bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Renal Morphological Changes in the Early Stage of Microalbuminuria in Adolescents With IDDM
Authors: Rudberg Susanne , Østerby Ruth , Dahlquist Gisela , Nyberg Gudrun , Persson Bengt
Published: March 2007

OBJECTIVE

To evaluate the impact of glycemic control, blood pressure, lipid levels, glomerular filtration rate (GFR), age, and duration of IDDM on the degree of structural glomerular changes in the transitional stage of microalbuminuria.

RESEARCH DESIGN AND METHODS

Fifteen adolescents (seven boys and eight girls) with > 5 years of duration of IDDM and with low-grade microalbuminuria (15–30 micrograms/min) participated. Seventeen living kidney donors served as healthy control subjects. Five-year mean HbA1c; 5-year mean systolic and diastolic blood pressure; GFR, cholesterol, and triglycerides 2–5 years before renal biopsy; age; and duration of IDDM were investigated and related to basement membrane thickness (BMT), mesangial and matrix volume fractions, and the overall glomerulopathy index [(BMT/10 + mat/glom, %) + matrix star volume].

RESULTS

BMT and the overall diabetic glomerulopathy were increased in diabetic patients as compared with control subjects (P < 0.001), whereas matrix volume fraction, but not mesangial volume fraction, tended to be increased (P = 0.11). In multivariate analysis, BMT was predicted by 5-year mean HbA1c, diabetes duration, and previous GFR (R2 = 0.71, P = 0.003). With matrix volume fraction as the dependent variable, BMT and diabetes duration were the only significant determinants (R2 = 0.63, P = 0.003). Diabetes duration, 5-year mean HbA1c, and GFR were the variables with an independent influence on the overall diabetic glomerulopathy index (R2 = 0.72, P = 0.003). Preceding blood pressure and lipid levels or age had no significant independent influence on these morphometric measures.

CONCLUSIONS

In the very early stage of microalbuminuria in IDDM adolescents, a high percentage of the variation in BMT and overall severity of glomerulopathy is explained by prolonged hyperglycemia and diabetes duration. Previous glomerular hyperfiltration may also add to the prediction of these morphological changes.
Incidence of Childhood-Onset IDDM in Black African-Heritage Populations in the Caribbean
Authors: Tull Eugene S , Jordan Oscar W , Simon Lester , Laws Mervyn , Smith D Orlando , Vanterpool Heskitt , Butler Cleve ,   The Caribbean African Heritage IDDM Study (CAHIS) Group
Published: March 2007

OBJECTIVE

To compare incidence rates of childhood-onset IDDM among black African-heritage populations age 0–19 years in the Caribbean region.

RESEARCH DESIGN AND METHODS

Population-based registries for IDDM were established on the eastern Caribbean islands of Antigua, Barbados, Dominica, St. Croix, St. Kitts, St. Thomas, and Tortola using standardized criteria from the World Health Organization (WHO) Multinational Project for Childhood Diabetes (DiaMond). Average annual incidence rates (IR) with 95% CI for 0–19 years olds were computed using the DiaMond Registry program for the 5-year period from 1989 to 1993. Poisson regression analysis was used to determine differences in incidence rates.

RESULTS

The highest incidence rate for 0–19 year olds was for the black African-heritage population of St. Croix (IR 10.09 per 100,000; 95% CI 4.35–19.89), one of the U.S. Caribbean islands. A significant (P < 0.05) 3.9 variation in IDDM incidence across the registries was found when the IR for St. Croix was compared to the IR for Barbados (IR 2.57 per 100,000; 95% CI 0.90–4.64).

CONCLUSIONS

The variation in childhood-onset IDDM incidence rates among the black populations of the eastern Caribbean islands is consistent with the geographic variation in IDDM incidence seen among African Americans in the U.S. Variation in incidence rates of childhood diabetes in black populations may reflect differences in level of white genetic admixture or exposure to environmental diabetogenic agents.
Prevalence of Latex-Specific IgE Antibodies in Atopic and Nonatopic Children With Type I Diabetes
Authors: Danne Thomas , Niggemann Bodo , Weber Bruno , Wahn Ulrich
Published: March 2007

OBJECTIVE

The potential induction of allergic sensitization to latex from insulin vial tops stimulated an investigation of the prevalence of specific IgE antibodies to latex in serum and the relationship to atopic disease in children with diabetes.

RESEARCH DESIGN AND METHODS

In a cross-sectional study, serum samples of 112 children with type I diabetes (age: 15 [5–18] years; diabetes duration: 6 [1–14] years; median [range]) were investigated for total IgE, IgE screening for inhalational and nutritional allergens, and specific IgE antibodies to latex.

RESULTS

Specific IgE antibodies for inhalational and/or nutritional allergens was found in 42 (38%) children (atopic group). Seven children (6%) exhibited specific IgE antibodies (0.61 [0.40–3.84] kU/I) to latex in serum although none reported clinical symptoms of latex allergy. All latex-sensitized children were found in the atopic group. This prevalence of latex sensitization of 17% (7/42) in atopic children with diabetes is comparable with the frequency described in atopic children without diabetes. These seven patients had higher serum total IgE antibody levels (328 [113–1,000] kU/I) than atopic patients without latex sensitization (n = 35; 124 [24–857] kU/I; P < 0.05) or patients without atopy (n = 70; 33 [2–339] kU/I; P < 0.001). No differences in age or diabetes duration were observed between either group.

