sung-Kwan , Yoon Young-Hee , Lee Ki-Up
Published: March 2007

OBJECTIVE

To determine the incidence and risk factors for the development and progression of diabetic retinopathy in Korean patients with NIDDM.

RESEARCH DESIGN AND METHODS

A total of 186 patients with NIDDM who did not have proliferative diabetic retinopathy (PDR) at baseline were prospectively studied for 5.3 ± 1.0 years in an outpatient clinic of a university hospital. The incidence and progression of diabetic retinopathy was determined by annual funduscopic examination by an ophthalmologist.

RESULTS

Of the 130 patients who were free of diabetic retinopathy at baseline, 30 developed it, giving an incidence of 44.4/1,000 person-years. Age and known duration of diabetes, mean fasting plasma glucose, and HbA1 levels during the follow-up period were higher in the patients who developed diabetic retinopathy. Of the 56 patients who had nonproliferative diabetic retinopathy at baseline, 11 developed PDR, giving an incidence of 37.5/1,000 person-years. The patients who progressed to PDR during follow-up (progressors) had a higher change of BMI and urinary albumin excretion rate at baseline and a higher mean HbA1 during the follow-up period than the nonprogressors. Cox proportional hazards analysis revealed that mean HbA1 was the only independent risk factor for both the development and progression of diabetic retinopathy.

CONCLUSIONS

The incidence of PDR in Korean NIDDM patients is comparable to that reported in other populations. Poor glycemic control is the most important risk factor for both the development and progression of diabetic retinopathy in NIDDM patients.
UKPDS 28: A Randomized Trial of Efficacy of Early Addition of Metformin in Sulfonylurea-Treated Type 2 Diabetes
Authors:   U.K. Prospective Diabetes Study Group
Published: March 2007

OBJECTIVE

To assess the efficacy over 3 years of the addition of metformin to maximum sulfonylurea therapy in type 2 diabetes.

RESEARCH DESIGN AND METHODS

This multicenter randomized open-controlled trial was conducted in outpatient diabetes clinics in 15 U.K. hospitals. A total of 591 subjects who had already been randomly allocated to sulfonylurea therapy were taking maximum doses with suboptimal glycemic control, i.e., raised fasting plasma glucose (FPG) concentrations of 6−15 mmol/l but no significant hyperglycemic symptoms. The main outcome measures included FPG, glycated hemoglobin, protocol-defined marked hyperglycemia, body weight, blood pressure, fasting plasma lipids, compliance, and hypoglycemia and other side effects.

RESULTS

After the addition of metformin, FPG concentrations decreased by mean (95% CI) −0.47 (−0.82 to −0.13) mmol/l over 3 years compared with an increase of 0.44 (0.07−0.81) mmol/l in subjects on sulfonylurea alone (P < 0.00001). Median FPG concentrations at 3 years were 8.6 vs. 9.9 mmol/l, respectively (P < 0.00001), and HbA1c values were 7.5 and 8.1%, respectively (P = 0.006). Adjustment for baseline BMI or FPG concentration did not affect response to therapy. Only 7% of those allocated to sulfonylurea plus metformin developed protocol-defined marked hyperglycemia compared with 36% of those allocated to sulfonylurea alone (P < 0.0001). Fasting plasma lipids, body weight, and blood pressure did not change significantly. The incidence of hypoglycemic episodes did not differ between groups: 4% on sulfonylurea plus metformin and 2% on sulfonylurea alone (NS).

CONCLUSIONS

Early addition of metformin improved glycemic control in patients with suboptimal glycemic control while taking maximum sulfonylurea therapy, irrespective of obesity or baseline FPG concentrations.
Carotid Artery Stiffness is Increased in Microalbuminuric IDDM Patients
Authors: Lambert Jan , Smulders Ronald A , Aarsen Mieke , Donker Ab J M , Stehouwer Coen D A
Published: March 2007

OBJECTIVE

In IDDM, the development of microalbuminuria, which is associated with an elevation in blood pressure within the normal range, is a risk factor for future cardiovascular disease. Vascular stiffness might be one of the factors involved because it increases systolic blood pressure and the workload of the heart.