CONCLUSIONS

Sensitization to latex is found exclusively in children with atopic sensitization and appears to be related to atopic disease and not to frequent contact to latex through insulin injections. However, atopic patients may be at risk for reactions secondary to latex from insulin vials and syringes.
Comparative Effects of Glibenclamide and Metformin on Ambulatory Blood Pressure and Cardiovascular Reactivity in NIDDM
Authors: Sundaresan Purnima , Lykos Denise , Daher Ali , Diamond Terence , Morris Richard , Howes Laurence G
Published: March 2007

OBJECTIVE

To compare the effects of chronic glibenclamide and metformin therapy on blood pressure (BP) and cardiovascular responsiveness in patients with NIDDM.

RESEARCH DESIGN AND METHODS

Fourteen patients with NIDDM received metformin or glibenclamide for 1 month in a double-blind, randomized crossover study. At the end of each treatment period, patients were tested for forearm vascular responsiveness to intrabrachial arterial infusion of diazoxide (an ATP-sensitive potassium channel opener), acetylcholine, sodium nitroprusside, and norepinephrine, BP responses to intravenous infusions of NE and angiotensin II, BP responses to cold pressor testing and isometric exercise, and 24-h ambulatory BP monitoring.

RESULTS

Metformin and glibenclamide produced similar glycemic control. Mean 24-h BPs did not differ between the two groups, but mean 24-h heart rates were significantly lower (75 ± 6 bpm vs. 80 ± 6 bpm) on glibenclamide therapy than on metformin. Plasma norepinephrine levels were significantly higher on glibenclamide (6.41 ± 1.77 vs. 4.26 ± 1.54 mmol/l, P < 0.01), and systolic BP responses to intravenous norepinephrine and angiotensin II were significantly higher on glibenclamide than on metformin (P < 0.02 and P < 0.05, respectively). Systolic BP responses to cold pressor testing appeared higher on glibenclamide than on metformin, but the difference did not quite achieve statistical significance (P = 0.052). Baseline forearm vascular resistance did not differ between the two drugs, nor did forearm vascular resistance responses to diazoxide, acetylcholine, sodium nitroprusside, and norepinephrine differ.

CONCLUSIONS

Glibenclamide therapy is accompanied by greater systolic BP responses to norepinephrine and angiotensin II and higher plasma norepinephrine levels than those that occur on metformin therapy. Lower heart rates on glibenclamide therapy despite evidence of greater sympathetic activity suggests that glibenclamide may have negative chronotropic effects.
Comparison of Metabolic Control in a Cross-Sectional Study of 2,873 Children and Adolescents With IDDM from 18 Countries
Authors: Mortensen Henrik B , Hougaard Philip ,   For the Hvidøre Study Group on Childhood Diabetes
Published: March 2007

OBJECTIVE

To obtain an estimate of the current level of metabolic control in children and adolescents with IDDM, the Hvidøre Study Group on Childhood Diabetes decided to establish a formal collaboration among countries to gather and exchange data for comparative purposes.

RESEARCH DESIGN AND METHODS

This cross-sectional non-population-based survey involved 22 pediatric departments from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from March through August 1995 on 2,873 children who were born in 1977 or later and seen in the outpatient clinics. HbA1c levels were determined once and analyzed centrally (normal range, 4.4–6.3%; mean, 5.4%). Year of birth, sex, duration of diabetes, height, body weight, insulin regimen, and number of episodes of severe hypoglycemia during the past 3 months were recorded.

RESULTS

Average HbA1c was 8.6 ± 1.7%, but varied significantly (P < 0.0001) between centers. Hypoglycemia resulting in unconsciousness and/or seizures was related to younger age (0–8 years) and lower HbA1c level. The incidence, based on the 3-month period, was 22 per 100 patient-years. Sixty percent of the children (n = 1,707) had two injections daily, while 37% (n = 1,071) were on three or more. HbA1c increased during maturation for both sexes. No difference in glycemic control was found among adolescents treated with two, three, and four or more daily injections. Adolescents on four or more injections received significantly (P < 0.001) more insulin. Girls on four or more injections had significantly (P < 0.01) higher BMI than girls on twice-daily insulin.

CONCLUSIONS

In the participating centers with a multidisciplinary team, only one third of the patients had an HbA1c level of < 8%.
Pubertal Growth, Sexual Maturation, and Final Height in Children With IDDM: Effects of age at onset and metabolic control
Authors: Salerno Mariacarolina , Argenziano Alessandro , Di Maio Salvatore , Gasparini Nicoletta , Formicola Stefania , De Filippo Glanpaolo , Tenore Alfred
Published: March 2007

OBJECTIVE

To evaluate growth and pubertal development in children with IDDM and the influence of the age at onset of IDDM and the degree of metabolic control on final height.

RESEARCH DESIGN AND METHODS

We conducted a retrospective evaluation of 62 subjects followed longitudinally both clinically and metabolically from the onset of IDDM until final height was reached.