RESEARCH DESIGN AND METHODS

We investigated carotid artery stiffness with a noninvasive ultrasound method in 24 microalbuminuric and 53 normoalbuminuric IDDM patients and in 54 healthy control subjects.

RESULTS

The distensibility coefficient, a measure of intrinsic vascular wall elasticity, was decreased in microalbuminuric IDDM (21.6 × 10−3/kPa) as compared with normoalbuminuric IDDM (24.8 × 10−3/kPa) and control subjects (25.9 × 10−3/kPa; P = 0.02). This result was based on a higher blood pressure in microalbuminuric patients. After correction for the difference in blood pressure, the distensibility coefficients were similar in the three groups. In the two diabetic patient groups taken together, age, blood pressure, female sex, diabetes duration, and cigarette smoking were determinants of a decreased distensibility.

CONCLUSIONS

Blood pressure is a major determinant of increased arterial stiffness in microalbuminuric IDDM patients. Increased arterial stiffness may contribute to the accelerated progression of complications if concomitant hypertension exists.
Descriptive Epidemiology of IDDM in Hokkaido, Japan: The Childhood IDDM Hokkaido Registry
Authors: Matsuura Nobuo , Fukuda Katsuhiro , Okuno Akimasa , Harada Shohei , Fukushima Naoki , Koike Akemi , Ito Yoshiya , Hotsubo Tomoyuki
Published: March 2007

OBJECTIVE

To identify the incidence of IDDM with regard to sex, age, family history of diabetes, season, and 5-year period of childhood IDDM among children ages 0–14 years from a population-based epidemiological study in Hokkaido, Japan, from 1973 to 1992.

RESEARCH DESIGN AND METHODS

Registration of all new IDDM cases in Hokkaido was conducted by the Childhood IDDM Hokkaido Registry Study Group from 1973 to 1992. The cases were selected from among 1) patients who were admitted to the member hospitals of the study group, 2) patients who answered a questionnaire distributed to hospitals and diabetic clinics throughout Hokkaido, and 3) patients whose cases were recorded in free-treatment medical records of urban and rural districts. The case ascertainment rate was estimated to be 100%. Differences in incidence with regard to sex, age, family history of diabetes, season, and year period were analyzed by the Poisson regression analysis by GENMOD.

RESULTS

During the 20-year period studied, 396 cases (181 boys, 215 girls) of abruptonset IDDM were registered. Statistically significant differences in annual incidence were found according to sex (female), age (8–14 years), history (having no diabetes in family), season (spring), and 5-year period.

CONCLUSIONS

This is the first population-based, long-term epidemiological study of childhood IDDM from Japan. We observed a significantly higher annual incidence (per 100,000/year) of IDDM in female subjects (1.81), older age-groups (2.25 for 8–14 years), subjects with no family history of diabetes (1.26), diabetes onset in the spring (2.20), and an increased trend over the 20 years. In addition, the heterogeneity of IDDM among Japanese children needs to be elucidated.
Lactic Acidosis Rates in Type 2 Diabetes
Authors: Brown Jonathan B , Pedula Kathryn , Barzilay Joshua , Herson Michael K , Latare Peggy
Published: March 2007

OBJECTIVE

To provide a context for the interpretation of lactic acidosis risk among patients using metformin, we measured rates of lactic acidosis in patients with type 2 diabetes before metformin was approved for use in the U.S.

RESEARCH DESIGN AND METHODS

Using electronic databases of hospital discharge diagnoses and laboratory results maintained by a large, nonprofit health maintenance organization (HMO), we identified possible lactic acidosis events in three geographically and racially diverse populations with type 2 diabetes. We then reviewed hard-copy clinical records to confirm and describe each event and determine its likely cause(s).

RESULTS

From <41,000 person-years of experience, we found four confirmed, three possible, and three borderline cases of lactic acidosis. In each case, we identified at least one severe medical condition that could have caused the acidosis. The annual confirmed event rate is similar to published rates of metformin-associated lactic acidosis.