RESULTS

Height at diagnosis was within the normal percentiles in boys (0.5 ± 1.0 standard deviation score [SDS]) and girls (0.4 ± 1.0 SDS), but above the genetic target height (−1.0 ± 0.9 SDS in boys and −1.1 ± 0.6 SDS in girls; P = 0.0001 for both comparisons). Although a lesser height gain was observed during the ensuing years, the final height reached by boys (−0.4 ± 1.1 SDS) and girls (−0.4 ± 0.9 SDS) was higher than the genetic target height. Blunted total pubertal growth was observed both in boys (24.5 ± 3.6 cm) and girls (20.1 ± 4.2 cm). The decrease in height gain was independent of the duration of IDDM, the degree of metabolic control, or the insulin requirement. The greater the height at diagnosis, with respect to the genetic target height, the lesser was the subsequent height gain to reach final adult height (r = 0.34, p < 0.01). BMI increased with age as normally occurs in healthy children, independent of the duration of disease and the degree of metabolic control. Pubertal development began and progressed normally both in boys and girls. In boys, a testicular volume of 4 ml was reached at a mean age of 12.1 ± 0.9 years. In girls, breast enlargement occurred at a mean age of 10.4 ± 1.2 years and the mean age of menarche was 12.8 ± 1.4 years. Pubertal development and progression occurred independent of the age at onset of IDDM, the glycemic control, or the insulin requirement during the pubertal period.

CONCLUSIONS

Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.
Effects of Aspirin or Basic Amino Acids on Collagen Cross-Links and Complications in NIDDM
Authors: Contreras Ivan , Reiser Karen M , Martinez Nahir , Giansante Elda , Lopez Tulio , Suarez Nancy , Postalian Sarkis , Molina Miguel , Gonzalez Freddy , Sanchez Maria R , Camejo Manuel , Blanco Maria C
Published: March 2007

OBJECTIVE

To determine if long-term therapy with aspirin or basic amino acids for subjects with NIDDM reduces the severity of clinical complications and/or reduces tissue levels of markers of glycooxidative damage.

RESEARCH DESIGN AND METHODS

Subjects with NIDDM were administered either aspirin (100 mg/day) or a combination of basic amino acids consisting of L-arginine (2 g/day) plus L-lysine (0.5 g/day) for 1 year. The study was double-blind and placebo-controlled. The presence and severity of retinopathy, nephropathy, and neuropathy were assessed in all subjects at 4-month intervals, as were serum blood glucose, glycohemoglobin levels, and presence of albuminuria. Collagen cross-linking and collagen glycation were measured in skin collagen obtained by biopsy at the beginning and the end of the study. Skin biopsies were also obtained from age-matched control subjects.

RESULTS

Skin samples obtained from NIDDM subjects at the beginning of the study had significantly increased levels of glucitolyllysine, pentosidine, and hydroxypyridinium, as compared with age-matched control subjects. Pentosidine levels were significantly correlated with severity of retinopathy and neuropathy, but not nephropathy. Subjects receiving aspirin, but not amino acids or placebo, had significantly decreased levels of skin pentosidine after 1 year of therapy.

CONCLUSIONS

It is concluded that 1) low-dose aspirin may reduce glycooxidative damage in people with NIDDM, and 2) treatment may need to continue for more than 1 year before clinical status improves.
The Role of Dynamic Plantar Pressures in Diabetic Foot Ulcers
Authors: Stess Richard M , Jensen Shayne R , Mirmiran Roya
Published: March 2007

OBJECTIVE

The significance of plantar pressure studies in detecting sites of plantar ulceration in diabetic patients was investigated.

RESEARCH DESIGN AND METHODS

A total of 97 diabetic patients participated in this study. History and physical data, such as history of smoking, type of diabetes, ankle/brachial indexes, and the presence of protective sensory threshold, were collected. Using the EMED-SF plantar pressure analyzer, dynamic pressure variables, such as normalized peak pressure of maximum pressure picture (MPP), pressure-time integral (PTI), and force-time integral (FTI), were measured in each foot. Statistical analysis included descriptive statistics and analyses of variance.

RESULTS

Out of 97 patients, 34 patients had no history of neuropathy and plantar ulceration (the diabetic control [DC] group). Another 14 patients had neuropathy with no previous history of plantar ulcers (the DN group), whereas the remainder of the patients had a history of peripheral neuropathy with plantar ulceration (the DU group). There were significant increases in MPP (P < 0.004) and PTI (P < 0.0004) levels in the DU group when compared with the DC group with the highest pressure present under the 4th and 5th metatarsal heads. No statistical significance existed among groups when comparing FTI levels.

CONCLUSIONS

Neuropathic patients have an increase in dynamic plantar foot pressures placing them at risk for plantar ulceration. Instruments such as the EMED-SF system can be helpful in detecting possible sites of plantar ulcerations by locating the areas of maximum pressure.
Open-Flow Microperfusion of Subcutaneous Adipose Tissue for On-Line Continuous Ex Vivo Measurement of Glucose Concentration
Authors: Trajanoski Zlatko , Brunner Gernot A , Schaupp Lukas , Ellmerer Martin , Wach Paul , Pieber Thomas R , Kotanko Peter , Skrabal Falko
Published: March 2007

OBJECTIVE

To evaluate a novel technique for on-line continuous glucose measurement in subcutaneous adipose tissue, and to investigate its accuracy for detection of hypoglycemia.

RESEARCH DESIGN AND METHODS

The method combined an open-flow microperfusion of subcutaneous adipose tissue using a double lumen catheter and an extracorporeal sensor cell. An isotonic ion-free solution was perfused through the inner lumen of the catheter, equilibrated with the subcutaneous tissue fluid, and sampled through the outer lumen. The recovery was continuously monitored as the ratio between the measured sampled fluid conductivity and the subcutaneous tissue fluid conductivity (assumed to have a constant value of 1.28 S/m at 25°C). Glucose concentration was calculated on-line from the measured glucose in the sampled fluid and the measured recovery in healthy volunteers during hyperglycemic glucose loads (n = 8), hypoglycemic hyperinsulinemic clamp (n = 6), and a 24-h monitoring period (n = 7).

RESULTS

Subcutaneous glucose concentrations in the fasting state were 94% of the plasma glucose concentrations in arterialized venous samples. According to the error grid analysis, 96.9% of the on-line measured subcutaneous glucose concentrations during hyperglycemia and 96.3% during hypoglycemia were in accurate or acceptable zones. The mean differences between the measured subcutaneous glucose and the actual plasma glucose concentration were −0.06–3.3 mmol/l (hyperglycemia), and −0.6–1.1 mmol/l (hypoglycemia).

CONCLUSIONS

By combining open-flow microperfusion, glucose sensor, and conductivity measurement, glucose concentration in the subcutaneous adipose tissue can be monitored on-line, extracorporeally, and continuously without any in vivo calibration, and gives accurate measurements during hyper- and hypoglycemia.
ACE Inhibitor Use Is Associated With Hospitalization for Severe Hypoglycemia in Patients With Diabetes
Authors: Morris Andrew D , Boyle Douglas I , McMahon Alexander D , Pearce Hilary , Evans Josie M.M , Newton Ray W , Jung Roland T , MacDonald Thomas M ,   The Darts/Memo Collaboration
Published: March 2007

OBJECTIVE

To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship.

RESEARCH DESIGN AND METHODS

The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort.

RESULTS

Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2–8.3, P = 0.023), whereas use of β-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3–3.3) and 1.7 (95% CI 0.2–2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2–16.0).

CONCLUSIONS

The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.
Weight Gain and the Risk of Developing Insulin Resistance Syndrome
Authors: Everson Susan , Glodberg Debbie E , Helmrich Susan P , Lakka Timo A , Lynch John W , Kaplan George A , Salonen Jukka T
Published: March 2007

OBJECTIVE

Obesity and weight gain have been associated independently with hypertension, hyperinsulinemia, and dyslipidemia; however, prior research has not looked at the relation between weight gain from early adulthood to middle age and the development of this cluster of risk factors, known as insulin resistance syndrome.

RESEARCH DESIGN AND METHODS

The association between weight gain over 30 years (defined as the difference between measured weight in middle age and participant recall of their weight at age 20) and the odds of developing insulin resistance syndrome at middle age was examined in a population-based sample of 2,272 eastern Finnish men.

RESULTS

Each 5% increase in weight over the reported weight at age 20 was associated with nearly a 20% greater risk of insulin resistance syndrome by middle age, after adjustment for age and height. Moreover, there was a strong graded association between categories of weight gain and risk of insulin resistance syndrome. Men with weight increases of 10–19%, 20–29%, or ≥30% since age 20 were 3.0, 4.7, or 10.6 times more likely to have insulin resistance syndrome, respectively, by middle age, compared with men within 10% of their weight at age 20. Adjustments for age, height, physical activity, smoking, education, and parental history of diabetes did not alter these findings.

CONCLUSIONS

The odds of having developed the hemodynamic and metabolic abnormalities that characterize insulin resistance syndrome by middle adulthood were increasingly higher the greater the weight gain over the preceding 30 years. This study adds to the literature identifying deleterious effects of weight gain from young to middle adulthood.
Abnormally Decreased HbA1c Can Be Assessed With Erythrocyte Creatine in Patients With a Shortened Erythrocyte Age
Authors: Jiao Yufei , Okumiya Toshika , Saibara Toshiji , Park Keunsik , Sasaki Masahide
Published: March 2007

OBJECTIVE

To investigate whether erythrocyte creatine can serve as a corrective index for HbA1c in patients with a shortened mean age of erythrocytes.

RESEARCH DESIGN AND METHODS

HbA1c and creatine in density-fractionated erythrocytes from 18 normal subjects were measured. HbA1c and erythrocyte creatine in the whole blood of 43 patients with liver cirrhosis (LC), 14 patients with hemolytic anemia (HA), 38 other patients with high reticulocyte counts (HRC) (>2.2%), and 59 normal subjects were also measured. The patients in this study all had normal blood glucose levels. A correction formula derived from the linear regression equation for the correlation between HbA1c and erythrocyte creatine was used to correct the patients' HbA1c values.

RESULTS

Among density-fractionated erythrocytes, the young cells exhibited low HbA1c and high creatine values. With progressively increasing density, HbA1c gradually increased and creatine gradually decreased. In the whole blood samples, the HbA1c values were significantly lower (P < 0.001) in LC, HA, and HRC patients than in normal subjects. By contrast, the erythrocyte creatine values were significantly higher (P < 0.001) in LC, HA, and HRC patients than in normal subjects. A linear correlation between HbA1c Cy) and erythrocyte creatine (x) was observed (y = −0.224x + 5.00; n = 154; r = −0.70; P < 0.001). Based on the regression equation, a correction formula was obtained. Low HbA1c values (<4.3%) were found in 24 of the 43 LC patients, 12 of the 14 HA patients, and 20 of the 38 HRC patients. After correction of the HbA1c values, 15 of the 24 LC patients, 9 of the 12 HA patients, and 16 of the 20 HRC patients had HbAlc values within the normal range.