CONCLUSIONS

Lactic acidosis occurs regularly, although infrequently, among persons with type 2 diabetes, at rates similar to its occurrence among metformin users. The medical conditions with which both metformin-associated and naturally occurring lactic acidosis cooccur are also its potential causes. The observed association between metformin and lactic acidosis may be coincidental rather than causal. This possibility merits further study.
Effect of Bacille Calmette-Guérin Vaccination on C-Peptide Secretion in Children Newly Diagnosed With IDDM
Authors: Elliott John F , Marlin Karen L , Couch Robert
Published: March 2007

OBJECTIVE

To determine whether administration of bacille Calmette-Guerin (BCG) vaccination to newly diagnosed IDDM patients can help preserve C-peptide secretion over the subsequent 18 months.

RESEARCH DESIGN AND METHODS

Twenty-six IDDM patients, all of whom had been diagnosed within the previous year, had basal C-peptide levels >0.06 nmol/1, and had negative reactions to Mantoux's test, were randomized pairwise as they presented and were given either 0.1 ml (100 μg) BCG vaccine or 0.1 ml saline intradermally. Both the patients and the investigators were blinded to the treatment. Fasting and glucagon-induced C-peptide levels and HbA1c were measured in all patients at enrollment and at 1, 3, 6, 9, 12, and 18 months after vaccination, and insulin dose was recorded at each visit.

RESULTS

At enrollment, there was no significant difference in age, duration of diabetes, insulin dose, HbA1c, or fasting C-peptide levels between the BCG-vaccinated and control groups. The mean basal and stimulated C-peptide levels in the BCG-treated group did not differ significantly from those in the control group at any time during the 18 months of followup, and there was no difference in insulin dose or HbA1c at any time between the groups.

CONCLUSIONS

BCG vaccination in children who have been recently diagnosed with IDDM does not affect the progressive decline in C-peptide levels or alter the clinical course of the disease.
Optimal Provision of Daytime NPH Insulin in Patients Using the Insulin Analog Lispro
Authors: Ahmed Abu Baker , Home Philip D
Published: March 2007

OBJECTIVE

Insulin lispro improves early postprandial blood glucose control but can result in late interprandial hyperglycemia. As an approach to resolving this problem, we performed a randomized, crossover study with four treatment arms, comparing the daytime metabolic profile after either premeal lispro alone or premeal lispro with optimal daytime NPH insulin and with standard human regular insulin.

RESEARCH DESIGN AND METHODS

Twelve C-peptide negative type 1 diabetic patients were studied on four separate study days, at least 7 days apart. On each study day, patients received one of the four study insulin treatments, in random order, with identical meals and snacks. The four treatments were 1) premeal human regular insulin before lunch and supper at unchanged dose; 2) premeal lispro (unchanged dose) at lunchtime and dinner; 3) prelunch reduced-dose lispro (70%) before lunch and supper with supplemental lunchtime NPH and with a 6-h interval until dinner; and 4) pre-lunch reduced-dose lispro (70%) before lunch and supper with supplemental lunchtime NPH and with a 8-h interval until dinner. All patients were using their usual premeal plus basal insulin regimen during the period of the study, with human regular insulin before meals and NPH insulin at bedtime.

RESULTS

Postprandial blood glucose concentrations (1230–1500) were lower after reduced or usual lispro dose compared with human regular insulin (5.5 ± 0.2 and 5.6 ± 0.2 vs. 8.2 ± 0.5 mmol/l, P < 0.001), with no difference between the lispro doses. However, preprandial (1800) blood glucose levels deteriorated to higher levels after usual-dose lispro alone compared with either human regular insulin (P < 0.05) or reduced-dose lispro plus NPH (P < 0.05) (8.9 ± 0.3 vs. 7.1 ± 0.8 and 6.4 ± 0.4 mmol/l), with no difference between human regular insulin and reduced-dose lispro plus NPH. During the 2 h between the usual and delayed mealtime, blood glucose concentrations remained controlled on lispro plus NPH (2000: 6.5 ± 0.4 mmol/l).

CONCLUSIONS

Reduced-dose lunchtime lispro plus NPH maintained the improvement in postprandial blood glucose control with no deterioration in interprandial blood glucose control, even up to a late meal.
Increased Nitrotyrosine in the Diabetic Placenta: Evidence for oxidative stress
Authors: Lyall Fiona , Gibson Janice L , Greer Ian A , Brockman Diane E , Eis Annie L , Myatt Laslie
Published: March 2007

OBJECTIVE

To evaluate the presence of nitrotyrosine (NT) residues in placental villous tissue of diabetic pregnancies as an index of vascular damage linked to oxidative stress.

RESEARCH DESIGN AND METHODS

Villous tissue was collected and Hash frozen after delivery from 10 class C and D IDDM patients (37.9 ± 3.2 weeks) and 10 normotensive pregnant individuals (37.5 ± 3.8 weeks). Serial sections of tissue were immunostained with specific antibodies to NT, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and manganese superoxide dismutase (MnSOD). Sections were scored for intensity of immunostaining (0–3) by three observers blinded to the identity of tissue.

RESULTS

All tissues demonstrated immunostaining for eNOS in both syncytiotrophoblast and stem villous vascular endothelium with no apparent differences between groups. Immunostaining for iNOS was seen in the villous stroma, but again was not different between the two groups. Significantly more intense NT staining was apparent in vascular endothelium and villous stroma (both P < 0.02) of diabetic placentas. The endothelium of large villous vessels of diabetic tissues also showed more intense immunostaining for MnSOD (P < 0.01).

CONCLUSIONS

In these diabetic pregnancies, we were unable to show increased eNOS, unlike previous findings in preeclamptic pregnancies. The presence of NT may indicate vascular damage in the diabetic placenta due to peroxynitrite action formed from increased synthesis/interaction of nitric oxide and superoxide. The apparently paradoxical increase in MnSOD expression may be an adaptive response to increased superoxide generation.
Plasma homocysteine concentrations in patients with type 1 diabetes.
Authors: Cronin C C , McPartlin J M , Barry D G , Ferriss J B , Scott J M , Weir D G
Published: March 2007

OBJECTIVE: To determine the plasma concentration of total homocysteine (tHcy), a recognized risk factor for vascular disease, in patients with type 1 diabetes and to examine the relationships with age, sex, duration of diabetes, microvascular complications and neuropathy, and folic acid concentration. RESEARCH DESIGN AND METHODS: Plasma tHcy and folic acid concentrations were measured in a randomly selected cohort of type 1 diabetic patients (n = 119), well characterized as regards microvascular complications, and in a matched control group (n = 51). RESULTS: Plasma tHcy was higher in male than in female control subjects (geometric mean [95% CI]: 9.3 [8.0-10.9] vs. 6.1 [5.2-7.2] micromol/l, P < 0.001), as previously described, but there was no sex difference in diabetic patients. Plasma tHcy significantly correlated with age in patients (r = 0.348, P < 0.01) but not in control subjects (r = 0.007, P = 0.96). Male patients without microvascular complications had lower plasma tHcy concentrations than did male control subjects (6.2 [5.1-7.5] vs. 9.3 [8.0-10.9] micromol/l, P < 0.001), but values in female patients without complications were similar to those of female control subjects. Plasma folic acid concentration was higher in diabetic patients than in control subjects. The expected negative association between plasma tHcy and folic acid was stronger in control subjects than in patients. CONCLUSIONS: Subnormal tHcy concentrations in male patients, the absence of a sex difference, and the positive association with age indicate that homocysteine metabolism differs between type 1 diabetic patients and control subjects. Homocysteine is unlikely to be of pathogenic significance in patients, particularly male subjects, with early microvascular disease and/or neuropathy.
Fasting plasma glucose in screening for diabetes in the Taiwanese population.
Authors: Chang C J , Wu J S , Lu F H , Lee H L , Yang Y C , Wen M J
Published: March 2007