CONCLUSIONS

HbA1c decreased in inverse proportion to the increase in erythrocyte creatine because of a shortened mean age of erythrocytes. The abnormally decreased HbA1c value could be assessed with erythrocyte creatine.
Family Environment, Glycemic Control, and the Psychosocial Adaptation of Adults With Diabetes
Authors: Trief Paula M , Grant William , Elbert Katja , Weinstock Ruth S
Published: March 2007

OBJECTIVE

To evaluate whether the family system variables of adults with diabetes relate to the adequacy of metabolic control or the psychosocial adaptation to the illness.

RESEARCH DESIGN AND METHODS

A total of 150 insulin-requiring adults were assessed on a single occasion. They completed two family system measures (the Family Environment Scale [FES] and the Diabetes Family Behavior Checklist [DFBC]), two quality-of-life measures (the Diabetes Quality of Life Scale and the Medical Outcomes Study Health Survey-36), and one measure of cognitive appraisal (the Appraisal of Diabetes Scale). Glycemic control was assessed using HbA1c results. Demographic data (age, sex, diabetes type, duration of diabetes, and number of diabetes-related medical complications) were gathered from the patients' charts.

RESULTS

Concerning glycemic control, none of the family system measures were significant predictors of HbA1c. Older age and longer duration of diabetes predicted higher HbA1c values. For psychosocial adaptation, when family members behaved in ways that supported the diabetes care regimen (measured by the DFBC), the individual with diabetes was more satisfied with his or her adaptation to the illness and reported less interference in role function due to emotional problems. Family cohesion (measured by the FES) also related to better physical function. Women reported higher levels of diabetes satisfaction. The Appraisal of Diabetes Scale predicted glycemic control and psychosocial adaptation.

CONCLUSIONS

For insulin-treated adults with diabetes, family system variables do not relate to glycemic control, but they do relate to psychosocial adaptation. Future work should explore the impact of family-centered interventions on adaptation, sex differences in adaptation, and the use of the Appraisal of Diabetes Scale as a first-line clinical screening tool.
Transient Improvement in Glycemic Control: The impact of pregnancy in women with IDDM
Authors: Gold Anne E , Reilly Catherine , Walker James D
Published: March 2007

OBJECTIVE

Good glycemic control throughout pregnancy in patients with diabetes is of paramount importance but often appears to deteriorate in the postpartum period. The aim of this study was to ascertain the timing of the improvement in glycemic control associated with pregnancy in women with IDDM and to examine changes in glycemic control after delivery.

RESEARCH DESIGN AND METHODS

Peripartum glycemic control was assessed in a retrospective study of 30 women with IDDM whose age was 28 ± 6 years (means ± SD) and whose diabetes duration was 14 ± 6 years.

RESULTS

Mean total HbA1 fell incrementally from a peak at 2–3 years preconception to a nadir between 24 weeks and term, only to return to preconception levels within a year after delivery. Of the 30 women, 15 (50%) attained an HbA1 in the nondiabetic range for pregnancy at some point during their pregnancy, and 7 (23%) women achieved this by 24 weeks gestation. Women with an HbA1 > 9% at booking had a significantly higher HbA1 at 0–6 and 6–12 months preconception, and throughout pregnancy their HbA1 was significantly higher. After delivery, attendance rates at routine diabetes review clinics were low, with 11% of women not attending for longer than 24 months.

CONCLUSIONS

Nearly all women with IDDM can achieve near normoglycemia during pregnancy, irrespective of previous glycemic control, although those with high HbA1 levels at booking are less likely to achieve this. After delivery, glycemic control deteriorates. Efforts to improve glycemic control should be intensified in the preconception period and maintained after delivery. The poor postpartum attendance at diabetes clinics requires specific action.
Advances Toward the Implantable Artificial Pancreas for Treatment of Diabetes
Authors: Jaremko Jacob , Rorstad Otto
Published: March 2007

Recent research on development of the implantable artificial pancreas for treatment of diabetes is reviewed, based on a Medline literature search that focused on glucose sensors, insulin pumps, and pump control systems. To achieve a closed feedback loop, a clinically applicable implantable artificial pancreas requires miniaturization and coordination of three components: an insulin pump, a blood glucose monitor, and a control system. Recent clinical studies have demonstrated that implantable insulin pumps are feasible for satisfactory control of diabetes for over a year, with the major complication being obstruction of the infusion catheter. Research on continuous glucose sensors has predominantly used the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable glucose oxidase sensors have been limited by local factors causing unstable signal output, whereas optical sensors must overcome interference by substances with absorption spectra similar to glucose. Investigators have developed control algorithms in an effort to stabilize operation of the integrated artificial pancreas in the face of variations in sensor output and pump function. The ultimate goals of fully automatic glucose control by an artificial pancreas include prevention or delay of chronic complications of diabetes, lowered risk of hypoglycemia, and less patient inconvenience and discomfort than with multiple daily glucose self-tests and insulin injection. The recent developments of optical glucose sensing, radiotelemetry systems to link pump and sensor, and miniaturization and refinement of insulin pumps are significant steps toward a clinically applicable artificial pancreas.
Postprandial Insulin Lispro: A new therapeutic option for type 1 diabetic patients
Authors: Schernthaner Guntram , Wein Wolfgang , Sandholzer Klaudia , Equiluz-Bruck Susanna , Bates Peter C , Birkett Martin A
Published: March 2007

OBJECTIVE

For intensified insulin therapy of type 1 diabetes, bolus injection of regular human insulin 30–15 min before a meal is currently recommended. This randomized study is aimed to determine whether insulin lispro (LIS), a new insulin analog with a rapid onset of action, can provide comparable blood glucose (BG) control by injection after the meal.