OBJECTIVE: To reveal the relationship between fasting and 2-h postload plasma glucose and to examine the appropriate fasting glucose cutoff as the primary screening test for diabetes. RESEARCH DESIGN AND METHODS: We recruited 5,303 subjects from preventive services of the National Cheng Kung University Hospital. Exclusion criteria were age <20 years, pregnancy, known diabetes, and a history of recent surgery, trauma, or illness. All subjects received the 75-g oral glucose tolerance test. The relationship between fasting and 2-h glucose was examined. Sensitivities, specificities, efficiency, and predictive values were assessed at different cutoffs of fasting glucose for prediction of diabetes. RESULTS: The best fit model for the relationship between fasting and 2-h glucose was fasting glucose = 4.914-0.060 x (2-h glucose) + 0.0144 x (2-h glucose)2. From this model, the fasting glucose was 6.0 mmol/l when 2-h glucose was 11.1 mmol/l. A fasting glucose with 6.25 mmol/l gave the same diabetes prevalence as the World Health Organization 2-h glucose criterion. When 7.8 mmol/l was the fasting glucose cutoff, the sensitivity was 28.5%. Lowering the cutoff from 7.8 to 7.0 mmol/l increased the sensitivity by 11.2% and slightly reduced the specificity and positive predictive value. If the cutoffs were 6.25 and 6.0 mmol/l, the sensitivity increased and the specificity and the positive predictive value decreased accordingly. CONCLUSIONS: Our results suggest that fasting glucose as a screening criterion for diabetes could be revised downward to 7.0 mmol/l, because the slight reduction of positive predictive value was more than balanced by an apparent increase of sensitivity and insignificant change of specificity.
Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index.
Authors: Kovatchev B P , Cox D J , Gonder-Frederick L A , Young-Hyman D , Schlundt D , Clarke W
Published: March 2007

OBJECTIVE: To evaluate the clinical/research utility of the low blood glucose index (LBGI), a measure of the risk of severe hypoglycemia (SH), based on self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODS: There were 96 adults with IDDM (mean age 35+/-8 years, duration of diabetes 16+/-10 years, HbA1 8.6+/-1.8%), 43 of whom had a recent history of SH (53 did not), who used memory meters for 135+/-53 SMBG readings over a month, and then for the next 6 months recorded occurrence of SH. The SMBG data were mathematically transformed, and an LBGI was computed for each patient. RESULTS: The two patient groups did not differ with respect to HbA1, insulin units per day, average blood glucose (BG) and BG variability. Patients with history of SH demonstrated a higher LBGI (P < 0.0005) and a trend to be older with longer diabetes duration. Analysis of odds for future SH classified patients into low- (LBGI <2.5), moderate- (LBGI 2.5-5), and high- (LBGI >5) risk groups. Over the following 6 months low-, moderate-, and high-risk patients reported 0.4, 2.3, and 5.2 SH episodes, respectively (P = 0.001). The frequency of future SH was predicted by the LBGI and history of SH (R2 = 40%), while HbA1, age, duration of diabetes, and BG variability were not significant predictors. CONCLUSIONS: LBGI provides an accurate assessment of risk of SH. In the traditional relationship history of SH-to-future SH, LBGI may be the missing link that reflects present risk. Because it is based on SMBG records automatically stored by many reflectance meters, the LBGI is an effective and clinically useful on-line indicator for SH risk.
Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group.
Authors: Home P D , Lindholm A , Hylleberg B , Round P
Published: March 2007

OBJECTIVE: To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment. RESEARCH DESIGN AND METHODS: This was a multicenter randomized double-blind crossover study of 90 male subjects with type 1 diabetes. Insulin aspart or soluble human insulin was administered before meals, and NPH insulin was administered at bedtime as basal therapy. Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile. RESULTS: The 24-h plasma glucose control obtained with insulin aspart, as assessed by excursions of blood glucose outside a predefined normal range (4.0-7.0 mmo/l), was superior (22% reduction in excursion, P < 0.01). Fructosamine levels remained unchanged with insulin aspart, with daytime glycemic control superior but nighttime glycemic control inferior. Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postprandial blood glucose control after lunch and dinner (P < 0.05) without deterioration of preprandial blood glucose control. Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin (20 vs. 44 events, P < 0.002). Insulin aspart was well tolerated. CONCLUSIONS: In comparison with human insulin, insulin aspart can improve postprandial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes. For its full potential to be realized, it will need to provide better control of nighttime hyperglycemia.
An analysis of dynamic forces transmitted through the foot in diabetic neuropathy.
Authors: Shaw J E , van Schie C H , Carrington A L , Abbott C A , Boulton A J
Published: March 2007