RESEARCH DESIGN AND METHODS

Eighteen type 1 diabetic subjects injected regular insulin (REG) at 40, 20, or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a standardized test meal. BG excursions and area under the curve of BG excursions (AUC) at the six visits were compared by analysis of variance. Hypoglycemic events (BG ≤2.78 mmol/1) were evaluated in relation to the achieved postprandial BG control.

RESULTS

Mean AUC values were 2.00, 2.55, and 3.33 mmol · h · 1−1 for REG given 40, 20, and 0 min before the test meal, respectively, and −2.19, −2.15, and 1.98 mmol · h · 1−1 for LIS given 20 and 0 min before and 15 min after the start of the test meal, respectively. LIS injected 20 min (−20) or immediately (0) before the meal was significantly more effective in controlling postprandial BG excursion (P < 0.001) than any REG treatment. Postprandial injection of LIS (15) did not compromise postprandial BG control and resulted in less hypoglycemia. REG −40 and LIS −20 were associated with early hypoglycemia, but other hypoglycemic events were equally distributed among groups.

CONCLUSIONS

The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS. LIS injected immediately after a standard meal provided postprandial BG control at least as good as REG injected from 40 to 0 min before the meal. Postprandial injection of LIS is an attractive new therapeutic option.
Comparison of Human Regular and Lispro Insulins After Interruption of Continuous Subcutaneous Insulin Infusion and in the Treatment of Acutely Decompensated IDDM
Authors: Attia Najya , Jones Timothy W , Holcombe John , Tamborlane William V
Published: March 2007

OBJECTIVE

To compare the rapidity of metabolic decompensation after interruption of CSII between human regular and lispro insulin and to compare these two insulins in the correction of the hyperglycemia and ketosis of mildly decompensated IDDM. Lispro insulin may be especially useful for insulin pump therapy (continuous subcutaneous insulin infusion [CSII]).

RESEARCH DESIGN AND METHODS

A total of 18 patients with well-controlled IDDM (HbA1c 7.7 ± 1.1%, age 30 ± 11 years) were studied. All were being treated with CSII (nine with human regular and nine with lispro insulin). The study consisted of two phases: 1) an insulin interruption phase, in which the basal insulin infusion was stopped (at 0300) and plasma insulin, glucose, and β-O-hydroxybutyrate (β-OHB) were measured every 15–60 min for 6 h after interruption of the insulin infusion and 2) an insulin replacement phase, which involved measuring plasma insulin, glucose, and (β-OHB for 2 h after a single injection of either human regular or lispro insulin to correct the hyperglycemia and ketosis that developed during the first phase of the study.

RESULTS

After interruption of the basal insulin infusion during the insulin interruption phase, plasma insulin levels fell gradually in both groups to nadir values of 1.6 ± 0.8 and 2.0 ±1.2 μU/ml in the regular insulin- and insulin lispro-treated groups, respectively. Plasma glucose concentrations rose to 13.8 ±1.9 and 16.0 ±1.7 mmol/1 in the regular insulin- and insulin lispro-treated groups, respectively. No significant differences were seen between the therapy groups at any time in the insulin levels or in the concentrations of plasma glucose or (β-OHB. In the insulin replacement phase, insulin levels rose more rapidly in those treated with lispro insulin, reaching a greater peak value (e.g., at 60 min, plasma insulin 25 ± 3.4 vs. 15.6 ± 2.6 μUsol;ml, P < 0.05). In association with this, plasma glucose decreased to a lower nadir after lispro insulin (9.7 ± 0.4 vs. 13.7 ± 0.7 mmol/1, lispro- vs. regular-treated groups at 120 min after insulin administration, P <0.01). β-OHB levels decreased rapidly in both groups.

CONCLUSIONS

In patients treated with CSII, interruption of the basal insulin infusion in the middle of the night does not result in more rapid metabolic decompensation in patients treated with lispro compared with those treated with regular human insulin. Lispro insulin is effective in treating mild ketosis and hyperglycemia, and its rapid action may be advantageous in the “sick day” management at home of patients with IDDM.
Metabolic Control and Quality-of-Life Self-Assessment in Adolescents With IDDM
Authors: Guttmann-Bauman Ines , Flaherty Brian P , Strugger Melissa , McEvoy Robert C
Published: March 2007

OBJECTIVE

To examine the relation between metabolic control and self-assessed quality of life in adolescents with IDDM.

RESEARCH DESIGN AND METHODS

The Diabetes Quality of Life (DQOL) questionnaire for youths was given to 69 subjects with IDDM aged 10-20 years at the time of their outpatient visit. Subjects with IDDM of < 1 year's duration or with documented psychotic disorder or mental retardation were excluded. Metabolic control was assessed by the mean HbA1c during the preceding year (long-term), by a single HbA1c at the time of the visit (short-term), and by the number of acute events related to IDDM in the preceding year.

RESULTS

The DQOL score correlated with mean HbA1c (β = 6.13, R2 = 0.22, P = 0.0122) and single HbA1c (β = 3.94, R2 = 0.18, P = 0.05). Self-health assessment was the best predictor of DQOL score (β = −44.42, R2 = 0.45, P < 0.0001). The Worries subscale score on DQOL correlated with the occurrence of acute events (β = 6.97, R2 = 0.2, P = 0.006), but did not correlate with either HbA1c level. Correlations of mean HbA1c with the predictors were stronger than the correlations of single HbA1c with the same predictors.

CONCLUSIONS

Metabolic control and quality of life are two important outcomes of IDDM care. In our study, adolescents in better metabolic control report better quality of life. Both components need to be addressed in developing successful diabetes treatment strategies for adolescents with IDDM.
Effects of Sickle Cell Trait and Hemoglobin C Trait on Determinations of HbA1c by an Immunoassay Method
Authors: Roberts William L , McCraw Mary , Cook Curtiss B
Published: March 2007

OBJECTIVE

A number of studies, including the Diabetes Control and Complications Trial (DCCT), have shown that good glycemic control, as assessed by GHb measurements, can reduce the chronic complications of diabetes. The National Glycohemoglobin Standardization Program (NGSP) was established to insure that GHb measurements by different methods were comparable and could be related to the candidate reference method used in the DCCT. The measurement of HbA1c in patients with Hb variants is one area not directly addressed by the NGSP. Therefore, we assessed the comparability of two DCCT-traceable methods in samples with Hb variants.

RESEARCH DESIGN AND METHODS

Samples containing HbAA, HbAC, and HbAS were collected from diabetic and nondiabetic patients. HbA1c concentrations were measured by a high-performance liquid chromatography method (Bio-Rad Diamat) and an immunoassay that is suitable for use in a physician's office (Bayer DCA 2000).

RESULTS

The two methods compared well for samples with HbAA and HbAS. However, for samples containing HbAC the immunoassay method showed relative positive biases of 8.4 and 10.4% at HbA1c levels of 7 and 9%, respectively, such that the two methods would not be judged comparable according to NGSP guidelines.

CONCLUSIONS

The DCA 2000 HbA1c immunoassay method showed significant positive bias in patients with HbC trait. One possible clinical implication of this overestimation is overly rigorous glycemic control with a concomitant increase in hypoglycemia. This may be especially important in certain ethnic populations, such as African-Americans, who have a relatively high prevalence of HbC trait.
Pramlintide, a Synthetic Analog of Human Amylin, Improves the Metabolic Profile of Patients With Type 2 Diabetes Using Insulin
Authors: Thompson Robert G , Pearson Leeanne , Schoenfeld Steven L , Kolterman Orville G ,   The Pramlintide in Type 2 Diabetes Group
Published: March 2007

OBJECTIVE

To examine the effects of 4 weeks of subcutaneous administration of pramlintide, a synthetic analog of human amylin, on metabolic control in patients with type 2 diabetes using insulin.

RESEARCH DESIGN AND METHODS

Serum fructosamine, HbA1c, and fasting plasma lipids were measured in 203 patients in a randomized double-blind placebo-controlled parallel-group multicenter trial using doses of 30 μg q.i.d., 60 μg t.i.d., and 60 μg q.i.d.

RESULTS

Statistically significant reductions in serum fructosamine concentrations were observed in the pramlintide 30 μg q.i.d. group (17.5 ± 4.9 μmol/l, P = 0.029), the pramlintide 60 μg t.i.d. group (24.1 ± 4.9 μmol/l, P = 0.003), and the 60 μg q.i.d. group (22.6 ± 4.1 μmol/l, P = 0.001) compared with the placebo group (3.5 ± 3.8 μmol/l). There were also statistically significant shifts in the proportion of patients with an abnormal serum fructosamine concentration at baseline that normalized at week 4 within the pramlintide 60 μg t.i.d. group and the 60 μg q.i.d. group. Consistent with the fructosamine results, there were statistically significant reductions in HbA1c in the pramlintide 30 μg q.i.d. group (0.53 ± 0.07%, P = 0.0447), the pramlintide 60 μg t.i.d. group (0.58 ± 0.07%, P < 0.0217), and the pramlintide 60 μg q.i.d. group (0.51 ± 0.08%, P = 0.0242) compared with the placebo group (0.27 ± 0.08%). Total cholesterol concentrations were also statistically significantly reduced in both the pramlintide 60 μg t.i.d. group (8.4 mg/dl, P < 0.01) and 60 μg q.i.d. group (10.5 mg/dl, P < 0.01) compared with placebo (1.2 mg/dl). Body weight decreased in both of the pramlintide 60 μg groups, but the trend did not achieve statistical significance. The incidence of hypoglycemia was similar in all treatment groups.

CONCLUSIONS

Reductions in serum fructosamine, plasma total and LDL cholesterol concentrations, and HbA1c support the hypothesis that pramlintide may improve metabolic control in patients with type 2 diabetes using insulin.
Reversion From Type 2 Diabetes to Nondiabetic Status: Influence of the 1997 American Diabetes Association criteria
Authors: Burke James P , Haffner Steven M , Gaskill Sharon P , Williams Kenneth L , Stern Michael P
Published: March 2007

OBJECTIVE

To determine the incidence and the rate of reversion of type 2 diabetes to a nondiabetic status in the 7- to 8-year follow-up of the San Antonio Heart Study, and to determine the influence of the recent 1997 American Diabetes Association (ADA) criteria for diabetes on these rates. Individuals who revert have been problematic for those developing criteria for the diagnosis of type 2 diabetes. Few studies have addressed this issue using 1979 National Diabetes Data Group/1980 World Health Organization (WHO) criteria.