OBJECTIVE: Biomechanical studies in diabetic neuropathy have clearly demonstrated abnormal foot pressures, but information on other aspects of gait is limited. This study aimed to investigate and describe the forces transmitted through the foot during walking in diabetic subjects with varying degrees of peripheral neuropathy and to determine if abnormalities in these forces might contribute to the risk of plantar ulceration. RESEARCH DESIGN AND METHODS: Subjects from the following groups were included: healthy control subjects (C); diabetic control subjects (D); subjects with diabetic neuropathy (DN); subjects with previous neuropathic ulceration (DNU); and subjects with Charcot neuro-arthropathy (CH). Gait analysis was performed as subjects walked over a Kistler force plate. Peak forces were measured (as percent body weight) in the vertical and horizontal planes. Comparisons were made between all of the groups and between each diabetic group and a healthy control group matched for walking speed. RESULTS: There were 181 subjects studied. In comparison with that of the speed-matched controls, the mean peak vertical force was higher in each of the diabetic groups, especially in the most neuropathic subjects (DNU, 113 vs. 110%, P < 0.01). This increase was entirely due to higher forces during heel contact (DNU, 111 vs. 106%, P < 0.001). The single peak force occurred during heel strike (rather than during foot push-off) in 23-38% of footsteps of healthy and diabetic control subjects but in 53-73% of footsteps of neuropathic subjects. There was also a trend for higher peak medial forces (CH, 6.2 vs. 5.5%, P < 0.05). CONCLUSIONS: Diabetic neuropathy is associated with a change in the time pattern of the forces transmitted through the foot and an increase in the vertical forces through the heel. The magnitude of the changes is small in absolute terms, but these changes may contribute to the risk of plantar foot ulceration.
Erectile dysfunction in diabetic subjects in Italy. Gruppo Italiano Studio Deficit Erettile nei Diabetici.
Authors: Fedele D , Coscelli C , Santeusanio F , Bortolotti A , Chatenoud L , Colli E , Landoni M , Parazzini F
Published: March 2007

OBJECTIVE: Our objective was to analyze the prevalence and risk factors for erectile dysfunction (ED) in men with diabetes in Italy in a cross-sectional study. RESEARCH DESIGN AND METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of IDDM or NIDDM who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: Of the 9,868 diabetic men interviewed, 3,534 (35.8%) reported ED. The prevalence increased with age, from 4.6% in men aged 20-29 to 45.5% in those aged > or =60 years (test for trend, P = 0.0001). After taking into account the confounding role of age, men with NIDDM reported ED less frequently than did men with IDDM (odds ratio [OR], 0.7; 95% CI 0.6-0.8). In comparison with men reporting diabetes lasting < or =5 years, the ORs for ED were 1.3 and 2.0 for subjects with diabetes lasting 6-10 and 11-30 years, respectively. In comparison with men with good metabolic control, the ORs for ED were 1.7 and 2.3 in men with fair and poor control, respectively. A history of diabetes-related arterial, retinal, or renal diseases and neuropathy was associated with an increased risk of ED. Finally, in comparison with never-smokers, the ORs for ED were 1.5 (95% CI 1.3-1.6) for current smokers and 1.4 (95% CI 1.3-1.6) for ex-smokers. The OR increased with number of cigarettes smoked per day: in comparison with men smoking <12 cigarettes per day, the OR was 1.5 (95% CI 1.3-1.7) for those smoking > or =30 cigarettes day. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men with diabetes.