RESEARCH DESIGN AND METHODS

We studied 3,682 Mexican-American and non-Hispanic white men and nonpregnant women who completed both the baseline and follow-up examination of the San Antonio Heart Study. Incidence and reversion rates were calculated using both the 1980 WHO and the 1997 ADA criteria. Risk factors for reversion were identified, and the best fitting model using multiple logistic regression was determined using both the 1980 WHO and the 1997 ADA criteria.

RESULTS

Using the 1997 ADA criteria, the age-adjusted incidences of type 2 diabetes for Mexican-American men and women were 10.8 and 12.2%, respectively. For non-Hispanic white men and women, the age-adjusted incidence rates were 5.5 and 5.1%, respectively. Similar age-adjusted incidences were recorded using the 1980 WHO criteria. The reversion rate for individuals with type 2 diabetes was 11.5% using the 1980 WHO criteria and 12.5% using the 1997 ADA criteria. These rates were not significantly different. Numerous risk factors for reversion were identified. The best fitting model, after controlling for age, sex, and ethnicity, included baseline 2-h glucose level, baseline HDL cholesterol, and previous diagnosis of diabetes. The models were the same for both the 1980 WHO and the 1997 ADA criteria.

CONCLUSIONS

There was no significant difference in the incidence or the reversion rates for diabetic subjects using either 1980 WHO or 1997 ADA criteria. In addition, the risk factors for reversion were very similar using either set of criteria. The revision of the ADA criteria did not have a significant influence on reversion in this study.
Global Burden of Diabetes, 1995–2025: Prevalence, numerical estimates, and projections
Authors: King Hilary , Aubert Ronald E , Herman William H
Published: March 2007

OBJECTIVE

To estimate the prevalence of diabetes and the number of people with diabetes who are ≥20 years of age in all countries of the world for three points in time, i.e., the years 1995, 2000, and 2025, and to calculate additional parameters, such as sex ratio, urban-rural ratio, and the age structure of the diabetic population.

RESEARCH DESIGN AND METHODS

Age-specific diabetes prevalence estimates were applied to United Nations population estimates and projections for the number of adults aged ≥20 years in all countries of the world. For developing countries, urban and rural populations were considered separately

RESULTS

Prevalence of diabetes in adults worldwide was estimated to be 4.0% in 1995 and to rise to 5.4% by the year 2025. It is higher in developed than in developing countries. The number of adults with diabetes in the world will rise from 135 million in 1995 to 300 million in the year 2025. The major part of this numerical increase will occur in developing countries. There will be a 42% increase, from 51 to 72 million, in the developed countries and a 170% increase, from 84 to 228 million, in the developing countries. Thus, by the year 2025, >75% of people with diabetes will reside in developing countries, as compared with 62% in 1995. The countries with the largest number of people with diabetes are, and will be in the year 2025, India, China, and the U.S. In developing countries, the majority of people with diabetes are in the age range of 45–64 years. In the developed countries, the majority of people with diabetes are aged ≥65 years. This pattern will be accentuated by the year 2025. There are more women than men with diabetes, especially in developed countries. In the future, diabetes will be increasingly concentrated in urban areas.

CONCLUSIONS

This report supports earlier predictions of the epidemic nature of diabetes in the world during the first quarter of the 21st century. It also provides a provisional picture of the characteristics of the epidemic. Worldwide surveillance of diabetes is a necessary first step toward its prevention and control, which is now recognized as an urgent priority.
Troglitazone Use in Insulin-Treated Type 2 Diabetic Patients
Authors: Buse John B , Gumbiner Barry , Mathias Nancy P , Nelson Debra M , Faja Barbara W , Whitcomb Randall W ,   The Troglitazone Insulin Study Group
Published: March 2007

OBJECTIVE

To determine the ability of troglitazone to reduce requirements for injected insulin while maintaining blood glucose levels in insulin-treated patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

This 26-week double-blind study with open-label extension included patients who had failed previous oral antidiabetic medication and took ≥30 but <150 U of insulin daily The 222 patients in the double-blind study received 200 or 400 mg troglitazone once daily or matching placebo. The primary end point was the proportion of patients meeting the target of ≥50% reduction in injected insulin and either a 15% reduction in fasting blood glucose or a blood glucose <7.8 mmol/l. Insulin dose was reduced 25% based on a study-specific algorithm whenever fasting blood glucose was reduced 5% from baseline. Also of interest were changes in insulin dose and HbA1c. The open-label extension included 173 patients. They received 200 mg of troglitazone with optional titration to 400 mg, and insulin dose was adjusted based on investigators' standards of care. Open-label measures were change in insulin dose, HbA1c, and fasting serum glucose (FSG).

RESULTS

In the double-blind phase, 22 and 27% of the 200- and 400-mg troglitazone groups, respectively, reached target, compared with placebo (7%) (P < 0.01). Insulin dose reductions of 13 ± 3, 30 ± 3, and 41 ± 3 U were observed for placebo, 200-, and 400-mg troglitazone groups, respectively HbA1c decreased 0.09 ± 0.14% for placebo, 0.13 ± 0.14% for 200 mg, and 0.41 ± 0.14% for 400 mg (P < 0.05) troglitazone. In the open-label extension, troglitazone treatment resulted in >50% reduction from baseline in daily insulin dose and decreases in HbA1c of 1% and in FSG of >17%.

CONCLUSIONS

Troglitazone decreases daily injected insulin dose requirements and improves glycemic control in insulin-treated patients with type 2 diabetes.